Synthesis And Property Studies Of Substituted Isoxazole And Pyrazole N-containing Heterocyclic Compounds

Isoxazole and pyrazole N-containing heterocyclic compounds with unique structural characteristics have a variety of biological and pharmacological properties,which results in extensive application prospects in medicine,pesticides and organic synthesis.Especially,the synthesis and application in medicine of isoxazole and pyrazole have attracted much attention owing to their anti-inflammatory,antibacterial,analgesic performance.In addition,some pyrazole derivatives have significant solvent discoloration and electroluminescent properties,which were widely applied in the display materials.In this paper,the synthesis of the different substituted isoxazole and pyrazole derivatives were studied using different substituted benzaldehydes as raw materials.Firstly,3-aryl-5-((prop-2-yn-1-yloxy)methyl)isoxazole and 3-arylisoxazole-5-carbaldehyde were synthesized from substituted benzaldehydes.Herein,different substituted benzaldehydes were firstly oximated by hydroxylamine hydrochloride,and chlorinated with N-chlorosuccinimide,and then reacted with propargyl alcohol by 1,3-dipolar cycloaddition to obtain(3-arylisoxazol-5-yl)methanol.Furthermore,The corresponding 3-aryl-5-((prop-2-yn-1-yloxy)methyl)isoxazole and 3-arylisoxazole-5-carbaldehyde were obtained by etherification and oxidation of(3-arylisoxazol-5-yl)methanol,respectively.Next,6-chloro-N-hydroxynicotinimidoyl chloride was synthesized from 2-chloro-5-(chloromethyl)pyridine,which was firstly hydrolyzed to(6-chloropyridin-3-yl)methanol,and then was selectively oxidized to 6-chloronicotinaldehyde by I2.Furthermore,6-chloro-N-hydroxynicotinimidoyl chloride was obtained by reacted successively with hydroxylamine hydrochloride and N-chlorosuccinimide.Moreover,3-(6-chloropyridin-3-yl)-5-(((3-(2-methoxyphenyl)isoxazol-5-yl)methoxy)methyl)isoxazole was synthesized starting from 3-(2-methoxyphenyl)-5-((prop-2-yn-1-yloxy)methyl)isoxazole and 6-chloro-N-hydroxynicotinimidoyl using Zn as a catalyst.The reaction condition was optimized,and other eight new bisisoxazole derivatives were synthesized in 56–73% yield under the optimal condition(ultrasonic radiation).According to the American Institute of Clinical and Laboratory Standards(CLSI)recommended antibacterial drug susceptibility test method,the antimicrobial activity of nine target compounds was studied.3-(6-chloro-3-pyridine)-5-(((3-(2-methoxyphenyl)isoxazol-5-yl)methoxy)methyl)isoxazole and 3-(2-Chlorophenyl)-5-(((3-(6-chloro-3-pyridyl)isoxazol-5-yl)methoxy)methyl)isoxazole have better antibacterial effect on the selected fungi Candida albicans ATCC 10231,and both of their minimum inhibitory concentration(MIC)were 4 ?g/m L.Finally,nine 1,3,5-trisubstituted pyrazole derivatives were obtained by the reaction between 1-(4-chlorophenyl)-3-arylprop-2-en-1-ones and(4-chlorophenyl)hydrazine hydrochloride under reflux condition.1-(4-chlorophenyl)-3-arylprop-2-en-1-ones were synthesized using 9 different substituted benzaldehydes and 1-(4-chlorophenyl)ethanone as raw materials under ultrasound condition.The yields of the synthesized 1,3,5-trisubstituted pyrazole derivatives were 74–96%.By testing UV and fluorescence spectra of the synthesized pyrazole derivatives,the corresponding fluorescence quantum efficiency(0.48–0.60)was calculated.The maximum UV absorption wavelength range of the synthesized target products was 360–370 nm,and the maximum fluorescence emission wavelength was 457–472 nm,which emited blue color mainly.It suggested that 1,3,5-trisubstituted pyrazole derivatives have potential application in the luminescent material field.In addition,all synthesized target products were characterized by HRMS,FT-IR,~1H and 13 C NMR,and their structures were confirmed.