Synthesis Of Neonicotine Derivatives And Polysubstituted Quinoline Amides

The new nicotine derivatives have good biological activities,and many drugs contain the new nicotine skeleton structure.The quinone methylation have widely concerned being to it is a good Michael addition substrate.Therefore,the two biological active molecules were spliced to the quinone methylate substituted neonicotinoid derivatives.To date,The quinone methylation usually used as acceptor of 1,6-addition,and the works that involved in the 1,6-addition companying with oxygen autoxidation are very limited.Consequently,it is important to explore the synthetic route of quinone methylate substituted neonicotinine derivatives.Quinoline-4-carboxamides have attracted the attention of more and more experts due to their various biological activities.However,the methods for the synthesis of quinoline-4-carboxamides are still limited due to the need to form an amide-bond between the carboxyl group of carboxylic acid and an amine which is usually based on condensing agents.Recently,some novel methods to construct amide bonds have been reported including the palladium-catalysed to form a quinolinamide bond.These methods have obvious shortcomings,such as long reaction time,low yield participation of metal catalysts in the reaction,etc.Therefore,to construct quinoline-4-carboxamides by one step are very meaningful.It is also suitable for combination and parallel synthesis of quinolone-4-carboxamide or natural products.Based on the importance of nicotine derivatives substituted with quinone methylate and the activity of quinolone amide compounds,the main work of this paper is as follows:The first chapter,the 1,1-enediamine,the novel nicotine derivatives and quinolone amide compounds are briefly reviewed.The second chapter,1,1-enediamine ?-2 or 1,1-ethylenediamine ?-3 and quinone methylate ?-1 were used as raw materials at refluxing in acetone and promoted by Cs₂CO₃,The yield of the neonicotinine derivative of?E?-type structure ?-4 or?Z?-type structure ?-5 was 70%?92%.???The third chapter,49 quinolones ?-4/?-5 were prepared by the reaction of isatin ?-1 with 1,1-enediamine ?-2/?-3 in Et OH:H₂O=1:2 and acatalyzed by NH₂SO₃H.give the target compound with the yield up to 95%.???The structure of these two kinds of compounds was characterized by ¹H NMR,¹³C NMR,IR,HRMS and other methods.The novel nicotine derivatives and Quinoline-4-carboxamides were determined by X-Ray single crystal diffraction.The structure of the compound was confirmed.