An Acetal Acylation Methodology for Producing Diversity of Trihalomethyl- 1,3‑dielectrophiles and 1,2-Azole Derivatives

Abstract

1 = 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.

Trifluoromethyl‐β‐dicarbonyls as Versatile Synthons in Synthesis of Heterocycles

“…Bareño et al disclosed [3 + 2] cyclocondensation of trifluoromethyl-β-diketones 1 and hydroxylamine hydrochloride 55 to afford 5-hydroxy-5-trifluoromethyl-4,5-dihydroisoxazoles 237 regiospecifically (Scheme 75). [162] Pavlik et al reported the synthesis of 3-phenyl-5-(trifluoromethyl)isoxazole 239 by dehydration of 3-phenyl-5hydroxy-5-trifluoromethylisoxazoline 238, obtained by the cyclocondensation of 1,1,1-trifluoro-4-phenylbutane-2,4-dione 1 with hydroxylamine hydrochloride 55, using p-TsOH (Scheme 76). [163] Compound 238 in the 13 Aggarwal et al explored reaction of trifluoromethyl-βdiketones 1 with hydroxylamine 55 at variable pH (Scheme 77).…”