Studies On The Green Synthesis Of Polysubstituted Pyrazole Derivatives

Polysubstituted pyrazole derivative is a kind of important pharmaceutical intermediates because of their five-membered heterocyclic strutures containing two nitrogen atoms.Both the nitrogen and carbon atoms could be substituted by other groups or heteroatoms.Thus,many of such compoundsare biologically active,and have gained more and more attention in medical field.However,in terms of preparation,conventional methods normally used expensive catalysts,environmentally unfriendly bases,or harsh reaction conditions.Such methods are not only expensive,but most importantly,they do not meet the concept of green synthesis.In the current thesis,the following two aspects are studied for the green synthesis of polysubstituted pyrazole derivatives:(1)Study on copper-catalyzed green synthesis of polysubstituted pyrazole derivatives.The method used inexpensive copper iodide as a catalyst,sodium acetate as a base,and anhydrous ethanol as a solvent for reaction at 60~oC for 18h.various arylsulfonyl hydrazides containing groups of different electronic and steric effects in reaction with1,3-diketone compounds.Hydrazides having an ortho,meta or para substituent on the phenyl group can be converted to the corresponding pyrazoles in good to excellent yields,and both electron donating and the electron withdrawing groups hardly affect the reactivity.Heteroarylsulfonyl hydrazides are compatible,but aliphatic sulfonyl hydrazides are not suitable substrates for this reaction.When an asymmetric diketone substrate was used as the substrate,the corresponding product was formed in excellent regioselectivity and yield.(2)Study on green synthesis of polysubstituted pyrazole derivatives under metal free conditions.The method is carried out at 50~oC for 9h with ethyl acetate as a solvent,and various arylsulfonyl hydrazides containing different groups could react with 1,3-dicarbonyl compound,and no obvious electronic effect was observed.The scope of substrate is broad,and both electron-withdrawing and electron-donating groups can be involved.When asymmetrical 1,3-dicarbonyl compounds were used,two isomeric forms of product were obtained.The reaction is highly efficient and environmentally friendly,as the reaction condition is mild and the yield is high with different substrates.