Page 682 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

664 The usual hydrolysis mechanism in strongly acidic solutions involves addition
of water to the O-protonated amide followed by dissociation of the tetrahedral
CHAPTER 7 intermediate.
Addition, Condensation
+
and Substitution O H OH OH
+
Reactions of Carbonyl + O H +
Compounds RCNH 2 + H 2 O RCNH 2 RCN H 3 + NH 3 RCO 2 H + NH 4
RCOH
+ OH
O H 2
There is almost no exchange of oxygen with water during acid-catalyzed hydrolysis
of amides. 53 Since a tetrahedral intermediate is involved, the lack of exchange means
that it must react exclusively by elimination of the nitrogen substituent. This result is
reasonable, because the amino group is the most basic site and is the preferred site
of protonation in the tetrahedral intermediate. The protonated amine is a much better
leaving group than the hydroxide ion.
Acylimidazoles and related amides in which the nitrogen atom is part of an
aromatic ring hydrolyze much more rapidly than aliphatic amides. A major factor is
the decreased resonance stabilization of the carbonyl group, which is opposed by the
participation of the nitrogen lone pair in the aromatic sextet.

O O O –
RC N N RC N + N – RC N + N
unfavorable
The acid-catalyzed hydrolysis of imidazolides is accelerated by protonation of N(3),
54
which increases the leaving-group ability of the ring, and accumulation of additional
nitrogens in the ring (triazoles, tetrazoles) further increased that ability. 55

7.4.4. Acylation of Nucleophilic Oxygen and Nitrogen Groups

The conversion of alcohols to esters by O-acylation and of amines to amides by
N-acylation are fundamental organic reactions that are the reverse of the hydrolyses
discussed in the preceding sections. In Section 3.4 of Part B we discuss these reactions
from the point of view of synthetic applications and methods.
Although the previous two sections of this chapter emphasized hydrolytic
processes, two mechanism that led to O or N-acylation were considered. In the
discussion of acid-catalyzed ester hydrolysis, it was pointed out that this reaction is
reversible (p. 654). Thus it is possible to acylate alcohols by acid-catalyzed reaction
with a carboxylic acid. This is called the Fischer esterification method. To drive
the reaction forward, the alcohol is usually used in large excess, and it may also be
necessary to remove water as it is formed. This can be done by azeotropic distillation
in some cases.

H +
RCO H + R'OH RCO 2 R' + H O
2
2
53 R. A. McClelland, J. Am. Chem. Soc., 97, 5281 (1975); For cases in which some exchange does occur,
see H. Slebocka-Tilk, R. S. Brown, and J. Olekszyk, J. Am. Chem. Soc., 109, 4620 (1987); A. J. Bennet,
H. Slebocka-Tilk, R. S. Brown, J. P. Guthrie, and A. J. Jodhan, J. Am. Chem. Soc., 112, 8497 (1990).
54 T. H. Fife, Acc. Chem. Res., 26, 325 (1993).
55
J. F. Patterson, W. P. Huskey, and J. L. Hoggs, J. Org. Chem., 45, 4675 (1980); B. S. Jursic and
Z. Zdravkovski, Theochem, 109, 177 (1994).