Synthesis of 3,4-dihydro -6-(2-hydroxy-5-(hydroxymethyl) phenyl)-4-phenylpyrimidine-2(1H)- Thione by Biginelli Approach
S. Y. Mane *
Department of Chemistry, Shivneri College, Shirur (A), Dist. Latur, 413544, MS, India.
K. G. Huge
Department of Chemistry, K. K. M. College, Manwat, Dist. Parbhani, Pin-431505, MS, India.
*Author to whom correspondence should be addressed.
Abstract
Pyrimidine-2-thione derivatives are biologically active heterocycles widely explored in medicinal chemistry. The Biginelli reaction offers a simple and efficient route for their synthesis, driving interest in developing improved and environmentally friendly protocols.The development of an effective and practical Biginelli reaction procedure for the preparation of 3,4-dihydro-6-(2-hydroxy-5-(hydroxymethyl) phenyl)-4-phenylpyrimidine-2(1H)-thione derivatives is reported. Three-component condensation reaction of 1-(2-hydroxy-5-(hydroxymethyl)phenyl) ethanone, aryl-aldehydes, and thiourea in the presence of DABCO as an organobase catalyst, using ethanol as the green solvent, under refluxing condition has been accomplished. Some notable features associated with this protocol are mild reaction conditions, simple process, reduce reaction time to 2.5 hr., and high product yield 85 %. DABCO plays a vital role in improving the reactivity of this condensation reaction by inducing smooth cyclocondensation in the absence of corrosive acidic catalysts. The obtained pyrimidine-2-thione derivatives have been isolated by simple purification methods and characterized through the study of melting points and spectral data. An environment-friendly synthetic method for the preparation of pyrimidine-2-thiones bearing biological activity is described herein.
Keywords: Pyrimidine-2-thiones, organobase catalyst, cyclocondensation, environmentally benign, DABCO, Biginelli approach