DAST promotes the synthesis of new 5-(trifluoromethyl)-3-(1,1-difluoroethan-2-yl)-1H-pyrazoles

This study describes, firstly, the synthesis of a new precursor, 4,6,6-trimethoxy-1,1,1-trifluorohex-3-en-2-one (1), from the trifluoroacetylation reaction of 1,1,3,3-tetramethoxybutane, in 65% yields. Afterwards, the reaction of 1 with two hydrazines (NH2NHR, where R = 2-furanoyl, C6F5) led to a new series of 4,5-dihydro-1H-pyrazoles, containing an acetal-protected aldehyde function as substituent, in 90-97% yields. In a subsequent step, the dehydration reactions of these 4,5-dihydro-1H-pyrazoles gave the respective aromatic 1H-pyrazoles. Finally, we report the results of the deprotection reactions of the acetals to obtain the respective aldehyde function, as well as, the subsequent fluorination reaction using DAST, leading to new difluorinated derivatives in 55-60% yields. (C) 2009 Elsevier Ltd. All rights reserved.