Study On Aza-Michael Reactions Of Aromatic N-Heterocycles With α,β-Unsaturated Imides

Aza-Michael reaction is one of the most important methods to form C-N bond and to synthesize β-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(including asymmetric version) have attracted more chemi sts’ attention and many significant progresses have been achieved. However, compared to the comprehensively studied N-nucleophile, amine and hydroxylamine, the weak-nucleophilic aromatic N-heterocycles participated aza-Michael reactions are rarely reported. Therefore, to explore a convenient and efficient method for aza-Michael addition of aromatic N-heterocycles to α,β-unsaturated imides with broad scope of substrate is significant and challenging.Based on surveying of literatures, the aza-Michael reactions of parazole and benzotriazole with α,β-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 of aromatic nitrogen heterocyclesThe application of aromatic N-heterocycles as agrochemicals and pharmaceuticals and the progress of their aza-Michael reaction was reviewed in this chapter. The advance of aza-Michael reactions of aromatic N-heterocycles with α,β-unsaturated aldehydes, α,β-unsaturated ketones, α,β-unsaturated esters were summarized especially.Chapter 2 The aza-Michael reaction of parazole to α,β-unsaturated imidesIn this chapter, a Li Cl-catalyzed aza-Michael addition of pyrazole to α,β-unsaturated imides was developed. The cheaper and easily obtained catalyst, excellent selectivity, high yield, simple operation, and broad scope of substrate make this protocol more practical. Both aromatic and aliphatic unsaturated imides were smoothly transformed into corresponding β-(N1-pyrazolyl) products in 53~93% yields. The new protocol is also suitable to nitroalkene and its potential application is widespread.Chapter 3 The selective aza-Michael reaction of 1H-benzotriazole to α,β-unsaturated imidesIn this chapter, a selective aza-Michael reaction of 1H-benzotriazole to α,β-unsaturated imides with alkali salt as catalyst was developed. By regulating of catalyst and solvent, the N1-and N2-adducts could be respectively obtained in high regioselectivities and yields. In addition, the method has the advantages of simple operation, high efficiency and good selectivity.