Studies On The Synthesis Of Unsymmetrically Substituted 1,4-Dihydropyridines

1,4-Dihydropyridines (1,4-DHPs) are a kind of important nitrogen-containing heterocyclic compounds, mostly with physiological activities, which also have a wide range of applications in biology and medicine. In recent 30 years, DHPs calcium channel blockers have found broad clinical applications in the treatment of cardiovascular diseases. Nifedipine, the first generation of DHPs calcium channel blocker, is primarily used as coronary diastolic medicine. The second generation of DHPs calcium channel blockers such as Nimodipine, Nitrendipine, Nisoldipine, Nicardipine, Isradipine and the third generation of DHPs calcium channel blockers, for example, Amlodipine Lacidipine, Manidipine, Cilnidipine are also used constantly as cardiovascular drugs. Most of them can regulate calcium ion channels and lower blood pressure. Moreover, they have the functions of antivirus, antibacterial and antiphlogistic. Noteworthly, such compounds and the derivatives also have broad prospects in the field of anti-cancer.Except for nifedipine, most of this kind of the drugs have one or more chiral center. At present, these compounds are commonly used in the form of racemic modification.The best known procedure for the preparation of 1,4-DHPs is the classical Hantzsch reaction. However, this method involves a long reaction time 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 also not acceptable in the context of green synthesis.The present thesis is aimed at the synthesis of unsymmetrically substituted Hantzsch 1,4-dihydropyridines.1. Under microwave irradiation and solvent- and catalyst-free conditions, 50 of unsymmetrically substituted 1,4-dihydropyridines have been synthesized via one-pot two-step modified Hantzsch condensation reaction of acromatic aldehydes, acetoacetate, ethyl benzoylacetate and ammonium acetate, of which 45 of the compounds have not been reported in the literature.2. We have optimized the reaction conditions from reaction temperature, microwave power, solvents, catalysts, reactant ratio and reaction time.3. The structures of the compounds prepared have been characterized by the 1H NMR, IR, 13C NMR, MS spectra and elemental analysis. Two crystals structures of the compounds have been achieved by single crystal X-ray crystallographic analysis. The molecular structures have been confirmed unambiguously and have not been reported in the literature.In the thesis, one-pot two-step synthesis of unsymmetrically substituted Hantzsch 1,4-dihydropyridines which promoted by microwave irradiation under solvent- and catalyst-free conditions have been performed and studied comprehensively. It is the correct target products that proved the feasibility and availability of this method. Furthermore, these 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 synthesis.The present thesis improved and modified the Hantzsch synthesis of the unsymmetrically substituted 1,4-dihydropyridines, which enriched the reserch of these kind of 1,4-dihydropyridines and promoted the further studies of medicinal applications of the unsymmetrically substituted 1,4-dihydropyridine compounds.