Journal of Organic Chemistry 2008-05-02

Improved regioselectivity in pyrazole formation through the use of fluorinated alcohols as solvents: synthesis and biological activity of fluorinated tebufenpyrad analogs.

Santos Fustero, Raquel Román, Juan F Sanz-Cervera, Antonio Simón-Fuentes, Ana C Cuñat, Salvador Villanova, Marcelo Murguía

Index: J. Org. Chem. 73(9) , 3523-9, (2008)

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Abstract

The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity.