Cyclic analogues of β-adrenergic blocking agents cis- and trans-3-Amino-6-bromochroman-4-ols

Abstract

N-(6-Bromo-4-oxochroman-3-yl)acetamide (4; R = Ac) can be reduced by sodium borohydride to the cis-N-(6-bromo-4-hydroxychroman-3-yl)acetamide (6) and this can be hydrolysed to give the cis-3-amino-6-bromochroman-4-ol (7) or converted into the corresponding trans-3-amino-6-bromo- chroman-4-ol (12) by chlorination with inversion followed by hydrolysis of the chloride (8) to the alcohol with retention of configuration. The assignment of configuration of the 3,4-substituted chromans is based on the value of the coupling constants between the H3 proton and the methylene protons on C2 and is supported by an observed difference in the rate of hydrolysis of the two N-(6-bromo-4-chlorochroman-3-yl)acetamides.