“Reported, but Still Unknown.” A Closer Look into 3,4-Bis- and 3,4,5-Tris(trifluoromethyl)pyrazoles

Abstract

Straightforward practical synthetic approaches to 3,4-bis- and 3,4,5-tris(trifluoromethyl)pyrazoles have been developed. The key step of the both syntheses is a transformation of the carboxylic group in a pyrazole core into the trifluoromethyl group by sulfur tetrafluoride. The elaborated synthetic protocols allow gram-scale preparation of the target products. The obtained compounds are comprehensively characterized by means of crystallographic analysis, determination of pK(a) values and fluorescence measurements.

Efficient one-pot synthesis of 5-perfluoroalkylpyrazoles by cyclization of hydrazone dianions

“…The product was isolated as a brown solid ( 9,139.8,136.5,129.2,129.2(2C),128.6,128.5,128.5,128.3 (q,J = 38.3 Hz),127.2,126.2,126.2,122.8,120.7 (q,J = 269.6 Hz), 120.1 (q, J = 1.8 Hz), 28.9,19.4 (d,J = 1.3 Hz). GC-MS (EI, 70 eV): m/z (%) = 314 (100), 245 (33), 218 (10), 142 (13), 115 (10), 77 (27) …”

“…Trifluoromethylated and perfluoroalkylated pyrazoles represent pharmacologically relevant core structures 8 which are present in many important drugs and agrochemicals, such as Celecoxib (antiarthritic), Mavacoxib (antiarthritic), Razaxaban (anticoagulant), Fluazolate (herbicide), Penthiopyrad (fungicide). 9,10 The development of new methods for the synthesis of pyrazole derivatives has become extremely important in recent years. 1 Conventional methods for the synthesis of pyrazoles are based on the cyclocondensation of hydrazines with 1,3-dielectrophiles, such as 1, 3-dicarbonyl or α,β-unsaturated carbonyl compounds.…”

“…19 F NMR (282 MHz, CDCl 3 ) δ -57.38 (s). 13 C NMR (75 MHz, CDCl 3 ) δ 156 9,. 148.6, 139.4, 132.9 (q, J = 39.0 Hz), 129.8, 129.1, 129.1 (2C), 128.8, 125.8, 125.8, 120.9, 120.6, 120.0 (q, J = 269.0 Hz), 111.3, 110.3 (q, J = 2.5 Hz), 55.5.…”

Synthesis and Antifungal Activity of N-(Substituted pyridinyl)-1-methyl(phenyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide Derivatives

“…Intermediate 2 was prepared by reacting compound 1 with hydrazine hydrate [14]. The intermediates 3 and 7 were synthesized from ethyl 3-(trifluoromethyl)-1 H -pyrazole-4-carboxylate ( 2 ) with different methods.…”

An approach to (4-fluoroalkyl-1-alkyl-1H-pyrazol-3-yl)methylamines

“…For the fluorination of the carboxylic acid 15, obtained by oxidation of 5a with potassium permanganate, sulfur tetrafluoride was used (Scheme 4) [22]. It should be noted that to the best of our knowledge, no examples of fluorination of the carboxylic acids with SF 4 in the presence of phtalimide moiety was reported previously.…”