Synthesis Of 2-pyrazoline Derivatives From Ketazines Catalyzed By Ionic Liquids

Cyclization of ketazines to synthesize 2-pyrazoline derivatives is an important method,which has 100%atom utilization.The existing catalysts(such as oxalic acid,crystalline iodine,etc.)may have several problems such as large pollution,low catalytic efficiency,and difficult separation.The development of green and high-efficiency catalysts is of great significance to synthesis of 2-pyrazoline derivatives by cyclization of ketazines.Three types of catalyst include Lewis acid ionic liquids,sulfonic acid ionic liquids and polymeric ionic liquids were prepared,which significantly impoved the efficiently of the cyclization of ketazines.Combined with density functional theory(DFT)calculations,the reaction mechanism of ketazine cyclization to 2-pyrazoline derivatives is deeply revealed,which provides data and theoretical support for the research and development of ketazine cyclization process.The main contents are summarized as follows:(1)Fe-based Lewis acid catalyst system was developed and application for the cyclization reaction of ketazines.The experiment results show that,under the optimal conditions(4 mol%FeCl3,80?,6 h),the conversion of acetone azine can reach 95%,with 99%selectivity of 3,5,5-trimethyl-2-pyrazoline.The DFT calculation results show that the cyclization of ketazines contain two steps:configuration transformation step and ring-closing step.The ring-closing step with the highest barrier energy of transition state(40.32 kcal/mol)is the rate-determing step.Inadditon,the electrostatic potential(ESP)and electronic localization(ELF)analyses show that the addition of FeCl3 can significantly change the ESP distribution of ketazines,which can decrease the barrier energy of transition step and increase the conversion of ketazines.(2)Fe-based Lewis acid ionic liquids with adjustable acidity were designed and synthesized to catalyze the ketazines cyclization reaction to prepare 2-pyrazoline derivatives.The catalytic effects of Lewis acid ionic liquids show that[Bmim]Cl·2.0FeCl3 has the highest catalytic efficiency,and the conversion of acetone azine can reach 96%within 5 h.The substrate expansion experiment of ketazines shows that the smaller carbon number of the ketazine substituent R group,the higher conversion of ketazines,the order of activity follows:methyl(96%)>ethyl(88%)>n-propyl(82%)>n-butyl(75%).In the case of same carbon number group,the reaction effect of R group being n-alkane is better than that of corresponding iso-alkane,the order of conversion follows:n-propyl(82%)>isopropyl(45%),n-butyl(75%)>isobutyl(43%)>tert-butyl(11%).(3)Br(?)nsted sulfonic acid ionic liquids were designed and synthesized,which realized the efficient catalysis of ketazines to prepare 2-pyrazoline derivatives.With sulfonate as the proton-donating group,9 ionic liquid catalysts were obtained through the regulation of hydrophobic groups,alkyl chain length,and anions.The experimental results show that[PsBim][CF3SO3]has the highest catalytic performance,the conversion of acetone azine can reach 98%within 4 hours,and the selectivity remains 99%.The DFT calculation results show that the anion and cation of ionic liquids can act synergistically effect on the ketazines molecule,reducing the transition state free energy barrier both of configuration transformation step and cyclization step.The configuration transformation step can be completed spontaneously at room temperature(half-life t1/2=1.34×10-2 h),which was further verified by experiments.(4)A series of polymerized ionic liquid microsphere catalysts were designed and synthesized to construct the heterogeneous catalytic system.The molecular dynamics diameter simulation results show that the maximum molecular dynamics diameter of ketazine and 2-pyrazoline is 10.56 A,which is smaller than the average pore diameter of the microspheres of 32.40 A,indicating that the ketazine and 2-pyrazoline derivative molecules can freely enter and exit the inside of the microsphere material.The experimental results show that the molar ratio of vinylimidazole(VIM),divinylbenzene(DVB),and porogen toluene is a key factor in controlling the surface morphology and internal pore structure of polymeric ionic liquid microspheres.When the molar ratio of VIM,DVB and porogen is 1:1:6,the BET specific surface area of polymerized ionic liquid microspheres is the largest(498.8 m2/g),the catalytic activity is the highest,and the conversion and selectivity are 95%and 99%,respectively.