Studies On The Green Synthesis Of Biginelli Reaction

Green chemistry and sustainable development demand the designing chemical processes with a view of reduction or even elimination of the use and production of hazardous materials. Recent studies have focused on the limiting the use of organic solvents and replacing them with new, environmentally benign media. The chemical industry is interested in these cost-effective, alternative solvents and processes. The most commonly used green reaction media are supercritical fluids, ionic liquids, water, and solvent-free conditions, etc.Pyrimidine rings, as the essential structure unit in biological systems, exist widely in nature. Studies on the synthesis and conversions, biological activity and metabolism of pyrimidine derivatives are significant.In recent years, much attention has been focused on the synthesis of 3, 4- dihydropyrimidin-2(1H)-ones (DHPMs) due to their significant biological activities and pharmacological properties. The best known procedure for the preparation of DHPMs is the classical Biginelli reaction. However, this method involves a long reaction time, harsh reaction conditions and unsatisfactory yields. A number of improved procedures have been reported, but many of them suffer from drawbacks such as hazardous organic solvents, expensive catalysts and tedious work-up. These are not acceptable in the context of green synthesis.In the present thesis, three series of 3, 4-dihydropyrimidin-2(1H)-ones (DHPMs) have been synthesized under aqueous or solvent-free conditions.1. Under solvent-free conditions, 25 compounds have been synthesized by the Biginelli reaction of aldehydes, acetoacetate and urea with hydrochloric acid as catalyst: 24 compounds of 3, 4-dihydropyrimidin-2(1H)-ones and 1 compound of 1, 4- dihydropyridine.It has been found that 4 oxidized compounds are obtained belonging to pyrimidines from the reactions of the regioselective oxidation of 3, 4-dihydropyrimidin-2(1H)- ones.2. Under solvent-free conditions, 11 compounds have been synthesized with the Biginelli reaction of aromatic aldehydes, ethyl benzoylacetate and urea with hydrochloric as catalyst: 10 compounds of 3, 4-dihydropyrimidin-2(1H)-ones and 1 compound of pyrimidines.3. Under solvent-free conditions, 10 compounds have been synthesized from the novel Biginelli reaction of ortho-hydroxy aromatic aldehydes,β-ketoesters and urea (thiourea) with hydrochloric as catalyst: 5 of oxygen-bridged tricyclic compounds; 3 of dihydropyrimidinones and other 2 compounds.4. In the thesis, fifty compounds have been synthesized and sixteen of them are new ones. The structures of the compounds prepared have been characterized by the 1H NMR and IR spectra and new compounds have also been confirmed by 13C NMR and MS spectra and elemental analysis. Twenty-two crystal structures of the compounds have been achieved by single crystal X-ray crystallographic analysis and the molecular structures have been confirmed unambiguously. Seventeen single crystal structures were not found in the literature.The green synthesis of 3, 4-dihydropyrimidin-2(1H)-ones have been performed and studied successfully in aqueous medium or under solvent-free conditions in this thesis. Theses protocols have the advantages of environmentally benign, economy, short reaction time, high yields, and simple work-up procedure, which are acceptable in the context of green chemistry.