Study On Nucleophilic Acylation Of Aromatic Aldehydes And Aromatic Halides Catalyzed By N-heterocyclic Carbenes

Benzophenone compounds are an important organic intermediate.The traditional ways of synthesizing benzophenone are electrophilic substitution and coupling reaction.The substrates are limited,and the reaction requires the use of an excess of Lewis acid or a transition metal compound as a catalyst which can damage the environment.N-heterocyclic carbene as an organic small molecule catalyst can catalyze the nucleophilic acylation of aromatic aldehydes with aromatic halides,which provides a new idea for the synthesis of benzophenone compounds.In this paper,two types of catalysts were synthesized: imidazolium carbene precursors and thiazolium carbene precursors.Among them,the imidazolium carbene precursors were divided into tetrafluoroborates and hexafluorophosphates according to the different anions.The product structure was determined by measuring the melting point of the product,the infrared spectrum,and the nuclear magnetic spectrum.The nucleophilic acylation of aromatic aldehydes and p-fluoronitrobenzene was studied by using the carbene precursors.Different carbene precursors,the time,the temperature and the amount of the catalyst were optimized by using p-fluorobenzaldehyde and p-fluoronitrobenzene as the reaction substrates.The optimum conditions were as follows: using 1-butyl-3-methylimidazolium tetrafluo roborate as carbene precursor,the reaction time 1 h,the reaction temperature 0 ?,DMF as the solvent,the amount of catalyst was the amount of reactant 20 mmol%.And the effects of different substituents on the reaction were investigated.At the same time,the recycling of imidazolium catalyst was investigated.The nucleophilic acylation of substituted aromatic aldehydes and3,4-difluoronitrobenzene was studied by using the imidazolium carbene precursors.Different carbene precursors,the time,the temperature and the amount of the catalyst were optimized by using 2-fluorobenzaldehyde and 3,4-difluoronitrobenzene as the reaction substrates.The optimum conditions were as follows: using 1-butyl-3-methyl imidazolium tetrafluo roborate as carbene precursor,the reaction time 1 h,the reaction temperature 0 ?,DMF as the solvent,the amount of catalyst was the amount of reactant20 mmol%.Under the optimum conditions,2-fluorobenzaldehyde,2,4-difluoro phenylaldehyde,2,5-difluorophenylaldehyde and 2,6-difluorobenzaldehyde reacted with3,4-difluoronitrobenzene.The yields were 76%,42%,42% and 32%,respectively.Xanthone was a kind of important bioactive natural products.This paper provides a new method for synthesis of xanthone.At first,the nucleophilic acylation of o-methoxybe nzaldehyde and 3,4-difluoronitrobenzene catalyzed by N-heterocyclic carbine is performed.Then the intermediate of benzophenone with o-methoxy group has a demethylation reaction,and the methoxy is tranfered into hydroxyl groups.Finally,the intermediate of demethylation has an intramolecular cyclization reaction to produce xanthone.The 1,3-dimethylimidazolium iodide was used as carbene precursor to catalyze the reactions of 2-methoxybenzaldehyde,2,4-dimethoxybenza-ldehyde,2,6-dimethoxybe nzaldehyde and 2-methoxy-5-bromobenzaldehyde with 3,4-difluoronitrobenzene,respectively.The yields were 63%,75%,42% and 65%,respectively.2'-fluoro-4-nitrobenzop henone,2-fluoro-2'4'-methoxy-4-nitrobenzop-henone and 5'-bromo-2-fluoro-2'-methox y-4-nitrobenzophen-one were demethylated.The reaction yields were 52%,85% and60%,respectively.Under the action of cesium carbonate,nitro-2'-hydroxy-2-fluoro-b enzophenone,2-fluoro-2'-hydroxy-4-n-itrobenzophenone,5-bromo-fluoro-2-hydroxy-4'-nitrobenzophenone underwent an intramolecular cyclization reaction to produce the corresponding xanthones.All the reaction yields were about 92%.