Page 245 - Advanced Organic Chemistry Part B - Reactions & Synthesis

3.1.2. Halides 217
The prominent role of alkyl halides in the formation of carbon-carbon bonds SECTION 3.1
by enolate alkylation was evident in Chapter 1. The most common precursors for Conversion of Alcohols
alkyl halides are the corresponding alcohols and a variety of procedures have been to Alkylating Agents
developed for this transformation. The choice of an appropriate reagent is usually
dictated by the sensitivity of the alcohol and any other functional groups present in
the molecule. In some cases, the hydrogen halides can be used. Unsubstituted primary
4
alcohols can be converted to bromides with hot concentrated hydrobromic acid. Alkyl
chlorides can be prepared by reaction of primary alcohols with hydrochloric acid–
5
zinc chloride. Owing to the harsh conditions, these procedures are only applicable
to very acid-stable molecules. These reactions proceed by the S 2 mechanism and
N
elimination, and rearrangements are not a problem for primary alcohols. Reactions
of hydrogen halides with tertiary alcohols proceed by the S 1 mechanism, so these
N
reactions are preparatively useful only when the carbocation intermediate is unlikely
6
to give rise to rearranged product. In general, these methods are suitable only for
simple, unfunctionalized alcohols.
Another general method for converting alcohols to halides involves reactions
with halides of certain nonmetallic elements. Thionyl chloride, phosphorus trichloride,
and phosphorus tribromide are the most common examples of this group of reagents.
These reagents are suitable for alcohols that are neither acid sensitive nor prone to
structural rearrangement. The reaction of alcohols with thionyl chloride initially results
in the formation of a chlorosulfite ester. There are two mechanisms by which the
chlorosulfite can be converted to a chloride. In aprotic nucleophilic solvents, such as
dioxane, solvent participation can lead to overall retention of configuration. 7

O
ROH + SOCl 2 ROSCl +HCl
O
+
O O + ROSCl O O–R + SO 2 + Cl – R–Cl + O O

In the absence of solvent participation, chloride attack on the chlorosulfite ester leads
to product with inversion of configuration.

O
ROH + SOCl 2 ROSCl + HCl
O
–
Cl R – OS – Cl R – Cl + SO 2 + Cl

Primary and secondary alcohols are rapidly converted to chlorides by a 1:1 mixture of
SOCl and benzotriazole in an inert solvent such as CH Cl . 8
2
2
2
4 E. E. Reid, J. R. Ruhoff, and R. E. Burnett, Org. Synth., II, 246 (1943).
5
J. E. Copenhaver and A. M. Wharley, Org. Synth., I, 142 (1941).
6
J. F. Norris and A. W. Olmsted, Org. Synth., I, 144 (1941); H. C. Brown and M. H. Rei, J. Org. Chem.,
31, 1090 (1966).
7 E. S. Lewis and C. E. Boozer, J. Am. Chem. Soc., 74, 308 (1952).
8
S. S. Chaudhari and K. G. Akamanchi, Synlett, 1763 (1999).