Synthesis of Xanthene Derivatives having Antispasmodic Action. VI. : Derivatives of Xanthene and Thioxanthene-9-malonic Acids

Abstract

Xanthenatom-9-ol (I) undergoes condensation with many compounds possessing an active hydrogen atom but not with diethyl malonate under ordinary conditions. Diethyl xanthene-9-malonate (IV) was obtained by the reaction of silver xanthene-9-malonate and ethyl iodide. I underwent facile condensation with ethyl malonate to form monoethyl xanthene-9-malonate (V) which was derived to 2-diethylaminoethyl ethyl xanthene-9-malonate hydro chloride (VI) and ethyl xanthene-9-malonamate (VII). In a similar manner, diethyl thioxan thene-9-malonate (XI), monoethyl thioxanthene-9-malonate (XII), 2-diethylaminoethyl ethyl thioxanthene-9-malonate hydrochloride (XIII), and ethyl thioxanthene-9-malonamate (XIV) were synthesized from thioxanthen-9-ol (VIII). Oxidation of XII with hydrogen peroxide gave monoethyl thioxanthene-9-malonate 10, 10-dioxide (XV) which was derived to 2-diethylaminoethyl ethyl thioxanthene-9-malonate 10, 10-dioxide hydrochloride (XVII). Oxidation of XIV gave ethyl thioxanthene-9-malonamate 10, 10-dioxide (XVIII). Antiacetylcholine action of XVII is stronger than that of 2-diethylaminoethyl thioxanthene-9-acetate 10, 10-dioxide hydrochloride, but both VI and XIII have weaker antiacetylcholine, anti-barium chloride, and antihistamine activities than the corresponding acetate derivatives.