title: Improved regioselectivity in pyrazole formation through the use of fluorinated alcohols as solvents: synthesis and biological activity of fluorinated tebufenpyrad analogs.
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.
authors.affiliation: Departamento de Química Orgánica, Universidad de Valencia, E-46100 Burjassot, Spain. santos.fustero@uv.es
authors.forename: Santos
authors.initials: S
authors.lastname: Fustero
authors.forename: Raquel
authors.initials: R
authors.lastname: Román
authors.forename: Juan F
authors.initials: JF
authors.lastname: Sanz-Cervera
authors.forename: Antonio
authors.initials: A
authors.lastname: Simón-Fuentes
authors.forename: Ana C
authors.initials: AC
authors.lastname: Cuñat
authors.forename: Salvador
authors.initials: S
authors.lastname: Villanova
authors.forename: Marcelo
authors.initials: M
authors.lastname: Murguía
mesh_terms: 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
chemical_list: 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