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

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 1:1 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]

Reactions with 6-substituted-2-thiouracil-5-carbonitrites, synthesis of tetrazolo [1,5-c] and ditetrazolo [1,5 -a: 1,5-c] pyrimidines

Heating a ternary mixture of 6-furyl or 6-thienyl-4- oxo- 1, 2, 3, 4 - tetrahydro-2- thioxopyrimidine-5-carbonitrile [I a, b], chloroacetic acid and a suitable aromatic or heterocyclic aldehyde, led to the formation of 2- arylmethylene-2, 3- dihydro-3, 5 - dioxo-7- substituted- 5H- thiazolo [3, 2 - a] pyrimidine-6-carbonitriles [II a- i]. Alkylation of Ia, gave the s-alkyl derivatives IVa, b. Compounds IV and the thienyl analogue V reacted with benzylamine to give the 2- benzylamino derivatives. Heating IVa and V with phosphorus oxychloride gave the corresponding 4- chloropyrimidine derivatives [VIIa, b]. The 4- phenylthio-, 4-phenylhydrazino-, 4-benzylamino and 4- anilino-2- ethylthio-6- thienylpyrimidine-5- carbonitriles [VIIIa- d] were prepared from VIIb. Whereas compound VIIa gave, on heating with hydrazine hydrate, the 4-hydrazino-2-ethylthio and the 2, 4-dihydrazino derivatives IXa and X, respectively, compound VIIb gave only the 4-hydrazine derivative IXb. The latter compound reacted with nitrous acid to give 5-ethylthio-7-thienyltetrazolo [1, 5-c] pyrimidine-8-carbonitril XI. Diazotization of X led to the formation of 5-furyl ditetrazolo [1, 5-a, 1, 5-c] pyrimidine-6-carbonitrile [XII]