One-pot Synthesis Pyrazole From Propargyl Alcohol Catalyzed By Bi（OTf）₃

Pyrazole is a nitrogen-containing five-membered heterocyclic ring,which exists in medicines,natural products and materials,and plays a very important role in the development of medicine,agriculture and chemical industry.Since Knorr reported the method of synthesizing pyrazole using 1,3-diketone compounds in 1883,many methods of synthesizing pyrazole have been developed.How to use other types of substrates to efficiently and simply construct the framework of pyrazole is a valuable and challenging task.The research of this subject is based on substituted propynol derivatives,iodosuccinimide and hydrazine hydrate as raw materials,iodine-intercepted Meyer-Schuster rearrangement under the catalysis of bismuth trifluoromethanesulfonate Reaction and intermolecular ring-forming reaction,so as to realize the one-pot synthesis of substituted pyrazole.This thesis is divided into two parts:The first part is to use 10%Bi（OTf）₃ as catalyst,1,4-dioxane as solvent,and iodosuccinimide as electrophile to intercept the Meyer-Schuster rearrangement reaction to constructα-iodo-α,β-unsaturated carbonyl compounds.The scope of application of propynol and the possibility of preparation in grams of this reaction were also studied;in the second part,based on the optimized reaction conditions,the cyclization reaction ofα-iodo-α,β-unsaturated carbonyl compounds under the action of hydrazine hydrate was studied,and finally the synthesis of pyrazole compounds from propynol was realized.In the experiment,we studied the application scope of the substrate and the gram-level preparation of the one-pot method.We also designed several control experiments,and based on the experimental results,we put forward a conjecture about the possible reaction process of the reaction.The advantages of this synthetic method developed in the article are as follows.First,a cheap,low-load catalyst is used;second,the reaction can tolerate various types of propargyl alcohol;third,the gram-scale scale-up experiment shows that the reaction has the possibility of large-scale production;fourth,the reaction obtains the product in a moderate to good yield;fifth,the experimental operation is simple and no additional separation is required.These advantages make this reaction a valuable method for constructing pyrazole derivatives.