Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl chromene-3-carbaldehyde derivatives

Abstract

The Vilsmeier-Haack reaction of active methylene compounds led to the formation of b-halo carbaldehydes, which constitute a class of compounds that served as useful intermediates towards construction of different heterocyclic compounds (1). Accordingly, some of b-chlorocarbaldehydes were described to react with phenylhydrazine and 2-mercapto acetic acid and its ethyl ester to give the corresponding pyrazolo and thieno derivatives (2-6). Pawar and Rajput (7) reported the synthesis of 5-anilinothiazolo- [5,4-d]isoxazole from 4-chloro-2-anilinothiazol-5-carbaldehyde with hydroxylamine hydrochloride. As it is known, oxime ethers have found many uses in recent years as nonsteroidal anti-inflammatory drugs (8), insect growth regulators (9), materials with steroidal effect (10), and as antimicrobial agents (11).In continuation of our study on hindered b-chlorocarbaldehydes (6), it seemed to be interesting to react some hindered b-chlorocarbaldehydes with some hydrazines, thiosemicarbazide, and hydroxylamine hydrochloride and to evaluate the pharmacological activity of the new products as anti-inflammatory and anti-ulcerogenic agents. Some new hydrazono 5a,b, thiosemicarbazono 6a-c, and oximo chromenes 7a-c were prepared via the reaction of the corresponding b-chlorocarbaldehyde 3 with hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride, respectively. In addition, ether derivatives 8a-h were prepared from the corresponding aldoximes 7a-c. The new products were tested for anti--inflammatory and ulcerogenic score activities compared to indomethacin.