Ammonia Halogenation Reactions - Dehydrogenation Of Amine Synthesis

In rencent years, N-protectedα,β-dehydroamino derivatives have played an important role in the fields of organic synthesis and pharmaceutical development as the intermediates of preparing many heterocyclic compounds, biological active substances and molecule probe in medicine. Many efforts on the research of N-protectedα,β-dehydroamino derivatives have been made with the focus on its application, while reports on its synthesis have some shortcoming, especially the synthesis methods with moderate reaction conditions, cheap and accessible starting materials, wide scope of substrates, short reaction time, high yield, easy disposal, and enviromently friendliness.Based on the existing reseach results of aminobromination addition on carbon-carbon double bond in our lab, three new methods of synthesizing N-protectedα,β-dehydroamino derivatives have been invetstigated in the paper. The new methods with the basis of aminobromination reaction and the organic small molecule thiourea as catalyzer are following:1. Achieved by the elimination reaction of aminobromogenated products which was catalyzed by thiourea; 2. Achieved from Aminobromination/elimination reaction of the alkene catalyzed by thiourea as one-pot method; 3. Achieved by the elimination reaction of aminobromogenated products in the aqueous phase catalyzed by the thiourea.Reviews and summaries on research progress about the synthesis and application of N-protectedα,β-dehydroamino derivatives was made in the first chapter, based on which the research aim in the paper was established.In the second chapter, a new reaction system of synthesizing N-protectedα,β-dehydroamino derivatives was established under normal temperature normal pressure from aminohalogenated products as the starting materials, thiourea as the catalyzer, K2CO3 as the base, and DMF and CH2Cl2 as the solvents. In order to convert different aminobromogenated products into N-protectedα,β-dehydroamino derivatives, the influence of different structural substrates on reaction time and yield was respectively studied. The results shown that this new system had a wide use of substrates, high yield, quick reaction rate and absolute regioselectivity. In the last part, possible reaction mechanism of the system was proposed.Another new method called one-pot was established in the third chapter with olefins as starting materials. Aminobromination reaction of the alkene was accorded by the addition of thiourea, K2CO3 and DMF without purification, and one or six hours later N-protectedα,β-dehydroamino derivatives could be obtained. The results shown that the method had a wide scope of substrate (33 example), high yield (up to 99%), quick reaction time (4 hours or longer), and high regioselectivity. Potential reaction mechanism is discussed.The conversion of aminobromogenated products into N-protectedα,β-dehydroamino derivatives in water catalyzed by the thiourea was developed in the fourth chapter. Green synthesis method in water catalyzed by thiourea, K2CO3 as the base was realized under normal temperature and normal pressure. The reaction activity of different aminobromogenated products were studied with the emphasis on the influence of different substitute groups on reaction time and yield. The results shows that the water play an important role in achiving the high yield, easy disposal, environmental friendliness and other advantages.In summary, three unique methods of synthesizing of N-protectedα,β-dehydroamino derivatives were investigated. These synthesis methods combined many of these strong points, such as moderate reaction conditions, cheap and accessible starting materials, wide scope of substrates, short reaction time, high yield, easy disposal, and enviromently friendliness. Possible reaction mechanisms were proposed on the basis of experiment and muti-factors which affect the reactions activity have been investigated.