A New Method For The Synthesis Of 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine Derivatives

In this work,two new methods for the synthesis of 2,3-dihydro-1H-pyrrolo[2,3b]pyridine derivatives from ortho-bromoamine ester and ortho-bromoamine ketone with 2-amino-1,1,3-tricyanopropene(malondinitrile dimer)as nucleophilic reagent and alkaki as catalysts had been established.This method boasts for its simple operation,easily-obtained raw materials and metal-free catalysis.The products can be used in heteropolycyclic chemistry,natural antibiotics,synthesis of anticancer drugs and structural modification of natural products.Initially,the relating researches have been illustrated in this section.In this respect,we summarized the widespread application of pyridine,dihydropyrrolopyridine,pyrrolopyridine skeleton materials in the fields of chemical industries and medicines,and the current research methods for the synthesis of dihydropyrrolopyridine,which laid a theoretical foundation for the above-mentioned new methods in this paper.The first part(Chapter 2)mainly introduces the research on the synthesis of dihydropyrrolopyridine derivatives from ortho-bromoamine ester with malononitrile dimer.Based on the research of aminoholegenation of olefince in our group,when ortho-bromoamine ester was the substrate and malononitrile dimer was the nucleophile,a new method for the synthesis of dihydropyrrolopyridine derivatives was established.In this condition,CH3OH was used as the solvent,K3PO4 was used as the accelerator,and the reaction temperature was 50?.With optimized conditions in hands,the reaction substrate was expanded and 17 new compounds were obtained.The study found that whether substrate is a ?-amino-?-bromo or a ?-bromo-?-amino ester compound,the target product can be obtained in a high yield(up to 94%).In addition,the method metioned above was also suitable for the reaction of o-bromoamine hydrocarbon with malondionitrile dimer.Then,four new compounds were obtained.Given the results,we representatively selected six dihydropyrrolopyridine derivatives as substrates(3a,3d,3h,3m,3'c,3'e),the oxidative dehydrogenation reactions had been studied.The results were that they can be successfully converted into corresponding pyrrolopyridine derivatives(3aa,3dd,3hh,3mm,3'cc,3'ee).The second part(Chapter 3)mainly introduces the research of synthesizing dihydropyrrolopyridine derivatives from ortho-bromoamine ketone with malononitrile dimer.Using ortho-bromoamine ketone(2a)and malononitrile dimer as raw materials,the reaction conditions were explored and found that reaction could proceed without inert gas protection.Finally,17 new compounds were obtained at 50? in EtOH solvent and with K3PO4 as accelerator.Based on this,we also selected a substrate(6a)as the reactant of oxidative dehydrogenation template reaction.The result was that it can be successfully converted into pyrrolopyridine compound(6aa).Based on the experimental results,we predict that the 3,3' and 6,6' compounds can also be converted into the corresponding pyrrolopyridine compounds by oxidative dehydrogenation.All new compounds were confirmed by 1H NMR,13C NMR,IR,HRMS(ESI),and possible reaction mechanisms were proposed.