The synthesis of 1,3-diazepine derivatives by the ring expansion of alkyl 4-chloromethyl-1,2,3,4-tetrahydro-6-methyl-2- oxopyrimidine-5-carboxylates

Abstract

Alkyl 4-chloromethyl-1,2,3,4-tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylates are obtained from the reaction of 1,2-dichloroethyl ethyl ether with alkyl 3-ureidocrotonates. Reaction of the chloromethyl compounds with basic nucleophilic reagents causes ring expansion and leads, in high yield, to 7-substituted 2,3,6,7-tetrahydro-2-oxo-1H-1,3-diazepine derivatives. In the case of sulfhydryl ion, intramolecular Michael addition follows ring expansion and gives derivatives of 3-oxo-8-thia-2,4-diazabicyclo[3.2.1]octane, whose structures are established by spectroscopic examination and chemical degradation. The alkyl 7-alkoxy-2,3,6,7-tetrahydro-2-oxo-1H-1,3-diazepine-5-carboxylates react rapidly with acid to give alkyl 1-carbamoyl-2-methylpyrrole-3-carboxylates. Mechanisms are suggested for these rearrangement reactions.