The syntheses of pharmaceutical intermediates in supercritical fluids

Reactions such as ammonolyses of esters to amides and of mesylates to amine s, asymmetric hydrogenations, and the condensation of trimethylhydroquinone with isophytol to D,L-alpha -tocopherol in supercritical fluids are report ed. Ammonolysis of a mesylate with anhydrous supercritical ammonia can lead to the corresponding amine in high yield (up to 96%), representing an inte resting alternative to the normally practiced azide substitution/hydrogenat ion sequence to introduce an amino function. The synthesis of D,L-alpha -to copherol in supercritical carbon dioxide or nitrous oxide by condensation o f trimethylhydroquinone with isophytol in the presence of various Bronsted or Lewis acids, especially an imide or its metal salts, as catalysts is an interesting alternative to existing processes.