Study On Aza-Michael Reactions Of Indazole And Pyrazole

Aza-Michael reaction is one of the most important methods to form C-N bond and to synthesize ?-amino carbonyl compounds in organic chemistry. It is often used to build the basic skeleton of complex natural products and pharmaceutically active molecules. Because of its feature of atomic economy, the researches on it have attracted more chemists' attention and many significant progresses have been achieved.?,?-Unsaturated ketone is a common kind of Michael acceptor. The heterocyclic compounds reported in aza-Michael reaction of ?,?-unsaturated ketones are mainly purine, benzotriazole, benzo imidazole, phenyl tetrazole, 1,2,4-triazole and pyrazole. However, the aza-Michael reaction of indazole with ?,?-unsaturated ketones have not been investigated systematically.Based on surveying of literatures, the aza-Michael reactions of indazole with ?,?-unsaturated ketones and pyrazole with ?,?-unsaturated imides were systematically studied focusing on their presented drawbacks. As a result, some positive results have been achieved.This thesis is divided into three chapters:Chapter 1 Progress in aza-Michael reaction and application of indazoles and pyrazolesThe application of pyrazoles and indazoles compound in medicine, agriculture, industry and the progress of their aza-Michael reaction were reviewed in this chapter. It focuses on the aza-Michael additions of indazoles and pyrazoles to ?,?-unsaturated aldehydes, ketones and esters.Chapter 2 The aza-Michael reaction of indazoles to ?,?-unsaturated ketonesIn this chapter, a DBU-catalyzed aza-Michael reaction of indazole with ?,?-unsaturated ketones is described. A variety of aromatic and aliphatic enones are well tolerated and afford the corresponding N1-substituted 1H-indazoles in high to excellent yields with exclusive N1-regioselectivity. The use of a metal-free catalyst, good substrate tolerance, mild reaction conditions, and high atom economy make this procedure a direct and facile method for the preparation of N1-substituted 1H-indazoles. The new protocol is also suitable to 5-nitro-indazole and its potential application is widespread.Chapter 3 The catalytic asymmetric aza-Michael reaction of pyrazole to ?,?-unsaturated imidesIn this chapter, the catalytic asymmetric aza-Michael reactions of pyrazole with ?,?-unsaturated imide were investigated. We expect to obtain N1-substitued pyrazoles with good enantioselectivity and high yields by regulating the catalysts, solvents and temperatures. However, experimental results showed that the examined catalysts have not displayed desirable activity to the reaction.