The Novel Cyanation Reactions With Formamide As Cyanide Source

Nitriles are widely found in many natural products,pharmaceuticals,dyes and agrochemicals.They also serve as multifunctional precursors for the synthesis of a range of compounds such as amines,amides,aldehydes,oximes,ketones and carboxylic acids.In the past few decades,the main way to introduce cyano group into aromatic compounds has been achieved by transition metal catalyzed cyanation of aryl halides.However,excess cyano anions often result in deactivation of transition metal catalysts and serious environmental problems.In order to solve these problems,a series of non-metal cyano sources have been developed in recent years.Using a non-metallic cyano source instead of metal cyanides in cyanidation has obvious advantages.This non-metallic cyan source is green and practical,and has few environmental problems.Therefore,the development of non-metal cyano source for the synthesis of nitriles is of great significance.This dissertation is consisted of three parts:In the first part of the study,a Ni-catalyzed cyanation of cyano group from dehydration of foramide and aryl halides was initially developed for the facile and efficient synthesis of aromatic nitriles.The protocol uses formamide as a practical,non-toxic cyano source,and produces water as the sole by-product,meeting the requirements of green chemistry.This protocol not only avoids the use of highly toxic metal cyanide,but also solves the problem that the concentration of cyano anions is too high to deactivate the catalyst.The method exhibits excellent functional group tolerance,high conversion rate,and the isolated yield is as high as 94%.This protocol can also efficiently synthesize phenothiazine antipsychotic drugs（prozinonitrile）,which has great application prospects.In the second part of the study,a Ni-catalyzed hydrocyanation of formamide and alkynes was developed for the facile and efficient synthesis of acrylonitrile derivatives.This protocol not only avoids the use of highly toxic metal cyanide,but also solves the problem that the concentration of cyano is too high to deactivate the catalyst.The raw materials are commercially available,and this method has great application value.By optimizing the conditions systematically,the optimal condition for the hydrocyanation of the alkyne using a formamide as the cyano source:Diphenylacetylene（6a,0.2 mmol）,Ni（acac）₂（0.01 mmol,5 mol%）,Co（acac）₂（0.02mmol,10 mol%）,Xantphos（0.03 mmol,15 mol%）,formamide（1.0 mL）,anisole（0.6mL）,sealed in air（1 atm）heated at 150°C for 24 h.This method exhibits excellent functional group tolerance,high conversion rate,and high separated yield.This reaction provides a new protocol for the hydrocyanation of alkyne and the synthesis of acrylonitrile.In the third part of the study,a chemoselective[2+2+2]annulation of cheap aromatic nitrile,short chain aliphatic nitrile and formamide was developed for the facile and efficient synthesis of 1,3,5 triazines based on the first part of the research on the cyanation of aryl halides.