Hantzsch Reaction Of Green Synthesis

Green, sustainable chemistry involves the designing of chemical processes with a view to reducing or even eliminating the use and production of hazardous materials. Recent endeavors have focused on 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.In recent years, much attention has been focused on the synthesis of 1,4-dihydro- pyridines (1, 4-DHPs) due to their significant biological activities and pharmacolo- gical properties. 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.In the present thesis, a variety of 1, 4-dihydropyridines have been synthesized under aqueous or solvent-free conditions.1. From the reactions of aromatic aldehydes, acetoacetate and ammonium acetate with phase-transfer catalyst, 25 products have been synthesized under aqueous conditions: 16 compounds of 1, 4-dihydropyridines and 9 other compounds.When salicyic aldehyde was used, dimethyl 2-[2-hydroxyphenyl]-4, 6-dimethyl-1, 2-dihydropyridine-3, 5-dicarboxylate (7a), methyl 2, 4-dimethyl-5-oxo-5H-chromeno [4, 3-b]pyridine-3-carboxylate (7b), ethyl 2, 4-di-methyl-5-oxo-5H-chromeno[4, 3-b]pyridine-3-carboxylate (8a), methyl 2, 4-dimethyl-5-oxo-5H-chromeno[3, 4-c]py- ridine-1-carboxylate (7d), ethyl 5-oxo-5H-chromeno[3, 4-c]pyridine-1-carboxylate (8b), 2-(2-hydroxyphenyl)-4-methyl-5H-chromeno[3, 4-c]pyridine-5-one (8c), ethyl 2-(3-methyl-5-oxo-chromeno[4, 3-b]pyridin-2-yl)-propanoate (8d) and one bridged compound (8e) have been prepared 2. From a combination of aromatic aldehydes, ethyl benzoylacetate and ammonium acetate under solvent-free conditions, 18 products have been obtained: 9 compounds of 1, 4-dihydro- pyridines and 9 other compounds.When 2-nitrobenzaldehyde was used, only diethyl 2, 6-diphenyl-4-[2-nitrosop- henyl]pyridine-3, 5-dicarboxylate (13b) and diethyl 2, 6-diphenyl-4-[2-nitrophenyl]-1, 4-dihydropyridine-3, 5-dicarboxylate (13a) have been found by flash column chromatography with Al2O3. Methyl 6-hydroxy-2, 4-dimethyl-5-oxo-5, 6-dihydro- benzo[h][1, 6]naphthyridine-3-carboxylate (15a), ethyl 6-hydroxy-2, 4- dimethyl-5- oxo-5,6-dihydrobenzo[h][1,6]naphthyridine-3-carboxylate(15b) and ethyl 6-hydroxy-2,4-di-phenyl-5-oxo-5,6-dihydrobenzo[h][1,6]naphthyridine-3-carboxylate (15c) have also been obtained, which are by-products of the reaction of 2-nitrobenzaldehyde,β-ketoester and ammonium acetate.When salicyic aldehyde or 2-hydroxy-1-naphthaldehyde was used, 3-benzoyl- coumarin (16a) and 3-benzoylbenzo[f]coumarin (16b) have been gained and the synthetic protocols for coumarin derivatives under solvent-free conditions have been developed. When piperidine was used as catalyst,α-(o-hydroxybenzyl)benzoyl- acteylpiperidine (16c) has been gotten, which is the saturated condensation product of the Knoevenagel reaction.3. The molecular structures of the products prepared were characterized by the 1H NMR and IR spectra, new compounds were also confirmed by 13C NMR and MS spectra and elemental analysis, of which 18 crystal structures have been achieved by single crystal X-ray diffraction crystallographic analysis to confirm the molecular structures.The green synthesis of 1, 4-dihydropyridines have been performed and studied in aqueous medium and under solvent-free conditions in this thesis. Theses protocols have the advantages of environmentally benign, economy, short reaction time, high yields, and simple experimental work-up procedure, so these are acceptable in the context of green chemistry.