6. Nucleophile Substitutionen an Carbons?urederivaten 6-A1 Pivalins?urepyrrolidid aus Pivaloylchlorid und Pyrrolidin 6-A2 tert-Butylcyclohexenylketon aus Pivalins?urepyrrolidid (6-A1) und dem von 1- Bromcyclohexen (4-A3) abgeleiteten Grignard-Reagenz NHO Cl O NCHCl3, Pyridin O Mg Br 6-A2 6-A1 O Cl NH Cl O N -Cl O N 6-A 1 Mg Br + N O MgBr HCl O NH O 6-A2 H -H H -H , NH- 6-A3 (R)-3-Hydroxybutters?uremethylester aus Poly-[(R)- 3-hydroxybutters?ure] ClCH2CH2Cl / CH3OH H2SO4 O O H HO n OMe OOH 6-A3 O OH H HO n MeOH O OH H HO nOH Me ~H O OH H OH2nO Me O OMe OH O OH HO n-1 - -H2O 6-A4 2-Methyl-2,5-decandiol aus -Pentyl- -butyrolacton O nC5H11 O OH HO nC5H11 MeMgI 6-A4 O nC5H11 O Me MgI O nC5H11 O Me MgI OO nC5H11 Me MgI MgI O O nC5H11MgI MgI OH HO nC5H11 +NH4Cl -2 NH3,-2 MgICl 6-B1 Fluoren-9-carbaldehyd aus Fluoren CHO NaH, HCO2Et 6-B1 HH NaH -H2 Na O H OEt OEtH O H O H OEt H -HOEt O H -H 6-B2 Sebacins?uredichlorid aus Sebacins?ure 6-B3 Sebacins?urediamid aus Sebacins?uredichlorid (6- B2) O Cl (CH2)8 Cl O O OH (CH 2)8 HO O SOCl2 O H2N (CH2)8 NH2 O NH3 (w??rig) 6-B2 6-B3 O OH (CH 2)8 HO O S Cl O Cl O OH (CH 2)8 O O S O Cl +Cl H O OH (CH 2)8 O O S O Cl +Cl + H O OH (CH 2)8 O O S O Cl Cl H + -HCl / -SO2 O OH (CH 2)8 Cl O O Cl (CH2)8 Cl Oanalog O Cl (CH2)8 Cl O NH 3 O Cl (CH2)8 Cl O NH3 O Cl (CH2)8 NH3 O Cl O Cl (CH2)8 NH2 O O H2N (CH2)8 NH2 O analog - HCl 6-B4 Octanal aus N-Formylpiperidin und dem Grignardreagenz aus 1-Bromoctan (2-A1) 1) Mg, Et2O 2) Hept Br Hept O NO 6-B4 Hept Br Mg (SET) Hept MgBr Hept MgBr N O NHept OH MgBr NHHept OH MgBr H Hept O -HN 6-C1 Acetylsalicyls?ure aus Salicyls?ure CO2H HO CO2H OAc O OO H2SO4 6-C1 CO2H HO O OHO CO2H O H O O O ~H CO2H O O O O H- HOAc CO2H OAc 6-C1 6-C2 Sebacins?uremonomethylester aus Sebacins?ures?uredimethylester 6-C3 10-Methyl-10-hydroxy-undecans?ure aus Sebacins?uremonomethylester (6 C2) 6-C4 Sebacins?ureethylmethylester aus Sebacins?uremonomethylester (6-C2) O MeO (CH2)8 OH OO MeO (CH2)8 OMe O 1) Ba(OH)2 2) H3O 1) MeMgI OH (CH2)8 OH O 1) Cl-CO-OEt 2) EtOH O MeO (CH2)8 OEt O 2) NH4Cl/H2O 6-C2 6-C3 6-C4 O MeO (CH2)8 OMe O OH O MeO (CH2)8 OMe O OH O MeO (CH2)8 O OH + OMe O MeO (CH2)8 O O -HOMe +H O MeO (CH2)8 OH O 6-C2 O O (CH2)8 OMe O 6-C2 Me MgI O O (CH2)8 OMe O MgI +NH4 / -NH3 H Me MgI -CH4 O O (CH2)8 OMe O MgI H -HOMe O O (CH2)8 O Me MgI O O (CH2)8 O H OH (CH2)8 OH O 6-C3 O OH(H2C)8MeO O 6-C2 + NEt3 - HNEt3 O O(H2C)8MeO O O Cl OEt O O(H2C)8MeO O O ClO Et O O(H2C)8MeO O O OEt Cl O O(H2C)8MeO O O OEtCl (H2C)8MeO O Cl O EtOH (H2C)8MeO O Cl O OH Et (H2C)8MeO O O OEt H -H O MeO (CH2)8 OEt O 6-C4 + O O OEt - CO2/OEt 6-D1 (S)-Hydroxybernsteins?uredimethylester aus (S)- ?pfels?ure HO O H O O O H MeO O OMe O HOH+ (Ionen- austauscher) MeOH 6-D1 HO O H O O O H H HO O H O OH O H CH3OH HO O H O OH O H O Me H ~HHO O H O OH2 O H O Me HO O O H OH OMe -H2O -H HO O OMe O HO MeO O OMe O HO 6-D2 1-(Phenylacetyl)imidazol aus Phenylessigs?ure und 1,1‘-Carbonyldiimidazol N O N O N NN N 6-D2 O O H O O H O N NN N O O + O N NN N H O O O N N N N H O O O N N N N H O N O N N O N H ~H O N O N N O N H -CO2/ -N N H O N N 6-D3 Benzylethylketon aus 1-(Phenylacetyl)imidazol (6- D2) und Ethylmagnesiumbromid O N N EtMgBr 6-D3 O O N N Et MgBr O N NEt MgBr H O NH NEt MgBr O N N H 6-D4 Fumars?ure-tert-butylethylester aus Fumars?uremonoethylester, tert-Butanol und DCC N NC COOH EtOOC COOtBu EtOOC 6-C4 t-BuOH EtOOC O O N NC N N C H H EtOOC O O + EtOOC N NC O O EtO2C N HN O O H HO O O EtO2C NH NHO O O EtO2C N NHOH ~H O EtO2C O + O NH NH 6-E1/2 1-Chlor-2-methyl-1-(piperidin-1-yl)propen aus iso- Butters?urepiperidid O N Cl N Cl Cl N Et3N 6-E1/2 ClCl O O O N O N ClCl O O O Cl O O Cl N O O Cl N O ClO O Cl N O Cl -CO2/-CO Cl N Cl H Et3N Cl N -HEt3N 6-E3N-Boc-L-Alanin-(N-methoxy-N-methylamid aus N-Boc- L-Alanin 6-E4(S)-4-(tert-Butoxycarbonylamino)-1-pentin-3-on aus N- Boc-L-Alanin-(N-methoxy-N-methylamid (6-E3) O HO H3C BocNH O N CH3 BocNH OCH3 CH3 1) ClCOOCH3 2) CH3ONHCH3 O CH3 BocNH [Li *NH2CH2CH2NH2] 6-E3 6-E4 O HO H3C BocNH Cl O OMe O O H3C BocNH H O Cl OMe O O H3C BocNH O OMe +Cl +H -CO2/-HOMe O H3C BocNH Cl NH Me OMe O CH3 BocNH Cl NH OMe Me -Cl -H CH3 BocNH NH OMe Me O O N CH3 BocNH OC H3 CH3 6-E3 O N CH3 BocNH OCH3 CH3 6-E3 Li *NH2CH2CH2NH2 O NBocNH OCH3 CH3 6-E3 Li NH2 NH2 H O NBocNH OCH3 CH3 H O CH3 BocNH 6-E4 6-F1L-Phenylalaninmethylester-hydrochlorid aus L- Phenylalanin Cl SOCl2/MeOH H3N CO2 Ph H3N Ph O OMe 6-F1 H3N Ph O O S O Cl Cl H3N Ph O O Cl S O Cl H3N Ph O O Cl S O ClH 3N Ph O ClCl MeOH H3N Ph O Cl O Me H Cl -HCl H3N Ph O O Cl Me H3N Ph OMe O Cl -SO2 6-F2 N-(Benzyloxycarbonyl)-L-asparagins?ure aus L- Asparagins?ure 6-F3 N-(Benzyloxycarbonyl)-L-asparagins?ureanhydrid aus N-Benzyloxycarbonyl-L-asparagins?ure (6-F2) 6-F4 N-(Benzyloxycarbonyl)-aspartam aus N- (Benzyloxycarbonyl)-L-asparagins?ureanhydrid (6-F3) und L- Phenylalaninmethylester (6-F1) 2) PhCH2OCOCl 1) MgO/H2O/Et2O OH OH O O NH2 OH OH O O NHO O Ph NHO O Ph O O O Ac2O H2N Ph O OMe N H Ph O OMe O CO2H NH (aus 6-F1) O O 6-F2 3) HCl 6-F4 Ph OH OH O O NH2 Ph O O Cl MgO -H2O O O O O H2N Mg O O O O NH2 Mg Cl O O Ph -H O O O O NH Mg Cl O O Ph O O O O NH Mg OOPh +2H2O -Mg(OH)2OH OH O O NHO O Ph 6-F2 OH OH O O NHO O Ph O OO O OH O O NHO O Ph O O O O OH O O NHO O Ph O O O ~H H O OH O O NHO O Ph O - HOAc H OH NHO O Ph O O O ~H O NHO O Ph O O O H - HOAc O NHO O Ph O O H2N Ph O OMe O NHO O Ph O O NHO O Ph O O O NH2 O OM e Ph ~H NHO O Ph O O O NH O OM e Ph 6F-3 HNHO O Ph O O NH OMeO Ph H O 6F-4 O O NHO O Ph O O O O H O 7. Umwandlungen von Carboxylverbindungen und Nitrilen ineinander 7-A1 Malons?ure aus Cyanessigs?ure CN CO2H 2) CaCl2 CO 2 CO2 CO2H CO2HHCl Ca2 1) NaOH C CO2H N + C CO2 N Na OH Na +H2O -OH C CO2 HNOH OH +OH -H2O C CO2 NH O +H2O -OH C CO2 NH2 O HO C CO2 NH2O OH +H2O -OH C CO2 NH3O OH C CO2 O OH ? -NH3 C CO2 O OH 2) CaCl2 +OH / -H2O C CO2 O O Ca2+2 HCl -CaCl2 CO2H CO2H 7-A2 Glycinethylesterhydrochlorid aus 1,3,5- Tris(cyanmethyl)-1,2,3,4,5,6-perhydrotriazin (9-A3) NH3EtO2C Cl HCl gasN N N CNNC CN EtOH abs. 7-A2 N N N CNNC CN H N N N CNC CN NH EtOH N N N CNC CN NH OEt H ~HN N N CNC NC NH2 OEtH2ON N N CNC NC NH3 OEt ~H O H -NH3, -H N N N CNC NC OEt O +H N N N C NC NC OEt O H N N N H2C C NC NC OEt O H H2ON N N C NC NC OEt O H OH -H N N N C NC NC OEt O H OH+H H N N N C NC NC OEt O H H + O H H H O H H 3x+H3N C OEt O Cl 3x 7-B1 Sebacins?uredinitril aus Sebacins?urediamid (6-B3) O H2N (CH2)8 NH2 O NC (CH2)8 CN SOCl2 7-B1 O H2N (CH2)8 NH2 O + Cl S Cl O -Cl O H2N (CH2)8 NH2 O S O Cl -HO H2N (CH2)8 NH O S O Cl-SO2 / -Cl O H2N (CH2)8 NH -H O H2N (CH2)8 N +SOCl2, -2HCl / -SO2 NC (CH2)8 CN 7-B2 Pentaacetyl-D-glucons?urenitril aus D-Glucoseoxim (9-B3) 7. B-2 NaAc, HOAcCHNOH HO OH O H HO OH CN OAc AcO AcO AcO OAc Ac2O C H HO OH O H HO OH O O O N OH C HO OH O H HO OH N O O H + O O H ~H C HO OH O H HO OH N + HO O O O O C HO OH O H HO OH N O O O ~H C HO O O H HO OH N O O OH -CH3COOH C HOAcOO H HO OH NCN OAc AcO AcO AcO OAc (1) (1) (2) (2) 2 7-C1/2 Methylbernsteins?ure aus 3-Cyanbutans?ure CO2HNC CO2O2C Ba(OH)2 CO2HHO2C HNO3 CO2Et NaCN EtOH, H2O H2O, ? Ba2 7-C1/C2 C CO2H H C N +OH CO2 C NHO +OH, -H2O H2O -OHCO2 C NHHO +OH -H2O CO2 C NHO +H2O -OH CO2 C NH2O +OH CO2 C NH2O OH +H2O -OH CO2 C NH3O OH -NH3 ? CO2 C O OH+OH -H2O CO2 C O O Ba2+ +HNO3 CO2H C O OH O OEt CN C O OEt CN +H2O -OH C O OEt CN H C O OEt CN OH C O OEt CN OH -OEt 7-D1 (1-Naphthyl)acetonitril aus 1- (Chlormethyl)naphthalin (5-D4) 7-D2 (1-Naphthyl)acetamid aus (1-Naphthyl)acetonitril (7-D1) NaCN EtOH, H2O Cl CN HCl /H2O O NH2 7-D1 b) 7-D2 Cl CN SN2 CN + Cl C N +H Cl C N H + Cl H2O C N H OH2 Cl C N H OH HCl + C N H2 OH Cl -HCl C N H2 O O NH2 7-E1 D-Gulons?ure- -lacton aus D-Xylose O OH OH O O H O 1) Ba(OH)2*6 H2O HO OH OH OH OH CN 3) kristallisieren aus MeOCH2CH2OH 2) H2SO4NaCN HO CHO OH OH OH NH4Cl HO CHO OH OH OH +NH4 -NH3 HO OH OH OH O CN HO OH OH OH OH C N +OH HO OH OH OH OH C N HO H2O HO OH OH OH OH C N HO H +OH -H2O HO OH OH OH OH C N O H +H2O -OH HO OH OH OH OH C NH2 O HO OH O OH OH C NH2 OH ~H HO OH O OH OH C NH3 O -OH HO OH O OH OH C NH3 O - 7-E2 Pyridin-3-carbonitril aus Pyridin-3-carboxamid CH2Cl2N NH2 O N CN 7-E2 Cl3CCOCl / NEt3 N NH2 O Cl CCl3 O + N NH2 O C O Cl CCl3 N NH2 O C O C Cl 3 Cl -HCl N NH O C O CCl3 -CO2-CCl3 N NH + -HCCl3 N CN 7-F1 -Phenylalanin aus 2-Amino-2-phenylpropionitril (9-F4) 7-F1 1) HCl / H2O / ? 2) Pyridin (9. F-4) CNH2N CO2H3N CH2N N 2HCl -2Cl CH3N NH H2O CH3N NH OH2 ~H CH3N NH2 H2O OH CH3N NH2 OH2 OH ~H CH3N NH3 OH OH CH3N NH3 OH OH + -NH4Cl CO2H3N 8. Umwandlungen von Kohlens?urederivaten und Heterocumulenen ineinander 8-C3 Natrium-(S)-2-amino-6-guanidinocapronat aus S- Ethylthiouronium-bromid und L-Lysin 8-C2 S H2N NH2 S H3N NH Et Br NaH2N CO2 NH3 4 2) 1) NaOH CO2 NH2 4 H NHN NH2 EtBr S H2N NH2 Et Br S H2N NH2 Et Br S H3N NH Et Br H2N CO 2 NH3 4 S H2N NH2 Et Br H2N CO 2 NH3 4 -SEt H2N NH2 Br H2N CO2 NH3 4 -H -H-H Na CO2 NH2 4 H NHN NH2 8-D3 3-[3-(Dimethylamino)propyl]-1-ethylcarbodiimid aus Ethylisocyanat und 3-Dimethylamino-1-propylamin 2) p-TsCl, Et3N NEtCO 1) NMe2H2N NMe2N C NEt 8-D3 + NEt3 NMe2H2N HNEt3 + NMe2HN NEt C O + Cl S O O CH3 S O O CH3OCNEt NMe2HN NMe2NCEtN Cl -Cl OTs +NEt3 -HNEt3, -OTs NMe2NCEtN H 8-E3/4 (4-Methoxyphenyl)isothiocyanat aus p-Anisidin 8-E3/4 MeO NH2 CS 2 Et3N MeO H N S S EtNH3 ClCO2Et Et3N MeO N C S MeO NH2 C S S MeO H2 N S S MeO H2 N S S Et3N OMe H N S S EtNH3 Cl OEt O - EtNH3OMe N S SEtO O H Et3N -Et3NH MeO N C S + SEtO O Et3NH SHEtO O SEtHO O EtOH + S C O 8-E3 (1)(2) 8-F2 1,3-Di-(tert-butoxycarbonylamino)benzol aus m- Phenylendiamin mit Di-tert-butyldicarbonat 8-F3 m-Phenylendiisocyanat aus 1,3-Di-(tert- butoxycarbonylamino)benzol (8-F2) 8-F2 8-F3 H2N NH2 t-BuO O Ot-Bu O O N H N H Ot-Bu O t-BuO O N N BCl3, NEt3 C OCO H2N NH2 t-BuO O Ot-Bu O O N H2 H2N Ot-Bu O O O Ot-Bu Boc-Anhydrid! O O Ot- Bu- N H2 H2N O Ot-Bu-HN H H2N O Ot-Bu N H N H Ot-Bu O t-BuO O N H Nt-BuO O Ot-Bu O BCl3 H8-F2 BCl3 +NEt3 -HNEt3, -BCl3, N H Nt-BuO O C O -Ot-Bu N N C OCO dto. 9. Umsetzung von Hetero-Nucleophilen mit Aldehyden bzw. Ketonen 9-A3 1,3,5-Tris(cyanmethyl)-1,2,3,4,5,6-perhydrotriazin aus Formaldehyd N N N CNNC CN C O / NH4ClCH3COOH NaCN H H 9-A3 C O H H NH4 C OH H H + NH3 NH3 H OH H ~H NH2 H OH2HNH2 HHH3N NH2 HH NH3 - H H2N NH2 OH H H H2N NH2 OH ~H H 2N NH OH2 - H2O H2N NHH 3N CH 2 H2N NH H3N O HHH2N NH H2NHO ~H HN NH H2NH2O - H2O HN NH N H2 - H HN NH N H O HH HN NH N HO H ~HHN NH N H2O CN HN NH N NC N N N NC CNNC analog -H H 9-A4 1,2:5,6-Diisopropyliden-D-mannit aus D-Mannit HO OH OH OH OH OH MeO OMe O O HO OH O O SnCl2 9-A4 MeO OMe + SnCl 2 O OMe SnCl2Me MeO + MeOSnCl2 HO OH OH OH OH OH MeO HO OH OH OH OH O OMe H ~H HO OH OH OH OH O OMe H HO OH OH OH OH O - MeOH HO OH OH OH O O H - H HO OH OH OH O O O O HO OH O O 9-B3 D-Glucoseoxim aus D-Glucose CHNOH OH HO HO HO OH65 °C NH2OH 9. B-3 O HO HO HO OH OHCHO OH HO HO HO OH OH HO HO HO OH O H NH2OH OH HO HO HO OH O H NH2-OH ~H OH HO HO HO OH OH2 H N-OH- H2O OH HO HO HO OH N OH O HO HO HO OH H N OH 9-B4 Chinoxalin aus o-Phenylendiamin und Glyoxal 9. B-4 + 1) NaHSO3 , H2O 2) Na2CO3 N NNH2 NH2 O O NH2 NH2 O HO + H2 N NH2 OH H O ~H H N NH2 OH2 H O H N NH2 O - H N NH2 O analog N N 9-C4 Meldrum’s S?ure aus Aceton und Malons?ure O O O OOH OH O O Me2C=O, Ac2O, H2SO4 9-C4 OH OH O O O O O OH OH O O OH O O H OH OH O O OH + O O- HOAc OH OH O O O O OH OH O O O O OH OH O O O O O O HO HO O O O O HO OH O O O O O OH -HOAc -H O O O O 9-D4 2,5-Dimethylpyrrol aus 2,5-Hexandion 9-D4 O O NH (NH4)2CO3 ? O O NH4 O O H + NH3 NH3 OHO ~HNH 2 OH2O -H2O O NH2 O NH O NH2 O NH2 ~H -H N H HO +H N H H2O -H2O N N H H H -H 9-F4 2-Amino-2-phenylpropionitril aus Acetophenon NaCN, NH4Cl 9-F4 O CNH 2N O NH4 OH + NH3 OH NH3~H OH2 NH2 -H2O NH2 CN CNH2N 10. Praktikumswoche 10. Addition von H-Nucleophilen oder Metallorganylen an Aldehyde bzw. Ketone 10-A3 endo-1,3,3-Trimethylbicyclo[2.2.1]heptan-2-ol aus (-)-Fenchon 10-A3O OH NaBH4 O H Angriff an der weniger konkaven Seite O H H OH 10-A4 syn-2,2-Dimethyl-4-phenyl-3-pentanol aus 2- Phenylpropionaldehyd Rac Rac Rac 10-A4 O H OH t-Bu 1) t-BuMgBr 2) HCl, H2O O H BrMg Angriff von vorne O t-Bu PhH Me OH Nu- 10-B1 (9-Fluorenyl)methanol aus Fluoren-9-carbaldehyd (6-B1) 10-B1 OHO NaBH4 O H O H H 10-B2 Cyclohexylcarbinol aus Formaldehyd und dem Grignardreagenz aus Chlorcyclohexan 10-B2 MgCl 2) H2O / H2SO4 CH2OHO H H 1) O H H MgCl C H H O H 10-B3 endo-1,3,3-Trimethylbicyclo[2.2.1]heptan-2-ol aus (-)-Fenchon 10-B3O OH 1) EtMgBr 2) HCl, H2O O MgBr H H H H2C CH2 O O H Mg Br sechsgliedrig 10-B4 anti-2,2-Dimethyl-4-phenyl-3-pentanol aus 2,2- Dimethyl-4-phenyl-3-pentanon Rac Rac 10-B4 O t-Bu OH t-Bu NaBH4 O t-Bu H OH t-Bu PhH Me Ot-Bu Nu- 10-C1/2 Bis[4-(dimethylamino)phenyl]phenylmethanol und Malachitgrün aus 4,4’-Bis(4-dimethylamino)benzophenon 10-C2 a) O NMe2 NMe2 OH MgBr 2) NH4Cl, H2O 1) Me2N Me2N NMe2 BF4 HBF4, Ac2O Me2N 10- C1 O Me2N Me2N BrMg NMe2 O Me2N NH4Cl NMe2 OH Me2N H NMe2Me2N NMe2 Me2N -H2O 10-C3 endo-1,2,3,3-Tetramethylbicyclo[2.2.1]heptan-2-ol aus (-)-Fenchon O OH 1) MeMgI 2) HCl, H2O 10-C3 O H3C MgI O Alkylierung, da kein β H 10-C4 syn- und anti-2-Phenyl-3-pentanol aus 2- Phenylpropionaldehyd Rac Rac Rac 10-C4 O H CH3 1) CH3MgI 2) HCl, H2O OH OH + 7 : 3 CH3 O H H3C MgI CH3 O Haups?chlich Cram 10-D1/2 1-Phenyl-3,4-tetrahydro-1-naphthol und 3,4- Dihydro-1-phenyl-naphthalin aus a-Tetralon 10-D1 O HO 2) NH4Cl, H2O 1) PhMgBr (CH3CO)2O10-D2 a) O BrMg O HO NH4Cl O O O O O O O O O O O H O O H - H E1 10-D3 exo-2-Ethyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2- ol aus (+)-Campher 10-D3 O OH1) EtMgBr 2) NH4Cl, H2O O Et MgBr O 10-D4 anti- und syn-2-Phenyl-3-butanol aus 2-Phenyl-3- pentanon RacRac Rac 10-D4 O Me Me Me OH OH + 7 : 3 NaBH4 O Me H Me O H 10-E1/2 Vinyl-b-ionol und Anhydro(vinyl-?-ionol) aus b- Ionon (3-E4) 10-E1 O MgBr OH 2) NH4Cl, H2O 1) 5n H2SO4 4h RT10-E2 a) O MgBr O NH4Cl H2O OH H OH2 H -H2O -H 10-E3 (+)-Isoborneol aus (+)-Campher 10-E3O OH NaBH4 O H O HCl OH 10-E4 trans- und cis-4-tert-Butylcyclohexanol aus 4-tert- Butylcyclohexanon 10-E4 O NaBH4 t-Bu t-But-Bu H OH H OH + 8 : 2 O t-Bu H H H H H t-Bu H O t-Bu H O + 10-F1 threo- und erythreo-1-(3,4-Dihydro-2H-pyran-2-yl)- 1-propanol aus 3,4-Dihydro-2H-pyran-2-aldehyd Rac Rac O O EtMgBr; HCl, H2O O OH O OH H O O HMg Et H O Mg Et OH O O MgBr O O O O 10-F2 cis-1-Ethinyl-4-tert-butylcyclohexanol aus 4-tert- Butylcyclohexanon t-Bu O NH2 NH2 O Li t-Bu OH OH H H H H Li NH2 NH2 O H NH NH2 Li 10-F3 (+)-Isoborneol aus (+)-Campher O OH 1) i-BuMgBr 2) NH4Cl, H2O O H H3C Mg Br O OH H H3C 10-F4 cis,cis-3,5-Diphenylcyclohexanol aus cis-3,5- Diphenylcyclohexanon 10-F4 O NaBH4 Ph Ph OHPh Ph O Ph Ph H OPh Ph OHPh Ph H2O 11. Praktikumswoche 11. Umsetzung von Heteroatom-stabilisierten C- Nucleophilen mit Aldehyden bzw. Ketonen 11-A1 trans-4-Bromzimts?ureethylester aus 4- Brombenzaldehyd und Triethylphosphonacetat 11-A1 CHO CO2Et BrBr C Br O H EtO C H2 P O O OEt OEt EtO P O O OEt OEt NaH, THF NaH EtO C H P O O OEt OEt EtO C H P O O OEt OEt Ylen Na Br O P(OEt) 2 O OEt O Br O P(OEt) 2 O OEt O - H2 CO2Et Br O P O OEt OEt 11-B1 cis-4-Bromzimts?ureethylester aus 4- Brombenzaldehyd und (Ethoxycarbonyl)methylphosphons?urediphenylester 11-B1 CO2Et ("TRITON B") P CO2Et PhO OPh O BrBr O PhCH2(CH3)2N+OH-, MeOH EtO C H2 P O O OEt OEt NaH EtO C H P O O OPh OPh EtO CH P O O OPh OPh Ylen Na - H2 Br O Br O P(OPh) 2 O OEt O Br O P(OPh) 2 O OEt O CO2Et Br O P O OPh OPh 11-C1 1,3-Bis(4-phenylbutadienyl)benzol aus Zimtaldehyd und m-Xylylen-bis(triphenylphosphoniumchlorid) 11-C1 Ph3P PPh3 Cl Cl LiOMe, EtOH O Ph3P PPh3 O Me H Ph3P PPh3 O Ph3P PPh3 O PPh3 PPh3 PPh3 11-D1 3-(3-Methyl-2-buten-1-yl)indol aus Indolcarbaldehyd (5-B6) und dem Instant-Ylid Isopropylidentriphenylphosphoran 11-D1"Instant-Ylid" [Me2CHP(C6H5)3Br + NaNH2] O O Me2C PPh3 H NH2 + NH3Me2C PPh3 Me2C PPh3 Me2C PPh3 O Ph3 P + O PPh3 11-E1 trans, E-5,9-Dimethyl-2,4,8-decatriens?ureethylester aus Geranial und (Ethoxycarbonylmethylen)triphenylphosphoran O CO2Et 11-E1 Ph3P CO2Et O Ph3P CO2Et Ph3P CO2Et PPh3O CO2Et CO2Et OPPh3 11-F1 E, E-2,5,9-Trimethyl-2,4,8-decatriens?ureethylester aus Geranial und [1-(Ethoxycarbonyl)ethyliden]triphenylphosphoran O CO2Et Ph3P CO2Et 11-F1 O Ph3P CO2Et Ph3P CO2Et PPh3O CO2EtCO2Et OPPh3 12. Chemie von Enaminen und Enolen 12-A2 1-(N-Morpholino)cylopenten aus Cyclopentanon und Morpholin 12-A3 2-(2-Methylbutyliden)cyclopentanon aus 1-(N- Morpholino)cylopenten (12-A2) und Isovaleraldehyd 12-A3 O N H O N O + ? 12-A2 O 2) HCl 1) -H2O O N H O + N O O H ~ H + H N O OH2 - H2O N O H N O N O O ~ H H O O Analog gehen auch 12-B2/B3, 12-E2/E3 und 12-F2/F3, allerdings dort Protonierung mit pTsOH !! N O OH N O - OH N O OH2 H O H ~ H N O O H H O H - H O 12-A4 (Acetamido)malons?urediethylester aus Malons?urediethylester 12-A4 EtO2C EtO2C NH OAc2O/AcOH EtO2C EtO2C EtO2C EtO2C NOH AcOH/H2O NaNO2 Zn EtO2C EtO2C H O OEt EtO O N O H O OEt EtO O N O O OEt OEt O N O - H O OEt OEt O N O H H O OEt OEt O N OH2 - H- H2O O OEt OEt O N Zn SET Zn O OEt OEt O NH e H 2 e 2 H O OEt OEt O NH2 H O OEt OEt O N H2 HO O O O O O O OEt OEt O N H2 H O O O O OEt OEtO N H2 H O O O O OEt OEt O N H O HO O 12-B2 1-(N-Morpholino)cyclohexen aus Cyclohexanon und Morpholin 12-B3 2-Oxocyclohexan-1-carbons?ureethylester aus 1-(N- Morpholino)cyclohexen (12-B2) 12-B2 12-B3 N H O N O + Η+, Toluol, ? O (-H2O) O OEt O 1) Cl OEt O 2) 2n HCl Mechanismus siehe 12 A2/3 12-B3 N O O OEt O1) Cl OEt O 2) 2n HCl N O Cl OEt O N O Cl OEt O O OEt O vgl. 12-C4 12-B4 Phenacylbromid aus Acetophenon 12-B4 CH3 O CH2Br O Br2, AcOH CH3 O Br BrCH2 OH - Br H C OH H HH - H CH2Br OH - HCH2Br O 12-C2 2-Methyl-1,3-cyclopentandion aus Bernsteins?ure und Propionylchlorid 12-C3 2-Methyl-2-(3-oxobutyl)-1,3-cyclopentandion aus 2- Methyl-1,3-cyclopentandion (12-C2) und Methylvinylketon 12-C4 (7aS)-7a-Methyl-2,3,5,6,7,7a-hexahydro-1H-inden- 1-on aus 2-Methyl-2-(3-oxobutyl-1,3-cyclopentandion (12- C3) 12-C3 12-C2 Cl O O OH O HO + O O O HO O O O AlCl3 12-C4 H2N CO2 H O O 2) H2SO4 DMF 1) HO OH O OH Cl O AlCl3 HO OH O OH O Cl - HCl O OH O OH O ~ H O OH O OH HO O HO O OH OH O O O O H - CO2 O O O HO OHO H O O OH O O O - H HO O O H2N CO2 H O O N HO2C H O N HO2C H O O N O2C H OH ~ H H O H O N O2C H HO H2O ONH O2C H HO HO ~ H ONH O2C H HO HO H2N CO2 H O HO O H - H2O O O - H O O 12-D2 2-Pyrrolidino-3,4-dihydro-6-methoxynaphthalin aus 6-Methoxy-2-tetralon 12-D3 6-Methoxy-1-benzyl-2-tetralon aus 2-Pyrrolidino- 3,4-dihydro-6-methoxynaphthalin (12-D2) O OMe N OMe N H Toluol, ? (-H2O) 12-D2 12-D3 O OMe 2) AcOH, H2O 1) PhCH2Br O OMe NH O OMe NH Ph ~ H OH OMe N OMe N H - H2O BrSN2 OMe N H3O vgl. 12-C4 O OMe Ph 12-D4 2,5-Dibromadipins?urediethylester aus Adipins?ure 12-D4 EtO2C CO2Et Br Br HO2C CO2H 1) SOCl2, Br2 2) EtOH HO2C C O OH S O ClCl HO2C C O OH S O ClCl HO2C C O OH S O Cl Cl - Cl- - SO2 HO2C C OH Cl HO2C C O Cl - H C C O Cl Cl O C C O Cl Cl OH Br BrC C O Cl Cl OH Br - H HOC C O Cl Cl O Br C C O Cl Cl O Br Br - Cl- (1) (1) (2) (2) C C O H O Cl O Br Br - HC C O O Cl O Br Br C C O O O O Br Br 12-E2 1-(N-Pyrrolidino)cyclohexen aus Cyclohexanon und Pyrrolidin 12-E3 3-(2-Oxocyclohexyl)propions?ureethylester aus 1- (N-Pyrrolidino)cyclohexen (12-E2) und Acryls?ureethylester 12-E2 N O N H OEt O 1) O CO2Et 2) H2O, ? + Η+, Toluol, ? (-H2O) 12-E3 Mechanismus siehe unter 12 A2/3 12-E4 2,4-Dibrom-3-pentanon aus 3-Pentanon 12-E4 O O Br Br Br2, PBr3 (kat) -10 bis 0°C O P Br Br Br O P Br Br Br H - H O P Br Br Br Br Br - Br O P Br Br Br Br - PBr3 O Br O Br Br 12-F2 1-(N-Piperidino)cyclohexen aus Cyclohexanon und Piperidin 12-F3 1,10-Bis-(2-oxocylohexyl)-1,10-decandion aus 1- (N-Piperidino)cyclohexen (12-F2) und Sebacins?uredichlorid (6-B2) 12- F2 N H N + Η+, Toluol, ? O (-H2O) Mechanismus siehe unter 12 A2/3 12-F3 O O O O 8 O O 8Cl Cl 1) , Et3N 2) HCl/H2O 12-F4 -Brom- -butyrolacton aus -Butyrolacton 12-F4 O O O O Br Br2, P O Br Br Br H2O 3 Br2 + 2 P 2 PBr3 O O P Br Br Br O O Br P Br Br Br - PBr3 O Br HO OH Br HO H H OH Br H2O Br Br Br - H2O; -Br - HO Br Br Br H O H Br O Br H2O Br - H OH Br O Br - Br O OH Br - H O O Br 13. Chemie von Aldeyd-, Keton- und Esterenolaten 13-A1 Acetylbernsteins?urediethylester aus Acetessigester und Chloressigs?ureethylester O CO2Et OEt O O OEt O 1) Na, EtOH 2) ClCH2CO2Et Na Na OEt 0.5H2 OEt O O H OEt HOEt OEt O O HOEt OEt O ONa Cl OEt O Na Cl OEt OONa Na O CO2Et O OEt Weniger wichtige meso. GF, da 14 kcal/mol Ester-Mesomerie fehlt!!! 13-A2 4-Oxopentancarbons?ureethylester aus Acetylbernsteins?urediethylester (13-A1) O CO2Et OEt O O CO2EtH3BO3 O CO2Et O OEt B OH OH OH δ+ CO2Et O OEt O B HO OH OH δ+ δ?δ?δ? CO2Et O OEt O B HO OH OH δ+ δ? O OEt O B HO OH OH EtO2C OH2 ~H O O O B HO OH OH EtO2C OH H Et H3BO3 HOEt O O OH O O Et H2O O O O Et O O H OH O O Et OH O O Et O O O Et CO2 13-A3 Sorbins?ure aus Malons?ure und Crotonaldehyd 13-A3 CHO CO2H + Pyridin, DO HO HO O O OHHO O H H N O OH OH O H O OHOH O H N H H H O H O OH OH O H N H H H O OH OH OHO H N H H HO OH OH OHO N N H H HO OH O OH O N H OH H H O O HO OH H CO2 H H O O H H ~H H H H H O O H H H H H H O O H H H 13-A4 3-Hydroxy-2-methylpentanal aus Propionaldehyd 13-A4 CHO OH CHO KOH, MeOH H O H H H O H H O H H O H O H K KH H3O H2O H OHO H OH O = OH H2O 13-B1 5-(1-Hydroxy-2-phenylethyliden)-2,2-dimethyl-1,3- dioxan-4,6-dion aus Meldrums S?ure (9-C4) und Phenylessigs?urechlorid O O O O + O O O O OH Cl O Pyridin CH2Cl2 O O O O H H N O O O O H H N Cl O O O O O H Cl O NH ~H N O O O O H Cl OH N O O O O Cl OH N H ~H3O H2O H-Cl N O O O O OH 13-B2 3-Oxo-4-phenylbutters?uremethylester aus 5-(1- Hydroxy-2-phenylethyliden)-2,2-dimethyl-1,3-dioxan-4,6- dion (13-B1) 13-B1 13-B2 O O O O OH MeOH, ? O OMe O O O O O HO MeOH O O O HO OH Me O O OH O HO O O ~H O HO O HO O O O O HO O O O H OH O HO O O O ~H ~H O O O H CO2 H O O O H O O O O O HO O O H ~H 13-B3 1,2,4,5-Tetraphenylpentan-1,5-dion aus Desoxybenzoin Ph OPh Ph O Ph O Ph Ph CH2O, KOH 13-B3 Ph O Ph OH H H H 2O Ph O Ph H K K O H O Ph O H Ph K H2O OH H HO Ph O H Ph OH H2O H HO Ph O Ph K K OH Ph O Ph K Ph O Ph Ph O Ph O Ph Ph Ph O Ph O Ph Ph +H 13-B4 2-Methyl-3-oxo-pentans?ureethylester aus Propions?ureethylester OEt OEt O O O Na 13-B4 OEt O H H Na SET -H OEt O H SET -H OEt O H OEt O H H2 OEt O OEt O O OEt -OEt OEt O O 13-C1 2-Oxo-5,6-diphenyl-3-cyclohexen-1- carbons?ureethylester aus Benzalacetophenon und Acetessigs?ureethylester 13-C2 3,5-Diphenyl-2-cyclohexen-1-on aus 2-Oxo-5,6- diphenyl-3-cyclohexen-1-carbons?ureethylester (13-C1) 13-C3 1-Ethyl-2-oxocyclopentan-1-carbons?ureethylester aus 2-Oxocyclopentan-1-carbons?ureethylester 13-C4 3-Ethyl-2-oxocyclopentan-1-carbons?ureethylester aus 1-Ethyl-2-oxocyclopentan-1-carbons?ureethylester (13- C3) 13-D1 1-Phenyl-1-penten-3-on aus Benzaldehyd und Ethylmethylketon 13-D2 6-Methyl-5-hepten-2-on aus Citral 13-D3 Curcumin aus Vanillin und Acetylaceton 13-D4 Dimedon aus Mesityloxid und Malons?urediethylester 13-E1 Indan-1,3-dion aus Phthals?urediethylester und Essigs?ureethylester 13-E2 (+)-3-(Trifluoracetyl)campher aus (+)-Campher und Trifluoressigs?ureethylester 13-E3 3-Cyclopenten-1,1-dicarbons?ure aus Malons?uredimethylester und cis-1,4-Dichlor-2-buten 13-E4 4-Hydroxy-4-methyl-2-pentanon aus Aceton 13-F1 (3-Oxocyclohexyl)essigs?ure aus Malons?urediethylester und 2-Cyclohexen-1-on 13-F2 3-(Methylthio)-1-(phthalimido)propan-1,1- dicarbons?urediethylester aus (Phthalimido)malons?urediethylester (2-C1) 13-F3 rac-Methionin 3-(Methylthio)-1- (phthalimido)propan-1,1-dicarbons?urediethylester (13-F2) 13-F4 7,16-Dioxodocosandis?ure aus 1,10-Bis(2- oxocylohexyl)-1,10-decandion (12-F3)