One Pot Synthesis Of N-sulfonylamidines Through Copper Bromide Catalysis

N-sulfonylamidine and its derivatives hve a very important position in the organic chemistry,pharmaceutical chemistry,pesticides and other fields.and are often used as intermediates to synthesize natural products with biological activity,heterocyclic compounds and and drugs.N-sulfonylamidine compounds can also be used as catalysts and coordinate with metal to catalyze the organic reaction.In recent years,the research on its synthesis methods has been reported.These methods mainly include:(1)N-sulfonylamidine was synthesized by Hinsberg reaction from sulfonyl chloride and amidine hydrochloride in the presence of a base;(2)N-sulfonylamidine was synthesized by the reaction of sulfonyl azide,alkyne and secondary amine under the catalysis of copper(I);(3)N-sulfonylamidine was synthesized from the reaction of sulfonyl azide with tertiary amine under the catalysis of DEAD or Fe C l3;(4)N-sulfonylamidine is synthesized from the reaction of sulfonamide with formamide under the catalysis of Na I/TBHP or NBS.However,the disadvantage of the above method is that the expensive raw materials of above synthetic methods are not easy to get or need to be synthesized in advance,there are more by-products in the reaction,the scope of application of the substrate was narrow,the amount of catalyst is large,some reactions require precious metals to participate,and some reaction conditions were not easy to control.Therefore,the method of synthesizing N-sulfonylamidine with simple,convenient and mild conditions is one of the research hotspots of chemical and medical workers,and it is also one of the most chal enging fields.In this paper,a new method for the rapid and efficient synthesis of N-sulfonylamidine compounds by one-pot method is proposed by cheap and easily available sulfonyl chloride,sodium azide and tertiary amine or secondary amine reaction under the catalysis of copper bromide.Compared with the reported method,this method has the significant advantages,such as cheap and easily available raw material and catalyst,easy to save,one pot reaction,simple and convenient operation,and wide range of application.Furthermore,the experimental mechanism was studied and discussed by experimental means of free radical blocking and nitrogen protection.This paper mainly elaborates from the following aspects: 1.In this paper,the properties,synthesis methods and practical application of N-sulfonylamidine and its derivatives were systematically summarized and summarized in the first chapter.2.The p-toluenesulfonyl chloride,sodium azide and triethylamine as the basic reaction raw materials in the second chapter,the amount of reactants,the type and amount of catalyst,the type of solvent,the reaction time and react ion temperature were systematically optimized,the optimum reaction conditions were obtained : 0.5 mmol of sulfonyl chloride,0.6 mmol of sodium azide,0.5 mmol of tertiary amine,5 mol% of copper bromide were added in 5.0 ml of 1,2-dichloroethane,and the mixture was stirred at 70 °C for 3 hours,the product yield was 78%;The optimum reaction conditions were received by using p-toluenesulfonyl chloride,sodium azide and diethylamine as the basic reaction materials: 0.5 mmol of sulfonyl chloride and 1.0 mmol of sodium azide,1.25 mmol of secondary amine and 5 mol% of copper bromide were stirred respectively in 5.0 m L of 1,2-dichloroethane at 70 °C for 1 hour,The reaction solution of the secondary amine and the copper bromide was slowly added dropwise to the reaction solution of the sulfonyl chloride and the sodium azide,and the reaction was continued for 2 hours after the dropwise addition.3.The applicability of the template reaction was examined under the optimum reaction conditions.Twenty-five target products were synthesized efficiently with a variety of benzenesulfonyl chloride and various tertiary amines.Then the experimental mechanism was studied and discussed by experimental means of free radical blocking and nitrogen protection,and the experimental mechanism of this reaction was put forward,the reaction mechanism is as follows:4.The applicability of the template reaction was examined under the best reaction conditions.Twenty-five target products were synthesized efficiently with a variety of benzenesulfonyl chloride and various secondary amines,which proved that the reaction has certain applicability.And the mechanism of the reaction was proposed based on the reported literature and the research foundation o f this laboratory.the reaction mechanism is as follows:...