Synthesis ofbis-3-alkyl-5-arylhydantoins andbis-3-alkyl-5-arylthiohydantoins separated by two and four carbon atoms

Synthesis of 1,2- and 1,4-bis-thiohydantoins and hydantoins employing ethylenediamine and 1,4-diaminobutane as spacers is described. Compounds containing a two carbon bridge were synthesized by alkylation of ethylene diamine with two equivalents of N-t-butyl-alpha-(p-toluenesulfonyloxy)phenylacetamide 3. The phenyl isothiocyanate adduct of 3 cyclized in refluxing toluene to form la, Other isothiocyanate or isocyanate adducts derived from alkylation product 4 required hydrolysis to induce cyclization. Compounds 1b-1f were obtained in this way. Compounds with a four carbon bridge were obtained by reaction of two equivalents of methyl alpha-bromophenyl acetate and 1,4-diaminobutane to produce N,N'-bis-[(alpha-phenyl-amethoxycarbonyl)methyl]butylenediamine 6. The isothiocyanate or isocyanate adducts from 6 cyclized, without hydrolysis, to form compounds 2a-2e.