Phase‐Transfer Catalysis by Poly (Ethyleneglycol) 600 in the Biltz Synthesis of Phenytoin

Abstract

Abstract A reinvestigation of the Biltz synthesis of phenytoin was undertaken to selectively produce the hydantoin derivative instead of a mixture of the hydantoin and the glycoluryl derivative. A solution of this problem was found in carrying out the reaction in a two‐phase system (n‐butanol:water) and in the presence of a phase‐transfer catalyst (poly(ethyleneglycol)600). In these conditions, a 87–93 yield of phenytoin can be obtained. Extension of this approach to the synthesis of other hydantoin derivatives was also found superior to one‐phase conditions.