Study On The Method Of Ring Expansion Of Quinolones To Synthesize Benzazepines

Many biologically active compounds contain benzazepine skeletons.Due to the existence of seven-membered rings,benzazepine compounds are more difficult to synthesize than five-membered and six-membered rings,and they are also subject to ring Impact.Quinolone is a benzo six-membered nitrogen heterocyclic structure,which was discovered and synthesized a long time ago,and the synthesis methods are various.In this thesis,a new method for synthesizing benzazepine compounds was developed by studying the ring expansion reaction of quinolone compounds using diethylα-chlorophosphonate and α-halocarboxylate as ring-expanding reagents.It is of great significance to contribute to the synthesis of azepine compounds.This paper mainly studies the following three parts:1.Using N-methylaniline and EMME as raw materials and PPA as condensing agent,the corresponding quinolone compounds were synthesized by one-pot two-step method.Under the same method and conditions,the substrate expansion was carried out,and a variety of quinolone derivatives with different substituents were successfully synthesized,which provided a substrate for the study of the ring expansion reaction.At the same time,diethyl α-chlorophosphonate was synthesized as a ring-expanding reagent.2.A template reaction for quinolone compound ring expansion to synthesize benzazepine compounds was established.After many conditions optimization,the optimal reaction conditions were screened out,and the optimal yield of the template reaction was 88 %.Under the optimal reaction conditions,a series of benzazepine compounds were synthesized by substrate expansion,and most of them had good yields,which proved the feasibility of the ring expansion reaction.3.Using α-halogenated carboxylate as the ring-expanding reagent,the quinolone compound was subjected to the ring-expanding reaction,and the corresponding benzazepine compound was also successfully obtained.A variety of differentα-halogenated carboxylic acid esters,such as methyl ester,ethyl ester,isopropyl ester,tert-butyl ester,benzyl ester,etc.,have been expanded,and good yields have been achieved.The effect of halogen on the ring expansion reaction was explored,and the results of the ring expansion reaction of ethyl fluoroacetate,ethyl chloroacetate and ethyl bromoacetate were compared.The rate is much lower than that of ethyl chloroacetate.Also tried to use p-toluenesulfonyl chloride methane as the ring-expanding reagent to carry out the ring-expansion reaction,and successfully synthesized the corresponding benzazepine compounds.