有机化学（英文原版）：End of Book

APPENDIX 1 PHYSICAL PROPERTIES A-1 Compound name Alkanes Methane Ethane Propane Butane 2-Methylpropane Pentane 2-Methylbutane 2,2-Dimethylpropane Hexane Heptane Octane Nonane Decane Dodecane Pentadecane Icosane Hectane Cycloalkanes Cyclopropane Cyclobutane Cyclopentane Cyclohexane Cycloheptane Cyclooctane Cyclononane Cyclodecane Cyclopentadecane Alkenes and cycloalkenes Ethene (ethylene) Propene 1-Butene 2-Methylpropene Cyclopentene Molecular formula CH 4 C 2 H 6 C 3 H 8 C 4 H 10 C 4 H 10 C 5 H 12 C 5 H 12 C 5 H 12 C 6 H 14 C 7 H 16 C 8 H 18 C 9 H 20 C 10 H 22 C 12 H 26 C 15 H 32 C 20 H 42 C 100 H 202 C 3 H 6 C 4 H 8 C 5 H 10 C 6 H 12 C 7 H 14 C 8 H 16 C 9 H 18 C 10 H 20 C 15 H 30 C 2 H 4 C 3 H 6 C 4 H 8 C 4 H 8 C 5 H 8 Melting point, °C H11002182.5 H11002183.6 H11002187.6 H11002139.0 H11002160.9 H11002129.9 H11002160.5 H1100216.6 H1100294.5 H1100290.6 H1100256.9 H1100253.6 H1100229.7 H110029.7 10.0 36.7 115.1 H11002127.0 H1100294.0 6.5 H1100213.0 13.5 9.6 60.5 H11002169.1 H11002185.0 H11002185 H11002140 H1100298.3 Boiling point, °C (1 atm) H11002160 H1100288.7 H1100242.2 H110020.4 H1100210.2 36.0 27.9 9.6 68.8 98.4 125.6 150.7 174.0 216.2 272.7 205 (15 mm) H1100232.9 13.0 49.5 80.8 119.0 149.0 171 201 112.5 (1 mm) H11002103.7 H1100247.6 H110026.1 H11002 6.6 44.1 Structural formula CH 4 CH 3 CH 3 CH 3 CH 2 CH 3 CH 3 CH 2 CH 2 CH 3 (CH 3 ) 3 CH CH 3 (CH 2 ) 3 CH 3 (CH 3 ) 2 CHCH 2 CH 3 (CH 3 ) 4 C CH 3 (CH 2 ) 4 CH 3 CH 3 (CH 2 ) 5 CH 3 CH 3 (CH 2 ) 6 CH 3 CH 3 (CH 2 ) 7 CH 3 CH 3 (CH 2 ) 8 CH 3 CH 3 (CH 2 ) 10 CH 3 CH 3 (CH 2 ) 13 CH 3 CH 3 (CH 2 ) 18 CH 3 CH 3 (CH 2 ) 98 CH 3 CH 2 ?CH 2 CH 3 CH?CH 2 CH 3 CH 2 CH?CH 2 (CH 3 ) 2 C?CH 2 (Continued) TABLE A Selected Physical Properties of Representative Hydrocarbons A-2 APPENDIX 1 Molecular formula C 2 H 2 C 3 H 4 C 4 H 6 C 4 H 6 C 6 H 10 C 6 H 10 C 8 H 14 C 9 H 16 C 10 H 18 C 6 H 10 C 5 H 10 C 5 H 10 C 6 H 12 C 6 H 12 C 7 H 14 C 8 H 16 C 10 H 20 C 6 H 6 C 7 H 8 C 8 H 8 C 8 H 10 C 8 H 10 C 10 H 8 C 13 H 12 C 19 H 16 Melting point, °C H1100281.8 H11002101.5 H11002125.9 H1100232.3 H11002132.4 H1100278.2 H1100279.6 H1100236.0 H1100240.0 H11002104.0 H11002138.0 H11002134.1 H11002138.0 H1100274.6 H11002119.7 H11002104 H1100280.0 5.5 H1100295 H1100233 H1100213 H1100294 80.3 26 94 Boiling point, °C (1 atm) H1100284.0 H11002 23.2 8.1 27.0 71.4 37.7 126.2 160.6 182.2 83.1 30.2 38.4 63.5 73.5 94.9 119.2 172.0 80.1 110.6 145 138 136.2 218 261 Compound name Alkynes Ethyne (acetylene) Propyne 1-Butyne 2-Butyne 1-Hexyne 3,3-Dimethyl-1-butyne 1-Octyne 1-Nonyne 1-Decyne Cyclohexene 1-Pentene 2-Methyl-2-butene 1-Hexene 2,3-Dimethyl-2-butene 1-Heptene 1-Octene 1-Decene Arenes Benzene Toluene Styrene p-Xylene Ethylbenzene Naphthalene Diphenylmethane Triphenylmethane Structural formula HCPCH CH 3 CPCH CH 3 CH 2 CPCH CH 3 CPCCH 3 CH 3 (CH 2 ) 3 CPCH (CH 3 ) 3 CCPCH CH 3 (CH 2 ) 5 CPCH CH 3 (CH 2 ) 6 CPCH CH 3 (CH 2 ) 7 CPCH CH 3 CH 2 CH 2 CH?CH 2 (CH 3 ) 2 C?CHCH 3 CH 3 CH 2 CH 2 CH 2 CH?CH 2 (CH 3 ) 2 C?C(CH 3 ) 2 CH 3 (CH 2 ) 4 CH?CH 2 CH 3 (CH 2 ) 5 CH?CH 2 CH 3 (CH 2 ) 7 CH?CH 2 (C 6 H 5 ) 2 CH 2 (C 6 H 5 ) 3 CH CH 3 CH CH 2 CH 3 H 3 C CH 2 CH 3 TABLE A Selected Physical Properties of Representative Hydrocarbons (Continued) APPENDIX 1 A-3 Boiling point, °C (1 atm) Density, g/mL (20°C) Fluoride H1100278 H1100232 H110023 H1100211 16 65 92 143 Chloride H1100224 12 47 35 78 68 68 51 108 134 183 114 142 Bromide 3 38 71 59 102 91 91 73 129 155 202 138 167 Iodide 42 72 103 90 130 120 121 99 157 180 226 166 192 Chloride 0.903 0.890 0.859 0.887 0.873 0.878 0.847 0.884 0.879 0.892 1.005 0.977 Bromide 1.460 1.353 1.310 1.276 1.261 1.264 1.220 1.216 1.175 1.118 1.388 1.324 Iodide 2.279 1.933 1.739 1.714 1.615 1.597 1.603 1.570 1.516 1.439 1.336 1.626 1.694 Structural formula CH 3 X CH 3 CH 2 X CH 3 CH 2 CH 2 X (CH 3 ) 2 CHX CH 3 CH 2 CH 2 CH 2 X CH 3 CHCH 2 CH 3 (CH 3 ) 2 CHCH 2 X (CH 3 ) 3 CX CH 3 (CH 2 ) 3 CH 2 X CH 3 (CH 2 ) 4 CH 2 X CH 3 (CH 2 ) 6 CH 2 X X X W X Compound name Alkyl Halides Halomethane Haloethane 1-Halopropane 2-Halopropane 1-Halobutane 2-Halobutane 1-Halo-2-methylpropane 2-Halo-2-methylpropane 1-Halopentane 1-Halohexane 1-Halooctane Halocyclopentane Halocyclohexane Compound Aryl Halides C 6 H 5 X o-C 6 H 4 X 2 m-C 6 H 4 X 2 p-C 6 H 4 X 2 1,3,5-C 6 H 3 X 3 C 6 X 6 Halogen substituent (X)* Fluorine Chlorine Bromine Iodine mp H1100241 H1100234 H1100259 H1100213 H110025 5 bp 85 91 83 89 76 80 mp H1100245 H1100217 H1100225 53 63 230 bp 132 180 173 174 208 322 mp H1100231 7 H110027 87 121 327 bp 156 225 218 218 271 mp H1100231 27 35 129 184 350 bp 188 286 285 285 *All boiling points and melting points cited are in degrees Celsius. TABLE B Selected Physical Properties of Representative Organic Halogen Compounds A-4 APPENDIX 1 Compound name Alcohols Methanol Ethanol 1-Propanol 2-Propanol 1-Butanol 2-Butanol 2-Methyl-1-propanol 2-Methyl-2-propanol 1-Pentanol 1-Hexanol 1-Dodecanol Ethers Dimethyl ether Diethyl ether Dipropyl ether Diisopropyl ether 1,2-Dimethoxyethane Diethylene glycol dimethyl ether (diglyme) Cyclohexanol Ethylene oxide Tetrahydrofuran Melting point, °C H1100294 H11002117 H11002127 H1100290 H1100290 H11002115 H11002108 26 H1100279 H1100252 26 H11002138.5 H11002116.3 H11002122 H1100260 25 H11002111.7 H11002108.5 Boiling point, °C (1 atm) 65 78 97 82 117 100 108 83 138 157 259 H1100224 34.6 90.1 68.5 83 161 161 10.7 65 Solubility, g/100 mL H 2 O H11009 H11009 H11009 H11009 9 26 10 H11009 0.6 Insoluble Very soluble 7.5 Slight 0.2 H11009 H11009 3.6 H11009 H11009 (Continued) Structural formula CH 3 OH CH 3 CH 2 OH CH 3 CH 2 CH 2 OH (CH 3 ) 2 CHOH CH 3 CH 2 CH 2 CH 2 OH CH 3 CHCH 2 CH 3 (CH 3 ) 2 CHCH 2 OH (CH 3 ) 3 COH CH 3 (CH 2 ) 3 CH 2 OH CH 3 (CH 2 ) 4 CH 2 OH CH 3 (CH 2 ) 10 CH 2 OH W OH CH 3 OCH 3 CH 3 CH 2 OCH 2 CH 3 CH 3 CH 2 CH 2 OCH 2 CH 2 CH 3 (CH 3 ) 2 CHOCH(CH 3 ) 2 CH 3 OCH 2 CH 2 OCH 3 CH 3 OCH 2 CH 2 OCH 2 CH 2 OCH 3 OH O O TABLE C Selected Physical Properties of Representative Alcohols, Ethers, and Phenols APPENDIX 1 A-5 Compound name Phenols Phenol o-Cresol m-Cresol p-Cresol o-Chlorophenol m-Chlorophenol p-Chlorophenol o-Nitrophenol m-Nitrophenol p-Nitrophenol 1-Naphthol 2-Naphthol Pyrocatechol Resorcinol Hydroquinone Melting point, °C 43 31 12 35 7 32 42 45 96 114 96 122 105 110 170 Boiling point, °C 182 191 203 202 175 214 217 217 279 279 285 246 276 285 Solubility, g/100 mL H 2 O 8.2 2.5 0.5 1.8 2.8 2.6 2.7 0.2 1.3 1.6 Slight 0.1 45.1 147.3 6 TABLE C Selected Physical Properties of Representative Alcohols, Ethers, and Phenols (Continued) (Continued) Compound name Aldehydes Formaldehyde Acetaldehyde Propanal Butanal Benzaldehyde Melting point, °C H1100292 H11002123.5 H1100281 H1100299 H1100226 Boiling point, °C (1 atm) H1100221 20.2 49.5 75.7 178 Solubility, g/100 mL H 2 O Very soluble H11009 20 4 0.3 Structural formula HCH X O CH 3 CH X O CH 3 CH 2 CH X O CH 3 CH 2 CH 2 CH X O C 6 H 5 CH X O TABLE D Selected Physical Properties of Representative Aldehydes and Ketones A-6 APPENDIX 1 Compound name Ketones Acetone 2-Butanone 2-Pentanone 3-Pentanone Cyclopentanone Cyclohexanone Acetophenone Benzophenone Melting point, °C H1100294.8 H1100286.9 H1100277.8 H1100239.9 H1100251.3 H1100245 21 48 Boiling point, °C (1 atm) 56.2 79.6 102.4 102.0 130.7 155 202 306 Solubility, g/100 mL H 2 O H11009 37 Slight 4.7 43.3 Insoluble Insoluble Structural formula CH 3 CCH 3 X O CH 3 CCH 2 CH 3 X O CH 3 CCH 2 CH 2 CH 3 X O CH 3 CH 2 CCH 2 CH 3 X O C 6 H 5 CCH 3 X O C 6 H 5 CC 6 H 5 X O O O TABLE D Selected Physical Properties of Representative Aldehydes and Ketones (Continued) Carboxylic acids Dicarboxylic acids Compound name Formic acid Acetic acid Propanoic acid Butanoic acid Pentanoic acid Decanoic acid Benzoic acid Oxalic acid Malonic acid Succinic acid Glutaric acid Melting point, °C 8.4 16.6 H1100220.8 H110025.5 H1100234.5 31.4 122.4 186 130–135 189 97.5 Boiling point, °C (1 atm) 101 118 141 164 186 269 250 Sublimes Decomposes 235 Solubility, g/100 mL H 2 O H11009 H11009 H11009 H11009 3.3 (16°C) 0.003 (15°C) 0.21 (17°C) 10 (20°C) 138 (16°C) 6.8 (20°C) 63.9 (20°C) Structural formula HCO 2 H CH 3 CO 2 H CH 3 CH 2 CO 2 H CH 3 CH 2 CH 2 CO 2 H CH 3 (CH 2 ) 3 CO 2 H CH 3 (CH 2 ) 8 CO 2 H C 6 H 5 CO 2 H HO 2 CCO 2 H HO 2 CCH 2 CO 2 H HO 2 CCH 2 CH 2 CO 2 H HO 2 CCH 2 CH 2 CH 2 CO 2 H TABLE E Selected Physical Properties of Representative Carboxylic Acids and Dicarboxylic Acids APPENDIX 1 A-7 Melting point, °C H1100292.5 H1100280.6 H1100250 H1100285 H11002104 H1100267.5 H1100219 H1100218 10 H1100210.5 H1100292.2 H1100250 3 H11002117.1 H11002114.7 Boiling point, °C H110026.7 16.6 77.8 68 66 45.2 129 134.5 184.5 106.4 6.9 55.5 62.4 107 2.9 89.4 Solubility, g/100 mL H 2 O Very high H11009 H11009 H11009 H11009 Slightly soluble H11009 H11009 H11009 Very soluble Very soluble Soluble 41 H11009 Compound name Alkylamines Methylamine Ethylamine Butylamine Isobutylamine sec-Butylamine tert-Butylamine Hexylamine Cyclohexylamine Benzylamine Piperidine Primary amines Dimethylamine Diethylamine N-Methylpropylamine Secondary amines N-Methylpiperidine Trimethylamine Triethylamine Tertiary amines Structural formula CH 3 NH 2 CH 3 CH 2 NH 2 CH 3 CH 2 CH 2 CH 2 NH 2 (CH 3 ) 2 CHCH 2 NH 2 CH 3 CH 2 CHNH 2 (CH 3 ) 3 CNH 2 CH 3 (CH 2 ) 5 NH 2 C 6 H 5 CH 2 NH 2 NH 2 W CH 3 (CH 3 ) 2 NH (CH 3 CH 2 ) 2 NH CH 3 NHCH 2 CH 2 CH 3 N H (CH 3 ) 3 N (CH 3 CH 2 ) 3 N N CH 3 (Continued) TABLE F Selected Physical Properties of Representative Amines A-8 APPENDIX 1 Melting point, °C H110026.3 H1100214.7 H1100230.4 44 H1100214 H1100210 72.5 71.5 114 148 H1100257 H1100263 2.4 127 Boiling point, °C 184 200 203 200 209 230 232 284 306 332 196 205 194 365 Compound name Arylamines Aniline o-Toluidine m-Toluidine p-Toluidine o-Chloroaniline m-Chloroaniline p-Chloroaniline o-Nitroaniline m-Nitroaniline p-Nitroaniline Primary amines N-Methylaniline N-Ethylaniline Secondary amines N,N-Dimethylaniline Triphenylamine Tertiary amines TABLE F Selected Physical Properties of Representative Amines (Continued) APPENDIX 2 ANSWERS TO IN-TEXT PROBLEMS A-9 Problems are of two types: in-text problems that appear within the body of each chapter, and end- of-chapter problems. This appendix gives brief answers to all the in-text problems. More detailed discussions of in-text problems as well as detailed solutions to all the end-of-chapter problems are provided in a separate Study Guide and Student Solutions Manual. Answers to part (a) of those in-text problems with multiple parts have been provided in the form of a sample solution within each chapter and are not repeated here. CHAPTER 1 1.1 4 1.2 All the third-row elements have a neon core containing 10 electrons (1s 2 2s 2 2p 6 ). The ele- ments in the third row, their atomic numbers Z, and their electron configurations beyond the neon core are Na(Z H1100511)3s 1 ; Mg(Z H11005 12)3s 2 ; Al(Z H11005 13) 3s 2 3p x 1 ; Si(Z H11005 14) 3s 2 3p x 1 3p y 1 ; P (Z H11005 15) 3s 2 3p x 1 3p y 1 3p z 1 ; S (Z H11005 16) 3s 2 3p x 2 3p y 1 3p z 1 ; Cl (Z H11005 17) 3s 2 3p x 2 3p y 2 3p z 1 ; Ar (Z H11005 18) 3s 2 3p x 2 3p y 2 3p z 2 . 1.3 Those ions that possess a noble gas electron configuration are (a) K H11001 ; (c) H H11002 ; (e) F H11002 ; and (f) Ca 2H11001 . 1.4 Electron configuration of C H11001 is 1s 2 2s 2 2p 1 ; electron configuration of C H11002 is 1s 2 2s 2 2p 3 . Nei- ther C H11001 nor C H11002 possesses a noble gas electron configuration. 1.5 1.6 1.7 (b) (c) 1.8 Carbon bears a partial positive charge in CH 3 Cl. It is partially negative in both CH 4 and CH 3 Li, but the degree of negative charge is greater in CH 3 Li. 1.9 (b) Sulfur has a formal charge of H110012 in the Lewis structure given for sulfuric acid, the two oxygens bonded only to sulfur each have a formal charge of H110021, and the oxygens and hydrogens of the two OH groups have no formal charge; (c) none of the atoms have a formal charge in the Lewis structure given for nitrous acid. 1.10 The electron counts of nitrogen in ammonium ion and boron in borohydride ion are both 4 (half of 8 electrons in covalent bonds). Since a neutral nitrogen has 5 electrons in its valence shell, an electron count of 4 gives it a formal charge of H110011. A neutral boron has 3 valence electrons, so that an electron count of 4 in borohydride ion corresponds to a formal charge of H110021. H C H H CC N FF CC F F CH H H H HH C FH A-10 APPENDIX 2 1.11 1.12 (b) (c) (d) (e) (f) 1.13 (b) (CH 3 ) 2 CHCH(CH 3 ) 2 (c) (d) 1.14 1.15 (b) CH 3 CH 2 CH 2 OH, (CH 3 ) 2 CHOH, and CH 3 CH 2 OCH 3 . (c) There are seven isomers of C 4 H 10 O. Four have ±OH groups: CH 3 CH 2 CH 2 CH 2 OH, (CH 3 ) 2 CHCH 2 OH, (CH 3 ) 3 COH, and . Three have C±O±C units: CH 3 OCH 2 CH 2 CH 3 , CH 3 CH 2 OCH 2 CH 3 , and (CH 3 ) 2 CHOCH 3 1.16 (b) (c) and C O H11002 O O H11002 C O O H11002 O H11002 C O H11002 O O H11002 C O H11002 O H11002 O C HO O O H11002 H C O H11002 O O CH 3 CHCH 2 CH 3 OH H N H C O O H CH 2 CH CH 2 CH 2 CH 2 CH 2 C(CH 3 ) 3 HOCH 2 CHCH(CH 3 ) 2 CH 3 H C H H C H C H O CH H H H C H H N H C H H C H H H C H H C H Cl H ClCl C H H C H H ClH C C H HHH HH C C HH H N H H HH H9254H11001 H9254H11001 H9254H11001H9254H11001 H9254H11001 B H H HH H9254H11002 H9254H11002 H9254H11002H9254H11002 H9254H11002 APPENDIX 2 A-11 (d) and 1.17 The H±B±H angles in BH 4 H11002 are 109.5° (tetrahedral). 1.18 (b) Tetrahedral; (c) linear; (d) trigonal planar 1.19 (b) Oxygen is negative end of dipole moment directed along bisector of H±O±H angle; (c) no dipole moment; (d) dipole moment directed along axis of C±Cl bond, with chlorine at negative end, and carbon and hydrogens partially positive; (e) dipole moment directed along bisec- tor of H±C±H angle, with oxygen at negative end; (f) dipole moment aligned with axis of lin- ear molecule, with nitrogen at negative end. 1.20 The sp 3 hybrid state of nitrogen is just like that of carbon except nitrogen has one more electron. Each N±H bond in NH 3 involves overlap of an sp 3 hybrid orbital of N with a 1s orbital of hydrogen. The unshared pair of NH 3 occupies an sp 3 orbital. 1.21 Carbon and silicon are both sp 3 -hybridized. The C±Si bond involves overlap of a half- filled sp 3 orbital of carbon with a half-filled sp 3 hybrid orbital of silicon. The C±H and Si±H bonds involve hydrogen 1s orbitals and sp 3 hybrid orbitals of C and Si, respectively. The princi- pal quantum number of the valence orbitals of silicon is 3. 1.22 (b) sp 2 ; (c) carbon of CH 2 group is sp 2 , and carbon of C?O is sp; (d) two doubly bonded carbons are each sp 2 , while carbon of CH 3 group is sp 3 ; (e) carbon of C?O is sp 2 , and carbons of CH 3 group are sp 3 ; (f) two doubly bonded carbons are each sp 2 , and carbon bonded to nitro- gen is sp. CHAPTER 2 2.1 2.2 CH 3 (CH 2 ) 26 CH 3 2.3 The molecular formula is C 11 H 24 ; the condensed structural formula is CH 3 (CH 2 ) 9 CH 3 . Carboxylic acidKetone OH O OH HO O Energy 2p 2s Ground electronic state of nitrogen 2sp 3 sp 3 Hybrid state of nitrogen 2p 2s Higher energy electronic state of nitrogen B O O H11002 O H11002 B O O H11002 O H11002 B O O H11002 O H11002 B O H11002 O H11002 O A-12 APPENDIX 2 2.4 2.5 (b) CH 3 (CH 2 ) 26 CH 3 ; (c) undecane 2.6 2.7 (b) CH 3 CH 2 CH 2 CH 2 CH 3 (pentane), (CH 3 ) 2 CHCH 2 CH 3 (2-methylbutane), (CH 3 ) 4 C (2,2- dimethylpropane); (c) 2,2,4-trimethylpentane; (d) 2,2,3,3-tetramethylbutane 2.8 CH 3 CH 2 CH 2 CH 2 CH 2 ± (pentyl, primary); (1-methylbutyl, sec- ondary); (1-ethylpropyl, secondary); (CH 3 ) 2 CHCH 2 CH 2 ± (3-methylbutyl, primary); CH 3 CH 2 CH(CH 3 )CH 2 ± (2-methylbutyl, primary); (1,1-dimethyl- propyl, tertiary); and (1,2-dimethylpropyl, secondary) 2.9 (b) 4-Ethyl-2-methylhexane; (c) 8-ethyl-4-isopropyl-2,6-dimethyldecane 2.10 (b) 4-Isopropyl-1,1-dimethylcyclodecane; (c) cyclohexylcyclohexane 2.11 2,2,3,3-Tetramethylbutane (106°C); 2-methylheptane (116°C); octane (126°C); nonane (151°C) 2.12 2.13 13,313 kJ/mol 2.14 Hexane (CH 3 CH 2 CH 2 CH 2 CH 2 CH 3 ) H11022 pentane (CH 3 CH 2 CH 2 CH 2 CH 3 ) H11022 isopentane [(CH 3 ) 2 CHCH 2 CH 3 ] H11022 neopentane [(CH 3 ) 4 C] 2.15 (b) Oxidation of carbon; (c) reduction of carbon CHAPTER 3 3.1 (b) Butane; (c) 2-methylbutane; (d) 3-methylhexane 3.2 Red circles gauche: 60° and 300°. Red circles anti: 180°. Gauche and anti relationships occur only in staggered conformations; therefore, ignore the eclipsed conformations (0°, 120°, 240°, 360°). 3.3 Shape of potential energy diagram is identical with that for ethane (Figure 3.4). Activation energy for rotation about the C±C bond is higher than that of ethane, lower than that of butane. 3.4 (b) (c) (d) 3.5 (b) Less stable; (c) methyl is equatorial and down X A 3 X A 3 X A 9O 2 6CO 2 6H 2 OH11001H11001 (CH 3 ) 2 CHCHCH 3 (CH 3 ) 2 CCH 2 CH 3 CH 3 CH 2 CHCH 2 CH 3 CH 3 CH 2 CH 2 CHCH 3 orandorCH 3 CHCHCH 3 CH 3 CH 3 CH 3 CH 2 CCH 3 CH 3 CH 3 orCH 3 CH 2 CHCH 2 CH 3 CH 3 APPENDIX 2 A-13 3.6 3.7 Ethylcyclopropane: 3384 kJ/mol (808.8 kcal/mol); methylcyclobutane: 3352 kJ/mol (801.2 kcal/mol) 3.8 1,1-Dimethylcyclopropane, ethylcyclopropane, methylcyclobutane, and cyclopentane 3.9 cis-1,3,5-Trimethylcyclohexane is more stable. 3.10 (b) (c) (d) 3.11 3.12 Other pairs of bond cleavages are also possible. 3.13 (b) (c) (d) 3.14 CHAPTER 4 4.1 Substitutive name: Functional class names: CH 3 CH 2 CH 2 CH 2 Cl 1-Chlorobutane n-Butyl chloride or butyl chloride 1-Chloro-2-methylpropane Isobutyl chloride or 2-methylpropyl chloride (CH 3 ) 2 CHCH 2 Cl CH 3 CHCH 2 CH 3 Cl 2-Chlorobutane sec-Butyl chloride or 1-methylpropyl chloride 2-Chloro-2-methylpropane tert-Butyl chloride or 1,1-dimethylethyl chloride (CH 3 ) 3 CCl N CH 3 H11013 CH 3 CH 3 CH 2 CH 3 CH 2 CH 3 CH 3 CH 2 CH 3 CH CH 2 and CH 2 C(CH 3 ) 3 H H CH 3 C(CH 3 ) 3 H H 3 C H C(CH 3 ) 3 HH H 3 C CH 3 C(CH 3 ) 3 A-14 APPENDIX 2 4.2 4.3 4.4 The carbon—bromine bond is longer than the carbon—chlorine bond; therefore, although the charge e in the dipole moment expression H9262 H11005 e H11080 d is smaller for the bromine than for the chlo- rine compound, the distance d is greater. 4.5 Hydrogen bonding in ethanol (CH 3 CH 2 OH) makes its boiling point higher than that of dimethyl ether (CH 3 OCH 3 ), in which hydrogen bonding is absent. 4.6 4.7 K a H11005 8 H11003 10 H1100210 ; hydrogen cyanide is a weak acid. 4.8 Hydrogen cyanide is a stronger acid than water; its conjugate base (CN H11002 ) is a weaker base than hydroxide (HO H11002 ). 4.9 4.10 Greater than 1 4.11 4.12 (b) (CH 3 CH 2 ) 3 COH H11001 HCl ±￡ (CH 3 CH 2 ) 3 CCl H11001 H 2 O (c) CH 3 (CH 2 ) 12 CH 2 OH H11001 HBr ±￡ CH 3 (CH 2 ) 12 CH 2 Br H11001 H 2 O 4.13 (CH 3 ) 2 C H11001 CH 2 CH 3 4.14 1-Butanol: Rate-determining step is bimolecular; therefore, S N 2. 1. CH 3 CH 2 CH 2 CH 2 O H H11001 H Br Br H11002fast H CH 3 CH 2 CH 2 CH 2 O H11001 H H11001 (CH 3 ) 3 CO Cl H9254H11002H9254H11001 H H H11001 Cl H11002 Conjugate base H Cl Acid (CH 3 ) 3 CO H O Base H11001 H (CH 3 ) 3 CO H O Conjugate acid H11001 Cl H11002 Conjugate base H11001 H11001 HH 3 N Conjugate acid H 3 N Base H11001 H Cl Acid CH 3 CH 2 CH 2 CH 2 OH Primary CH 3 CHCH 2 CH 3 OH Secondary (CH 3 ) 2 CHCH 2 OH Primary Tertiary (CH 3 ) 3 COH Substitutive name: Functional class names: CH 3 CH 2 CH 2 CH 2 OH 1-Butanol n-Butyl alcohol or butyl alcohol 2-Methyl-1-propanol Isobutyl alcohol or 2-methylpropyl alcohol (CH 3 ) 2 CHCH 2 OH CH 3 CHCH 2 CH 3 OH 2-Butanol sec-Butyl alcohol or 1-methylpropyl alcohol 2-Methyl-2-propanol tert-Butyl alcohol or 1,1-dimethylethyl alcohol (CH 3 ) 3 COH APPENDIX 2 A-15 2. 2-Butanol: Rate-determining step is unimolecular, therefore, S N 1. 1. 2. 3. 4.15 4.16 (b) The carbon—carbon bond dissociation energy is lower for 2-methylpropane because it yields a more stable (secondary) radical; propane yields a primary radical. (c) The carbon—carbon bond dissociation energy is lower for 2,2-dimethylpropane because it yields a still more stable ter- tiary radical. 4.17 Initiation: Propagation: 4.18 CH 3 CHCl 2 and ClCH 2 CH 2 Cl 4.19 1-Chloropropane (43%); 2-chloropropane (57%) 4.20 (b) (c) Br C(CH 3 ) 2 CH 3 Br H11001Cl C Cl H H Dichloromethane H11001 Cl Cl Chlorine Cl C H H Chloromethyl radical Chlorine atom Cl Cl Chlorine atom H11001H11001Cl CH H H Chloromethane Cl C H H Chloromethyl radical ClH Hydrogen chloride Cl Cl Chlorine Cl ClH11001 2 Chlorine atoms (CH 3 ) 2 CCH 2 CH 3 Br H11002 H11001 CHCH 3 H11001 CH 3 CH 2 Br CH 3 CH 2 CHCH 3 fast H11001 O CH 3 CH 2 CHCH 3 H11001 HH CH 3 CH 2 CHCH 3 H11001 slow O HH O CH 3 CH 2 CHCH 3 H H11001 fast H Br Br H11002 H11001 O CH 3 CH 2 CHCH 3 H11001 HH CH 2 CH 3 CH 2 CH 2 Br H11002 H O H11001 H slow CH 3 CH 2 CH 2 CH 2 Br H11001 H O H A-16 APPENDIX 2 CHAPTER 5 5.1 (b) 3,3-Dimethyl-1-butene; (c) 2-methyl-2-hexene; (d) 4-chloro-1-pentene; (e) 4-penten-2-ol 5.2 5.3 (b) 3-Ethyl-3-hexene; (c) two carbons are sp 2 -hybridized, six are sp 3 -hybridized; (d) there are three sp 2 –sp 3 H9268 bonds and three sp 3 –sp 3 H9268 bonds. 5.4 5.5 5.6 (b) Z; (c) E; (d) E 5.7 5.8 (CH 3 ) 2 C?C(CH 3 ) 2 5.9 2-Methyl-2-butene (most stable) H11022 (E)-2-pentene H11022 (Z)-2-pentene H11022 1-pentene (least sta- ble) 5.10 Bulky tert-butyl groups are cis to one another on each side of the double bond and cause the alkene to be highly strained and unstable. 5.11 (c) (d) CH 3 1 3 2 H H H H CH 3 3 2 1 CH 3 CH 3 CH 2 CH 3 H CC 2-Methyl-2-pentene CH 3 H CH 2 CH 3 CH 3 CC (E)-3-Methyl-2-pentene CH 3 H CH 2 CH 3 CH 3 CC (Z)-3-Methyl-2-pentene CH 3 (CH 2 ) 7 H (CH 2 ) 12 CH 3 H CC 1-Pentene cis-2-Pentene trans-2-Pentene 2-Methyl-1-butene 2-Methyl-2-butene 3-Methyl-1-butene 1-Chlorocyclopentene 1 5 4 3 2 Cl 3-Chlorocyclopentene 2 3 5 1 Cl 4 5 4 3 2 1 Cl 4-Chlorocyclopentene APPENDIX 2 A-17 (e) (f) 5.12 (b) Propene; (c) propene; (d) 2,3,3-trimethyl-1-butene 5.13 (b) (c) 5.14 1-Pentene, cis-2-pentene, and trans-2-pentene 5.15 (b) and (c) and H 2 O HH H11001 H H H H11001 H 3 O H11001 H11001 H H11001 OH 2 OH 3 H11001 OH H H11001 H H 2 OH11001 CH 2 H11001H 3 O H11001 CH 2 H H11001 H 2 O H CH 3 H11001H 3 O H11001 CH 3 H11001 H H H 2 O H 3 C OH CH 3 H11001 H11001 H 2 O Major and H Minor CH 3 Major CH 2 Minor and 1 H CH 3 H 5 2 3 4 H H CH 3 3 2 1 5 4 A-18 APPENDIX 2 5.16 5.17 (b) (CH 3 ) 2 C?CH 2 ; (c) CH 3 CH?C(CH 2 CH 3 ) 2 ; (d) CH 3 CH?C(CH 3 ) 2 (major) and CH 2 ?CHCH(CH 3 ) 2 (minor); (e) CH 2 ?CHCH(CH 3 ) 2 ; (f) 1-methylcyclohexene (major) and methylenecyclohexane (minor) 5.18 CH 2 ?CHCH 2 CH 3 , cis-CH 3 CH?CHCH 3 , and trans-CH 3 CH?CHCH 3 . 5.19 5.20 CHAPTER 6 6.1 2-Methyl-1-butene, 2-methyl-2-butene, and 3-methyl-1-butene 6.2 2-Methyl-2-butene (112 kJ/mol, 26.7 kcal/mol), 2-methyl-1-butene (118 kJ/mol, 28.2 kcal/mol), and 3-methyl-1-butene (126 kJ/mol, 30.2 kcal/mol) 6.3 (b) (c) (d) 6.4 (b) (c) (d) 6.5 6.6 Addition in accordance with Markovnikov’s rule gives 1,2-dibromopropane. Addition oppo- site to Markovnikov’s rule gives 1,3-dibromopropane. 6.7 Absence of peroxides: (b) 2-bromo-2-methylbutane; (c) 2-bromobutane; (d) 1-bromo-1-eth- ylcyclohexane. Presence of peroxides: (b) 1-bromo-2-methylbutane; (c) 2-bromobutane; (d) (1-bro- moethyl)cyclohexane. CH 3 C CH 3 CH 3 CH CH 2 CH 3 C CH 3 CH 3 CHCH 3 H11001 CH 3 C CH 3 CH 3 Cl CHCH 3 CH 3 C CH 3 CH 3 CHCH 3 H11001 CH 3 C CH 3 CH 3 CHCH 3 Cl HCl Cl H11002 Cl H11002 CH 3 shift CH 3 CH 2 H11001 CH 3 CHCH 2 CH 3 H11001 (CH 3 ) 2 CCH 2 CH 3 H11001 Cl CH 3 CH 2 CH 3 CHCH 2 CH 3 Cl (CH 3 ) 2 CCH 2 CH 3 Cl H (CH 3 ) 3 C (CH 3 ) 3 C O H11002 Br H11002 Cl H11002 H11001H 2 C C(CH 3 ) 2 H11001HCH 3 O CH 3 O H CH H C CH 3 CH 3 H11002 Cl CH 3 CH 3 H OH H H11001 H11002H 2 O H11002H H11001 CH 3 H H11001 CH 3 CH 3 H CH 3 H11001 CH 3 CH 3 APPENDIX 2 A-19 6.8 6.9 The concentration of hydroxide ion is too small in acid solution to be chemically sig- nificant. 6.10 is more reactive, because it gives a tertiary carbocation when it is protonated in acid solution. 6.11 E1 6.12 (b) (c) (d) (e) (f) HOCH 2 CH 2 CH(CH 2 CH 3 ) 2 6.13 6.14 6.15 2-Methyl-2-butene (most reactive) H11022 2-methyl-1-butene H11022 3-methyl-1-butene (least reactive) 6.16 (b) (c) (d) 6.17 cis-2-Methyl-7,8-epoxyoctadecane 6.18 cis-(CH 3 ) 2 CHCH 2 CH 2 CH 2 CH 2 CH?CH(CH 2 ) 9 CH 3 6.19 2,4,4-Trimethyl-1-pentene 6.20 6.21 Hydrogenation over a metal catalyst such as platinum, palladium, or nickel CHAPTER 7 7.1 (c) C-2 is a stereogenic center; (d) no stereogenic centers. 7.2 (c) C-2 is a stereogenic center; (d) no stereogenic centers. (CH 3 ) 3 CBr (CH 3 ) 2 CCH 2 (CH 3 ) 2 C OH CH 2 Br NaOCH 2 CH 3 heat Br 2 H 2 O Br CH 3 OH BrCH 2 CHCH(CH 3 ) 2 OH (CH 3 ) 2 C OH Br CHCH 3 Br 82 Br 82 Br H H 3 C H HO H H 3 CCH 3 CH 3 CHCH(CH 2 CH 3 ) 2 OH OH H CH 2 OH CH 3 CHCH 2 CH 3 OH CH 3 CH 3 H11001 CCCH 2 CH 3 Cyclohexene H 2 SO 4 OSO 2 OH Cyclohexyl hydrogen sulfate A-20 APPENDIX 2 7.3 (b) (Z)-1,2-Dichloroethene is achiral. The plane of the molecule is a plane of symmetry. A second plane of symmetry is perpendicular to the plane of the molecule and bisects the carbon- carbon bond. (c) cis-1,2-Dichlorocyclopropane is achiral. It has a plane of symmetry that bisects the C-1±C-2 bond and passes through C-3. (d) trans-1,2-Dichlorocyclopropane is chiral. It has neither a plane of symmetry nor a cen- ter of symmetry. 7.4 [H9251] D H11002 39° 7.5 Two-thirds (66.7%) 7.6 (H11001)-2-Butanol 7.7 (b) R; (c) S; (d) S 7.8 (b) 7.9 (b) (c) (d) 7.10 S 7.11 7.12 2S,3R 7.13 2,4-Dibromopentane 7.14 cis-1,3-Dimethylcyclohexane 7.15 RRR RRS RSR SRR SSS SSR SRS RSS 7.16 Eight 7.17 Epoxidation of cis-2-butene gives meso-2,3-epoxybutane; trans-2-butene gives a racemic mixture of (2R,3R) and (2S,3S)-2,3-epoxybutane. 7.18 No. The major product cis-1,2-dimethylcyclohexane is less stable than the minor product trans-1,2-dimethylcyclohexane. 7.19 7.20 No 7.21 (S)-1-Phenylethylammonium (S)-malate H OH H OH CO 2 H CO 2 H HO H OH H CO 2 H CO 2 H and S S R S Erythro H OH H NH 2 CH 3 CH 3 Erythro HO H H 2 N H CH 3 CH 3 Threo HO H NH 2 H CH 3 CH 3 Threo H 2 N H OH H CH 3 CH 3 H OH CH CH 2 CH 3 H CH 2 Br CH 3 CH 2 CH 3 FCH 2 H CH 3 CH 2 CH 3 F F H 3 C H APPENDIX 2 A-21 CHAPTER 8 8.1 (b) CH 3 OCH 2 CH 3 (c) (d) (e) CH 3 CPN (f) CH 3 SH (g) CH 3 I 8.2 ClCH 2 CH 2 CH 2 CPN 8.3 No 8.4 8.5 Hydrolysis of (R)-(H11002)-2-bromooctane by the S N 2 mechanism yields optically active (S)-(H11001)- 2-octanol. The 2-octanol obtained by hydrolysis of racemic 2-bromooctane is not optically active. 8.6 (b) 1-Bromopentane; (c) 2-chloropentane; (d) 2-bromo-5-methylhexane; (e) 1-bromodecane 8.7 8.8 Product is (CH 3 ) 3 COCH 3 . The mechanism of solvolysis is S N 1. 8.9 (b) 1-Methylcyclopentyl iodide; (c) cyclopentyl bromide; (d) tert-butyl iodide 8.10 Both cis- and trans-1,4-dimethylcyclohexanol are formed in the hydrolysis of either cis- or trans-1,4-dimethylcyclohexyl bromide. 8.11 A hydride shift produces a tertiary carbocation; a methyl shift produces a secondary carbo- cation. 8.12 (b) (c) (d) cis- and trans-CH 3 CH?CHCH 3 and CH 2 ?CHCH 2 CH 3 8.13 8.14 (b) CH 3 (CH 2 ) 16 CH 2 I; (c) CH 3 (CH 2 ) 16 CH 2 CPN; (d) CH 3 (CH 2 ) 16 CH 2 SH; (e) CH 3 (CH 2 ) 16 CH 2 SCH 2 CH 2 CH 2 CH 3 CH 3 CHCH 2 CH 3 OCH 3 OCH 2 CH 3 (CH 3 ) 3 C OCH 3 H H11001 (CH 3 ) 3 C OCH 3 H11002H H11001 H11001 (CH 3 ) 3 C OCH 3 H H11001 (CH 3 ) 3 C H11001 OCH 3 H H11001(CH 3 ) 3 C Br (CH 3 ) 3 C H11001 Br H11002 CH 3 CH(CH 2 ) 5 CH 3 NO 2 CH 3 CH(CH 2 ) 5 CH 3 ONO and HO H CH 3 CH 2 (CH 2 ) 4 CH 3 CH 3 N H11001 N H11002 NCH 3 OC O CH 3 (CH 2 ) 16 CH 2 OH H11001 CH 3 SCl O O pyridine CH 3 (CH 2 ) 16 CH 2 OS O O CH 3 H11001 HCl A-22 APPENDIX 2 8.15 The product has the R configuration and a specific rotation [H9251] D of H110029.9°. 8.16 CHAPTER 9 9.1 9.2 CH 3 CH 2 CH 2 CPCH (1-pentyne), CH 3 CH 2 CPCCH 3 (2-pentyne), (CH 3 ) 2 CHCPCH (3-methyl-1-butyne) 9.3 The bonds become shorter and stronger in the series as the electronegativity increases; N±H longest and weakest, H±F shortest and strongest. 9.4 (b) (c) (d) 9.5 (b) (c) 9.6 Both CH 3 CH 2 CH 2 CPCH and CH 3 CH 2 CPCCH 3 can be prepared by alkylation of acety- lene. The alkyne (CH 3 ) 2 CHCPCH cannot be prepared by alkylation of acetylene, because the required alkyl halide, (CH 3 ) 2 CHBr, is secondary and will react with the strongly basic acetylide ion by elimination. 9.7 (CH 3 ) 3 CCCH 3 Br Br (CH 3 ) 3 CCHCH 2 Br Br (CH 3 ) 3 CCH 2 CHBr 2 or or CH 3 C CCH 2 O H 2-Butyn-1-ol (stronger acid) H11001 NH 2 H11002 Amide ion (stronger base) K H11022H11022 1 CH 3 C CCH 2 O H11002 2-Butyn-1-olate anion (weaker base) H11001 NH 3 Ammonia (weaker acid) CH 2 CH H Ethylene (weaker acid) H11001 NH 2 H11002 Amide ion (weaker base) NH 3 Ammonia (stronger acid) K H11021H11021 1 CH 2 CH H11002 Vinyl anion (stronger base) H11001 HC C H Acetylene (stronger acid) H11001 CH 2 CH 3 H11002 Ethyl anion (stronger base) K H11022H11022 1 HC H11002 C Acetylide ion (weaker base) H11001 Ethane (weaker acid) CH 3 CH 3 H11001C H11002H11002 C Carbide ion C H11002 C H Acetylide ion HOHO Water H11001 HO H11002 Hydroxide ion C H11002 C H Acetylide ion HOHO Water H11001 H O H11002 Hydroxide ion H11001 H C C H Acetylene CH 3 CH 2 C(CH 3 ) 2 Cl H 2 O C H 3 C CH 3 (CH 2 ) 5 H OTs HO C (CH 2 ) 5 CH 3 H CH 3 HC CH CH 3 C CH CH 3 C CCH 2 CH 2 CH 2 CH 3 1. NaNH 2 , NH 3 2. CH 3 Br 1. NaNH 2 , NH 3 2. CH 3 CH 2 CH 2 CH 2 Br HC CH CH 3 CH 2 CH 2 C CH CH 3 CH 2 CH 2 C CCH 2 CH 3 1. NaNH 2 , NH 3 2. CH 3 CH 2 Br 1. NaNH 2 , NH 3 2. CH 3 CH 2 CH 2 Br APPENDIX 2 A-23 9.8 (b) (c) ; then proceed as in parts (a) and (b). (d) (e) ; then pro- ceed as in part (d). 9.9 or 9.10 Oleic acid is cis-CH 3 (CH 2 ) 7 CH?CH(CH 2 ) 7 CO 2 H. Stearic acid is CH 3 (CH 2 ) 16 CO 2 H. 9.11 Elaidic acid is trans-CH 3 (CH 2 ) 7 CH?CH(CH 2 ) 7 CO 2 H. 9.12 9.13 (b) (c) 9.14 O H H O H11001 H H H CH 3 CH 2 CCH 3 O H11001H11001CH 3 CH 2 H11001 O CCH 3 H O H H H11001 H O H H CH 3 CH OH CCH 3 H11001H11001 CH 3 CH 2 H11001 OH CCH 3 CH 3 C CCH 3 H 2 O, Hg 2H11001 H 2 SO 4 CH 3 C OH CHCH 3 CH 3 CCH 2 CH 3 O CH 3 CHCl 2 CH 3 CHBr 2 2HCl1. NaNH 2 , NH 3 2. H 2 O HC CH CH 3 CHCl 2 CH 2 CHCl HCl CH 3 C CH CH 3 C CCH 2 CH 2 CH 2 CH 3 1. NaNH 2 , NH 3 2. CH 3 CH 2 CH 2 CH 2 Br H 2 Lindlar Pd Li, NH 3 C H H CH 2 CH 2 CH 2 CH 3 C H 3 C C HH CH 2 CH 2 CH 2 CH 3 C H 3 C HC CH CH 3 (CH 2 ) 5 C CH CH 3 (CH 2 ) 6 CH 3 1. NaNH 2 , NH 3 2. CH 3 (CH 2 ) 5 Br H 2 Pt HC CH CH 3 CH 2 CH 2 C CH CH 3 CH 2 CH 2 C CCH 2 CH 2 CH 3 CH 3 (CH 2 ) 6 CH 3 1. NaNH 2 , NH 3 2. CH 3 CH 2 CH 2 Br 1. NaNH 2 , NH 3 2. CH 3 CH 2 CH 2 Br H 2 Pt CH 3 CH 2 OH BrCH 2 CH 2 Br H 2 SO 4 heat CH 2 CH 2 Br 2 1. NaNH 2 2. H 2 O HC CH CH 3 CHCl 2 1. NaNH 2 2. H 2 O HC CH CH 3 C CH 1. NaNH 2 2. CH 3 Br (CH 3 ) 2 CHBr CH 3 CH CH 2 NaOCH 2 CH 3 CH 3 CH 2 CH 2 OH CH 3 CH CH 2 CH 3 C CH H 2 SO 4 heat Br 2 1. NaNH 2 2. H H11001 CH 3 CHCH 2 Br Br A-24 APPENDIX 2 9.15 2-Octanone is prepared as shown: 4-Octyne is prepared as described in Problem 9.9 and converted to 4-octanone by hydration with H 2 O, H 2 SO 4 , and HgSO 4 . 9.16 CH 3 (CH 2 ) 4 CPCCH 2 CH 2 CPC(CH 2 ) 4 CH 3 CHAPTER 10 10.1 (b) (c) 10.2 10.3 (b) (c) 10.4 (Propagation step 1) (Propagation step 2) 10.5 2,3,3-Trimethyl-1-butene gives only . 1-Octene gives a mixture of as well as the cis and trans stereoisomers of BrCH 2 CH?CH(CH 2 ) 4 CH 3 . 10.6 (b) All the double bonds in humulene are isolated. (c) Two of the double bonds in cembrene are conjugated to each other but isolated from the remaining double bonds in the molecule. (d) The CH?C?CH unit is a cumulated double bond; it is conjugated to the double bond at C-2. 10.7 1,2-Pentadiene (3251 kJ/mol, 777.1 kcal/mol); (E)-1,3-pentadiene (3186 kJ/mol, 761.6 kcal/mol); 1,4-pentadiene (3217 kJ/mol, 768.9 kcal/mol) Br CHCH(CH 2 ) 4 CH 3 CH 2 (CH 3 ) 3 CC CH 2 Br CH 2 Br H H11001H H11001Br Br Br H H H11001 Br H H11001 H Br Allylic CH 3CH3 H H H H Allylic Allylic Allylic Allylic CH 3 Br and CH 3 Cl H11001 C(CH 3 ) 2 C(CH 3 ) 2 H11001 CH 2 CH 3 H11001 C CH 2 CH 2 CH 3 C CH 2 H11001 HC CH CH 3 (CH 2 ) 4 CH 2 C CH 1. NaNH 2 , NH 3 2. CH 3 (CH 3 ) 4 CH 2 Br H 2 O, H 2 SO 4 HgSO 4 CH 3 (CH 2 ) 4 CH 2 CCH 3 O (d) AllylicAllylic HH APPENDIX 2 A-25 10.8 2-Methyl-2,3-pentadiene is achiral. 2-Chloro-2,3-pentadiene is chiral. 10.9 10.10 10.11 3,4-Dibromo-3-methyl-1-butene; 3,4-dibromo-2-methyl-1-butene; and 1,4-dibromo-2- methyl-2-butene 10.12 10.13 (b) CH 2 ?CHCH?CH 2 H11001 cis-NPCCH?CHCPN (c) 10.14 10.15 H9266 10.16 There is a mismatch between the ends of the HOMO of one 1,3-butadiene molecule and the LUMO of the other (Fig. 10.9). The reaction is forbidden. CHAPTER 11 11.1 (a) (b) 11.2 1,3,5-Cycloheptatriene resonance energy H11005 25 kJ/mol (5.9 kcal/mol). It is about six times smaller than the resonance energy of benzene. 11.3 (b) (c) NH 2 NO 2 Cl CH CH 2 CH 3 CO 2 HCH 3 CH 3 CO 2 H CO 2 H COCH 3 O H H O COCH 3 and CH 3 CH CH 2 CHCH H11001 O O O Cl O O H H (CH 3 ) 2 CCH Cl CH 2 CHCH 2 C CH 3 CH 2 CHCH 3 CHCH 2 CCH 2 CH 3 CH 2 CH 2 and(cis H11001 trans) A-26 APPENDIX 2 11.4 11.5 11.6 (b) 11.7 11.8 (b) C 6 H 5 CH 2 OC(CH 3 ) 3 (c) (d) C 6 H 5 CH 2 SH (e) C 6 H 5 CH 2 I 11.9 1,2-Dihydronaphthalene, 101 kJ/mol (24.1 kcal/mol); 1,4-dihydronaphthalene, 113 kJ/mol (27.1 kcal/mol) 11.10 (b) (c) (d) 11.11 Styrene, 4393 kJ/mol (1050 kcal/mol); cyclooctatetraene, 4543 kJ/mol (1086 kcal/mol) 11.12 Diels–Alder reaction 11.13 (b) Five doubly occupied bonding orbitals plus two half-filled nonbonding orbitals plus five vacant antibonding orbitals 11.14 Divide the heats of combustion by the number of carbons. The two aromatic hydrocarbons (benzene and [18]-annulene) have heats of combustion per carbon that are less than those of the nonaromatic hydrocarbons (cyclooctatetraene and [16]-annulene). On a per carbon basis, the aromatic hydrocarbons have lower potential energy (are more stable) than the nonaromatic hydrocarbons. 11.15 C 6 H 5 CH CH 2 O H11001 C 6 H 5 CO 2 HC 6 H 5 CHCH 2 Br OH C 6 H 5 CHCH 2 OH CH 3 NC 6 H 5 CH 2 N N H11002 H11001 CO 2 H CO 2 H (CH 3 ) 3 C OCH 3 O 2 N BrCH 2 CH 3 CH 3 H H H H H H H H11001 H H H H H H H H11001 H H H H H H H H11001 H H H H H H H H11001 H H H H H H H H11001 H H H H H H H H11001 H H H H H H H H11001 APPENDIX 2 A-27 11.16 11.17 11.18 (b) Cyclononatetraenide anion is aromatic. 11.19 Indole is more stable than isoindole. 11.20 11.21 CHAPTER 12 12.1 The positive charge is shared by the three carbons indicated in the three most stable reso- nance structures: Provided that these structures contribute equally, the resonance picture coincides with the MO treat- ment in assigning one third of a positive charge (H11001 0.33) to each of the indicated carbons. H H H H H HH H11001 H H H H H HH H11001 H H H H H HH H11001 H 3 O H11001 N N H N H N H11001 H N O Benzoxazole N S Benzothiazole N H Indole: more stable Isoindole: less stable NH Six-membered ring corresponds to benzene. Six-membered ring does not have same pattern of bonds as benzene. NH 3 H11001 H11002 HNH 2 H11002 H H H11001 H H H H H H11002 H H H H H H11002 H H H H H H11002 H H H H H H11002 H H H H H H11002 A-28 APPENDIX 2 12.2 12.3 12.4 The major product is isopropylbenzene. Ionization of 1-chloropropane is accompanied by a hydride shift to give , which then attacks benzene. 12.5 12.6 12.7 12.8 O CCH 2 CH 2 COH O OCH 3 OCH 3 CH 3 O O CCH 2 CH(CH 3 ) 2 H11001 H 2 SO 4 benzoyl peroxide, heat NBS NaOCH 2 CH 3 heat Br H H H H H H H11001 H H H H H H H H H H H11001 H11001 H H H H H H H11001 H H H H H H H H H H H11001 H H H11001H11001H OSO 2 OH H11002 OSO 2 OH CH 3 CHCH 3 H11001 CH 3 CH 3 H 3 C H 3 C SO 3 H NO 2 CH 3 CH 3 APPENDIX 2 A-29 12.9 (b) Friedel–Crafts acylation of benzene with , followed by reduction with Zn(Hg) and hydrochloric acid 12.10 (b) Toluene is 1.7 times more reactive than tert-butylbenzene. (c) Ortho (10%), meta (6.7%), para (83.3%) 12.11 12.12 (b) (c) 12.13 12.14 (b) (c) 12.15 The group ± H11001 N(CH 3 ) 3 is strongly deactivating and meta-directing. Its positively charged nitrogen makes it a powerful electron-withdrawing substituent. It resembles a nitro group. 12.16 12.17 (b) (c) (d) (e) (f) OCH 3 BrBr NO 2 OCH 3 NO 2 CH 3 OCH 3 NO 2 CH 3 C O NO 2 NO 2 O 2 N NO 2 Cl Cl CH 2 Cl Cl and Cl CH 2 Cl O 2 N CCH 2 CH 3 O O 2 N COCH 3 O and O 2 N NO 2 H11001 NH 2 BrH H11001 NH 2 BrH H11001 NH 2 BrH H11001 NH 2 BrH H11001 NH 2 Br H H11001 NH 2 Br H H11001 NH 2 Br H CH 2 Cl Deactivating ortho, para-directing CHCl 2 Deactivating ortho, para-directing CCl 3 Deactivating meta-directing (CH 3 ) 3 CCCl O A-30 APPENDIX 2 12.18 m-Bromonitrobenzene: p-Bromonitrobenzene: 12.19 12.20 The hydrogen at C-8 (the one shown in the structural formulas) crowds the ±SO 3 H group in the less stable isomer. 12.21 CHAPTER 13 13.1 1.41 T 13.2 25.2 MHz 13.3 (a) 6.88 ppm; (b) higher field; more shielded 13.4 H in CH 3 CCl 3 is more shielded than H in CHCl 3 . If H in CHCl 3 appears at H9254 7.28 ppm, then H in CH 3 CCl 3 appears 4.6 ppm upfield of 7.28 ppm. Its chemical shift is H9254 2.7 ppm. 13.5 The chemical shift of the methyl protons is H9254 2.2 ppm. The chemical shift of the protons attached to the aromatic ring is H9254 7.0 ppm. 13.6 (b) Five; (c) two; (d) two; (e) three; (f) one; (g) four; (h) three 13.7 (b) One; (c) one; (d) one; (e) four; (f) four 13.8 (b) One signal (singlet); (c) two signals (doublet and triplet); (d) two signals (both singlets); (e) two signals (doublet and quartet) 13.9 (b) Three signals (singlet, triplet, and quartet); (c) two signals (triplet and quartet); (d) three signals (singlet, triplet, and quartet); (e) four signals (three triplets and quartet) SO 3 H S Formed faster H SO 3 H More stable H SO 3 H H11001 CO 2 H NO 2 CO 2 HCH 3 Na 2 Cr 2 O 7 H 2 SO 4 , H 2 O, heat HNO 3 H 2 SO 4 Br Br NO 2 Br NO 2 HNO 3 H 2 SO 4 Br 2 FeBr 3 H11001 NO 2 Br NO 2 HNO 3 H 2 SO 4 Br 2 FeBr 3 APPENDIX 2 A-31 13.10 Both H b and H c appear as doublets of doublets: 13.11 (b) The signal for the proton at C-2 is split into a quartet by the methyl protons, and each line of this quartet is split into a doublet by the aldehyde proton. It appears as a doublet of quar- tets. 13.12 (b) Six; (c) six; (d) nine; (e) three 13.13 13.14 1,2,4-Trimethylbenzene 13.15 Benzyl alcohol. Infrared spectrum has peaks for O±H and sp 3 C±H; lacks peak for C?O. 13.16 HOMO–LUMO energy difference in ethylene is greater than that of cis,trans-1,3-cycloocta- diene. 13.17 2-Methyl-1,3-butadiene 13.18 (b) Three peaks (m/z 146, 148, and 150); (c) three peaks (m/z 234, 236, and 238); (d) three peaks (m/z 190, 192, and 194) 13.19 13.20 (b) 3; (c) 2; (d) 3; (e) 2; (f) 2 CHAPTER 14 14.1 (b) Cyclohexylmagnesium chloride 14.2 (b) 14.3 (b) CH 2 ?CHCH 2 MgCl (c) (d) MgBrMgI H11001 2Li H11001 LiBrCH 3 CHCH 2 CH 3 Br CH 3 CHCH 2 CH 3 Li CH 3 H 3 C CH 2 CH 3 Base peak C 9 H 11 H11001 (m/z 119) CH 3 CH 2 CH 2 CH 3 Base peak C 8 H 9 H11001 (m/z 105) CH 3 CH CH 3 H 3 C Base peak C 9 H 11 H11001 (m/z 119) OCH 3 H 3 C H9254 20 ppm H9254 55 ppm H9254 157 ppm C O 2 N C H c H b H a H b 12 Hz 2 Hz 16 Hz 2 Hz H c 2 Hz 2 Hz 14.4 (b) CH 3 (CH 2 ) 4 CH 2 OH H11001 CH 3 CH 2 CH 2 CH 2 Li ±￡ CH 3 CH 2 CH 2 CH 3 H11001 CH 3 (CH 2 ) 4 CH 2 OLi (c) C 6 H 5 SH H11001 CH 3 CH 2 CH 2 CH 2 Li ±￡ CH 3 CH 2 CH 2 CH 3 H11001 C 6 H 5 SLi A-32 APPENDIX 2 14.5 (b) (c) (d) 14.6 14.7 (b) and 14.8 (b) 14.9 (b) 14.10 (b) 14.11 14.12 Fe(CO) 5 CHAPTER 15 15.1 The primary alcohols CH 3 CH 2 CH 2 CH 2 OH and (CH 3 ) 2 CHCH 2 OH can each be prepared by hydrogenation of an aldehyde. The secondary alcohol can be prepared by hydro- genation of a ketone. The tertiary alcohol (CH 3 ) 3 COH cannot be prepared by hydrogenation. 15.2 (b) (c) (d) DCH 2 OD 15.3 15.4 (b) MgBr O CH 3 CH 2 COCH(CH 3 ) 2 C 6 H 5 COH D H CH 3 CCH 3 D OD CH 3 CHCH 2 CH 3 OH cis-2-Butene Br CH 3 CH 3 H H Br trans-2-Butene Br CH 3 H H CH 3 Br CH 2 LiCu(CH 3 ) 2 H11001 Br CH 3 CH 3 COCH 2 CH 3 O H110012C 6 H 5 MgBr H11001C 6 H 5 MgBr O CH 3 CCH 3 1. diethyl ether 2. H 3 O H11001 C 6 H 5 CCH 3 CH 3 OH H11001CH 3 MgI O C 6 H 5 CCH 3 1. diethyl ether 2. H 3 O H11001 C 6 H 5 CCH 3 CH 3 OH H11001H11001CH 3 CH 2 H11002 Ethyl anion H CCCH 2 CH 2 CH 2 CH 3 1-Hexyne C H11002 CCH 2 CH 2 CH 2 CH 3 Conjugate base of 1-hexyneEthane CH 3 CH 3 CH 3 CH 2 CH 2 COH CH 3 CH 3 CH 2 CH 2 CH 2 CH 3 OH C 6 H 5 CHCH 2 CH 2 CH 3 OH APPENDIX 2 A-33 15.5 15.6 cis-2-Butene yields the meso stereoisomer of 2,3-butanediol: trans-2-Butene gives equal quantities of the two enantiomers of the chiral diol: 15.7 Step 1: Step 2: Step 3: 15.8 (b) CH 3 OC O O COCH 3 O H O H11001 H11001H11001 OSO 2 OH H11002 OSO 2 OHH H H O H11001 O H H O H11001 H11001 H 2 O H CH 3 H H 3 C OsO 4 , (CH 3 ) 3 COOH (CH 3 ) 3 COH, HO H11002 H OH HHO CH 3 CH 3 H OH HHO CH 3 CH 3 H11001 H CH 3 CH 3 H OsO 4 , (CH 3 ) 3 COOH (CH 3 ) 3 COH, HO H11002 H OH OHH CH 3 CH 3 O O CH 3 CH 3 OCCH 2 CHCH 2 COCH 3 CH 3 HOCH 2 CH 2 CHCH 2 CH 2 OH 2CH 3 OHH11001 1. LiAlH 4 2. H 2 O O O CH 3 HOCCH 2 CHCH 2 COH CH 3 HOCH 2 CH 2 CHCH 2 CH 2 OH 1. LiAlH 4 2. H 2 O HOCH 2 CH 2 CH 2 CH 2 CH 2 OH HOCH 2 CH 2 CH 2 CH 2 CH 2 H H H11001 OH11001 OSO 2 OHH OSO 2 OH H11002 H11001 A-34 APPENDIX 2 15.9 15.10 15.11 (b) (c) 15.12 (b) One; (c) none 15.13 (b) (c) 15.14 15.15 15.16 The peak at m/z 70 corresponds to loss of water from the molecular ion. The peaks at m/z 59 and 73 correspond to the cleavages indicated: CHAPTER 16 16.1 (b) (c) 16.2 1,2-Epoxybutane, 2546 kJ/mol (609.1 kcal/mol); tetrahydrofuran, 2499 kJ/mol (597.8 kcal/mol) 16.3 O R R R O H H 2 C CHCH CH 2 O H 2 C CHCH 2 Cl O 59 OH CCH 3 CH 2 CH 3 CH 3 73 H11001 C H H CH 2 SH C H 3 C trans-2-Butene-1-thiol CH 3 CHCH 2 CH 2 SH CH 3 3-Methyl-1-butanethiol C HH CH 2 SH C H 3 C cis-2-Butene-1-thiol CH 3 (CH 2 ) 4 CH 2 OH 1-Hexanol CH 3 (CH 2 ) 4 CH 2 Br 1-Bromohexane CH 3 (CH 2 ) 4 CH 2 SH 1-Hexanethiol HBr heat 1. (H 2 N) 2 C?S 2. NaOH HCH O O H11001(CH 3 ) 2 CHCH 2 CH O C 6 H 5 CH 2 CH O H11001 CH 3 (CH 2 ) 5 CH O CH 3 C(CH 2 ) 5 CH 3 O O 2 NOCH 2 CHCH 2 ONO 2 ONO 2 acetic anhydride (CH 3 ) 3 C OH (CH 3 ) 3 C OCCH 3 O acetic anhydride (CH 3 ) 3 C OH (CH 3 ) 3 C OCCH 3 O APPENDIX 2 A-35 16.4 1,4-Dioxane 16.5 16.6 C 6 H 5 CH 2 ONa H11001 CH 3 CH 2 Br ±￡ C 6 H 5 CH 2 OCH 2 CH 3 H11001 NaBr and CH 2 CH 2 ONa H11001 C 6 H 5 CH 2 Br ±￡ C 6 H 5 CH 2 OCH 2 CH 3 H11001 NaBr 16.7 (b) (CH 3 ) 2 CHONa H11001 CH 2 ?CHCH 2 Br ±￡ CH 2 ?CHCH 2 OCH(CH 3 ) 2 H11001 NaBr (c) (CH 3 ) 3 COK H11001 C 6 H 5 CH 2 Br ±￡ (CH 3 ) 3 COCH 2 C 6 H 5 H11001 KBr 16.8 CH 3 CH 2 OCH 2 CH 3 H11001 6O 2 ±￡ 4CO 2 H11001 5H 2 O 16.9 (b) C 6 H 5 CH 2 OCH 2 C 6 H 5 (c) 16.10 16.11 Only the trans epoxide is chiral. As formed in this reaction, neither product is optically active. 16.12 (b) N 3 CH 2 CH 2 OH (c) HOCH 2 CH 2 OH (d) C 6 H 5 CH 2 CH 2 OH (e) CH 3 CH 2 CPCCH 2 CH 2 OH 16.13 Compound B 16.14 Compound A 16.15 trans-2-Butene gives meso-2,3-butanediol on epoxidation followed by acid-catalyzed hydrolysis. cis-2-Butene gives meso-2,3-butanediol on osmium tetraoxide hydroxylation. 16.16 The product has the S configuration. 16.17 Phenyl vinyl sulfoxide is chiral. Phenyl vinyl sulfone is achiral. 16.18 CH 3 SCH 3 H11001 CH 3 (CH 2 ) 10 CH 2 I will yield the same sulfonium salt. This combination is not as effective as CH 3 I H11001 CH 3 (CH 2 ) 10 CH 2 SCH 3 , because the reaction mechanism is S N 2 and CH 3 I is more reactive than CH 3 (CH 2 ) 10 CH 2 I in reactions of this type because it is less crowded. 16.19 CH 2 OCHCH 2 CH 3 CH 3 H11001 C 6 H 5 S H CH 3 (CH 2 ) 5 CH 3 C H11001H11001I OH 2 H11001 H11002 I I I H 2 O H11001H11001I OH I OH 2 H11001 IH H11002 I H11001 OH H11001 I H11002 I OH H11001H11001O OH H11001 IH H11002 I O H H11001 H11002H H11001HOCH 3 (CH 3 ) 2 C CH 2 (CH 3 ) 2 C CH 3 H11001 (CH 3 ) 3 C H OCH 3 H11001 (CH 3 ) 3 COCH 3 A-36 APPENDIX 2 CHAPTER 17 17.1 (b) Pentanedial; (c) 3-phenyl-2-propenal; (d) 4-hydroxy-3-methoxybenzaldehyde 17.2 (b) 2-Methyl-3-pentanone; (c) 4,4-dimethyl-2-pentanone; (d) 4-penten-2-one 17.3 No. Carboxylic acids are inert to catalytic hydrogenation. 17.4 17.5 Cl 3 CCH(OH) 2 17.6 17.7 Step 1: Step 2: Step 3: Formation of the hemiacetal is followed by loss of water to give a carbocation. Step 4: Step 5: Step 6: C 6 H 5 CH O H11001 HCH 3 CH 2 OCH 2 CH 3 C 6 H 5 CH H11001 OCH 2 CH 3 H11001 O H CH 2 CH 3 C 6 H 5 CH O H11001 HH OCH 2 CH 3 C 6 H 5 CH H11001 OCH 2 CH 3 H11001 HHO C 6 H 5 CH OH H11001 O H CH 2 CH 3 C 6 H 5 CH H11001 O H O H CH 2 CH 3 H11001 C 6 H 5 CH O C 6 H 5 CH O H11001 H H11001 H H11001 O H CH 2 CH 3 O H CH 2 CH 3 H11001 CH 2 CC N CH 3 O CH 3 COH O CH 3 CHCH 3 CH 2 OH 1. LiAlH 4 2. H 2 O PCC CH 2 Cl 2 O CH 3 CH OH CH 3 CHCH 2 CH 3 O CH 3 CCH 2 CH 3 CH 3 CH 2 MgBr H11001 1. diethyl ether 2. H 3 O H11001 PCC CH 2 Cl 2 CH 3 CH 2 OH CH 3 CH 2 MgBrCH 3 CH 2 Br HBr heat Mg diethyl ether C 6 H 5 CH OH OCH 2 CH 3 C 6 H 5 CH OH H11001 O H CH 2 CH 3 O H CH 2 CH 3 H11001 H11001 H11001 O H CH 2 CH 3 H C 6 H 5 C HO H OCH 2 CH 3 H11001 H11001 O H CH 2 CH 3 H C 6 H 5 C HOH H H11001 OCH 2 CH 3 H11001 O H CH 2 CH 3 APPENDIX 2 A-37 Step 7: 17.8 (b) (c) (d) 17.9 Step 1: Step 2: Step 3: Step 4: Step 5: Step 6: Step 7: C 6 H 5 CH O H11001C 6 H 5 CH H11001 O H O H CH 2 CH 3 H11001 H11001 O H CH 2 CH 3 H C 6 H 5 CH OH H11001 O H CH 2 CH 3 C 6 H 5 CH H11001 O H O H CH 2 CH 3 H11001 O H H C 6 H 5 CH H11001 OCH 2 CH 3 H11001 C 6 H 5 CH O H11001 HH OCH 2 CH 3 C 6 H 5 CH O H11001 HCH 3 CH 2 OCH 2 CH 3 O H CH 2 CH 3 C 6 H 5 CH H11001 OCH 2 CH 3 H11001 CH 3 (CH 3 ) 2 CHCH 2 CH 3 H 3 C OO CH 3 (CH 3 ) 2 CHCH 2 O O HC 6 H 5 OO C 6 H 5 CH OCH 2 CH 3 OCH 2 CH 3 C 6 H 5 CH O H11001 HCH 3 CH 2 OCH 2 CH 3 H11001H11001O H CH 2 CH 3 H11001 O H CH 2 CH 3 H C 6 H 5 CH OCH 2 CH 3 OCH 2 CH 3 C 6 H 5 CH O H11001 HCH 3 CH 2 OCH 2 CH 3 H11001H11001 O H CH 2 CH 3 H11001 O H CH 2 CH 3 H C 6 H 5 C O H11001 HH H OCH 2 CH 3 H11001 H11001 O H CH 2 CH 3 HH11001O H CH 2 CH 3 C 6 H 5 C HO H OCH 2 CH 3 C 6 H 5 CH OH OCH 2 CH 3 C 6 H 5 CH OH H11001 O H CH 2 CH 3 O H CH 2 CH 3 H11001H11001 H11001 O H CH 2 CH 3 H A-38 APPENDIX 2 17.10 17.11 (b) (c) (d) 17.12 (b) (c) 17.13 (b) CH 3 CH 2 CH 2 CH?CHCH?CH 2 (c) 17.14 (C 6 H 5 ) 3 P?CH 2 17.15 (b) 17.16 CH 3 CCH 2 CH 3 H11002 H11001 P(C 6 H 5 ) 3 CH 3 CHCH 2 CH 3 H11001 P(C 6 H 5 ) 3 Br H11002 NaCH 2 SCH 3 DMSO O X CH 3 CHCH 2 CH 3 Br CH 3 CHCH 2 CH 3 H11001 P(C 6 H 5 ) 3 Br H11002 H11001 (C 6 H 5 ) 3 P O CH 3 CH 2 CH 2 CH O HCHorH11001H11001(C 6 H 5 ) 3 P H11001 H11002 CH 2 CH 3 CH 2 CH 2 CH H11001 P(C 6 H 5 ) 3 H11002 CCH 3 CH 2 N C 6 H 5 CCH 3 OH N C 6 H 5 C CH 2 CH 3 CH 2 CCH 2 CH 3 N OH N CH 3 CH CCH 2 CH 3 C 6 H 5 C OH CH 3 NH C 6 H 5 C CH 3 N OH NHC(CH 3 ) 3 NC(CH 3 ) 3 C 6 H 5 CHNHCH 2 CH 2 CH 2 CH 3 OH C 6 H 5 CH NCH 2 CH 2 CH 2 CH 3 C O O CH 3 COH O C O O CH 3 CH 2 OH 1. LiAlH 4 2. H 2 O H 2 O H H11001 , heat HOCH 2 CH 2 OH H H11001 , heat CH 3 C COH OO CH 3 C CH 2 OH O APPENDIX 2 A-39 17.17 17.18 Hydrogen migrates to oxygen (analogous to a hydride shift in a carbocation). CHAPTER 18 18.1 (b) Zero; (c) five; (d) four 18.2 18.3 18.4 18.5 (b) (c) 18.6 (b) 18.7 (b) (c) CH O O H11002 CH O O H11002CH O O H11002 C 6 H 5 CCH O CCH 3 O H11002 C 6 H 5 CCHCCH 3 H11002 O O C 6 H 5 C CHCCH 3 OO H11002 C 6 H 5 CCH O CCH 3 HO C 6 H 5 C CHCCH 3 OOH and OH CH 3 and OH CH 3 C 6 H 5 C CH 2 OH CH 2 CCH 2 CH 3 OH CH 3 C CHCH 3 OH Cl 2 Cl 2 O ClCH 2 CCH 2 CH 3 O CH 3 CCHCH 3 Cl O ClCH 2 CCH 2 CH 3 O CH 3 CCHCH 3 Cl and HOC O H11001O C CH 3 O O H O CH 3 C OC O CCH 3 O H11001 COOH O C OH OOC O CH 3 Cl H11002 H11001CH 2 CCH 2 CH 3 Cl Cl OH ClCH 2 CCH 2 CH 3 Cl H11002 H11001 OH CH 3 C OH Cl Cl CHCH 3 H11001 OH CH 3 CCHCH 3 Cl A-40 APPENDIX 2 18.8 Hydrogen–deuterium exchange at H9251 carbons via enolate: 18.9 Product is chiral, but is formed as a racemic mixture because it arises from an achiral inter- mediate (the enol); it is therefore not optically active. 18.10 (b) (c) 18.11 (b) (c) 18.12 18.13 (b) (c) 18.14 18.15 Acrolein (CH 2 ?CHCH?O) undergoes conjugate addition with sodium azide in aqueous solution to give N 3 CH 2 CH 2 CH?O. Propanal is not an H9251,H9252-unsaturated carbonyl compound and cannot undergo conjugate addition. 18.16 18.17 CHAPTER 19 19.1 (b) (E)-2-butenoic acid; (c) ethanedioic acid; (d) p-methylbenzoic acid or 4-methylbenzoic acid. CH 3 CH 2 CH 2 CH 2 CH O CHCCH 3 LiCu(CH 3 ) 2 H11001 O C 6 H 5 CH 2 CCHC 6 H 5 O CH 2 CH 2 CCH 3 and C 6 H 5 C 6 H 5 H H 3 C HO O O CH 3 CCH 2 CCH 3 CH 2 O C 6 H 5 CHC 6 H 5 CH O CHCC(CH 3 ) 3 CH 3 CH 2 CH 2 CH O CH 2 CH 3 CCH NaOH H 2 O, heat H 2 Pt O CH 3 CH 2 CH 2 CH CH 3 CH 2 CH 2 CH 2 CHCH 2 OH CH 2 CH 3 (CH 3 ) 2 CHCH 2 CH HC CCH(CH 3 ) 2 O CH 3 CH 2 CHCH HO CH 3 CH 3 HC CCH 2 CH 3 O Cannot dehydrate; no protons on H9251-carbon atom H9251 (CH 3 ) 2 CHCH 2 CH OH HC CHCH(CH 3 ) 2 O CH 3 CH 2 CHCH HO CH 3 CH 3 HC CCH 2 CH 3 O CH 2 CCH 3 CH 3 O CH 3 O O CD 2 CCD 3 CH 3 O CH 3 O O 5D 2 OH11001 K 2 CO 3 APPENDIX 2 A-41 19.2 The negative charge in cannot be delocalized into the carbonyl group. 19.3 (b) CH 3 CO 2 H H11001 (CH 3 ) 3 CO H11002 BA CH 3 CO 2 H11002 H11001 (CH 3 ) 3 COH (The position of equilibrium lies to the right.) (c) CH 3 CO 2 H H11001 Br H11002 BA CH 3 CO 2 H11002 H11001 HBr (The position of equilibrium lies to the left.) (d) CH 3 CO 2 H H11001 HCPC : H11002 BA CH 3 CO 2 H11002 H11001 HCPCH (The position of equilibrium lies to the right.) (e) CH 3 CO 2 H H11001 NO 3 H11002 BA CH 3 CO 2 H11002 H11001 HNO 3 (The position of equilibrium lies to the left.) (f) CH 3 CO 2 H H11001 H 2 N H11002 BA CH 3 CO 2 H11002 H11001 NH 3 (The position of equilibrium lies to the right.) 19.4 (b) (c) (d) 19.5 HCPCCO 2 H 19.6 The “true K 1 ” for carbonic acid is 1.4 H11003 10 H110024 . 19.7 (b) The conversion proceeding by way of the nitrile is satisfactory. Since 2-chloroethanol has a proton bonded to oxygen, it is not an appropriate substrate for con- version to a stable Grignard reagent. (c) The procedure involving a Grignard reagent is satisfactory. The reaction of tert-butyl chloride with cyanide ion proceeds by elimination rather than substi- tution. 19.8 Water labeled with 18 O adds to benzoic acid to give the tetrahedral intermediate shown. This intermediate can lose unlabeled H 2 O to give benzoic acid containing 18 O. 19.9 (b) HOCH 2 (CH 2 ) 13 CO 2 H; (c) 19.10 CH 3 (CH 2 ) 15 CHCO 2 H Br CH 3 (CH 2 ) 15 CHCO 2 H I NaI acetone Br 2 PCl 3 CH 3 (CH 2 ) 15 CH 2 CO 2 H HOCH 2 CH OH CH 2 HO 2 C H 2 C H OH CO 2 H CH 2 C 6 H 5 C OH OH 18 OH C 6 H 5 C O 18 OH H11002H 2 O H11002H 2 O 18 O C 6 H 5 COH Mg 1. CO 2 2. H 3 O H11001 (CH 3 ) 3 CCl (CH 3 ) 3 CMgCl (CH 3 ) 3 CCO 2 H NaCN hydrolysis HOCH 2 CH 2 Cl HOCH 2 CH 2 CN HOCH 2 CH 2 CO 2 H O CH 3 SCH 2 CO 2 H O O CH 3 CCO 2 H OH CH 3 CHCO 2 H O CH 3 COO H11002 A-42 APPENDIX 2 19.11 (b) (c) 19.12 (b) CHAPTER 20 20.1 (b) (c) (d) (e) (f) (g) 20.2 Rotation about the carbon–nitrogen bond is slow in amides. The methyl groups of N,N- dimethylformamide are nonequivalent because one is cis to oxygen, the other cis to hydrogen. 20.3 (b) (c) (d) (e) (f) 20.4 (b) O C 6 H 5 COCC 6 H 5 O C 6 H 5 COCC 6 H 5 Cl OO H H11001 HCl O C 6 H 5 COH O C 6 H 5 CN(CH 3 ) 2 O C 6 H 5 CNHCH 3 O C 6 H 5 COCH 2 CH 3 O C 6 H 5 COCC 6 H 5 O C 6 H 5 CH 3 CH 2 CHC N O C 6 H 5 CH 3 CH 2 CHCNHCH 2 CH 3 O C 6 H 5 CH 3 CH 2 CHCNH 2 O CH 3 CH 2 CH 2 COCH 2 CHCH 2 CH 3 C 6 H 5 O C 6 H 5 CH 3 CH 2 CHCOCH 2 CH 2 CH 2 CH 3 O C 6 H 5 CH 3 CH 2 CHCOCCHCH 2 CH 3 C 6 H 5 O H11002CO 2 CH 3 CCH(CH 3 ) 2 O CH 3 C C OH CH 3 CH 3 C C O H O CH 3 C O CH 3 H 3 C CH 3 C 6 H 5 CHCO 2 H via C OH O C O H O C CH 3 CH 3 (CH 2 ) 6 CH 2 CO 2 H via CH 3 (CH 2 ) 6 CH C HO C H O O O APPENDIX 2 A-43 (c) (d) (e) (f) 20.5 20.6 20.7 (b) (c) (d) CO H11002 Na H11001 CO H11002 Na H11001 O O CN(CH 3 ) 2 CO H11002 O O H 2 N(CH 3 ) 2 H11001 O CH 3 CNH 2 H11001 CH 3 CO 2 H11002 H11001 NH 4 CH 3 C O H11001 CH 3 C O H11001 O C 6 H 5 COCC 6 H 5 OO C 6 H 5 COH O C 6 H 5 CCl H11001 HClH11001 O C 6 H 5 COH O C 6 H 5 CCl H11001 HClH11001 H 2 O O C 6 H 5 COHC 6 H 5 COH Cl O H H11001 HCl O C 6 H 5 CN(CH 3 ) 2 C 6 H 5 CN(CH 3 ) 2 Cl O H (CH 3 ) 2 NH H11001 (CH 3 ) 2 NH 2 H11001 Cl H11002 O C 6 H 5 CNHCH 3 C 6 H 5 CNHCH 3 Cl O H CH 3 NH 2 H11001 CH 3 NH 3 H11001 Cl H11002 O C 6 H 5 COCH 2 CH 3 C 6 H 5 COCH 2 CH 3 Cl O H H11001 HCl A-44 APPENDIX 2 20.8 (b) (c) (d) 20.9 20.10 Step 1: Protonation of the carbonyl oxygen Step 2: Nucleophilic addition of water Step 3: Deprotonation of oxonium ion to give neutral form of tetrahedral intermediate C 6 H 5 C HO OH OCH 2 CH 3 H11001H11001C 6 H 5 C O H11001 HH OH OCH 2 CH 3 O H H H H11001 O H H O H H C 6 H 5 C OCH 2 CH 3 OH H11001 C 6 H 5 C O H11001 HH OH OCH 2 CH 3 H11001 C 6 H 5 C OCH 2 CH 3 O C 6 H 5 C OCH 2 CH 3 OH H11001 H11001 H H11001 O H H H11001 O H H OH HOCH 2 CHCH 2 CH 2 CH 2 OH (C 5 H 12 O 3 )CH 3 CO 2 Hand O O OH O HHO H11002 O COH CO H11002 O H11001 H 2 O O O N(CH 3 ) 2 O H (CH 3 ) 2 NH CN(CH 3 ) 2 CO H11002 H 2 N(CH 3 ) 2 H11001 O O O CH 3 CNH 2 O H 4 N OCCH 3 H11001H11002 CH 3 C NH 2 O OCCH 3 O HH 3 N H11001 APPENDIX 2 A-45 Step 4: Protonation of ethoxy oxygen Step 5: Dissociation of protonated form of tetrahedral intermediate Step 6: Deprotonation of protonated form of benzoic acid 20.11 The carbonyl oxygen of the lactone became labeled with 18 O. 20.12 20.13 The isotopic label appeared in the acetate ion. 20.14 Step 1: Nucleophilic addition of hydroxide ion to the carbonyl group Step 2: Proton transfer from water to give neutral form of tetrahedral intermediate Step 3: Hydroxide ion-promoted dissociation of tetrahedral intermediate H11001H11001H11001HO H11002 HOHC 6 H 5 C OH H O OCH 2 CH 3 C 6 H 5 C OH O OCH 2 CH 3 H11002 H11001H11001H OH C 6 H 5 C OH OH OCH 2 CH 3 C 6 H 5 C OH O H11002 OCH 2 CH 3 OH H11002 C 6 H 5 C OCH 2 CH 3 O H11001HO H11002 C 6 H 5 C OH O H11002 OCH 2 CH 3 CH 3 (CH 2 ) 12 CO OC(CH 2 ) 12 CH 3 OO OC(CH 2 ) 12 CH 3 O H11001H11001 C 6 H 5 C OH O C 6 H 5 C OH O H H11001 O H H H H11001 O H H HOCH 2 CH 3 C 6 H 5 C OH H H11001 OH OCH 2 CH 3 H11001C 6 H 5 C OH OH H11001 C 6 H 5 C HO H H11001 OH OCH 2 CH 3 H11001C 6 H 5 C HO OH OCH 2 CH 3 H11001 H H11001 O H H O H H A-46 APPENDIX 2 Step 4: Proton abstraction from benzoic acid 20.15 20.16 20.17 (b) (c) 20.18 20.19 Step 1: Protonation of the carbonyl oxygen Step 2: Nucleophilic addition of water Step 3: Deprotonation of oxonium ion to give neutral form of tetrahedral intermediate CH 3 C OH OH NHC 6 H 5 H11001H11001CH 3 C O H11001 HH OH NHC 6 H 5 O H H H H11001 O H H O H H CH 3 C NHC 6 H 5 OH H11001 H11001 CH 3 C O H11001 HH OH NHC 6 H 5 CH 3 C NHC 6 H 5 O H11001 H H11001 O H H CH 3 C NHC 6 H 5 OH H11001 H11001 O H H CNH 2 CO H11002 NH 4 H11001 O O O HCN(CH 3 ) 2 CH 3 OHHN(CH 3 ) 2 O HCOCH 3 H11001H11001 O CH 3 CNHCH 3 O CH 3 CO H11002 CH 3 NH 3 H11001 2CH 3 NH 2 O O CH 3 COCCH 3 H11001H11001 OH OCH 3 CH 3 CSCH 2 CH 2 OC 6 H 5 O OH CH 3 NHCCH 2 CH 2 CHCH 3 H11001H11001HOHC 6 H 5 C O O H11002 C 6 H 5 C HO O OH H11002 APPENDIX 2 A-47 Step 4: Protonation of amino group of tetrahedral intermediate Step 5: Dissociation of N-protonated form of tetrahedral intermediate Step 6: Proton-transfer processes 20.20 Step 1: Nucleophilic addition of hydroxide ion to the carbonyl group Step 2: Proton transfer to give neutral form of tetrahedral intermediate Step 3: Proton transfer from water to nitrogen of tetrahedral intermediate Step 4: Dissociation of N-protonated form of tetrahedral intermediate H11001H11001H11001HO H11002 H 2 O HN(CH 3 ) 2 HC OH O H NH(CH 3 ) 2 H11001 HC OH O H11001H11001H OH OH H11002 HC OH OH N(CH 3 ) 2 HC OH OH NH(CH 3 ) 2 H11001 H11001H11001H OH OH H11002 HC OH O H11002 N(CH 3 ) 2 HC OH OH N(CH 3 ) 2 H11001HO H11002 HC OH O H11002 N(CH 3 ) 2 HCN(CH 3 ) 2 O H 2 NC 6 H 5 H 3 NC 6 H 5 H11001 H11001 H11001 O H H H O H H H11001 H11001H11001 CH 3 C OH O CH 3 C OH O H H11001 O H H H H11001 O H H H 2 NC 6 H 5 H11001CH 3 C OH OH H11001 CH 3 C OH H H11001 OH H NC 6 H 5 CH 3 C OH H H11001 OH H NC 6 H 5 H11001CH 3 C OH OH NHC 6 H 5 H11001 H H11001 O H H O H H A-48 APPENDIX 2 Step 5: Irreversible formation of formate ion 20.21 20.22 20.23 In acid, the nitrile is protonated on nitrogen. Nucleophilic addition of water yields an imino acid. A series of proton transfers converts the imino acid to an amide. 20.24 The imine intermediate is . CHAPTER 21 21.1 Ethyl benzoate cannot undergo the Claisen condensation. Claisen condensation product of Claisen condensation product of ethyl pentanoate: ethyl phenylacetate: 21.2 (b) (c) C CH 3 O O OCH 2 CH 3 O CH 3 C O OCH 2 CH 3 O O C 6 H 5 C 6 H 5 CH 2 CCHCOCH 2 CH 3 O O CH 2 CH 2 CH 3 CH 3 CH 2 CH 2 CH 2 CCHCOCH 2 CH 3 NH C 6 H 5 CCH 2 CH 3 O C 6 H 5 CCH 2 CH 3 CH 3 CH 2 CN C 6 H 5 MgBrH11001 1. diethyl ether 2. H 2 O, H H11001 , heat H11001H11001H11001RC NH 2 O RC NH OH H H11001 O H H H H11001 O H H H11001 H O H H RC NH 2 O H11001H 2 O RC NH OH 2 H11001 RC NH OH RC N H11001 H H 2 O H 3 O H11001 CH 3 CH 2 OH CH 3 CH 2 Br CH 3 CH 2 CN PBr 3 or HBr NaCN O CH 3 COH O CH 3 CNH 2 CH 3 CNCH 3 CH 2 OH Na 2 Cr 2 O 7 , H 2 O H 2 SO 4 , heat 1. SOCl 2 2. NH 3 P 4 O 10 O CH 3 CH 2 CH 2 CNH 2 CH 3 CH 2 CH 2 CO 2 HCH 3 CH 2 CH 2 NH 2 1. SOCl 2 2. NH 3 Br 2 H 2 O, NaOH H11001H11001HOHHC O O H11002 HC HO O OH H11002 APPENDIX 2 A-49 21.3 (b) (c) 21.4 21.5 21.6 (b) (c) 21.7 (b) (c) 1. NaOCH 2 CH 3 2. HO H11002 , H 2 O 3. H H11001 4. heat H11001 O O CH 3 CCH 2 COCH 2 CH 3 CH 2 CHCH 2 Br CH 2 CHCH 2 CH 2 CCH 3 O 1. NaOCH 2 CH 3 2. HO H11002 , H 2 O 3. H H11001 4. heat C 6 H 5 CH 2 Br H11001 O O CH 3 CCH 2 COCH 2 CH 3 O C 6 H 5 CH 2 CH 2 CCH 3 CH 3 O O H11002 CH 3 CH 2 O CH 3 O O H11002 OCH 2 CH 3 H11001 CH 2 CH 2 C C CH 3 CH 2 O O O CHCH 3 H11002 CH 3 O O H11002 CH 3 CH 2 O C 6 H 5 CHCH O COCH 2 CH 3 O C 6 H 5 CHCCOCH 2 CH 3 OO COCH 2 CH 3 O O 1. HO H11002 , H 2 O 2. H H11001 3. heat 1. NaOCH 2 CH 3 2. H H11001 O COCH 2 CH 3 O O O CH 3 CH 2 OCCH 2 CH 2 CH 2 CH 2 COCH 2 CH 3 NaOCH 2 CH 3 ethanol 1. HO H11002 , H 2 O 2. H H11001 3. heat H11001CH 3 (CH 2 ) 5 CH 2 Br CH 2 (COOCH 2 CH 3 ) 2 CH 3 (CH 2 ) 5 CH 2 CH(COOCH 2 CH 3 ) 2 CH 3 (CH 2 ) 5 CH 2 CH 2 COH O NaOCH 2 CH 3 ethanol 1. HO H11002 , H 2 O 2. H H11001 3. heat H11001 CH 2 (COOCH 2 CH 3 ) 2 CH 3 CH 2 CHCH 2 CH(COOCH 2 CH 3 ) 2 CH 3 CH 3 CH 2 CHCH 2 Br CH 3 CH 3 CH 2 CHCH 2 CH 2 COH CH 3 O A-50 APPENDIX 2 (d) 21.8 21.9 21.10 21.11 21.12 NaOCH 2 CH 3 O C 6 H 5 CH 2 COCH 2 CH 3 H11001 O CH 3 CH 2 OCOCH 2 CH 3 C 6 H 5 CH(COOCH 2 CH 3 ) 2 O H O CH 3 CH 2 H11002 S N NNa H11001 CH 3 CH 2 CH 2 CH CH 3 O H O CH 3 CH 2 S H11002 N NNa H11001 CH 3 CH 2 CH 2 CH CH 3 COCH 2 CH 3 COCH 2 CH 3 CH 3 CH 2 CH 2 CH C CH 3 CH 2 CH 3 O O H11001 H 2 NCNH 2 O H O H O CH 3 CH 2 O N N CH 3 CH 2 CH 2 CH CH 3 CH 2 (COOCH 2 CH 3 ) 2 2. NaOCH 2 CH 3 , CH 3 CH 2 Br Br W CH 3 CH 2 CH 2 CH C(COOCH 2 CH 3 ) 2 CH 3 CH 2 CH 3 1. NaOCH 2 CH 3 , CH 2 CH 2 CH 2 CHCH 3 NaOCH 2 CH 3 O O CH 3 CCH 2 COCH 2 CH 3 H11001 BrCH 2 CH 2 CH 2 CH 2 Br 1. HO H11002 , H 2 O 2. H H11001 , heat CCH 3 CO 2 CH 2 CH 3 O CCH 3 H O NaOCH 2 CH 3 CH 3 Br NaOCH 2 CH 3 CH 3 Br O O CH 3 CCH 2 COCH 2 CH 3 O O CH 3 CCHCOCH 2 CH 3 CH 3 O O CH 3 CCCOCH 2 CH 3 CH 3 H 3 C O CH 3 CCH(CH 3 ) 2 1. HO H11002 , H 2 O 2. H H11001 3. heat NaOCH 2 CH 3 ethanol 1. HO H11002 , H 2 O 2. H H11001 3. heat H11001C 6 H 5 CH 2 Br CH 2 (COOCH 2 CH 3 ) 2 C 6 H 5 CH 2 CH(COOCH 2 CH 3 ) 2 C 6 H 5 CH 2 CH 2 COH O NaOCH 2 CH 3 CH 3 CH 2 Br H 2 NCNH 2 O X C 6 H 5 C(COOCH 2 CH 3 ) 2 CH 2 CH 3 C 6 H 5 CH(COOCH 2 CH 3 ) 2 H O H O CH 3 CH 2 O N N C 6 H 5 APPENDIX 2 A-51 21.13 21.14 (b) (c) (d) CHAPTER 22 22.1 (b) 1-Phenylethanamine or 1-phenylethylamine; (c) 2-propen-1-amine or allylamine 22.2 N,N-Dimethylcycloheptanamine 22.3 Tertiary amine; N-ethyl-4-isopropyl-N-methylaniline 22.4 22.5 pK b H11005 6; K a of conjugate acid H11005 1 H11003 10 H110028 ; pK a of conjugate acid H11005 8 22.6 log (CH 3 NH 3 H11001 /CH 3 NH 2 ) H11005 10.7 H11002 7 H11005 3.7; (CH 3 NH 3 H11001 /CH 3 NH 2 ) H11005 10 3.7 H11005 5000 22.7 Tetrahydroisoquinoline is a stronger base than tetrahydroquinoline. The unshared electron pair of tetrahydroquinoline is delocalized into the aromatic ring, and this substance resembles ani- line in its basicity, whereas tetrahydroisoquinoline resembles an alkylamine. 22.8 (b) The lone pair of nitrogen is delocalized into the carbonyl group by amide resonance. (c) The amino group is conjugated to the carbonyl group through the aromatic ring. 22.9 Cl 2 400°C NH 3 CH 2 CHCH 3 CH 2 CHCH 2 Cl CH 2 CHCH 2 NH 2 H 2 NC CH 3 O H 2 N H11001 C CH 3 H11002 O C 6 H 5 N H O CCH 3 C 6 H 5 N H O CCH 3 H11002 H11001 NH 2 O H11002 O N H11001 H11002 H11001 NH 2 O H11002 O N H11001 1. LDA, THF 2. cyclohexanone 3. H 2 O CH 3 CO 2 C(CH 3 ) 3 OH CH 2 CO 2 C(CH 3 ) 3 1. LDA, THF 2. C 6 H 5 CHO 3. H 2 O O O CHC 6 H 5 OH 1. LDA, THF 2. CH 3 I C 6 H 5 CHCO 2 CH 3 CH 3 C 6 H 5 CH 2 CO 2 CH 3 O CH 2 CCH 3 O A-52 APPENDIX 2 22.10 Isobutylamine and 2-phenylethylamine can be prepared by the Gabriel synthesis; tert-butyl- amine, N-methylbenzylamine, and aniline cannot. (b) (d) 22.11 (b) Prepare p-isopropylnitrobenzene as in part (a); then reduce with H 2 , Ni (or Fe H11001 HCl or Sn H11001 HCl, followed by base). (c) Prepare isopropylbenzene as in part (a); then dinitrate with HNO 3 H11001 H 2 SO 4 ; then reduce both nitro groups. (d) Chlorinate benzene with Cl 2 H11001 FeCl 3 ; then nitrate (HNO 3 , H 2 SO 4 ), separate the desired para isomer from the unwanted ortho isomer, and reduce. (e) Acetylate benzene by a Friedel–Crafts reaction (acetyl chloride H11001 AlCl 3 ); then nitrate (HNO 3 , H 2 SO 4 ); then reduce the nitro group. 22.12 (b) (c) (d) 22.13 (b) (c) CH 2 ?CH 2 22.14 (b) Prepare acetanilide as in part (a); dinitrate (HNO 3 , H 2 SO 4 ); then hydrolyze the amide in either acid or base. (c) Prepare p-nitroacetanilide as in part (a); then reduce the nitro group with H 2 (or Fe H11001 HCl or Sn H11001 HCl, followed by base). 22.15 N O N H 3 C H 3 C N H11001 O H11002 N H 3 C H 3 C (CH 3 ) 3 CCH 2 C?CH 2 W CH 3 H 2 , Ni C 6 H 5 CH O H11001 HN C 6 H 5 CH 2 N H 2 , Ni C 6 H 5 CH O H11001 (CH 3 ) 2 NH C 6 H 5 CH 2 N(CH 3 ) 2 H 2 , Ni C 6 H 5 CH O H11001 C 6 H 5 CH 2 NH 2 C 6 H 5 CH 2 NHCH 2 C 6 H 5 O O NH NH C 6 H 5 CH 2 CH 2 Br H11001 O O NK O O NCH 2 CH 2 C 6 H 5 H 2 NNH 2 C 6 H 5 CH 2 CH 2 NH 2 H11001 O O NH NH (CH 3 ) 2 CHCH 2 Br H11001 O O NK O O NCH 2 CH(CH 3 ) 2 H 2 NNH 2 (CH 3 ) 2 CHCH 2 NH 2 H11001 APPENDIX 2 A-53 22.16 The diazonium ion from 2,2-dimethylpropylamine rearranges via a methyl shift on loss of nitrogen to give 1,1-dimethylpropyl cation. 22.17 Intermediates: benzene to nitrobenzene to m-bromonitrobenzene to m-bromoaniline to m- bromophenol. Reagents: HNO 3 , H 2 SO 4 ; Br 2 , FeBr 3 ; Fe, HCl then HO H11002 ; NaNO 2 , H 2 SO 4 , H 2 O, then heat in H 2 O. 22.18 Prepare m-bromoaniline as in Problem 22.17; then NaNO 2 , HCl, H 2 O followed by KI. 22.19 Intermediates: benzene to ethyl phenyl ketone to ethyl m-nitrophenyl ketone to m- aminophenyl ethyl ketone to ethyl m-fluorophenyl ketone. Reagents: propanoyl chloride, AlCl 3 ; HNO 3 , H 2 SO 4 ; Fe, HCl, then HO H11002 ; NaNO 2 , H 2 O, HCl, then HBF 4 , then heat. 22.20 Intermediates: isopropylbenzene to p-isopropylnitrobenzene to p-isopropylaniline to p-iso- propylacetanilide to 4-isopropyl-2-nitroacetanilide to 4-isopropyl-2-nitroaniline to m-isopropylni- trobenzene. Reagents: HNO 3 , H 2 SO 4 ; Fe, HCl, then HO H11002 ; acetyl chloride; HNO 3 , H 2 SO 4 ; acid or base hydrolysis; NaNO 2 , HCl, H 2 O, and CH 3 CH 2 OH or H 3 PO 2 . CHAPTER 23 23.1 C 6 H 5 CH 2 Cl 23.2 (b) (c) (d) 23.3 23.4 23.5 FF FF FF OCH 3 F FF FF OCH 3 H11002 F F FF FF H11001H11001OCH 3 H11002 F H11002 BrBr NO 2 OCH 2 CH 3 N CH 3 O F H11001 O H11002 O H11002 NO 2 NO 2 NHCH 3 NO 2 NO 2 NH 2 NO 2 NO 2 SCH 2 C 6 H 5 CH 3 CCH 2 NH 2 CH 3 CH 3 HONO H11002N 2 CH 3 C CH 3 CH 3 H11001 CH 2 N N CH 3 CCH 2 CH 3 H11001 CH 3 A-54 APPENDIX 2 23.6 Nitrogen bears a portion of the negative charge in the anionic intermediate formed in the nucleophilic addition step in 4-chloropyridine, but not in 3-chloropyridine. 23.7 A benzyne intermediate is impossible because neither of the carbons ortho to the intended leaving group bears a proton. 23.8 3-Methylphenol and 4-methylphenol (m-cresol and p-cresol) 23.9 CHAPTER 24 24.1 (b) (c) (d) 24.2 Methyl salicylate is the methyl ester of o-hydroxybenzoic acid. Intramolecular (rather than intermolecular) hydrogen bonding is responsible for its relatively low boiling point. 24.3 (b) p-Cyanophenol is stronger acid because of conjugation of cyano group with phenoxide oxygen. (c) o-Fluorophenol is stronger acid because electronegative fluorine substituent can stabi- lize negative charge better when fewer bonds intervene between it and the phenoxide oxygen. 24.4 24.5 then H11001 H11002 OH OH H11002 OH H 2 O H11002 OH Cl H11002 H11001H 2 OH11001H11001 H Cl C O H O OCH 3 OH Cl OH NO 2 OH CH 2 C 6 H 5 OH O H N H11002 Cl H H H Y is more stable and formed faster than Y N Cl H H11002 HH H H11002SO 3 2H11002 H11002 OH SO 3 H11002 CH 3 OHCH 3 H11001SO 3 H11002 CH 3 H11002 OH APPENDIX 2 A-55 24.6 (b) (c) (d) 24.7 (b) (c) 24.8 24.9 p-Fluoronitrobenzene and phenol (as its sodium or potassium salt) 24.10 CHAPTER 25 25.1 (b) L-Glyceraldehyde; (c) D-glyceraldehyde 25.2 L-Erythrose 25.3 25.4 L-Talose H OH HO H HO H CH 2 OH CHO OH CHCH CH 3 CH 2 C 6 H 5 OCH 2 CHCH 3 OH H11001 C 6 H 5 CCl O C 6 H 5 OCC 6 H 5 O C 6 H 5 OH HClH11001 OH H11001 CH 3 COCCH 3 OO CH 3 CONa O NaOH OCCH 3 O H11001 CCH 2 CH 3 CH 3 OH O O CH(CH 3 ) 2 N H 3 C OH CH 3 Br (CH 3 ) 3 C OH A-56 APPENDIX 2 25.5 (b) (c) (d) 25.6 (b) (c) (d) 25.7 67% H9251, 33% H9252 25.8 25.9 (b) 25.10 O OCH 3 OH HOCH 2 HO HO H9251 O OCH 3 OH HOCH 2 HO HO H9252 H OH H OH HO H HO H CH 3 CHO CO H OH CH 2 OH CH 2 OH CO HO H CH 2 OH CH 2 OH O OH OH OH HO HOCH 2 O OH HO HO OH O OH OH HOCH 2 HO HO HO H HOH OH H O HO H HOH OH H O and H OH H OHH OH HHOCH 2 O H OH H OHH OH H HOCH 2 O and HOCH 2 HO H HOH OH HH O HOCH 2 HO H HOH OH H H O and APPENDIX 2 A-57 25.11 The mechanism for formation of the H9252-methyl glycoside is shown. The mechanism for for- mation of the H9251 isomer is the same except that methanol approaches the carbocation from the axial direction. 25.12 25.13 No. The product is a meso form. 25.14 All (b) through (f) will give positive tests. 25.15 L-Gulose 25.16 The intermediate is an enediol, 25.17 (b) Four equivalents of periodic acid are required. One molecule of formaldehyde and four molecules of formic acid are formed from each molecule of D-ribose. (c) Two equivalents (d) Two equivalents CHAPTER 26 26.1 Hydrolysis gives CH 3 (CH 2 ) 16 CO 2 H (2 mol) and (Z)-CH 3 (CH 2 ) 7 CH?CH(CH 2 ) 7 CO 2 H (1 mol). The same mixture of products is formed from 1-oleyl-2,3-distearylglycerol. 26.2 CH 3 C S ACP OH SCoA CH CH HC OCH 3 HH O O O O H11001 O HCH H11001 O O HC HC HOCH 2 OCH 3 O HCO 2 H HOCH OH O CCH 2 OP(OH) 2 O HO O OH HOCH 2 HO OH CH O OH HOCH 2 HO O H HOCH 2 HO HO O H H11001 HOCH 2 HO HO H Cl H CH 3 O ± ± O O H11001 CH 3 H H HOCH 2 HO HO O OCH 3 H HOCH 2 HO HO A-58 APPENDIX 2 26.3 26.4 R in both cases 26.5 26.6 26.7 26.8 Tail-to-tail link Cembrene OH Vitamin A H9251-Phellandrene OH Menthol CH O Citral CO 2 H HO HO O CH 3 (CH 2 ) 14 CO(CH 2 ) 15 CH 3 O CH 3 (CH 2 ) 12 CS O ACP CH 3 (CH 2 ) 12 CCH 2 C O O ACP H H9251-Selinene OH Farnesol CO 2 H OH O Abscisic acid CH 3 (CH 2 ) 12 CHCH 2 CS OH O ACP CH 3 (CH 2 ) 12 CH 2 CH 2 CS O ACPCH 3 (CH 2 ) 12 CH O CHCS ACP APPENDIX 2 A-59 26.9 26.10 26.11 Four carbons would be labeled with 14 C; they are C-1, C-3, C-5, and C-7. 26.12 (b) Hydrogens that migrate are those originally attached to C-13 and C-17 (steroid num- bering); (c) the methyl group attached to C-15 of squalene 2,3-epoxide; (d) the methyl groups at C-2 and C-10 plus the terminal methyl group of squalene 2,3-epoxide. 26.13 All the methyl groups are labeled, plus C-1, C-3, C-5, C-7, C-9, C-13, C-15, C-17, C-20, and C-24 (steroid numbering). 26.14 The structure of vitamin D 2 is the same as that of vitamin D 3 except that vitamin D 2 has a double bond between C-22 and C-23 and a methyl substituent at C-24. CHAPTER 27 27.1 (b) R; (c) S 27.2 Isoleucine and threonine 27.3 (b) (c) (d) CH 2 CHCO 2 H11002H11002 O NH 2 CH 2 CHCO 2 H11002 HO NH 2 CH 2 CHCO 2 H11002H11002 O H11001 NH 3 or CH 2 CHCO 2 H11002 HO H11001 NH 3 OH H Isoborneol O Camphor OPP OPP H11001 OPP HH H11002H H11001 H 2 O OPP OH A-60 APPENDIX 2 27.4 At pH 1: At pH 9: At pH 13: 27.5 27.6 27.7 Treat the sodium salt of diethyl acetamidomalonate with isopropyl bromide. Remove the amide and ester functions by hydrolysis in aqueous acid; then heat to cause to decarboxylate to give valine. The yield is low because isopropyl bromide is a secondary alkyl halide, because it is sterically hindered to nucleophilic attack, and because elimination competes with substitution. 27.8 violet dye N H CHR O O NH 2 H O O H 2 O H11001 RCH O O O O H11002 OH N H O O O O N H CHR O O CO 2 O O N CH O R O H11002 H C OH H11001 OH OH O O H11002H 2 O O O O O O NCHCO 2 H11002 R H 3 NCHCO 2 H11002 W H11001 R (CH 3 ) 2 CHC(CO 2 H) 2 H11001 NH 3 (CH 3 ) 2 CHCH O (CH 3 ) 2 CHCHCN NH 2 (CH 3 ) 2 CHCHCO 2 H11002 H11001 NH 3 NH 4 Cl NaCN 1. H 2 O, HCl, heat 2. HO H11002 (CH 3 ) 2 CHCH 2 CO 2 H (CH 3 ) 2 CHCHCO 2 H Br (CH 3 ) 2 CHCHCO 2 H11002 H11001 NH 3 Br 2 P NH 3 H 2 NCH 2 CH 2 CH 2 CH 2 CHCO 2 H11002 NH 2 H 3 NCH 2 CH 2 CH 2 CH 2 CHCO 2 H11002 H11001 NH 2 H 3 NCH 2 CH 2 CH 2 CH 2 CHCO 2 H H11001 H11001 NH 3 APPENDIX 2 A-61 27.9 Glutamic acid 27.10 (b) (c) (d) (e) (f) One-letter abbreviations: (b) AF; (c) FA; (d) GE; (e) KG; (f) D-A-D-A 27.11 (b) (c) (d) (e) (f) 27.12 Tyr-Gly-Gly-Phe-Met; YGGFM 27.13 27.14 Val-Phe-Gly-Ala Val-Phe-Ala-Gly 27.15 OS N CH 2 C 6 H 5 C 6 H 5 HN Val-Gly-Phe-Ala Val-Gly-Ala-Phe Val-Phe-Gly-Ala Val-Phe-Ala-Gly Val-Ala-Gly-Phe Val-Ala-Phe-Gly Phe-Gly-Ala-Val Phe-Gly-Val-Ala Phe-Ala-Gly-Val Phe-Ala-Val-Gly Phe-Val-Gly-Ala Phe-Val-Ala-Gly Gly-Ala-Phe-Val Gly-Ala-Val-Phe Gly-Phe-Ala-Val Gly-Phe-Val-Ala Gly-Val-Ala-Phe Gly-Val-Phe-Ala Ala-Gly-Phe-Val Ala-Gly-Val-Phe Ala-Phe-Gly-Val Ala-Phe-Val-Gly Ala-Val-Gly-Phe Ala-Val-Phe-Gly N H H CH 3 O CO 2 H11002 CH 3 H H 3 N H11001 N H O CO 2 H11002 H H 3 NCH 2 CH 2 CH 2 CH 2 H 3 N H11001 H11001 N H CH 2 CH 2 CO 2 H11002 H O CO 2 H11002 H 3 N H11001 N H CH 3 H O CO 2 H11002 H C 6 H 5 CH 2 H 3 N H11001 N H CH 2 C 6 H 5 H O CO 2 H11002 H H 3 C H 3 N H11001 H 3 NCHCNHCHCO 2 H11002 H11001 CH 3 CH 3 O H 3 NCHCNHCH 2 CO 2 H11002 H11001 H11001 H 3 NCH 2 CH 2 CH 2 CH 2 O H 3 NCH 2 CNHCHCO 2 H11002 H11001 CH 2 CH 2 CO 2 H11002 O H 3 NCHCNHCHCO 2 H11002 H11001 C 6 H 5 CH 2 CH 3 O H 3 NCHCNHCHCO 2 H11002 H11001 CH 3 CH 2 C 6 H 5 O A-62 APPENDIX 2 27.16 27.17 27.18 An O-acylisourea is formed by addition of the Z-protected amino acid to N,NH11032-dicyclo- hexylcarbodiimide, as shown in Figure 27.13. This O-acylisourea is attacked by p-nitrophenol. 27.19 Remove the Z protecting group from the ethyl ester of Z-Phe-Gly by hydrogenolysis. Cou- ple with the p-nitrophenyl ester of Z-Leu; then remove the Z group of the ethyl ester of Z-Leu- Phe-Gly. 27.20 Protect glycine as its Boc derivative and anchor this to the solid support. Remove the pro- tecting group and treat with Boc-protected phenylalanine and DCCI. Remove the Boc group with HCl; then treat with HBr in trifluoroacetic acid to cleave Phe-Gly from the solid support. 27.21 F O O N H HN OCR O O 2 NH11001OHO 2 N RC O NRH11032 NHRH11032 H H11001 O C RH11032NHCNHRH11032 O H11001 H 2 Pd C 6 H 5 CH 2 OCNHCHCNHCHCOCH 2 C 6 H 5 O O O CH 3 CH 2 CH(CH 3 ) 2 Ala-Leu H 3 NCHCO 2 H11002 H11001 (CH 3 ) 2 CHCH 2 H 2 NCHCO 2 CH 2 C 6 H 5 (CH 3 ) 2 CHCH 2 H11001 C 6 H 5 CH 2 OH 1. H H11001 , heat 2. HO H11002 H 3 NCHCO 2 H11002 H11001 CH 3 H11001 C 6 H 5 CH 2 OCCl O C 6 H 5 CH 2 OCNHCHCO 2 H O CH 3 C 6 H 5 CH 2 OCNHCHCO 2 H C 6 H 5 CH 2 OCNHCH 2 CH 2 CH 2 CH 2 O O H 2 NCHCOCH 2 C 6 H 5 O (CH 3 ) 2 CHCH 2 H11001 DCCl C 6 H 5 CH 2 OCNHCHCO 2 H O CH 3 C 6 H 5 CH 2 OCNHCHCNHCHCOCH 2 C 6 H 5 O O O CH 3 CH 2 CH(CH 3 ) 2 APPENDIX 2 A-63 27.22 (b) Cytidine (c) Guanosine 27.23 The codons for glutamic acid (GAA and GAG) differ by only one base from two of the codons for valine (GUA and GUG). HOCH 2 OH OH HH H 2 N O N N N HN HH O HOCH 2 OH OH HH NH O NH 2 N HH O A-64 APPENDIX 3 LEARNING CHEMISTRY WITH MOLECULAR MODELS: USING SPARTANBUILD AND SPARTANVIEW Alan J. Shusterman, Department of Chemistry, Reed College, Portland, OR Warren J. Hehre, Wavefunction, Inc., Irvine, CA SpartanBuild: AN ELECTRONIC MODEL KIT SpartanBuild is a program for building and displaying molecular models. It gives detailed information about molecular geometry (bond lengths and angles) and stability (strain energy). The program is located on the CD Learning By Modeling included with your text and may be run on any Windows (95/98/NT) or Power Macintosh computer. SpartanBuild is intended both to assist you in solving problems in the text (these problems are matched with the following icon) and more generally as a “replacement” to the plastic “model kits” that have been a main- stay in organic chemistry courses. The tutorials that follow contain instructions for using SpartanBuild. Each tutorial gives instructions for a related group of tasks (install software, change model display, etc.). Computer instructions are listed in the left-hand column, and comments are listed in the right-hand column. Please perform these instructions on your computer as you read along. BUILDING A MODEL WITH ATOMS One way to build a model is to start with one atom and then add atoms one at a time as needed. For example, propanal, CH 3 CH 2 CH?O, can be assembled from four “atoms” (sp 3 C, sp 3 C, sp 2 C, and sp 2 O). SpartanBuild is “CD-protected.” The CD must remain in the drive at all times. Starting the program opens a large Spar- tanBuild window (blank initially), a model kit, and a tool bar. Models are as- sembled in the window. Restart SpartanBuild to continue. Installing SpartanBuild 1. Insert Learning By Modeling CD. 2. Double-click on the CD’s icon. Starting SpartanBuild 3. Double-click on the SpartanBuild icon. Quitting SpartanBuild 4. Select Quit from the File menu. APPENDIX 3 A-65 You start building propanal using an sp 3 C from the model kit. Note that five dif- ferent types of carbon are available. Each is defined by a particular number of unfilled valences (these are used to make bonds) and a particular “idealized geometry.” Valences that are not used for bonds are automatically turned into hydrogen atoms, so it is nor- mally unnecessary to build hydrogens into a model. You can rotate a model (in this case, just an sp 3 C), move it around the screen, and change its size using the mouse in conjunction with the keyboard (see the follow- ing table). Try these operations now. To finish building propanal, you need to add two carbons and an oxygen. Start by adding another sp 3 C (it should still be selected), and continue by adding an sp 2 C and an sp 2 O. Atoms are added by clicking on unfilled valences in the model (the valences turn into bonds). If you make a mistake at any point, you can undo the last operation by selecting Undo from the Edit menu, or you can start over by selecting Clear from the Edit menu. This selects the carbon atom with four single valences. To finish building propanal, CH 3 CH 2 CH?O 3. If necessary, click on sp 3 C in the model kit. Operation Rotate Translate Scale PC Move mouse with left button depressed. Move mouse with right button depressed. Press shift key, and move mouse with right button depressed. Mac Move mouse with button depressed. Press option key, and move mouse with button depressed. Simultaneously press option and control keys, and move mouse with button depressed. Atom button Atom label Ideal bond angles Unfilled valences sp 3 C 109.5° 4 single C sp 2 C 120° 2 single 1 double C trigonal C 120° 3 single C H11001 sp C 180° 1 single 1 triple C delocalized C 120° 1 single 2 partial double C The button becomes highlighted. A carbon atom with four unfilled va- lences (white) appears in the Spartan- Build window as a ball-and-wire model. Starting to build propanal, CH 3 CH 2 CH?O If necessary, start SpartanBuild. 1. Click on in the model kit. 2. Click anywhere in the window. A-66 APPENDIX 3 MEASURING MOLECULAR GEOMETRY Three types of geometry measurements can be made using SpartanBuild: distances between pairs of atoms, angles involving any three atoms, and dihedral angles involv- ing any four atoms. These are accessible from the Geometry menu and from the tool- bar. Try these operations now. CHANGING MODEL DISPLAY The ball-and-wire display is used for model building. Although it is convenient for this purpose, other model displays show three-dimensional molecular structure more clearly and may be preferred. The space-filling display is unique in that it portrays a molecule as a set of atom-centered spheres. The individual sphere radii are taken from experi- mental data and roughly correspond to the size of atomic electron clouds. Thus, the space-filling display attempts to show how much space a molecule takes up. Changing the Model Display 1. One after the other, select Wire, Tube, Ball and Spoke, and Space Filling from the Model menu. Geometry Menu Distance Angle Dihedral PC Mac This makes a carbon–carbon single bond (the new bond appears as a dashed line). This selects the carbon atom with one double and two single valences. This makes a carbon–carbon single bond. Bonds can only be made between va- lences of the same type (single H11001 single, double H11001 double, etc.). This selects the oxygen atom with one double valence. This makes a carbon–oxygen double bond. Note: If you cannot see which va- lence is the double valence, then rotate the model first. 4. Click on the tip of any unfilled va- lence in the window. 5. Click on sp 2 C in the model kit. 6. Click on the tip of any unfilled va- lence in the window. 7. Click on sp 2 O in the model kit. 8. Click on the tip of the double un- filled valence in the window. APPENDIX 3 A-67 BUILDING A MODEL USING GROUPS Organic chemistry is organized around “functional groups,” collections of atoms that dis- play similar structures and properties in many different molecules. SpartanBuild simpli- fies the construction of molecular models that contain functional groups by providing a small library of prebuilt groups. For example, malonic acid, HO 2 C±CH 2 ±CO 2 H, is easily built using the Carboxylic Acid group. BUILDING A MODEL USING RINGS Many organic molecules contain one or more rings. SpartanBuild contains a small library of prebuilt structures representing some of the most common rings. For example, trans- 1,4-diphenylcyclohexane can be constructed most easily using Benzene and Cyclo- hexane rings. This removes the existing model from the SpartanBuild window. This indicates that a ring is to be selected. This makes this ring appear in the model kit. This places an entire cyclohexane ring in the window. Building trans-1,4-phenylcyclohexane 1. Select Clear from the Edit menu. 2. Click on the Rings button. 3. Select Cyclohexane from the Rings menu. 4. Click anywhere in the SpartanBuild window. trans-1,4-Diphenylcyclohexane H H This removes the existing model from the SpartanBuild window. This indicates that a functional group is to be selected This makes this group appear in the model kit. The carboxylic acid group has two struc- turally distinct valences that can be used to connect this group to the model. The “active” valence is marked by a small cir- cle and can be changed by clicking any- where on the group. A new carbon–carbon bond forms and an entire carboxylic acid group is added to the model. This adds a second carboxylic acid group to the model. Building malonic acid, HO 2 C±CH 2 ±CO 2 H 1. Select Clear from the Edit menu 2. Click on sp 3 C in the model kit, then click in the SpartanBuild window. 3. Click on the Groups button in the model kit. 4. Select Carboxylic Acid from the Groups menu. 5. Examine the unfilled valences of the carboxylic acid group, and find the one marked by a small circle. If necessary, click on the group to make this circle move to the va- lence on carbon. 6. Click on the tip of any unfilled va- lence in the window. 7. Click on the tip of any unfilled va- lence on carbon. A-68 APPENDIX 3 ADDITIONAL TOOLS Many models can be built with the tools that have already been described. Some mod- els, however, require special techniques (or are more easily built) using some of the Spar- tanBuild tools described in the following table. This makes this ring appear in the model kit. This adds an entire benzene ring to the model. This adds a second benzene ring to the model. 5. Select Benzene from the Rings menu. 6. Click on the tip of any equatorial unfilled valence. 7. Click on the tip of the equatorial unfilled valence directly across the ring (the valence on C-4). Tool Make Bond Break Bond Delete Internal Rotation Atom Replacement PC Mac Use Click on two unfilled valences. The valences are replaced by a bond. Click on bond. The bond is replaced by two unfilled valences. Click on atom or unfilled valence. Deleting an atom removes all unfilled valences associated with atom. Click on bond to select it for rotation. Press Alt key (PC) or space bar (Mac), and move mouse with button depressed (left button on PC). One part of the model rotates about the selected bond relative to other part. Select atom from model kit, then double- click on atom in model. Valences on the new atom must match bonds in the model or replacement will not occur. Example X X N N MINIMIZE: GENERATING REALISTIC STRUCTURES AND STRAIN ENERGY In some cases, the model that results from building may be severely distorted. For exam- ple, using Make Bond to transform axial methylcyclohexane into bicyclo[2.2.1]heptane (norbornane) gives a highly distorted model (the new bond is too long and the ring has the wrong conformation). APPENDIX 3 A-69 The distorted structure can be replaced by a “more reasonable” structure using an empir- ical “molecular mechanics” calculation. This calculation, which is invoked in Spartan- Build by clicking on Minimize, automatically finds the structure with the smallest strain energy (in this case, a structure with “realistic” bond distances and a boat conformation for the six-membered ring). It is difficult to tell which models contain structural distortions. You should “minimize” all models after you finish building them. Molecular mechanics strain energies have another use. They can also be used to com- pare the energies of models that share the same molecular formula, that is, models that are either stereoisomers or different conformations of a single molecule (allowed com- parisons are shown here). SpartanBuild reports strain energies in kilocalories per mole (1 kcal/mol H11005 4.184 kJ/mol) in the lower left-hand corner of the SpartanBuild window. SpartanView: VIEWING AND INTERPRETING MOLECULAR-MODELING DATA Learning By Modeling contains a program, SpartanView, which displays preassembled molecular models, and also a library of SpartanView models to which you can refer. These models differ in two respects from the models that you can build with Spartan- Build. Some models are animations that show how a molecule changes its shape during a chemical reaction, vibration, or conformation change. Others contain information about electron distribution and energy that can only be obtained from sophisticated quantum chemical calculations. The following sections describe how to use SpartanView. SpartanView models are intended to give you a “molecule’s eye view” of chemi- cal processes and to help you solve certain text problems. The text uses the following icon to alert you to corresponding models on the CD. Each icon corresponds to a model or a group of models on the CD. All of the mod- els for a given chapter are grouped together in the same folder. For example, the mod- els for this appendix are grouped together in a folder named “Appendix.” The location make bond minimize versus Anti Gauche versusversus A-70 APPENDIX 3 of models within each folder can be determined by paying attention to the context of the icon. When an icon accompanies a numbered figure or problem, the figure or problem number is used to identify the model on the CD. When an icon appears next to an unnum- bered figure, the name of the model is listed next to the icon. Some SpartanView procedures are identical to SpartanBuild procedures and are not described in detail. In particular, the same mouse button-keyboard combinations are used to rotate, translate, and scale models. Also, the same menu commands are used to change the model display and obtain geometry data. Please refer back to the SpartanBuild instructions for help with these operations. START SpartanView, OPEN AND CLOSE MODELS, SELECT AND MOVE “ACTIVE” MODEL One difference between SpartanView and SpartanBuild is the number of models that the two programs can display. SpartanBuild can display only a single model, but Spartan- View allows the simultaneous display of several models. Only one SpartanView model can be “active” at any time, and most mouse and menu operations affect only the “active” model. The following tutorials contain instructions for using SpartanView. Please perform these operations on your computer as you read along. SpartanView and SpartanBuild are lo- cated on Learning By Modeling. Both programs are “CD-protected.” This causes the SpartanView window to open. The window is blank initially. “Appendix A” in the Appendix folder contains three models: water, methanol, and hydrogen chloride. This makes hydrogen chloride the active model. The name of the active model is displayed at the top of the SpartanView window. Only one model can be active at any time. Rotation and translation affect only the active model, but scaling affects all mod- els on the screen. Close affects only the active model. Installing Spartan View 1. Insert SpartanView CD. 2. Double-click on the CD’s icon. Starting SpartanView 3. Double-click on the SpartanView icon. Opening models 4. Select Open from the File menu. 5. Double-click on “Appendix,” then double-click on “Appendix A.” Making hydrogen chloride, HCI, the “ac- tive” model 6. Move the cursor to any part of the hydrogen chloride model, and click on it. Moving a model 7. Rotate, translate, and scale the ac- tive model using the same mouse and keyboard operations as those used with SpartanBuild. Closing model 8. Select Close from the File menu. APPENDIX 3 A-71 QUANTUM MECHANICAL MODELS Most of the SpartanView models on the CD have been constructed using quantum mechanical calculations, although some simplifications have been used to accelerate the calculations. This means that the models, although closely resembling real molecules, never precisely duplicate the properties of real molecules. Even so, the models are suf- ficiently similar to real molecules that they can usually be treated as equivalent. This is important because models can contain more types of information, and models can be constructed for molecules that cannot be studied in the laboratory. Also, models can be joined together to make “animations” that show how molecules move. MEASURING AND USING MOLECULAR PROPERTIES SpartanView models provide information about molecular energy, dipole moment, atomic charges, and vibrational frequencies (these data are accessed from the Properties menu). Energies and charges are available for all quantum mechanical models, whereas dipole moments and vibrational frequencies are provided for selected models only. Energy is the most useful molecular property because changes in energy indicate whether or not a chemical reaction is favorable and how fast it can occur. SpartanView reports energies in “atomic units,” or au (1 au H11005 2625.5 kJ/mol). The energy of any sys- tem made up of infinitely separated (and stationary) nuclei and electrons is exactly 0 au. A molecule’s energy can therefore be thought of as the energy change that occurs when its component nuclei and electrons are brought together to make the molecule. The “assembly” process releases a vast amount of energy, so molecular energies are always large and negative. The energies of two molecules (or two groups of molecules) can be compared as long as they contain exactly the same nuclei and exactly the same number of electrons, a condition that is satisfied by isomers. It is also satisfied by the reactants and products of a balanced chemical reaction. For example, the energy change, H9004E, for a chemical reaction, A H11001 B → C H11001 D, is obtained by subtracting the energies of the reactant mol- ecules from the energies of the product molecules: H9004E H11005 E C H11001 E D H11002 E A H11002 E B . H9004E is roughly equivalent to the reaction enthalpy, H9004H°. The same type of computation is used to calculate the activation energy, E act . This energy is obtained by subtracting the ener- gies of the reactant molecules from that of the transition state. The calculated energy of water (H1100275.5860 au) is displayed at the bottom of the screen. The calculated magnitude of the dipole moment of water (2.39 D) is displayed at the bottom of the screen. The calculated direction is indicated by a yellow arrow. Making water the active model 1. Move the cursor to any part of the water model, and click on it. Measuring the calculated energy 2. Select Energy from the Properties menu. 3. Click on Done when finished. Measuring the dipole moment 4. Select Dipole Moment from the Properties menu. 5. Click on Done when finished. A-72 APPENDIX 3 DISPLAYING MOLECULAR VIBRATIONS AND MEASURING VIBRATIONAL FREQUENCIES Molecular vibrations are the basis of infrared (IR) spectroscopy. Certain groups of atoms vibrate at characteristic frequencies and these frequencies can be used to detect the pres- ence of these groups in a molecule. SpartanView displays calculated vibrations and frequencies for selected models. Calculated frequencies are listed in units of (cm H110021 ) and are consistently larger than observed frequencies (observed frequency H11005 0.9 H11003 calculated frequency is a good rule of thumb). DISPLAYING ELECTROSTATIC POTENTIAL MAPS One of the most important uses of models is to show how electrons are distributed inside molecules. The “laws” of quantum mechanics state that an electron’s spatial location can- not be precisely specified, but the likelihood of detecting an electron at a particular loca- tion can be calculated (and measured). This likelihood is called the “electron density” (see Chapter 1), and SpartanView can display three-dimensional graphs that show regions of high and low electron density inside a molecule. The electron density at a given location is equivalent to the amount of negative charge at that location. Thus, a hydrogen atom, which consists of a proton and an elec- tron, can be thought of as a proton embedded in a “cloud” of negative charge. The total amount of charge in the cloud exactly equals the charge on a single electron, but the charge at any given point in the cloud is considerably smaller and varies as shown in the following graph. Electron density Distance from nucleus 0 r Frequencies (in cm H110021 ) are listed in nu- merical order from smallest (or imagi- nary) at the top to largest at the bottom. A checkmark indicates the active vibra- tion (only one vibration can be displayed at a time). Atom motions are exagger- ated to make them easier to see. Vibrations appear most clearly when a molecule is displayed as a ball-and-spoke model. Double-clicking on an active vibration deactivates it. Displaying a list of vibrational frequen- cies for water 1. Select Frequencies from the Prop- erties menu. Displaying a vibration 2. Double-click on a frequency to make it active. 3. Click on OK to close the window. 4. Select Ball and Spoke from the Model menu. Stopping the display of a vibration 5. Repeat step 1, double-click on the active vibration, and click on OK. APPENDIX 3 A-73 The graph shows that negative charge (or electron density) falls off as one goes farther away from the nucleus. It also shows that the charge cloud lacks a sharp bound- ary, or “edge.” The apparent lack of an edge is problematic because we know from exper- imental observations that molecules do, in fact, possess a characteristic size and shape. SpartanView models solve this problem by using an arbitrarily selected value of the elec- tron density to define the edge of a molecule’s electron cloud. The program searches for all of the locations where the electron density takes on this edge value. Then it connects these locations together to make a smooth surface called a “size density surface,” or more simply, a “density surface.” Such density surfaces can be used as quantum mechanical “space-filling” models. The size and shape of density surfaces are in good agreement with the size and shape of empirical space-filling models, and the amount of electron density that lies outside the density surface is usually inconsequential. A density surface marks the edge of a charge cloud, but it does not tell us how electron density is distributed inside the cloud. We can get a feel for the latter by cal- culating the electrostatic potential at different points on the density surface. The elec- trostatic potential at any point (x, y, z) on the density surface is defined as the change in energy that occurs when a “probe” particle with H110011 charge is brought to this point start- ing from another point that is infinitely far removed from the molecule (see figure). If the energy rises (positive potential), the probe is repelled by the molecule at point (x, y, z). If the energy falls (negative potential), the probe is attracted by the molecule. The electrostatic potential gives us information about the distribution of electron density in the molecule because the potential at point (x, y, z) is usually influenced most by the atom closest to this point. For example, if a molecule is neutral and the potential at point (x, y, z) is positive, then it is likely that the atom closest to this point has a net positive charge. If the potential at (x, y, z) is negative, then it is likely that the closest atom has a net negative charge. The size of the potential is also useful. The larger the potential at a given point, the larger the charge on the nearest atom. These rules for assigning atomic charges work well for most neutral molecules, but they do not work for ions. This is because an ion’s overall charge dominates the potential near the ion. For example, positive ions generate a positive potential every- where around the ion. The rules also fail for atoms with highly distorted electron clouds. In such cases, positive and negative potentials are both found near the atom, and the charge is ambiguous. Infinite distance Density surface Move probe Probe x, y, z? H11001 H11001 A-74 APPENDIX 3 SpartanView uses color to display the value of the electrostatic potential on the density surface. These colored diagrams are called “electrostatic potential maps” or just “potential maps.” Different potentials are assigned different colors as follows: red (most negative potential on the map) H11021 orange H11021 yellow H11021 (green) H11021 blue (most positive potential on the map). The following potential map of water shows how this works (refer to the ball-and-spoke model for the molecule’s orientation). The most negative potential (red) is found near oxygen, and the most positive potentials (blue) are found near the hydrogens. Thus, we can assign a partial negative charge to oxygen and partial positive charges to the hydrogens. The potential map of water tells us the relative charges on oxygen and hydrogen, but it does not tell us if these charges are large or small. To discover this, we need to know the magnitude of the potentials. As it turns out, the most positive potentials (the blue regions) on this map are about 250 kJ/mol—a large value for a neutral molecule— so the atomic charges must be fairly large. Potential maps can be used to compare electron distributions in different molecules providing all of the maps assign the same color to the same potential, that is, the maps all use the same color–potential scale. A “normal” potential map for methane (CH 4 ) is shown on the left (by “normal” we mean that the map displays the most negative potential as red and the most positive potential as blue). This map tells us that carbon carries a partial neg- ative charge and the hydrogens carry partial positive charges. But, just like before, the map does not tell us the magnitude of these charges. One way to get at this information is to reassign the colors using the color–potential scale that was previously used to make water’s potential map (see preceding discussion). This gives a new map that looks more or less green everywhere. This fact, along with the total absence of red and blue, tells us that the potentials, and the atomic charges, in methane are much smaller than those in water. (The most positive potential on methane’s map is only 50 kJ/mol.) normal color assignments color assignments based on water molecule’s potential map (see above) APPENDIX 3 A-75 CHEMICAL APPLICATIONS OF ELECTROSTATIC POTENTIAL MAPS Potential maps are a very powerful tool for thinking about a variety of chemical and physical phenomena. For example, water’s potential map suggests that two water mole- cules will be attracted to each other in a way that brings a positive hydrogen in one mol- ecule close to the negative oxygen in the other molecule (see figure). This type of inter- molecular bonding is called a “hydrogen bond.” Significant hydrogen bonding does not SpartanView uses the word “density” to identify size density surfaces. The size density surface is similar in size and shape to a space-filling model. This removes the size density surface. The red part of the map identifies oxy- gen as a negatively charged atom, and the blue part identifies the most posi- tively charged hydrogen atom. Making methanol the active model 1. Move the cursor to any part of the methanol model, and click on it. Displaying a size density surface 2. Select Density from the Surfaces menu, then select Transparent from the sub-menu. Stopping the display of a surface 3. Select Density from the Surfaces menu, then select None from the sub-menu. Displaying an electrostatic potential map 4. Select Potential Map from the Sur- faces menu, then select Solid from the sub-menu. Closing all of the models. 5. Select Close All from the File menu. Size density surface (top left), space-filling model (top right), potential map (bottom left), and tube model (bottom right) for methanol. A-76 APPENDIX 3 occur between methane molecules because methane molecules create much smaller potentials. Potential maps can also be useful predictors of chemical reactivity. For example, the nitrogen atoms in ethylamine, CH 3 CH 2 NH 2 , and in formamide, O?CHNH 2 , appear to be identical, and we might therefore predict similar chemical reactivity patterns, but the potential maps of these compounds tell a different story. The potential map of eth- ylamine (see following figure, left) shows a region of negative potential that coincides with the location of the lone-pair electron density. This nitrogen is a good electron donor and can act as a base or nucleophile. Formamide’s map (see figure, right), on the other hand, shows that the oxygen atom might act as an electron donor, but not the nitrogen atom. The nitrogen atoms in these compounds are very different, and they will display different chemical behavior as well. The same kinds of comparisons can also be applied to the short-lived (and there- fore hard-to-observe) molecules that form during a chemical reaction. The potential maps of n-butyl cation, CH 3 CH 2 CH 2 CH 2 H11001 , and tert-butyl cation, (CH 3 ) 3 C H11001 , show us that these highly reactive species differ in significant ways. The electrostatic potentials for n-butyl cation vary over a wider range, and the positive charge is clearly associated with the end carbon (see following figure, left). tert-Butyl cation’s map, by comparison, shows a much smaller range of potentials (see figure, right). The central carbon is positively charged, but the potential never becomes as positive as those found in n-butyl cation. This tells us that some of the electron density normally associated with the methyl groups has been transferred to the central carbon. APPENDIX 3 A-77 As a final example, we compare potential maps of the reactants, transition state, and products for an S N 2 reaction, Cl H11002 H11001 CH 3 Br → ClCH 3 H11001 Br H11002 . The reactant and product maps show negatively charged chloride and bromide ions, respectively; there- fore, this reaction causes electron density to shift from one atom to another. The transi- tion state map is distinctive in that it shows partial negative charges on both Cl and Br, that is, the negative charge is delocalized over Cl and Br in the transition state. DISPLAYING MOLECULAR ORBITAL SURFACES SpartanView displays molecular orbitals as colored surfaces. An orbital surface connects points in space where the selected orbital has a particular numerical magnitude, and dif- ferent colors are used to indicate surfaces corresponding to negative and positive values of the orbital. The most important molecular orbitals are the so-called frontier molecular orbitals. These are the highest (energy) occupied molecular orbital (HOMO), and lowest (energy) unoccupied molecular orbital (LUMO). The following picture shows the LUMO sur- face for the hydrogen molecule, H 2 . The LUMO consists of two separate surfaces, a red Cl H11002 H11001 CH 3 ±Br [Cl---CH 3 ---Br] H11002 Cl±CH 3 H11001 Br H11002 CH 3 CH 2 CH 2 CH 2 H11001 (CH 3 ) 3 C H11001 A-78 APPENDIX 3 surface surrounding one hydrogen and a blue surface surrounding the other. The colors tell us that the orbital’s value is negative near one hydrogen, and positive near the other. We can also tell from this that the orbital’s value must pass through zero somewhere in the empty space between the two surfaces (the “zero” region is called a “node”). Any node that crosses the bonding region makes an orbital “antibonding” and raises the orbital’s energy. As a rule, electrons are only found in low-energy bonding orbitals, but this can change during a chemical reaction. Molecular orbitals are useful tools for identifying reactive sites in a molecule. For exam- ple, the positive charge in allyl cation is delocalized over the two terminal carbon atoms, and both atoms can act as electron acceptors. This is normally shown using two reso- nance structures, but a more “compact” way to see this is to look at the shape of the ion’s LUMO (the LUMO is a molecule’s electron-acceptor orbital). Allyl cation’s LUMO appears as four surfaces. Two surfaces are positioned near each of the terminal carbon atoms, and they identify allyl cation’s electron-acceptor sites. Appendix B contains two models: ethyl- ene and butane. The HOMO (left) and LUMO (right) of ethyl- ene. Moving into “Appendix B” and making ethylene the active model 1. Select Open from the File menu and double click on “Appendix B.” Move the cursor to any part of the ethylene model, and click on it. C HC H H C H H H11001 C HC H H C H H H11001 APPENDIX 3 A-79 DISPLAYING SpartanView SEQUENCES (ANIMATIONS) SpartanView can display atom motions that occur during a conformational change or chemical reaction. The scroll bar slides back and forth, and the “step” label is updated during the animation. You can rotate, translate, and scale the model at any point during the animation. The animation and the scroll bar stop at the current step in the sequence. The scroll bar jumps to a new position, and the step label is updated, to show the current location in the sequence. All properties (energy, dipole moment, atomic charges) and geometry parame- ters (distance, angle, dihedral angle) can be animated or stepped through. Making butane the active model 1. Move the cursor to any part of the butane model, and click on it. Animating a sequence 2. Click on the “arrow” button in the lower left-hand corner of the win- dow. Stopping the animation 3. Click on the “double bar” button in the lower left-hand corner of the window. Stepping through a sequence 4. Click on the “bar-arrows” at the right end of the scroll bar. Measuring a property for a sequence 5. Select Energy from the Properties menu. 6. Repeat step 4 to see other ener- gies. Quitting SpartanView 7. Select Quit from the File menu. This displays the LUMO of ethylene. This is an unoccupied antibonding molecular orbital. The orbital is no longer displayed. This displays the HOMO of ethylene. This is an occupied bonding molecular or- bital. Displaying an orbital surface 2. Select LUMO from the Surfaces menu, then select Transparent from the sub-menu. Stopping the display of an orbital sur- face 3. Select LUMO again from the Sur- faces menu, then select None from the sub-menu. 4. Select HOMO from the Surfaces menu, then select Transparent from the sub-menu. C-1 CREDITS INTRODUCTION Pages 3, 4, 5 Stamps are courtesy of James O. Schreck, Professor of Chemistry, University of Northern Colorado. CHAPTER 11 Page 410 (Figure 11.5) was generated using crystallographic coordinates obtained from the Center for Computational Materi- als Science at the United States Naval Research Laboratory via http://cst-www.nrl.navy.mil/lattice/struk/a9.html. Page 411 (Figure 11.7) was obtained from the Center for Nanoscale Science and Technology at Rice University via http://cnst.rice.edu/images/Tube1010a.tif. CHAPTER 13 Page 488 (Figure 13.1) is from M. Silberberg, Chemistry, 2nd ed., p. 260. McGraw-Hill, New York, 2000. Page 517 (Figure 13.24) is courtesy of Simon Fraser/Science Photo Library/Photo Researchers, Inc. Newcastle upon Tyne. Page 524 (Figure 13.32) is adapted from R. Isaksson, J. Roschester, J. Sandstrom, and L. G. Wistrand, Journal of the Ameri- can Chemical Society, 1985, 107, 4074–4075 with permission of the American Chemical Society. Page 527 (Figure 13.34) is from M. Silberberg, Chemistry, 2nd ed., p. 56. McGraw-Hill, New York, 2000. Page 530 (Figure 13.38) is adapted from H. D. Durst and G. W. Gokel, Experimental Organic Chemistry, 2nd ed., McGraw- Hill, New York, 1987. Mass spectra are reproduced with permission from “EPA/NIH Mass Spectral Data Base,” Supplement I, S. R. Heller and G. W. A. Milne, National Bureau of Standards, 1980. CHAPTER 25 Page 994 (Figure 25.8) is adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID: 4TF4. Sakon, J., Irwin, D., Wilson, D. B., Karplus, P. A., Structure and Mechanism of Endo/Exocellulase E4 from Thermomono- spora Fusca. To be published. CHAPTER 26 Page 1035 (Figure 26.9c) is adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID: 1CLE. Ghosh, D., Wawrzak, Z., Pletnev, V. Z., Li, N., Kaiser, R., Pangborn, W., Jornvall, H., Erman, M., Duax, W. L., Structure of Uncomplexed and Linoleate-Bound Candida Cholesterol Esterase. To be published. CHAPTER 27 Page 1084 is adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID: 1PID. Brange, J., Dodson, G. G., Edwards, D. J., Holden, P. H., Whittingham, J. L., A Model of Insulin Fibrils Derived from the X-Ray Crystal Structure of a Monomeric Insulin (Despentapeptide Insulin). To be published. Page 1085 (Figure 27.16) is adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID: 2SLK. Fossey S. A., Nemethy, G., Gibson, K. D., Scheraga, H. A., Conformational Energy Studies of Beta-Sheets of Model Silk Fibroin Peptides. I. Sheets of Poly(Ala-Gly) Chains. Biopolymers 31, pp. 1529 (1991). Page 1087 (Figure 27.18) is adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID: 2CTB. Teplyakov, A., Wilson, K. S., Orioli, P., Mangani S., The High Resolution Structure of the Complex between Car- boxypeptidase A and L-Phenyl Lactate. To be published. Page 1089 (Figure 27.21) is adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID: 1VXH. Yang, F., Phillips Jr., G. N., Structures of Co-, Deoxy- and met-Myoglobins at Various Ph Values. To be published. Page 1090 and page 1097 (Figure 27.25) is adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID: 1DDN. White, A., Ding, X., Vanderspek, J. C., Murphy J. R., Ringe, D., Structure of the Metal-Ion-Activated Diphtheria Toxin Repressor/Tox Operator Complex. Nature 394, pp. 502, (1998). Page 1100 (Figure 27.28) is adapted from crystallographic coordinates deposited with the Protein Data Bank. PDB ID: 6TNA. Sussman, J. L., Holbrook, S. R., Warrant, R. W., Church, G. M., Kim, S. H., Crystal Structure of Yeast Phenylala- nine T-RNA. I. Crystallographic Refinement. J.Mol.Biol. 123, pp. 607, (1978). I-1 Abscicic acid, 1027 Absolute configuration, 267–271, 292 Absorption of electromagnetic radiation, 489 in infrared spectroscopy, 518 in nuclear magnetic resonance spectroscopy, 490–493 in ultraviolet-visible spectroscopy, 524–525 Absorptivity. See Molar absorptivity Acetaldehyde, 655 bond angles, 657 enolization of, 706 formation of, in biological oxidation of ethanol, 600–602 preparation of from ethylene, 248, 598 by hydration of acetylene, 356 reactions of aldol addition, 716 with hexylmagnesium bromide, 555 hydration, 663 in Strecker synthesis of D,L-alanine, 1061–1062 Acetaldol, 716 Acetals, 668–672, 689 glycosides as, 989 hydrolysis of, 670, 672 preparation of, 669–671, 672, 689 as protecting group, 671–672 Acetamide electrostatic potential map, 777 Acetanilide, 879 preparation and nitration of, 887 reduction of, 879 resonance in, 886 Acetic acid acidity of, 740–742, 746, 747 conversion to mevalonic acid, 1028, 1032–1033 electrostatic potential maps acetate ion, 741, 742 acid, 739, 742 esterification of, 594, 610 industrial preparation and use of, 750, 783 natural occurrence of, 4, 736, 750 natural products derived from, 1015–1050 Acetic anhydride, 775 electrostatic potential map, 777 in Friedel-Crafts acylation, 455, 471, 473, 478, 784 preparation of, 783 reactions of with alcohols, 610, 785, 789 with arylamines, 785, 886 with H9251-D-glucopyranose, 1004 with glycine, 1063 with phenols, 949, 951–952, 963 with salicylic acid, 952 with sucrose, 1010 UV absorption, 818 Acetoacetic ester synthesis, 839–841, 850. See also Ethyl acetoacetate Acetoacetyl acyl carrier protein, 1021 Acetoacetyl coenzyme A, 1021, 1032 Acetone bond angles, 657 enolization of, 704, 706 electrostatic potential map, 701 reactions of aldol condensation, 720 bromination, 704–705 cyanohydrin formation, 667 hydration, 663 reductive amination of, 903 Wittig reaction, 690 as solvent, 305 Acetonitrile electrostatic potential map, 777 UV absorption, 818 Acetophenone, 407, 455, 656 acidity of, 710 acylation of enolate, 837 phenylhydrazone, 674 reactions of aldol condensation, 720 bromination, 473 with butyllithium, 582 chlorination, 474 with ethylmagnesium bromide, 559 nitration, 473 Acetyl chloride, 775 electrostatic potential map, 774, 777 reactions of with arylamines, 886 with tert-butyl alcohol, 610 with phenol, 951 UV absorption, 818 Acetyl coenzyme A in fatty acid biosynthesis, 1019–1022 formation from pyruvic acid, 1016 reactions of, 1016 structure, 1016 in terpene biosynthesis, 1032 Acetylene acidity of, 336, 344–346, 552 alkylation of, 336, 346–348, 359 bonding in, 14, 40–42, 47, 54, 341–343 conversion to cyclooctatetraene, 422 electrostatic potential map, 339, 342 Grignard reagent of, 553 hydration of, 356 preparation of, 339–340 structure of, 341–342 N-Acetyl-D-galactosamine, 995, 996 N-Acetyl-D-glucosamine, 988 Acetylide ion, 336, 345–346, 348. See also Sodium acetylide O-Acetylsalicylic acid. See Aspirin Achiral molecules, 260, 290 meso forms, 279–282 symmetry elements in, 264–265 Acid anhydrides. See Carboxylic acid anhydrides Acid-base properties of amino acids, 1057–1061 Acid-base reactions, 133–137, 344–346, 551–553, 604, 708–711, 864–865 Acid catalysis of acetal formation, 669–671, 672 of acetal hydrolysis, 672 of amide hydrolysis, 805–807, 821 of dehydration of alcohols, 182, 185–190, 200, 419, 591 of epoxide ring opening, 632–633, 635–637, 646 of ester hydrolysis, 791–794, 820 of esterification, 593–594, 610, 754–757, 767 of ether formation, 592–593, 610, 625–626, 644 of glycoside formation, 990 of hydration of alkenes, 225–227, 249 of hydration of alkynes, 355–356, 361 of nitrile hydrolysis, 815–816, 822 of nucleophilic acyl substitution, 786–787, 949 of nucleophilic addition to aldehydes and ketones, 665–667, 690–691 Acid dissociation constants, K a and pK a , 134, 336, 343, 345–346, 552, 710, 745–749, 864–865, 944. See also Acidity Acidity of acetylene and alkynes, 336, 343, 344–346, 358, 552 of alcohols, 135 of aldehydes, 710 of alkanes, 344–345, 552 of ammonia, 135, 345–346, 848 of ammonium ions, 135, 864–865 of benzene, 552 of carbonic acid, 749 of carboxylic acids, 740–749, 765–766 substituent effects on, 745–748 of 1,3,5-cycloheptatriene, 429 of 1,3-cyclopentadiene, 428 definition of Arrhenius, 134 Br?nsted-Lowry, 134–136 Lewis, 143 INDEX INDEX I-2 of dicarboxylic acids, 748 of diethyl malonate, 842 of diisopropylamine, 848 of H9252-diketones, 710 of esters, 848 of ethane, 343, 552 of ethanol, 135, 552, 740–741 of ethyl acetoacetate, 839 of ethylene, 343, 552 of hydrocarbons, 343–346, 552 table of hydrogen fluoride, 135, 345 of H9252-keto esters, 832–834, 839, 850 of ketones, 710 of methane, 344–345, 552 of phenols, 942–945, 962 quantitative relationships, 743 of representative compounds, 135 table, 552 table of substituted benzoic acids, 747–748 of thiols, 604, 723 of water, 135, 345, 552 Aconitic acid, 299, 772 Acrolein, 384, 721, 723, 729 Acrylic acid, 737, 747 Acrylonitrile, 14, 247, 815 Activated complex, 93. See also Transition state Activation energy, 93. See also Energy of activation Active ester, 1080 Acylation. See Friedel-Crafts acylation; Nucleophilic acyl substitution Acyl carrier protein, 1019–1022 Acyl cations, 454, 784 Acyl chlorides carbon-chlorine bond distance, 778 enolization, 760 Friedel-Crafts acylation with, 453–457, 478, 780, 951 infrared absorption frequency, 519, 817 nomenclature of, 775 preparation of, 454, 754, 780 reactions of, 780–783, 819–820 with alcohols, 594, 595, 610, 781, 789 with ammonia and amines, 781, 802, 820, 882, 886 with carboxylic acids, 781 with phenols, 949, 951–952 with water, 781, 782 resonance in, 778 Acyl group, 654, 775 Acyl halides, 775. See also Acyl chlorides Acyl transfer reactions. See Nucleophilic acyl substitution Addition-elimination mechanism of nucleophilic aromatic substitution, 923–927, 932–933 Addition polymers, 247 Addition reactions. See also Aldehydes; Alkenes; Alkynes; Dienes; Ketones 1,2 addition versus 1,4 addition, 379–382, 392, 722–723 anti addition, 212, 233–234, 236, 237, 250, 284, 351–352, 356–357 Diels-Alder cycloaddition, 382, 392–393 of benzyne, 931–932 electrophilic to alkenes, 213–220, 223–243, 244–245, 249–251, 284–286 to alkenylbenzenes, 419–421, 435 to alkynes, 352–357, 361 table to conjugated dienes, 379–382, 392 free-radical, to alkenes, 220–223, 245–246, 251 hydrogenation of alkenes, 208–213, 249, 285 of alkenylbenzenes, 419–420 of alkynes, 350–351, 360 of dienes, 374–375 and Markovnikov’s rule alkenes, 214–219, 251 alkynes, 352–354, 356, 361 nucleophilic to aldehydes and ketones, 663–700 to H9251,H9252-unsaturated aldehydes and ketones, 722–724, 728 syn addition, 212, 230, 239–240, 250, 285, 351 Ad E 3 mechanism, 353 Adenine, 431, 1091 Adenosine, 989, 1091 Adenosine 3H11032-5H11032-cyclic monophosphate (cyclic AMP), 1093 Adenosine diphosphate, 1093 Adenosine 5H11032-monophosphate, 1092 Adenosine triphosphate, 1093 reaction with methionine, 641 S-Adenosylmethionine, 314, 641 Adipic acid polyamides from, 840 ADP. See Adenosine diphosphate Adrenaline, 272–273, 640. See also Epinephrine Agent Orange, 955 AIDS (acquired immune deficiency syndrome), 1098 H9252-Alanine, 1052 Alanine, 1054, 1059 biosynthesis of, 1063–1065 electrophoresis of, 1060–1061 electrostatic potential map, 1053 ethyl ester, 1063 synthesis, 1061 Alanyglycine, 1067–1068 electrostatic potential map, 1067 Alcohols acidity of, 135, 740–741, 943 biological oxidation of, 600–602 bonding, 129 as Br?nsted bases, 135–136 classification of, 128, 160 in Friedel-Crafts reactions, 950 hydrogen bonding in, 130–131, 134, 160, 322 hydrogen-deuterium exchange in, 166, 510 infrared spectra, 519 table inorganic esters of, 595–596, 610 mass spectra, 607 naturally occurring, 580 nomenclature of, 127–128, 159, 169 nuclear magnetic resonance spectra carbon, 606 proton, 509–510, 605–607 physical properties, 130–133, 160 preparation of from epoxides, 587–588, 608, 632, 635 from Grignard reagents, 553–555, 557, 560–561, 572, 573, 582, 583, 608, 790 by hydration of alkenes, 225–227, 249, 581 by hydroboration-oxidation, 227–233, 250, 581 by hydrolysis of alkyl halides, 582 from organolithium reagents, 554–556, 572, 573, 582, 608 by reduction of carbonyl compounds, 583, 608, 790 via alkyl hydrogen sulfates, 224–225 reactions of, 591 table, 610 table with acyl chlorides, 594–595, 610, 781 with aldehydes and ketones, 668–672, 689 with carboxylic acid anhydrides, 595, 610, 785–787 conversion to ethers, 590–593, 610, 625–626, 644 dehydration, 182, 185–190, 200, 379, 419, 591 esterification, 593–595, 610, 754–757, 767, 789 with hydrogen halides, 137–146, 160–162, 329–330, 332, 591 with inorganic acids, 595–596, 610 oxidation, 596–602, 611 table with phosphorus tribromide, 147, 161, 591 with thioesters, 800 with thionyl chloride, 147, 161, 591 with p-toluenesulfonyl chloride, 326, 332, 591 solubility in water, 132–133 Aldaric acids, 1000 Aldehydes acidity of, 710 aldol condensation, 715–720, 728 classification of carbons in, 702 enolization of, 705–707, 727 infrared spectra, 519, 684–685 mass spectra, 687 naturally occurring, 659 nomenclature of, 654–656, 688 nuclear magnetic resonance spectra, 496, 513, 684–686 nucleophilic addition to, 663–682 physical properties, 658 preparation of hydroformylation of alkenes, 661, 732 oxidation of primary alcohols, 596, 597, 611, 659 ozonolysis of alkenes, 241–242, 660 reactions of acetal formation, 668–672, 689 with amines, 672–677, 689, 690, 882 cyanohydrin formation, 667–668, 689 with derivatives of ammonia, 674 I-3 INDEX Aldehydes—Cont. with Grignard reagents, 555, 572, 573, 662, 722 halogenation, 703–705, 727 hydration, 663–667, 689 hydrogenation, 583–584, 662 with organolithium reagents, 554–556, 572, 573, 662 oxidation, 682, 691 reduction, 662 with Wittig reagents, 677–681, 690 in reductive amination, 879–881, 903 in Strecker synthesis of amino acids, 1061–1062 structure and bonding, 657–658, 688 Alder, Kurt, 382 Alditols, 998 Aldohexose, 976–978 Aldolase, 1003 Aldol condensation, 715–720, 728 intramolecular, 718, 724, 728 mixed, 719–720, 728 retro-, 1003 Aldonic acids, 999–1000 Aldopentose, 976–978 Aldoses, 973, 1007 Fischer projection formulas of, 977 Aldotetrose, 974–976 Alicyclic hydrocarbons, 68. See also Cycloalkanes Aliphatic hydrocarbon, definition of, 53, 399 Alizarin, 958 Alkadienes, 372–390. See also Dienes preparation of, 378–379 relative stabilities, 374–375 ultraviolet-visible spectra, 524–526 Alkaloids, 869 Alkanes, 53–88 acidity of, 344–345, 552 chiral, 262 conformations of, 89–98, 117–118 infrared spectra, 519–521 IUPAC names of unbranched, 62 table mass spectra, 529–530 nomenclature of, 61–68 physical properties, 71–74 preparation of hydrogenation of alkenes, 208–209, 243 hydrogenation of alkynes, 350 using organocopper reagents, 561–563, 573 reactions of combustion, 74–77 dehydrogenation, 168, 181 halogenation, 54, 126, 148, 153–159, 161, 162–163 relative stability of isomers, 75–76 Alkatetraene, 374 Alkatriene, 374 Alkenes, 167–258 acidity of, 345 bonding in, 38–40, 42, 170–172, 198 cycloalkenes, 170, 180–181, 199 as dienophiles, 382, 384 electrophilic addition to, 213–220, 223–243, 244–245, 249, 274, 284–285 E-Z notation, 173–175, 199 free-radical addition to, 220–223, 245–246, 251 in Friedel-Crafts reactions, 452, 453 heats of combustion, 176–178 heats of hydrogenation, 209–212 infrared spectra, 519 table, 520–521 isomers, 172–181, 199 relative stabilities of, 176–181, 199 naturally occurring, 167, 168 nomenclature of, 167–170, 198 physical properties of, 174–176 preparation of, 168, 181–198, 200 table from alkynes, 350–352, 360 dehydration of alcohols, 182–190, 200, 419, 591 dehydrogenation of alkanes, 168, 181, 419 dehydrohalogenation of alkyl halides, 190–198, 200, 419 Hofmann elimination, 883–885, 904 Wittig reaction, 677–681, 690 reactions of, 208–258 allylic halogenation, 370–372, 391 with dibromocarbene, 566 Diels-Alder reaction, 382 392–393 epoxidation, 238–240, 250, 274, 630, 645 halogen addition, 233–236, 250, 420 halohydrin formation, 236–238, 250, 630–631 hydration, 225–227, 249 hydroboration-oxidation, 227–233, 250 hydroformylation, 661 hydrogenation, 208–213, 249, 285, 419 with hydrogen halides, 213–223, 251, 249, 275, 420 hydroxylation, 590, 637 with iodomethylzinc iodide, 563–564, 571 ozonolysis, 240–242, 251, 660 polymerization, 244–247, 251–252, 289, 421, 567–570, 573 with sulfuric acid, 223–225, 249 stereoisomerism in, 172–175, 199, 284 Alkenylbenzenes, 419–421, 435 Alkenyl cations, 353 Alkenyl groups, 169–170 Alkenyl halides, 303 Alkenyl radical, 352 Alkoxide ions as bases in elimination, 190–191, 565 as nucleophiles, 303, 304, 312–313, 626–627, 644 substitution versus elimination in reactions with alkyl halides, 323–325, 332, 626–627 Alkylamines. See Amines Alkylation of acetoacetic ester, 839–841, 850 of acetylene and alkynes, 336, 346–348, 359 of ammonia, 872–875, 901 of H9252-diketones, 726, 729 of ester enolates, 848–849 Friedel-Crafts, 445, 450–453, 478, 479 of malonic ester, 842–845, 852 Alkyl azides preparation of, 304, 324, 723, 873 reduction of, 877, 902 Alkylbenzenes. See also Arenes free-radical halogenation of, 414–416, 435 infrared spectra, 520–521 mass spectra, 531–532 oxidation of, 416–417, 435 preparation of, 445, 450–453, 455–456, 478, 563 Alkyl cyanides. See Nitriles Alkyl fluorides, 625 Alkyl groups classification of, 65–66 nomenclature of, 65–66, 83, 127 splitting patterns in proton magnetic resonance spectra, 503–505 stabilizing effect of in aldehydes and ketones, 658, 664 in alkenes, 176–178, 199 in alkynes, 350 in carbocations,140–143, 162, 317 in free radicals, 149–153 steric hindrance to nucleophilic substitution by, 310–312 Alkyl halides bonding in, 129 classification of, 128 in Friedel-Crafts alkylation reactions, 445, 450–453, 478, 479 in Gabriel synthesis of amines, 875–876, 902 naturally occurring, 713 nucleophilic substitution in, 302–325, 331 table, 346–348, 359, 626–627, 644, 725–726, 729, 839–845 crown-ether catalysis of, 625 phase-transfer catalysis of, 871–872 nomenclature of, 127, 159 physical properties, 130–133 preparation of from alcohols, 137–147, 160–162, 329–330 from alkanes, 148, 153–159, 161–163 from alkenes, 213–216, 220–226 reactions of with alkynide ions, 346–348, 359 with amines, 883, 904 with ammonia, 872–875, 901 dehydrohalogenation, 190–198, 200, 419 with H9252-diketones, 725–726, 729 with lithium, 549–550, 571 with lithium dialkylcuprates, 561–563, 573 with magnesium, 550–551, 571 with sodium azide, 303, 304, 322, 324, 873 with thiourea, 604, 609 with triphenylphosphine, 680 INDEX I-4 with typical nucleophiles, 304 table in Williamson ether synthesis, 626–627, 644, 954, 1004 solubility in water, 132 Alkyl hydrogen sulfates, 223–224, 249 Alkyl hydroperoxides, 397, 627–628 Alkyl iodides nucleophilic substitution in, 305–306, 331 preparation of, 305 Alkyloxonium ions. See Oxonium ions Alkynes, 339–364 acidity of, 343, 344–346, 358, 552, 556 bonding in, 341–343, 358 cyclic, 341, 344 as dienophiles, 385 infrared spectra, 519 table naturally occurring, 340 nomenclature of, 340 physical properties, 341 preparation of, 346–349, 359 table alkylation of acetylene and terminal alkynes, 346–348, 359 from geminal and vicinal dihalides, 348–349, 359 reactions of, 349–357, 360 table, 361 table alkylation of, 346–348, 359, 672 as Br?nsted acid, 343, 344–346, 358, 556 halogen addition to, 356–357, 361 hydration of, 355–356, 361, 660 hydrogenation of, 350–351, 360 hydrogen halide addition to, 352–354, 361 metal-ammonia reduction of, 351–352, 360 ozonolysis of, 357 structure, 341–343 Allene(s), 373, 377–378 chiral, 378 heat of hydrogenation, 374–375 structure and bonding, 377–378 Allinger, N. L., 97 D-Alloisoleucine, 1057 Allonolactone, 1009 D-Allose, 977 Allyl, 365, 390 alcohol, 366 bromide, 366, 841, 954 cation, 366 chloride, 366, 371 group, 169–170, 365 Allylic, 366 carbocations, 365, 366–369, 379–382, 390 free radicals, 365, 370–372, 390–391 halogenation, 370–372, 391 rearrangement, 369, 390 Allyl phenyl ether Claisen rearrangement of, 957–958 preparation of, 954 Altronolactone, 1009 D-Altrose, 977 Aluminum chloride catalyst for Friedel-Crafts reaction, 445, 450–456, 478, 660 catalyst for Fries rearrangement, 952 Amide ion. See also Sodium amide as base, 346–349, 359, 556, 848 in nucleophilic aromatic substitution reactions, 927–931 Amides. See also Imides; Lactams; Peptides infrared spectra, 519 table, 817 as intermediates in hydrolysis of nitriles, 815–816 mass spectrometry of, 818 nomenclature of, 776, 879 preparation of, 781, 785, 791, 799–803, 820, 821, 874, 886 reactions of dehydration, 814 Hofmann rearrangement, 807–813, 822, 874 hydrolysis, 804–807, 808, 887 protonation, 805 reduction, 879, 903 resonance in, 779, 886 rotational energy barrier, 779 structure, 779–780 Amines, 858–916. See also Aniline; Diazonium salts basicity, 864–870, 901 classification, 859 infrared spectra, 519 table, 897–898 mass spectra, 900 naturally occurring, 869–870 nomenclature of, 859–861, 900 nuclear magnetic resonance spectra carbon, 899 proton, 898–899 physical properties, 863–864 preparation of, 872–881, 901–903 alkylation of ammonia, 872–875, 901 Gabriel synthesis, 875–876, 902 Hofmann rearrangement, 807–813, 822 reduction of nitrogen-containing compounds, 877–881, 902–903 reductive amination, 879–881, 903 pyramidal inversion in, 290 reactions, 881–897, 904–907 with acyl chlorides, 781, 820, 882, 886 with aldehydes and ketones, 672–677, 689–690, 882 with alkyl halides, 883, 904 with carboxylic acid anhydrides, 785, 820, 886, 887 electrophilic aromatic substitution in arylamines, 886–888, 904 with esters, 799–800, 801 Hofmann elimination, 883–885, 904 nitrosation, 888–892, 904–905 structure and bonding, 861–863, 900–901 Amino acid analyzer, 1071 Amino acid racemization, 1057 Amino acids acid base properties, 1057–1060 analysis, 1060–1061, 1070–1071 classification, 1052 constituents of proteins, 1054–1055 table preparation of, 1061–1063 reactions of, 675, 1063–1066 stereochemistry, 1052, 1056–1057, 1103 zwitterionic structure, 1057, 1103 p-Aminobenzoic acid, 888, 897 4-Aminobutanoic acid. See H9253-Aminobutyric acid 3-Amino-2-butanol, 279, 873 H9253-Aminobutyric acid, 1052 1-Aminocyclopropanecarboxylic acid in ethylene biosynthesis, 168, 1052 3-Aminopropanoic acid. See H9252-Alanine Amino sugars, 988 Ammonia acidity of, 135, 345, 552, 848 basicity of, 135 boiling point, 131 bond angles, 29 nucleophilicity, 313 reaction of with alkyl halides, 872–875, 901 with epoxides, 634, 873 with esters, 799–800 with H9251-halo carboxylic acids, 760, 874, 1061 with methyllithium, 553 with H9251,H9252-unsaturated carbonyl compounds, 728 in reductive amination, 879–881, 903 as solvent, 346, 351–352 Ammonium salts acetate, 742 carbamate, 802–803 cyanate, 2 formal charge of nitrogen in, 18 nomenclature of, 860 AMP. See Adenosine 5H11032-monophosphate Amphoteric, 1057 Amylopectin, 993–994 Amylose, 994 Anabolic steroids, 1041 Analysis amino acid, 1070–1071 amino acid racemization, 1057 GC/MS, 530–531 retrosynthetic, 557–560, 564, 570–571, 679, 680, 840, 843 structure determination by instrumental methods, 487–545 Anandamide, 1019 Androgens, 1040, 1041 Androstenedione, 1041 Angle strain, 98, 117 in [10]-annulene, 425 in cycloalkanes, 98–99 in cycloalkynes, 341, 344 in cyclobutane, 98, 107–108 in cyclohexane, 99 in cyclopropane, 98, 107, 118 in cyclopropene, 180 in epoxides, 621 Angstrom unit, 22 Aniline, 407, 859. See also Arylamines; Diazonium salts basicity of, 866–868 electrostatic potential map, 862 isolation, 859 I-5 INDEX Aniline—Cont. physical properties, 864 reactions of acylation, 886–887 bromination, 466 diazotization, 891 in reductive amination, 880 resonance in, 863 structure and bonding, 861–863 Anion radical intermediates in Birch reduction, 413 in metal-ammonia reduction of alkynes, 351–352 in reaction of alkyl halides with metals, 549–550, 551 Anisole, 407 bromination of, 463 Friedel-Crafts acylation of, 478, 660 preparation of, 954 Annelation. See Annulation Annulation, 724 Annulenes, 423–426, 436, 544 Anomeric carbon, 978 Anomeric effect, 985 Anthracene, 408–409 Anti addition. See Addition reactions Antibiotics carbohydrate components of, 988 enediyne, 344 H9252-lactam, 803 macrolide, 758–759 polyether, 624 sulfa drugs, 896–897 Antibody, 995 Anticodon, 1100 Anti conformation, 92 alkanes, 94, 97, 118 in elimination reactions, 194–196, 200 ethers, 621 meso-2,3-butanediol, 279–280 peptides and proteins, 1067–1068 Antigen, 995 Anti-Markovnikov addition, 220 D-Apiose, 988, 1011 Aprotic solvents, 322, 875 D-Arabinitol, 1009 D-Arabinose, 977, 1006, 1009 L-Arabinose, 976, 1001 Arachidic acid, 1018, 1025 Arachidonic acid, 1018, 1025 Aramid polymers, 809 Archaea, 58, 299 Arene oxides, 409, 948, 1064 Arenes, 54, 398–442 biological oxidation, 409, 417, 948, 1064 infrared spectra, 519 table nuclear magnetic resonance spectra carbon, 513 table proton, 495–496 Arenium ion, 444 L-Arginine, 1055, 1059 electrostatic potential map, 1053 Aromatic compounds and aromaticity, 54, 398–442 annulenes, 423–426, 436 benzene, 399–406 heterocyclic, 430–433, 436–437 Hückel’s rule, 423–430, 432–433, 436 ionic, 426–430, 436 nomenclature of, 406–408, 434 physical properties, 411, 434 polycyclic, 408–409, 434 reactions of Birch reduction, 412–414, 434 electrophilic aromatic substitution, 443–486 side-chain reactivity, 414–421, 435 table. (see also Arenes; Electrophilic aromatic substitution; individual compounds, for example: Aniline; Benzene etc.) Arrhenius, Svante, 134 Artificial sweeteners, 997–998 Arylamines basicity of, 865, 866–868 nomenclature of, 859–861 preparation of, 878 reactions of acylation, 886–888 electrophilic aromatic substitution, 466, 886–888, 904 nitrosation, 891–895 in reductive amination, 880 structure and bonding, 861–863 (see also Aniline; Diazonium salts) Aryl cyanides. See Nitriles Aryl esters Fries rearrangement of, 952 in peptide bond formation, 1080 preparation of, 949, 951–952, 963 Aryl ethers cleavage by hydrogen halides, 956–957, 964 preparation of, 954–956, 964 Aryl halides, 303, 917–938 bond dissociation energies, 918 naturally occurring, 920 physical properties of, 918 preparation of from aryl diazonium salts, 892–893, 905–906, 919 halogenation of arenes, 445, 448–450, 478, 919 reactions of electrophilic aromatic substitution, 469–470, 921 formation of Grignard reagent, 550, 921 with lithium, 549 nucleophilic aromatic substitution, 922–931, 932–933, 946, 956, 1071–1072 structure and bonding, 917–918 Ascaridole, 1046 Ascorbic acid (vitamin C), 164, 771, 980, 1001 L-Asparagine, 1054, 1059 electrostatic potential map, 1053 Aspartame, 997–998 L-Aspartic acid, 1055, 1059 electrophoresis of, 1060–1061 electrostatic potential map, 1053 Aspirin, 51, 164 inhibition of prostaglandin biosynthesis by, 1025 preparation of, 952–954 Asymmetric center. See Stereogenic center Atactic polymers, 289, 567 Atomic number, 7 and the sequence rule, 173 ATP. See Adenosine triphosphate Axial bonds in cyclohexane, 100–105, 119 Azeotropic mixture, 593, 670 Azide ion, 28, 303, 304, 313, 322, 324, 723, 873 Azo coupling, 895–897, 951 Azo dyes, 896–897 AZT. See Zidovudine Baeyer strain theory, 98 Baeyer-Villiger oxidation, 683–684, 691, 789 Barbiturates, 845–846 Barton, Sir Derek, 99 Base pairs, 1094–1096 Base peak, 527 Bases, used in elimination reactions, 190–191, 348–349, 359, 565 Basicity of amines, 864–870, 901 constant K b and pK b , 864–865, 901 definition Arrhenius, 134 Br?nsted-Lowry, 134–136 Lewis, 143 of Grignard reagents, 551–553, 556 of heterocyclic amines, 868 of leaving groups, 306, 327 table, 890 and nucleophilicity, 323–325 of organolithium compounds, 551–553 Beeswax, 61, 70, 1024 Bender, Myron, 794, 797 Bending vibrations in infrared spectroscopy, 518 Benedict’s reagent, 998–999, 1009 Benzal chloride, 415 Benzaldehyde, 407 diethyl acetal of, 669 preparation of, 659 reactions of Claisen-Schmidt condensation, 720, 728 with methylamine, 673, 873 nitration, 467, 873 reductive amination, 881 with vinyllithium, 556 Benzenamine, 859. See also Aniline Benzene, 54, 399–406, 433–434 acidity of, 552, 577 Birch reduction of, 413–414 derivatives, nomenclature of, 406–408 electrophilic aromatic substitution in, 445 table bromination, 445, 448–450, 473 chlorination, 445, 450 Friedel-Crafts acylation, 445, 453–457, 473, 474 Friedel-Crafts alkylation, 445, 450–453, 478 INDEX I-6 nitration, 445, 447–448, 473 sulfonation and disulfonation, 445, 448–449, 468 electrostatic potential map, 398 heat of hydrogenation, 403–404 as industrial chemical, 399 isolation and discovery, 399 mass spectrum, 527–528 molecular orbitals, 405, 424 nuclear shielding in, 495 stability of, 403–404, 433 structure and bonding, 399–403 Kekulé formulation, 399–402, 433 orbital hybridization model, 405 resonance description, 402–403 (see also Arenes; Aromatic compounds and aromaticity) Benzenecarbaldehyde. See Benzaldehyde Benzenecarboxylic acid. See Benzoic acid Benzenediazonium chloride, 891, 951 1,2-Benzenedicarboxylic acid, 737 1,4-Benzenedicarboxylic acid, 750 condensation polymers of, 809 Benzenediols, 940. See also Hydroquinone; Pyrocatechol; Resorcinol Benzenesulfonic acid preparation of, 445, 448–449 reactions of, 468, 947 (Benzene)tricarbonylchromium, 567 Benzimidazole, 431 Benzo[a]pyrene, 409 Benzofuran, 430 Benzoic acid, 399, 407, 737 acidity of, 747 esterification of, 593, 754–757 by oxidation of toluene, 417 Benzonitrile, 776 Benzophenone, 656 Benzothiophene, 430 Benzotrichloride, 415 Benzoyl chloride, 468, 781, 782 Benzoyl peroxide, 415 Benzyl alcohol, 659 infrared spectrum, 523 1 H NMR spectrum, 509 Benzylamine, preparation of, 875–876 Benzyl bromide, 408 Benzyl cation, 412, 418, 527 Benzyl chloride nucleophilic substitution in, 626, 729, 752, 783 preparation of, 415 reaction of with lithium dimethylcuprate, 573 with magnesium, 571 with N-potassiophthalimide, 875 Benzyl group, 408 Benzylic halides, nucleophilic substitution in, 417–419 Benzylic halogenation, 414–416, 435 Benzyloxycarbonyl protecting group in peptide synthesis, 1077–1079, 1104 Benzyl radical, 412, 414–415 Benzyne bonding in, 928, 930 Diels-Alder reactions of, 931–932 electrostatic potential map, 930 generation of, 929, 931–932, 933 as intermediate in nucleophilic aromatic substitution, 927–931 Berg, Paul, 1102 Bergstrom, Sune, 1025 Berthelot, Pierre-Eugéne Marcellin, 339 Berzelius, J?ns Jacob, 1–2, 22 Bicarbonate, 749 Bicyclic ring systems, 114–115, 120 as products in Diels-Alder reactions, 386, 932 Big-bang theory, 6 Bile acids and bile salts, 1039, 1044 Bimolecular elementary step, 136, 143 elimination, 192–196, 201 (see also E2 mechanism) nucleophilic substitution (see S N 2 mechanism) Biological isoprene unit. See Isopentenyl pyrophosphate Biosynthesis of amino acids, by transamination, 1063–1065 of cholesterol, 1036–1037 of ethylene, 168 of fatty acids, 1019–1022 of organohalogen compounds, 713 of phenols, 948 of prostaglandins, 1025 of terpenes, 1028–1034 Biot, Jean-Baptiste, 265 Biphenyl, 408, 466, 485 Birch, Arthur J., 412 Birch reduction, 412–414, 434 Bisabolene, 1046 Bloch, Felix, 490 Bloch, Konrad, 1035 Blood-group glycoproteins, 995, 996 Boat conformation of cyclohexane, 99–100, 119 Boc. See tert-Butoxycarbonyl Boiling points of alcohols, 130–131, 160, 790 of alkanes, 57, 71–74, 790 of alkyl halides, 130–132, 160, 306 of amines, 863–864 of carboxylic acids, 739 of esters, 790 and intermolecular attractive forces, 71–74, 130–132, 658 and intramolecular hydrogen bonds, 942 of thiols, 604 Bond angles acetaldehyde, 657 acetone, 657 acetylene, 341–342, 343 ammonia, 29 aniline, 862 [10]-annulene, 425 benzene, 402 boron trifluoride, 29 carbon dioxide, 30 cyclohexane, 99 cyclopropane, 98, 106–107 dialkyl ethers, 621 and electron-pair repulsions, 26, 28–29 enol of 2,4-pentanedione, 708 ethane, 57, 343 ethylene, 38–40, 171, 343 ethylene oxide, 621 formaldehyde, 657 formic acid, 738 methane, 28, 37, 57 methanol, 129, 621, 940 methylamine, 861, 862 phenol, 940 water, 29, 621 Bond dissociation energy, 13, 151–153, 155 acetylene, 343 aryl halides, 918 benzene, 918 ethane, 151, 343, 918 ethylene, 171, 343, 918 ethyl halides, 918 and halogenation of methane, 155 2-methylpropane, 151, 152, 414 peroxides, 220 propane, 151 propene, 370, 414 table, 151 vinyl halides, 918 Bond distances acetic acid, 742 acetylene, 341–342, 343 alkyl halides, 129 allene, 377 ammonium acetate, 742 benzene, 402 1,3-butadiene, 375 carbon-chlorine,778 carbon-sulfur, 800 cyclobutadiene derivative, 423 cyclooctatetraene, 423 dimethyl ether, 621 enol of 2,4-pentanedione, 708 ethane, 37, 57, 343 ethyl chloride, 918 ethylene, 38, 171, 343 ethylene oxide, 621 formic acid, 738 methane, 57 methanol, 129 methylamine, 861, 862 phenol, 940 propene, 171, 343 propyne, 343 vinyl halides, 918 Bonding in acetylene, 14, 40–42, 47, 341–343, 358 in alcohols, 129 in aldehydes and ketones, 657–658, 688 in alkenes, 38–40 170–172, 198 in alkyl halides, 129 in alkynes, 341–343, 358 in allene, 377–378 in amines, 861–863 in aryl halides, 917–918 in benzene, 402–403, 405, 424 in benzyne, 928, 930 in carbocations, 140–143 I-7 INDEX Bonding—Cont. in carboxylic acid derivatives, 777–779 in carboxylic acids, 738–739 in conjugated dienes, 375 in ethers and epoxides, 621 in ethane, 37 in ethylene, 14, 38–40, 47, 170–171 in formaldehyde, 14, 657 in free radicals, 149–150 in hydrogen, 12, 32–35 in methane, 13, 35–37 models, comparison of, 42–43 in phenols, 940–941 in H9251,H9252-unsaturated aldehydes and ketones, 720–721 Bond lengths. See Bond distances Bond-line formulas, 21, 59, 171. See also Carbon skeleton diagrams Bonds axial and equatorial, 100–105, 119 bent, in cyclopropane, 106 carbon-metal, 546–548 covalent, 12–14 double, 14, 171, 198 hydrogen bonds, 130–133, 622 ionic, 11–12 partial, 136 H9266 in acetylene, 42, 47, 341–342 in ethylene, 40, 47, 170–171, 198 in formaldehyde, 657 polar covalent, 15–16 dipole moments of, 16 table H9268 in acetylene, 40–42, 341–342 in ethane, 37 in ethylene, 38–40, 170–171, 198 in methane, 35–37 three-center two-electron, 230 triple, 14, 341–342 Borane, 228 Borneol, 1032 Borodin, Aleksandr, 715 Borohydride ion, 18. See also Sodium borohydride Boron trifluoride, 29, 31 Bradykinin, 1076 Branched-chain carbohydrates, 988 Brevicomin, 694 Broadband decoupling, 515 Bromination of aldehydes, 703–705 of alkanes, 158–159, 161 of alkenes electrophilic, 233–236, 250, 284–285, 420 free-radical, 371–372, 391 of alkynes, 356–357 of benzene, 445, 448–450 benzylic, of alkylbenzenes, 415–416, 435 of carboxylic acids, 759–760, 767 of conjugated dienes, 382 electrophilic aromatic substitution acetophenone, 473 p-aminobenzoic acid, 888 aniline, 466, 895 anisole, 463 benzene, 445, 448–450, 473 3-benzyl-2,6-dimethylphenol, 949 4-chloro-N-methylaniline, 471 m-fluorophenol, 948 nitrobenzene, 469, 919 p-nitrotoluene, 471 phenol, 478, 950 of ketones, 703–705, 727 Bromine. See also Bromination oxidation of carbohydrates by, 999–1000, 1009 reaction with amides, 807–813, 822 Bromobenzene Friedel-Crafts acylation of, 921 preparation of, 445, 448 reactions of with lithium, 549 with magnesium, 550, 921 1-Bromobutane, 138, 220. See also Butyl bromide alkylation of acetylene, 346–348 ethyl acetoacetate, 840 o-nitrophenol, 963 nucleophilic substitution in, 322 2-Bromobutane, 128, 215 alkylation of diethyl malonate, 843–844 preparation of, 138, 330 Bromochlorofluoromethane as a chiral molecule, 260 electrostatic potential map, 159 Fischer projections, 271 Bromoform, 494, 711–712, 727. See also Tribromomethane Bromohydrin. See Halohydrins 2-Bromo-2-methylbutane elimination reactions, 191, 197 substitution versus elimination in, 325 2-Bromo-3-methylbutane, rearrangement in hydrolysis of, 319–320 1-Bromo-2-methylpropane. See Isobutyl bromide Bromonium ion. See Halonium ion (R)- and (S)-2-Bromooctane, stereochemistry of hydrolysis of, 307–308, 319 N-Bromosuccinimide, reagent for allylic bromination, 371, 391 benzylic bromination, 415–416, 435 Br?nsted, Johannes, 134 Br?nsted acid. See Acidity Br?nsted base. See Basicity Brown, Herbert C., 228 Buckminsterfullerene, 410–411 1,3-Butadiene addition of halogens to, 382, 392 addition of hydrogen halides to, 379–382, 392 conformations, 376–377 Diels-Alder reactions of, 382, 387–388 electrostatic potential map, 365 industrial preparation of, 378 H9266-molecular orbitals, 397–398 polymers of, 382–383 structure and bonding, 375–377 Butanal aldol condensation, 716–717, 718 dipole moment, 721 heat of combustion, 658 infrared spectrum, 685 reductive amination of, 880 Butanamine. See Butylamine Butane, 61. See also n-Butane chlorination of, 156–158 conformations of, 94–97, 118 n-Butane, 57. See also Butane 2,3-Butanediol, stereoisomers, 279–280 Butanoic acid biosynthesis of, 1020–1022 bromination of, 760 1-Butanol acid-catalyzed ether formation from, 592, 625 conversion to 1-bromobutane, 138 dehydration, 189–190 Fischer esterification of, 789 2-Butanol. See also sec-Butyl alcohol enantiomers, 267–269 reaction with hydrogen bromide, 139, 330 stereogenic center in, 262, 268 2-Butanone enolization of, 706 heat of combustion, 658 proton magnetic resonance spectrum, 686 1-Butene, 169, 172 addition of hydrogen bromide to, 215, 220 addition of sulfuric acid to, 249 boiling point, 658 dipole moment of, 176 heat of combustion, 177 heat of hydrogenation, 209–211 cis- and trans-2-Butene, 172–173 dipole moments of, 176 heats of combustion, 177 heats of hydrogenation, 209–211 Butlerov, Alexander, 3 tert-Butoxycarbonyl, protecting group in peptide synthesis, 1078–1079, 1083, 1104 sec-Butyl acetate, 594 n-Butyl alcohol. See 1-Butanol sec-Butyl alcohol, 594. See also 2-Butanol tert-Butyl alcohol. See also 2-Methyl-2- propanol acidity of, 135 dehydration of, 182, 186 esterification of, 610, 781 reaction with hydrogen chloride, 138, 139–146 Butylamine acylation of, 882 infrared spectrum, 898 Butyl bromide. See also 1-Bromobutane preparation from 1-butanol, 138 reaction of with lithium, 549 with sodium cyanide, 871 tert-Butyl bromide, nucleophilic substitution in, 315–317 INDEX I-8 tert-Butyl cation, 140, 141, 143–146 electrostatic potential map, 126 intermediate in acid-catalyzed hydration of 2-methylpropene, 226 dehydration of tert-butyl alcohol, 186 Friedel-Crafts alkylation of benzene, 451 nucleophilic substitution, 315–317 reaction of tert-butyl alcohol with hydrogen chloride, 140,143–146 stability of, 141 n-Butyl chloride. See 1-Chlorobutane sec-Butyl chloride. See 2-Chlorobutane tert-Butyl chloride. See also 2-Chloro- 2-methylpropane by chlorination of 2-methylpropane, 158 in Friedel-Crafts reaction, 445, 450–451 preparation from tert-butyl alcohol, 138–139, 143–144 reaction with lithium, 549 solvolysis of, 321, 366 tert-Butylcyclohexane, conformations, 105 4-tert-Butylcyclohexyl bromide, rate of elimination of cis and trans isomers, 194–196 Butyl group, 66. See also n-Butyl group n-Butyl group, 66. See also Butyl group sec-Butyl group, 66. See also 1-Methylpropyl group tert-Butyl group, 66. See also 1,1-Dimethylethyl group large size of, 105, 107, 113–114, 179, 310–311 tert-Butyl hydroperoxide, 589–590, 608 Butyllithium preparation of, 549 reactions of, 551, 582 tert-Butyllithium, 549 n-Butyl mercaptan, in skunk fluid, 85, 604 sec-Butyl methyl ether, 628 tert-Butyl methyl ether, 626 tert-Butyloxonium ion intermediate in dehydration of tert-butyl alcohol, 186 hydration of 2-methylpropene, 226 hydrolysis of tert-butyl bromide, 305–306 reaction of tert-butyl alcohol with hydrogen chloride, 140, 142–145 sec-Butyl phenyl ketone, enolization of, 714–715 Butyl radical, 157 sec-Butyl radical, 157 tert-Butyl radical, 152 1-Butyne, 340, 347 2-Butyne, 340, 347 Butyraldehyde. See Butanal Butyric acid, 750. See also Butanoic acid c, speed of light, 488 Caffeine, 1091 Cahn, R. S., 174 Cahn-Ingold-Prelog (CIP) system of stereochemical notation chiral molecules, 268–271, 292 priority rules, 173–174, 175 table Calcium carbide, 340 Calicene, 441 Camphene, 115 Cantharadin, 783 H9280-Caprolactam, 803 Carbamic acid, 812 esters, 813, 857 Carbanion, 345, 548 basicity of, 345, 552–553 bonding in, 345 enolate ion, 709 as intermediate in nucleophilic aromatic substitution, 923–927 Carbenes and carbenoids, 565–566, 571–572 Carbenium ions, 140. See also Carbocations Carbinolamine intermediates, 672–673, 674 Carbobenzoxy. See Benzyloxycarbonyl Carbocations acyl cations, 453–455 alkenyl cations, 353 allylic, 365, 366–369, 379–382, 390 arenium ions, 444 (see also Cyclohexadienyl cation) benzylic, 418, 421 tert-butyl cation, 140, 141, 143–146, 186, 226, 315–317, 451 capture by nucleophiles, 142, 143–144, 226, 316 as intermediates in acetal formation, 669–670, 989 as intermediates in biosynthesis of cholesterol, 1036 of terpenes, 1028–1032 as intermediates in glycoside formation, 990 as intermediates in reactions of alcohols dehydration, 185–189, 200–201 with hydrogen halides, 140–146, 160–162, 329–330, 332 as intermediates in reactions of alkenes acid-catalyzed hydration, 225–226 addition of hydrogen halides, 213–214, 216–220, 251 addition of hydrogen halides to conjugated dienes, 379–382, 392 addition of sulfuric acid, 224 polymerization, 244–245 as intermediates in reactions of alkyl diazonium salts, 890 as intermediates in reactions of alkyl halides E1 elimination, 196–198, 201 Friedel-Crafts alkylation, 451–453, 479 S N 1 nucleophilic substitution, 143–146, 315–320, 331 isopropyl cation, 141, 224 methyl cation, 141 tert-pentyl cation, 929 rearrangements, 187–189, 201, 219–220, 319–320, 331, 452, 479 structure, bonding, and stability, 140–143, 162 triphenylmethyl, 418–419 Carbohydrates, 972–1014 aldoses, 973 amino sugars, 988 branched-chain carbohydrates, 988 chain extension, 1001, 1009 classification, 972–973 configurations of D-aldoses, 974–978 mnemonic for, 978 cyclic hemiacetal formation in, 978–984 deoxy sugars, 987 determination of ring size, 1004–1006 disaccharides, 972–973, 991–993, 1008 Fischer determination of glucose structure, 996, 1014 Fischer projection formulas, 973–974, 1007 furanose forms, 978–981, 1007 glycolysis, 1002–1004, 1015 glycoproteins, 995–996 glycosides, 988–991, 1008 Haworth formulas, 980 ketoses, 973, 986–987 mutarotation in, 985–986, 1008 photosynthesis, 976, 1015 polysaccharides, 993–995, 1008 pyranose forms, 981–984, 1007 reactions of acylation, 1004, 1010 cyanohydrin formation, 1001, 1009 epimerization, 1002 ether formation, 1004, 1010 isomerization, 1002 oxidation, 998–1001, 1009 periodic acid cleavage, 1005–1006, 1010 reduction, 996–998, 1009 retro-aldol cleavage, 1003–1004 Carbolic acid, 943. See also Phenol Carbon 13 C isotope nuclear magnetic resonance, 510–517 14 C as isotopic label in Claisen rearrangement, 957 nucleophilic aromatic substitution via benzyne, 928, 931 terpene biosynthesis, 1033–1034 clusters, 410–411 formation in stars, 6 Carbon dioxide, 14 bond angles in, 30 and carbonic acid, 749 in fatty acid and terpene biosynthesis, 1020–1021, 1033 in industrial preparation of urea, 802–803 in Kolbe-Schmitt reaction, 952–954, 963 reaction with Grignard reagents, 750–752, 766 Carbonic acid, acidity of, 749 Carbonic anhydrase, 749 Carbonium ions, 140. See also Carbocations Carbon monoxide binding to hemoglobin and myoglobin, 1089 reactions of, 566, 580, 661 Carbon skeleton diagrams, 21. See also Bond- line formulas Carbon tetrachloride, 30, 132. See also Tetrachloromethane Carbon tetrafluoride, 13 I-9 INDEX Carbonyl group. See also Acyl chlorides; Aldehydes; Amides; Carboxylic acid anhydrides; Carboxylic acids; Esters; Ketones and functional groups, 56 infrared absorption frequencies, 519, 817 stabilization by substituents, 658, 738–739, 777–779 structure and bonding, 657–658, 688 Carboxamides. See Amides Carboxylate salts electron delocalization in, 740–741, 742 micelle formation, 744–745 nomenclature of, 742 as nucleophiles, 303, 304, 313 Carboxylation of Grignard reagents, 750–752, 766 of phenol, 952–954, 963 Carboxylic acid anhydrides Friedel-Crafts acylation with, 455, 471, 473–474, 478, 660, 784, 921 infrared absorption, 817 nomenclature of, 775 preparation of, 781, 783–784 reactions of with alcohols, 594–595, 610, 785–787, 789, 820 with amino acids, 1063 with ammonia and amines, 785, 820, 886–888 with carbohydrates, 1004, 1010 hydrolysis, 785 with phenols, 949–952, 963 resonance in, 778 Carboxylic acid chlorides. See Acyl chlorides Carboxylic acid derivatives, 774–830. See also Acyl chlorides; Amides; Carboxylic acid anhydrides; Esters; Nitriles nomenclature of, 775–776 relative reactivity of, 780 table spectroscopic analysis, 817–818 structure and bonding, 777–779 Carboxylic acids, 736–773. See also Carbonic acid; Dicarboxylic acids acidity of, 740–742, 745–748, 765–766 derivatives of, 774–830 dicarboxylic acids, 748, 760–761 dipole moments, 739 hydrogen bonding in, 739 infrared spectra, 519 table, 763–764 nomenclature of, 737–738 nuclear magnetic resonance spectra, 763–764 physical properties, 739 preparation of carboxylation of Grignard reagents, 750–752, 766 hydrolysis of nitriles, 752–753, 766, 815–816 by malonic ester synthesis, 842–845, 852 oxidation of aldehydes, 682, 751 oxidation of alkylbenzenes, 416–417, 751 oxidation of primary alcohols, 596, 611, 751 protecting group for, 1079 reactions of, 753–763 with acyl chlorides, 781, 820 decarboxylation, 760–763, 767–768 esterification, 593–594, 610, 754–757, 767, 789 H9251-halogenation, 759–760, 767 reduction, 587, 608, 659, 754 with thionyl chloride, 454, 754, 780 salts of, 742–745, 766 site of protonation in, 756–757 structure and bonding, 738–739, 765 Carboxypeptidase A, 1086–1088 Carboxypeptidases, 1071 Carcinogen, 409 benzene, 417 polycyclic aromatic hydrocarbons, 409 H9252-Carotene, 676, 1027, 1042 Carotenoids, 1042, 1044 Carothers, Wallace H., 4, 809 Carvone, odors of (R) and (S) enantiomers, 272 Catalyst, 5. See also Acid catalysis; Enzymes; Hydrogenation Cation radicals in mass spectrometry, 526 Cellobiose, 991–992 Cellulose, 994 Cembrene, 1027 Center of symmetry, 264–265 in meso-2,3-butanediol, 280 Cephalexin, 803 Cephalosporins, 803 Cerebrosides, 1047 Chair conformation of cyclohexane and derivatives, 99–107, 110–114, 119, 510 of piperidine, 116 of pyranose forms of carbohydrates, 982–984 of tetrahydropyran, 621 Chargaff, Erwin, 1094 Chemical Abstracts, 63, 859 Chemical shift of carbon, 512–513, 535 equivalence and replacement test for, 498–500 of protons, 493–500, 509, 510, 534, 535 scale (H9254), 493–494 tables, 496 ( 1 H), 513 ( 13 C) Chiral, definition of, 260 Chiral axis. See Stereogenic axis Chiral center. See Stereogenic center Chiral drugs, 273 Chiral molecules, 259–263, 290 absolute configuration, 267, 292 Fischer projection formulas, 271–272, 278, 280, 292–293 formation of in chemical reactions, 274–276, 284–285, 293 with multiple stereogenic centers, 276–286, 293 with one stereogenic center, 260–263, 291 optical activity in, 265–267, 293 and R, S notation, 268–271, 292 Chiral recognition, 272–273 Chitin, 988 Chloral, 664 Chlorination electrophilic of acetophenone, 474 of aldehydes and ketones, 703–705, 711, 713, 727 of benzene, 445 of benzoyl chloride, 468 of 2-methylacetanilide, 888 free-radical of alkanes, 148, 153–159, 161, 162, 166 of ethane, 54, 156 of methane, 148–149, 153–155 of propene, 371 of toluene, 415 (see also Chlorine) Chlorine. See also Chlorination addition of to alkenes, 233–234 to conjugated dienes, 382 to propyne, 356 oxidation of alcohols by, 599 Chlorobenzene carbon-chlorine bond energy, 918 conversion to phenol, 920, 931, 947 dipole moment of, 918 mass spectrum, 529 nitration of, 469–470 nucleophilic aromatic substitution in, 920–921, 931 1-Chlorobutane, 156–157 2-Chlorobutane, 156–157 Chlorocyclobutane, 156 Chlorocyclohexane. See also Cyclohexyl chloride dipole moment, 918 1-Chloro-2,4-dinitrobenzene, nucleophilic substitution in, 922 Chloroethane, 54, 156, 918. See also Ethyl chloride Chlorofluorocarbons (CFCs), 148 Chloroform, 132. See also Trichloromethane biosynthesis of, 713 1 H nuclear magnetic resonance spectrum of, 494 Chloroform-d, solvent for NMR spectroscopy, 494 Chlorohydrin. See Halohydrins Chloromethane, 148. See also Methyl chloride biosynthesis of, 713 boiling point of, 132 dipole moment of, 129 electrostatic potential map, 129 1-Chloro-2-methylpropane, 158. See also Isobutyl chloride 2-Chloro-2-methylpropane, 158. See also tert- Butyl chloride p-Chloronitrobenzene, nucleophilic substitution in, 922–925 electrostatic potential map, 917 Chloronium ion. See Halonium ion INDEX I-10 1-Chloropentane, 1 H and 13 C NMR spectra, 511 Chlortetracycline, 920 2-Chloro-1,3,5-trinitrobenzene, 922 Cholesterol, 580, 1034–1038, 1044 biosynthesis of, 1036–1037 7-dehydro, 1038 Cholic acid, 116, 283, 1039 Choline, 1022 Chromatography, 530–531, 1070–1071 Chromic acid oxidation of alcohols, 596–600, 611, 660, 751 of alkylbenzenes, 415, 435, 751 of phenols, 958 Chromophore, 526 Chrysanthemic acid, 71 Chymotrypsin, 1071 Cicutoxin, 340 Cimetidine, 431 Cinnamaldehyde, 173 CIP. See Cahn-Ingold-Prelog Cis and trans descriptors of stereochemistry, 108–109, 172–173, 199 s-Cis conformation, 376–377 Citral, 659, 1027 Citric acid, 299, 772 Citronellal, 1033–1034 Citronellol, 580 Claisen, Ludwig, 832 Claisen condensation, 832–835, 851 intramolecular (see Dieckmann reaction) mixed, 836–837, 851 Claisen rearrangement, 957–958, 964 Claisen-Schmidt condensation, 720, 728 Clathrate, 58 Clemmensen reduction, 456–457, 474, 662 Cocaine, 869 Codon, 1096–1100 Coenzymes, 1088–1090. See also Vitamin acetyl coenzyme A, 1016–1017, 1032 coenzyme B 6 , 675 coenzyme B 12 , 568 coenzyme Q (see Ubiquinone) heme, 1088 NAD, NAD H11001 , NADH, NADPH (see Nicotinamide adenine dinucleotide) Cofactors. See Coenzymes Coke, 339 Columbus, Christopher, 383 Combinatorial synthesis, 1084 Combustion of alkanes, 74–77, 83. See also Heat of combustion Common names. See Nomenclature Concerted reaction, 136 bimolecular elimination, 192–196, 200–201 bimolecular nucleophilic substitution, 146, 306–315, 331 Diels-Alder reaction, 382 and orbital symmetry, 388–390 Condensation polymers, 809–810 Condensation reaction, 592 aldol, 715–720, 728 Claisen, 832–835, 851 Claisen-Schmidt, 720, 728 ether formation, 592–593, 610, 625–626, 644 Fischer esterification, 593–594, 595, 610, 754–757, 767, 789 Condensed structural formulas, 19, 59 Configuration absolute and relative, 267–268, 291–292 of aldoses, 977 of alkenes cis and trans, 172–173, 180–181, 199 E and Z, 173–175, 180–181, 199 of disubstituted cycloalkanes, cis and trans, 108–114 and Fischer projections, 271–272, 292–293 notational systems H9251 and H9252, 980 cis and trans, 108–109 D-L, 973–978, 1007 erythro and threo, 278 R-S, 268–271 Conformation(s), 89 of alkanes butane, 94–97, 118 ethane, 90–93, 117 higher alkanes, 97–97, 118 of 1,3-butadiene, 376–377, 391–392 chiral, 281 s-cis and s-trans, 376–377, 391–392 of cycloalkanes, 98–116, 118–120 cyclobutane, 107–108 cyclohexane and derivatives, 99–107, 110–114, 118–119, 281, 510 cyclopentane, 108 medium and large rings, 108 eclipsed, 90, 92, 117 of ethers, 621 of heterocyclic compounds, 116–117, 621 of hydrogen peroxide, 89 and nuclear magnetic resonance spectroscopy, 510 peptides and proteins, 1067–1068, 1084–1086 pyranose forms of carbohydrates, 982–984 staggered, 90–92, 117–118 Conformational analysis. See Conformation Conformer, 90. See also Conformation Coniine, 869 Conjugate acids and bases, 134–136, 344–346, 552, 709, 742, 864–865 Conjugate addition. See also Michael reaction of bromine to 1,3-butadiene, 382 of hydrogen bromide to 1,3-butadiene, to H9251,H9252-unsaturated aldehydes and ketones, 722–725, 728–729, 846–847, 852 Conjugation in alkenylbenzenes, 419–420 in allylic systems, 366–372, 379–382, 390 in benzylic carbocations, 418 in benzylic free radicals, 414 in dienes, 372–377, 524–525 (see also Dienes, conjugated) energy, 374–375 in H9251,H9252-unsaturated aldehydes and ketones, 720–721 Connectivity. See Constitution Constitution, 19 Constitutional isomers, 22, 45, 172, 291 of alkanes, number of, 60 table Coordination polymerization, 246, 383, 567–570, 573 Copolymer, 383 Copper (I) salts in preparation of lithium dialkylcuprates, 561–562, 571 reactions with aryl diazonium ions, 892, 893–894, 907, 919 Corey, Elias J., 557, 840 Corey, Robert B., 1084 Corticosteroids (cortisol and cortisone), 1040, 1044 Couper, Archibald S., 3 Coupling constant (J), 503, 506, 507–508 dihedral angle dependence, 544 Covalent bond, 12–14, 44 Cracking, in petroleum refining, 70 Crafts, James M., 451 m-Cresol, 939 acidity of, 944 13 C NMR spectrum, 513–514, 960–961 o-Cresol, 950 p-Cresol acidity of, 944 carboxylation, 954 infrared spectrum, 960 nitration of, 950 1 H NMR spectrum, 960–961 preparation of, 946 Crick, Francis H. C., 1094, 1100 Critical micelle concentration, 744 Crown ethers, 622–624, 644 electrostatic potential map, 619, 623 Cumene, 248, 969. See also Isopropylbenzene Cumulated diene. See Allenes; Dienes Cuprates. See Lithium diorganocuprates Curl, Robert F., 410 Curved arrows fishhook, 150 and resonance structures, 367, 371 to show electron movement, 133 Cyanide ion basicity of, 324, 722 in formation of cyanohydrins, 667–668 as nucleophile, 303, 304, 313, 323, 324, 327, 722–723 Cyanohydrins and carbohydrate chain extension, 1001, 1009 hydrolysis of, 753 naturally occurring, 668, 695 preparation of, 667–668, 689, 814 Cyclic AMP, 1093 Cycloaddition, 382 molecular orbital treatment of, 388–390 Cycloalkanes, 68–69, 98–116, 118–120 angle strain in, 98, 107–108 bicyclic, polycyclic, and spirocyclic, 114–116, 120 conformations of, 98–116, 118–120 I-11 INDEX Cycloalkanes—Cont. heats of combustion, 98 table nomenclature of, 66–69 sources of, 69–71 Cycloalkenes, 170, 180–181 nomenclature of, 170 stereoisomeric, 180–181, 192 Cycloalkynes, 341, 344 Cyclobutadiene, 422, 423, 424, 436 Cyclobutane angle strain in, 98, 108 chlorination of, 156 conformations of, 107–108 heat of combustion of, 98 Cyclobutyl chloride, 156 Cyclodecane, 98, 161 (E)- and (Z)-Cyclodecene, 192 Cyclodecyl bromide, 192 Cyclodecyl chloride, 161 Cycloheptatriene, 427 Cycloheptatrienide anion, 429 Cycloheptatrienyl cation, 427–428, 436 trans-Cycloheptene, 180 Cyclohexadienone-phenol rearrangement, 968 Cyclohexadienyl anion intermediate in nucleophilic aromatic substitution, 923–927, 933 Cyclohexadienyl cation intermediate in electrophilic aromatic substitution, 444–447, 449, 450, 451, 454, 458–462, 465–466, 470, 475, 477, 926 Cyclohexane, 68, 70, 118–119 bond angles in, 99 conformational analysis of, 99–103, 118–119 disubstituted derivatives, 110–114, 281 monosubstituted derivatives, 104–107 heat of combustion, 98 1 H NMR spectrum of, 510 Cyclohexanol infrared spectrum, 605, 606 preparation of, 224 reactions of dehydration, 182 with hydrogen bromide, 138 oxidation, 597 Cyclohexanone H9251 chlorination of, 703 and ethylene glycol, cyclic acetal from, 671 preparation of, 597 reaction of with ethylmagnesium bromide, 662 with isobutylamine, 673 with methylenetriphenylphosphorane, 677 with morpholine, 690 with pyrrolidine, 882 with sodium acetylide, 556 reductive amination of, 880 Cyclohexene derivatives of, preparation by Diels-Alder reaction, 382, 392–393 preparation of dehydration of cyclohexanol, 182 dehydrohalogenation, 190 reactions of alkylation of benzene with, 452 with N-bromosuccinimide, 371 with dibromocarbene, 566 epoxidation, 637 hydroxylation, 590, 637 with sulfuric acid, 224 trans stereoisomer, 180 Cyclohexylamine, 859 basicity of, 865 preparation of, 880 reductive amination by, 903 Cyclohexyl chloride. See also Chlorocyclohexane H9252-elimination of, 190 Grignard reagent from, 550, 555 Cyclononyne, 341 1,3-Cyclooctadiene, UV-VIS spectrum, 524 Cyclooctane, 98 Cyclooctatetraene, 422–424, 436 dianion, 429 Cyclooctene addition of chlorine to, 234 epoxidation of, 239 trans stereoisomer, 180 Cyclooctyne, 341 Cyclopentadiene acidity of, 428 Diels-Alder reactions of, 386 reaction with hydrogen chloride, 379–380 Cyclopentadienide anion, 428, 436 Cyclopentane, 70 conformations of, 108, 120 heat of combustion, 98 Cyclopentanol nitrate ester, 610 preparation of, 584 reaction with phosphorus tribromide, 147 Cyclopentanone Baeyer-Villiger oxidation of, 695 enamine of, 674 enol content of, 727 hydrogenation of, 584 hydrogen-deuterium exchange in, 713–714 reaction with methylmagnesium chloride, 555 Cyclopentene bromine addition to, 234 halohydrins of, 236–238 Cyclopentyl bromide, 147, 478 Cyclopentyl cyanide, 304 Cyclopentylmethanol 582, 591 Cyclopropane(s), 68 angle strain and bonding in, 106–107 cis- and trans-1,2-dimethyl-, 109–110 1,1-dihalo, 566 heat of combustion of, 98 preparation of, 563–565, 571 structure of, 107 torsional strain in, 107 Cyclopropanecarboxylic acid, 587 Cyclopropene, 180 Cyclopropenyl cation, 429 Cyclopropyllithium, 572 L-Cysteine, 1055, 1059 electrostatic potential map, 1053 disulfide formation in, 1069–1070, 1073–1074, 1087 Cytidine, 1092 Cytosine, 1089, 1095 Dacron, 809 L-Daunosamine, 988 DCCI. See N,NH11032-Dicyclohexylcarbodiimide DDT (dichlorodiphenyltrichloroethane), 938 Deamination reactions, 890, 894, 895, 907 De Broglie, Louis, 7 Debye, Peter J. W., 16 Debye unit, 16 cis- and trans-Decalin, 115 Decane, 62 mass spectrum of, 529–530 1-Decanol, 227–228, 660 Decarboxylation H9251-amino acids, 1065–1066 H9252-keto acids, 762–763, 767–768, 838, 840–841, 850 malonic acid derivatives, 760–762, 767–768, 842, 843–845, 852 1-Decene hydroboration-oxidation of, 227–228, 582 hydroxylation of, 590 Decoupling of alcohol protons in 1 H NMR, 509–510, 535 in 13 C NMR, 515 Dehydration in aldol condensation, 717–719, 720 in preparation of alkenes from alcohols, 182–190, 200, 379, 419, 591 of cyclic anhydrides, 784 of dienes, 379, 392 of nitriles from amides, 813–815 Dehydrogenation of alcohols, 661 biological of butane, 378 of ethane, 168, 181 of ethylbenzene, 419, 453 of ethylene, 340 of propane, 168, 181 of succinic acid, 182 Dehydrohalogenation. See also Elimination reactions of alkyl halides, 190–198, 200, 419 of bromocyclodecane, 192 of 2-bromo-2-methylbutane, 191, 197 of 5-bromononane, 192 of cis- and trans-4-tert-butylcyclohexyl bromide, 194–196 of 1-chloro-1-methylcyclohexane, 200 of 1-chlorooctadecane, 191 of cyclohexyl chloride, 190 of dihalides, 348–349, 359 of menthyl and neomenthyl chloride, 206 in preparation of alkenes, 190–198, 200 of alkenylbenzenes, 419 INDEX I-12 of alkynes, 348–349, 359 of dienes, 379 Delocalization energy, 374. See also Resonance energy Denaturation of ethanol, 581 of proteins, 1087 Dendrolasin, 1046 Deoxyribonucleic acid (DNA) and protein biosynthesis, 1096–1100 purine and pyrimidine bases in, 1090–1093 replication of, 1095 sequencing of, 1100–1103 structure of, 1094–1097 2-Deoxy-D-ribose, 987, 1010, 1092 Deoxy sugars, 987, 1008 DEPT, 515–517, 537 Detergents, 745 Deuterium oxide, 166, 510, 713–714, 763 Dextrorotatory, 266 Diacetylene, 340 Dianabol, 1041 Diastereomers, 277–288, 291 formation of, 284–285 Diastereotopic protons, 495, 507 1,3-Diaxial repulsion, 104 Diazonium salts, 890–897, 904–905 azo coupling of, 895–897, 936 conversion to arenes, 894–895, 907 aryl cyanides, 894, 907 aryl halides, 892–894, 905–906, 919 phenols, 892, 905, 946, 947, 962 preparation of, 891 Diborane, 228. See also Hydroboration- oxidation Dibromocarbene, 565–566 1,2-Dibromocyclopropane, stereoisomers of, 282 1,2-Dibromoethane, 234 Dibromoindigo, 920 Dibutyl ether, 592, 625 Dicarboxylic acids acidity of, 748 cyclic anhydrides from, 784 decarboxylation, 760–762, 767–768, 842, 843–845, 852 nomenclature of, 738 in preparation of polyamides and polyesters, 809–810 Dichlorocarbene, 565 Dichlorocyclohexane isomers, 281 Dichlorodiphenyltrichloroethane. See DDT (E)-1,2-Dichloroethene, plane of symmetry in, 264 Dichloromethane, 29–30, 132, 148 N,NH11032-Dicyclohexylcarbodiimide in preparation of esters, 1080 peptides, 1079–1081, 1083, 1104 Dieckmann reaction, 835–836, 851 Dielectric constant and rate of nucleophilic substitution, 320–322, 331 of various solvents, 321, 322 table Diels, Otto, 382 Diels-Alder reaction, 382, 392–393 of benzyne, 931–932 orbital symmetry analysis of, 388–390 Dienes. See also Alkadienes conjugated, 365, 372–377, 390–393, 524–525 1,2 and 1,4 addition to, 379–382, 392 conformations of, 376–377, 391–392 Diels-Alder reactions of, 382, 388–390, 392–393 electron delocalization in, 374–377 electrophilic addition reactions of, 379–382, 392 polymers, 383 preparation of, 378–379, 391 resonance energy, 374 cumulated, 373, 377–378 heats of hydrogenation, 374–375, 403–404 isolated, 372, 379 stability of various classes, 374–377, 391 Dienophiles, 382–385, 932 Diethyl acetamidomalonate, 1062 Diethyl adipate. See Diethyl hexanedioate Diethylamine basicity, 866 infrared spectrum, 898 Diethyl carbonate, acylation of ketones with, 836–837 Diethylene glycol dimethyl ether. See Diglyme Diethyl ether, 619 cleavage by hydrogen bromide, 629 conformation of, 621 dipole moment of, 622 hydrogen bonding to water electrostatic potential map, 622 peroxide formation in, 627–628 physical properties of, 622 preparation of, 592 as solvent for Grignard reagents, 550 Diethyl hexanedioate Dieckmann cyclization of, 835 Diethyl malonate acidity of, 842 barbiturates from, 845–846 enolate electrostatic potential map, 831 enol content, 854 in malonic ester synthesis, 842–845, 852 Michael addition to methyl vinyl ketone, 846–847 preparation of, 857 Diethylstilbestrol (DES), 1050 Diglyme, 228, 620 Dihaloalkanes alkynes from, 348–349, 359 geminal, 348–349, 359 reaction with diethyl malonate, 844–845 vicinal, 233, 348–349, 359 Dihedral angle. See Torsion angle 1,3-Dihydroxyacetone, 1010 phosphate, 1003 2,3-Dihydroxybutanoic acid, stereoisomers of, 276–278 L-3,4-Dihydroxyphenylalanine, 1066 Diiodomethane, 564 Diisopropyl ether, 625 Diketones, intromolecular aldol condensation of, 718, 724, 728 1,3-Diketones acidity of, 710–711 alkylation of, 724–726, 729 enolization of, 707–708 preparation of, 837 Dimer, 244 1,2-Dimethoxyethane, 620 Dimethylallyl pyrophosphate, 1029 Dimethylamine, nitrosation of, 889 3,3-Dimethyl-2-butanol dehydration and rearrangement of, 187–189 2,3-Dimethyl-1-butene, 186, 187–188 2,3-Dimethyl-2-butene, 186, 187–188 1 H NMR chemical shifts, 496 heat of hydrogenation, 211 3,3-Dimethyl-1-butene, 188 cis- and trans-1,2-Dimethylcyclohexane, 110, 111–112 cis- and trans-1,3-Dimethylcyclohexane, 110, 112 cis- and trans-1,4-Dimethylcyclohexane, 110–111 cis- and trans-1,2-Dimethylcyclopropane, 109–110 Dimethyl ether bond distances and bond angles, 621 N,N-Dimethylformamide, 322, 875 1,1-Dimethylethyl group, 66 2,2-Dimethylpropane, 73 2,2-Dimethylpropyl group, 66 Dimethyl sulfate, 596 Dimethyl sulfide, 241 Dimethyl sulfoxide as solvent in elimination reactions, 191, 349 in nucleophilic substitution reactions, 303, 322, 327, 752 in Wittig reaction, 677, 680 2,4-Dinitrophenylhydrazine, 674 Diols cyclic acetals from, 670–672 cyclic ethers from, 593 geminal, 663–667 nomenclature of, 589 oxidative cleavage of, 602–603, 609 polyesters from, 809 preparation of, 589–590 vicinal (see Vicinal diols) Dioxane, 620 Dioxin, 955 Diphenylamine, basicity of, 867 Diphenylmethane, acidity of, 577 Diphepanol, 575 Dipole-dipole attractions, 72, 130 in esters, 788 in ethyl fluoride, 130 and hydrogen bonding, 130–133, 622 Dipole-induced dipole attractions, 72, 130 Dipole moment, 15–16, 46 I-13 INDEX of alcohols, 129 of aldehydes and ketones, 657, 721 of alkanes, 72 of alkyl halides, 129 of carbon tetrachloride, 30 of carboxylic acids, 739 of chlorobenzene, 918 of chlorocyclohexane, 918 of chloroethene, 176 of chloromethane, 129 of trans-1-chloropropene, 176 of 1,2-dichloroethane, 125 of dichloromethane, 30 of diethyl ether, 622 of esters, 788 of ethanol, 130 of ethylene, 176 of ethylene oxide, 622 of fluoroethane, 130 of four-carbon alkenes, 176 of methanol, 129 and molecular geometry, 30–31 of propanal, 657 of propane, 130 of propene, 176 of tetrahydrofuran, 622 of water, 129 Dipropyl ether 1 H NMR spectrum, 642 infrared spectrum, 642 preparation of, 644 Directing effects of substituents. See Elec- trophilic aromatic substitution Disaccharide, 973, 991–993, 1008. See also Cellobiose; Lactose; Maltose; Sucrose Disparlure, 239 Distortionless enhancement of polarization transfer. See DEPT Disulfides carboxypeptidase A, 1087 H9251-keratin, 1085 lipoic acid, 117, 605 oxytocin, 1069–1070 preparation of, 605 Diterpenes, 1026 DMF. See N,N-Dimethylformamide DNA. See Deoxyribonucleic acid DNA sequenator, 1102 Dodecane, 62 photochemical chlorination of, 166 1-Dodecene, epoxidation of, 239 L-Dopa. See L-3,4-Dihydroxylphenylalanine Dopamine, 1066 Double bond, 14, 38–40, 170–172 Double helix, 1094–1096. See also Deoxyribonucleic acid Drugs. See also AIDS; Antibiotics chiral, 273 generic names of, 63 Dyes, 896–897 E (stereochemical prefix), 173–175, 199 E1 mechanism, 196–198 E2 mechanism, 190–196, 201, 323–325 Eclipsed conformations, 90–93, 97, 117 and Fischer projections, 278, 280 Ectocarpene, 297–298 Edman, Pehr, 1074 Edman degradation, 1074–1076 Edman sequenator, 1076 Eicosanoic acid. See Icosanoic acid Eigen, Manfred, 137 Elaidic acid, 351 Elastomer, 383 Electromagnetic radiation, 488–489 Electron affinity, 11 Electron configuration and orbital hybridization, 35, 38, 41 of selected atoms, 10 Electron delocalization in allylic carbocations, 366–369, 379–382 in allylic radicals, 370 in benzylic carbocations, 418 in benzylic radicals, 414 in carbocations, 142 in carboxylate ions, 740–741, 779 in carboxylic acid derivatives, 777–780 in conjugated dienes, 374–377 in enolates, 708–711, 832, 839, 842, 850 and resonance, 23–26, 45 in H9251,H9252-unsaturated aldehydes and ketones, 720–721 Electron-dot structures. See Lewis structural formulas. Electronegativity, 15 and chemical shift, 494–495 and polar covalent bonds, 15–16 relation to s character at carbon, 343 of selected elements, 15 table, 547 table Electronic effects, 178 18-Electron rule, 566 Electrons excitation of, 524–526 n → H9266*, 526 H9266 → H9266*, 524–525 nuclear shielding by, 493, 495 quantum numbers, 8 valence, 10 wave properties of, 7 Electrophile, 142–143. See also Addition reactions; Electrophilic aromatic substitution Electrophilic addition. See Addition reactions Electrophilic aromatic substitution, 443–486 of arylamines, 886–888 azo coupling, 895–897, 951 of benzene, 444–457 mechanism, 444–447 of Friedel-Crafts acylation, 453–454 of Friedel-Crafts alkylation, 451 of halogenation, 448–451 of nitration, 447–448 of sulfonation, 448–449 in phenols, 463, 948–950 substituent effects in, 457–474, 477, 479–480 table, 464 summary tables, 446, 478, 950 Electrophoresis of amino acids, 1060–1061 and nucleic acid sequencing, 1101 Electropositive, 15 Electrostatic potential, 27 Electrostatic potential map acetamide, 777 acetate ion, 741, 742 acetic acid, 739, 742 acetic anhydride, 777 acetone enol, 701 acetonitrile, 777 acetyl chloride, 774, 777 acetylene, 339, 342 amino acids, 1053 aniline, 862 benzene, 398 benzyne, 930 bromochlorofluoromethane, 159 1,3-butadiene, 365 tert-butyl cation, 126 calicene, 441 chloromethane, 129 1-chloro-4-nitrobenzene, 917 18-crown-6, 619 and K H11001 complex, 623 diethyl ether-water hydrogen bonding, 622 diethyl malonate enolate, 831 dodecanoic acid, 1015 ethane, 53 ethoxide ion, 741 ethyl acetate, 777 ethylene, 167, 214, 342, 658 ethylenebromonium ion, 208 ethylene glycol, 579 ethyl thioacetate, 777 ferrocene, 546 formaldehyde, 654 formic acid, 736 glucose, 972 hydrogen bonding in ethanol, 131 in phenol, 942 between phenol and water, 942 hydrogen chloride, 214 methane, 27 methanol, 129 methylamine, 858 methyl cation, 143 methylenetriphenylphosphorane, 678 methyl fluoride, 548 methyllithium, 548 nitronium ion, 443 phenol, 939, 942 propanoyl cation, 454 S N 2 transition state, 302 tetramethylsilane, 487 urea, 1 water, 942 Elements of unsaturation, 533. See Index of hydrogen deficiency Elimination-addition mechanism, 927–931, 933 Elimination reactions, 167–206 H9251, 566 H9252, 181–198 anti, 194–196, 200 competition with substitution, 323–325, 332 dehydration of alcohols, 181–193, 200, INDEX I-14 419 dehydrohalogenation of alkyl halides, 190–198, 200, 419 dehydrohalogenation of geminal and vicinal dihalides, 348–349, 359 dehydrogenation of alkanes, 168, 181, 419 E1 mechanism, 196–198 E2 mechanism, 192–196, 201, 323–325 Hofmann elimination, 883–885, 904 in preparation of alkenes, 168, 181–198, 200 of alkenylbenzenes, 419 of alkynes, 348–349, 359 of dienes, 378–379, 391 Zaitsev rule, 184, 191, 199, 200 Emulsin, 992–993 Enamines, preparation of, 674–675, 677, 690 Enantiomeric excess, 266 Enantiomers, 259–260, 291 of bromochlorofluoromethane, 260, 271 of 2-butanol, 267–269 configurational notation D-L, 973–974 R-S, 267–271 conformational, 281 and Fischer projections, 271–272, 292, 974 formation of, 274–276 optical rotations, 266–267 physical properties of, 272–274 Enantioselective synthesis, 276, 1063 Enantiotopic protons, 500 End group analysis, 1071–1076 Endorphins, 1068–1069 Endothermic reaction, 11 and relation to bond energies, 155 Enediols, as intermediates in reactions of carbohydrates, 999, 1002, 1010 Enediyne antibiotics, 344 Energy, units of, 11 Energy of activation, 93 and carbocation stability, 143–146, 317 and free-radical stability, 157–158 for pyramidal inversion, 290 in reaction of alcohols with hydrogen halides, 143 for rotation about double bond, 172–173 and single-bond rotation, 93, 376–377 and temperature, 93–94 Enkephalins, 1068–1069 Enol of acetyl coenzyme A, 1016 content of aldehydes and ketones, 705–708, 727 of 1,3-diketones, 707–708 as intermediate in conjugate addition to H9251,H9252-unsaturated aldehydes and ketones, 722 H9251 halogenation of aldehydes and ketones, 703–707, 727 in hydration of alkynes, 355–356, 361 in racemization of (R)-sec-butyl phenyl ketone, 715 Enolate ions, 708–711, 727 acylation of, 832–838, 851 alkylation of, 724, 725–726, 729, 839–845, 850, 852 of esters, 831–857 in Claisen condensation, 832–835, 851 in Dieckmann reaction, 835, 851 and hydrogen-deuterium exchange, 713–715 intermediate in aldol condensation, 715–720, 728 in conjugate addition to H9251,H9252-unsaturated carbonyl compounds, 722, 728–729 in haloform reaction, 711–712, 727 Enolization, 705–708, 727. See also Enol mechanism of acid catalyzed, 706 base catalyzed, 708 Entgegen (E), 173–175, 199 Enthalpy, 74, 106–107, 155 Entropy, 106 and ionization of carboxylic acids, 747 Envelope conformation, 108, 120 Environmentally benign synthesis, 598–599 Enzymes aconitase, 772 alcohol dehydrogenase, 600 aldolase, 1003 carbonic anhydrase, 749 carboxypeptidases, 1071, 1086–1088 chymotrypsin, 1071 emulsin, 992–993 fatty acid synthetase, 1019 fumarase, 276 haloalkane dehalogenase, 314 lactase, 993 lactic acid dehydrogenase, 602, 681 maltase, 992–993 monooxygenases, 638, 684 pepsin, 1071 phosphoglucose isomerase, 1002 restriction enzymes, 1101 reverse transcriptase, 1098 RNA polymerase, 1096 succinate dehydrogenase, 182 triose phosphate isomerase, 1004 trypsin, 1071 Epichlorohydrin, 85 Epimers, 1002 Epinephrine, 640, 869, 1066. See also Adrenaline Epoxidation of alkenes, 238–240, 250, 630, 645 biological of arenes, 948, 1064 of squalene, 638, 1036 of (E)- and (Z)-2-butene, 285 propene, 274 Epoxides biosynthesis of, 637–638, 1064 nomenclature of, 238–239, 620 preparation of, 238–240, 250, 274, 630–632, 645 reactions of, 632–637 with ammonia, 634 in biological processes, 637–638 with Grignard reagents, 587–588, 608, 632, 635 with lithium aluminum hydride, 635 with nucleophilic reagents, 632–637, 645–646 1,2-Epoxycyclohexane hydrolysis of, 637 preparation of, 631 reactions of with hydrogen bromide, 637 with sodium azide, 877 1,2-Epoxycyclopentane reaction with sodium ethoxide, 633 1,2-Epoxypropane preparation of, 632 reaction with phenylmagnesium bromide, 635 stereogenic center in, 263, 274 Equatorial bonds in cyclohexane, 100–103, 119 Equilibrium constants for enolization, 706, 727 for hydration of aldehydes and ketones, 663 table relation to H9004G°, 106 Ergosterol, 1039 Ernst, Richard R., 492 Erythro, stereochemical prefix, 278 Erythromycin, 758 D-Erythrose, 975 furanose forms, 978–981 L-Erythrose, 975 Essential amino acids, 1054–1055 fatty acids, 1024 oils, 1025 Esterification. See also Esters of amino acids, 1063, 1079 Fischer, 593–594, 610, 754–757, 767, 789 of glycerol, 1022–1023 of phenols, 949–952, 963 Esters enolates of, 831–857 infrared spectra, 519 table, 817 of inorganic acids, 595–596, 610 lactones, 758–759, 788 naturally occurring, 787–788 nomenclature of, 775–776 nuclear magnetic resonance spectra, 817 physical properties, 788, 790 preparation by Baeyer-Villiger oxidation, 683–684, 691, 789 preparation from alcohols with acyl chlorides, 594, 595, 610, 781, 789, 820 with carboxylic acid anhydrides, 595, 610, 785–787, 789, 820 by Fischer esterification, 593–594, 595, 610, 754–757, 767, 789 reactions, 790–800 with ammonia and amines, 791, 799–800 Claisen condensation, 832–835, 836–837, 851 Dieckmann reaction, 835–836, 851 Esters—Cont. with Grignard reagents, 560–561, 572, I-15 INDEX 583, 790 hydrolysis of, acid catalyzed, 791–794, 820 hydrolysis of, base promoted, 791, 794–799, 820 reduction of, 587, 790 resonance in, 778 thioesters, 800 waxes, 1024 Estradiol, 1040 Estrogens, 1040 Ethane, 56–57 acidity of, 343, 345, 552 bond angles and bond distances in, 57, 343 bond dissociation energies in, 343 bonding in, 37, 46 chlorination of, 54, 156 conformations of, 90–93, 117–118 dehydrogenation of, 168 electrostatic potential map, 53 1 H chemical shift, 495 in natural gas, 56 1,2-Ethanediol. See Ethylene glycol Ethanoic acid. See Acetic acid Ethanol, 128, 130, 580–581 acidity of, 135, 740–741 and benzaldehyde, acetal from, 669 biological oxidation of, 600–602 13 C chemical shifts, 606 conversion to diethyl ether, 592 dehydration of, 182 dipole moment of, 130, 863 by fermentation, 580–581 hydrogen bonding in, 130–131 industrial preparation of, 223, 581 physical properties of, 130, 132–133, 580 reduction of aryl diazonium salts by, 894, 907 Ethene, 38, 167. See also Ethylene Ethers, 619–653, 954–958. See also Epoxides as anesthetics, 647, 649 crown ethers, 622–624, 644 1 H chemical shifts, 641, 647 infrared spectra, 641 mass spectra, 643 nomenclature of, 619–620 physical properties of, 622 polyethers, 622–624 preparation of from alcohols, 590–593, 610, 625–626, 644 from carbohydrates, 1004, 1010 Williamson ether synthesis, 626–627, 644, 954, 964 reactions of Claisen rearrangement of allyl aryl ethers, 957–958, 964 cleavage by hydrogen halides, 628–630, 645, 956–957, 964 oxidation of, 627 structure and bonding in, 621 Ethoxide ion electrostatic potential map, 741 Ethyl acetate Claisen condensation of, 832–835 electrostatic potential map, 777 enolate of, 833–834, 849 1 H NMR spectrum, 817 reaction with pentylmagnesium bromide, 583 saponification, 796 Ethyl acetoacetate in acetoacetic ester synthesis, 839–841, 847, 850 enolate addition to H9251,H9252-unsaturated ketones, 847 preparation of, 832–835 Ethyl alcohol. See Ethanol Ethylamine, basicity of, 866 Ethylbenzene benzylic bromination of, 416 dehydrogenation of, 419, 453 Ethyl benzoate acylation of ketone enolates by, 837–838 hydrolysis of, 794, 799 reaction with phenylmagnesium bromide, 572 reduction of, 587, 790 saponification of, 799 Ethyl bromide, 1 H NMR spectrum, 503–504 Ethyl butanoate, Claisen condensation of, 851 Ethyl chloride, 48, 156. See also Chloroethane Ethyl cinnamate, 788 Ethyl cyanoacetate, 857 Ethylene, 168. See also Ethene acidity of, 343, 345, 552 biosynthesis of, 168 bond dissociation energies in, 343 bonding in, 14, 38–40, 47, 54, 170–171, 198 discovery, 168 electrostatic potential map, 167, 214, 342, 658 1 H chemical shift, 495 heat of hydrogenation, 209, 211 as industrial chemical, 168, 248, 453, 598 H9266 molecular orbitals of, 386–387 natural occurrence, 168 preparation of dehydration of ethyl alcohol, 182 dehydrogenation of ethane, 168, 181 reactions of alkylation of benzene, 453 with bromine, 234 dehydrogenation, 340 hydration of, 226 hydrogenation of, 208 oxidation of, 598 polymerization of, 245–246, 247, 567–570, 573 with sulfuric acid, 224 structure of, 35, 171, 343 Ethylenebromonium ion, 235–236 electrostatic potential map of, 208 Ethylene dibromide. See 1,2-Dibromoethane Ethylene glycol, 248, 589, 635–636 electrostatic potential map, 579 polyesters, 809 Ethylene oxide, 116, 238, 248, 620. See also Oxirane dipole moment, 622 industrial preparation of, 248, 598 reactions with nucleophiles, 587–588, 608, 632–633, 635–636 structure of, 620, 621 Ethyl fluoroacetate reaction with ammonia, 791 with cyclohexylamine, 799 Ethyl group, 65 spin-spin splitting in, 503–504 Ethyl hydrogen sulfate, 223 Ethylmagnesium bromide, reaction of with acetophenone, 559 with alkynes, 556 with cyclohexanone, 662 Ethyl 3-oxobutanoate. See Ethyl acetoacetate Ethyloxonium ion as intermediate in dehydration of ethyl alcohol, 187 in formation of diethyl ether, 592 Ethyl pentanoate, Claisen condensation of, 838 Ethyl propanoate Claisen condensation of, 835 saponification, 796 Ethyl thioacetate electrostatic potential map, 777 Ethyl p-toluenesulfonate, 326 Ethyne. See Acetylene Ethynyl group, 340 European bark beetle, 615 Exothermic reaction, 11, 74 and relation to bond energies, 155 Faraday, Michael, 383, 399 Farnesene, 167 Farnesol, 1026, 1027 pyrophosphate, 1029–1030 Fats, 788, 1017–1019 Fatty acids, 788, 795, 1017–1019 biosynthesis of, 1060–1063 essential, 1025 esters of, 788, 1022–1024 fats as sources of, 788, 795, 1017 Fehling’s solution, 999 Fermentation, 580–581 Ferrocene, 567 electrostatic potential map, 546 Fibroin, 1085 Fibrous proteins, 1086 Field effect, 747 Fieser, Louis F., 978 Fieser, Mary, 978 Fingerprint region of infrared spectrum, 519 First point of difference rule, IUPAC nomenclature, 68, 408, 859 Fischer, Emil, 271 determination of glucose structure by, 996, 1014 Fischer esterification. See Esterification; Esters Fischer projection formulas, 271–272, 278, 280, 292, 595 H9251-amino acids, 1056, 1103 carbohydrates, 973–974, 1007 of meso stereoisomer, 280 tartaric acids, 286 INDEX I-16 Flagpole hydrogens, 99–100 Fluorinated hydrocarbons, boiling points, 130, 132 Fluorine electron-dot structure of F 2 , 13 electronegativity, 15 magnetic resonance spectroscopy of 19 F, 544 reaction with alkanes, 148, 155 Fluorobenzene physical properties, 941 preparation of, 919 Fluorocyclohexane, 105, 107 1-Fluoro-2,4-dinitrobenzene, 923, 1071–1072 Fluoroethane, attractive forces in, 130 Fluoromethane. See Methyl fluoride p-Fluoronitrobenzene, nucleophilic aromatic substitution in, 923–925, 956 m-Fluorophenol, bromination, 948 p-Fluorophenol, O-acylation, 949 Formal charge, 15–19, 41 Formaldehyde, 241, 654 electrostatic potential map, 654, 658 hydration of, 663–667 industrial preparation of, 580, 661 in mixed aldol addition, 719 reaction with Grignard reagents, 555, 557, 572 structure and bonding, 14, 28–29, 657 Formic acid, 164, 737 natural occurrence, 750 structure and bonding, 738–739 Fourier-transform spectroscopy infrared (FT-IR), 519 nuclear magnetic resonance (FT-NMR), 492, 515 Fragmentation in mass spectrometry, 529–530 Fragment condensation in peptide synthesis, 1080 Free energy, relation to equilibrium constant, 106–107, 740 Free radical, 149–159, 162–163 allylic, 365, 370–372, 390–391 benzylic, 414 bonding in, 149, 162 chain reactions of, 153–159, 162–163 as intermediates in addition of hydrogen bromide to alkenes, 220–223, 251 allylic halogenation, 370–372, 391 benzylic halogenation, 415 halogenation of alkanes, 148–159, 162–163 polymerization of alkenes, 245–246 stabilization by alkyl groups, 149–150, 162 Freons, 48 Friedel, Charles, 451 Friedel-Crafts acylation with acyl chlorides, 446, 453–454, 780, 951 of anisole, 478, 660 of benzene, 453–457, 473–474 of bromobenzene, 473, 921 with carboxylic acid anhydrides, 455, 784, 921 of 2-ethylacetanilide, 888 of furan, 476 mechanism of, 454 of naphthalene, 474–475 of phenol, 951 scope and limitations, 479 table of p-xylene, 471 Friedel-Crafts alkylation with alcohols, 950 with alkenes, 453 with alkyl halides, 446, 450–451, 478 of benzene, 450–453, 478 of o-cresol, 950 scope and limitations, 479 table Fries rearrangement, 952 Frontier orbitals, 386 D-Fructose, 973, 986, 1002 6-phosphate, 1003 Fukui, Kenichi, 390 Fullerenes, 410–411 Fumarase, 276 Fumaric acid, 182, 276 Functional class nomenclature of alcohols, 128 of alkyl halides, 127 Functional groups, 55–56, 80, 126 and infrared spectroscopy, 487, 518, 536 tables of, inside front cover, 55, 56 transformation of, by nucleophilic substitution, 303–305 Furan, 430 bonding in, 432 electrophilic aromatic substitution in, 476 Furanose forms of carbohydrates, 978–981 Furfural, 430, 682, 751 G (symbol for free energy), 106 GABA. See H9253-Aminobutyric acid Gabriel, Siegmund, 875 Gabriel synthesis, 875–876, 902 D-Galactal, 991 D-Galactitol, 998, 999 D-Galactose, 977 natural occurrence, 976 pyranose form, 983–984 reduction of, 998 Gas chromatography (GC), 530–531 Gasoline, 70 Gauche conformation, 92, 117 of butane, 94, 118 Gel electrophoresis. See Electrophoresis Geminal coupling, 507 Geminal dihalides by hydrogen halide addition to alkynes, 354, 361 in preparation of alkynes, 348–349, 359 Geminal diols. See Diols Generic names of drugs, 63 Genetic code, 1100 Geneva rules, 63 Genome, 1100 Geometric isomers, 109, 202. See also Stereoisomers Geraniol, 205, 1030 pyrophosphate, 1029–1030 Geranylgeraniol, 1030 Gilbert, Walter, 1102 Globular proteins, 1086 H9251-D-Glucopyranose, 982, 985. See also D-Glucose pentaacetate, 1004 H9252-D-Glucopyranose, 982, 985, 1007. See also D-Glucose D-Glucose, 580, 973, 976. See also H9251-D-Glucopyranose; H9252-D- Glucopyranose conversion to D-fructose, 1002 electrostatic potential map, 972 epimerization of, 1002 Fischer determination of structure, 996, 1014 hydrogenation of, 612 metabolism, 1015 methyl glycosides, 990–991 mutarotation of, 985–986 natural occurrence, 976 oxidation of, 1000 6-phosphate, 1003 pyranose form, 981–983 L-Glucose, 1001 D-Glucuronic acid, 1000 L-Glutamic acid, 1055, 1059, 1063–1065 electrostatic potential map, 1053 L-Glutamine, 1055, 1059 electrostatic potential map, 1053 Glycals, 991 D-Glyceraldehyde Fischer projection formula, 974 3-phosphate, 1003 L-Glyceraldehyde, 974 Glycerol. See also Phosphoglycerides esters, 788, 795, 1017–1018, 1022–1023, 1043 Glycine, 1054, 1056, 1059 acetylation, 1063 acid-base properties, 1057–1061 electrostatic potential map, 1053 ethyl ester, 1079, 1080 Glycogen, 995 Glycolysis, 1002–1004, 1093 Glycoproteins, 995 Glycosides, 988–991, 1008. See also Disaccharide; Polysaccharide Goodyear, Charles, 383 Gossypol, 947 Grain alcohol, 128. See also Ethanol Graphite, 410 Grignard, Victor, 550 Grignard reagents acetylenic, 553, 556–557 basicity of, 551–553, 570 preparation of, 550–551, 571 reactions of with aldehydes, 555, 572, 661, 662 carboxylation, 750–752, 766 with epoxides, 587–588, 608, 632, 635 with esters, 560–561, 572, 583, 790 with formaldehyde, 555, 557, 572, 582 Grignard reagents—Cont. with ketones, 555, 559, 572, 662 with nitriles, 816–817, 822 I-17 INDEX with H9251,H9252-unsaturated aldehydes and ketones, 722 Griseofulvin, 920 Guaiacol, 956 Guanine, 1091, 1094–1100 Guanosine, 1092 D-Gulose, 977 Gum benzoin, 399 Gutta percha, 383 Gutte, Bernd, 1083–1084 h (symbol for Planck’s constant), 488 H (symbol for enthalpy), 74 H9004H° and bond dissociation energy, 155 and heats of reaction, 74 relation to free energy, 106–107 Half-chair conformation, 103 Halides. See Acyl chlorides; Alkenyl halides; Alkyl halides; Aryl halides H9251-Halo aldehydes, preparation of, 703 H9251-Halo carboxylic acids nucleophilic substitution in, 760 preparation of, 759–760, 767 reaction with ammonia, 760, 874 Halogen addition. See also Bromine; Chlorine to alkenes, 233–236, 250, 284–285 to alkynes, 356–357, 361 to conjugated dienes, 382 Halogenation. See also Bromination; Chlorination aldehydes and ketones, 703–705, 713, 727 carboxylic acids, 759–760, 767 electrophilic aromatic substitution, 446, 448–450, 466, 468–469, 471–474, 478, 919 free radical of alkanes, 54, 126, 148–159, 162–163 allylic, 370–372, 392 benzylic, 414–416 Halohydrins conversion to epoxides, 630–632, 645 from epoxides, 637 preparation of, from alkenes, 236–238, 250 H9251-Halo ketones, preparation of, 703, 727 Halonium ion, 235–238, 250 Halothane, 48 Hammond, George S., 145 Hammond’s postulate, 145 Hassel, Odd, 99 Haworth, Sir Norman, 980 Haworth formulas, 980 Heat of combustion, 74 aldehydes and ketones, 658 alkanes, 74–77 alkenes, 176–178 cycloalkanes, 98 table dimethylcyclohexanes, 110 table cis- and trans-1,2-dimethylcyclopropane, 109 Heat of formation, 77 Heat of hydrogenation, 209 alkadienes, 374–375 alkenes, 209–212 alkynes, 350–351 allene, 375 benzene, 404 butene isomers, 209–211 1,3-cyclohexadiene, 404 (Z )-1,3,5-hexatriene, 404 Heat of reaction, 77, 155 H9251-Helix, 1084–1086 Hell-Volhard-Zelinsky reaction, 759–760, 767 Heme, 1088 Hemiacetal, 669 cyclic, of carbohydrates, 978–984 Hemiketal. See Hemiacetal Hemoglobin, 1089–1090 Henderson-Hasselbalch equation, 743, 865 Heptanal cyclic acetal of, 670 oxime, 674 preparation of, 597 in reductive amination, 880 Heptane, 62 photochemical chlorination of, 166 1-Heptanol oxidation of, 597 reaction with hydrogen bromide, 138 2-Heptanone, 363, 840 3-Heptanone, 13 C NMR spectrum, 687 Heroin, 869 Hertz, Heinrich R., 488 Heterocyclic compounds. See also Furan; Purine; Pyridine; Pyrimidine; Pyrrole aliphatic, 116–117, 620 aromatic, 430–433, 436–437, 1090–1091 electrophilic aromatic substitution in, 475–476 nucleophilic aromatic substitution in, 927 basicity of heterocyclic amines, 868 Heterogeneous reaction, 209 Heterolytic bond cleavage, 150, 302–303 Hexachlorophene, 51 Hexafluoroacetone, 664 Hexafluorobenzene, 926, 966 Hexafluoroethane, 132 Hexane, 62 conformation of, 97 infrared spectrum, 519, 520 n-Hexane, 59, 62. See also Hexane Z-1,3,5-Hexatriene heat of hydrogenation of, 404 1-Hexene addition of bromine, 250 heat of hydrogenation, 211 infrared spectrum, 519, 521 cis-3-Hexene, reaction of, with hydrogen bromide, 214 Hexylmagnesium bromide, reaction of with acetaldehyde, 555 with ethylene oxide, 588 1-Hexyne, 556 1-Hexynylmagnesium bromide, 556–557 High-density lipoprotein, 1038 Highest occupied molecular orbital. See HOMO Histamine, 1066 L-Histidine, 1055, 1059 decarboxylation of, 1066 electrostatic potential map, 1053 Hodgkin, Dorothy Crowfoot, 568 Hofmann, August W., 399, 807, 884 Hofmann elimination, 883–885, 904 Hofmann rearrangement, 807–813, 822 Hofmann rule, 884 HOMO (highest occupied molecular orbital), 386 Homologous series, 59, 75 HOMO-LUMO interactions in pericyclic reactions cycloaddition, 388–390 HOMO-LUMO transitions in ultraviolet- visible spectroscopy, 524–525 Homolytic bond cleavage, 150 Hückel, Erich, 423 Hückel’s rule, 423–429, 432–433, 436 Huffman, Donald, 410 Hughes, Edward D., 306, 315, 336 Hund’s rule, 10 Hybrid orbitals. See Orbital hybridization Hydration of aldehydes and ketones, equilibria in, 663–667, 689 of alkenes acid-catalyzed, 225–227, 249, 581 hydroboration-oxidation, 227–233, 250, 582 of alkynes, 355–356, 361, 660 enzyme-catalyzed, of fumaric acid, 276 Hydrazine cleavage of peptides, 1107 reaction with aldehydes and ketones, 674 with N-alkylphthalimides, 876 in Wolff-Kishner reduction, 456, 662 Hydrazones, 674 Hydride shift alcohol dehydration, 189–190, 201 cholesterol biosynthesis, 1036 electrophilic addition to alkenes, 219–220 Friedel-Crafts alkylation, 452, 479 in reaction of alcohols with hydrogen halides, 330 in S N 1 reactions, 320 Hydroboration-oxidation, 227–233, 250, 582 Hydroformylation, 661, 732 Hydrogen. See also Hydrogenation; Nuclear magnetic resonance spectroscopy covalent bonding in, 12 formation of, 6 molecular orbitals, 34–35 nuclear spin states, 490–491 Hydrogenation. See also Heat of hydrogenation; Hydrogenolysis of benzyl of aldehydes and ketones, 583–584, 608 of alkadienes, 374–375 of alkenes, 208–213, 249 of alkenylbenzenes, 419–420, 435 of alkyl azides, 877 INDEX I-18 of alkynes, 350–351, 360 of benzene, 403–404 of carbohydrates, 996, 1009 of carbon monoxide, 580 catalysts for, 208–209, 350–351 of esters, 587 of imines, 879–880 of ketones, 584, 608 mechanism, 210 of nitriles, 877 of nitroarenes, 878 stereochemistry of, 212–213, 285 Hydrogen bonding, 130 in alcohols, 130–133, 160 in amines, 863–864 in carboxylic acids, 739 between ethers and water, 622 intramolecular in enol of 2,4-pentanedione, 708 in o-nitrophenol, 942 in peroxyacetic acid, 240 in salicylate ion, 953 in nucleic acid bases, 1094–1096 in peptides and proteins, 1084–1086 in phenols, 941–942 and solvent effects on rate of nucleophilic substitution, 322 Hydrogen bromide acidity of, 135–137 electrophilic addition to alkenes, 213–216 to alkynes, 353, 361 to conjugated dienes, 379–382, 392 to styrene, 435 free-radical addition to alkenes, 220–223, 251, 421 to alkynes, 354 reaction of with alcohols, 137–138, 146, 161, 329–330, 591 with epoxides, 635, 637 with ethers, 628–630, 645, 956 Hydrogen carbonate ion. See Bicarbonate Hydrogen chloride acidity of, 135 addition of to alkenes, 213, 216, 219–220, 249 to alkynes, 354 to conjugated dienes, 379–380, 392 electrostatic potential map of, 214 reaction with alcohols, 137–140, 143–146, 161, 330 Hydrogen cyanide acid-dissociation constant, 134, 135, 324, 722 addition to aldehydes and ketones, 667–668, 689, 814 H9251,H9252-unsaturated aldehydes and ketones, 722 geometry of, 28 in Kiliani-Fischer synthesis, 1001, 1009 Lewis structure, 14 Hydrogen-deuterium exchange in alcohols, 166, 510 in carboxylic acids, 763 in cyclopentanone, 714 Hydrogen fluoride, 14, 15 acidity of, 135 addition to alkynes, 354 Hydrogen halides. See also Hydrogen bromide; Hydrogen chloride; Hydrogen fluoride; Hydrogen iodide acidity of, 135 addition of to alkenes, 213–223, 249 to alkenylbenzenes, 420–421, 435 to alkynes, 352–354, 361 to conjugated dienes, 379–382, 392 reactions of with alcohols, 137–140, 143–146, 160–162, 329–330, 332, 591 with epoxides, 635, 637 with ethers, 628–630, 645, 956–957, 964 Hydrogen iodide acidity of, 135 cleavage of ethers, 628, 964 reaction with alcohols, 137 Hydrogenolysis, of benzyl esters, 1078–1079 Hydrogen peroxide conformations of, 89 oxidation of dialkyl sulfides by, 639 oxidation of organoboranes by, 228, 230–232 Hydrogen sulfide acidity of, 324 anion of basicity of, 324 as a nucleophile, 303, 304, 313, 324 boiling point, 604 Hydrolysis of acetals, 671, 672 of acyl chlorides, 781, 782 of alkyl halides, 312, 315, 582 of alkyl hydrogen sulfates, 224 of amides, 804–807, 808, 887 of H9251-bromo carboxylic acids, 760 of 2-bromooctane, stereochemistry of, 307–308, 319 of tert-butyl bromide, 315–316 of carboxylic acid anhydrides, 785 of carboxylic acid derivatives, relative rate, 780 table of cyanohydrins, 753 of epoxides, 635–637 of esters, 791–799, 820 of nitriles, 752–753, 766, 815–816 of peptides and proteins, 1070–1071 Hydronium ion, 134, 135. See also Oxonium ion Hydrophilic, 744 Hydrophobic effect, 74 Hydroquinone, 940, 958 Hydroxide ion as base, 135, 191, 345, 604, 709, 742 as nucleophile, 306–315, 665, 712, 794–799, 808 o-Hydroxybenzoic acid, 737. See also Salicylic acid Hydroxylamine, 674 Hydroxylation of alkenes anti, 637 syn, 590 Hyperconjugation, 142 Hypophosphorous acid, 894, 907 Hz (symbol for Hertz), unit of frequency, 488 Ibuprofen, 85, 273, 768 Icosane, 62 Icosanoic acid, 1018 D-Idose, 977 Iijima, Sumio, 411 Imidazole, 431, 868 Imides, 804 Imines in addition of Grignard reagents to nitriles, 816 in biological chemistry, 675–676, 1065 as intermediates in reductive amination, 879–880 preparation of, 672–673, 689 stereoisomers, 695 Iminium ion, 880 Imino acid, 815–816 Indene, 420 Index of hydrogen deficiency, 532–533 Indigo, 4, 98, 859 Indole, 430–431 Induced dipole-induced dipole forces, 72–74, 76, 130. See also van der Waals forces Inductive effect, 141 and acidity of carboxylic acids, 740, 745–748 in acyl chlorides, 778 of alkyl groups in aldehydes and ketones, 658, 664 in alkenes, 176–178, 199 in alkynes, 350 in carbocations, 141–143, 162, 317 of trifluoromethyl group, 461, 664 Industrial preparation of of acetaldehyde, 598 of acetic acid, 750 of acetic anhydride, 783 of acetone, 661, 947, 969 of acetylene, 340 of aldehydes, 661 of benzene, 399 of 1,3-butadiene, 378 of chloromethanes, 148 of 1,2-epoxypropane, 632 of ethanol, 223 of ethylene, 168, 181 of ethylene oxide, 248, 598 of formaldehyde, 580, 661 of isopropyl alcohol, 224 of methanol, 579–580 of phenol, 920, 947, 969 of propene, 168, 181 of styrene, 419, 453 of terephthalic acid, 750 of urea, 802–803 Infrared spectra. See also Infrared spectroscopy benzyl alcohol, 522, 523 I-19 INDEX butanal, 685 butylamine, 898 tert-butylbenzene, 520–521 p-cresol, 960 cyclohexanol, 605–606 diethylamine, 898 dipropyl ether, 642 hexane, 520 2-hexanol, 520, 522 2-hexanone, 522–523 1-hexene, 520–521 4-phenylbutanoic acid, 764 Infrared spectroscopy, 518–523, 536. See also Infrared spectra absorption frequencies table, 519 alcohols, 519, 520, 605 aldehydes and ketones, 519, 520, 522, 684–685 amines, 897–898 carboxylic acids and derivatives, 519, 763–764, 817 ethers and epoxides, 641 nitriles, 519, 817 phenols, 960 Ingold, Sir Christopher, 4 and stereochemical notation, 174, 268–271 and studies of reaction mechanisms electrophilic aromatic substitution, 447 elimination, 192–194 nucleophilic substitution, 144, 146, 306, 315 Initiation step, 149, 153–154, 221, 246 Initiators of free-radical reactions, 220–221, 245–246, 415–416 Insulin, 1070, 1073–1074, 1080 Integration and NMR peak area measurement, 497 International Union of Pure and Applied Chemistry. See IUPAC Inversion of configuration complete, in S N 2 reactions, 307–309, 331 partial, S N 1 reactions, 318–319, 331 Iodination of alkanes, 148 of alkenes, 233 of arenes, 450 Iodobenzene, 563, 919 Iodomethane. See Methyl iodide Iodomethylzinc iodide preparation of, 564, 571 reactions with alkenes, 563–565, 572 Ion-exchange chromatography, 1070–1071 Ionic bonds, 11–12, 44 Ionization constant. See Acid dissociation constants Ionization energy, 11 Ionization potential. See Ionization energy H9251- and H9252-Ionone, 1049 Ionophore, 624, 1023 Iron, reduction of nitroarenes by, 878 Iron(III) salts as catalysts in halogenation of arenes, 446, 448–450 Isoamyl acetate, in bananas, 85, 788 Isobutane, 57. See also 2-Methylpropane Isobutene. See 2-Methylpropene Isobutyl chloride, 158, 452 Isobutylene, 167. See also 2-Methylpropene Isobutyl group, 66. See also 2-Methylpropyl group Isobutyl radical, 158 Isocitric acid, 772 Isocyanates, as intermediates in Hofmann rearrangement, 812–813 Isoelectric point, 1058–1059 Isoelectronic, 47–48 Isolated diene, 372, 391 L-Isoleucine, 1054, 1059 electrostatic potential map, 1053 Isomers, 2 alkanes, 57–61 alkenes, 172–174, 198–199 classification, 291 table constitutional, 22, 45, 57 keto-enol, 355, 705–707 number of, 60 stereoisomers (see Stereoisomers) Isopentane, 59–61. See also 2-Methylbutane Isopentenyl pyrophophate, 1028–1030, 1033–1034, 1044 Isoprene, 383, 1026 Isoprene rule, 1028 Isoprenoid compounds. See Terpenes Isopropenyl group, 169–170 Isopropyl alcohol, 19, 128 industrial preparation of, 224 properties of, 581 Isopropylbenzene. See also Cumene conversion to phenol, 947, 969 nitration, 878 Isopropyl chloride, 1 H NMR spectrum, 505 Isopropylcyclohexane, 105 Isopropyl group, 65. See also 1-Methylethyl group size of, 105, 107, 310–311 spin-spin splitting in, 505 Isopropyl hydrogen sulfate, 223, 224 Isopropyl radical, 151–152 Isoquinoline, 430 Isotactic polymers, 288–289, 570 Isotopes. See also Carbon; Hydrogen- deuterium exchange in biosynthetic studies, 1033–1034 H-D exchange in alcohols, 166, 510 H-D exchange in carboxylic acids, 763 H-D exchange in cyclopentanone, 714 in study of reaction mechanisms bromine addition to alkenes, 234 Claisen rearrangement, 957 ester hydrolysis, 794, 796–797 esterification, 754 hydrolysis of chlorobenzene, 931 nucleophilic aliphatic substitution, 336 nucleophilic aromatic substitution, 928, 931 Isotopic clusters in mass spectrometry, 528–529 IUPAC (International Union of Pure and Applied Chemistry), 63. See also Nomenclature, IUPAC J (symbol for coupling constant), 503 Joule (SI unit of energy), 11 K (symbol for equilibrium constant) relation to H9004G°, 106–107 Karplus, Martin, 544 Kazan, University of, 3 Kekulé, August, 3, 399–402 Kendrew, John C., 1087 H9251-Keratin, 1085 Ketals. See Acetals Ketene, 783 H9252-Keto acids, decarboxylation, 762–763, 768, 838, 840–841, 850 Keto-enol isomerism, 355, 705–707 Keto-enol tautomerism. See Keto-enol isomerism H9252-Keto esters acidity of, 831 alkylation of, 839–841, 850 Michael addition of, 846–847 nomenclature of, 832 preparation of by acylation of ketones, 837–838, 851 by Claisen condensation, 832–835, 851 by Dieckmann reaction, 835–836, 851 by mixed Claisen condensation, 836–837, 851 H9251-Ketoglutaric acid, 1063–1065 Ketones acidity of, 710 chemical shifts, 1 H and 13 C, 684–687 classification of carbons in, 702 enolization of, 703–711, 727 infrared absorption frequencies, 519, 523, 684 naturally occurring, 659 nomenclature of, 656, 688 physical properties of, 658 preparation of, 659–661 by acetoacetic ester synthesis, 839–841, 850 by decarboxylation of H9252-keto acids, 838, 850 by hydration of alkynes, 355–356, 361, 660 from nitriles, 816–817, 822 by oxidation of secondary alcohols, 597, 611, 659–661 by ozonolysis of alkenes, 660 reactions of acetal formation, 669–671, 672, 689 acylation via enolate, 837–838, 851 aldol condensation, 718, 720, 728 Baeyer-Villiger oxidation, 683–684, 691, 789 Clemmensen reduction, 456–457, 474, 662 cyanohydrin formation, 667–668, 689 with derivatives of ammonia, 674 enamine formation, 674–675, 677, 690 with ester enolates, 849 INDEX I-20 with Grignard reagents, 555, 559, 572, 662 halogenation, 703–705 hydration, 663–667, 689 imine formation, 672–673, 689 with organolithium reagents, 554–556, 572, 582, 662 reduction, 583–587, 608, 662 reductive amination, 879–881, 903 Wittig reaction, 677–681, 690 Wolff-Kishner reduction, 456, 662 spectroscopy, 684–687 structure and bonding, 657–658, 688 Ketoses, 973, 986–987, 1007 Kevlar, 809 Kharasch, Morris S., 220 Kiliani-Fischer synthesis, 1001, 1009 Kinetic control, 380–381 O-acylation of phenols, 952 addition to conjugated dienes, 380–381, 392 to H9251,H9252-unsaturated aldehydes and ketones, 723 Kinetic studies of elimination reactions of alkyl halides, 192–193 of ester hydrolysis, 796 of H9251-halogenation of aldehydes and ketones, 704 of nucleophilic aromatic substitution, 923 of nucleophilic substitution, 306, 315–318, 331 Kolbe, Hermann, 952 Kolbe-Schmitt reaction, 952–953, 963 Kossel, Walter, 12 Kr?tschmer, Wolfgang, 410 Krebs cycle, 1064 Kroto, Harold W., 410 Lactams, 803 Lactase, 993 Lactic acid, 737, 1015 biological oxidation of, 602 (S) enantiomer by enzymic reduction of pyruvic acid, 681–682, 1015 Lactones, 758–759, 788 formation of in Baeyer-Villiger oxidation of cyclic ketones, 695 by oxidation of carbohydrates, 1000 Lactose, 993 Laetrile, 1012 Lanosterol, 1035–1037 Lapworth, Arthur, 703 Lauric acid, 1018 Lavoisier, Antoine-Laurent, 1 LDA. See Lithium diisopropylamide Leaving groups and their basicity, 306, 327 table halides, 192–193, 302, 305–306, 331 table nitrogen of diazonium ions, 890 in nucleophilic aromatic substitution, 923 p-toluenesulfonates, 326–329 Le Bel, Joseph Achille, 259 Le Chatelier’s principle, 227 Lecithin. See Phosphatidylcholine Lenthionine, 117 L-Leucine, 1054, 1059 electrostatic potential map, 1053 Leucine enkephalin, 1068–1069 Leukotrienes, 1025 Levorotatory, 266 Levulinic acid, 772 Lewis, Gilbert N., 3, 12 Lewis acid, 143 Lewis base, 143 as nucleophile, 143, 312–314 Lewis structural formulas, 12–14, 42–43, 44 formal charges in, 16–19 multiple bonding in, 14 and resonance, 23–26 writing of, 20 table Lexan, 809 Liége rules, 63 Limonene, 71, 263, 1031 Linalool, 262 Linear H9251-olefins, 569, 577, 661 Linamarin, 989, 1012 Lindlar palladium, 350–351, 360 Linoleic acid, 1018, 1025 Linolenic acid, 1018 Lipids, 1015–1050. See also Fats; Oils; Phospholipids; Steroids; Terpenes; Waxes Lipoic acid, 117, 605 Lipophilic, 744 Lister, Joseph, 943 Lithium electronegativity, 15, 547 reaction with alkyl and aryl halides, 549–550, 571 reduction of alkynes, 351–352 Lithium aluminum hydride, reducing agent for aldehydes and ketones, 584–587, 608, 662 alkyl azides, 877, 902 amides, 879, 903 carboxylic acids, 587, 608, 659, 754 epoxides, 635 esters, 587, 608, 790 nitriles, 877, 902 table, 608 Lithium dialkylcuprates. See Lithium diorganocuprates Lithium diisopropylamide (LDA), 848–849 Lithium dimethylcuprate. See Lithium diorganocuprates Lithium diorganocuprates conjugate addition to H9251,H9252-unsaturated ketones, 724–725, 729 preparation of, 561–562, 571 reactions with alkenyl, alkyl, and aryl halides, 562–563, 573 Locant, numerical prefix in IUPAC nomenclature of, 64, 169 London dispersion forces. See van der Waals forces Lovastatin, 1038 Low-density lipoprotein, 1038 Lowry, Thomas M., 133 Luciferin, 431 Lucite, 828 Lycopene, 525, 1042 Lynen, Feodor, 1035 L-Lysine, 1055, 1059 electrophoresis of, 1060–1061 electrostatic potential map, 1053 D-Lyxose, 977 McGwire, Mark, 1041 Macrolide antibiotics, 758 Magnesium, reaction of with alkyl and aryl halides, 550–551, 571 Magnetic field induced, and nuclear shielding, 494–495 strength of, 491, 493 Magnetic resonance imaging (MRI), 517 Maleic anhydride, 783, 784 dienophile in Diels-Alder reaction, 384, 393 (S)-Malic acid, 276 as resolving agent, 287–288 Malonic acid, 737 acidity of, 748 decarboxylation of, 760–762, 767–768 Malonic ester synthesis 842–845, 852 Malonyl coenzyme A, 1020–1021, 1033 Maltase, 992–993 Maltose, 991–992, 999 Mandelic acid, 737 D-Mannose, 977 conversion to D-fructose, 1002 epimerization of, 1002 L-Mannose, 1001 Markovnikov, Vladimir, 215 Markovnikov’s rule, 215 in addition to alkenes, 214–219 to alkynes, 352–354, 356, 361 Mass spectrometer, 526–527 Mass spectrometry, 526–532, 536 alcohols, 607 aldehydes and ketones, 687 amines, 900 carboxylic acid derivatives, 818 ethers, 643 and gas chromatography, 530–531 phenols, 961–962 Mass-to-charge ratio (mlz), 527 Mauveine, 4 Mayo, Frank R., 220 Maytansine, 920 Maxam, Allan, 1102 Mechanism, 3 acetal formation, 669–670, 989 Ad E 3, 683 Baeyer-Villiger oxidation, 683 bimolecular nucleophilic substitution, 146, 160, 306–312, 331 table biosynthesis of amino acids by transamination, 1065 of cholesterol, 1036–1037 Mechanism—Cont. of fatty acids, 1019–1022 terpenes, 1028–1034 Birch reduction, 413 I-21 INDEX chromic acid oxidation, 599–600 Claisen condensation, 833–834 Claisen rearrangement, 957–958 cyanohydrin formation, 668 DCCI promoted peptide bond formation, 1081 decarboxylation of malonic acid, 761 dehydration of alcohols, 185–187, 199–201 dehydrohalogenation of alkyl halides, 192–198, 201 Dieckmann reaction, 835 Diels-Alder reaction, 384 dimerization of 2-methylpropene, 244 DNA replication, 1095 Edman degradation, 1074–1076 electrophilic addition to alkenes, 213–220, 224 electrophilic aromatic substitution, 444–447, 477 bromination, of benzene, 450 Friedel-Crafts acylation, of benzene, 454 Friedel-Crafts alkylation, of benzene, 451 nitration, of benzene, 447 sulfonation, of benzene, 448 elimination E1, 196–198 E2, 192–196, 201, 323–325 enamine formation, 674 enol conversion to ketone, 355 enolization, 706, 709 epoxidation, 240 epoxide ring opening, 634, 636 esterification, 756–757 ether cleavage, 629 ether formation, 592 free-radical addition of hydrogen bromide to alkenes, 220–223, 251 glycosidation, 990 halogenation addition to alkenes, 234–236, 284–285 allylic, of alkenes, 371 H9251, of aldehydes and ketones, 703–707 bromination, of benzene, 450 chlorination, of methane, 153–156 halohydrin formation, 236–238 Hofmann rearrangement, 811–812 hydration of aldehydes and ketones, 665, 666 of alkenes, 226 of alkynes, 355 hydride reduction of aldehydes and ketones, 585–587 hydroboration-oxidation, 230–233 hydrogenation of alkenes, 210 hydrogen halide addition to alkenes, 213–220, 275 to alkynes, 353 hydrolysis of acyl chlorides, 782 of amides, 805–806, 808 of carboxylic acid anhydrides, 786 of esters, 792–794 of nitriles, 815–816 saponification, 798 imine formation, 672 nitration of benzene, 447 nucleophilic alkyl substitution S N 1, 143–144, 162, 315–321, 331 table S N 2, 146, 162, 306–312, 331 table nucleophilic aromatic substitution addition-elimination, 923–927, 932–933 elimination-addition, 927–931, 933 polymerization of ethylene coordination polymerization, 569 free-radical polymerization, 245–246 proton transfer, 136–137 reaction of alcohols with hydrogen halides, 137–146, 160–162, 329–330, 332 reduction of alkynes by sodium in ammonia, 352 unimolecular nucleophilic substitution, 143–144, 162, 315–321, 331 Wittig reaction, 679 Meisenheimer, Jacob, 937 Meisenheimer complex, 937 Menthol, 164, 298, 580, 1027 Menthyl chloride, 206 Meparfynol, 575 Meprobamate, 857 Mercaptans. See Thiols Mercury (II) compounds, 356 Merrifield, R. Bruce, 1082–1084. See also Solid-phase peptide synthesis Mesityl oxide, 721 Meso stereoisomer, 279–282 Messenger RNA. See Ribonucleic acid, messenger Mestranol, 575 Meta (m) directing groups, 461–463, 464 table, 466–469, 477, 480 disubstituted aromatic compounds, 406 Metal-ammonia reduction of alkynes, 351–352, 360 arenes (see Birch reduction) Metal-ion complexes of ethers, 622 Metallocenes, 567, 569 Methane, 56–57 acidity of, 344–345, 553 bonding in, 35–37, 46, 56 chlorination, 148–149, 153–155 clathrates, 58 conversion to acetylene, 340 electrostatic potential map, 23, 27 natural occurrence, 56 physical properties, 57 structure, 13, 27, 28, 57 Methanesulfonic acid, 326 Methanogens, 58 Methanoic acid. See Formic acid Methanol, 128, 579–580 bond distances and bond angles, 129 13 C NMR, 899 dehydrogenation of, 661 dipole moment of, 129 electrostatic potential map, 129 esterification of, 754–757 industrial preparation of, 579–580 nitration of, 596 properties of, 580 Methide anion, 344 Methine group, 57 L-Methionine, 641, 1054, 1059 electrostatic potential map, 1053 Methionine enkephalin, 1068–1069 Methyl alcohol, 128. See also Methanol Methyl acetate UV absorption, 818 Methylamine basicity of, 865, 866 13 C NMR, 899 electrostatic potential map, 858 reaction with benzaldehyde, 873 structure and bonding, 861–863 Methyl benzoate in mixed Claisen condensation, 836 preparation of, 593, 754–757 Methyl bromide nucleophilic substitution in, 306–307, 309 reaction with triphenylphosphine, 680 2-Methylbutane, 73. See also Isopentane 2-Methyl-2-butanol dehydration of, 183 preparation of, 225 3-Methyl-2-butanol preparation of, 229 reaction with hydrogen chloride, 330 2-Methyl-2-butene acid catalyzed hydration, 225, 581 hydroboration-oxidation, 229 hydrogenation of, 209 preparation of from 2-bromo-2-methylbutane, 191, 197 2-methyl-2-butanol, 183 reaction of with hydrogen bromide, 223 with hydrogen chloride, 215–216 3-Methyl-2-butenyl pyrophosphate. See Dimethylallyl pyrophosphate; Isopentenyl pyrophosphate Methyl cation, 141 electrostatic potential map, 143 Methyl chloride, 132. See also Chloromethane Methylcyclohexane, conformations of, 104–105 2-Methylcyclohexanol, dehydration of, 183 1-Methylcyclopentene addition of hydrogen chloride, 215 hydroboration-oxidation, 230–233 Methylenecyclohexane, 677 Methylene group, 57 prefix, 170 Methylenetriphenylphosphorane, 677, 680 electrostatic potential map, 678 1-Methylethyl group, 65. See also Isopropyl group Methyl fluoride electrostatic potential map, 548 1 H chemical shift, 495 Methyl H9251-D-glucopyranoside, 990, 999 tetra-O-methyl ether, 1004 Methyl H9252-D-glucopyranoside, 990 Methyl group, 34 Methyl iodide. See also Iodomethane nucleophilic substitution, 312, 359, 726 reaction with amines, 883 INDEX I-22 Methyllithium, 553 electrostatic potential map, 548 Methylmagnesium halides reaction of with butanal, 572 with cyclopentanone, 555 with methyl 2-methylpropanoate, 561 with 1-phenyl-1-propanone, 559 Methyl methacrylate. See Methyl 2-methylpropenoate Methyl 2-methylpropenoate hydrolysis, 795 reaction with ammonia, 799 Methyl migration in alcohol dehydration, 187–189 in cholesterol biosynthesis, 1036–1037 Methyl nitrate, 596 Methyl nitrite, 22, 24 2-Methylpentane, 64 bromation of, 158 3-Methylpentane, 64 2-Methylpropanal acidity of, 710 1 H NMR, 685 reaction with tert-butylamine, 689 2-Methylpropane, 65. See also Isobutane acidity of, 552 bond dissociation energies in, 151–152, 414 chlorination, 158 Methyl propanoate 1 H NMR spectrum, 817 in mixed Claisen condensation, 836 2-Methyl-2-propanol, 138. See also tert-Butyl alcohol acid-catalyzed dehydration, 182 2-Methylpropene. See also Isobutene; Isobutylene addition of hydrogen bromide to, 215 addition of methanol to, 626 bromohydrin formation, 237 dimerization, 244 dipole moment, 176 heat of combustion, 177 hydration mechanism, 226 preparation of, 182 1-Methylpropyl group, 66. See also sec-Butyl group 2-Methylpropyl group, 66. See also Isobutyl group N- Methylpyrrolidone, 803 Methyl radical dimerization, 154 intermediate in chlorination of methane, 153–154 structure and stability, 150 Methyl salicylate, 788, 942 Methyltrioctylammonium chloride, 871 Methyl vinyl ketone reaction with diethyl malonate, 846–847 in Robinson annulation, 724, 728 Mevalonic acid, 758, 1028, 1033, 1044 Mevalonolactone, 759, 772 Micelle, 744–745, 795 Michael, Arthur, 724 Michael reaction, 724, 846–847, 852. See also Conjugate addition; H9251,H9252- Unsaturated carbonyl compounds Microscopic reversibility, 227 Microwaves, 488, 545 Mitscherlich, Eilhardt, 399 MM3, 97 Models. See Molecular models and modeling Molar absorptivity, 524 Molecular biology, 1094, 1100 Molecular dipole moments. See Dipole moment Molecular formula, 19, 51, 532–533 Molecular ion, 526 Molecular models and modeling, 27–28, 96–97 Molecular orbitals allyl cation, 397 [10]-annulene, 425 benzene, 407, 424 bonding and antibonding, 34–35 1,3-butadiene, 397–398 cyclobutadiene, 424 cycloheptatrienyl cation, 427–428 cis, trans-1,3-cyclooctadiene, 524 cyclooctatetraene, 424 cyclopentadienide anion, 428 ethylene, 386–397 frontier, 386 highest occupied (HOMO), 386, 524 hydrogen, 34–35 lowest unoccupied (LUMO), 386, 524 H9266 and H9266*, 386–387, 524–525 H9268 and H9268*, 34–35, 386 Monensin, 624 Monosaccharide, 972. See also Carbohydrates Monoterpene, 1026 Morphine, 869 Morpholine, 690 MRI. See Magnetic resonance imaging Multifidene, 298 Multiplets. See also Spin-spin splitting in 13 C NMR spectra, 515, 535 in 1 H NMR spectra, 500–509, 534–535 Muscarine, 297 Mutarotation, 985–986, 1007 Myoglobin, 1089 Myosin, 1085 Myrcene, 1026 Myristic acid, 1018 n (prefix), 57, 61 H9263 (symbol for frequency), 488 n H11001 1 splitting rule, 500, 508 NAD, NAD H11001 , NADH, NADPH. See Nicotinamide adenine dinucleotide Nanotubes, 411 Naphthalene, 398, 408–409 electrophilic aromatic substitution in, 474–475 1-Naphthol, azo coupling of, 897 2-Naphthol, nitrosation of, 950 Natta, Giulio, 246, 567–570, 573 Natural gas, 57, 69 Nembutal, 845 Neomenthol, 164 Neomenthyl chloride, 206 Neopentane, 60. See also 2,2-Dimethylpropane Neopentyl group, 66. See also 2,2-Dimethylpropyl group Neopentyl halides, nucleophilic substitution in, 312 Neoprene, 4, 383 Neryl pyrophosphate, 1030–1031 Neurotransmitters, 869, 1066 Newman, Melvin S., 90 Newman projections, 90–92, 94, 99 Nickel, hydrogenation catalyst, 208, 209, 403, 583–584 Nickel carbonyl, 566 Nicotinamide adenine dinucleotide coenzyme in epoxidation of alkenes, 638, 1036 fatty acid biosynthesis, 1020 formation of acetyl coenzyme A, 1016 oxidation of alcohols, 600–602 reduction of pyruvic acid, 681–682 structure of, 600 Nicotine, 51, 272, 274, 869 Ninhydrin, 1063 Nirenberg, Marshall, 1108 Nitration of acetanilide, 887 of acetophenone, 473 of benzaldehyde, 467, 873 of benzene, 446, 447–448, 473 of p-tert-butyltoluene, 471 of chlorobenzene, 469–470 of p-cresol, 950 of fluorobenzene, 478 of p-isopropylacetanilide, 886 of p-methylbenzoic acid, 472 of phenol, 463, 950 of toluene, 457, 458–460, 474 of (trifluoromethyl)benzene, 458, 461–462 of m-xylene, 472 Nitric acid nitration of arenes by, 447–448 oxidation of carbohydrates, 1000 of p-xylene, 750 reaction with alcohols, 595–596, 610 Nitriles. See also Cyanohydrins H9251-amino, as intermediates in Strecker synthesis, 1061–1062 hydrolysis of, 752–753, 766, 815–816 infrared absorption, 817 nomenclature of, 776 preparation of from alkyl halides, 304, 324, 752, 814 from aryl diazonium salts, 894, 905 by dehydration of amides, 814 reaction with Grignard reagents, 816–817 reduction, 877, 902 m-Nitroaniline, diazotization of, 893, 904, 905 o-Nitroaniline, diazotization of, 907 p-Nitroaniline basicity of, 867 bromination of, 904 preparation of, 887 Nitrobenzene electrophilic aromatic substitution in, 469, I-23 INDEX 919 preparation of, 446, 447–448, 474 Nitro group electron-withdrawing effect of, 464, 469, 926, 944–945 reduction, 878, 902 Nitromethane, 20, 22, 24–25 Nitronium cation, 447 m-Nitrophenol acidity of, 944, 945 preparation of, 905, 946 o-Nitrophenol acidity of, 944 intramolecular hydrogen bonding, 942 reaction with acetic anhydride, 951, 963 butyl bromide, 964 p-Nitrophenol acidity of, 944 esters of, in peptide bond formation, 1080 Nitrosamines, 889 Nitrosation amines, 888–891, 904–905 phenols, 950 N-Nitrosodimethylamine, 889 N-Nitrosonornicotine, 889 N-Nitrosopyrrolidine, 889 Nitrous acid, 888–895. See also Nitrosation Nobel, Alfred, 596 Noble gas electron configuration, 11 Nodal properties p orbitals, 9 of H9266 orbitals and pericyclic reactions, 386–390 surfaces, 8 Nomenclature common names of alcohols, 128 of alkanes, 61 of alkenes, 167–170 of alkenyl groups, 170 of alkyl groups, 65–66, 83, 127 of carboxylic acids, 767, 798 functional class, 127, 159 historical development of, 63 IUPAC of acyl halides, 775 of alcohols, 127–128, 159 of aldehydes, 654–655, 688 of alkadienes, 374 of alkanes, 61–69, 81–82 table of alkenes, 167–170, 198 of alkyl groups, 65–66, 83 table of alkyl halides, 127, 159 of alkynes, 340 of amides, 776 of amines, 859–861, 900 of benzene derivatives, 406–408 of bicyclic ring systems, 115 of carboxylic acid anhydrides, 775 of carboxylic acids, 737–738 of cycloalkanes, 68–69, 82 table of diols, 589 of epoxides, 238, 620 of esters, 775 of ethers, 619–620 of H9252-keto esters, 832 of ketones, 656, 688 of lactones, 758–759 of nitriles, 776 of organometallic compounds, 547, 570 of sulfides, 620 of thiols, 604 stereochemical notation cis and trans, 108–109 D-L, 973–978, 1007 erythro and threo, 278 E-Z, 173–175, 199 R-S, 268–271 substitutive, 127, 159 Nomex, 809 Norepinephrine, 640, 1066 Norethindrone, 1042 Nuclear magnetic resonance spectra carbon 1-chloropentane, 511 m-cresol, 514 3-heptanone, 687 methanol, 899 methylamine, 899 1-phenyl-1-pentanone, 516 proton benzyl alcohol, 509 2-butanone, 686 chloroform, 494 1-chloropentane, 511 p-cresol, 961 1,1-dichloroethane, 501 dipropyl ether, 642 ethyl acetate, 817 ethyl bromide, 503 isopropyl chloride, 505 methoxyacetonitrile, 497 4-methylbenzyl alcohol, 899 4-methylbenzylamine, 898–899 2-methylpropanal, 685 methyl propanoate, 817 m-nitrostyrene, 508 4-phenylbutanoic acid, 764 2-phenylethanol, 607 2,3,4-trichloroanisole, 507 Nuclear magnetic resonance spectroscopy carbon, 510–517, 535 alcohols, 606 aldehydes and ketones, 686–687 amines, 899 in biosynthetic studies, 1034 carboxylic acid derivatives, 818 carboxylic acids, 763–764 ethers, 643 and magnetic field strength, 491–493 proton, 490–510, 535 alcohols, 509–510, 535 aldehydes and ketones, 684–687 amines, 898–899 carboxylic acid derivatives, 817–818 carboxylic acids, 763–764 chemical shift, 493–497, 534 and conformations, 510, 535 ethers and epoxides, 641–642 interpretation, 497–500, 534 nuclear shielding, 493–494 phenols, 960–961 spin-spin splitting, 500–509 Nuclear spin states, 490–491 Nucleic acids, 1093–1103. See also Deoxyribonucleic acid; Ribonucleic acid Nucleophiles, 142–143, 162, 302–305 relative reactivity, 312–315 solvation and reactivity, 322–323 Nucleophilic acyl substitution, 774–830 of acyl chlorides, 780–783, 820 of amides, 804–807, 808, 821 of carboxylic acid anhydrides, 783–787, 820 of esters, 790–800, 820 of thioesters, 800 Nucleophilic addition to aldehydes and ketones, 663–682, 688–691 to H9251,H9252-unsaturated aldehydes and ketones, 722–724, 725, 728, 846–847, 852 Nucleophilic alkyl substitution alcohols, 139–146 alkyl halides, 302–325, 680, 752, 814, 839–845 alkyl p-toluenesulfonates, 326–328, 332 allylic halides, 366–369, 390, 840 benzylic halides, 417–419 crown ether catalysis of, 625 epoxides, 632–637 enzyme-catalyzed, 314 H9251-halo carboxylic acids, 760 phase-transfer catalysis of, 871–872 Nucleophilic aryl substitution, 922–931, 932–933, 946, 956 Nucleosides, 1091–1092 Nucleotides, 1092–1093 Nylon, 4, 809 Octadecanoic acid, 737 Octane isomers, heats of combustion and relative stability, 75–76 Octane number of gasoline, 71 2-Octanol, 555 reaction with hydrogen bromide, 330 Octet rule, 13, 44 Off-resonance decoupling, 515 Oil of wintergreen. See Methyl salicylate Oils. See Fats Olah, George A., 74 Olefin, 168. See also Alkenes H9251-Olefins. See Linear H9251-olefins Oleic acid, 173, 737, 1018 Oligosaccharide, 973 Opsin, 676 Optical activity, 265–267, 291 and chemical reactions, 274–276, 284–285, 292, 307–308, 318–319, 328, 330, 714–715 Optical purity, 266 Optical resolution. See Resolution Orbital hybridization model for bonding, 35–42, 46–47 sp in acetylene and alkynes, 40–42, 47, INDEX I-24 341–343, 358 in alkenyl cations, 353 in allenes, 377–378 sp 2 in alkadienes, 375–377 in aniline, 862–863 in benzene, 405 in carbocations, 141, 161–162 in ethylene and alkenes, 38–40, 47, 170–172, 198 in formaldehyde, 657 in free radicals, 150, 162 sp 3 in alkyl halides, 129 in ethane, 37, 46, 57 in methane, 35–37, 46, 57 in methanol, 129 in methylamine, 861, 862 Orbital symmetry, 397 and Diels-Alder reaction, 388–390 Orbitals atomic, 7–11 hybrid orbitals, 35–42, 46 molecular (see Molecular orbitals) Organic chemistry, historical background of, 1–6 Organoboranes, 228, 230–233 Organocopper compounds. See Lithium diorganocuprates Organolithium reagents basicity of, 551–553, 570 preparation of, 549–550, 571 reaction of with aldehydes and ketones, 554–556, 572, 573, 582 with epoxides, 587–588 with nitriles, 817 Organomagnesium compounds. See Grignard reagents Organometallic compounds, 546–578. See also Grignard reagents; Lithium diorganocuprates; Organolithium reagents; Organozinc compounds Organozinc compounds, 563–565, 571, 572 Ortho (o), disubstituted organic compounds, 406 Ortho-para directing groups, 457–461, 463–466, 464 table, 469–470 Osmium tetraoxide, 589–590, 608 Oxalic acid, 164, 748 Oxane, 593 Oxaphosphetane, 679 Oxazole, 431 Oxidation. See also Epoxidation; Hydroxylation of alkenes; Ozonolysis of alcohols, 596–600, 611, 659–661, 751 of aldehydes, 682, 691, 751 of alkylbenzenes, 416–417, 435, 750, 751 biological, 409, 417, 600–602 of carbohydrates, 998–1001, 1009 of ketones, 683–684, 691 of phenols, 958–959, 964 of vicinal diols, 602–603, 609 Oxidation-reduction in organic chemistry, 78–80, 83 Oximes, 674 Oxirane, 620. See also Ethylene oxide Oxolane, 620. See also Tetrahydrofuran Oxonium ions, 134, 135–136, 226 in dehydration of alcohols, 185–187, 190, 198 in epoxide ring opening, 635–636 in ether cleavage, 629 in reaction of alcohols with hydrogen halides, 140, 143–146, 160–161, 329 in solvolysis reactions, 312, 315–318 Oxo process. See Hydroformylation Oxyacetylene torch, 350 Oxygen biological storage and transport of, 1089–1090 isotopic labels, 754, 794, 796–797 Oxytocin, 1069–1070 Ozone, bonding in, 23, 240 Ozonide, 240 Ozonolysis of alkenes, 240–242, 251, 660 of alkynes, 357 Palladium hydrogenation catalyst, 208, 209, 583–584 Lindlar, 350–351, 360 Palmitic acid, 1018 Papain, 1071 Para ( p), disubstituted organic compounds, 406 Paraffin hydrocarbon, 74. See also Alkanes Partial rate factors, 460, 462, 470, 485 Pasteur, Louis, 286 Pauli exclusion principle, 9 Pauling, Linus, 3, 15 electronegativity scale, 15 and orbital hybridization model, 36 and peptide structure, 1084–1086 PCBs. See Polychlorinated biphenyls PCC. See Pyridinium chlorochromate PDC. See Pyridinium dichromate Pedersen, Charles J., 622 Penicillin G, 803 1,3- and 1,4-Pentadiene, relative stabilities, 374–375 2,3-Pentadiene, enantiomers, 378 Pentane, 62, 73, 512 conformation of, 97 n-Pentane, 59. See also Pentane 2,4-Pentanedione acidity of, 710–711 H9251-alkylation of, 726 enol content of, 707–708 Pentanenitrile hydrogenation of, 877 preparation of, 871 1-Pentanol esterification, 610 reaction with thionyl chloride, 161 3-Pentanol, dehydration, 185 3-Pentanone cyanohydrin, 689 mass spectrum, 687 Pentobarbital, 845 Pentothal sodium, 846 Pentyl azide, 873 Pepsin, 1071 Peptide bond, 1051, 1067 geometry of, 1068–1069 preparation of, 1079–1083 Peptides, 1067–1088 amino acid analysis, 1070–1071 classification of, 1051 end-group analysis of, 1071–1076 hydrolysis of, 1070–1071 structure of, 1051, 1067–1070 (see also Proteins) synthesis of, 1076–1084 Pericyclic reactions, 382–383, 958 Periodic acid cleavage of carbohydrates, 1005–1006, 1010 of vicinal diols, 602–603, 609 anti Periplanar, 195 syn Periplanar, 195 Perkin, William Henry, 4 Peroxide effect, 220 Peroxides initiators of free-radical reactions, 220–221, 415–416 by oxidation of ethers, 627–628 Peroxyacetic acid, 741 epoxidation of alkenes, 239–240, 250, 630, 645 Peroxybenzoic acid, 683–684 Perutz, Max F., 1087 Petrochemicals, 5, 168 Petroleum, 69 refining, 69–70 PGE 1 , PGE 2 , and PGF 1H9251 . See Prostaglandins Pharmacology, 897 Phase-transfer catalysis, 871–872, 901 H9251-Phellandrene, 1027 Phenacetin, 967 Phenanthrene, 408–409 Phenobarbital, 846 Phenol(s), 939–971 acidity of, 942–945, 962 electrostatic potential maps, 939, 942 formation of, in Claisen rearrangement, 957, 964 hydrogen bonding, 941–942 naturally occurring, 946–948 nomenclature of, 407, 939–940 physical properties, 941–942 preparation from aryl diazonium salts, 892, 905, 946, 947, 962 benzenesulfonic acid, 947 chlorobenzene, 920, 947 cumene, 947 Phenol(s)—Cont. reactions of O-alkylation, 954, 964 azo coupling, 951 bromination, 948–950 carboxylation, 952–954, 963 I-25 INDEX electrophilic aromatic substitution, 463, 948–951 esterification, 949–952, 963 Friedel-Crafts acylation, 951 Friedel-Crafts alkylation, 950 Kolbe-Schmitt reaction, 952–954, 963 nitration, 463, 950 nitrosation, 950 oxidation, 958–959, 964 sulfonation, 950 resonance in, 941 spectroscopic analysis, 960–961 structure and bonding, 940–941 Phenylacetic acid H9251-halogenation, 760 preparation of, 752 L-Phenylalanine, 1054, 1059 N-benzyloxycarbonyl derivative, 1077–1079 electrostatic potential map, 1053 in PKU disease, 1065 Phenylalanylglycine, synthesis of, 1077–1081 Phenyl benzoate, Fries rearrangement of, 952 2-Phenyl-2-butanol p-nitrobenzoate, 595 preparation of, 559 Phenylbutazone, 856 2-Phenylethanol 1 H NMR spectrum, 607 trifluoroacetate, 595 1-Phenylethylamine, resolution, 287–288 Phenyl group, 408 Phenylhydrazine, reaction of, with aldehydes and ketones, 674 Phenylisothiocyanate, 1074–1075 Phenylketonuria (PKU disease), 1065 Phenyllithium, 549 Phenylmagnesium bromide carboxylation of, 752 preparation of, 550, 921 reaction of with 2-butanone, 559 with 1,2-epoxypropane, 635 with ethyl benzoate, 572 with methanol, 551 2-Phenylpropene hydroxylation of, 608 Phenylpyruvic acid, 1065 Phenylthiohydantoin, 1074–1075 Pheromone aggregating of cockroach, 59, 62 of European elm bark beetle, 615 alarm pheromone of ant, 659 of bees, 659 sex attractant of boll worm moth, 827 of codling moth, 202 of female gypsy moth, 239 of female house fly, 173, 363 of female Japanese beetle, 788 of female tiger moth, 86 of female winter moth, 696 of greater wax moth, 659 of honeybee, 203 of male Oriental fruit moth, 788 of Mediterranean fruit fly, 202 of Western pine beetle, 694 Phosphatidic acid, 1022 Phosphatidylcholine, 1022–1023 Phosphines as nucleophiles, 680 optically active, 290 Phosphoglucose isomerase, 1002 Phosphoglycerides, 1022 Phospholipid bilayer, 1023 Phospholipids, 1022–1023 Phosphoric acid catalyst for alcohol dehydration, 182, 183, 187 esters of, 596 Phosphorous acid, esters, 596 Phosphorus pentoxide, 814 Phosphorus tribromide, reaction with alcohols, 147, 161 Phosphorus ylides. See Ylides Photochemical initiation of addition of hydrogen bromide to alkenes, 222, 251 of free-radical reactions, 156, 222, 251 Photon, 488 Photosynthesis, 976, 1015 Phthalhydrazide, 876 Phthalic acid. See 1,2-Benzenedicarboxylic acid Phthalic anhydride, 783, 785, 804 Phthalimide, 804 potassium salt of, in Gabriel synthesis, 875–876, 902 Physical properties. See entry under specific compound class Physostigmine, 908 Phytane, 64 H9251-Pinene, 167, 1032 hydroboration-oxidation of, 230 hydrogenation of, 213 H9252-Pinene, 1032 Piperidine, 116, 781, 973 basicity, 868 in reductive amination, 880 pK a , 134. See also Acidity pK b , 864. See also Basicity PKU disease. See Phenylketonuria Planck, Max, 488 Planck’s constant, 488 Plane of symmetry, 264–265 in meso-2,3-butanediol, 279 cis-1,2-dibromocyclopropane, 282 Plane-polarized light, 265–267 Platinum, hydrogenation catalyst, 208, 209, 249, 403, 583–584 Pleated H9252-sheet, 1084, 1085 Poison ivy, allergens in, 968 Polar covalent bonds. See Bonds, polar covalent Polarimeter, 265–267 Polarizability, 132 and nucleophilicity, 313–315 Polar solvents, 303, 320–323 Polyamides, 809–810 Polyamines, 870 Polychlorinated biphenyls, 938 Polycyclic hydrocarbons aliphatic, 114–116 aromatic, 408–409, 474–475 and cancer, 409 Polyesters, 809 Polyethers, 622–625 Polyethylene, 245–246, 247, 248, 567–570, 573 Polyisoprene, 247, 383 Polymer(s), 244–247 of dienes, 383 polyamides, 809–810 polyesters, 809 stereoregular, 288–289, 293, 567–570, 573 vinyl, 247 Polymerization cationic, 244 condensation polymers, 809–810 coordination, 246, 289, 383, 567–570, 573 free-radical, 245–246 Polynucleotides. See Nucleic acids Polypeptide, 1051. See also Peptides; Proteins Polypropylene, 246, 247, 248, 288–289, 570 Polysaccharide, 973, 993–995, 1008 Polystyrene, 247, 248, 421 Polyurethanes, 248 Poly(vinyl alcohol), 828 Poly(vinyl chloride), 170, 247, 248 Porphyrin, 1089 Potassiophthalimide. See Phthalimide Potassium tert-butoxide base in elimination reactions, 191, 349, 565–566 Potassium dichromate. See also Chromic acid oxidation oxidation of alcohols, 596–597, 599 oxidation of aldehydes, 682, 751 Potassium permanganate oxidation of alcohols, 597, 751 oxidation of aldehydes, 751 oxidation of alkylbenzenes, 416, 435, 751 Potential energy, 75 diagrams, 136–137 addition of hydrogen bromide to 1,3-butadiene, 381 bimolecular elimination (E2), 194 bimolecular nucleophilic substitution (S N 2), 309 branched versus unbranched alkanes, 75 carbocation formation, 146 carbocation rearrangement, 189 conformations of 1,3-butadiene, 376–377 conformations of butane, 95 conformations of cyclohexane, 103 conformations of ethane, 93 electrophilic aromatic substitution, 446, 459, 462 hydration of aldehydes and ketones, 666 and Markovnikov’s rule, 217 proton transfer, 137 reaction of tert-butyl alcohol with INDEX I-26 hydrogen chloride, 143 unimolecular nucleophilic substitution (S N 1), 143, 316 and heat of combustion, 75–76, 109, 177 and heat of hydrogenation, 210 Pott, Sir Percivall, 409 Prelog, Vladimir, 174 Priestley, Joseph, 383 Principal quantum number, 8 Primary carbon, 65 Pristane, 85 Progesterone, 1042 L-Proline, 1052, 1054, 1059, 1085 electrostatic potential map, 1053 Prontosil, 896 1,3-Propadiene. See Allene Propagation step, 153–154, 157, 163, 221–222, 415 Propanal, 657, 658 Propane attractive forces in, 130 bond dissociation energies in, 151–152 conformational analysis of, 95 dehydrogenation of, 168, 181 dipole moment of, 130, 863 in natural gas, 56 2-Propanol, 128. See also Isopropyl alcohol Propene, 167–168 addition of sulfuric acid to, 224 allylic chlorination of, 371 bond dissociation energy of, 370, 414 bond distances in, 171, 343, 375 dipole moment of, 176 epoxidation of, 274 heat of hydrogenation of, 211, 374–375 hydration rate of, 226 as industrial chemical, 248 polymerization of, 246, 288–289, 570 structure, 171 Propylene, 167. See also Propene Propylene glycol, 589 Propylene oxide, 248. See also 1,2- Epoxypropane Propyl group, 65 Propyl radical, 151–152 Prostacyclins, 1045 Prostaglandins, 736, 1024–1025 Prosthetic groups. See Coenzymes Protease inhibitors, 1099 Protecting groups acetals as, 671–672 for amino acids, 1077–1079 for arylamines, 886–888 Protein Data Bank, 1087 Proteins amino acid analysis of, 1070–1071 biosynthesis of, 1096–1100 glycoproteins, 995–996 hydrolysis of, 1070–1071 structure of primary, 1067, 1070–1076, 1084 quaternary, 1089 secondary, 1084–1086 tertiary, 1086–1089 synthesis of, 1076–1084 Protic solvents, 322 Proton magnetic resonance spectra. See Nuclear magnetic resonance spectra Proton magnetic resonance spectroscopy. See Nuclear magnetic resonance spectroscopy Proton-transfer reactions. See Acid-base reactions Pseudoionone, 1049 Purcell, Edward, 490 Purine(s), 431, 1090–1091 hydrogen bonding in, 1095–1096 nucleosides of, 1091–1092 nucleotides of, 1092–1093 polynucleotides of, 1093–1103 Putrescine, 870 Pyramidal inversion, 290 Pyranose forms of carbohydrates, 981–984, 1007 Pyrethrins, 1047 Pyridine, 430 acylation catalyst, 594, 781, 783 basicity of, 868 bonding in, 432 electrophilic aromatic substitution in, 475–476 Pyridinium chlorochromate (PCC), 597, 611, 660 Pyridinium dichromate (PDC), 597, 611, 660 Pyridoxal phosphate, 675 Pyrimidine(s), 1090–1091 hydrogen bonding in, 1095–1096 nucleosides of, 1091–1092 nucleotides of, 1092–1093 polynucleotides of, 1093–1103 Pyrocatechol, 940, 956 Pyrrole, 430 bonding in, 432 electrophilic aromatic substitution in, 476–477 Pyrrolidine, 116 acetylation of, 874 enamine of, 677, 882 Pyruvic acid acetyl coenzyme A from, 1016 biological reduction of, 681–682 biosynthesis of, 602, 1015 conversion to L-alanine, 1063–1065 Quantized energy states, 489–490 Quantum, 488 Quantum numbers, 7, 8 Quaternary ammonium salts, 861 hydroxides, Hofmann elimination of, 883–885, 904 as phase-transfer catalysts, 871–872, 901 preparation of, 874, 883 Quaternary carbon, 65 Quaternary structure of proteins, 1089 Quinine, 869 Quinoline, 430 Quinones, 958–959, 964 Racemic mixture, 266, 274, 291 resolution of, 286–288, 293 Racemization and chair-chair interconversion, 281 via enol, 714–715 in S N 1 reactions, 318–319 Radio waves, 488 Random coils, 1085 Rare gas. See Noble gas Rate constant, 145 Rate-determining step, 144, 162, 796 Rate of reaction. See also Substituent effects and carbocation stability, 139–146, 315–318 effect of catalyst on, 209 effect of temperature on, 93–94, 145 Rearrangement in alcohol dehydration, 187–190, 201 allylic, 369, 381–382, 390 in Baeyer-Villiger oxidation, 683–684, 789 Claisen rearrangement, 957–958, 964 in electrophilic addition to alkenes, 219–220 in Friedel-Crafts alkylation, 452, 479 Fries rearrangement, 952 Hofmann rearrangement, 807–813, 822 in reactions of alcohols with hydrogen halides, 330, 332 in S N 1 reactions, 319–321 Reducing sugar, 999 Reduction, 78–80. See also Hydrogenation; Hydrogenolysis of aldehydes and ketones, 583–587, 589, 608, 662 of amides, 879, 903 of aryl diazonium salts, 894, 907 of azides, 877, 902 Birch reduction, 412–414, 434 of carbohydrates, 996–998, 1009 of carbonyl groups, agents for, 608 table of carboxylic acids, 587, 608, 659, 754 Clemmensen, 456–457, 474, 662 of esters, 587, 608 of imines, 879–880 metal-ammonia reduction of alkynes, 351–352 of nitriles, 877, 902 of nitro groups, 878, 902 Wolff-Kishner, 456, 662 Reductive amination, 879–881, 903 Refining of petroleum, 69–70 Reforming, in petroleum refining, 70 Regioselectivity addition of bromine to 1,3-butadiene, 382 addition of hydrogen halides to 1,3-butadiene, 379–382 allylic halogenation, 370–372, 392 dehydration of alcohols, 183–185, 199–200, 379, 392, 419 dehydrohalogenation of alkyl halides, 191–192, 197, 199–200, 379, 419 Regioselectivity—Cont. electrophilic addition to alkenes, 216–219, 224, 225–230, 236–238, 251 electrophilic aromatic substitution, 457–477 elimination-addition mechanism of I-27 INDEX nucleophilic aromatic substitution, 927–931 epoxide ring opening, 632–637, 646 Hofmann elimination, 883–885, 904 hydration of alkynes, 355–356, 361 hydroboration-oxidation, 228–233, 250 and Markovnikov’s rule, 216–219, 251 and regiospecificity, 285 and Zaitsev’s rule, 183–184, 199 Relative configuration, 267 Resolution, 286–288, 293 Resonance, 3, 23–26, 45 aldehydes and ketones, 467, 658 allylic carbocations, 366–369 allyl radical, 370 amides, 779, 886 aniline, 863 benzene, 402–403 benzylic carbocations, 418 benzylic radicals, 414 carboxylic acid derivatives, 777–780 carboxylic acids, 739 cyclohexadienyl anions, 925 cyclohexadienyl cations, 444, 458–462, 465, 466, 467, 470, 475 enolate ions, 709–711 formic acid, 739 H9252-keto ester anions, 832 p-nitroaniline, 867 ozone, 23, 240 phenol, 941 phenoxide anions, 943, 945, 953 protonated benzoic acid, 756 protonated ketone, 665 rules for, 24–25 table H9251,H9252-unsaturated carbonyl compounds, 721 Resonance energy [18]-annulene, 426 anthracene, 408–409 benzene, 403–404, 433 conjugated dienes, 374–375 cycloctatetraene, 422 1,3,5-hexatriene, 404 naphthalene, 408–409 phenanthrene, 408–409 Resorcinol, 940 acetylation, 949 Restriction enzymes, 1101 Retention of configuration, 233, 307–308 in acylation of alcohols, 595 in Baeyer-Villiger oxidation, 683–684 in ester hydrolysis, 797 in Hofmann rearrangement, 813 Retinal, 676 Retinol, 580, 676 Retro-aldol cleavage, 1003 Retrosynthetic analysis acetoacetic ester synthesis, 840 Grignard synthesis of alcohols, 557–560, 570–571 malonic ester synthesis, 843 Simmons-Smith reaction, 565 Wittig reaction, 679–680 Reverse transcriptase, 1098 L-Rhamnonolactone, 1009 L-Rhamnose, 1009 Rhodium, hydrogenation catalyst, 208, 209 Rhodopsin, 676 9-H9252-D-Ribofuranosyladenine. See Adenosine 1-H9252-D-Ribofuranosyluracil. See Uridine Ribonuclease, 1083–1084 Ribonucleic acid (RNA), 1090–1094 messenger (mRNA), 1096–1100 polymerase, 1096 purine and pyrimidine bases in, 1090–1091 ribosomal (rRNA), 1096 transfer (tRNA), 1096 D-Ribose, 976, 977 cyanohydrin, 1009 2-deoxy, 1010, 1027 furanose and pyranose forms, 980–982, 984, 1007 D-Ribulose, 986 Rickets, 1039 Ring flipping. See Ring inversion Ring inversion cyclohexane, 103, 119, 510 substituted cyclohexanes, 104–107, 110–114, 119 RNA, mRNA, rRNA, and tRNA. See Ribonucleic acid Roberts, John D., 928 Robinson, Sir Robert, 4, 402, 724 Robinson annulation, 724, 728 Rotamer, 90. See also Conformation Rotational energy barrier alkenes, 172–173 amides, 779 butane, 94–95 conjugated dienes, 376–377 ethane, 93–94 R-S-notational system, 268–271, 291 Rubber, 383 Rubbing alcohol, 18, 128. See also Isopropyl alcohol Ruzicka, Leopold, 1028 S (symbol for entropy), 106 Sabatier, Paul, 208, 209, 550 Sabinene, 1049 Saccharic acids. See Aldaric acids Saccharin, 997 Salicylic acid, 737 acetylation of, 952 acidity of, 953 synthesis of, 952–954 Samuelsson, Bengt, 1025 Sandmeyer reactions, 892, 894, 906–907, 919 Sanger, Frederick, 1070–1074, 1101–1102 Sanger’s reagent. See 1-Fluoro-2,4- dinitrobenzene H9251-Santonin, 1046 Saponification, 794–799 Sawhorse diagrams, 90–91 Saytzeff. See Zaitsev, Alexander M. Schiemann reaction, 892, 893, 905 Schiff’s base, 673, 689. See also Imines Schr?dinger, Erwin, 7 Schr?dinger equation. See Wave equation Scientific method, 217 Secobarbital, 845 Seconal, 845 Secondary carbon, 65 Secondary structure, 1084–1086 Selectivity. See Regioselectivity; Stereoselective reactions H9251-Selinene, 1026, 1027 Semicarbazide, 674 Semicarbazones, 674 Sequence rule application to alkene stereochemistry, 173–175, 199 and R-S notation, 268–271, 291 L-Serine, 1055, 1059 electrostatic potential map, 1053 Serotonin, 869 Sesquiterpene, 1026 Sesterpene, 1026 Sex attractant. See Pheromone, sex attractant Sex hormones, 1040–1042, 1044 Shared-electron pair bond. See Covalent bond Shielding of nuclei in NMR spectroscopy, 493–495. See also Chemical shift Sickle-cell anemia, 1089–1090, 1100 Sigma bond, 32 Sigmatropic rearrangement, 958 Silk, 1085 Siloac, Edward, 272 Silver oxide, 883, 958, 964 Simmons, Howard E., 564 Simmons-Smith reaction (reagent), 564 Simvastatin, 1038 Sinigrin, 989 Sites of unsaturation. See Index of hydrogen deficiency SI units, 11, 23 Skew boat conformation of cyclohexane, 100 Smalley, Richard, 410 Smith, Ronald D., 564 S N 1 mechanism, 143–146, 162, 315–321, 331 table S N 2 mechanism, 146, 162, 306–312, 331 table Soap manufacture, 795 mode of action, 744–745 Sodium, reaction with alkynes, 351–352, 360 arenes, 412–414, 434 Sodium acetylide, 336, 547 preparation of, 346, 347 reaction with alkyl halides, 335–336, 347–348 cyclohexanone, 556 Sodium alkoxides as bases in elimination reactions, 190–191, 323–325 preparation of, 190 in Williamson ether synthesis, 626–627, 644 Sodium amide as base, 346–349, 359, 556 reaction with aryl halides, 927–931 Sodium borohydride reduction INDEX I-28 of aldehydes and ketones, 583–587, 608, 662 of aryl diazonium ions, 894 of carbohydrates, 996–998, 1009 Sodium cyanoborohydride, 881 Sodium dichromate. See also Chromic acid; Potassium dichromate oxidation of alcohols, 597, 611 oxidation of alkylbenzenes, 416, 435, 474 Sodium 1-dodecyl sulfate (SDS), 745, 1061 Sodium ethoxide as base in acetoacetic ester synthesis, 839–841 in Claisen and Dieckmann condensations, 832, 836 in elimination reactions, 190, 323–325 in malonic ester synthesis, 842–844 reaction with epoxides, 633 Sodium hydride, 837 Sodium hypochorite, 599 Sodium iodide, 305 Sodium lauryl sulfate, 745. See also Sodium 1-dodecyl sulfate Sodium metaperiodate, 639 Sodium methoxide reaction with aryl halides, 922–926 Sodium stearate, 744 Solid-phase peptide synthesis, 1082–1084 Solvation and nucleophilicity, 313–315 Solvent effects, and rate of nucleophilic substitution, 320–323, 331 Solvolysis of alkyl halides, 312–313, 315–321 of allylic halides, 366–369, 390 of benzylic halides, 417–418 Somatostatin, 1107 Sondheimer, Franz, 426 Sorbitol, 612 Space-filling models, 27. See also Molecular models and modeling and steric hindrance, 311 Specific rotation, 266 Spectrometer, 489 mass, 526–527 nuclear magnetic resonance, 491–493 Spectroscopy, 487–545. See also Mass spectrometry general principles, 488–489, 533–534 13 C NMR, 510–517, 535 1 H NMR, 490–510, 534–535 infrared, 518–522, 536 ultraviolet-visible, 522–526, 536 Speed of light, 488 Spermaceti, 1024 Spermidine, 870 Spermine, 870 Spin-spin coupling, 502 Spin-spin splitting in 13 C NMR, 535 in 19 F NMR, 544 in 1 H NMR, 500–509, 534–535 n H11001 1 rule, 500, 508 Spirocyclic hydrocarbons, 114, 120 Spiropentane, 114 Splitting diagrams AX to AM to AB, 506 doublet of doublets, 508 quartet, 502 triplet, 504 Squalene, 638, 1027, 1028, 1036, 1044 Squalene 2,3-epoxide, 638 in cholesterol biosynthesis, 1036, 1037 Staggered conformation, 90–92, 117 Stanozolol, 1041 Starch, 994 Stearic acid, 737 Stearolic acid, 351 Sterculic acid, 180 Stereocenter. See Stereogenic center Stereochemistry, 259–301 and chemical reactions bimolecular nucleophilic substitution (S N 2), 307–310, 328, 331 ester hydrolysis, 797 hydrogenation of alkenes, 212–213, 285 that produce chiral molecules, 274–276 that produce diastereomers, 284–285 unimolecular nucleophilic substitution (S N 1), 318–319, 331 (see also Stereoselective reactions; Stereospecific reactions) Fischer projection formulas H9251-amino acids, 1056, 1103 carbohydrates, 973–974, 977, 1007 chiral molecules, 271–272, 292 two stereogenic centers, 276–278, 280, 293 notational systems cis and trans, 108–109, 172–173, 199 D and L, 973–978, 1007, 1052, 1056–1057 E and Z, 173–175, 199 erythro and threo, 278 R and S, 268–271, 292 (see also Stereoisomers) Stereoelectronic effects bimolecular elimination, 194–196, 201 nucleophilic substitution, 308 Stereogenic axis, 378 Stereogenic center, 260–263, 276–283, 290 absolute configuration, 268–271 in 2-butanol, 262, 267–269 in chiral molecules, 260–263, 268, 271, 276 and Fischer projections, 271–272, 278, 292–293, 973–974, 1007, 1052, 1056–1057 formation of in chemical reactions, 274–276, 284–285 phosphorus, 290 sulfur, 290 Stereoisomers, 22, 108–114, 120 alkenes, 172–175, 199 diastereomers, 276–288, 291 enantiomers, 259–276, 291 endo and exo, 681 epimers, 1002 maximum number of, 282–283, 293 Stereoregular polymers, 288–289, 293, 570 Stereoselective reactions, 212, 285 addition to carbonyl groups, 681–682 alcohol dehydration, 185 dehydrohalogenation of alkyl halides, 191–192 enzyme-catalyzed hydration of fumaric acid, 276 hydrogenation of alkenes, 212, 285 metal-ammonia reduction of alkynes, 351–352, 360 Stereospecific reactions, 284–286 Baeyer-Villiger oxidation, 683–684 bimolecular (E2) elimination, 194–196 bimolecular nucleophilic substitution (S N 2), 307–309, 328, 331 table Diels-Alder reaction, 385, 392–393 epoxidation of alkenes, 238–240, 250, 285, 630 epoxide formation from bromohydrins, 631 epoxide ring opening, 634, 637 halogen addition to alkenes, 233–236, 250, 284–286 halogen addition to alkynes, 357 Hofmann elimination, 884 Hofmann rearrangement, 813 hydroboration of alkenes, 229–230, 250 hydrogenation of alkenes, 212, 285 hydrogenation of alkynes, 350–351, 360 hydroxylation of alkenes, 590, 637 Simmons-Smith reaction, 564–565 Steric effects, 95 in bimolecular nucleophilic substitution (S N 2), 310–312, 331 in cyclohexane derivatives, 104 in electrophilic aromatic substitution, 471–472 in Hofmann elimination, 885 in hydration of aldehydes and ketones, 663–667 in hydroboration of alkenes, 230 in hydrogenation of H9251-pinene, 212–213 in sodium borohydride reduction, 681 and stability of isomeric alkenes, 177–181, 199, 211 and stereoselectivity, 285, 681 Steric hindrance, 95, 213, 681 in bimolecular nucleophilic substitution (S N 2), 310–312, 331 Steric strain, 95, 96, 179 Steroids, 283, 1034–1042 Strain. See Angle strain; Torsional strain; van der Waals strain Strain energy minimization, 96 Strecker, Adolf, 1062 Strecker synthesis, 1062 Streptimidone, 298 Stretching vibrations and infrared spectroscopy, 518 Structural formulas Fischer projections, 271–272, 292–293, 973–974, 977, 1007, 1056, 1103 Lewis dot structures, 12 Newman projections, 90–92, 95 Structural formulas—Cont. of organic molecules, 19–21 sawhorse, 90–91 wedge-and-dash, 26, 28, 91 Structural isomers. See Constitutional isomers Structural theory, 3 I-29 INDEX Styrene, 407 addition of bromine, 420 addition of hydrogen bromide, 421, 435 industrial preparation of, 248, 399, 419, 453 polymers, 247, 421, 1082 copolymer with 1,3-butadiene, 383 Substituent effects on acidity of carboxylic acids, 745–748 of phenols, 944–945 on basicity of amines, 865–868 on equilibrium, hydration of aldehydes and ketones, 663–667 on rate of acid-catalyzed hydration, 226 of bimolecular nucleophilic substitution (S N 2), 310–312, 331 of bromine addition to alkenes, 236 of epoxidation, 239–240 of nucleophilic aromatic substitution, 922–926 of unimolecular elimination, 196–197 of unimolecular nucleophilic substitution (S N 1), 145–146, 315–318, 331, 366–367, 417–419 on rate and regioselectivity in electrophilic aromatic substitution, 457–477, 926 on stability of aldehydes and ketones, 658 of alkenes, 176–180, 199 of carbocations, 140–142, 145–146, 162, 367, 417–419 of carbon-carbon triple bonds, 350 of free radicals, 149–153, 162, 414–415 (see also Field effect; Inductive effect; Steric effects) Substitution reactions, 126, 139–146, 302–338 allylic free radical, 370–372, 390–391 nucleophilic, 368–369, 390 of aryl diazonium salts, 892–894, 905–907 benzylic free radical, 414–416, 435 nucleophilic, 417–419, 435 electrophilic aromatic, 443–486 nucleophilic acyl, 774–830 nucleophilic aliphatic, 143–146, 302–338 nucleophilic aromatic, 922–933, 956 Substitutive nomenclature, 127–128, 159 Succinic acid, 182, 804 Succinic anhydride, 455, 804 Succinimide, 371, 416, 804 Sucralose, 997–998 Sucrose, 973, 993, 999 octaacetate, 1010 Sulfa drugs, 896–897 Sulfanilamide, 896 Sulfenic acids, 605 Sulfhydryl group, 603 Sulfides alkylation of, 640–641, 647 oxidation of, 639–640, 646–647 preparation of, 638, 646 Sulfinic acids, 605 Sulfonate esters nucleophilic substitution reactions of, 326–328, 332 preparation of, 326, 332, 591 Sulfonation of benzene, 446, 448–449 of benzenesulfonic acid, 468 of 2,6-dimethylphenol, 950 of 1,2,4,5-tetramethylbenzene, 478 Sulfones, 639, 647 Sulfonic acids, 326, 446, 605 Sulfonium salts, 640–641, 647 Sulfoxides. See also Dimethyl sulfoxide as solvent optically active, 290 preparation of, 638, 647 Sulfuric acid. See also Sulfonation addition to alkenes, 223–225, 249 as catalyst for alcohol dehydration, 182 dimerization of alkenes, 244–245 Fischer esterification, 593 hydration of alkenes, 225–227, 249 nitration of arenes, 448 esters of, 596 Sulfur trioxide, 448 Syndiotactic polymer, 288–289, 293 Synthon, 840 Système International d’Unités. See SI unit 2,4,5-T. See 2,4,5-Trichlorophenoxyacetic acid Talaromycin A, 694 D-Talose, 977 Tariric acid, 340 Tartaric acids, 286 Tautomerism. See Keto-enol tautomerism Teflon, 13, 247 Terephthalic acid. See 1,4- Benzenedicarboyxylic acid Termination step, 154–156 Terpenes, 1025–1034, 1044 biosynthesis of, 1028–1034 classification, 1026 and isoprene rule, 1028 H9251-Terpineol, 1031 Tertiary carbon, 65 Tertiary structure, 1086–1089 Tesla, Nikola, 491 Tesla unit of magnetic field strength, 491 Testosterone, 1040 Tetrachloromethane, 132, 148. See also Carbon tetrachloride Tetrafluoroethylene, 14 Tetrafluoromethane, 13 Tetrahedral geometry and sp 3 hybridization, 35–37 and VSEPR, 26–29, 45 Tetrahedral intermediate, 755 Claisen condensation, 833 Dieckmann condensation, 835 Fischer esterification, 756–757, 767 in hydrolysis of acyl chlorides, 782–783 of amides, 806, 808 of carboxylic acid anhydrides, 786–787 of esters, 792–794, 798, 820 in reaction of esters with ammonia, 800 H9004 9 -Tetrahydrocannabinol, 947, 1019 Tetrahydrofuran, 116, 620. See also Oxolane acid-catalyzed cleavage, 630 complex with borane, 228 dipole moment of, 622 as solvent, 550 Tetrahydropyran, 620, 621. See also Oxane Tetrahymanol, 1046 Tetramethylsilane, 493, 512 electrostatic potential map, 487 Tetrapeptide, 1051 Tetraterpene, 1026 Thalidomide, 273 Theobromine, 1091 Thermochemistry, 77 Thermodynamic control addition of hydrogen bromide to 1,3-butadiene, 381–382, 392 addition to H9251,H9252-unsaturated aldehydes and ketones, 722–724 Fries rearrangement, 952 glycoside formation, 991 Kolbe-Schmitt reaction, 952–954 Thiazole, 431 Thiirane, 620 Thioesters acetyl coenzyme A, 1016–1017 nucleophilic acyl substitution in, 800 Thiols acidity of, 604–605, 609, 638 conjugate addition to H9251,H9252-unsaturated carbonyl compounds, 723 oxidation of, 605, 611 physical properties of, 604 preparation of, 603–604, 609 Thionyl chloride, 18 reactions of with alcohols, 147, 161, 591 carboxylic acids, 454, 754, 780 Thiopental sodium, 846 Thiophene, 430 bonding in, 432 electrophilic aromatic substitution in, 477 Thiourea, 604, 846 Threo, stereochemical prefix, 278 L-Threonine, 1055, 1059 electrostatic potential map, 1053 D-Threose, 975 L-Threose, 975 Thymidine, 1092 Thymine, 1090 Thymol, 947 Thyroxine, 273–274 Tin, reduction of nitro groups by, 878, 902 Toluene, 398, 399 benzylic halogenation of, 415 bond dissociation energy, 414 nitration of, 457–460, 474 oxidation of, 417 physical properties of, 941 p-Toluenesulfonic acid INDEX I-30 as acid catalyst, 670 acidity of, 326, 327 esters preparation of, 326, 332, 591 as substrates in nucleophilic aliphatic substitution, 326–328, 332 nucleophilic aromatic substitution in, 946 p-Toluenesulfonyl chloride, reaction with alcohols, 326, 332, 591 o-Toluidine, 894 Torsional strain boat conformation of cyclohexane, 99 cyclobutane, 107–108 cyclopentane, 108 cyclopropane, 107 eclipsed conformation of butane, 95–96 eclipsed conformation of ethane, 92 Torsion angle, 91–92 Tosylates. See p-Toluenesulfonic acid, esters Transamination, 1063–1065 s-Trans conformation, 376–377 Transcription, 1096 Transfer RNA. See Ribonucleic acid, transfer Transition metal organometallic compounds, 566, 572–573 Transition state and activation energy, 93 addition of bromine to alkenes, 236 bimolecular elimination (E2), 193–194 bimolecular nucleophilic substitution (S N 2), 146, 307, 309, 318, 329, 331 electrostatic potential map, 302 bond rotation in ethane, 93 carbocation rearrangement, 188–189 conversion of primary alcohols to primary alkyl halides, 146, 162, 329 Diels-Alder reaction, 384 double-bond rotation, 172–173 epoxide ring opening, 634, 635 free-radical halogenation, 157 hydrolysis of ethyl bromide, 318 nucleophilic capture of carbocation, 142, 143, 316 oxonium ion dissociation, 144–146 proton transfer, 136–137, 143 unimolecular nucleophilic substitution (S N 1), 143–146, 316 Translation, 1096–1100 Tranylcypromine, 907 Triacylglycerols. See Glycerol, esters Tribromomethane. See also Bromoform dibromocarbene from, 565–566 Tricarboxylic acid cycle, 1064 Trichloroacetic acid, 746 Trichloromethane, 148. See also Chloroform boiling point of, 132 2,4,5-Trichlorophenol, 955 2,4,5-Trichlorophenoxyacetic acid, 955 cis-9-Tricosene, 363 Triethylamine, 866 Trifluoroacetic acid, 766 p-(Trifluoromethyl)aniline, 867 (Trifluoromethyl)benzene, nitration of, 457–458, 461–462 Triglycerides. See Glycerol, esters Trigonal planar geometry and sp 2 hybridization, 38–40, 141, 171, 405, 657 and VSEPR, 28–29 Trigonal pyramidal geometry, 28–29 Trimer, 244 Trimethylamine, 863 2,2,4-Trimethylpentane, 244 photochemical chlorination of, 166 Trimethyl phosphate, 596 Trimethyl phosphite, 596 Trimyristin, 795–796 Triose phosphate isomerase, 1004 Tripeptide, 1051 Triphenylamine, 867 Triphenylmethane, 577 Triphenylmethyl perchlorate, 419 Triphenylphosphine, 680 Triple bond, 14, 40–42, 47, 339, 341–343. See also Bonds in benzyne, 928, 930 Tristearin, 788, 1017–1018 Triterpenes, 1026 biosynthesis of, 637–638, 1030, 1035–1037 Trityl. See Triphenylmethyl Trivial names. See Common names Tropylium cation. See Cycloheptatrienyl cation Trypsin, 1071 L-Tryptophan, 1054, 1059 electrostatic potential map, 1053 Twist boat. See Skew boat conformation of cyclohexane Tyrian purple, 4, 46, 920 L-Tyrosine, 1054, 1059, 1064 electrostatic potential map, 1053 Ubiquinone, 959 Ultraviolet-visible spectroscopy, 522–526, 536 alcohols, 607 aldehydes and ketones, 686–687 amines, 899–900 carboxylic acids and derivatives, 765, 818 ethers and epoxides, 643 phenols, 961 Unimolecular elementary step, 144 elimination, 196–198, 201 (see also E1 mechanism) nucleophilic substitution, 143–146, 315–321 (see also S N 1 mechanism) H9251,H9252-Unsaturated aldehydes and ketones conjugate addition to, 722–725, 728–729, 846–847, 852 preparation of, 717–720, 729 resonance in, 721 stabilization of, 720–721 Uracil, 1090 Urea from ammonium cyanate, 2 electrostatic potential map, 1 industrial synthesis of, 802 reaction of, with diethyl malonate, 845 Urethans, 813. See also Carbamic acid, esters Urey, Harold C., 754 Uridine, 1091 Uronic acids, 1000–1001 Valence-bond theory, 32–34, 42, 46 Valence electrons, 10 and Lewis structures, 20 Valence-shell electron pair repulsion and molecular geometry, 26–29, 45 L-Valine, 1054, 1059 electrostatic potential map, 1053 L-Vancosamine, 988 van der Waals forces attractive, 72–74 and stability of isomeric alkanes, 76 repulsive, 74, 95, 99–100, 104 in stereoisomers, 110, 178–180, 199 (see also van der Waals strain) van der Waals radius, 74, 96, 99 van der Waals strain, 95. See also Steric effects; Steric hindrance; Steric strain alkenes, 178–180, 199 [10]-annulene, 425 axial substituents in cyclohexane, 104–107 boat conformation of cyclohexane, 99 butane, 95, 96 S N 2 reactions, 310–312 in stereoisomers, 110, 120, 178–180, 199 Vane, John, 1025 Van’t Hoff, Jacobus, 259, 265 Vernolepin, 758 Veronal, 845 Vibrations of methylene group, 518 Vicinal coupling, 500, 534 dihedral angle dependence, 544 Vicinal dihalides. See Dihaloalkanes, vicinal Vicinal diols, 589 cyclic acetals from, 670–671, 672 preparation of, 589–590 reaction with periodic acid, 602–603, 609 Vicinal halohydrins. See Halohydrins Vinyl chloride, 48, 170, 176, 247, 248, 550 Vinyl group, 169–170 Vinyl halides. See Alkenyl halides; Vinyl chloride Vinylic, 366 Vinyllithium, 556 Vinylmagnesium chloride, 550 Visible light, 488 Vision, chemistry of , 675–676 Vitalism, 2 Vitamin, 858 A, 676, 1027 B 6 , 675 B 12 , 568 C (see Ascorbic acid) D 3 , 1038–1039, 1044 K, 959 von Baeyer, Adolf, 97, 845 VSEPR. See Valence-shell electron pair repulsion Vulcanization, 383 Walden, Paul, 308 Walden inversion, 308 I-31 INDEX Wallach, Otto, 1028 Water acidity of, 134–135, 345, 552 bond angles, 28–29 dipole moment of, 129 solubility of alcohols in, 132 Watson, James D., 1094 Wave equation, 7 Wave function, 7 Wavelength, 488 Wave number, 518 Waxes, 1024 Wedge-and-dash structural formulas, 26, 28, 91 Whitmore, Frank C., 187 Williamson, Alexander, 626 Williamson ether synthesis, 626–627, 644, 954–956 intramolecular, 631 Willst?tatter, Richard, 422 Wittig, Georg, 677 Wittig reaction, 677–681, 690 Wohler, Friederich, 2 Wolff-Kishner reduction, 456, 662 Wood alcohol, 128, 579 Woodward, Robert B., 390, 616 Woodward-Hoffmann rules, 390 Wool, 1085 Wotiz, John, 401 Wurtz, Charles-Adolphe, 3 X-ray crystallography and structure of carbohydrates, 982, 985, 996 nucleic acids, 1094 proteins, 1084 vitamin B 12 , 568 X-rays, 488 m-Xylene, 406 nitration of, 472 o-Xylene, 406 Birch reduction of, 434 p-Xylene, 406 Friedel-Crafts acylation of, 471 oxidation of, 750 D-Xylonic acid, 1000 D-Xylose, 977 furanose forms, 981 oxidation, 1000 L-Xylulose, 986 Yields in chemical reactions, 138 Ylides, 677–681 Z (abbrevation for benzyloxycarbonyl group), 1078 Z (stereochemical prefix), 173–175, 199 Z (symbol for atomic number), 7 Zaitsev, Alexander M., 184 Zaitsev’s rule, 184, 191, 199, 200 Zidovudine, 1098 Ziegler, Karl, 246, 569 Ziegler-Natta catalyst, 246, 383, 567–570 Zigzag conformations of alkanes, 97 Zinc in carboxypeptidase A, 1086–1088 in Clemmensen reduction, 456–457, 474 electronegativity of, 547 in hydrolysis of ozonides, 241 Zinc-copper couple, 564 Zusammen, (Z), 173–175, 199 Zwitterion, 1057, 1103 WHERE TO FIND IT A GUIDE TO FREQUENTLY CONSULTED TABLES AND FIGURES Acids and Bases Dissociation Constants for Selected Br?nsted Acids (Table 4.2, p. 135) Acidities of Hydrocarbons (Table 14.2, p. 552) Acidities of Carboxylic Acids (Table 19.2, p. 746) Acidities of Phenols (Table 24.2, p. 944) Acidities of Substituted Benzoic Acids (Table 19.3, p. 748) Acid-Base Properties of Amino Acids (Tables 27.2 and 27.3, p. 1059) Basicities of Alkylamines (Table 22.1, p. 866) Basicities of Arylamines (Table 22.2, p. 867) Classification of Isomers (Table 7.2, p. 291) Free-Energy Difference-Composition Relationship in an Equilibrium Mixture (Figure 3.17, p. 107) IUPAC Nomenclature Names of Unbranched Alkanes (Table 2.4, p. 62) Rules for Alkanes and Cycloalkanes (Table 2.7, pp. 81–82) Rules for Alkyl Groups (Table 2.8, p. 83) Reactivity Nucleophilicity of Some Common Nucleophiles (Table 8.4, p. 313) Leaving Groups in Nucleophilic Substitution (Table 8.8, p. 327) Substituent Effects in Electrophilic Aromatic Substitution (Table 12.2, p. 464) Spectroscopy Correlation Tables Proton Chemical Shifts (Table 13.1, p. 496) 13 Chemical Shifts (Table 13.3, p. 513) Infrared Absorption Frequencies (Table 13.4, p. 519) Stereochemistry Cahn-Ingold-Prelog Priority Rules (Table 5.1, p. 175) Absolute Configuration Using Cahn-Ingold-Prelog Notation (Table 7.1, p. 269) Fisher Projections of D-Aldoses (Figure 25.2, p. 977) Structure and Bonding Electronegativities of Selected Atoms (Table 1.2, p. 15; Table 14.1, p. 547) How to Write Lewis Structures (Table 1.4, p. 20) Rules of Resonance (Table 1.5, pp. 24–25) Bond Dissociation Energies (Table 4.3, p. 151) Bond Distances, Bond Angles, and Bond Energies in Ethane, Ethene, and Ethyne (Table 9.1, p. 342) Structures of H9251-Amino Acids (Table 27.1, pp. 1054–1055) 1 H 1.008 2 He 4.003 3 Li 6.941 4 Be 9.012 11 Na 22.99 12 Mg 24.31 19 K 39.10 20 Ca 40.08 37 Rb 85.47 38Sr 87.62 55 Cs 132.9 56 Ba 137.3 87Fr (223) 88 Ra (226) 21 Sc 44.96 22Ti 47.88 39 Y 88.91 40Zr 91.22 71 Lu 175.0 72Hf 178.5 103 Lr (260) 104 Rf (261) 23 V 50.94 24Cr 52.00 41 Nb 92.91 42 Mo 95.94 73Ta 180.9 74W 183.9 105Db (262) 106 Sg (266) 25 Mn 54.94 26 Fe 55.85 43 Tc (98) 44 Ru 101.1 75 Re 186.2 76 Os 190.2 107Bh (262) 108 Hs (265) 27 Co 58.93 45 Rh 102.9 77 Ir 192.2 109 Mt (266) 57 La 138.9 58 Ce 140.1 60 Nd 144.2 61 Pm (145) 62 Sm 150.4 63 Eu 152.0 59Pr 140.9 89 Ac (227) 90 Th 232.0 92 U 238.0 93 Np (237) 94 Pu (242) 95 Am (243) 91 Pa (231) 28Ni 58.69 29 Cu 63.55 46 Pd 106.4 47 Ag 107.9 78Pt 195.1 79 Au 197.0 30 Zn 65.39 48 Cd 112.4 80 Hg 200.6 64 Gd 157.3 65 Tb 158.9 67 Ho 164.9 68Er 167.3 69 Tm 168.9 70 Yb 173.0 66 Dy 162.5 96 Cm (247) 97 Bk (247) 99 Es (252) 100Fm (257) 101Md (258) 102No (259) 98Cf (251) 31 Ga 69.72 32 Ge 72.61 49In 114.8 50 Sn 118.7 81Tl 204.4 82 Pb 207.2 33 As 74.92 51 Sb 121.8 83Bi 209.0 34 Se 78.96 35Br 79.90 52Te 127.6 53 I 126.9 84 Po (209) 85At (210) 36Kr 83.80 54 Xe 131.3 86 Rn (222) 5 B 10.81 6 C 12.01 13Al 26.98 14Si 28.09 7 N 14.01 15 P 30.97 8 O 16.00 9F 19.00 16 S 32.07 17Cl 35.45 10 Ne 20.18 18Ar 39.95 34567 3B(3) 4B(4) 5B(5) 6B(6) 7B(7) (9) (10) 1B (11) 2B (12) 3A (13) 4A (14) 5A (15) 6A (16) 7A (17) 8A (18) 2 167 (8) 1A(1) 2A(2) 8B LanthanidesActinides TRANSITION ELEMENTS INNER TRANSITION ELEMENTS MAIN–GR OUP ELEMENTS MAIN–GR OUP ELEMENTS P eriod 110 111 112 (269) ( 272 )( 277 ) Metals (main-group)Metals (transition)Metals (inner transition)MetalloidsNonmetals P eriodic T a b le of the Elements As of mid-1999, elements 110 through 112 have not yet been named.