Studies Of Detosylative(Deutero) Alkylation Of Indoles And Phenols

The trideuteromethylation reaction is significant for the synthesis of drug molecules containing trideuteromethyl groups.This thesis mainly studies an one-step deprotection and(deutero)methylation reaction of tosylative indoles and phenols compounds as well as expand the(deutero)alkylation reaction and preliminarily study its application.In this work,a series of N-methyl indoles and O-methyl aryl ethers were synthesized using potassium methanol(KOCH₃)as the methylation reagent together with the substrates of tosylative indoles and phenols.Then the synthesis of deuteromethyl indoles and phenolic compounds was achieved using deuterated potassium methanol(KOCD₃)as the deuteromethyl source.The alkylation of indoles with in situ formed alkoxides by mixing potassium tert-butoxide with the corresponding alcohol was also explored and the corresponding desired products were obtained including N-CD₃-and ¹³CH₃-labeled indoles compounds.Besides,an one-pot alkylation reaction of unprotected indoles was developed.Also the local anesthetic drug molecule pomocaine and its deuterium-substitutions were synthesized based on deprotected alkylation of phenolic compounds.The whole(deuterio)alkylation method features mild reaction conditions,a broad substrate scope and the required raw materials are relatively cheap and easy to obtain compared with the traditional alkylation regent such as(deuterated)iodomethane or dimethyl sulfate.