Regiospecific one-pot synthesis of new trifluoromethyl substituted heteroaryl pyrazolyl ketones

Abstract

These 2-pyrazolines showed interesting antimycobacterial activity in vitro. Thus, considering the biological importance of 2-pyrazolines and some ketone derivatives and the fact that the reactions to obtain structurally similar compounds, employing aryl or heteroarylhydrazides and fluorinated βdiketones (CF 3 COCH 2 COCF 3 or CF 3 COCH 2 COR) are rare in the literature [20-25], we have recently reported a new regiospecific synthetic method to obtain a series of six 3-aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1 H-1picolinoylpyrazoles, in a one-step reaction and in good yields from the reaction of β-methoxyvinyl trifluoromethyl ketones with 2-pyridinecarboxamidrazone [26]. However, this work [26] allowed to obtain only picolinoyl derivatives under acid condition. Moreover, the 2pyridinecarboxamidrazone was previously obtained with some experimental difficulty. Although the possibility of preparing trihalomethylated pyrazoles and pyrazolines by a regiospecific cyclocondensation reaction of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoro(chloro)-3-alken-2-ones with hydrazines has long been explored by our research group [27], a general and system atic methodology that allows the synthesis of new interesting trifluoromethyl substituted heteroaryl pyrazolyl ketones (trifluoromethylated heteroaroylpyrazoles) was not yet developed. In view of these observations, we became interested in heterocycles, which may play an important role in the physiological processes of living or ganisms. Thus, on the course of our research program concerning the application of 4-alkoxy-4-alkyl(aryl)-1,1,1-trihalo-3-alken-2-ones to obtain new trihalomethylated heterocycles, we wish to report the regiospecific synthesis of a new series of 3alkyl(aryl)-5-trifluoromethyl-5-hydroxy-1-(heteroaroyl)4,5-dihydro-1H-pyrazoles and some aromatic derivatives which have been obtained from the cyclocondensation reaction of 2-thiophenecarboxylic hydrazide, furoic