Reduction of Trifluoromethyl-containing 4-Nitroso- and 4-Arylazopyrazoles as a Method for 4-Amino-3-trifluoromethylpyrazoles Synthesis

Modifications of 4‐Amino‐substituted 5‐Phenyl‐3‐(trifluoromethyl)pyrazoles for the Development of New Analgesics

“…Their regioisomeric structure was assigned using the difference in the chemical shifts of the fluorine atoms of the CF 3 group in the 19 F NMR spectra. The 19 F NMR spectrum of compound 5 has a chemical shift of the CF 3 group at δ 100.77 ppm, which corresponds to the 5‐CF 3 ‐isomer, and a similar signal for 3‐CF 3 ‐aminopyrazole 6 is observed at δ 104.48 ppm [30,42] . The 13 C NMR spectra of aminopyrazoles 5 , 6 are characterized by the presence of quartet signals of carbon atoms of the C−CF 3 group at δ 116.32 and 129.14 ppm, respectively.…”

“…The initial compounds 1 a , b , 2 a , b [29] and 1 c [30] were synthesized by referring previously published methods.…”

“…The 19 F NMR spectrum of compound 5 has a chemical shift of the CF 3 group at δ 100.77 ppm, which corresponds to the 5-CF 3isomer, and a similar signal for 3-CF 3 -aminopyrazole 6 is observed at δ 104.48 ppm. [30,42] The 13 C NMR spectra of aminopyrazoles 5, 6 are characterized by the presence of quartet signals of carbon atoms of the CÀ CF 3 group at δ 116.32 and 129.14 ppm, respectively. The change of the alkylation direction with butyl bromide in comparison with methylation can be explained by HSAB theory, [43][44][45] According to XRD data, compound 7 a is 1-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-3-phenylthiourea (Figure 3).…”

“…[27,28] The combination of these two trends has allowed us to develop diversely bioactive trifluoromethyl-containing 4-aminopyrazoles, availability of which is due to the ease of reduction of their 4-nitroso-and 4-aryldiazenyl-substituted precursors. [29,30] N-unsubstituted 4-aminopyrazoles were found to have high anti-radical activity in both in vitro and ex vivo tests, [29] 1methyl-5-phenyl-3-(trifluoromethyl)pyrazole-4-aminium chloride demonstrated significant antitumor activity against HeLa cells with IC 50 0.074 μM and selectivity index > 1351. For 4-amino-3-(trifluoromethyl)pyrazoles with a phenyl fragment in position 5, pronounced analgesic activity in combination with moderate acute toxicity was revealed in in vivo "hot plate" experiments.…”

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

“…reported that the reaction of polyfluoroalkyl‐containing 2‐arylhydrazinylidene 1,3‐dicarbonyl compounds 144 with ethyl (triphenylphosphoranylidene)acetate 427 in boiling toluene chemo‐ and regioselectively leads to 3‐6‐carbonyl‐functionalized 2‐aryl‐5‐(polyfluoroalkyl)‐pyridazin‐3‐ones 428 in 46–77 % yield (Scheme 149). [248] Initial addition of the nucleophilic center of phosphorus ylide 427 A to one of the carbonyl groups of 2‐arylhydrazinylidene 1,3‐dicarbonyl compounds 144 by the Wittig reaction could afford regioisomeric products 5‐(polyfl uoroalkyl)pyridazin‐3‐one 428 or 6‐(polyfluoroacyl)pyridazin3‐one 429 following the pathway a or b. Reaction involves nucleophilic addition of ylide 427 A at a polyfluoroacyl group (path a) to give intermediate 428 A , followed by condensation of an amino group of the arylhydrazone moiety with the ester function of the ylide residue to form pyridazine ring 428 B and aromatization through elimination of triphenylphosphine oxide to afford compound 428 .…”