IMPROVED SYNTHESIS OF SUBSTITUTED PYRIMIDIN-2-ONE DERIVATIVES USING MICROWAVE AND ULTRASOUND IRRADIATION

Abstract

ABSTRACT Various substituted 4-oxo-2-thioxo tetrahydropyrimidine, 2-oxo dihydropyrimidine, 3,6-disubstituted and 4,5-disubstituted tetrahydropyrimidin-2-one derivatives containing different functional groups have been synthesized under microwave and ultrasound irradiation. The 3,6-disubstituted derivatives were prepared by reacting substituted pyrimidine derivatives synthesized under ultrasound irridation, with ethybromoacetate and product formed was converted to respective hydrazide derivatives, which were further condensed with various aromatic aldehydes. The 4,5-disubstituted tetrahydropyrimidines derivatives were synthesized simply by reacting substituted pyrimidine derivatives synthesized using modified biginelli reaction with various aromatic amines. The IR, 1 H NMR and mass spectral data confirmed the structure of the newly synthesized compounds. Keywords: Biginelli reaction, pyrimidine, Microwave, Ultrasound. INTRODUCTION Pyrimidine is a parent group of various heterocyclic compounds, which have attracted attention for long time. Pyrimidine derivatives play a vital role in many biological processes, the ring system being present in nucleic acids, several vitamins and coenzymes, uric acid and other purines. Uracil, thymine, and cytosine are three of the six bases found in the nucleotides, which contain pyrimidine ring. It is evident from the literature that pyrimidine derivatives have been found to have various pharmacological activities. Pyrimidine ring is the backbone of several calcium channel blocker[1], antibacterial[2], antifungal Step-I:Synthesis of 5-carbonitrile-6-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine:[10 ] A mixture of ethyl cyanoacetate (0.01 mol), an aldehyde (0.01 mol) and thiourea (0.01 mol) in ethanol (20 ml) containing potassium carbonate (0.01 mol) was refluxed for 5 h. The potassium salt of product, which is precipitated during reaction, was collected and washed with ethanol and tetrahydrofuran. The crude salt was stirred in water at approximately 80° C; stirring was continued until the clear solution is obtained. After cooling the solution was acidify by acetic acid, and stirring was continued for 30 min. The deposited crystals thus formed were collected and washed well with water and dried in air. Recrystallization from acetic acid gave pure product. Desai Sujit Arun et al