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

J Org Chem. 2008 May 2;73(9):3523-9. doi: 10.1021/jo800251g. Epub 2008 Apr 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acari / drug effects
  • Alcohols / chemistry*
  • Animals
  • Fluorine Compounds / chemical synthesis*
  • Fluorine Compounds / chemistry
  • Fluorine Compounds / pharmacology*
  • Methylation
  • Molecular Structure
  • Phenylhydrazines / chemistry
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Solvents / chemistry*
  • Stereoisomerism

Substances

  • Alcohols
  • Fluorine Compounds
  • Phenylhydrazines
  • Pyrazoles
  • Solvents
  • 4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide
  • pyrazole