Synthesis and biological properties of 2-(4-chlorophenyl)-3-morpholin-4-yl-(4-alkoxyphenyl)alkanol hydrochlorides

Abstract

New 2-(4-chlorophenyl)-3-morpholin-4-yl-1-(4-alkoxyphenyl)propan-1-ones were synthesized via aminomethylation of 2-(4-chlorophenyl)-1-(4-alkoxyphenyl)ethanones. Reduction of the former by lithium aluminum hydride produced 2-(4-chlorophenyl)-3-morpholin-4-yl-1-(4-alkoxyphenyl)propan-1-ols. Reaction of them with Grignard reagents gave 2-(4-chlorophenyl)-1-morpholin-4-yl-3-(4-alkoxyphenyl)alkan-3-ols. The synthesized compounds exhibited pronounced anticonvulsive and some peripheral n-cholinolytic activities while showing no antibacterial activity. In continuation of research on the synthesis and biological properties of aminoketones and the corresponding secondary and tertiary aminoalcohols, a new series of 3-morpholinopropan-1-ones (III – VI) and their derivatives (VII – XXX) were prepared [1-5]. The starting materials for the synthesis of the 3-morpholinopropan-1-ones (III and IV) were 2-(4-chlorophenyl)-1-(4-alkoxyphenyl)ethanones (I and II), which were prepared by Friedel—Krafts reactions [4]. Mannich reactions of the latter with paraformaldehyde and morpholine in EtOH gave the 2-(4-chlorophenyl)-3-morpholin-1-yl-1-(4-alkoxyphenyl)propan-1-ones (III and IV) [1]. Reaction of III and IV with hydroxylamine hydrochloride in EtOH in the presence of Py produced the oximes (VII and VIII). Reduction by LiAlH 4 in anhydrous Et 2 Oo f the 3-morpholinopropiophenones led to 2-(4-chlorophenyl)-3morpholin-1-yl-1-(4-alkoxyphenyl)propan-1-ols (IX and X) whereas reaction with Grignard reagents in Et 2 O afforded 2-(4-chlorophenyl)-1-morpholin-4-yl-3-(4-alkoxyphenyl)alk an-3-ols (XIII – XXI). The synthesized aminoketones and aminoalcohols were converted to the corresponding hydrochlorides (V, VI, XI, XII, XXII – XXX) in order to study their biological activity.