A New Method For The Synthesis Of Tetraaryl-substituted Pyrazoles

Pyrazoles,which have a wide range of biological and pharmaceutical activities,play an important role in the research and development of drugs and pesticides.Tetraarylsubstituted pyrazoles exhibit excellent applications in medicine,pesticides,ligands and luminescent materials.In order to expand new properties and applications of these compounds,more and more researchers have explored the synthetic methods of tetraarylsubstituted pyrazoles.However,the reported methods generally have the disadvantages of low yield,small range of substrates,the use of precious metal catalysts and multi-step operation,which limit the scope of application of these reactions.Therefore,it is particularly important to find a new synthetic method with high selectivity,wide application range of substrates and short route to construct tetraarylsubstituted pyrazoles.A series of 1,3,4,5-tetraarylsubstituted pyrazoles were synthesized by a new1,3-dipolar cycloaddition/SO₂ extrusion reaction with a yield of up to 90.4%.The main contents of this paper include the following aspects:（1）N-methyl-1,3-dihydrobenzoisothiazole-2,2-dioxide was synthesized from 2-bromoaniline by acylation,N-methylation and intramolecular cyclization.1,3-Dihydrobenzoisothiazole-2,2-dioxide was synthesized by acylation,chlorination and Buchwald-Hartwig coupling.Knoevenagel condensation reactions with aromatic aldehydes resulted in a series of dipolarophiles.The synthetic routes of dipolarophiles were determined,and the conditions of Buchwald-Hartwig coupling reaction and Knoevenagel condensation reaction were optimized.（2）Nitrile imine precursors were obtained from phenylhydrazine and benzoyl chloride by substitution reaction and chlorination reaction.The synthetic route of nitrile imide was discussed and the optimum chlorination conditions were screened.（3）The reaction conditions for the preparation of tetraaryl substituted pyrazole compounds by 1,3-dipole cycloaddition/SO₂ extrusion reaction in series desulfurization were optimized in terms of solvent,base and temperature.（4）Under the optimized reaction conditions,the range of substrates was extended,and the effects of different nitrile imine and dipolephiles on the reaction were also discussed.The results showed that the substituents on the dipole were in favor of the reaction,while the steric resistance and electronic effect of the substituents on the dipole had no significant effect on the reaction.Heteroaromatic substituted methylenebenzoisothiazoledioxideand3-benzomethylene-1,3-dihydrobenzoisothiazole-2,2-dioxide without protective group on N atom were also suitable for this method.In addition,the E-configuration of the dipolephile and E-Z isomers had no effect on the reaction and the aimed products were obtained in good yield.（5）The structure of the products was characterized by ¹H NMR,¹³C NMR and HRMS.The stereo configuration of the product was determined by X-ray single crystal diffraction,and the reaction mechanism was deduced.（6）Photophysical properties and aggregation induced emisson of newly synthesized tetraaryl substituted pyrazoles were studied.It was found that the relative quantum yields of the aggregates of products was up to 0.83,the Stokes shift was between 10400-14000 cm^-1,and some of the products had obvious aggregation-induced emisson effect.In this article,tetraarylsubstituted pyrazoles can be synthesized in one step with high yield.The method has the advantages of mild reaction conditions,high regioselectivity,wide range of substrates.It provides a methodological basis for the synthesis of new tetraarylsubstituted pyrazoles and has important value for enriching the research of biological activity of these compounds.