Four Organic Reactions In Ionic Liquid Microemulsions

"Green Chemistry" is the dominant direction of current chemistry development. The biocatalytic reactions in ionic liquid based microemulsions and the reactions catalyzed by ionic liquid based microemulsions are the new ways and methods to achieve the goal of "green chemistry". But the enzyme catalytic promiscuity in ionic liquid microemulsions were rarely reported. Here, 1-butyl-3-methylimidazolium hexafluorophosphate([Bmim][PF₆], a hydrophobic ionic liquid, was selected as oil phase, and the enzyme-catalyzed Henry reaction, Markovnikov addition reaction and asymmetric aldol reaction, in w / IL microemulsions were explored,and [Bmim][PF₆]-based Microemulsions catalyzed Knoevenagel condensation reaction was also found.The Henry reaction in [Bmim][PF₆]-based microemulsions promoted by acylase: An environmentally-friendly, enzyme-promoted procedure for the Henry reaction was first studied using water-in-[Bmim][PF₆] microemulsions as reaction medium. The reaction conditions were optimized using 4- nitrobenzaldehyde and nitromethane as a model reaction, and the effect of ω0 value, Tx-100 volume, the amount of enzyme, temperature on the reaction were investigated. The Amano acylase from Aspergillus oryzae showed better catalytic activity for the addition reactions of nitromethane with a series of aromatic aldehydes, and a highest yield of 90% was obtained, While the 12 kinds of substrates were expand, and the yields of 22%-90% were achieved.The Markovnikov addition reaction in [Bmim][PF₆]-based Microemulsions promoted by BSA: A novel strategy to effect Markovnikov addition between azoles and vinyl esters was developed, in which a ’promiscuous’ enzyme, protease or protein, were utilized as the catalyst in in in Tx-100 / H2 O / [Bmim][PF₆] microemulsions. The bovine serum albumin（BSA） showed better catalytic effect. The reaction conditions were optimized using imidazole and vinyl acetate as a model reaction, and the effect of the amount of BSA, temperature, substrate molar ratio on the reaction were investigated. A highly efficient protocol for Markovnikov ’s addition using ionic liquid microemulsions as a catalytic green solvent as well as catalyst is described. Interestingly, Ionic liquid microemulsions and BSA so-catalyzed Markovnikov’s addition reaction was proved. By this strategy, a series of pharmaceutically active azole derivatives were synthesized in moderate to yields from 50% to 90%. This strategy is advantageous to the development of ionic liquid microemulsions application in biocatalysis technology.The asymmetric aldol reaction co-catalyzed by trypsin and N-heterocyclic compounds in [Bmim][PF₆]-based microemulsions: The asymmetric aldol reaction of aldehydes and ketones could be performed under trypsin and N-heterocyclic compounds used as co-catalyst in Tx-100 / H2 O / [[Bmim][PF₆] microemulsions. The reaction conditions were optimized using 4- nitrobenzaldehyde and acetone as a model reaction, Some control experiments have been designed to demonstrate that either trypsin or N-heterocyclic compounds could not catalyze the tandem reaction. The trypsin showed the highest activity in the presence of imidazole and has been used to catalyze the asymmetric aldol reactionbetween different aldehydes and ketones. Under the optimum reaction conditions,, acetone and 13 kinds of aromatic aldehydes were used to expand the asymmetric aldol reaction,and yields of 12%-90 % of the 13 kinds of aldol reaction products were achieved.And cyclohexanone and 7 kinds of aromatic aldehydes were aslo used to expand the asymmetric aldol reaction, but the lower yields were obtained at Longer period of time compared with the former. Although these products do not stereoselective, but This method has provided a new strategy to perform the asymmetric aldol reaction and expanded the application of biocatalysts[Bmim][PF₆]-based microemulsions catalyzed Knoevenagel condensation reaction: First, The effect of ionic liquid microemulsions dosage and temperature on the reaction were investigated,and The results show that the typical Knoevenagel condensation was carried out smoothly in the presence of Tx-100 / H2 O / [Bmim][PF₆] microemulsions, and 95% of yield was obtained using malononitrile and nitrobenzaldehyde as substrates at 35 ℃ for 1.5 h. Then, under the optimized conditions, six aromatic aldehyde and malononitrile or nitrile acetate were used to expand the Tx-100 / H2 O / [Bmim]PF₆ microemulsions catalyzed Knoevenagel reaction, the yields from 77% to 95% were achieved with mild and environment-friendly conditions at a short time. This method is not only a green synthesis method, but also expands the application of ionic liquid microemulsions.In conclusion, these studies expand applications of ionic liquid microemulsion, and promote the development of green chemistry and enzymatic reactions.