The synthesis of 3-alkyl-5-trifluoromethyl-1H- pyrazole-1-carboxamides, 3-alkyl-5-trifluoromethyl-1H-pyrazole-1-thiocarboxamides, and 2-(3-alkyl-5-trifluoromethyl-1H-pyrazol-1-yl)-thiazoles derivatives are reported. [3 + 2] cyclocondensations for a series of long alkyl chain 1,1,1-trifluoro-4-methoxyalk-3-en-2-ones and semicarbazide or thiosemicarbazide were carried out in ethanol, an eco-friendly medium. The series of trifluoromethyl-1H-pyrazol-1-yl-thiocarboxamide following a [3 + 2] cyclocondensation with 2-bromoacetophenone were converted into two series of 2-(3-alkyl-5-trifluoromethyl-1H-pyrazol-1-yl)-thiazoles. Good yields (69-96%) of the isolated products were obtained. The structures of the new long alkyl chain 1H-pyrazoles and 2-(1H-pyrazol-1-yl)thiazoles were characterized using 1H, 13C, and 19F nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization tandem mass spectrometric (ESI MS/MS) data. Moreover, some of the products were evaluated for their antimicrobial activity against Gram-negative Escherichia coli American Type Culture Collection (ATCC) 35218, Salmonella enteritidis ATCC 13076, and Pseudomonas aeruginosa ATCC 15692; and Gram-positive Staphylococcus aureus ATCC 6538, methicillin resistant Staphylococcus aureus (MRSA clinical isolate), Streptococcus sp. (clinical isolate), and Candida albicans ATCC 14053 and Candida krusei ATCC 6258 fungi. All the tested 1H-pyrazoles exhibited antibacterial and antifungal activities at the tested concentrations. The compounds from series 4 were found to be powerful against MRSA.

A series of functionalized 1,1,1-trihalo-4-methoxy-3-alken-2-ones [CX3C(O)CR1=CROMe, where X = F or Cl; R = n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-tridecyl, (CH2)2CH=C(Me)2, (CH2)2Ph, (CH2)2-(4-HOC6H4), (CH2)2-(4-MeOC6H4), (CH2)2CO2Me, (CH2)3CO2Me, CH(SMe)CH3, CH2(2-MeOC6H4), and R1 = H, and R = H and R1 = n-decyl] were synthesized from respective alkyl methyl ketones or aldehyde via acetal acylation using trifluoroacetic anhydride and trichloroacetyl chloride. 1,1,1-Trihalo-4-methoxy-3-alken-2-ones with acid-compatible substituents were easily hydrolyzed to respective trihalomethyl-1,3-diketones. The 1,1,1-trihalo-4-methoxy-3-alken-2-ones and/or respective trihalomethyl-1,3-diketones were reacted regiospecifically with hydroxylamine hydrochloride, leading to isoxazole derivatives, and with hydrazines, leading to respective 1H-pyrazole derivatives. The structures of all compounds were assigned based on nuclear magnetic resonance (NMR) and mass spectrometric data. This method represents an efficient pathway for the regioselective trihaloacetylation of asymmetrically substituted alkyl methyl ketones and highly self-condensing aldehydes. Moreover, this approach allows the introduction of biologically recognizable moieties, such as those from levulinic acid, sulcatone (prenyl), benzylacetone, anisylacetone, and raspberry ketone, as synthetic molecular targets.