Page 677 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

7.4.2. Aminolysis of Esters 659

Esters react with ammonia and amines to give amides. The mechanism involves SECTION 7.4
nucleophilic attack of the amine at the carbonyl group, followed by expulsion of the Substitution Reactions of
Carboxylic Acid
alkoxy group from the tetrahedral intermediate. The identity of the rate-determining
Derivatives
step depends primarily on the leaving-group ability of the alkoxy group. 41 With
relatively good leaving groups such as phenols or trifluoroethanol, the slow step is
expulsion of the oxygen leaving group from a zwitterionic tetrahedral intermediate A.
With poorer leaving groups, breakdown of the tetrahedral intermediate occurs only
after formation of the anionic species B.

O O – O
+
RCOR' + R"NH 2 R"N H COR' R'NHCR + R'O –
2
R
A H +
OH O –
R"NHCOR' R"NHCOR'
H +
C R B R

Aminolysis of esters often exhibits general base catalysis in the form of reaction
rate terms that are second order in the amine. The amine is believed to assist depro-
tonation of the zwitterionic tetrahedral intermediate. 42 Deprotonation of the nitrogen
facilitates breakdown of the tetrahedral intermediate because the increased electron
density at nitrogen favors expulsion of an alkoxide ion.

H O – H O – O
B: H N + COR B + H + R" N COR R"NHCR
R" R R

Detailed mechanistic studies have been carried out on aminolysis of substituted
aryl acetates and aryl carbonates. 43 Aryl esters are considerably more reactive than
alkyl esters because phenoxide ions are better leaving groups than alkoxide ions. The
tetrahedral intermediate formed in aminolysis can exist in several forms that differ in
the extent and the site of protonation.

41
F. M. Menger and J. H. Smith, J. Am. Chem. Soc., 94, 3824 (1972); A. C. Satterthwait and W. P. Jencks,
J. Am. Chem. Soc., 96, 7018 (1974).
42 W. P. Jencks and M. Gilchrist, J. Am. Chem. Soc., 88, 104 (1966); J. F. Kirsch and A. Kline, J. Am.
Chem. Soc., 91, 1841 (1969); A. S. Shawali and S. S. Biechler, J. Am. Chem. Soc., 89, 3020 (1967);
J. F. Bunnett and G. T. Davis, J. Am. Chem. Soc., 82, 665 (1961).
43
W. P. Jencks and M. Gilchrist, J. Am. Chem. Soc., 90, 2622 (1968); A. Satterthwait and W. P. Jencks,
J. Am. Chem. Soc., 96, 7018 (1974); A. Satterthwait and W. P. Jencks, J. Am. Chem. Soc., 96, 7031
(1974); M. J. Gresser and W. P. Jencks, J. Am. Chem. Soc., 99, 6970 (1977).