| SYNTHESIS |
developed a process to produce l-menthol from the readily available raw material m-cresol.
Alkylation of m-cresol generates thymol. Hydrogenation of thymol yields four pairs of diastereomers: -menthol, -isomenthol, -neomenthol, and -neoisomenthol. Acylation of this mixture using a stereoselective lipase yields l-menthyl acetate in at least 96% enantiomeric excess (ee). l-Menthyl acetate is separated from the unreacted isomers by distillation. Hydrolysis yields l-menthol. The enzymatic resolution has been demonstrated in a continuous process at 1 kg per hour. Enzyme activity is retained even after 2,000 hours of operation. Furthermore, isomerization/racemization of the unreacted isomers regenerates the original mixture of diastereomers, which is routed again to enzyme resolution. Over several cycles, thymol is almost fully converted to l-menthol.
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