Study On The Synthesis Of Pyrazole Compounds From Alkynes And Trimethylsilyl Diazomethane Catalyzed By Silver Salt

Pyrazole,a five-membered heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms,is a motif containing small molecules and possess a wide range of anti-bacterial,anti-inflammatory,anti-viral,anti-cancer,antioxidant and analgesic activities and low toxicity.It has been found versatile applications in pharmaceutical agrochemical industries and advanced functional materials.In this paper,an atom-economic route to pyrazoles has been developed.In the presence of silver?I?as catalyst,TMSCHN₂?trimethylsilyldiazomethane?can be reacted with alkynes,or propargylic alcohols via 1,3-dipolar cycloaddition to provide various pyrazole compounds,respectively.First,4-methoxyl-phenylacetylene was chosen as the standard substrate to react with TMSCHN₂,different reaction conditions including catalysts,solvents and temperatures were optimized carefully.Finally,we found that silver carbonate as catalyst,and 1,4-dioxane as solvent,the reaction of4-methoxyl-phenylacetylene with TMSCHN₂ at 80°C can afford 87%of5-?4-methoxyphenyl?-1H-pyrazole in 4 hours.Under the same reaction condition,TMSCHN₂ can also react with propargyl alcohol through 1,3-dipolar cycloaddition to provide corresponding pyrazoles in good yields.In most reactions,TMSCHN₂ behaves as a 1,3-dipole for the preparation of[C–N–N]azoles,in this reaction,TMSCHN₂ also served as a reagent of[C-N-N]synthon.The treatment of alkynes or propargylic alcohols with TMSCHN₂ catalyzed by silver?I?produced 5-substituted pyrazole compounds?15 products,yield 42-88%?and 5-substituted pyrazole methanone?5 products,yield 65-87%?,which underwent a desilylation process leaving the trimethylsilyl group.In this paper,we have developed a silver catalyzed 1,3-dipolar cycloaddition of trimethylsilylmethane with easily available alkynes and propargylic alcohols,leading to various 5-substituted pyrazole derivatives.The substituents at 5-position can be aryl,heteroaryl,alkene and alkyl group,and the reaction is atom economic.It can be a good method to generate pyrazole products.We have also studied the ¹H and ¹³C nuclear magnetic resonance?NMR?spectra of pyrazole compounds.The effect of electric quadrupole momentum of nitrogen 14(¹⁴N)on the spectra of pyrazole compounds was also investigated.All the pyrazoles synthesized in this paper were analyzed by ¹H,¹³C NMR spectra.The structure of product 5-?4-methoxyphenyl?-1H-pyrazole was confirmed by X-ray single crystal diffraction.The structure of product 5-?naphthalen-2-yl?-1H-pyrazole was certified by¹H and ¹³C NMR and Two-dimensional spectra such as COSY/HSQC/HMBC/NOESY spectral data analysis.