Jones M., Fleming S.A. Organic Chemistry

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17.7 Reactions of Carboxylic Acids 859

Ketones

Malonic acids

Acids

Monoester of

carbonic acid

Alcohols

β-Keto acids

+ CO

(> 60%)

(> 70%)

(~100%)

~25 ⬚

HOR

30 ⬚C

GENERAL REACTIONS

SPECIFIC EXAMPLES

WEB 3D

FIGURE 17.54 Three kinds of carboxylic acid that decarboxylate (lose CO

) easily.

(b)

(a)

HHO

We will defer discussion of the decarboxylation of β-keto acids until we learn

the utility of such compounds in Chapter 19, but carbonates and malonic acids will

be mentioned here.

Carbonic acid (H

or HOCOOH) is itself unstable, although its salts are

isolable and familiar as sodium bicarbonate and sodium carbonate:

PROBLEM 17.22 Show the product for each of the following reactions:

Carbonic acid

(unstable)

Sodium bicarbonate

(stable)

Sodium carbonate

(stable)

–

860 CHAPTER 17 Carboxylic Acids

FIGURE 17.55 Monoesters of

carbonic acid decarboxylate easily, but

carbonates (acid diesters) do not.

Monoesters of carbonic acid lose carbon dioxide easily. The loss of carbon dioxide

is irreversible, because the gaseous carbon dioxide escapes.The diesters of carbonic

acid (carbonates) are stable (Fig. 17.55).

Carboxylic acids can be electrochemically decarboxylated to give, ultimately, a

hydrocarbon composed of two R groups. This reaction, called the Kolbe electrolysis

after Hermann Kolbe (1818–1884), involves an electrochemical oxidation of the

carboxylate anion to give the carboxyl radical. Loss of carbon dioxide gives an alkyl

radical that can dimerize to give the hydrocarbon (Fig. 17.57).

Carbamic acid Urea

(stable)

Carbamate

(stable)

N H

NNH

WEB 3D

FIGURE 17.56 Carbamic acids

decarboxylate, but urea and

carbamates are stable.

electrochemical

oxidation

Kolbe

2 CO

( 75%)

–

THE GENERAL CASE

A SPECIFIC EXAMPLE

FIGURE 17.57 The Kolbe electrolysis is a source of molecules, , made up of two R groups from .R

COOHR

Stable carbonate

(no H to be removed)

ROH

HOR

–

Similarly, carbamic acid, the amide derivative of carbonic acid, is also unstable,

and loses carbon dioxide to give amines (Fig. 17.56). The diamide, urea, and car-

bamates, which cannot lose carbon dioxide, are stable.

17.7 Reactions of Carboxylic Acids 861

17.7h Formation of Alkyl Bromides: The Hunsdiecker Reaction The

carboxyl radical encountered in Figure 17.57 is also the active ingredient in the

Hunsdiecker reaction in which alkyl bromides are formed from acids (Heinz

Hunsdiecker, 1904–1981; Cläre Dieckmann Hunsdiecker, 1903–1995). Although

this reaction is named for the Hunsdieckers, this reaction was actually discovered

by Alexander Borodin, the Russian composer-physician-chemist. Borodin is far

more famous for his somewhat schmaltzy music rather than his excellent chem-

istry. This reaction was first done by Borodin in 1861, 81 years before the

Hunsdieckers! Typically, the silver salt of the acid is used and allowed to react with

bromine.The first step is the formation of the hypobromite (Fig. 17.58). On heat-

ing, the weak oxygen–bromine bond breaks homolytically to give the carboxyl rad-

ical and a bromine atom. As in the Kolbe reaction, the carboxyl radical undergoes

decarboxylation to give an alkyl radical. In this case, however, the alkyl radical can

carry the chain reaction further by reacting with the hypobromite to produce an

alkyl bromide and another molecule of carboxyl radical as shown in Figure 17.58.

For a review of radical chain reactions, see Chapter 11, pp. 481ff.

AgBr

A hypobromite

Product Recycles

–+

(67%)

BrCH

CCl

THE GENERAL CASE

A SPECIFIC EXAMPLE

FIGURE 17.58 The decarboxylation

of the carboxylate radical is also

involved in the Hunsdiecker reaction,

a synthesis of alkyl bromides from

carboxylic acids. The recycling, chain-

propogating carboxyl radical is

highlighted.

Summary

That’s a lot of material. Many new kinds of compounds have appeared and there

may seem to be an overwhelming number of new reactions.Don’t be dismayed! Most

involve versions of the addition–elimination reaction. Keep this generalization

in mind and you will be able to figure out what is happening in these reactions

relatively easily. It is not necessary, or productive, to try to memorize all this

material. What is far more effective is to learn the basic process well, and then

practice applying it in different circumstances.

862 CHAPTER 17 Carboxylic Acids

PROBLEM 17.23 Suggest a mechanism for the hydroxide ion–induced hydrolysis

(saponification) of a fat to a fatty acid.

In this chapter we learned that carboxylic acids can be used to make

polyamides and polyesters. We also learned the reactions that use organic acids

to make acid chlorides, acid anhydrides,esters, amides, ketones, and primary alco-

hols. Finally, we’ve learned about a few decarboxylation reactions of carboxylic

acids. Perhaps the most important of the reactions in this chapter are acid chlo-

ride formation and Fischer esterification. You certainly will encounter these two

reactions often in your study of organic chemistry.

17.8 Special Topic: Fatty Acids

We have spent many pages looking at the reactions of carboxylic acids. Now let’s

consider a class of molecules found extensively in Nature, called fatty acids.

These compounds contain long unbranched hydrocarbon chains with a single

carboxylic acid at one end. The properties of such molecules are strongly influ-

enced by the presence of both the long-chain and the acid group. Most fatty acids

in Nature are even-numbered long-chain acids because they are formed by a

process that puts the hydrocarbon chain together two carbons at a time using

an acetic acid derivative.

The fatty acids are usually found in plants and animals as the corresponding fat

or oil (Fig. 17.59), a fatty acid triester of glycerol. The fatty acid triesters that are

solids at room tempertature are called fats and those that are liquid at room tem-

perature are known as oils. The base-induced hydrolysis of these esters is called

saponification. We will learn more about this reaction in Chapter 18.

(CH

)

2. H

O /H

1. KOH/H

A fat

Glycerol

n = 10 Lauric acid

n = 12 Myristic acid

n = 14 Palmitic acid

n = 16 Stearic acid

n = 18 Arachidic acid

(CH

)

(CH

)

Fatty acid

WEB 3D

(CH

)

FIGURE 17.59 Some fatty acids that can be made from the hydrolysis of fats.

CoA stands for coenzyme A, one of many molecules necessary to promote an enzymatic reaction.

Fatty acids are most important molecules. For example, part of our body’s ener-

gy supply comes from a pathway that starts with the hydrolysis of a fat to fatty acids,

such as palmitic acid, which is then converted into a thioester (

).R

SCoA

17.8 Special Topic: Fatty Acids 863

The thioester is repetitively cleaved by enzymes to give multiple two-carbon units

(Fig. 17.60). These acetyl groups are called acetyl-CoA, and are fed into the Krebs

cycle, a series of reactions in which acetyl-CoA is oxidized to CO

O O

CH CH

OCH

HS CH

Palmitate

Acetyl-CoA

8 CoA-SH

CoA-SH

SCoA

(CH

)

CoA

FIGURE 17.60 Enzymes ultimately

convert fatty acids such as palmitate,

a 16-carbon fatty acid, into eight

molecules of acetyl-CoA.

(CH

)

Palmitate

CoA-SH

Acetyl-CoA

SCoA

(CH

)

Myristate

Same carbon

SCoA

(CH

)

βα

FIGURE 17.61 Fatty acids are deconstructed two carbons at a time. Note that the β carbon

of the palmitic acid becomes the carbonyl carbon of the 14-carbon acid.

Thus, it seems that the methyl group of acetyl-CoA must be the α carbon of

the original fatty acid and the β carbon of the fatty acid becomes the carbonyl car-

bon of myristate (Fig. 17.61). We will come back to this reaction in Chapter 19, but

you should be able to appreciate both the extent and difficulty of the task that Nature

faces here—How to break the α–β bond in palmitate? That’s no simple task, and

we shall need the material in Chapter 19 to solve it.

Fatty acids often have double bonds in the carbon chain. The presence of double

bonds in the triester fat affects their solubility and melting points. Saturated fats (those

having no double bonds) are solids, and there are well-documented health concerns

with diets that are high in saturated fat content. Fatty acids with trans double bonds

are also likely to be solid, one of the reasons for recent “trans-fat” health concerns.

When fatty acids have cis double bonds, their corresponding triesters are oils, liq-

uids at room temperature. Because the cis double bond results in poorer stacking

between the chains, these molecules do not solidify as easily as their trans counter-

parts (Fig. 17.62).

864 CHAPTER 17 Carboxylic Acids

Saturated fat

cis Unsaturated fat (oil)

trans Unsaturated fat (trans fat)

FIGURE 17.62 The triesters with no

double bonds can stack much better

than the triesters with a cis double

bond.Trans fats also line up well

and have higher melting points than

cis fats.

Soap bubbles are thin films made

from long-chain carboxylic acid salts

that are aligned with each other.

17.8 Special Topic: Fatty Acids 865

There are many fatty acids that are necessary for proper cellular function.

Humans make most of the fatty acids that are needed. However, the omega-3 fatty

acids (Fig. 17.63) are an essential part of our diet. Omega-3 fatty acids belong to

a family of long-chain carboxylic acids that have a cis double bond at the third

carbon from the end of the chain. The specific molecules differ in chain length

and in the number of additional double bonds in the chain.The FDA has report-

ed data that suggest omega-3 fatty acids reduce the risk of coronary heart disease.

␣-Linolenic acid (ALA)

(Z, Z, Z )-9,12,15-Octadecatrienoic acid

(Z, Z, Z, Z, Z )-5,8,11,14,17-

Eicosapentaenoic acid (EPA)

(all Z )-4,7,10,13,16,19-

Docsahexaenoic acid (DHA)

FIGURE 17.63 The omega-3 fatty

acids involved in cellular function: α-

linolenic acid (ALA),

eicosapentaenoic acid (EPA), and

docosahexaenoic acid (DHA).

Omega-3 fatty acids are found in high concentrations in fish oil. Fish do not actu-

ally synthesize these compounds, but obtain them from algae. Even higher concen-

trations of omega-3 fatty acids are found in flaxseed oil. Lingonberry and kiwi are

also rich in these compounds.

866 CHAPTER 17 Carboxylic Acids

There is another topic of importance related to fatty acids. Soaps are the sodi-

um salts of long-chain fatty acids, and work in the following way.These compounds

contain both a highly polar end, the carboxylic acid salt, and a most nonpolar end,

the long-chain hydrocarbon end (Fig. 17.64). The polar end is soluble in polar

solvents such as water, but the nonpolar, hydrocarbon end is not. In aqueous solu-

tion,the hydrophobic (water-hating) hydrocarbon ends cluster together at the inside

of a sphere, protected from the aqueous environment by the hydrophilic (water-

loving) polar acid-salt groups forming the interface with the polar water molecules.

Such aggregates are called micelles. The cleaning ability of soaps comes from the

oil-capturing property of the hydrophobic portion of the micelle, which can remove

oil and grease from a surface.The micelle is soluble in water and so it washes away

the non-water-soluble oil and grease.

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

COO

–

A micelle

(CH

)

base

A fatty acid

(CH

)

A soap

ONa

–

(b)

(a)

FIGURE 17.64 (a) The formation of a soap from a fatty acid.

(b) In polar media, soaps form micelles, with the hydrophobic

hydrocarbon chains directed toward the center of a sphere, away

from the polar solvent.The outside of the sphere contains the

polar carboxylate anions and their positive counterions.

Similar micellar species are formed from detergents, which are synthetic soaps.

One of the most common synthetic soaps is a long-chain sulfonic acid salt

(Fig. 17.65). Because detergents are industrially synthesized, they haven’t always

been biodegradable. Perhaps not surprisingly, the key to chemists finding an

17.9 Summary 867

A long-chain

hydrocarbon

–

S R

–

Grease

(b)

(a)

FIGURE 17.65 (a) A synthetic soap, a detergent, and (b) a micelle of

the detergent solubilizing a grease glob.

PROBLEM 17.24 What process do you suppose Nature uses to degrade the long-

chain detergent?

environmentally friendly soap was recognizing that Nature can oxidatively cleave

long-chain carbon compounds, but does not do as well with branched alkyl groups.

Using this “green” recognition has given us biodegradable detergents.

17.9 Summary

New Concepts

Carboxylic acids exhibit several kinds of reactivity. So far, we have

seen many kinds of molecules (aldehydes and ketones, for exam-

ple) that can be both electrophiles and nucleophiles. But car-

boxylic acids are even more polyreactive.They are Brønsted acids

through proton loss from the hydroxyl group. They are also elec-

trophiles (Lewis acids) through reaction at the carbonyl carbon.

Carboxylic acids act as Brønsted bases and nucleophiles (Lewis

bases) through reaction at the more basic carbonyl oxygen.

The Brønsted acidity of carboxylic acids, long thought to

rest largely upon the delocalization of the carboxylate anion

produced by ionization, is also dependent on the inductive

effect of the polarized carbonyl group.

868 CHAPTER 17 Carboxylic Acids

Most of the new reactions in this chapter are examples of

addition–elimination processes. This mechanism has appeared

occasionally before, but it is emphasized in this chapter for the

first time. Any carbonyl compound bearing a leaving group can

be attacked by a nucleophile to give a tetrahedral intermediate

(addition) that can then expel the leaving group (elimination)

(Fig. 17.66).

For carboxylic acids, the success of an addition–elimination

reaction depends on the transformation of the carboxyl hydroxyl

group into a better leaving group. This conversion is often done

through protonation in acid-catalyzed reactions. The best exam-

ple is Fischer esterification, and its cyclic variation, lactone for-

mation (Fig. 17.33).

The carboxyl OH can also be made into a better leaving

group through other chemical conversions. An excellent exam-

ple is acid chloride formation in which a chlorosulfite ester is

first produced. Addition of chloride to the carbonyl group of

the ester leads to an intermediate that can eliminate sulfur

dioxide and chloride, thus producing the acid chloride

(Figs. 17.42 and 17.43).

The acid chlorides contain an excellent leaving group,

and addition–elimination reactions are common (Fig. 17.44).

Occasionally, the carboxylate anion can be used as a displac-

ing agent in an S

2 reaction. In order for this reaction to be

successful, the Lewis acid partner in the reaction must be very

reactive (Fig. 17.30).

The electrochemical reaction of carboxylate anions

leads to hydrocarbons (Kolbe electrolysis). Other reactions

involving decarboxylations are briefly mentioned

(Fig. 17.54).

Key Terms

acid anhydride (p. 855)

activating agent (p. 850)

amide (p. 850)

carbamates (p. 860)

carbamic acid (p. 860)

carboxylate anion (p. 832)

decarboxylation (p. 858)

detergent (p. 866)

fatty acids (p. 862)

Fischer esterification (p. 841)

Hunsdiecker reaction (p. 861)

hydrophilic (p. 866)

hydrophobic (p. 866)

Kolbe electrolysis (p. 860)

lactam (p. 851)

lactone (p. 849)

micelle (p. 866)

ortho esters (p. 846)

saponification (p. 862)

soap (p. 866)

tetrahedral intermediate

(p. 842)

urea (p. 860)

Reactions, Mechanisms, and Tools

addition

–

RNu

Tetrahedral intermediate

elimination

FIGURE 17.66 The addition–elimination reaction.

Syntheses

SOCl

PCl

A chlorosulfite

ester (an

activated acid) is

an intermediate

2. Acids1. Acid Halides

Other oxidizing agents (listed above) work

HNO

[O] = KMnO

, HNO

, CrO

, RuO

OHR

[O]