Studies On The Application Of NHPI Esters In Selective Phenolic Acylation And Coumarin Alkylation

Phenolic ester structures are a kind of basic units in scientific research and industrial production,which are widely found in natural products,pharmaceuticals,agrochemicals and functional materials,etc.For example,the coumarins are a kind of natural products with the endo-phenolic ester structure,which show good fluorescence activity.Here,the acylation of phenols to synthesize phenolic esters and the alkylation of coumarins to modify phenolic esters are developed by using N-hydroxyphthalimide ester（NHPI ester）as acyl source and alkyl source,respectively.The specific research content and results are as follows:1.The selective acylation of phenols with NHPI esters is developed to synthesize phenolic esters under the promotion of inorganic bases.The reaction prodceeds by using K₂CO₃ as additions and NHPI esters as acyl source under condensing agents-,catalysts-and traditional acylating reagents-free conditions（acyl halides and acid anhydrides）,giving various esters in good to excellent yields at room temperature.A series of sensitive functional groups,such as hydroxyl group,ester group,aldehyde group,amino group and azo group,are well toleranced.Notably,on the basis of significant differences in phenolic and alkydic acidity,selective acylation of phenolic hydroxyl group is achieved in the presence of alcoholic hydroxyl group.In addition to phenols,naphthols,pyridinols,quinolinols,and thiophenols are all suitable reaction substrates,and the expected products are produced in high yields.Gram-scale production of the acylation reaction is tried,which furnishs desired product in satisfactory yield with the recovery of N-hydroxyphthalimide（NHPI）.Finally,this acylation program has been applied to the synthesis of estrogen drugs,food-grade spices and gemfibrozil analogs,which further emphasize the broad application value.A possible reaction mechanism is offered by analyzing experimental results and literature.2.Photocatalytic selective alkylation modification of the endo-phenolic ester structure of coumarins is developed.As readily accessible,stable,and cheap mediators,the use of Na I and PPh₃ allows this reaction occurs under metal-free,oxidant-free and blue LEDs irradiation conditions with excellent regioselectivity to generate 3-alkylated coumarin derivatives by using NHPI ester as the alkylation reagents.Further functional modification could be accomplished with good functional group compatibility.In addition,quinoxalinones are also viable substrates for this reaction,giving the corresponding 3-alkylated products in satisfactory yields.Mechanistically,photocatalytic free-radical process is probably involved in the alkylation of coumarins and TMEDA could improve the photoactivity of the system.