Synthesis and diuretic activity of 3-sulfamoyl-4-chlorobenzoylhydrazones of 4-acetylphenoxyacetic acid and its derivatives

Abstract

Earlier we reported [1] that 3-sulfamoyl-4-chlorobenzoylhydrazones of some aromatic aldehydes exhibited diuretic and saluretic activity, although the effect could be observed only for a rather short time. This behavior could be attributed to the fact that these hydrazones are rapidly hydrolyzed in the organism with the formation of a 3-sulfamoyl-4-chlorobenzoic acid hydrazide (I), capable of producing weak diuretic action, and the corresponding carbonyl compounds possessing no diuretic properties.It was therefore of interest to synthesize and study 3-sulfamoyl-4-chlorobenzoylhydrazones of carbonyl compounds that would exhibit diuretic activity by themselves. We have succeeded in finding such compounds among the derivatives of 4-acetylphenoxyacetic acid [2].The initial hydrazide I was synthesized by heating a mixture of 3-sulfamoyl-4-chlorobenzoic acid ethyl ester (II) and hydrazine hydrate for 10 min at 70 -75~ in the absence of solvent. This reaction gives a target product of higher purity and provides a higher yield as compared to the method described in [3]. 3-Sulfamoyl-4-chlorobenzoylhydrazones of4-acetylphenoxyacetic acid and its derivatives (III-VIII) were obtained by the condensation reaction between hydrazide I and the corresponding carbonyl compounds in a 2-propanol medium in the presence of a catalytic amount of acetic acid. The proposed structures of compounds III-VIII were confirmed by data of elemental analyses (corresponding to I Samara State Medical University, Samara, Russia. 543 the empirical formulas) and the results of UV, IR, and IH NMR spectroscopic measurements. The UV spectra of III-VIII exhibit two absorption maxima: at 285 -300 and 328 -349 nm. The IR spectra of compounds III-VIII display the following characteristic absorption bands (cm-l): 3370-3435, 3305-3360, 3185-3215 (N-H in SO2NH2 and CONH), and 1710-1725 (COOR'). The IH NMR spectra of III-VIII contain signals at 8 = 11.04 -11.30 ppm attributed to protons of the CONHN=C group. EXPERIMENTAL CHEMICAL PARTThe IR spectra were measured on a Specord M-80 spectrophotometer using samples pelletized with KBr. The IH NMR spectra were recorded on a Bruker W-80 spectrometer (working frequency, 80 MHz) using DMSO-d6 as the solvent and HMDS as the internal standard. The UV spectra were measured on a SF-26 spectrophotometer in acetonitrile solutions.3-Sulfamoyl-4-ehlorobenzoie acid hydrazide (I). A mixture of 26.4 g (0.1 mole) of compound II and 40 g (0.8 mole) of hydrazine hydrate was heated to 70~ treated for 10 min at 70 -75~ and cooled to room temperature. To this mixture was added 150 ml of water and then glacial acetic acid to pH 7.5. Finally, the reaction mixture was cooled to 0~ and the precipitate was filtered, washed with 300 ml of water, and dried at I05~ to obtain 23.0-23.5 g (92-94%) of a white product; m.p., 216-218~Crystallization from water gives 4.6 g of the product per 100 ml water (yield, 75 -80%) 3-Sulfamoyl--4-chlorobenzoylhydrazones (Ill-VIII). To a hot solution of 2.5 g (10 mmole) of compound I in 40 ml