The synthesis of optically active 5‐phenylhydantoins

Abstract

A number of reagents have been examined for effecting the conversion of an optically pure 2‐phenylhydantoic acid to an optically active 5‐phenylhydantoin. Trifluoroacetic anhydride (TFAA method) and dilute hydrochloric acid (acid‐catalysis method) proved to be the reagents of choice. The dependence of the kinetics of racemization of the 5‐phenylhydantoin system on temperature has been studied in dilute hydrochloric acid solution to support the conclusion that 5‐phenylhydantoins prepared by the acid‐catalysis method are nearly, if not entirely, optically uniform.

Poly(ethylene) glycols and mechanochemistry for the preparation of bioactive 3,5-disubstituted hydantoins

“…The preparation of ethotoin in solution is restricted to only two publications, 36,37 involving either cyclization of 5-ethyl-2phenylhydantoic acid 36 or rearrangement of ethyl N-Boc-phenylglycinamide 37 (70% and 60% yield respectively) under anhydrous conditions, both strongly acid-catalyzed conditions.…”

Green metrics in mechanochemistry

“…Consequently, the E -factor was better than traditional solution-based procedures. 72–74 For instance, for N -phenylmorpholine-4-carboxamide 13a , the E -factor (without work-up) was 1.21 (91% yield) vs. 103 (99% yield) in solution.…”

“…Consequently, the E-factor was better than traditional solution-based procedures. [72][73][74] Scheme 2 Mechanical synthesis of amides using uronium-type reagents.…”

Green metrics in Mechanochemistry

“…Consequently, the E-factor was better than traditional solution-based procedures. 44,45,46 For instance, for N-phenylmorpholine-4-carboxamide 13a, the E-factor (without work-up) was 1.21 (91% yield) vs 103 (99% yield) in solution.…”