Page 281 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Scheme 3.5. Acid-Catalyzed Esterification 253

1 a SECTION 3.4
ArSO H
3
CH CO H + HOCH CH 2 CH 2 Cl CH 3 CO 2 CH 2 CH 2 CH 2 Cl Interconversion of
2
2
3
benzene, Carboxylic Acid
removal of water 93–95% Derivatives
2 b H SO 4
2
HO CC CCO H + CH OH 25°C, 4 days CH 3 O CC CCO CH 3
2
2
2
3
2
(20 equiv) 72–88%
3 c
H 2 SO 4
CH CH CHCO H + CH CHCH CH 3 CH CH CHCO CHCH CH 3
3
2
3
2
3
2
2
benzene,
OH removal of water CH 3 85–90%
4 d HCl
PhCHCO H + C H OH PhCHCO 2 2 5
C H
2 5
2
(excess) 78°C, 5 h
OH OH 82–86%
5 e
O
H C H C CO 2 CH 3
2
2
ArSO H
3
O + CH OH
3
(excess) 67–68°C, CO CH
O 40 h 2 3
80–90%
a. C. F. H. Allen and F. W. Spangler, Org. Synth., III, 203 (1955).
b. E. H. Huntress, T. E. Lesslie, and J. Bornstein, Org. Synth., IV, 329 (1963).
c. J. Munch-Petersen, Org. Synth., V, 762 (1973).
d. E. L. Eliel, M. T. Fisk, and T. Prosser, Org. Synth., IV, 169 (1963).
e. H. B. Stevenson, H. N. Cripps, and J. K. Williams, Org. Synth., V, 459 (1973).
(DCCI) is often used for coupling carboxylic acids and amines to give amides. Since
amines are better nucleophiles than alcohols, the leaving group in the acylation reagent
need not be as reactive as is necessary for alcohols. The p-nitrophenyl 132 and 2,4,5-
trichlorophenyl 133 esters of amino acids are sufficiently reactive toward amines to be
useful in amide synthesis. Acyl derivatives of N-hydroxysuccinimide are also useful
for synthesis of peptides and other types of amides. 134 135 Like the p-nitrophenyl esters,
the acylated N-hydroxysuccinimides can be isolated and purified, but react rapidly
with free amino groups.
O O
2
1
O R O R O O R 2 O R 1 O
XCNHCHCO N + H NCHCY XCNHCHCNHCHCY + HO N
2
O O
The N-hydroxysuccinimide that is liberated is easily removed because of its solubility
in dilute base. The relative stability of the anion of N-hydroxysuccinimide is also
responsible for the acyl derivative being reactive toward nucleophilic attack by an
132
M. Bodanszky and V. DuVigneaud, J. Am. Chem. Soc., 81, 5688 (1959).
133 J. Pless and R. A. Boissonnas, Helv. Chim. Acta, 46, 1609 (1963).
134 G. W. Anderson, J. E. Zimmerman, and F. M. Callahan, J. Am. Chem. Soc., 86, 1839 (1964).
135
E. Wunsch and F. Drees, Chem. Ber., 99, 110 (1966); E. Wunsch, A. Zwick, and G. Wendlberger,
Chem. Ber., 100, 173 (1967).