(S)-4-Bromo-alpha-methylbenzyl alcohol

clear colorless liquid

(S)-1-(4-Bromophenyl)ethanol is a building block used in organic synthesis of photochemically active and photophysical pthalocyanines.

Preparation of (S)-4-bromo-alpha-methylbenzyl alcohol from tetrafluorobenzene by methylation, carboxylation and reduction.

2,3,5,6-tetrafluorobenzene was reacted with n-LiBu, with TIHF as solvent, under argon protection, and then reacted with iodomethane to produce 2,3,5,6-tetrafluorotoluene; and then reacted with 4-methyl-2,3,5,6-tetrafluorobenzoic acid sequentially with n-LiBu, and CO2, using ether as solvent: next, ether was used as solvent and reacted with LiAH under argon protection to obtain (S)-4-bromo-alpha-methylbenzyl alcohol.

The raw material used in this route, tetrafluorobenzene, is expensive, and the reagents used in the synthesis, such as iodomethane and lithium aluminum hydride, are also very expensive; moreover, the reaction conditions are harsh, requiring low-temperature operation at -45 or even -70. The total yield of the reaction is very low, less than 1%, and it is difficult to industrialize the production.

The (±)-racemate is purified by distillation in a vacuum (b 90o/1mm, 119-121o/7mm, d 1.46) and it solidifies on cooling (m 36-37o) [Overberger et al. Org Synth