Page 246 - Advanced Organic Chemistry Part B - Reactions & Synthesis

218 N
N
CHAPTER 3 N
Functional Group H
Interconversion OH + SOCl 2 Cl
by Substitution,
Including Protection and 92%
Deprotection
This reagent combination also converts carboxylic acids to acyl chlorides (see
Section 3.4.1). The mechanistic basis for the special effectiveness of benzotriazole has
not yet been determined, but it seems likely that nucleophilic catalysis is involved.
Sulfinyl ester intermediates may be involved, because Z-2-butene-1,4-diol gives a
cyclic sulfite ester with one equivalent of reagent but the dichloride with two equivalents.

N
N N
N
N
N
O O H 1.2 equiv H 2.5 equiv
S HOCH CH OH ClCH CH Cl
SOCl 2 1.2 equiv 2 2 2 2
SOCl 2 2.5 equiv
O
Reaction with the hindered secondary alcohol menthol stops at the dialkyl sulfite ester.
The examples reported do not establish the stereochemistry of the reaction.
The mechanism for the reactions of alcohols with phosphorus halides can be illus-
trated using phosphorus tribromide. Initial reaction between the alcohol and phosphorus
tribromide leads to a trialkyl phosphite ester by successive displacements of bromide.
The reaction stops at this stage if it is run in the presence of an amine, which neutralizes
9
the hydrogen bromide that is formed. If the hydrogen bromide is not neutralized,
the phosphite ester is protonated and each alkyl group is converted to the halide by
nucleophilic substitution by bromide ion. The driving force for cleavage of the C−O
bond is the formation of a strong phosphoryl double bond.

ROH + PBr 3 (RO) P + 3 HBr
3
(RO) 3 P + HBr RBr + O P(OR) 2
H
OH
O P(OR) + HBr RBr + O POR
2
H H
OH H
O P OR + HBr RBr + O P(OH) 2
H

As C−Br bond formation occurs by back-side attack, inversion of the configu-
ration at carbon is anticipated. However, both racemization and rearrangement are
observed as competing processes. 10 For example, conversion of 2-butanol to 2-
butyl bromide with PBr is accompanied by 10–13% racemization and a small
3
9 A. H. Ford-Moore and B. J. Perry, Org. Synth., IV, 955 (1963).
10
H. R. Hudson, Synthesis, 112 (1969).