Benzyne Promoted Esterification Reactions

As a classical organic reaction,esterification reaction has a wide range of laboratory and industrial applications.Esters can generally be prepared via either dehydration between carboxylic acid and alcohol or transesterification with esters.Compared with dehydrative esterification,transesterification reaction possesses its advantages under certain circumstances.For instance,it can avoid the insoluble problem of some carboxylic acids in organic solvents during homogeneous esterification.However,traditional transesterification reaction also has certain shortcomings,such as necessity for acidic or basic catalysts,high reaction temperature,and long reaction time,limiting the synthetic application of transesterification reactions.As a highly reactive intermediate,benzyne cannot be isolated and purified due to its short life span.When participating in the reaction,benzyne can only be generated in situ from the corresponding benzyne precursors.In recent years,Kobayashi benzyne precursor has received extensive attention due to its mild generation conditions.It has been reported in the literature that,under mild conditions,both carboxylic acids and alcohols can participate in nucleophilic reactions with benzyne.This thesis proposes that benzyne can be used as an activating reagent chemoselectively in the presence of both carboxylic acid and alcohol,so that carboxylate preferentially and selectively attacks benzyne to generate phenolic esters;the obtained phenolic ester will then undergo further transesterification with alcohol to afford the desired esterification products.First,we tried one-pot reaction of Kobayashi benzyne precursor with benzoic acid and benzyl alcohol in the presence of fluoride ion.After optimizing the reaction conditions,benzyl benzoate was obtained in high yield.Next,we examined substrate scope and found that acid could react with various primary alcohols to obtain the corresponding esters in high yields as well.When secondary alcohols were employed as the substrate,the reaction must be carried out at high concentration with the utilization of potassium carbonate as the base.The reason is that the nucleophilicity of secondary alcohol is weaker than that of primary alcohol,and transesterification reaction needs to be carried out at high concentration.When sterically hindered carboxylic acids were used,potassium carbonate must be added as a base to ensure smooth reaction as well.In addition,we tried to apply this reaction system to lactonization reaction.The reaction to generate small ring lactones can obtain products with high yields.However,when the product is a seventeen-membered ring lactone,we failed to achieve the desired product in high yield.Moreover,we tried to examine a series of benzyne precursors with additional electron-withdrawing groups on the benzyne ring to perform the reaction,whereas the yield of lactonization remained unsatisfied.Our future work includes ways to improve the yield of macrolactonization.