Organic Chemistry

We have seen that the OH group of a carboxylic acid can be substituted to give a vari-
ety of carboxylic acid derivatives. Similarly, the OH groups of carbonic acid can be
substituted by other groups.

PROBLEM 37

What products would you expect to obtain from the following reactions?

a. d.

b. e.

c.methyl carbamate+methylamine f. b-ethylglutaric acid+acetyl chloride+¢

malonic acid+ 2 acetyl chloride urea+water+H+

phosgene+excess diethylamine urea+water

Summary 719

Summary

A carbonyl groupis a carbon double-bonded to an oxygen;
an acyl groupis a carbonyl group attached to an alkyl or
aryl group. Acyl halides, acid anhydrides, esters, and
amidesare called carboxylic acid derivativesbecause they
differ from a carboxylic acid only in the nature of the group
that has replaced the OH group of the carboxylic acid.
Cyclic esters are called lactones; cyclic amides are lactams.
There are symmetrical anhydridesand mixed anhydrides.
Carbonyl compoundscan be placed in one of two class-
es. Class I carbonyl compounds contain a group that can be
replaced by another group; carboxylic acids and carboxylic
acid derivatives belong to this class. Class II carbonyl com-
pounds do not contain a group that can be replaced by
another group; aldehydes and ketones belong to this class.
The reactivity of carbonyl compounds resides in the polarity
of the carbonyl group; the carbonyl carbon has a partial positive
charge that is attractive to nucleophiles. Class I carbonyl
compounds undergo nucleophilic acyl substitution reactions:
a nucleophile replaces the substituent that was attached to the
acyl group in the reactant. All Class I carbonyl compounds react
with nucleophiles in the same way: the nucleophile attacks the
carbonyl carbon, forming an unstable tetrahedral intermedi-
ate. (Generally, a compound with an carbon bonded to an
oxygen is unstable if the carbon is bonded to another
electronegative atom.) The tetrahedral intermediate reforms a
carbonyl compound by eliminating the weakest base.
A carboxylic acid derivative will undergo a nucleophilic
acyl substitution reaction provided that the newly added
group in the tetrahedral intermediate is not a much weaker
base than the group that was attached to the acyl group in the
reactant. The weaker the base attached to the acyl group, the
easier it is for both steps of the nucleophilic acyl substitution
reaction to take place. The relative reactivities toward nucleo-
philic acyl substitution: acyl halides acid anhydrides
carboxylic acids and esters amides carboxylate ions.
Hydrolysis,alcoholysis, and aminolysisare reactions in
which water, alcohols, and amines, respectively, convert one

7 7

7 7

sp^3

sp^3

compound into two compounds. A transesterification reac-

tionconverts one ester to another ester. Treating a carboxylic

acid with excess alcohol and an acid catalyst is called a

Fischer esterification. An ester with a tertiary alkyl group

hydrolyzes via an reaction.

The rate of hydrolysis can be increased by either acid or

the rate of alcoholysis can be increased by either acid

or An acid increases the rate of formation of the

tetrahedral intermediate by protonating the carbonyl oxy-

gen, which increases the electrophilicity of the carbonyl

group, and by decreasing the basicity of the leaving group,

which makes it easier to eliminate. Hydroxide (or alkox-

ide) ion increases the rate of formation of the tetrahedral

intermediate—it is a better nucleophile than water (or an

alcohol)—and increases the rate of collapse of the tetrahe-

dral intermediate. Hydroxide ion promotes only hydrolysis

reactions; alkoxide ion promotes only alcoholysis reac-

tions. In an acid-catalyzed reaction, all organic reactants,

intermediates, and products are positively charged or neu-

tral; in hydroxide-ion- or alkoxide-ion-promoted reactions,

all organic reactants, intermediates, and products are nega-

tively charged or neutral.

Fatsand oilsare triesters of glycerol. Hydrolyzing the

ester groups in a basic solution (saponification) forms glyc-

erol and fatty acid salts (soaps). Long-chain carboxylate ions

arrange themselves in spherical clusters called micelles. The

attractive forces of hydrocarbon chains for each other in

water are called hydrophobic interactions.

Amides are unreactive compounds but do react with water

and alcohols if the reaction mixture is heated in the presence

of an acid. Nitriles are harder to hydrolyze than amides. The

Gabriel synthesis, which converts alkyl halides into primary

amines, involves the hydrolysis of an imide.

Organic chemists activate carboxylic acids by converting

them into acyl halides or acid anhydrides. Cells activate car-

boxylic acids by converting them into acyl phosphates,acyl

pyrophosphates,acyl adenylates, and thioesters.

RO-.

HO-;

SN 1

Cl

phosgene

Cl OCH 3

dimethyl carbonate

CH 3 ONH 2

urea

H 2 NOH

carbamic acid

H 2 N OCH 3

methyl carbamate

H 2 N

C

O

C

O

C

O

C

O

C

O