Synthesis of 2, 3-Dihydro-1, 4-benzodioxin Derivatives. II. : 5(or 6)-Acyl 2, 3-Dihydro-1, 4-benzodioxin Derivatives : New Phenoxyacetic Acid Diuretics

Abstract

5(and 6)-Acyl-7, 8-dichloro-2, 3-dihydro-1, 4-benzodioxin-2-carboxylic acids (VI) and related compounds were synthesized and tested for diuretic and antihypertensive properties. These compounds (VI) were prepared by the reaction of 3, 4-dichloro-1, 2-dihydroxybenzene (2) with epibromohydrin (EBH) in the presence of a base and the Friedel-Crafts acylation, or by acylation of 2 and reaction with EBH, followed by oxidation. Acylation of 7, 8-dichlorodihydrobenzodioxin-2-ylmethanol (15a) gave the corresponding 5- and 6-acyl compounds, (17 and 10). Diuretic activity was generally observed when a 5-acyl substituent was present in the molecule. Compound 20e showed strong diuretic and antihypertensive activities, like indacrinone (II).