Synthesis and Antimycobacterial Evaluation of Novel Pyrazole-Isoxazolines and Pyrazole-Isoxazoles.

This study reports the synthesis of a new series of pyrazole-isoxazolines, at very good yields, from the cyclocondensation reaction of pyrazole-enaminones with hydroxylamine hydrochloride. Dehydration of the pyrazole-isoxazolines furnished another new series of the respective pyrazole-isoxazoles, at excellent yields. Both series of the obtained compounds were screened for antimycobacterial activity, and compounds 4 f and 5 c showed significant inhibition of bacterial growth with a time- and concentration-dependent bactericidal effect.

Regiocontrolled Synthesis of 1-Substituted-3(5)-carboxyalkyl-1-pyrazoles Using Trichloromethyl Enones.

In this work, we present a regiocontrolled methodology to prepare 1-substituted-3(5)-carboxyalkyl-1-pyrazoles using trichloromethyl enones as starting materials. It was found that the selectivity of the reaction depends on the nature of the hydrazine: when using arylhydrazine hydrochlorides, synthesis of the 1,3-regioisomer was achieved (22 examples, 37-97% yields), while the corresponding free hydrazine led exclusively to the 1,5-regioisomer (12 examples, 52-83% yields). The trichloromethyl group was used as a precursor for the carboxyalkyl moiety, furnishing a one-pot three-component regioselective protocol suitable for preparing both isomers at moderate to excellent yields.

Chemoselective -Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1)-ones Using 4-(Iodomethyl)pyrimidines.

This study reports two strategies for preparing -alkyl derivatives of 6-substituted-4-(trifluoromethyl)pyrimidin-(1)-ones: a linear protocol of alkylation, using a -building block followed by [3 + 3]-type cyclocondensation with 2-methylisothiourea sulfate and a convergent protocol based on direct alkylation, using 4-(iodomethyl)-2-(methylthio)-6-(trihalomethyl)pyrimidines. It was found that the cyclocondensation strategy is not feasible; thus, the direct chemoselective -alkylation was performed, and 18 derivatives of the targeted pyrimidines were obtained in 70-98% yields. The structure of the products was unambiguously determined via single crystal X-ray analyses and two-dimensional nuclear magnetic resonance experiments.

Substituent-Driven Selective -/-Alkylation of 4-(Trihalomethyl)pyrimidin-2(1)-ones Using Brominated Enones.

The selective - or -alkylation of 4-(trihalomethyl)pyrimidin-2(1)-ones, using 5-bromo enones/enaminones as alkylating agents, is reported. It was found that the selectivity toward the - or -regioisomer is driven by the substituent present at the 6-position of the pyrimidine ring, thus enabling the preparation of each isomer as the sole product, in 60-95% yields. Subsequent cyclocondensation of the enaminone moiety with nitrogen dinucleophiles led to pyrimidine-azole conjugates in 55-83% yields.