Synthesis of bis-3-alkyl-5-arylhydantoins and bis-3-alkyl-5-arylthiohydantoins separated by two and four carbon atoms

• Published in: Journal of heterocyclic chemistry 1999-09, Vol.36 (5), p.1179-1182
• Main Authors: Salerni, O. Leroy, Van Tyle, W. Kent, Mustra, David J., Emerich, Kevin S., Fuerst, Douglas E., Zia-Ebrahimi, M.
• Format: Article
• Language: English
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.5570360511

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 ethylenediamine with two equivalents of N‐t‐butyl‐α‐(p‐toluenesulfonyloxy)phenylacetamide 3. The phenyl isothiocyanate adduct of 3 cyclized in refluxing toluene to form 1a. 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 α‐bromophenyl acetate and 1,4‐diaminobutane to produce N,N'‐bis‐[(α‐phenyl‐α‐methoxycarbonyl)methyl]butylenediamine 6. The isothiocyanate or isocyanate adducts from 6 cyclized, without hydrolysis, to form compounds 2a‐2e.