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.

The synthesis of 5-[2-(trifluoromethylheteroaryl)-ethyl]-1,3,4-oxadiazoles derived from levulinic acid is reported. Cyclocondensations [4 + 1] between four different 5-[2-(trifluoromethylheteroaryl)propionylhydrazides derived from methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate obtained from levulinic acid, and electrophilic orthoesters RC(OR1)3 (where R = H, Me, Ph) and CS2 were carried out in a mild medium. Good yields (69-96%) of isolated products were obtained. The structures of the new ethylene-spaced biheterocycles were characterized using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization coupled to tandem mass spectrometric (ESI MS/MS) data.