Tese
Síntese e reações de 5-trifluormetil- 4,5-diidro-1H-1-pirazoltiocarboxamida 3(4)-substituídos
Fecha
2002-07-26Autor
Wastowski, Arci Dirceu
Institución
Resumen
This thesis describes the synthesis and application as bi-heterocyclic precursor a
series of 3-aryl[alkyl]-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-
pyrazolethiocarboxamides (2), which are easily obtained from the direct
cyclocondensation reaction of β-alkoxyvinyl trifluoromethyl ketones (1) with
thiosemicarbazide in methanol, under mild conditions (r.t - 450C, 20-24 h) and in good
yields (73-96%). Similarly, the 1H-1-pyrazolethiocarboxamide derivatives (2) were
dehydrated and the thiocarboxamide group hydrolyzed in an one-step reaction by stirring
with concentrated sulfuric acid under reflux for 4 hours to give the 3-aryl[alkyl]-5-
trifluoromethyl-1H-pyrazoles (3) in good yield (57-75%).
In a subsequent application reaction of 3-aryl[alkyl]-5-hydroxy-5-trifluoromethyl-
4,5-dihydro-1H-1-pyrazolethiocarboxamides (2), the synthesis of alkyl[aryl]-substituted
5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-methylpyrazoles (4) in good yields (68-
90%) from a new ring transformation reaction of alkyl[aryl]-substituted-5-hydroxy-5-
trifluoromethyl-4,5-dihydro-1H-1-pyrazolethiocarboxyamides (2) with methylhydrazine
in THF (2-7 hours a 20-250C), is reported. The thermal dehydration reaction of these
pyrazolines (4) furnished the respective N-methylpyrazoles (5).
Finally, a convenient method for the synthesis of a novel series of eighteen noncondensed
5,5-bicycles, specifically 2-(3-alkyl(phenyl)-5-hydroxy-5-trifluoromethyl-4,5-
dihydro-1H-pyrazol-1-yl)-4-phenyl-5-alkyl-thiazoles and -4,5,6,7-
tetrahydrobenzothiazoles (6), in good yields (57-98%), from the reaction of 3-alkyl(phenyl)-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-pyrazolethiocarboxamide
(2) with 2-bromoacetophenone, 2-bromopropiophenone and 2-bromocyclohexanone, is
reported. The dehydration of these compounds by stirring at reflux for 5 hours with a
mixture of concentrated sulfuric acid/acetic acid 1:10 v/v, led to the corresponding 2-[3-
alky(phenyl)-5-trifluoromethyl-1H-pyrazol-1-yl]-4-phenyl-5-alkylthiazoles and
respective -4,5,6,7-tetrahydrobenzothiazoles (7) in good yield (75-93%).