Synthesis of Pyrazoles by 1,3-Dipolar Cycloaddition under Aqueous Micellar Catalysis

Ethyl diazoacetate (EDA), which is easily prepared from ethyl glycinate and NaNO2, reacts in situ with alkynes in a water micelle environment without organic solvent to form pyrazoles. The reaction is pH dependent, as in the presence of protic catalysis (H2SO4 4%, pH 3.5) a mixture of 3,5- and 4,5-disubstituted pyrazoles was obtained, while, at pH 5.5, only the 3,5-disubstituted isomer was obtained. The presence of the surfactant TPGS-750-M was crucial to secure clean crude reaction mixtures and high yields of the products. The same protocol was successfully applied to the synthesis of substituted pyrazolines.

Automated summary

Ethyl diazoacetate (EDA) reacts with alkynes in a water micelle environment to form pyrazoles. The reaction outcome depends on the pH, with different substituted positions obtained under different pH conditions. The presence of a surfactant is crucial for obtaining high yields and clean products. The same method is applicable for the synthesis of substituted pyrazolines.