Studies On The Green Synthesis Of Hantzsch N-substitued 1, 4-dihydropyridines

Pyridine rings, as the essential structure unit in biological systems, exist widely in nature. Studies on the synthesis and conversions, biological activities and metabolism of pyridine derivatives are significant.In recent years, much attention has been focused on the synthesis of 1, 4-dihydropyridines (1,4-DHPs) due to their significant biological activities and pharmacological properties. Clinically, they are not only for the treatment of hypertension, angina, congestive heart failure, ischaemia and atherosclerosis and other cardiovascular diseases but in poultry and aquatic farming 1,4-dihydropyridines are of biological functions that can regulat endocrine, promote animal growth and improve the immune function. In recent years,1,4-dihydropyridine derivatives that are high-performance calcium antagonist attract more and more attention, such as Nifedipine, Felodipine and Isradipine, which are well-known as treatment of hypertension, vascular expansion and cancer. As well as its pharmaceutical properties and wide biological activities in the treatment of science,1,4-dihydropyridine derivatives caused widespread concern of researchers at home and abroad.The best known procedure for the preparation of 1,4-DHPs is the classical Hantzsch reaction. However, this method involves a long reaction time, harsh reaction conditions and unsatisfactory yields. A number of improved proce-dures 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.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. Recently, synthesis of organic compounds assisted by microwave irradiation under solvent free conditions is an improved technique due to its greater selectivity, rapid transfer of energy, significant practical simplicity and pure products.In the present thesis, a variety of N-substituted 1,4-dihydropyridines have been synthesized by microwave irradiation catalyzed with iodine under solvent-free conditions.1. Under microwave irradiation and solvent-free conditions,38 compounds have been synthesized by the Hantzsch reaction of aldehydes, acetoacetate and p-toluidine with iodine as catalyst:36 compounds of 1,4-dihydropyridines and 2 compounds of by-side products.2. Under microwave irradiation and solvent-free conditions,12 compounds of 1, 4-dihydropyridines have been synthesized with the Hantzsch reaction of aromatic aldehydes, ethyl acetoacetate and p-chloroaniline with iodine as catalyst.3. In the thesis, fifty compounds have been synthesized and thirty-one 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. Eight crystal structures of the compounds have been achieved by single crystal X-ray crystallographic analysis and the molecular structures have been confirmed unambiguously. All the single crystal structures were not found in the literature.The green synthesis of N-substitued 1,4-dihydropyridines have been performed and studied successfully by microwave irradiation catalyzed with iodine 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.