Studies with 2-thiazoline-4-one derivatives as potential uterus stimulants

ABSTRACT

2-Thiazolin-4-ones are biologically interesting molecules and their chemistry and pharmacology have received considerable interest. This prompted the author to synthesize some new 2-thiazolin-4-one derivatives for pharmacological screening. In this work, 2- cyanomethyl-2-thiazolin-4-one [1] has been prepared using Elnagd's procedure. [1] reacts with thioglycolic acid in refluxing pyridine to give the bis-2-thiazolin-4-one derivative [2]. A trial for Mannich reaction between [1] and morpholine, piperidine, and formaldehyde gave a product of molecular formula C10H13N3O2S and C11H15N3OS. These compounds may thus be formulated as 3, 4 or 5. Structure 5a,b was established for this product based on the IR spectrum which shows a conjugated CN b and at 2220 cm -1 and absence of an NH b and thus excluding structures [3] and [4]. Similar to behavior of [1], compound [2] reacts with formaldehyde and morpholine to yield a product of molecular formula C12H15N3O3S2. Another two possibilities exist, this was formulated as [7] rather than [6]. IR spectrum revealed an NH b and at 3500 cm -1, also 1H-NMR showed the absence of a CH signal. The reaction of [1] with benzylidene acetophenone, p- chlorobenzylidene-acetophenone, gave 11 adduct. This may be formulated as [8-10]. Structure [8a,b] is considered most likely based on IR spectrum which revealed the presence of an NH b and at 3200 cm -1, conjugated CN signal at 2220 cm -1 in addition to two carbonyl absorption b and s at 1730 and 1680 cm -1. Reaction of compound [1] with acetylene-dicarboxylic acid diethyl ester yield a product that may be formulated as [11] or isomeric [12]