Reaction of 3-Phenylglycidic Esters. IV. Reaction of Methyl 3-(4-Methoxyphenyl) glycidate with 2-Nitrophenol and Synthesis of 1, 5-Benzoxazepine Derivatives

Abstract

The reaction of methyl trans-3-(4-methoxyphenyl) glycidate (1) with 2-nitrophenol was investigated under various conditions. Generally, the reaction proceeded predominantly by cis-opening of the oxirane ring of 1 to give the threo-nitro ester (7). Selective trans-opening of 1 was observed only in the reaction with sodium 2-nitrophenoxide to give the erythro-nitro ester (8). Some 1, 5-benzoxazepine derivatives (16-19), 1-oxa analogues of diltiazem, were synthesized from 7 and 8 for pharmacological evaluation. Compound 18a showed the highest vasodilating activity in this series, but it was less active and more toxic than racemic diltiazem.