Radical Initiated Alkylation And Acylation Of Heterocyclic Compounds

As an important class of chemical backbones,nitrogen heterocycle has been widely developed and used in the fields of natural products,medicinal chemistry,and synthetic organic chemistry.It is precisely because such heterocycles play a vital role in various fields that the exploration of their functionalization over the years has been lasting.In the context of complex molecules,it is not easy to modify the nitrogen heterocycle directly,and most of them are through strategies such as intramolecular cyclization.On the other hand,in recent years,most methods for direct modification of nitrogen heterocyclic compounds are rely on the catalysis of noble metals.Therefore,it is particularly significant to explore a mild,eco-friendly and simple method to realize the direct modification of heterocyclic compounds in the later stage.As an important branch of functionalization,the research on alkylation and acylation is naturally attracting attention.Reports about alkylation are not uncommon,but alkylation of nitrogen heterocycles still needs to be further explored to be greener and easier to operate.Therefore,based on the above reasons,this work exploreed a new protocol for the alkylation and acylation of nitrogen heterocyclic compounds.This manscript mainly includes the following three aspects:Part 1: Summarize several common alkyl sources and briefly review and review the functionalization on quinoxalinone and 2H-indazole ring.Part II: Using aldehyde as alkyl source to study the C-3 alkylation of quinoxalinone under peroxide catalysis,we screened the reaction conditions,expanded the reaction substrate,and also explored the reaction mechanism.researched and validated.The method is simple and efficient,and provides a new route for the alkylation of nitrogen heterocycles.Part III: After the realization of the alkylation of quinoxalinone,2H-indazole is considered as a promising nitrogen heterocycle,and it has been widely used in research and development as a drug premise.We hope that the alkylation of 2H-indazole can also be achieved by a simple method.The reaction also uses aldehyde as the alkyl source,and the mechanism is verified after screening the reaction conditions and expanding the substrate.Simple conditions,convenient operation,environmentally friendly,and no metal catalysis are what differentiates this reaction from other existing related 2H-indazole alkylation methods.All in all.We have developed a greener,more efficient,metal-free,and widely applicable method for the alkylation of nitrogen heterocyclic compounds.From the perspective of organic synthesis,we provide a new idea of alkylation,which provides a reference for better realization of more efficient and environmentally friendly new methods in the future.