Jones M., Fleming S.A. Organic Chemistry

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17.1 Preview 829

This quotation comes from a 1944 issue of Walt Disney’s Comics and Stories,“Donald Duck the Mad Chemist.”

It was discovered by Peter P. Gaspar, then a postdoctoral fellow at Caltech, now a professor at Washington

University.Those of us who work with CH

have still not reproduced Professor Duck’s experiment with osmot-

ic fog, but a few of us are still trying.

If I mix CH

with NH

and boil the atoms in osmotic fog, I should get

speckled nitrogen!

—DONALD DUCK

He’s talking chemical talk!

—HUEY

But he knows nothing

—DEWEY

About chemicals!

—LOUIE

17.1 Preview

In this chapter, we explore the properties and chemistry of carboxylic acids (gen-

eral formula ). As with other functional groups, we will begin by

learning the IUPAC naming system, and then move on to structure. Carboxylic

acids have a rich chemistry; they are both acids (hence the name) and bases, and

we saw in Chapter 16 how the carbonyl group is a locus of reactivity. Although

many new reactions will appear in this chapter, most important will be the emer-

gence of a general reaction mechanism, addition–elimination, that we have

already seen briefly in Chapter 14. Chapter 18 will extend the exploration of this

process.

COOH

WORKED PROBLEM 17.1 What are the reactions we have learned for making car-

boxylic acids?

ANSWER Carboxylic acids can be made from oxidative ozonolysis of alkenes, by

oxidation of primary alcohols using dichromate under aqueous conditions, and

by oxidation of aldehydes.

ESSENTIAL SKILLS AND DETAILS

1. This chapter’s centerpiece is the Fischer esterification–acid hydrolysis equilibrium. If

you know this pair of reactions well, you will have much of this chapter under control.

The two mechanisms are exactly the reverse of each other—one is the “forward”

reaction, the other is the “backward”reaction.

2. The reaction of a carboxylic acid with two equivalents of an alkyllithium reagent,

followed by hydrolysis, yields a ketone. This reaction is a very effective way to make

these carbonyl compounds. Be sure you understand why two equivalents of alkyllithium

are necessary.

3. The reaction of LiAlH

with a carboxylic acid results in formation of a primary alcohol

through addition of two equivalents of hydride.

830 CHAPTER 17 Carboxylic Acids

17.2 Nomenclature and Properties

of Carboxylic Acids

In the IUPAC systematic nomenclature, the final “e”of the parent alkane is dropped,

the suffix “oic” is added, and the separate word “acid” is added. Diacids are named

similarly, except that the suffix is “dioic,”and the final “e”is not dropped.Cyclic acids

are named as “cycloalkanecarboxylic acids.”Table 17.1 shows some common mono-

and diacids along with some of their physical properties and common names, many

of which are still used.

COOH

TABLE 17.1 Some Carboxylic Acids and eir Properties

Structure Systematic Name Common Name bp (°C)

HCOOH

COOH

Methanoic acid Formic acid

Acetic acid

100.7

117.9Ethanoic acid

COOH

Propanoic acid Propionic acid 141

COOH

Butanoic acid Butyric acid 165.5

COOH

Pentanoic acid Valeric acid

Caproic acid

186

205Hexanoic acid

Propenoic acid Acrylic acid 141.6

Cyclopentanecarboxylic acid 216

mp (°C)

8.4

16.6

–20.8

–4.5

–33.8

–2

–7

Cyclohexanecarboxylic acid 232 31

Benzenecarboxylic acid Benzoic acid 249 122

ese are the pK

values for loss of the second proton.

CHCOOH

Ethanedioic acid Oxalic acid 190

HOOC

COOH

Propanedioic acid Malonic acid 136

HOOC

COOH

HOOC

(

)

COOH

HOOC

(

)

COOH

HOOC

(

)

COOH

HOOC

COOH

Butanedioic acid Succinic acid 188

Pentanedioic acid Glutaric acid ~300 99

Hexanedioic acid Adipic acid >300 156

cis-Butenedioic acid Maleic acid 140

trans-Butenedioic acid

cis Isomer

trans Isomer

Fumaric acid ~300

3.77

4.76

4.87

4.81

4.82

4.83

4.25

4.91

4.88

4.19

1.23

4.19

2.83

5.69

4.16

5.61

5.41

4.31

5.41

4.43

6.23

1.92

4.38

3.02

HOOC

COOH

WEB 3D

For substituted acids, the numbering of the longest chain begins with the acid

carbon itself, which is given the number “1”(Fig. 17.1). In cyclic compounds it is the

carbon attached to the “COOH”that is carbon “1”in naming.Because carboxylic acids

are the highest priority functional group, all functional groups except alkenes and

17.2 Nomenclature and Properties of Carboxylic Acids 831

(c)

(b)

(a)

This enantiomer

COOH

(f)

(racemic)

COOH

(e)

COOH

(d)

(g)

CH C

3-Bromobutanoic acid

(3-bromobutyric acid)

3,5-Dichlorohexanoic acid 3-Ethylbenzoic acid

(m-ethylbenzoic acid)

cis-4-Aminocyclohexane-

carboxylic acid

OHH

HHO

(E )-4-Hydroxy-2-pentenoic acid

FIGURE 17.1 Some carboxylic acids

and their names.

alkynes are listed as substituents in the prefix. Alkenes and alkynes are indicated in

the parent name. You will need to be able to recognize the condensed formula for a

carboxylic acid, which is RCOOH, often written as RCO

PROBLEM 17.2 Name the following compounds:

832 CHAPTER 17 Carboxylic Acids

Lithium benzoate Potassium 2-chlorobutanoateSodium propanoate

–

FIGURE 17.2 Some carboxylate salts

and their names.

125⬚

111⬚

Bond angles

124⬚

121⬚

118⬚

Bond lengths

1.10

1.32 A

⬚

1.23

0.97 1.11

⬚

FIGURE 17.3 The structure of formic

acid compared to that of

formaldehyde.

A carboxylate anion is the conjugate base of a carboxylic acid. Carboxylate anions

are encountered frequently in any study of organic chemistry.They are also often found

listed as contents of soaps and shampoos. So, it is worth learning the IUPAC system

for naming the carboxylates. We refer to RCOO



and its counterion (Li



,Na



,or



, for example) as a salt because the RCOO





is a result of an acidic hydrogen

replaced by a metal, which is the definition of a salt. The salt is named as if it were a

carboxylic acid, the suffix being changed from –ic acid to –ate.The name of the metal

counterion is added before the parent organic name as a separate word (Fig. 17.2). An

important property of carboxylate salts is that they are often soluble in water.

17.3 Structure of Carboxylic Acids

In Figure 17.3 we compare the structure of formic acid and the structure of formalde-

hyde.The structure of acids is essentially what one would expect by analogy to other

carbonyl compounds. The carbonyl carbons are sp

hybridized, and therefore

carbonyl compounds are planar.The strong carbon–oxygen double bonds are appro-

priately short, about 1.23 Å.

There are two complications with the structural picture. First, in solution the

simplest carboxylic acids are substantially dimerized (Fig.17.4).It is possible to form

two rather strong hydrogen bonds ( 7 kcal/mol, each) in the dimeric form, and this

energy gain accounts for the ease of dimer formation. In turn, the ease of dimer

formation helps explain the high boiling points (Table 17.1) of carboxylic acids.

Second, there are two energy minima for simple carboxylic acids formed by rota-

tion around the bond between the carbonyl carbon and OH oxygen. The

hydroxylic hydrogen can be anti to the carbonyl group, or eclipse it. We refer to these

conformations as s-trans and s-cis, respectively (p. 523) as shown in Figure 17.5.

These conformations are real energy minima separated in the gas phase by a barrier

of about 13 kcal/mol.The s-cis form for formic acid is more stable by about 6 kcal/mol.

Hydrogen bond

WEB 3D

FIGURE 17.4 A dimeric carboxylic acid.

s-cis s-trans

FIGURE 17.5 The s-cis and s-trans

forms of a simple carboxylic acid.

17.4 Infrared and Nuclear Magnetic Resonance Spectra of Carboxylic Acids 833

syn

anti

H H

PROBLEM 17.3 Explain why the s-cis form of the carboxylic acid is more stable

than the s-trans form.

PROBLEM 17.4 Calculate the equilibrium constant for the equilibrium between

s-cis and s-trans formic acid at 25 °C.

WORKED PROBLEM 17.5 Interconversion of the s-cis and s-trans forms can occur

very easily in acidic water solution. Devise a mechanism not involving simple

rotation about a bond.

ANSWER A series of protonations and deprotonations will do the job.

17.4 Infrared and Nuclear Magnetic Resonance

Spectra of Carboxylic Acids

The most prominent features of the IR spectra of carboxylic acids are the strong

absorption for the stretch at about 1710 cm

1

and the strong and very broad

band centered at 3100 cm

1

for the stretching frequencies.Figure 17.6 shows

the IR spectrum of acetic acid. As usual, conjugation of the carbonyl shifts the

stretch to a lower frequency by about 20 cm

1

.The stretching band

is broad for the same reasons that the stretching bands of alcohols are broad

(p. 710). There are many hydrogen-bonded dimers and oligomers with different

bond strengths present in any carboxylic acid sample.

The NMR spectra for a carboxylic acid are also informative. Hydrogens in

the position α to the carbonyl group of carboxylic acids are deshielded by both the

100

Transmittance (%)

Wavenumber (cm

–1

)

4006001200 100014001600180020003400 2800 220040004600 800

Microns (␮)

16 18 20 22 251514131211109875 5.5 63 3.5 4 4.52.4 2.6 2.82.2

0.0

0.4

0.5

0.6

0.8

1.0

2.0

0.3

0.05

0.2

0.1

Absorbance

FIGURE 17.6 The IR spectrum of acetic acid.

834 CHAPTER 17 Carboxylic Acids

electron-withdrawing nature of the carbonyl group and by local magnetic fields set

up by the circulation of electrons in the π bond.These hydrogens appear in the same

region as other hydrogens α to carbonyl groups at δ 2–2.7 ppm (see Table 15.4).

The acidic hydrogen of the RCOOH is the most deshielded hydrogen of all the typ-

ical organic functional groups. It usually appears in the region of δ 10–13 ppm as a

broad singlet. Like the hydrogen in the OH group of an alcohol, the hydrogen of a

carboxylic acid is exchangeable,and the signal vanishes when D

O is added to the sam-

ple and the OH becomes OD.Alcohol hydrogens rarely appear as low as δ 10–13 ppm.

The carbon of the carboxylic acid group is also strongly deshielded and appears down-

field,as do other carbonyl carbons in

C NMR spectra.The position is about 180 ppm,

slightly upfield of the chemical shifts of the carbonyl carbons of aldehydes and ketones.

17.5 Acidity and Basicity of Carboxylic Acids

Because carboxylic acids are both acids and bases, we might well expect that a rather

diverse chemistry would be found. Carboxylic acids wouldn’t be called acids if they

were not strong Brønsted acids. In fact, carboxylic acids are the organic functional

group that Nature uses as an acid, just as amines are the organic functional group

that Nature uses as its organic base. Table 17.1 gave the pK

values for some mono-

and dicarboxylic acids.

Organic acids (pK

 3–5) are much stronger acids than alcohols (pK

 15–17).

Reasons for this increased acidity are not hard to find, but assessing their relative

importance is more difficult. One explanation focuses on the formation of a

resonance-stabilized carboxylate anion after proton loss (Fig. 17.7).

Resonance-stabilized

carboxylate anion

base

–

WEB 3D

FIGURE 17.7 The formation of a

resonance-stabilized carboxylate

anion through removal of a proton

from the hydroxyl group of a

carboxylic acid.

Deprotonation of an alcohol gives an oxygen anion, an alkoxide, but the ion is

not stabilized by resonance (Fig. 17.8). It is reasonable to accept the notion that the

formation of the highly stabilized carboxylate is responsible for the high acidity of

carboxylic acids. Recently, however, this traditional view has been challenged by at

least three research groups with both theoretical and experimental arguments. In var-

ious ways, the research groups of Andrew Streitwieser (b. 1927) at Berkeley, Darrah

Thomas (b. 1932) at Oregon State, and Kenneth Wiberg (b. 1927) at Yale pointed

out the importance of the inductive effect of the highly polar carbonyl group. In

their view, the increased acidity of acetic acid over ethyl alcohol derives not from

Carboxylate,

resonance stabilized

....

base

–

base

–

(–)

Alkoxide, not

resonance stabilized

RCH

–

RCH

FIGURE 17.8 A comparison of carboxylate and alkoxide anions.

17.5 Acidity and Basicity of Carboxylic Acids 835

resonance stabilization of the carboxylate anion, but from the electrostatic stabiliza-

tion afforded the developing negative charge by the adjacent polar carbonyl group

in which the carbon bears a partial positive charge (Fig. 17.9).They reckon that res-

onance could account for no more than about 15% of the total stabilization.

WORKED PROBLEM 17.6 Explain why fluoroacetic acid has a lower pK

than acetic

acid (2.66 vs. 4.76).

ANSWER The structure of the anion formed by removal of a proton tells the story.

The dipole in the carbon–fluorine bond stabilizes the fluoroacetate anion, which

makes removal of the acidic proton easier.

–

FIGURE 17.9 Electrostatic

stabilization may account for the

acidity of carboxylic acids.The highly

polar carbonyl group stabilizes the

carboxylate anion.

Now we should ask why resonance might not be so important.The carboxylate anion

is surely delocalized,whereas the alkoxide ion is not.The key point is that the carbonyl

group of the acid is already so polar that little further delocalization can occur as the

anion is formed. The negative charge on the carbonyl oxygen and the positive charge

on the carbonyl carbon aren’t developed as the oxygen–hydrogen bond breaks; the

charges are already largely there! Both factors, the resonance stabilization of the car-

boxylate anion and the polarity of the carbonyl group, surely contribute to the acidity

of carboxylic acids.The question is only over their relative importance. We will use the

resonance stabilization argument,keeping in mind that there may be more to the story.

PROBLEM SOLVING

Watch out! Carboxylic acids are called acids because they are acidic. They will

deprotonate in base before they do any other reactions typical of compounds

containing carbonyl groups. “Everyone” forgets that seemingly simple fact, and

problem writers may try to trap you. Always remember: A carboxylic acid

deprotonates in base.

–

The δ

stabilizes the carboxylate anion

–

836 CHAPTER 17 Carboxylic Acids

The stabilization by electron-withdrawing groups pointed out in Problem 17.6

is a general phenomenon. As Table 17.2 shows, acids bearing electron-withdrawing

groups are stronger acids than their parent compounds. The further the electron-

withdrawing group is from the acid, the smaller the effect on the pK

(Fig. 17.10).

TABLE 17.2 Acidities of Some Substituted

Carboxylic Acids

Acid pK

Acetic 4.76

α-Chloroacetic 2.86

α,α-Dichloroacetic 1.29

α,α,α-Trichloroacetic 0.65

α-Fluoroacetic 2.66

α,α-Difluoroacetic 1.24

α,α,α-Trifluoroacetic 0.25

α-Bromoacetic 2.86

α-Iodoacetic 3.12

α-Nitroacetic 1.68

= 4.81

Butanoic acid

= 4.52

4-Chlorobutanoic acid

= 2.84

2-Chlorobutanoic acid

= 4.06

3-Chlorobutanoic acid

CCHCH

FIGURE 17.10 The greater the distance (number of bonds) between an electron-withdrawing group, here

chlorine, and the point of ionization, the less effect an electron-withdrawing group has on the acidity.

Carboxylic acids are electrophiles (Lewis acids) as well as Brønsted acids.

The presence of the carbonyl group ensures that. Remember all the addition reac-

tions of carbonyl groups encountered in Chapter 16. However, expression of the

Lewis acidity of the carbonyl carbon is often thwarted because the easiest reaction

with a nucleophile is not addition to the carbonyl group, but removal of the acid’s

OH hydrogen to give the carboxylate anion.Once it is formed, the carboxylate anion

is far more resistant to addition than an ordinary carbonyl because, in this case,

addition would introduce a second negative charge (Fig. 17.11).

base

(fast)

base

A dianion

(slow)

–

FIGURE 17.11 For carboxylic acids, the fastest reaction with a nucleophile is removal

of the acidic hydroxyl hydrogen to give the carboxylate anion.The anion that results

is resistant to addition reactions with a second nucleophile, which would introduce

a second negative charge.

17.5 Acidity and Basicity of Carboxylic Acids 837

–

Removal

of the acidic

hydrogen

Addition

to the

carbonyl

–

FIGURE 17.12 Some strong

nucleophiles can add to the

carboxylate anion. The organolithium

reagent is one example.

Finally, organic acids are nucleophiles (Lewis bases), and can react

with electrophiles (Lewis acids).The simplest reaction is the protona-

tion of a carboxylic acid. There are two possible sites for protonation,

the carbonyl oxygen and the hydroxyl oxygen (Fig. 17.13). Which will

it be?

The intermediate in which protonation has taken place at the car-

bonyl oxygen is resonance stabilized, whereas the species in which the

hydroxyl oxygen is protonated is not (Fig. 17.14). Moreover, protonation

of the hydroxyl oxygen is destabilized by the dipole in the carbon–oxy-

gen double bond,which places a partial positive charge on carbon. It will

not be energetically favorable to introduce a positive charge adjacent to

this already partially positive carbon. The more stable cation, in which

the carbonyl oxygen is protonated, is preferred.

Nevertheless, some especially strong nucleophiles are able to do this second addi-

tion. An example is the organolithium reagent,RLi, and shortly we will see the syn-

thetic consequences of this reaction. The formation of the dianion of Figure 17.12

is not as bad as it looks because the bond is substantially covalent. It is not

completely ionic.

WORKED PROBLEM 17.7 Anticipate a little.What synthetic use can you see for the

reaction in Figure 17.12? Hint: What will happen when water is added once the

dianion is formed?

ANSWER When water is added, a hydrate will be formed. You know from

Chapter 16 that simple hydrates are generally unstable relative to a carbonyl com-

pound and water. So, this reaction should be a good synthesis of ketones. It is, as

we will see on page 856.

–

Hydrate

Protonation of the

carbonyl oxygen

Protonation of the

hydroxyl oxygen

FIGURE 17.13 The two possible sites for

protonation of a carboxylic acid.

Resonance stabilization of the product

of protonation of the carbonyl group

Unstabilized by resonance,

destabilized by the C

O dipole

–

FIGURE 17.14 Delocalization

stabilizes the intermediate resulting

from protonation of the carbonyl

oxygen.The carbon–oxygen dipole

destabilizes the cation formed from

protonation of the hydroxyl group.

838 CHAPTER 17 Carboxylic Acids

For these reasons, carboxylic acids are more strongly basic at the carbonyl oxygen

than at the hydroxyl oxygen. Does this mean that the hydroxyl group is never proto-

nated? Certainly not, but reaction at the more basic site is favored and will be faster.

PROBLEM 17.8 Explain why the thermodynamic stability of the protonated car-

bonyl should influence the rate (a kinetic parameter) of protonation.

With so many possible sites for reaction we might expect a rich chemistry of

carboxylic acids.That idea would be exactly right. Figure 17.15 summarizes the sites

of reactivity we have discussed so far.

Lewis basicity (greater)

(nucleophile)

Lewis basicity (lesser)

(nucleophile)

Lewis acidity

(electrophile)

Brønsted acidity

(electrophile)

FIGURE 17.15 The various sites of

reactivity for a carboxylic acid.

Summary

We have learned how to name carboxylic acids and their salts.The properties of

carboxylic acids include their acidity, their propensity to form dimers, the solu-

bility in water of the corresponding salt, their resonance stabilization, and their

multiple sites of reactivity.These traits make them useful reagents both in Nature

and the chemistry lab.

SALICYLIC ACID

myriad uses. It was synthesized as early as 1853, and its

analgesic properties were recognized by a group at

Farbenfabriken Baeyer in 1897. It apparently works by

inhibiting the production of an enzyme, prostaglandin

cyclooxygenase, that catalyzes the synthesis of molecules

called prostaglandins. Prostaglandins are active in many

ways, one of which is to help transmit pain signals across

synapses. No prostaglandins, no signal transmission; no sig-

nal transmission, no pain.

The simple aromatic carboxylic acid, salicylic acid, is a plant

hormone and is involved in many of the marvelously com-

plex interactions between plants and animals that makes the

study of biology so fascinating. Here’s a typical example

involving the voodoo lily. The flower of the voodoo lily emits

foul odors that attract flies, and the flies are used to transmit

pollen from the male reproductive organs to the female organs

of another lily. In the late afternoon, salicylic acid triggers

the first of two surges of heat, some 10–20 °C above normal.

This first surge releases the odor and attracts the flies, which

become trapped and coated with pollen. A second heat wave

the next morning opens the flower, awakens the pollen-

covered flies, which escape until the afternoon when they

are attracted to another voodoo lily and deposit the pollen.

Salicylic acid is also an analgesic. Indeed, the chewing of

willow bark, which contains salicylic acid, has been used to

control pain for thousands of years. You are probably most

familiar with salicylic acid in its acetylated form, acetyl sali-

cylic acid, or aspirin. Aspirin is a versatile pain killer and has

OH O

Voodoo lily

Salicylic acid