Page 683 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

The second reaction that should be recalled is the aminolysis of esters (p. 659), which 665
leads to the formation of amides by N-acylation. The equilibrium constant for this
reaction is ordinarily favorable, but the reactions are rather slow. SECTION 7.4
Substitution Reactions of
RCO R' + R"NH 2 RCONHR" + R'OH Carboxylic Acid
2
Derivatives
The most common O- and N-acylation procedures use acylating agents that are
more reactive than carboxylic acids or their esters. Acyl chlorides and anhydrides
react rapidly with most unhindered alcohols and amines to give esters and amides,
respectively.

RCOCl (RCO) O
HCl + RCO R' R'OH 2 RCO 2 R' + RCO H
2
2
RCOCl (RCO) O
HCl + RCONHR" R"NH 2 2 RCONHR" + RCO 2 H
56
The general features of the mechanisms are well established. The nucleophilic species
undergoes addition at the carbonyl group, followed by elimination of the halide or
carboxylate group. Acyl halides and anhydrides are reactive acylating reagents because
of a combination of the polar effect of the halogen or oxygen substituent, which
enhances the reactivity of the carbonyl group, and the ease with which the tetrahedral
intermediate can expel these relatively good leaving groups.

O O –
RCX + R'OH RC OR' RCO R' + HX
2
X
–
O O
+
RCX + R"NH 2 RC N H R" RCONHR" + HX
2
X
X = halide or carboxylate
Acylation of alcohols is often performed in the presence of an organic base such
as pyridine. The base serves two purposes: it neutralizes the protons generated in
the reaction and prevents the development of high acid concentrations. Pyridine also
becomes directly involved in the reaction as a nucleophilic catalyst (see p. 657).

O O O –
R'OH
RCX + :N RC N + RC N + RCO R' + HN +
2
+
HO R'
X = halide or carboxylate
Pyridine is more nucleophilic than an alcohol toward the carbonyl center of an acyl
chloride. The product that results, an acylpyridinium ion, is, in turn, more reactive
toward an alcohol than the original acyl chloride. The conditions required for nucleo-
philic catalysis therefore exist, and acylation of the alcohol by acid chloride is faster
in the presence of pyridine than in its absence. Among the evidence that supports this

56
D. P. N. Satchell, Q. Rev. Chem. Soc., 17, 160 (1963).