A Synthetic Application of β-Aminoalanines to Some New 5-Dialkylaminomethyl-3-phenylhydantoin Derivatives

Abstract

5-Dialkylaminomethylhydantoins (3) were synthesized from β-aminoalanines (1) as the starting materials in two stages.Intermediate urea derivatives (2) prepared from the addition reaction of β-aminoalanines to phenyl isocyanate are easily cyclized to 5-dialkylaminomethylhydantoins (3) with good yields.The deamination reaction of some of the hydantoin derivatives (3a, 3b) in water were observed and resulted in the formation of 3-phenyl-5-methylenehydantoin (4).The hydantoin derivative (3b) regenerated a urea derivative (2c, d) by treatment with excess amounts of pyrrolidine or piperidine.Hydantoins (imidazolizine-2,4-diones) and related compounds are attracting considerable attention because of their chemical and biological properties.2][3][4] For example, recent studies regarding hormone receptor antagonists 2-4 have been reported which are based on a hydantoin scaffold.In connection with studies on β-aminoalanines, 5-8 the synthetic application of these novel β-aminoalanines for the preparation of hydantoin derivatives was investigated.This report describes the successful application for the new conventional procedure of 5-dialkylaminomethylhydantoin derivatives and some chemical properties of 5-dialkylaminomethylhydantoins.The synthetic procedure for the new 5-dialkylaminomethyl substituted hydantoin derivatives (3) by using racemic β-aminoalanines (1) 8 as starting materials is shown in Scheme 1.The first stage is a nucleophlic