Page 248 - Advanced Organic Chemistry Part B - Reactions & Synthesis

220 H C C H H 3 C C H
8 17
8 17
3
CHAPTER 3 H 3 C Br 2 , Ph 3 P H C
3
Functional Group
Interconversion
by Substitution, HO Br Ref. 16
Including Protection and
Deprotection
2,4,4,6-Tetrabromocyclohexa-2,5-dienone is also a useful bromine source.
Ph P
H 3
C 12 25 C H
O O Br O O 12 25
Br
OH O Br
Br
Br Ref. 17
Triphenylphosphine dichloride exhibits similar reactivity and can be used to
18
prepare chlorides. The most convenient methods for converting alcohols to chlorides
are based on in situ generation of chlorophosphonium ions 19 by reaction of tri-
phenylphosphine with various chlorine compounds such as carbon tetrachloride 20 or
hexachloroacetone. 21 These reactions involve formation of chlorophosphonium ions.

Ph 3 P + CCl 4 Ph P + Cl + – CCl 3
3
O O
Ph P + Cl CCCCl 3 Ph P + Cl + – CCl CCCl 3
3
3
3
2
The chlorophosphonium ion then reacts with the alcohol to give an alkoxyphosphonium
ion that is converted to the chloride.
Ph P + Cl + ROH Ph 3 P + OR + HCl
3
+ –
P + Cl Ph P O + R Cl
Ph 3 OR 3
Several modifications of procedures based on halophosphonium ion have been
developed. Triphenylphosphine and imidazole in combination with iodine or bromine
gives good conversion of alcohols to iodides or bromides. 22 An even more reactive
23
system consists of chlorodiphenylphosphine, imidazole, and the halogen, and has the
further advantage that the resulting phosphorus by-product diphenylphosphinic acid,
can be extracted with base during product workup.
O
Ph PCl + H N N + I 2 + ROH RI + Ph PH
2
2
A very mild procedure for converting alcohols to iodides uses triphenylphos-
phine, diethyl azodicarboxylate (DEAD), and methyl iodide. 24 This reaction occurs

16 D. Levy and R. Stevenson, J. Org. Chem., 30, 2635 (1965).
17
A. Tanaka and T. Oritani, Tetrahedron Lett., 38, 1955 (1997).
18 L. Horner, H. Oediger, and H. Hoffmann, Justus Liebigs Ann. Chem., 626, 26 (1959).
19
R. Appel, Angew. Chem. Int. Ed. Engl., 14, 801 (1975).
20 J. B. Lee and T. J. Nolan, Can. J. Chem., 44, 1331 (1966).
21
R. M. Magid, O. S. Fruchey, W. L. Johnson, and T. G. Allen, J. Org. Chem., 44, 359 (1979).
22
P. J. Garegg, R. Johansson, C. Ortega, and B. Samuelsson, J. Chem. Soc., Perkin Trans., 1, 681 (1982).
23 B. Classon, Z. Liu, and B. Samuelsson, J. Org. Chem., 53, 6126 (1988).
24
O. Mitsunobu, Synthesis, 1 (1981).