Cyclocondensation between fatty acid hydrazides and 1,1,1-trifluoro-4-alkoxy-3-alken-2-ones: Introducing a trifluoromethylated head onto fatty acid moieties

<p>This paper reports the regioselective synthesis of new trifluoromethylated lipid derivatives, namely, 1-(5-hydroxy-5-trifluoromethyl-3-alkyl-4,5-dihydro-1<i>H</i>-pyrazol-1-yl)alkan-1-ones, through cyclocondensation reactions between a series of fatty hydrazides (palmitoyl, stearoyl, and oleoyl hydrazides) obtained from fatty acids from renewable resources (1,1,1-trifluoro-4-alkoxy-3-alken-2-ones [F<sub>3</sub>CC(O)CH˭C(R<sup>1</sup>)OR, where R<sup>1</sup> = H and R˭Et; R<sup>1</sup> = –(CH<sub>2</sub>)<sub>6</sub>CH<sub>3</sub>, –(CH<sub>2</sub>)<sub>6</sub>CH<sub>3</sub>, –(CH<sub>2</sub>)<sub>8</sub>CH<sub>3</sub>, –(CH<sub>2</sub>)<sub>9</sub>CH<sub>3</sub>, –(CH<sub>2</sub>)<sub>10</sub>CH<sub>3</sub>, –(CH<sub>2</sub>)<sub>12</sub>CH<sub>3</sub>, –(CH<sub>2</sub>)<sub>2</sub>Ph], and R˭Me). Experimental observations showed that the lipophilic characteristic of 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1<i>H</i>-pyrazoles (<b>5–7</b>) prevent the acid catalyzed dehydration to aromatization of 1<i>H</i>-pyrazole ring, although in some cyclocondensations a proportion of the aromatic derivative 1-(5-trifluoromethyl-3-alkyl-1<i>H</i>-pyrazol-1-yl)alkan-1-one was obtained. All products were characterized using multinuclear (<sup>1</sup>H, <sup>13</sup>C, <sup>19</sup>F) NMR spectroscopy.</p>