Studies On The Green Synthesis Of N-Methyl Substituted Dihydropyrimidinones

Dihydropyrimidinones (DHPMs) have received great attention from syntheticand medicinal chemists due to their interesting biological applications. They exhibit awide range of medicinal applications such as antiviral antibacterial and antifungal,anticancer and calcium channel modulation.The classical synthesis of3,4-dihydropyrimidinone was three-componentone-pot Biginelli reaction of aldehyde, urea and ethyl acetoacetate under acidicconditions. The scope of the original cyclocondensation reaction was graduallyextended by variation of all three building blocks, allowing access to a large numberof structurelly diversified multifunctionalized DHPMs．In this thesis, the development of the Biginelli reaction are reviewed and a seriesof new methods for the synthesis of3,4-dihydropyrimidines. N-methyl substituteddihydropyrimidinones are described. Furthermore, these methods have the advantagesof short reaction time, simple work-up procedure, economy, high yield and underenvimumently friendly conditions, which are acceptable in the context of greensynthesis.The research results we made are presented as follows:1. Under microwave irradiation and solvent-free conditions,57of new N-Methylsubstituted dihydropyrimidinones have been synthesized via one-pot Biginellireaction of aldehydes, β-ketoester and methylurea with p-toluene sulfonic acid ascatalyst.2. We have optimized the reaction conditions from reaction catalysts,temperature, solvents, reactant ratio, reaction time and microwave power. Thesynthesis of N-Methyl substituted dihydropyrimidinone compounds optimum reactionconditions was determined by the five series of Biginelli reaction research, we concluded that p-toluenesulfonic acid (5mol%) as catalyst, solvent-free, microwave(XH-200A) irradiation power of450W, control the temperature of55C by infraredsensors, the reactant ratio of n (benzaldehyde): n (methylurea): n (β-ketoester)=1.0:1.1:1.5, the reaction time12-30min.3. The structures of the compounds prepared have been characterized by the1HNMR, IR,13C NMR, and HRMS spectra. Five crystals structures of the compoundshave been achieved by single crystal X-ray crystallographic analysis and themolecular structures have been confirmed unambiguously.In the thesis, one-pot Biginelli synthesis of N-substituted dihydropyrimidinonewhich promoted with p-toluene sulfonic acid as catalyst under microwave irradiationsolvent-free conditions have been performed and studied comprehensively. It is thecorrect target products that proved the feasibility of this protocol.The present thesis improved and modified the Biginelli reaction of theN-substituted3,4-dihydropyrimidinones, which enriched the reserch of these kind ofdihydropyrimidinones and promoted the further studies of medicinal applications ofthe DHPMs compounds.