Improved regioselectivity in pyrazole formation through the use of fluorinated alcohols as solvents: synthesis and biological activity of fluorinated tebufenpyrad analogs.
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.
Fustero
Santos
S
Departamento de Química Orgánica, Universidad de Valencia, E-46100 Burjassot, Spain. santos.fustero@uv.es
Román
Raquel
R
Sanz-Cervera
Juan F
JF
Simón-Fuentes
Antonio
A
Cuñat
Ana C
AC
Villanova
Salvador
S
Murguía
Marcelo
M
D000053:Acari / Q000187:drug effects; D000438:Alcohols / Q000737:chemistry*; D000818:Animals; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008745:Methylation; D015394:Molecular Structure; D010659:Phenylhydrazines / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012997:Solvents / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D017611:Fluorine Compounds; D010659:Phenylhydrazines; D011720:Pyrazoles; D012997:Solvents; C429623:4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide; C031280:pyrazole