Study On The Reaction Of 2-Alkynylbenzaldehydes And Diamines Compounds Catalyzed By Lewis Acid

In recent years,2-alkynylbenzaldehydes as the substrates containing both a formyl and an alkynyl have the important applications in organic synthesis.They could react with diamines compounds or hydrazines to synthesize various kinds of heterocyclic compounds,such as quinoline,isoquinoline,pyrazine,etc,which play an important skeleton in drugs,materials and natural products.Therefore,the reaction involving 2-alkynylbenzaldehydes has become the hot topics in the research of organic chemistry.In addition,the classical Sonogashira coupling reaction is an effective method to obtain 2-alkynylbenzaldehyde and its derivatives.The first chapter reviews the relevant reactions of 2-alkynylbenzaldehydes,such as the condensation,hydroamination,cyclization reaction,halogenated reaction,etc.The second chapter studied the oxidative coupling and dehydrogenation reaction of naphthalene-1,8-diamine(1)and 2-alkynylbenzaldehydes(2).The reaction using Cu(OAc)2 as a catalyst,oxygen as a green oxidant.The oxidative dehydrogenation coupling products(3)were unexpectedly after condensation,cyclization and hydroamination.In order to verify the possible mechanism,some intermediates,which of isoquinolino[2,1-a]perimidine(4)and the perimidine derivatives(5),were acquired via controlling the reaction conditions.In addition,the most crucial step in the reaction mechanism is disproportionation of copper acetate,and the different valences of copper in the reaction process were determined by HRMS analysis which further confirmed the feasibility of the reaction mechanism.The reaction not only provides a good method to synthesize fused heptacyclic quinolizino[3,4,5,6-kla]perimidine derivatives,but also provides a green method for oxidative dehydrogenation coupling of aromatic hydrogen.The third chapter studied two series of hydroamination reactions between 2-aminobenzenesulfonamide(2-aminobenzamides)and 2-alkynylbenzaldehydes.First,the reaction of 2-aminobenzenesulfonamide(7)and 2-alkynylbenzaldehydes was carried out catalyzed by iodine to obtain thiadiazino[3,2-a]isoquinoline derivatives(8).In order to verify the mechanism,we have captureed the possible reaction intermediats by controlling experimental condition,with thiadiazines being obtained as we expected(9).Subsequently,when 2-aminobenzenesulfonamide was replaced by 2-aminobenzamide(10),the similar reaction was performed in the presence of CuI to give isoindolo[1,2-b]quinazoline derivatives(11).Comparing with the spectral data and melting point of known compounds,it was confirmed that it was the more active hydrogen of amide hydrogenparticipated the hydroamination reaction in rather than that of the amino hydrogen on the 1-position of quinazoline in the literature.The fourth chapter studied the reaction of 2-aminobenzohydrazides(12)and 2-alkynylbenzaldehydes(2).The Lewis acid of indine was proved to be an efficient catalyst to promote the above reaction and obtain 5-benzoyl-phthalazino[1,2-b]quinazoline-8-one derivatives(13).The reaction result indicated that the iodine played multiple roles in this system.First,iodine may promote condensation and hydroamination reaction.Subsequently,it also makes the methylene into ketone via an oxidation in the presence of oxygen.In addition,in order to verify the mechanism,the relevant reaction intermediate products were also determined by HRMS analysis.The experimental results show that the reactions between the diamines and 2-aminobenzohydrazides were proved to an efficient method for the synthesis of some nitrogen heterocyclic compounds(quinazoline,isoquinoline,pyrazine,etc)catalyzed by different Lewis acids.In addition,the salient feature of the catalyst(copper salt and iodine)involves low price,little pollution,etc.Those methods provide a good way for drug synthesis in the future.