CHAPTER 19
CARBOXYLIC ACIDS
C
arboxylic acids, compounds of the type , constitute one of the most fre-
quently encountered classes of organic compounds. Countless natural products are
carboxylic acids or are derived from them. Some carboxylic acids, such as acetic
acid, have been known for centuries. Others, such as the prostaglandins, which are pow-
erful regulators of numerous biological processes, remained unknown until relatively
recently. Still others, aspirin for example, are the products of chemical synthesis. The
therapeutic effects of aspirin, welcomed long before the discovery of prostaglandins, are
now understood to result from aspirin’s ability to inhibit the biosynthesis of
prostaglandins.
The chemistry of carboxylic acids is the central theme of this chapter. The impor-
tance of carboxylic acids is magnified when we realize that they are the parent com-
pounds of a large group of derivatives that includes acyl chlorides, acid anhydrides,
esters, and amides. Those classes of compounds will be discussed in the chapter fol-
CH
3
COH
O
Acetic acid
(present in
vinegar)
HO
OH
O
(CH
2
)
6
CO
2
H
(CH
2
)
4
CH
3
PGE
1
(a prostaglandin; a small amount
of PGE
1
lowers blood pressure
significantly)
Aspirin
COH
O
O
OCCH
3
RCOH
O
X
736
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
lowing this one. Together, this chapter and the next tell the story of some of the most
fundamental structural types and functional group transformations in organic and bio-
logical chemistry.
19.1 CARBOXYLIC ACID NOMENCLATURE
Nowhere in organic chemistry are common names used more often than with the car-
boxylic acids. Many carboxylic acids are better known by common names than by their
systematic names, and the framers of the IUPAC nomenclature rules have taken a lib-
eral view toward accepting these common names as permissible alternatives to the sys-
tematic ones. Table 19.1 lists both the common and the systematic names of a number
of important carboxylic acids.
Systematic names for carboxylic acids are derived by counting the number of car-
bons in the longest continuous chain that includes the carboxyl group and replacing the
-e ending of the corresponding alkane by -oic acid. The first three acids in the table,
methanoic (1 carbon), ethanoic (2 carbons), and octadecanoic acid (18 carbons), illus-
trate this point. When substituents are present, their locations are identified by number;
numbering of the carbon chain always begins at the carboxyl group. This is illustrated
in entries 4 and 5 in the table.
19.1 Carboxylic Acid Nomenclature 737
TABLE 19.1 Systematic and Common Names of Some Carboxylic Acids
1.
2.
3.
4.
5.
6.
7.
9.
10.
11.
12.
8.
Methanoic acid
Ethanoic acid
Octadecanoic acid
2-Hydroxypropanoic acid
2-Hydroxy-2-phenylethanoic acid
Propenoic acid
(Z)-9-Octadecenoic acid
o-Hydroxybenzenecarboxylic acid
Propanedioic acid
Butanedioic acid
1,2-Benzenedicarboxylic acid
Systematic name
Benzenecarboxylic acid
Formic acid
Acetic acid
Stearic acid
Lactic acid
Mandelic acid
Acrylic acid
Oleic acid
Benzoic acid
Salicylic acid
Malonic acid
Succinic acid
Phthalic acid
Common nameStructural formula
HCO
2
H
CH
3
CO
2
H
CH
3
(CH
2
)
16
CO
2
H
CH
3
CHCO
2
H
W
OH
CH
2
?CHCO
2
H
CH
3
(CH
2
)
7
(CH
2
)
7
CO
2
H
HH
C?C
±
±
±
±
HO
2
CCH
2
CO
2
H
HO
2
CCH
2
CH
2
CO
2
H
CHCO
2
H
W
OH
CO
2
H
CO
2
H
OH
CO
2
H
CO
2
H
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Notice that compounds 4 and 5 are named as hydroxy derivatives of carboxylic
acids, rather than as carboxyl derivatives of alcohols. We have seen earlier that hydroxyl
groups take precedence over double bonds, and double bonds take precedence over halo-
gens and alkyl groups, in naming compounds. Carboxylic acids outrank all the common
groups we have encountered to this point.
Double bonds in the main chain are signaled by the ending -enoic acid, and their
position is designated by a numerical prefix. Entries 6 and 7 are representative carboxylic
acids that contain double bonds. Double-bond stereochemistry is specified by using either
the cis–trans or the E–Z notation.
When a carboxyl group is attached to a ring, the parent ring is named (retaining
the final -e) and the suffix -carboxylic acid is added, as shown in entries 8 and 9.
Compounds with two carboxyl groups, as illustrated by entries 10 through 12, are
distinguished by the suffix -dioic acid or -dicarboxylic acid as appropriate. The final -e
in the base name of the alkane is retained.
PROBLEM 19.1 The list of carboxylic acids in Table 19.1 is by no means exhaus-
tive insofar as common names are concerned. Many others are known by their
common names, a few of which follow. Give a systematic IUPAC name for each.
(a) (c)
(b) (d)
SAMPLE SOLUTION (a) Methacrylic acid is an industrial chemical used in the
preparation of transparent plastics such as Lucite and Plexiglas. The carbon chain
that includes both the carboxylic acid and the double bond is three carbon atoms
in length. The compound is named as a derivative of propenoic acid. It is not nec-
essary to locate the position of the double bond by number, as in “2-propenoic
acid,” because no other positions are structurally possible for it. The methyl group
is at C-2, and so the correct systematic name for methacrylic acid is 2-methyl-
propenoic acid.
19.2 STRUCTURE AND BONDING
The structural features of the carboxyl group are most apparent in formic acid. Formic
acid is planar, with one of its carbon–oxygen bonds shorter than the other, and with bond
angles at carbon close to 120°.
This suggests sp
2
hybridization at carbon, and a H9268 H11001 H9266 carbon–oxygen double bond
analogous to that of aldehydes and ketones.
Bond Distances
C?O
C±O
120 pm
134 pm
Bond Angles
H±C?O
H±C±O
O±C?O
124°
111°
125°
C H
O
HO
CO
2
HCH
3
(p-Toluic acid)
C
H
CO
2
HH
H
3
C
C
(Crotonic acid)
HO
2
CCO
2
H
(Oxalic acid)
CH
2
CH
3
CCO
2
H
(Methacrylic acid)
738 CHAPTER NINETEEN Carboxylic Acids
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Additionally, sp
2
hybridization of the hydroxyl oxygen allows one of its unshared
electron pairs to be delocalized by orbital overlap with the H9266 system of the carbonyl
group (Figure 19.1). In resonance terms, this electron delocalization is represented as:
Lone-pair donation from the hydroxyl oxygen makes the carbonyl group less elec-
trophilic than that of an aldehyde or ketone. The graphic that opened this chapter is an
electrostatic potential map of formic acid that shows the most electron-rich site to be the
oxygen of the carbonyl group and the most electron-poor one to be, as expected, the OH
proton.
Carboxylic acids are fairly polar, and simple ones such as acetic acid, propanoic
acid, and benzoic acid have dipole moments in the range 1.7–1.9 D.
19.3 PHYSICAL PROPERTIES
The melting points and boiling points of carboxylic acids are higher than those of hydro-
carbons and oxygen-containing organic compounds of comparable size and shape and
indicate strong intermolecular attractive forces.
A unique hydrogen-bonding arrangement, shown in Figure 19.2, contributes to
these attractive forces. The hydroxyl group of one carboxylic acid molecule acts as a
proton donor toward the carbonyl oxygen of a second. In a reciprocal fashion, the
hydroxyl proton of the second carboxyl function interacts with the carbonyl oxygen of
the first. The result is that the two carboxylic acid molecules are held together by
two hydrogen bonds. So efficient is this hydrogen bonding that some carboxylic acids
exist as hydrogen-bonded dimers even in the gas phase. In the pure liquid a mixture of
hydrogen-bonded dimers and higher aggregates is present.
In aqueous solution intermolecular association between carboxylic acid molecules
is replaced by hydrogen bonding to water. The solubility properties of carboxylic acids
are similar to those of alcohols. Carboxylic acids of four carbon atoms or fewer are mis-
cible with water in all proportions.
bp (1 atm):
2-Methyl-1-butene
31°C
O
2-Butanone
80°C
OH
2-Butanol
99°C
O
OH
Propanoic acid
141°C
H
OH
C
O
H
H11001
C
O
H11002
OH
H
H11001
O
H11002
C
OH
19.3 Physical Properties 739
FIGURE 19.1 Carbon
and both oxygens are sp
2
-
hybridized in formic acid.
The H9266 component of the
C?O group and the p or-
bital of the OH oxygen over-
lap to form an extended H9266
system that includes carbon
and the two oxygens.
A summary of physical prop-
erties of some representative
carboxylic acids is presented
in Appendix 1.
Examine the electrostatic
potential map of butanoic acid
on Learning By Modeling and
notice how much more intense
the blue color (positive charge)
is on the OH hydrogen than on
the hydrogens bonded to
carbon.
FIGURE 19.2 Attrac-
tions between regions of
positive (blue) and negative
(red) electrostatic potential
are responsible for intermo-
lecular hydrogen bonding
between two molecules of
acetic acid.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.4 ACIDITY OF CARBOXYLIC ACIDS
Carboxylic acids are the most acidic class of compounds that contain only carbon, hydro-
gen, and oxygen. With ionization constants K
a
on the order of 10
H110025
(pK
a
H11015 5), they are
much stronger acids than water and alcohols. The case should not be overstated, how-
ever. Carboxylic acids are weak acids; a 0.1 M solution of acetic acid in water, for exam-
ple, is only 1.3% ionized.
To understand the greater acidity of carboxylic acids compared with water and
alcohols, compare the structural changes that accompany the ionization of a representa-
tive alcohol (ethanol) and a representative carboxylic acid (acetic acid). The equilibria
that define K
a
are
Ionization of ethanol
Ionization of acetic acid
From these K
a
values, the calculated free energies of ionization (H9004G°) are 91 kJ/mol
(21.7 kcal/mol) for ethanol versus 27 kJ/mol (6.5 kcal/mol) for acetic acid. An energy
diagram portraying these relationships is presented in Figure 19.3. Since it is equilibria,
not rates, of ionization that are being compared, the diagram shows only the initial and
final states. It is not necessary to be concerned about the energy of activation, since that
affects only the rate of ionization, not the extent of ionization.
The large difference in the free energies of ionization of ethanol and acetic acid
reflects a greater stabilization of acetate ion relative to ethoxide ion. Ionization of ethanol
yields an alkoxide ion in which the negative charge is localized on oxygen. Solvation
forces are the chief means by which ethoxide ion is stabilized. Acetate ion is also sta-
bilized by solvation, but has two additional mechanisms for dispersing its negative charge
that are not available to ethoxide ion:
1. The inductive effect of the carbonyl group. The carbonyl group of acetate ion is
electron-withdrawing, and by attracting electrons away from the negatively charged
oxygen, acetate anion is stabilized. This is an inductive effect, arising in the polar-
ization of the electron distribution in the H9268 bond between the carbonyl carbon and
the negatively charged oxygen.
2. The resonance effect of the carbonyl group. Electron delocalization, expressed by
resonance between the following Lewis structures, causes the negative charge in
acetate to be shared equally by both oxygens. Electron delocalization of this type
is not available to ethoxide ion.
CH
3
C
H9254H11001
H9254H11002
O
H11002
OPositively polarized
carbon attracts elec-
trons from negatively
charged oxygen.
CH
2
group has
negligible effect
on electron density
at negatively
charged oxygen.
CH
3
CH
2
O
H11002
Acetic acid
CH
3
COH
O
Acetate ion
CH
3
CO
H11002
O
H
H11001
H11001 K
a
H11005
[H
H11001
][CH
3
CO
2
H11002
]
[CH
3
CO
2
H]
H11005 1.8 H11003 10
H110025
Ethanol
CH
3
CH
2
OH H
H11001
H11001
Ethoxide ion
CH
3
CH
2
O
H11002
K
a
H11005
[H
H11001
][CH
3
CH
2
O
H11002
]
[CH
3
CH
2
OH]
H11005 10
H1100216
740 CHAPTER NINETEEN Carboxylic Acids
Free energies of ionization
are calculated from equilib-
rium constants according to
the relationship
H9004G° H11005H11002RT In K
a
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
PROBLEM 19.2 Peroxyacetic acid is a weaker acid than acetic acid;
its K
a
is 6.3 H11003 10
H110029
(pK
a
8.2) versus 1.8 H11003 10
H110025
for acetic acid (pK
a
4.7). Why are
peroxy acids weaker than carboxylic acids?
Electron delocalization in carboxylate ions is nicely illustrated with the aid of elec-
trostatic potential maps. As Figure 19.4 shows, the electrostatic potential is different for
the two different oxygens of acetic acid, but is the same for the two equivalent oxygens
of acetate ion.
Likewise, the experimentally measured pattern of carbon–oxygen bond lengths in
acetic acid is different from that of acetate ion. Acetic acid has a short C?O and a long
C±O distance. In ammonium acetate, though, both carbon–oxygen distances are equal.
(CH
3
COOH)
O
X
CH
3
C
O
O
H11002
CH
3
C
O
H11002
O
or CH
3
C
O
H110021/2
O
H110021/2
19.4 Acidity of Carboxylic Acids 741
CH
3
CH
2
O
–
+H
+
CH
3
CH
2
OH
?G° = 91 kJ/mol
(21.7 kcal/mol)
?G° = 27 kJ/mol
(6.5 kcal/mol)
?G° = 64 kJ/mol
(15.2 kcal/mol)
Ethanol
Acetic acid
CH
3
CO
–
+H
+
O
CH
3
COH
O
FIGURE 19.3 Diagram
comparing the free energies
of ionization of ethanol and
acetic acid in water. The elec-
trostatic potential maps of
ethoxide and acetate ion
show the concentration of
negative charge in ethoxide
versus dispersal of charge in
acetate.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
For many years, resonance in carboxylate ions was emphasized when explaining
the acidity of carboxylic acids. Recently, however, it has been suggested that the induc-
tive effect of the carbonyl group may be more important. It seems clear that, even though
their relative contributions may be a matter of debate, both play major roles.
19.5 SALTS OF CARBOXYLIC ACIDS
In the presence of strong bases such as sodium hydroxide, carboxylic acids are neutral-
ized rapidly and quantitatively:
PROBLEM 19.3 Write an ionic equation for the reaction of acetic acid with each
of the following, and specify whether the equilibrium favors starting materials or
products:
(a) Sodium ethoxide (d) Sodium acetylide
(b) Potassium tert-butoxide (e) Potassium nitrate
(c) Sodium bromide (f) Lithium amide
SAMPLE SOLUTION (a) This is an acid–base reaction; ethoxide ion is the base.
The position of equilibrium lies well to the right. Ethanol, with a K
a
of 10
H1100216
(pK
a
16), is a much weaker acid than acetic acid.
H11001H11001CH
3
CO
2
H
Acetic acid
(stronger acid)
CH
3
CH
2
OH
Ethanol
(weaker acid)
CH
3
CH
2
O
H11002
Ethoxide ion
(stronger base)
CH
3
CO
2
H11002
Acetate ion
(weaker base)
RC H
O
O
Carboxylic
acid
(stronger
acid)
H11001 OH
H11002
Hydroxide
ion
(stronger
base)
K H11005 10
11
RC
O
O
H11002
Carboxylate
ion
(weaker
base)
H11001 H OH
Water
(weaker
acid)
NH
4
H11001
CH
3
C
OH
O
121 pm
136 pm
CH
3
C
O
H110021/2
O
H110021/2
125 pm
125 pm
742 CHAPTER NINETEEN Carboxylic Acids
(a)(b)
FIGURE 19.4 Elec-
trostatic potential maps of
(a) acetic acid and (b) acetate
ion. The negative charge
(red) is equally distributed
between both oxygens of ac-
etate ion.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.5 Salts of Carboxylic Acids 743
QUANTITATIVE RELATIONSHIPS INVOLVING CARBOXYLIC ACIDS
S
uppose you take two flasks, one containing pure
water and the other a buffer solution main-
tained at a pH of 7.0. If you add 0.1 mol of acetic
acid to each one and the final volume in each flask is
1 L, how much acetic acid is present at equilibrium?
How much acetate ion? In other words, what is the
extent of ionization of acetic acid in an unbuffered
medium and in a buffered one?
The first case simply involves the ionization of a
weak acid and is governed by the expression that de-
fines K
a
for acetic acid:
K
a
H11005H110051.8 H11003 10
H110025
Since ionization of acetic acid gives one H
H11001
for each
CH
3
CO
2
H11002
, the concentrations of the two ions are
equal, and setting each one equal to x gives:
K
a
H11005H110051.8 H11003 10
H110025
Solving for x gives the acetate ion concentration as:
x H11005 1.3 H11003 10
H110023
Thus when acetic acid is added to pure water, the ra-
tio of acetate ion to acetic acid is
H11005H110050.013
Only 1.3% of the acetic acid has ionized. Most of it
(98.7%) remains unchanged.
Now think about what happens when the same
amount of acetic acid is added to water that is
buffered at pH H11005 7.0. Before doing the calculation,
let us recognize that it is the [CH
3
CO
2
H11002
] ? [CH
3
CO
2
H]
ratio in which we are interested and do a little alge-
braic manipulation. Since
K
a
H11005
then
H11005
K
a
[H
H11001
]
[CH
3
CO
2
H11002
]
[CH
3
CO
2
H]
[H
H11001
][CH
3
CO
2
H11002
]
[CH
3
CO
2
H]
1.3 H11003 10
H110023
0.1
[CH
3
CO
2
H11002
]
[CH
3
CO
2
H]
x
2
0.1 H11002 x
[H
H11001
][CH
3
CO
2
H11002
]
[CH
3
CO
2
H]
This relationship is one form of the Henderson–
Hasselbalch equation. It is a useful relationship in
chemistry and biochemistry. One rarely needs to cal-
culate the pH of a solution—pH is more often mea-
sured than calculated. It is much more common that
one needs to know the degree of ionization of an
acid at a particular pH, and the Henderson–Hassel-
balch equation gives that ratio.
For the case at hand, the solution is buffered at
pH H11005 7.0. Therefore,
H11005H11005180
A very different situation exists in an aqueous solu-
tion maintained at pH H11005 7.0 from the situation in
pure water. We saw earlier that almost all the acetic
acid in a 0.1 M solution in pure water was nonion-
ized. At pH 7.0, however, hardly any nonionized
acetic acid remains; it is almost completely converted
to its carboxylate ion.
This difference in behavior for acetic acid in
pure water versus water buffered at pH H11005 7.0 has
some important practical consequences. Biochemists
usually do not talk about acetic acid (or lactic acid, or
salicylic acid, etc.). They talk about acetate (and lac-
tate, and salicylate). Why? It’s because biochemists
are concerned with carboxylic acids as they exist in di-
lute aqueous solution at what is called biological pH.
Biological fluids are naturally buffered. The pH of
blood, for example, is maintained at 7.2, and at this
pH carboxylic acids are almost entirely converted to
their carboxylate anions.
An alternative form of the Henderson–Hassel-
balch equation for acetic acid is
pH H11005 pK
a
H11001 log
From this equation it can be seen that when
[CH
3
CO
2
H11002
] H11005 [CH
3
CO
2
H], then the second term is log
1 H11005 0, and pH H11005 pK
a
. This means that when the pH of
a solution is equal to the pK
a
of a weak acid, the con-
centration of the acid and its conjugate base are
equal. This is a relationship worth remembering.
[CH
3
CO
2
H11002
]
[CH
3
CO
2
H]
1.8 H11003 10
H110025
10
H110027
[CH
3
CO
2
H11002
]
[CH
3
CO
2
H]
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
The metal carboxylate salts formed on neutralization of carboxylic acids are named
by first specifying the metal ion and then adding the name of the acid modified by replac-
ing -ic acid by -ate. Monocarboxylate salts of diacids are designated by naming both the
cation and hydrogen as substituents of carboxylate groups.
Metal carboxylates are ionic, and when the molecular weight isn’t too high, the sodium
and potassium salts of carboxylic acids are soluble in water. Carboxylic acids therefore
may be extracted from ether solutions into aqueous sodium or potassium hydroxide.
The solubility behavior of salts of carboxylic acids having 12–18 carbons is
unusual and can be illustrated by considering sodium stearate:
Sodium stearate has a polar carboxylate group at one end of a long hydrocarbon chain.
The carboxylate group is hydrophilic (“water-loving”) and tends to confer water solu-
bility on the molecule. The hydrocarbon chain is lipophilic (“fat-loving”) and tends to
associate with other hydrocarbon chains. The compromise achieved by sodium stearate
when it is placed in water is to form a colloidal dispersion of spherical aggregates called
micelles. Each micelle is composed of 50–100 individual molecules. Micelles form spon-
taneously when the carboxylate concentration exceeds a certain minimum value called
the critical micelle concentration. A representation of a micelle is shown in Figure 19.5.
Polar carboxylate groups dot the surface of the micelle. There they bind to water
molecules and to sodium ions. The nonpolar hydrocarbon chains are directed toward the
interior of the micelle, where individually weak but cumulatively significant induced-
dipole/induced-dipole forces bind them together. Micelles are approximately spherical
because a sphere encloses the maximum volume of material for a given surface area and
O
Na
H11001
O
H11002
Sodium stearate
(sodium octadecanoate)
CH
3
COLi
O
Lithium
acetate
Cl CONa
O
Sodium p-chlorobenzoate
HOC(CH
2
)
4
COK
O O
Potassium hydrogen
hexanedioate
744 CHAPTER NINETEEN Carboxylic Acids
FIGURE 19.5 A space-
filling model of a micelle
formed by association of car-
boxylate ions derived from a
fatty acid. In general, the
hydrophobic carbon chains
are inside and the carboxy-
late ions on the surface, but
the micelle is irregular, and
contains voids, channels, and
tangled carbon chains. Each
carboxylate is associated
with a metal ion such as Na
H11001
(not shown).
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
disrupts the water structure least. Because their surfaces are negatively charged, two
micelles repel each other rather than clustering to form higher aggregates.
It is the formation of micelles and their properties that are responsible for the
cleansing action of soaps. Water that contains sodium stearate removes grease by enclos-
ing it in the hydrocarbon-like interior of the micelles. The grease is washed away with
the water, not because it dissolves in the water but because it dissolves in the micelles
that are dispersed in the water. Sodium stearate is an example of a soap; sodium and
potassium salts of other C
12
–C
18
unbranched carboxylic acids possess similar properties.
Detergents are substances, including soaps, that cleanse by micellar action. A large
number of synthetic detergents are known. One example is sodium lauryl sulfate. Sodium
lauryl sulfate has a long hydrocarbon chain terminating in a polar sulfate ion and forms
soap-like micelles in water.
Detergents are designed to be effective in hard water, meaning water containing calcium
salts that form insoluble calcium carboxylates with soaps. These precipitates rob the soap
of its cleansing power and form an unpleasant scum. The calcium salts of synthetic deter-
gents such as sodium lauryl sulfate, however, are soluble and retain their micelle-forming
ability in water.
19.6 SUBSTITUENTS AND ACID STRENGTH
Alkyl groups have little effect on the acidity of a carboxylic acid. The ionization con-
stants of all acids that have the general formula C
n
H
2nH110011
CO
2
H are very similar to one
another and equal approximately 10
H110025
(pK
a
5). Table 19.2 gives a few examples.
An electronegative substituent, particularly if it is attached to the H9251 carbon,
increases the acidity of a carboxylic acid. As the data in Table 19.2 show, all the mono-
haloacetic acids are about 100 times more acidic than acetic acid. Multiple halogen sub-
stitution increases the acidity even more; trichloroacetic acid is 7000 times more acidic
than acetic acid!
The acid-strengthening effect of electronegative atoms or groups is easily seen as
an inductive effect of the substituent transmitted through the H9268 bonds of the molecule.
According to this model, the H9268 electrons in the carbon–chlorine bond of chloroacetate
ion are drawn toward chlorine, leaving the H9251-carbon atom with a slight positive charge.
The H9251 carbon, because of this positive character, attracts electrons from the negatively
charged carboxylate, thus dispersing the charge and stabilizing the anion. The more sta-
ble the anion, the greater the equilibrium constant for its formation.
Cl C C
H
O
O
H11002
H
H9254H11002 H9254H11001
Chloroacetate anion is
stabilized by electron-
withdrawing effect of
chlorine.
OO
H11002
S
O
H11002
Na
H11001
H11002
O
2H11001
Sodium lauryl sulfate
(sodium dodecyl sulfate)
19.6 Substituents and Acid Strength 745
Compare the electrosta-
tic potential maps of sodium lau-
ryl sulfate and sodium stearate
on Learning By Modeling.
Learning By Modeling
contains molecular models of
CH
3
CO
2
H11002
(acetate) and Cl
3
CCO
2
H11002
(trichloroacetate). Compare
these two ions with respect to
the amount of negative charge
on their oxygens.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Inductive effects fall off rapidly as the number of H9268 bonds between the carboxyl
group and the substituent increases. Consequently, the acid-strengthening effect of a halo-
gen decreases as it becomes more remote from the carboxyl group:
PROBLEM 19.4 Which is the stronger acid in each of the following pairs?
(a) (CH
3
)
3
CCH
2
CO
2
H or (CH
3
)
3
N
H11001
CH
2
CO
2
H
(b)
(c)
(d) CH
3
CH
2
CH
2
CO
2
HCH
3
SCH
2
CO
2
H
O
X
X
O
or
CH
3
CCO
2
H
O
X
CH
2
?CHCO
2
Hor
CH
3
CH
2
CO
2
HCH
3
CHCO
2
H
OH
W
or
ClCH
2
CO
2
H
Chloroacetic acid
K
a
H11005 1.4 H11003 10
H110023
pK
a
H11005 2.9
ClCH
2
CH
2
CO
2
H
3-Chloropropanoic acid
K
a
H11005 1.0 H11003 10
H110024
pK
a
H11005 4.0
ClCH
2
CH
2
CH
2
CO
2
H
4-Chlorobutanoic acid
K
a
H11005 3.0 H11003 10
H110025
pK
a
H11005 4.5
746 CHAPTER NINETEEN Carboxylic Acids
TABLE 19.2 Effect of Substituents on Acidity of Carboxylic Acids
Name of acid
*In water at 25°C.
Acetic acid
Standard of comparison.
Alkyl substituents have a negligible effect on acidity.
Propanoic acid
2-Methylpropanoic acid
2,2-Dimethylpropanoic acid
Heptanoic acid
H9251-Halogen substituents increase acidity.
Fluoroacetic acid
Chloroacetic acid
Bromoacetic acid
Dichloroacetic acid
Trichloroacetic acid
Ionization
constant K
a
*
1.8 H11003 10
H110025
1.3 H11003 10
H110025
1.6 H11003 10
H110025
0.9 H11003 10
H110025
1.3 H11003 10
H110025
2.5 H11003 10
H110023
1.4 H11003 10
H110023
1.4 H11003 10
H110023
5.0 H11003 10
H110022
1.3 H11003 10
H110021
2.7 H11003 10
H110024
3.4 H11003 10
H110023
2.1 H11003 10
H110022
pK
a
4.7
4.9
4.8
5.1
4.9
2.6
2.9
2.9
1.3
0.9
3.6
2.5
1.7
Structure
CH
3
CO
2
H
CH
3
CH
2
CO
2
H
(CH
3
)
2
CHCO
2
H
(CH
3
)
3
CCO
2
H
CH
3
(CH
2
)
5
CO
2
H
FCH
2
CO
2
H
ClCH
2
CO
2
H
BrCH
2
CO
2
H
Cl
2
CHCO
2
H
Cl
3
CCO
2
H
CH
3
OCH
2
CO
2
H
NPCCH
2
CO
2
H
O
2
NCH
2
CO
2
H
Electron-attracting groups increase acidity.
Methoxyacetic acid
Cyanoacetic acid
Nitroacetic acid
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
SAMPLE SOLUTION (a) Think of the two compounds as substituted derivatives
of acetic acid. A tert-butyl group is slightly electron-releasing and has only a mod-
est effect on acidity. The compound (CH
3
)
3
CCH
2
CO
2
H is expected to have an acid
strength similar to that of acetic acid. A trimethylammonium substituent, on the
other hand, is positively charged and is a powerful electron-withdrawing sub-
stituent. The compound (CH
3
)
3
N
H11001
CH
2
CO
2
H is expected to be a much stronger acid
than (CH
3
)
3
CCH
2
CO
2
H. The measured ionization constants, shown as follows, con-
firm this prediction.
Another proposal advanced to explain the acid-strengthening effect of polar sub-
stituents holds that the electron-withdrawing effect is transmitted through the water mol-
ecules that surround the carboxylate ion rather than through successive polarization of
H9268 bonds. This is referred to as a field effect. Both field and inductive contributions to
the polar effect tend to operate in the same direction, and it is believed that both are
important.
It is a curious fact that substituents affect the entropy of ionization more than they
do the enthalpy term in the expression
H9004G° H11005 H9004H° H11002 TH9004S°
The enthalpy term H9004H° is close to zero for the ionization of most carboxylic acids,
regardless of their strength. The free energy of ionization H9004G° is dominated by the
H11002TH9004S° term. Ionization is accompanied by an increase in solvation forces, leading to a
decrease in the entropy of the system; H9004S° is negative, and H11002TH9004S° is positive. Anions
that incorporate substituents capable of dispersing negative charge impose less order on
the solvent (water), and less entropy is lost in their production.
19.7 IONIZATION OF SUBSTITUTED BENZOIC ACIDS
A considerable body of data is available on the acidity of substituted benzoic acids. Ben-
zoic acid itself is a somewhat stronger acid than acetic acid. Its carboxyl group is attached
to an sp
2
-hybridized carbon and ionizes to a greater extent than one that is attached to
an sp
3
-hybridized carbon. Remember, carbon becomes more electron-withdrawing as its
s character increases.
PROBLEM 19.5 What is the most acidic neutral molecule characterized by the
formula C
3
H
x
O
2
?
Table 19.3 lists the ionization constants of some substituted benzoic acids. The
largest effects are observed when strongly electron-withdrawing substituents are ortho to
CH
3
CO
2
H
Acetic acid
K
a
H11005 1.8 H11003 10
H110025
(pK
a
4.8)
Acrylic acid
K
a
H11005 5.5 H11003 10
H110025
(pK
a
4.3)
CH
2
CHCO
2
H
Benzoic acid
K
a
H11005 6.3 H11003 10
H110025
(pK
a
4.2)
CO
2
H
(CH
3
)
3
CCH
2
CO
2
H
Weaker acid
K
a
H11005 5 H11003 10
H110026
(pK
a
H11005 5.3)
(CH
3
)
3
NCH
2
CO
2
H
H11001
Stronger acid
K
a
H11005 1.5 H11003 10
H110022
(pK
a
H11005 1.8)
19.7 Ionization of Substituted Benzoic Acids 747
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
the carboxyl group. An o-nitro substituent, for example, increases the acidity of benzoic
acid 100-fold. Substituent effects are small at positions meta and para to the carboxyl
group. In those cases the pK
a
values are clustered in the range 3.5–4.5.
19.8 DICARBOXYLIC ACIDS
Separate ionization constants, designated K
1
and K
2
, respectively, characterize the two
successive ionization steps of a dicarboxylic acid.
The first ionization constant of dicarboxylic acids is larger than K
a
for monocar-
boxylic analogs. One reason is statistical. There are two potential sites for ionization
rather than one, making the effective concentration of carboxyl groups twice as large.
Furthermore, one carboxyl group acts as an electron-withdrawing group to facilitate dis-
sociation of the other. This is particularly noticeable when the two carboxyl groups are
separated by only a few bonds. Oxalic and malonic acid, for example, are several orders
of magnitude stronger than simple alkyl derivatives of acetic acid. Heptanedioic acid, in
which the carboxyl groups are well separated from each other, is only slightly stronger
than acetic acid.
HO
2
CCO
2
H
Oxalic acid
K
1
6.5 H11003 10
H110022
(pK
1
1.2)
HO
2
CCH
2
CO
2
H
Malonic acid
K
1
1.4 H11003 10
H110023
(pK
1
2.8)
HO
2
C(CH
2
)
5
CO
2
H
Heptanedioic acid
K
1
3.1 H11003 10
H110025
(pK
1
4.3)
H
H11001
H11001 K
1
H11005 6.5 H11003 10
H110022
pK
1
H11005 1.2
Oxalic acid
HOC COH
O O
Hydrogen oxalate
(monoanion)
HOC CO
H11002
O O
K
1
H
H11001
H11001 K
2
H11005 5.3 H11003 10
H110025
pK
2
H11005 4.3
Oxalate
(Dianion)
H11002
OC CO
H11002
O O
Hydrogen oxalate
(monoanion)
HOC CO
H11002
O O
K
2
748 CHAPTER NINETEEN Carboxylic Acids
TABLE 19.3 Acidity of Some Substituted Benzoic Acids
Substituent in
XC
6
H
4
CO
2
H
*In water at 25°C.
1. H
2. CH
3
3. F
4. Cl
5. Br
6. I
7. CH
3
O
8. O
2
N
Ortho
6.3 H11003 10
H110025
(4.2)
1.2 H11003 10
H110024
(3.9)
5.4 H11003 10
H110024
(3.3)
1.2 H11003 10
H110023
(2.9)
1.4 H11003 10
H110023
(2.8)
1.4 H11003 10
H110023
(2.9)
8.1 H11003 10
H110025
(4.1)
6.7 H11003 10
H110023
(2.2)
Meta
6.3 H11003 10
H110025
(4.2)
5.3 H11003 10
H110025
(4.3)
1.4 H11003 10
H110024
(3.9)
1.5 H11003 10
H110024
(3.8)
1.5 H11003 10
H110024
(3.8)
1.4 H11003 10
H110024
(3.9)
8.2 H11003 10
H110025
(4.1)
3.2 H11003 10
H110024
(3.5)
Para
6.3 H11003 10
H110025
(4.2)
4.2 H11003 10
H110025
(4.4)
7.2 H11003 10
H110025
(4.1)
1.0 H11003 10
H110024
(4.0)
1.1 H11003 10
H110024
(4.0)
9.2 H11003 10
H110025
(4.0)
3.4 H11003 10
H110025
(4.5)
3.8 H11003 10
H110024
(3.4)
K
a
(pK
a
)* for different positions of substituent X
Oxalic acid is poisonous and
occurs naturally in a number
of plants including sorrel and
begonia. It is a good idea to
keep houseplants out of the
reach of small children, who
might be tempted to eat the
leaves or berries.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.9 CARBONIC ACID
Through an accident of history, the simplest dicarboxylic acid, carbonic acid, ,
is not even classified as an organic compound. Because many minerals are carbonate
salts, nineteenth-century chemists placed carbonates, bicarbonates, and carbon dioxide in
the inorganic realm. Nevertheless, the essential features of carbonic acid and its salts are
easily understood on the basis of our knowledge of carboxylic acids.
Carbonic acid is formed when carbon dioxide reacts with water. Hydration of car-
bon dioxide is far from complete, however. Almost all the carbon dioxide that is dis-
solved in water exists as carbon dioxide; only 0.3% of it is converted to carbonic acid.
Carbonic acid is a weak acid and ionizes to a small extent to bicarbonate ion.
The equilibrium constant for the overall reaction is related to an apparent equilibrium
constant K
1
for carbonic acid ionization by the expression
K
1
H11005H110054.3 H11003 10
H110027
pK
a
H11005 6.4
These equations tell us that the reverse process, proton transfer from acids to bicarbon-
ate to form carbon dioxide, will be favorable when K
a
of the acid exceeds 4.3 H11003 10
H110027
(pK
a
H11021 6.4). Among compounds containing carbon, hydrogen, and oxygen, only car-
boxylic acids are acidic enough to meet this requirement. They dissolve in aqueous
sodium bicarbonate with the evolution of carbon dioxide. This behavior is the basis of
a qualitative test for carboxylic acids.
PROBLEM 19.6 The value cited for the “apparent K
1
” of carbonic acid, 4.3 H11003
10
H110027
, is the one normally given in reference books. It is determined by measur-
ing the pH of water to which a known amount of carbon dioxide has been added.
When we recall that only 0.3% of carbon dioxide is converted to carbonic acid in
water, what is the “true K
1
” of carbonic acid?
Carbonic anhydrase is an enzyme that catalyzes the hydration of carbon dioxide
to bicarbonate. The uncatalyzed hydration of carbon dioxide is too slow to be effective
in transporting carbon dioxide from the tissues to the lungs, and so animals have devel-
oped catalysts to speed this process. The activity of carbonic anhydrase is remarkable;
it has been estimated that one molecule of this enzyme can catalyze the hydration of
3.6 H11003 10
7
molecules of carbon dioxide per minute.
As with other dicarboxylic acids, the second ionization constant of carbonic acid
is far smaller than the first.
The value of K
2
is 5.6 H11003 10
H1100211
(pK
a
10.2). Bicarbonate is a weaker acid than carboxylic
acids but a stronger acid than water and alcohols.
H
H11001
H11001
Carbonate ion
H11002
OCO
H11002
O
Bicarbonate ion
HOCO
H11002
O
K
2
[H
H11001
][HCO
3
H11002
]
[CO
2
]
H
H11001
H11001
Carbonic
acid
HOCOH
O
Bicarbonate
ion
HOCO
H11002
O
CO
2
Carbon
dioxide
H11001
Water
H
2
O
HOCOH
O
X
19.9 Carbonic Acid 749
The systematic name for bi-
carbonate ion is hydrogen
carbonate. Thus, the system-
atic name for sodium bicar-
bonate (NaHCO
3
) is sodium
hydrogen carbonate.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.10 SOURCES OF CARBOXYLIC ACIDS
Many carboxylic acids were first isolated from natural sources and were given names
based on their origin. Formic acid (Latin formica, “ant”) was obtained by distilling ants.
Since ancient times acetic acid (Latin acetum, “vinegar”) has been known to be present
in wine that has turned sour. Butyric acid (Latin butyrum, “butter”) contributes to the
odor of both rancid butter and ginkgo berries, and lactic acid (Latin lac, “milk”) has
been isolated from sour milk.
Although these humble origins make interesting historical notes, in most cases the
large-scale preparation of carboxylic acids relies on chemical synthesis. Virtually none
of the 3 H11003 10
9
lb of acetic acid produced in the United States each year is obtained from
vinegar. Instead, most industrial acetic acid comes from the reaction of methanol with
carbon monoxide.
The principal end use of acetic acid is in the production of vinyl acetate for paints and
adhesives.
The carboxylic acid produced in the greatest amounts is 1,4-benzenedicarboxylic
acid (terephthalic acid). About 5 H11003 10
9
lb/year is produced in the United States as a
starting material for the preparation of polyester fibers. One important process converts
p-xylene to terephthalic acid by oxidation with nitric acid:
You will recognize the side-chain oxidation of p-xylene to terephthalic acid as a
reaction type discussed previously (Section 11.13). Examples of other reactions encoun-
tered earlier that can be applied to the synthesis of carboxylic acids are collected in Table
19.4.
The examples in the table give carboxylic acids that have the same number of car-
bon atoms as the starting material. The reactions to be described in the next two sec-
tions permit carboxylic acids to be prepared by extending a chain by one carbon atom
and are of great value in laboratory syntheses of carboxylic acids.
19.11 SYNTHESIS OF CARBOXYLIC ACIDS BY THE CARBOXYLATION
OF GRIGNARD REAGENTS
We’ve seen how Grignard reagents add to the carbonyl group of aldehydes, ketones, and
esters. Grignard reagents react in much the same way with carbon dioxide to yield mag-
nesium salts of carboxylic acids. Acidification converts these magnesium salts to the
desired carboxylic acids.
HNO
3
CH
3
CH
3
p-Xylene
HO
2
CCO
2
H
1,4-Benzenedicarboxylic acid
(terephthalic acid)
CH
3
OH
Methanol
H11001 CO
Carbon
monoxide
cobalt or
rhodium catalyst
heat, pressure
CH
3
CO
2
H
Acetic acid
750 CHAPTER NINETEEN Carboxylic Acids
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Overall, the carboxylation of Grignard reagents transforms an alkyl or aryl halide
to a carboxylic acid in which the carbon skeleton has been extended by one carbon atom.
R
MgX
C
H9254H11002
H9254H11001
O
O
Grignard reagent
acts as a nucleophile
toward carbon dioxide
RCOMgX
O
Halomagnesium
carboxylate
H
H11001
H
2
O
Carboxylic
acid
RCOH
O
19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents 751
TABLE 19.4 Summary of Reactions Discussed in Earlier Chapters That Yield Carboxylic Acids
Reaction (section) and comments
Side-chain oxidation of alkylbenzenes (Section 11.13) A
primary or secondary alkyl side chain on an aromatic
ring is converted to a carboxyl group by reaction with a
strong oxidizing agent such as potassium permanga-
nate or chromic acid.
Oxidation of aldehydes (Section 17.15) Aldehydes are
particularly sensitive to oxidation and are converted to
carboxylic acids by a number of oxidizing agents,
including potassium permanganate and chromic acid.
Oxidation of primary alcohols (Section 15.10) Potassi-
um permanganate and chromic acid convert primary
alcohols to carboxylic acids by way of the correspond-
ing aldehyde.
General equation and specific example
Alkylbenzene
ArCHR
2
ArCO
2
H
Arenecarboxylic acid
KMnO
4
or
K
2
Cr
2
O
7
, H
2
SO
4
Primary
alcohol
RCH
2
OH RCO
2
H
Carboxylic acid
KMnO
4
or
K
2
Cr
2
O
7
, H
2
SO
4
2-tert-Butyl-3,3-
dimethyl-1-butanol
(CH
3
)
3
CCHC(CH
3
)
3
W
CH
2
OH
2-tert-Butyl-3,3-
dimethylbutanoic acid
(82%)
(CH
3
)
3
CCHC(CH
3
)
3
W
CO
2
H
H
2
CrO
4
H
2
O, H
2
SO
4
1. KMnO
4
, HO
H11002
2. H
H11001
OCH
3
CH
3
NO
2
3-Methoxy-4-
nitrotoluene
OCH
3
CO
2
H
NO
2
3-Methoxy-4-nitrobenzoic
acid (100%)
RCO
2
H
Carboxylic acidAldehyde
RCH
O
X
oxidizing
agent
K
2
Cr
2
O
7
H
2
SO
4
, H
2
O
CO
2
H
O
Furan-2-carboxylic acid
(furoic acid) (75%)
CH
O
O
Furan-2-carbaldehyde
(furfural)
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
The major limitation to this procedure is that the alkyl or aryl halide must not bear sub-
stituents that are incompatible with Grignard reagents, such as OH, NH, SH, or C?O.
19.12 SYNTHESIS OF CARBOXYLIC ACIDS BY THE PREPARATION
AND HYDROLYSIS OF NITRILES
Primary and secondary alkyl halides may be converted to the next higher carboxylic acid
by a two-step synthetic sequence involving the preparation and hydrolysis of nitriles.
Nitriles, also known as alkyl cyanides, are prepared by nucleophilic substitution.
The reaction is of the S
N
2 type and works best with primary and secondary alkyl
halides. Elimination is the only reaction observed with tertiary alkyl halides. Aryl and
vinyl halides do not react. Dimethyl sulfoxide is the preferred solvent for this reaction,
but alcohols and water–alcohol mixtures have also been used.
Once the cyano group has been introduced, the nitrile is subjected to hydrolysis.
Usually this is carried out in aqueous acid at reflux.
NaCN
DMSO
H
2
O,
H
2
SO
4
heat
CH
2
Cl
Benzyl chloride
CH
2
CN
Benzyl cyanide (92%)
CH
2
COH
O
Phenylacetic acid (77%)
H11001H11001 H11001RC N
Nitrile
2H
2
O
Water
NH
4
H11001
Ammonium
ion
H
H11001
heat
RCOH
O
Carboxylic
acid
X R
Primary or
secondary alkyl
halide
H11001 CN
H11002
Cyanide ion
RC N
Nitrile
(alkyl cyanide)
H11001 X
H11002
Halide ion
CH
3
CHCH
2
CH
3
Cl
2-Chlorobutane
CH
3
CHCH
2
CH
3
CO
2
H
2-Methylbutanoic acid
(76–86%)
1. Mg, diethyl ether
2. CO
2
3. H
3
O
H11001
1. Mg, diethyl ether
2. CO
2
3. H
3
O
H11001
Br
CH
3
9-Bromo-10-methylphenanthrene
CO
2
H
CH
3
10-Methylphenanthrene-9-
carboxylic acid (82%)
752 CHAPTER NINETEEN Carboxylic Acids
The mechanism of nitrile hy-
drolysis will be described in
Section 20.19.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Dicarboxylic acids have been prepared from dihalides by this method:
PROBLEM 19.7 Of the two procedures just described, preparation and carboxy-
lation of a Grignard reagent or formation and hydrolysis of a nitrile, only one is
appropriate to each of the following RX → RCO
2
H conversions. Identify the cor-
rect procedure in each case, and specify why the other will fail.
(a) Bromobenzene → benzoic acid
(b) 2-Chloroethanol → 3-hydroxypropanoic acid
(c) tert-Butyl chloride → 2,2-dimethylpropanoic acid
SAMPLE SOLUTION (a) Bromobenzene is an aryl halide and is unreactive toward
nucleophilic substitution by cyanide ion. The route C
6
H
5
Br → C
6
H
5
CN → C
6
H
5
CO
2
H
fails because the first step fails. The route proceeding through the Grignard
reagent is perfectly satisfactory and appears as an experiment in a number of
introductory organic chemistry laboratory texts.
Nitrile groups in cyanohydrins are hydrolyzed under conditions similar to those of
alkyl cyanides. Cyanohydrin formation followed by hydrolysis provides a route to the
preparation of H9251-hydroxy carboxylic acids.
19.13 REACTIONS OF CARBOXYLIC ACIDS: A REVIEW AND A
PREVIEW
The most apparent chemical property of carboxylic acids, their acidity, has already been
examined in earlier sections of this chapter. Three reactions of carboxylic acids—con-
version to acyl chlorides, reduction, and esterification—have been encountered in previ-
ous chapters and are reviewed in Table 19.5. Acid-catalyzed esterification of carboxylic
acids is one of the fundamental reactions of organic chemistry, and this portion of the
chapter begins with an examination of the mechanism by which it occurs. Later, in Sec-
tions 19.16 and 19.17, two new reactions of carboxylic acids that are of synthetic value
will be described.
1. NaCN
2. H
H11001
H
2
O, HCl
heat
CH
3
CCH
2
CH
2
CH
3
OH
CN
2-Pentanone
cyanohydrin
CH
3
CCH
2
CH
2
CH
3
OH
CO
2
H
2-Hydroxy-2-methyl-
pentanoic acid
(60% from 2-pentanone)
CH
3
CCH
2
CH
2
CH
3
O
2-Pentanone
Br
Bromobenzene
MgBr
Phenylmagnesium
bromide
CO
2
H
Benzoic acid
Mg
diethyl
ether
1. CO
2
2. H
3
O
H11001
BrCH
2
CH
2
CH
2
Br
1,3-Dibromopropane
NCCH
2
CH
2
CH
2
CN
1,5-Pentanedinitrile
(77–86%)
NaCN
H
2
O
H
2
O, HCl
heat
HOCCH
2
CH
2
CH
2
COH
O O
1,5-Pentanedioic acid
(83–85%)
19.13 Reactions of Carboxylic Acids: A Review and a Preview 753
Recall the preparation of
cyanohydrins in Section 17.7.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.14 MECHANISM OF ACID-CATALYZED ESTERIFICATION
An important question about the mechanism of acid-catalyzed esterification concerns the
origin of the alkoxy oxygen. For example, does the methoxy oxygen in methyl benzoate
come from methanol, or is it derived from benzoic acid?
The answer to this question is critical because it tells us whether the carbon–oxygen
bond of the alcohol or a carbon–oxygen of the carboxylic acid is broken during the ester-
ification.
COCH
3
O Is this the oxygen originally present
in benzoic acid, or is it the
oxygen of methanol?
754 CHAPTER NINETEEN Carboxylic Acids
TABLE 19.5 Summary of Reactions of Carboxylic Acids Discussed in Earlier Chapters
Reaction (section) and comments
Formation of acyl chlorides (Section 12.7)
Thionyl chloride reacts with carboxylic acids
to yield acyl chlorides.
Esterification (Section 15.8) In the presence
of an acid catalyst, carboxylic acids and
alcohols react to form esters. The reaction is
an equilibrium process but can be driven to
favor the ester by removing the water that
is formed.
Lithium aluminum hydride reduction (Sec-
tion 15.3) Carboxylic acids are reduced to
primary alcohols by the powerful reducing
agent lithium aluminum hydride.
General equation and specific example
Carboxylic
acid
RCO
2
H SOCl
2
Thionyl
chloride
SO
2
Sulfur
dioxide
H11001H11001HCl
Hydrogen
chloride
H11001RCCl
O
X
Acyl
chloride
Carboxylic
acid
RCO
2
H
Ester
RCORH11032
O
X
RH11032OH
Alcohol
H
2
O
Water
H11001H11001
H
H11001
SOCl
2
heat
CH
2
CO
2
H
CH
3
O
m-Methoxyphenylacetic acid m-Methoxyphenylacetyl chloride
(85%)
CH
2
CCl
O
X
CH
3
O
1. LiAlH
4
,
diethyl ether
2. H
2
O
CO
2
HF
3
C
p-(Trifluoromethyl)benzoic acid
CH
2
OHF
3
C
p-(Trifluoromethyl)benzyl
alcohol (96%)
Primary alcohol
RCH
2
OHRCO
2
H
Carboxylic
acid
1. LiAlH
4
, diethyl ether
2. H
2
O
H11001
H
2
SO
4
CO
2
H
Benzoic acid
CH
3
OH
Methanol
COCH
3
O
Methyl benzoate
(70%)
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
A clear-cut answer was provided by Irving Roberts and Harold C. Urey of Colum-
bia University in 1938. They prepared methanol that had been enriched in the mass-18
isotope of oxygen. When this sample of methanol was esterified with benzoic acid, the
methyl benzoate product contained all the
18
O label that was originally present in the
methanol.
The results of the Roberts–Urey experiment tell us that the C±O bond of the alco-
hol is preserved during esterification. The oxygen that is lost as a water molecule must
come from the carboxylic acid.
A mechanism consistent with these facts is presented in Figure 19.6. The six steps
are best viewed as a combination of two distinct stages. Formation of a tetrahedral
intermediate characterizes the first stage (steps 1–3), and dissociation of this tetrahedral
intermediate characterizes the second (steps 4–6).
The species connecting the two stages is called a tetrahedral intermediate because
the hybridization at carbon has changed from sp
2
in the carboxylic acid to sp
3
in the
intermediate before returning to sp
2
in the ester product. The tetrahedral intermediate is
formed by nucleophilic addition of an alcohol to a carboxylic acid and is analogous to
a hemiacetal formed by nucleophilic addition of an alcohol to an aldehyde or a ketone.
The three steps that lead to the tetrahedral intermediate in the first stage of esterification
are analogous to those in the mechanism for acid-catalyzed nucleophilic addition of an
alcohol to an aldehyde or a ketone. The tetrahedral intermediate cannot be isolated. It is
unstable under the conditions of its formation and undergoes acid-catalyzed dehydration
to form the ester.
Notice that the oxygen of methanol becomes incorporated into the methyl benzoate
product according to the mechanism outlined in Figure 19.6, as the observations of the
Roberts–Urey experiment require it to be.
Notice, too, that the carbonyl oxygen of the carboxylic acid is protonated in the
first step and not the hydroxyl oxygen. The species formed by protonation of the car-
bonyl oxygen is more stable, because it is stabilized by electron delocalization. The pos-
itive charge is shared equally by both oxygens.
Electron delocalization
in carbonyl-protonated
benzoic acid
C
6
H
5
C
OH
OH
H11001
C
6
H
5
C
H11001
OH
OH
Benzoic acid
C
6
H
5
C
OH
O
Methyl
benzoate
C
6
H
5
C
OCH
3
O
H11001H11001
steps 1–3
H
H11001
steps 4–6
H
H11001
Methanol
CH
3
OH
Water
H
2
OC
6
H
5
C OCH
3
OH
OH
Tetrahedral
intermediate
H
H11001
C
6
H
5
COH
O
Benzoic acid
C
6
H
5
COCH
3
O
18
O-enriched
methyl benzoate
H11001 CH
3
OH
18
O-enriched
methanol
H11001 H
2
O
Water
19.14 Mechanism of Acid-Catalyzed Esterification 755
In this equation, the red-
highlighted O signifies oxy-
gen enriched in its mass -18
isotope; analysis of isotopic
enrichment was performed
by mass spectrometry.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Protonation of the hydroxyl oxygen, on the other hand, yields a less stable cation:
Localized positive
charge in hydroxyl-
protonated benzoic
acid
C
6
H
5
C
O
O
H
H11001
H
756 CHAPTER NINETEEN Carboxylic Acids
Step 2: Protonation of the carboxylic acid increases the positive character of its
carbonyl group. A molecule of the alcohol acts as a nucleophile and attacks
the carbonyl carbon.
H
C
6
H
5
C H11001
The overall reaction:
Benzoic acid
OH
O
H
CH
3
Methanol
O
Step 1: The carboxylic acid is protonated on its carbonyl oxygen. The proton donor
shown in the equation for this step is an alkyloxonium ion formed by proton
transfer from the acid catalyst to the alcohol.
H
H11001
C
6
H
5
C H11001
Methyl benzoate
OCH
3
O
H
Water
O
C
6
H
5
C
H11001
H
Conjugate acid
of benzoic acid
O
H
C
6
H
5
C H11001
H
Benzoic acid
O
O
H
CH
3
CH
3
Methyloxonium ion
H
H11001
O
H11001
O
H11001
O
H
CH
3
O
Methanol
Step 3: The oxonium ion formed in step 2 loses a proton to give the tetrahedral
intermediate in its neutral form. This step concludes the first stage in the
mechanism.
H11001
H
Methanol Tetrahedral
intermediate
OH
OH
OCH
3
CH
3
Protonated form of
tetrahedral intermediate
OH
OH
H
H11001
H
Methyloxonium
ion
H
C
6
H
5
C
C
6
H
5
CC
6
H
5
C
C
6
H
5
C
H
Conjugate acid
of benzoic acid
O
H11001
O H
H
CH
3
CH
3
CH
3
Methanol
O
O
Protonated form of
tetrahedral intermediate
OH
OH
H
H11001
O
H11001
O
H11001
X
X
X
X
X
—Cont.
FIGURE 19.6 The mecha-
nism of acid-catalyzed ester-
ification of benzoic acid
with methanol.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
The positive charge in this cation cannot be shared by the two oxygens; it is localized
on one of them. Since protonation of the carbonyl oxygen gives a more stable cation,
that cation is formed preferentially.
PROBLEM 19.8 When benzoic acid is allowed to stand in water enriched in
18
O,
the isotopic label becomes incorporated into the benzoic acid. The reaction is cat-
alyzed by acids. Suggest an explanation for this observation.
In the next chapter the three elements of the mechanism just described will be seen
again as part of the general theme that unites the chemistry of carboxylic acid deriva-
tives. These elements are
1. Activation of the carbonyl group by protonation of the carbonyl oxygen
2. Nucleophilic addition to the protonated carbonyl to form a tetrahedral intermediate
3. Elimination from the tetrahedral intermediate to restore the carbonyl group
This sequence is one of the fundamental mechanistic patterns of organic chemistry.
19.14 Mechanism of Acid-Catalyzed Esterification 757
Step 4: The second stage begins with protonation of the tetrahedral intermediate on
one of its hydroxyl oxygens.
Tetrahedral
intermediate
OH
OH
H11001
Methyloxonium
ion
H
H
Hydroxyl-protonated
tetrahedral intermediate
H11001
O
OH
H11001
H
Methanol
Step 5: This intermediate loses a molecule of water to give the protonated form of
the ester.
H
Hydroxyl-protonated
tetrahedral intermediate
H11001
O
OH
H
H11001
Conjugate acid
of methyl benzoate
H
H
Water
O
H11001
O
H11001
OH
Step 6: Deprotonation of the species formed in step 5 gives the neutral form of the
ester product.
H
Methyloxonium
ion
H
Methyl
benzoate
O
H11001
H
Methanol
H11001
Conjugate acid
of methyl benzoate
H11001
O H
C
6
H
5
C
C
6
H
5
C
C
6
H
5
CC
6
H
5
C
OCH
3
OCH
3
CH
3
CH
3
C
6
H
5
C
C
6
H
5
C
OCH
3
CH
3
H
H11001
O
H
CH
3
O
OCH
3
OCH
3
OCH
3
O
X
XX
(Continued)
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.15 INTRAMOLECULAR ESTER FORMATION: LACTONES
Hydroxy acids, compounds that contain both a hydroxyl and a carboxylic acid function,
have the capacity to form cyclic esters called lactones. This intramolecular esterification
takes place spontaneously when the ring that is formed is five membered or six
membered. Lactones that contain a five-membered cyclic ester are referred to as
H9253-lactones; their six-membered analogs are known as H9254-lactones.
A lactone is named by replacing the -oic acid ending of the parent carboxylic acid
by -olide and identifying its oxygenated carbon by number. This system is illustrated in
HOCH
2
CH
2
CH
2
COH
O
4-Hydroxybutanoic acid
O
O
4-Butanolide
HOCH
2
CH
2
CH
2
CH
2
COH
O
5-Hydroxypentanoic acid
O
O
5-Pentanolide
758 CHAPTER NINETEEN Carboxylic Acids
CH
3
(an intermediate in the
biosynthesis of terpenes and
steroids)
OH
CH
2
O
O
CH
3
OH
O
O
O
O
CH CH
2
15-Pentadecanolide
Vernolepin
(an odor-enhancing substance
used in perfume)
(a tumor-inhibitory substance
that incorporates both a
H9253-lactone and a H9254-
lactone into its tricyclic
framework)
O
CH
3
N(CH
3
)
2
O
O
O
CH
3
OH
CH
3
O
H
3
C
OH
CH
3
O
CH
3
H
3
C
HO
CH
3
CH
3
OH
O
O
O
Erythromycin
(a macrolide antibiotic; drug production is by fermentation
processes, but the laboratory synthesis of this complex
substance has been achieved)
Mevalonolactone
CH
2
CH
3
O
FIGURE 19.7 Some
naturally occurring lactones.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
the lactones shown in the preceding equations. Both 4-butanolide and 5-pentanolide are
better known by their common names, H9253-butyrolactone and H9254-valerolactone, respectively,
and these two common names are permitted by the IUPAC rules.
Reactions that are expected to produce hydroxy acids often yield the derived lac-
tones instead if a five- or six-membered ring can be formed.
Many natural products are lactones, and it is not unusual to find examples in which
the ring size is rather large. A few naturally occurring lactones are shown in Figure 19.7.
The macrolide antibiotics, of which erythromycin is one example, are macrocyclic (large-
ring) lactones. The lactone ring of erythromycin is 14 membered.
PROBLEM 19.9 Write the structure of the hydroxy acid corresponding to each
of the following lactones. The structure of each lactone is given in Figure 19.7.
(a) Mevalonolactone
(b) Pentadecanolide
(c) Vernolepin
SAMPLE SOLUTION (a) The ring oxygen of the lactone is derived from the
hydroxyl group of the hydroxy acid, whereas the carbonyl group corresponds to
that of the carboxyl function. To identify the hydroxy acid, disconnect the O±C(O)
bond of the ester.
Lactones whose rings are three or four membered (H9251-lactones and H9252-lactones) are
very reactive, making their isolation difficult. Special methods are normally required for
the laboratory synthesis of small-ring lactones as well as those that contain rings larger
than six membered.
19.16 H9251 HALOGENATION OF CARBOXYLIC ACIDS: THE
HELL–VOLHARD–ZELINSKY REACTION
Esterification of carboxylic acids involves nucleophilic addition to the carbonyl group as
a key step. In this respect the carbonyl group of a carboxylic acid resembles that of an
aldehyde or a ketone. Do carboxylic acids resemble aldehydes and ketones in other ways?
Do they, for example, form enols, and can they be halogenated at their H9251-carbon atom
via an enol in the way that aldehydes and ketones can?
The enol content of a carboxylic acid is far less than that of an aldehyde or ketone,
and introduction of a halogen substituent at the H9251-carbon atom requires a different set
OO
H
3
C OH
Mevalonolactone
(disconnect bond indicated)
HOCH
2
CH
2
CCH
2
C
CH
3
OH
OH
O
Mevalonic acid
19.16 H9251 Halogenation of Carboxylic Acids: The Hell–Volhard–Zelinsky Reaction 759
viaCH
3
CCH
2
CH
2
CH
2
COH
O O
5-Oxohexanoic acid
1. NaBH
4
2. H
2
O, H
H11001
H
3
C
O
O
5-Hexanolide (78%)
CH
3
CHCH
2
CH
2
CH
2
COH
OH
O
5-Hydroxyhexanoic acid
The compound anisatin is an
example of a naturally occur-
ring H9252-lactone. Its isolation
and structure determination
were described in the journal
Tetrahedron Letters (1982),
p. 5111.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
of reaction conditions. Bromination is the reaction that is normally carried out, and the
usual procedure involves treatment of the carboxylic acid with bromine in the presence
of a small amount of phosphorus trichloride as a catalyst.
This method of H9251 bromination of carboxylic acids is called the Hell–Volhard–
Zelinsky reaction. This reaction is sometimes carried out by using a small amount of
phosphorus instead of phosphorus trichloride. Phosphorus reacts with bromine to yield
phosphorus tribromide as the active catalyst under these conditions.
The Hell–Volhard–Zelinsky reaction is of synthetic value in that the H9251 halogen can
be displaced by nucleophilic substitution:
A standard method for the preparation of an H9251-amino acid uses H9251-bromo carboxylic acids
as the substrate and aqueous ammonia as the nucleophile:
PROBLEM 19.10 H9251-lodo acids are not normally prepared by direct iodination of
carboxylic acids under conditions of the Hell–Volhard–Zelinsky reaction. Show how
you could convert octadecanoic acid to its 2-iodo derivative by an efficient
sequence of reactions.
19.17 DECARBOXYLATION OF MALONIC ACID AND RELATED
COMPOUNDS
The loss of a molecule of carbon dioxide from a carboxylic acid is known as decar-
boxylation.
RCO
2
H
Carboxylic acid
RH
Alkane
CO
2
Carbon dioxide
H11001
(CH
3
)
2
CHCH
2
CO
2
H
3-Methylbutanoic
acid
Br
2
PCl
3
NH
3
H
2
O
(CH
3
)
2
CHCHCO
2
H
Br
2-Bromo-3-methylbutanoic
acid (88%)
(CH
3
)
2
CHCHCO
2
H
NH
2
2-Amino-3-methylbutanoic
acid (48%)
CH
3
CH
2
CH
2
CO
2
H
Butanoic
acid
Br
2
P
K
2
CO
3
H
2
O, heat
CH
3
CH
2
CHCO
2
H
Br
2-Bromobutanoic
acid (77%)
CH
3
CH
2
CHCO
2
H
OH
2-Hydroxybutanoic
acid (69%)
R
2
CCO
2
H
H
Carboxylic acid
H11001 Br
2
Bromine
PCl
3
R
2
CCO
2
H
Br
H9251-Bromo
carboxylic acid
H11001 HBr
Hydrogen
bromide
Br
2
, PCl
3
benzene, 80°C
CH
2
COH
O
Phenylacetic acid
CHCOH
O
Br
H9251-Bromophenylacetic acid
(60–62%)
760 CHAPTER NINETEEN Carboxylic Acids
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Decarboxylation of simple carboxylic acids takes place with great difficulty and is rarely
encountered.
Compounds that readily undergo thermal decarboxylation include those related to
malonic acid. On being heated above its melting point, malonic acid is converted to acetic
acid and carbon dioxide.
It is important to recognize that only one carboxyl group is lost in this process.
The second carboxyl group is retained. A mechanism recognizing the assistance that one
carboxyl group gives to the departure of the other is represented by the equation
The transition state involves the carbonyl oxygen of one carboxyl group—the one that
stays behind—acting as a proton acceptor toward the hydroxyl group of the carboxyl
that is lost. Carbon–carbon bond cleavage leads to the enol form of acetic acid, along
with a molecule of carbon dioxide.
The enol intermediate subsequently tautomerizes to acetic acid.
The protons attached to C-2 of malonic acid are not directly involved in the process
and so may be replaced by other substituents without much effect on the ease of decar-
boxylation. Analogs of malonic acid substituted at C-2 undergo efficient thermal decar-
boxylation.
185°C
CO
2
H
CO
2
H
1,1-Cyclobutanedicarboxylic acid
H11001
Carbon
dioxide
CO
2
H
CO
2
H
Cyclobutanecarboxylic
acid (74%)
150–160°C
CH(CO
2
H)
2
2-(2-Cyclopentenyl)malonic acid
CH
2
CO
2
H
(2-Cyclopentenyl)acetic
acid (96–99%)
CO
2
Carbon
dioxide
H11001
Representation of
transition state in
thermal decarboxylation of
malonic acid
O
C
HO CH
2
C
O
O
H
O
C
HO CH
2
C
O
O
H
slow
O C O
Carbon dioxide
H11001
OH
C
HO CH
2
Enol form of
acetic acid
fast
O
HOCCH
3
Acetic acid
HO
2
CCH
2
CO
2
H
Malonic acid
(propanedioic acid)
CH
3
CO
2
H
Acetic acid
(ethanoic acid)
CO
2
Carbon dioxide
H11001
150°C
19.17 Decarboxylation of Malonic Acid and Related Compounds 761
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
PROBLEM 19.11 What will be the product isolated after thermal decarboxyla-
tion of each of the following? Using curved arrows, represent the bond changes
that take place at the transition state.
(a) (CH
3
)
2
C(CO
2
H)
2
(b)
(c)
SAMPLE SOLUTION (a) Thermal decarboxylation of malonic acid derivatives
leads to the replacement of one of the carboxyl groups by a hydrogen.
The transition state incorporates a cyclic array of six atoms:
Tautomerization of the enol form to 2-methylpropanoic acid completes the
process.
The thermal decarboxylation of malonic acid derivatives is the last step in a multi-
step synthesis of carboxylic acids known as the malonic ester synthesis. This synthetic
method will be described in Section 21.7.
Notice that the carboxyl group that stays behind during the decarboxylation of mal-
onic acid has a hydroxyl function that is not directly involved in the process. Compounds
that have substituents other than hydroxyl groups at this position undergo an analogous
decarboxylation.
The compounds most frequently encountered in this reaction are H9252-keto acids, that is,
carboxylic acids in which the H9252 carbon is a carbonyl function. Decarboxylation of
H9252-keto acids leads to ketones.
C
CH
2
C
H
OO
HO O
Bonding changes during
decarboxylation of malonic
acid
C
CH
2
C
H
OO
R O
Bonding changes during
decarboxylation of a H9252-keto acid
OCO
Carbon
dioxide
H11001C
HO
CH
3
OH
C CH
3
Enol form of
2-methylpropanoic acid
C
C
C
CH
3
H
3
C
H
OO
HO O
2,2-Dimethylmalonic
acid
(CH
3
)
2
C(CO
2
H)
2
2,2-Dimethylmalonic acid
(CH
3
)
2
CHCO
2
H
2-Methylpropanoic
acid
H11001 CO
2
Carbon
dioxide
heat
CCO
2
H
CH
3
CO
2
H
CH
3
(CH
2
)
6
CHCO
2
H
CO
2
H
762 CHAPTER NINETEEN Carboxylic Acids
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
PROBLEM 19.12 Show the bonding changes that occur, and write the structure
of the intermediate formed in the thermal decarboxylation of
(a) Benzoylacetic acid
(b) 2,2-Dimethylacetoacetic acid
SAMPLE SOLUTION (a) By analogy to the thermal decarboxylation of malonic
acid, we represent the corresponding reaction of benzoylacetic acid as
Acetophenone is the isolated product; it is formed from its enol by proton-
transfers.
The thermal decarboxylation of H9252-keto acids is the last step in a ketone synthesis
known as the acetoacetic ester synthesis. The acetoacetic ester synthesis is discussed in
Section 21.6.
19.18 SPECTROSCOPIC ANALYSIS OF CARBOXYLIC ACIDS
Infrared: The most characteristic peaks in the infrared spectra of carboxylic acids are
those of the hydroxyl and carbonyl groups. As shown in the infrared spectrum of
4-phenylbutanoic acid (Figure 19.8) the O±H and C±H stretching frequencies over-
lap to produce a broad absorption in the 3500–2500 cm
H110021
region. The carbonyl group
gives a strong band for C?O stretching at 1700 cm
H110021
.
1
H NMR: The hydroxyl proton of a CO
2
H group is normally the least shielded of all
the protons in an NMR spectrum, appearing 10–12 ppm downfield from tetramethyl-
silane, often as a broad peak. Figure 19.9 illustrates this for 4-phenylbutanoic acid. As
with other hydroxyl protons, the proton of a carboxyl group can be identified by adding
D
2
O to the sample. Hydrogen–deuterium exchange converts ±CO
2
H to ±CO
2
D, and
the signal corresponding to the carboxyl group disappears.
13
C NMR: Like other carbonyl groups, the carbon of the ±CO
2
H group of a car-
boxylic acid is strongly deshielded (H9254 160–185 ppm), but not as much as that of an alde-
hyde or ketone (190–215 ppm).
H11001 OCO
Carbon dioxide
CH
2
C
6
H
5
C
OH
Enol form of
acetophenone
C
O
H
O
CH
2 O
C
6
H
5
C
Benzoylacetic acid
RCCH
2
CO
2
H
O
H9252-Keto acid
heat fast
CO
2
Carbon dioxide
H11001 C
OH
RCH
2
Enol form of ketone
RCCH
3
O
Ketone
25°C
CH
3
CCCO
2
H
OCH
3
CH
3
2,2-Dimethylacetoacetic
acid
CH
3
CCH(CH
3
)
2
O
3-Methyl-2-butanone
H11001 CO
2
Carbon dioxide
19.18 Spectroscopic Analysis of Carboxylic Acids 763
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
764 CHAPTER NINETEEN Carboxylic Acids
Wave numbers
Microns
Transmittance (%)
C?O
OH and
CH
CH
2
CH
2
CH
2
COH
O
O
6.0 5.0 4.0 3.0 2.0 1.0 0.07.08.09.010.011.012.0
2.8 2.6 2.4 2.2 2.0
Chemical shift (δ, ppm)
±
FIGURE 19.8 The infrared spectrum of 4-phenylbutanoic acid.
FIGURE 19.9 The 200-MHz
1
H NMR spectrum of 4-
phenylbutanoic acid. The
peak for the proton of the
CO
2
H group is at H9254 12 ppm.
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
UV-VIS: In the absence of any additional chromophores, carboxylic acids absorb at a
wavelength (210 nm) that is not very useful for diagnostic purposes.
Mass Spectrometry: Aside from a peak for the molecular ion, which is normally easy
to pick out, aliphatic carboxylic acids undergo a variety of fragmentation processes. The
dominant fragmentation in aromatic acids corresponds to loss of OH, then loss of CO.
19.19 SUMMARY
Section 19.1 Carboxylic acids take their names from the alkane that contains the same
number of carbons as the longest continuous chain that contains the
±CO
2
H group. The -e ending is replaced by -oic acid. Numbering
begins at the carbon of the ±CO
2
H group.
Section 19.2 Like the carbonyl group of aldehydes and ketones, the carbon of a C?O
unit in a carboxylic acid is sp
2
-hybridized. Compared with the carbonyl
group of an aldehyde or ketone, the C?O unit of a carboxylic acid
receives an extra degree of stabilization from its attached OH group.
Section 19.3 Hydrogen bonding in carboxylic acids raises their melting points and
boiling points above those of comparably constituted alkanes, alcohols,
aldehydes, and ketones.
Section 19.4 Carboxylic acids are weak acids and, in the absence of electron-
attracting substituents, have dissociation constants K
a
of approximately
10
H110025
(pK
a
H11005 5). Carboxylic acids are much stronger acids than alcohols
because of the electron-withdrawing power of the carbonyl group (induc-
tive effect) and its ability to delocalize negative charge in the carboxy-
late anion (resonance effect).
RC
OH
O
Carboxylic acid
H11002H
H11001
H
H11001
Resonance description of electron
delocalization in carboxylate anion
R
O
C
O
H11002
O
H11002
RC
O
C H
O
RO
C
H11001
H11002
H
O
RO
C
H11001
H11002
H
O
RO
3-Ethylhexane
1
6
24
53
4-Ethylhexanoic acid
O
OH
6
53
24
1
e
H11002
H11002HO H11002CO
Ar
O
COH Ar
O
H11001
COH
M
H11001
Ar
H11001
CO
[M H11002 17]
H11001
Ar
H11001
[M H11002 (17 H11001 28)]
H11001
19.19 Summary 765
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Section 19.5 Although carboxylic acids dissociate to only a small extent in water, they
are deprotonated almost completely in basic solution.
Sections Electronegative substituents, especially those within a few bonds of the
19.6–19.7 carboxyl group, increase the acidity of carboxylic acids.
Section 19.8 Dicarboxylic acids have separate K
a
values for their first and second ion-
izations.
Section 19.9 Carbon dioxide and carbonic acid are in equilibrium in water. Carbon
dioxide is the major component.
Section 19.10 Several of the reactions introduced in earlier chapters can be used to pre-
pare carboxylic acids (See Table 19.4).
Section 19.11 Carboxylic acids can be prepared by the reaction of Grignard reagents
with carbon dioxide.
Section 19.12 Nitriles, which can be prepared from primary and secondary alkyl halides
by nucleophilic substitution with cyanide ion, can be converted to car-
boxylic acids by hydrolysis.
Likewise, the cyano group of a cyanohydrin can be hydrolyzed to
±CO
2
H.
CHCH
2
CH
2
CH
3
CN
2-Phenylpentanenitrile
CHCH
2
CH
2
CH
3
CO
2
H
2-Phenylpentanoic acid (52%)
H
2
O, H
2
SO
4
heat
1. Mg, diethyl ether
2. CO
2
3. H
3
O
H11001
Br
4-Bromocyclopentene
CO
2
H
Cyclopentene-4-carboxylic
acid (66%)
O C O H11001 H
2
O C
O
HO OH
0.3%
99.7%
CF
3
CO
2
H
Trifluoroacetic acid
K
a
H11005 5.9 H11003 10
H110021
(pK
a
H11005 0.2)
NO
2
CO
2
H
NO
2
O
2
N
2,4,6-Trinitrobenzoic acid
K
a
H11005 2.2 H11003 10
H110021
(pK
a
H11005 0.6)
COH
O
Benzoic acid
K
a
H11005 6.3 H11003 10
H110025
(stronger acid)
CO
H11002
O
Benzoate ion
CO
3
2H11002
Carbonate ion
HCO
3
H11002
Hydrogen carbonate ion
K
a
H11005 5 H11003 10
H1100211
(weaker acid)
H11001H11001
766 CHAPTER NINETEEN Carboxylic Acids
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Section 19.13 Among the reactions of carboxylic acids, their conversion to acyl chlo-
rides, primary alcohols, and esters were introduced in earlier chapters and
were reviewed in Table 19.5.
Section 19.14 The mechanism of acid-catalyzed esterification involves some key fea-
tures that are fundamental to the chemistry of carboxylic acids and their
derivatives.
Protonation of the carbonyl oxygen activates the carbonyl group toward
nucleophilic addition. Addition of an alcohol gives a tetrahedral inter-
mediate (shown in the box in the preceding equation), which has the
capacity to revert to starting materials or to undergo dehydration to yield
an ester.
Section 19.15 An intramolecular esterification can occur when a molecule contains both
a hydroxyl and a carboxyl group. Cyclic esters are called lactones and
are most stable when the ring is five or six membered.
Section 19.16 Halogenation at the H9251-carbon atom of carboxylic acids can be accom-
plished by the Hell–Volhard–Zelinsky reaction. An acid is treated with
chlorine or bromine in the presence of a catalytic quantity of phospho-
rus or a phosphorus trihalide:
This reaction is of synthetic value in that H9251-halo acids are reactive sub-
strates in nucleophilic substitution reactions.
Section 19.17 1,1-Dicarboxylic acids and H9252-keto acids undergo thermal decarboxylation
by a mechanism in which a H9252-carbonyl group assists the departure of car-
bon dioxide.
R
2
CHCO
2
H
Carboxylic
acid
H11001 X
2
Halogen
P or PX
3
R
2
CCO
2
H
X
H9251-Halo acid
H11001 HX
O
O
2-Methyl-4-pentanolide4-Hydroxy-2-
methylpentanoic acid
OH CO
2
H
RC
ORH11032
O
H11002H
2
O
H11001 H
H11001
RCORH11032
O H
H11001
O
RCORH11032
OH
HH
H11001
H
H11001
RC
OH
O
RC
OH
OH
H11001
H11001
RH11032OH
RC
OH
OH
RH11032
O
H
H11001
H11001RC
OH
OH
ORH11032 H
H11001
19.19 Summary 767
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
Section 19.18 Carboxylic acids are readily identified by the presence of strong infrared
absorptions at 1700 cm
H110021
(C?O) and between 2500 and 3500 cm
H110021
(OH), a
1
H NMR signal for the hydroxyl proton at H9254 10–12 ppm, and a
13
C signal for the carbonyl carbon near H9254 180 ppm.
PROBLEMS
19.13 Many carboxylic acids are much better known by their common names than by their sys-
tematic names. Some of these follow. Provide a structural formula for each one on the basis of its
systematic name.
(a) 2-Hydroxypropanoic acid (better known as lactic acid, it is found in sour milk and is
formed in the muscles during exercise)
(b) 2-Hydroxy-2-phenylethanoic acid (also known as mandelic acid, it is obtained from
plums, peaches, and other fruits)
(c) Tetradecanoic acid (also known as myristic acid, it can be obtained from a variety of fats)
(d) 10-Undecenoic acid (also called undecylenic acid, it is used, in combination with its
zinc salt, to treat fungal infections such as athlete’s foot)
(e) 3,5-Dihydroxy-3-methylpentanoic acid (also called mevalonic acid, it is an important
intermediate in the biosynthesis of terpenes and steroids)
(f) (E)-2-Methyl-2-butenoic acid (also known as tiglic acid, it is a constituent of various
natural oils)
(g) 2-Hydroxybutanedioic acid (also known as malic acid, it is found in apples and other fruits)
(h) 2-Hydroxy-1,2,3-propanetricarboxylic acid (better known as citric acid, it contributes to
the tart taste of citrus fruits)
(i) 2-(p-Isobutylphenyl)propanoic acid (an antiinflammatory drug better known as ibuprofen)
(j) o-Hydroxybenzenecarboxylic acid (better known as salicylic acid, it is obtained from
willow bark)
19.14 Give an acceptable IUPAC name for each of the following:
(a) CH
3
(CH
2
)
6
CO
2
H (e) HO
2
C(CH
2
)
6
CO
2
H
(b) CH
3
(CH
2
)
6
CO
2
K(f)CH
3
(CH
2
)
4
CH(CO
2
H)
2
(c) CH
2
?CH(CH
2
)
5
CO
2
H
(g)
(d)
(h) CH(CH
2
)
4
CO
2
H
CH
2
CH
3
H
3
C
C
HH
(CH
2
)
4
CO
2
H
C
CO
2
H
C
C
C
H
OO
X
RR
O
X H11005 OH: malonic acid
derivative
X H11005 alkyl or aryl: H9252-keto acid
R
C
C
H
O
X
R
Enol form of
product
H11002CO
2
XCCHR
2
O
X H11005 OH: carboxylic acid
X H11005 alkyl or aryl: ketone
768 CHAPTER NINETEEN Carboxylic Acids
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.15 Rank the compounds in each of the following groups in order of decreasing acidity:
(a) Acetic acid, ethane, ethanol
(b) Benzene, benzoic acid, benzyl alcohol
(c) Propanedial, 1,3-propanediol, propanedioic acid, propanoic acid
(d) Acetic acid, ethanol, trifluoroacetic acid, 2,2,2-trifluoroethanol, trifluoromethanesulfonic
acid (CF
3
SO
2
OH)
(e) Cyclopentanecarboxylic acid, 2,4-pentanedione, cyclopentanone, cyclopentene
19.16 Identify the more acidic compound in each of the following pairs:
(a) CF
3
CH
2
CO
2
HorCF
3
CH
2
CH
2
CO
2
H
(b) CH
3
CH
2
CH
2
CO
2
HorCH
3
CPCCO
2
H
(c)
(d)
(e)
(f)
(g)
19.17 Propose methods for preparing butanoic acid from each of the following:
(a) 1-Butanol (e) 2-Propanol
(b) Butanal (f) Acetaldehyde
(c) 1-Butene (g) CH
3
CH
2
CH(CO
2
H)
2
(d) 1-Propanol
19.18 It is sometimes necessary to prepare isotopically labeled samples of organic substances for
probing biological transformations and reaction mechanisms. Various sources of the radioactive
mass-14 carbon isotope are available. Describe synthetic procedures by which benzoic acid, labeled
with
14
C at its carbonyl carbon, could be prepared from benzene and the following
14
C-labeled
precursors. You may use any necessary organic or inorganic reagents. (In the formulas shown, an
asterisk indicates
14
C.)
(a) (b) (c) CO
2
*
HCH
O
X
*
CH
3
Cl
*
CO
2
H
O
or
CO
2
H
N
H
CO
2
H
O
CO
2
H
O
or
F
CO
2
H
F
FF
F or
FF
FF
F CO
2
H
CO
2
H
F
F
F
F
F
or
CO
2
H
CO
2
H
or
CO
2
H
Problems 769
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.19 Give the product of the reaction of pentanoic acid with each of the following reagents:
(a) Sodium hydroxide
(b) Sodium bicarbonate
(c) Thionyl chloride
(d) Phosphorus tribromide
(e) Benzyl alcohol, sulfuric acid (catalytic amount)
(f) Chlorine, phosphorus tribromide (catalytic amount)
(g) Bromine, phosphorus trichloride (catalytic amount)
(h) Product of part (g) treated with sodium iodide in acetone
(i) Product of part (g) treated with aqueous ammonia
(j) Lithium aluminum hydride, then hydrolysis
(k) Phenylmagnesium bromide
19.20 Show how butanoic acid may be converted to each of the following compounds:
(a) 1-Butanol (e) Phenyl propyl ketone
(b) Butanal (f) 4-Octanone
(c) 1-Chlorobutane (g) 2-Bromobutanoic acid
(d) Butanoyl chloride (h) 2-Butenoic acid
19.21 Show by a series of equations, using any necessary organic or inorganic reagents, how acetic
acid can be converted to each of the following compounds:
(a) H
2
NCH
2
CO
2
H (e) ICH
2
CO
2
H
(b) C
6
H
5
OCH
2
CO
2
H (f) BrCH
2
CO
2
CH
2
CH
3
(c) NCCH
2
CO
2
H (g)
(d) HO
2
CCH
2
CO
2
H (h) C
6
H
5
CH?CHCO
2
CH
2
CH
3
19.22 Each of the following reactions has been reported in the chemical literature and gives a sin-
gle product in good yield. What is the product in each reaction?
(a) (d)
(b)
(e)
(c)
(f)
19.23 Show by a series of equations how you could synthesize each of the following compounds
from the indicated starting material and any necessary organic or inorganic reagents:
(a) 2-Methylpropanoic acid from tert-butyl alcohol
(b) 3-Methylbutanoic acid from tert-butyl alcohol
HBr
benzoyl peroxide
CH
2
CH(CH
2
)
8
CO
2
H
Br
2
P
CO
2
H
H
2
O, acetic acid
H
2
SO
4
, heat
CH
2
CN
Cl
1. LiAlD
4
2. H
2
O
CO
2
H
1. Mg, diethyl ether
2. CO
2
3. H
3
O
H11001
CF
3
Br
ethanol, H
2
SO
4
H
3
C
H
CH
3
CO
2
H
C C
(C
6
H
5
)
3
P±CHCO
2
CH
2
CH
3
H11001
H11002
770 CHAPTER NINETEEN Carboxylic Acids
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
(c) 3,3-Dimethylbutanoic acid from tert-butyl alcohol
(d) HO
2
C(CH
2
)
5
CO
2
H from HO
2
C(CH
2
)
3
CO
2
H
(e) 3-Phenyl-1-butanol from
(f)
(g)
(h) 2,4-Dimethylbenzoic acid from m-xylene
(i) 4-Chloro-3-nitrobenzoic acid from p-chlorotoluene
(j) (Z)-CH
3
CH?CHCO
2
H from propyne
19.24 (a) Which stereoisomer of 4-hydroxycyclohexanecarboxylic acid (cis or trans) can form a
lactone? Make a molecular model of this lactone. What is the conformation of the cyclohexane
ring in the starting hydroxy acid? In the lactone?
(b) Repeat part (a) for the case of 3-hydroxycyclohexanecarboxylic acid.
19.25 Suggest reasonable explanations for each of the following observations.
(a) Both hydrogens are anti to each other in the most stable conformation of formic acid.
(b) Oxalic acid has a dipole moment of zero in the gas phase.
(c) The dissociation constant of o-hydroxybenzoic acid is greater (by a factor of 12) than
that of o-methoxybenzoic acid.
(d) Ascorbic acid (vitamin C), although not a carboxylic acid, is sufficiently acidic to cause
carbon dioxide liberation on being dissolved in aqueous sodium bicarbonate.
19.26 When compound A is heated, two isomeric products are formed. What are these two prod-
ucts?
19.27 A certain carboxylic acid (C
14
H
26
O
2
), which can be isolated from whale blubber or sardine
oil, yields nonanal and O?CH(CH
2
)
3
CO
2
H on ozonolysis. What is the structure of this acid?
CO
2
H
CO
2
H
Cl
Compound A
H
OH
HOCH
2
O
HO OH
O
Ascorbic acid
CO
2
HHO
from (E)-ClCH?CHCO
2
H
Cl
CO
2
H
Br
CO
2
H
from cyclopentyl bromide
C
6
H
5
CH
3
CHCH
2
CN
W
Problems 771
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.28 When levulinic acid was hydrogenated at high pressure over a nickel
catalyst at 220°C, a single product, C
5
H
8
O
2
, was isolated in 94% yield. This compound lacks
hydroxyl absorption in its infrared spectrum and does not immediately liberate carbon dioxide on
being shaken with sodium bicarbonate. What is a reasonable structure for the compound?
19.29 On standing in dilute aqueous acid, compound A is smoothly converted to mevalonolactone.
Suggest a reasonable mechanism for this reaction. What other organic product is also formed?
19.30 Suggest reaction conditions suitable for the preparation of compound A from 5-hydroxy-2-
hexynoic acid.
19.31 In the presence of the enzyme aconitase, the double bond of aconitic acid undergoes hydra-
tion. The reaction is reversible, and the following equilibrium is established:
(a) The major tricarboxylic acid present is citric acid, the substance responsible for the tart
taste of citrus fruits. Citric acid is achiral. What is its structure?
(b) What must be the constitution of isocitric acid? (Assume that no rearrangements accom-
pany hydration.) How many stereoisomers are possible for isocitric acid?
19.32 The
1
H NMR spectra of formic acid (HCO
2
H), maleic acid (cis-HO
2
CCH?CHCO
2
H), and
malonic acid (HO
2
CCH
2
CO
2
H) are similar in that each is characterized by two singlets of equal
intensity. Match these compounds with the designations A, B, and C on the basis of the appro-
priate
1
H NMR chemical shift data.
Compound A: signals at H9254 3.2 and 12.1 ppm
Compound B: signals at H9254 6.3 and 12.4 ppm
Compound C: signals at H9254 8.0 and 11.4 ppm
19.33 Compounds A and B are isomers having the molecular formula C
4
H
8
O
3
. Identify A and B
on the basis of their
1
H NMR spectra.
Compound A: H9254 1.3 ppm (3H, triplet); 3.6 ppm (2H, quartet); 4.1 ppm (2H, singlet); 11.1 ppm
(1H, broad singlet)
Compound B: H9254 2.6 ppm (2H, triplet); 3.4 ppm (3H, singlet); 3.7 ppm (2H triplet); 11.3 ppm
(1H, broad singlet)
HO
2
CCO
2
H
CH
2
CO
2
HH
C C
Aconitic acid
(4% at equilibrium)
Isocitric acid
(C
6
H
8
O
7
)
(6% at equilibrium)
Citric acid
(C
6
H
8
O
7
)
(90% at equilibrium)
H
2
OH
2
O
CH
3
CHCH
2
C
OH
CCO
2
H
5-Hydroxy-2-hexynoic acid
O
O
H
3
C
Compound A
CH
3
OO
CH
3
CH
2
CO
2
H
Compound A
O
O
CH
3
OH
Mevalonolactone
H
3
O
H11001
(CH
3
CCH
2
CH
2
CO
2
H)
O
X
772 CHAPTER NINETEEN Carboxylic Acids
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
19.34 Compounds A and B are carboxylic acids. Identify each one on the basis of its
1
H NMR
spectrum.
(a) Compound A (C
3
H
5
ClO
2
) (Figure 19.10).
(b) Compound B (C
9
H
9
NO
4
) has a nitro group attached to an aromatic ring (Figure 19.11).
Problems 773
3.8 3.6
3.0 2.8
6.0 5.0 4.0 3.0 2.0 1.0 0.07.08.09.010.011.012.0
Compound A
C
3
H
5
ClO
2
Chemical shift (δ, ppm)
6.0 5.0 4.0 3.0 2.0 1.0 0.07.08.09.010.011.012.013.0
8.2 8.0 7.8 7.6 7.4 4.0 3.8 1.8 1.6 1.4
Compound B
C
9
H
9
NO
4
1
1
22
3
Chemical shift (δ, ppm)
FIGURE 19.10 The 200-MHz
1
H NMR spectrum of com-
pound A (C
3
H
5
ClO
2
) (Prob-
lem 19.34a).
FIGURE 19.11 The 200-MHz
1
H NMR spectrum of com-
pound B (C
9
H
9
NO
4
) (Problem
19.34b).
Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
| 课件名称： | 有机化学（英文原版） |
| 课件分类： | 化学 |
| 课件类型： | 电子图书 |
| 文件大小： | 28.97MB |
| 下载次数： | 7 |
| 评论次数： | 5 |
| 用户评分： | 8.2 |
- 10. 有机化学（英文原版）：Chapt10
- 11. 有机化学（英文原版）：Chapt11
- 12. 有机化学（英文原版）：Chapt12
- 13. 有机化学（英文原版）：Chapt13
- 14. 有机化学（英文原版）：Chapt14
- 15. 有机化学（英文原版）：Chapt15
- 16. 有机化学（英文原版）：Chapt16
- 17. 有机化学（英文原版）：Chapt17
- 18. 有机化学（英文原版）：Chapt18
- 19. 有机化学（英文原版）：Chapt19
- 20. 有机化学（英文原版）：Chapt20
- 21. 有机化学（英文原版）：Chapt21
- 22. 有机化学（英文原版）：Chapt22
- 23. 有机化学（英文原版）：Chapt23
- 24. 有机化学（英文原版）：Chapt24
- 25. 有机化学（英文原版）：Chapt25
- 26. 有机化学（英文原版）：Chapt26
- 27. 有机化学（英文原版）：Chapt27
- 28. 有机化学（英文原版）：End of Book
