Synthesis And Property Studies Of Isoxazole-substituted Pyrazoline And Piperazine N-containing Heterocyclic Compounds

N-containing heterocyclic compounds isoxazole,pyrazoline and piperazine widely existed in natural products with good biological and pharmacological activities play a very important role in the field of organic synthesis.In particular,they are the structural units of many drugs,which have good antibacterial,anti-inflammatory and hypoglycemic effects,and are widely used in the field of medicine.In addition,theπbond conjugation of pyrazoline molecules leads to large dipole moment and hyperpolarizability,which makes pyrazoline derivatives have good fluorescence properties and can be used in the field of luminescent materials.In this paper,pyrazoline and piperazine derivatives containing isoxazole ring were synthesized using different substituted benzaldehydes as raw materials.Firstly,substituted benzaldehyde oximes were synthesized by the reaction of substituted benzaldehyde with hydroxylamine hydrochloride.Then,substituted benzaldehyde oximes reacted with NCS and propargyl alcohol under the catalysis of Zn Cl₂in one pot via 1,3-dipolar cycloaddition to obtain（3-arylisoxazol-5-yl）methanols.Secondly,3-arylisoxazole-5-carbaldehydes were synthesized by oxidation of（3-arylisoxazol-5-yl）methanols using iodine and TEMPO as oxidant.Subsequently,3-arylisoxazole-5-carbaldehydes reacted with p-chlorophenone to prepare1-（4-chlorophenyl）-3-（3-arylisoxazol-5-yl）prop-2-en-1-ones under alkaline conditions via hydroxyl aldehyde condensation.Nest,twelve novel pyrazoline derivatives containing isoxazole ring were synthesized between 1-（4-chlorophenyl）-3-（3-arylisoxazol-5-yl）prop-2-en-1-ones and substituted phenylhydrazine hydrochloride in 44–94%yield on the basis of the optimized condition.The structures of the target compounds were characterized and analysized using the modern analytical techniques.The corresponding fluorescence quantum efficiency（0.17–0.53）was calculated by testing UV and fluorescence spectra of the synthesized compounds,and the influence of substituents on the luminescent properties was discussed.Finally,5-（bromomethyl）-3-arylisoxazoles obtained starting from（3-arylisoxazol-5-yl）methanols and NBS reacted with anhydrous piperazine under the refluxing condition to synthesize new piperazine derivatives containing bis-isoxazole ring.Herein,the effects of catalyst,solvent,feed ratio and heating method on the yields of target compounds were investigated,and the optimum reaction conditions were determined.Eight kinds of 1,4-bis（（3-arylisoxazol-5-yl）methyl）piperazines were synthesized in 60–87%yield under the optimum reaction condition.The synthesized compounds were characterized by FT-IR,HRMS,¹H and ¹³C NMR.Their structure was verified.Moreover,according to the American Institute of Clinical and Laboratory Standards（CLSI）recommended antibacterial drug susceptibility test method,the antimicrobial activity of eight target compounds was studied.Among them,compounds 1,4-bis（（3-（4-tert-butyl）phenyl）isoxazol-5-yl）methyl)piperazine and 1,4-bis（（3-（4-methoxyphenyl）isoxazole-5-yl）methyl）piperazine showed better antibacterial effect on the tested strain Mycolicibacterium smegmatis MC²155,and the MIC values were 1.33±0.57（?）g/m L and 2.00±0.00（?）g/m L,respectively.In conclusion,pyrazoline ring and piperazine ring were integrated with isoxazole respectively by 1,3-dipolar cycloaddition,nucleophilic substitution,aldol condensation and nucleophilic addition.The fluorescence properties and antibacterial activities of these compounds were studied,and good results were obtained.