Design, Synthesis And Characterization Of Heterocyclic-fused Containing Of Benzo[h]Quinoline Skeleton

Benzo[h]quinoline and its derivatives are a very important class of heterocyclic compounds,widely present in natural products with a wide range of biological and pharmaceutical activities.Especially, planar poly-cyclic hetero-fused benzoquinoline compounds have shown potentanti-tumor and anti-cancer activities. Therefore, the development of new methods for thesynthesis of novel and interesting polycyclic hetero-fused benzoquinoline derivatives attractsinterests to organic synthetic chemists. Thus, the aim of thesis was to design a facilemethodology for the synthesis of such compounds. The present thesis was mainly consisted offour parts as follows:In the first part, through surveying the literatures concerning the synthesis and applicationsof benzoquioline derivatives，we made a review on the recent advance of such compounds.In the second part, we mainly described a simple and efficient procedure for the synthesis of2-（chloromethyl）benzoquinoline （2） by the direct cyclization of1-naphthylamine with4-chloro-acetoacetic acid ester in the presence of Vilsmeier reagent prepared from dimethylformamide andphosphorus oxychloride. After usual workup, compound （2） was obtained in a good yield of68%.In the third part, a simple, convenient, and high-yielding approach for the synthesis of aseries of new2-（benzofuran-2-yl）benzo[h]quinoline-3-carboxylic acid derivatives was developed,involving the one-pot synthesis reaction of ethyl2-（chloromethyl）benzo[h]quinoline-3-carboxylate （2） with various substituted salicylaldehydesas well as2-hydroxy-1-naphthaldehyde under mild reaction conditions. The characteristic featureof this reaction was that the Williamson ether synthesis, hydrolysis of an ester group, andcyclization reaction occurred in one-pot procedure, thereby resulting in good isolated yields of68-83%. The structures of all the new compounds （3a-g） were confirmed by ESI-MS, IR andNMR spectra.In the forth part,2-（phenoxymethyl）benzo[h]quinoline-3-carboxylic acid derivates （4a-g）was synthesized by the Williamson reaction of ethyl2-（chloromethyl）benzo[h]quinoline-3-carboxylate （2） with phenol or substituted phenolsfollowed by the ester hydrolysis reaction at3-position. The resulting acids4a-g were further treated by Eaton’s reagent （P₂O₅-MeSO₃H）, leading to the corresponding cyclized productsbenzo[h]benzo[6,7]oxepino[3,4-b]quinolin-8（14H）-one （4h-l） in good isolated yields of77-82%via intramolecular electrophilic cyclization reaction.In the fifth part, a series of novel2-styryl-3-carboxybenzoquinolines （5a-f） have beensynthesized, which involved the reaction between ethyl2-（chloromethyl）benzo[h]quinoline-3-carboxylate （2） and triethyl phosphate to afford thecorresponding Ylides followed by the reaction of Wittig-Horner with aromatic aldehydes andsubsequent basic hydrolysis. The resulting styrylquinoline-3-carboxylic acids （5a-k） could befurther treated by Eaton’s reagent to give the corresponding12H-benzo[4,5]tropono[1,2-b]benzoquinolines （5g-i） via intramolecular cyclization reaction.