Synthesis and ¹³C NMR of (trifluoromethyl)hydroxypyrazoles

Abstract

Reaction of ethyl 4,4,4‐trifluoroacetoacetate with methylhydrazine produced not only the previously reported 5‐hydroxy‐3‐(trifluoromethyl)pyrazole 1 but also its unknown isomer the 3‐hydroxy‐5‐(trifluoromethyl)pyrazole 4. The structure assignments are established based on 13C nmr spectra. Compound 1 was converted to 5‐chloro‐3‐(trifluoromethyl)pyrazolecarboxylic acid 3 in two steps.

Synthesis of trifluoromethylated pyrazoles from trifluoromethylenaminones and monosubstituted hydrazines

“…4.4. 1,: elutant CH 2 Cl 2 :cyclohexane (90: 10) 3ab: solid, 7%, 1 H NMR (CDCl 3 ): m,Har),7.75 (2H,dq,J ¼ 1:1 Hz,J ¼ 8:6 Hz,8.01 (1H,q,J ¼ 0:9 Hz,. 13 Calc.…”

“…The main synthetic methods to prepare such compounds involve [3 þ 2] atom fragments cyclization of various trifluoromethyl building blocks with hydrazines: acetylenic imines [5], acetylenic esters [6], acetylenic nitriles [7], alkoxyalkenones [8], b-diketones [2b,9], b-ketoesters [10], ketene dithiocetals [11].…”

Synthesis and Antitumor Activity of 5-Trifluoromethyl-2,4- dihydropyrazol-3-one Nucleosides

“…A variety of pharmacological agents bearing a trifluoromethyl group are of special interest as they exhibit wide ranging biological properties [1][2][3][4]. Many efficient methods for the introduction of a trifluoromethyl group into organic molecules have been developed.…”

Synthesis and bioactivities of novel trifluoromethylated pyrazole oxime ether derivatives containing a pyridyl moiety

“…Then, 5-hydroxypyrazole 5 was treated with POCl 3 and DMF to give 4-formyl-5-chloropyrazole 6 in 87% yield. 17 Subsequently, the substitution of 4-formyl-5-chloropyrazole 6 with phenols, benzenethiols, t-BuSH, and MeSNa under basic conditions, produced aldehydes 7a-7n (Scheme 2), 10a-10d (Scheme 3) in satisfactory yields. 18 Aldehydes 7a-7n, 10a-10d were then converted to the corresponding oximes 8a-8n, 11a-11d by hydroxylamine under basic conditions, 19 and further etherification of oximes 8a-8n, 11a-11d with the intermediate 4 under base promoting conditions generated the title compounds 9a-9n (Scheme 2), 12a-12d (Scheme 3).…”