Page 357 - Advanced Organic Chemistry Part B - Reactions & Synthesis

decreases the rate of acid-catalyzed enolization and thus retards the introduction of 329
a second halogen at the same site, so monohalogenation can usually be carried out
satisfactorily. In contrast, in basic solution halogenation tends to proceed to polyhalo- SECTION 4.3
genated products because the polar effect of a halogen accelerates base-catalyzed Electrophilic Substitution
to Carbonyl Groups
enolization. With methyl ketones, base-catalyzed reaction with iodine or bromine
leads ultimately to cleavage to a carboxylic acid. 115 These reactions proceed to the
trihalomethyl ketones, which are susceptible to base-induced cleavage.

O O – O –
X 2 RCO 2
R C CH 3 R C CX 3 R C CX
– OH 3 + HCX 3
OH

The reaction can also be effected with hypochlorite ion, and this constitutes a useful
method for converting methyl ketones to carboxylic acids.

O
) C
–
(CH ) C CHCCH 3 + OCl (CH 3 2 CHCO H
2
3 2
49–53%
Ref. 116
The most common preparative procedures involve use of the halogen,
usually bromine, in acetic acid. Other suitable halogenating agents include
N-bromosuccinimide, tetrabromocyclohexadienone, and sulfuryl chloride.

O O
Br 2
Br CCH 3 CH CO H Br CCH Br
2
3
2
69 –72%
Ref. 117
O O
Br
N-bromosuccinimide

CCl 4
Ref. 118

O O
CH
SO Cl 3
CH 3 2 2
Cl
83–85%
Ref. 119
115 S. J. Chakabartty, in Oxidations in Organic Chemistry, Part C, W. Trahanovsky, ed., Academic Press,
New York, 1978, Chap. V.
116
L. J. Smith, W. W. Prichard, and L. J. Spillane, Org. Synth., III, 302 (1955).
117
W. D. Langley, Org. Synth., 1, 122 (1932).
118 E. J. Corey, J. Am. Chem. Soc., 75, 2301 (1954).
119
E. W. Warnhoff, D. G. Martin, and W. S. Johnson, Org. Synth., IV, 162 (1963).