Ph₃P/ICH₂CH₂I System-promoted Formylation Of Aromatic Hydrocarbons

Aldehyde functionality commonly exists in medicines and natural products.Compounds containing aldehyde groups are widely used in pharmaceuticals,agrochemicals,life sciences,materials and many other fields.Therefore,the development of mild and convenient methods to introduce formyl or aldehyde groups into organic molecules has become an active research area in synthetic chemistry.Previously,we have found that triphenylphosphine(Ph₃P)could react with1,2-dihaloethane(XCH₂CH₂X)to generate halogen phosphonium species(Ph₃P⁺X X^-),which could activate hydroxyl and aldehyde groups to achieve deoxy functionalization of alcohols and aldehydes.We speculated that if N,N-dimethylformamide(DMF)is used as the reaction solvent,the Vilsmeier-type intermediate might be produced in the reaction system.In this thesis,we examined the use of the Ph₃P/ICH₂CH₂I system for the formylation of indoles in DMF.1.The introduction section of this thesis includes two parts:(1)the application of the formyl group,the formylation of aromatics and the named reactions for formylation are briefly described,and the Vilsmeier-Haack formylation is expounded;(2)The research background of formylation of arenes and heteroarenes is also summarized.2.The significance of the topic:If Vilsmeier intermediates can be simply and mildly generated from Ph₃P/ICH₂CH₂I system to realize the formylation of electron-rich substrates,it can provide an alternative formylation method for the synthesis of aldehyde intermediates,which are widely used in pharmaceuticals,agrochemicals,life sciences and materials.3.Direct formylation of indole compounds with Ph₃P/ICH₂CH₂I system was successfully achieved in DMF.For indoles containing methyl,methoxyl and other electron-donating groups,formylation can be carried out in one step.For indoles containing olefin,cyano,ester,aldehyde and other electron-withdrawing groups,a second step of hydrolysis is necessary to obtain the target products.This method features mild reaction conditions,convenient operations,metal-free,an air atmosphere for reactions,and moderate to good yields.Using this method,we successfully introduced the aldehyde group into indole derivatives.The synthesized products were characterized by ¹H NMR,¹⁹F NMR,¹³C NMR and MS spectroscopies.For the unknown compound,5-olefin indole-3-formaldehyde,the IR and melting point data were also obtained.