Studies On The Synthesis Of Biginelli Substituted Dihydropyrimidinones

Many 3, 4-dihydropyrimidin-2-ones (DHPMs) and their derivatives arepharmacologically important as calcium channel blockers, antihypertensive agents(SQ 32,547、SQ 32,926), andα1-1-a-antagonists. Moreover, several DHPMs have thefunctions of antivirus, antibacterial and antiphlogistic. Noteworthly, such compoundsand the derivatives also have broad prospects in the field of anti-cancer. Therefore,many synthetic methods for preparing such dihydropyrimidinone-5-carboxylate coreheterocyclic compounds have been developed.The classical synthesis of 3, 4-dihydropyrimidinone was three-componentone-pot Biginelli reaction of aldehyde, urea and ethyl acetoacetate under acidicconditions. In the early part of the 20th century, the scope of the originalcyclocondensation reaction was gradually extended by variation of all three buildingblocks, allowing access to a large number of structurelly diversifiedmultifunctionalized DHPMs．In this thesis, the development of the Biginelli reaction are reviewed and a seriesof new methods for the synthesis of 3, 4-dihydropyrimidines. N(1)-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, 53 of newN(1)-substituted dihydropyrimidinones have been synthesized via one-pot Biginellireaction of aldehydes,β-ketoester and p-tolylurea with p-toluene sulfonic acid as catalyst.2. We have optimized the reaction conditions from reaction catalysts,temperature, solvents, reactant ratio, reaction time and microwave power. Thesynthesis of N(1)-substituted dihydropyrimidinone compounds optimum reactionconditions was determined by the five series of Biginelli reaction research, weconcluded that p-toluenesulfonic acid (5 mol%) as catalyst, solvent-free, microwave(XH-200 A) irradiation power of 600 W, control the temperature of 60 C by infraredsensors, the reactant ratio of n (benzaldehyde): n (p-tolylurea): n (β-ketoester) =1.0:1.0:1.8, the reaction time 15-25 min.3. The structures of the compounds prepared have been characterized by the1HNMR, IR,13C NMR, and HRMS spectra. Six 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-substituted 3, 4-dihydropyrimidinones, which enriched the reserch of these kind ofdihydropyrimidinones and promoted the further studies of medicinal applications ofthe DHPMs compounds.