Synthesis And Process Improvement Of Small N And S Heterocyclic Drug Molecules

N and S heterocyclic compounds are widely exist in nature. This kind of heterocyclic compounds are common active drug molecules which have anti-inflammatory, antibacterial, anti-HIV, anti-hypertensive, anti-tumor and other important physiological and pharmaceutical activity. In recent years, with development of heterocyclic chemistry, the methods to synthesize this kind of heterocyclic compounds have been rapid development along with its applications in medicine chemistry. Herein, we tried to improve on the synthesis of N and S heterocyclic compounds and to improve some synthetic technology, getting a series of significant experimental results:1. Aromatic aldehydes and aromatic amines reacted with acrylonitrile in one-pot under refluxing acetic acid condition to obtain a series of benzimidazoles. Under the same condition, Schiff base reacted with acrylonitrile to obtain substituted quinolines. The two reaction mechanisms are all discussed. All the products are characterized by IR and NMR. crystal X-diffraction is also used to characterize the products.2. Lewis acid can work very well as catalyst to synthesize ethanolamines and benzamides. We first synthesized several substituted imines and diimines. Using different catalyst of Lewis acid we found that ZnCl2could translate imines into ethanolamines while BF3O(CH2CH3)2has perfect catalytic activity to the synthesis of benzamides from diimines. The reaction mechanisms are also discussed. All the products are all characterized by IR and NMR, crystal X-diffraction is also used to characterize the products.3. Spiro N-heterocyclic compounds were synthesized from ninhydri、sarcosine and chalcone by1,3-dipolar cycloaddition reaction. All the products are characterized by IR and NMR, crystal X-diffraction is also used to characterize one product.4. We improved the methods to synthesize substituted2-amino thiophenes, thieno[2,3-b]thiophene,2-bromo-4-nitroimidazole, substituted thiazoles and imidazo [1,2-a]pyridine by changing the molar ratio of starting materials. Defferent solvents and catalysts were all screened. Compared with the literature methods, our optimized method has many advantages of lower cost, reduced pollution, simple reaction process and higher yield. All the products are characterized by IR and NMR.