Chemical properties of derivatives of N-difluoromethyl-and N-2-H-tetrafluoroethylpyrazoles

Abstract

Nitration, chlorination, bromination, and iodination reactions have been investigated for pyrazole derivatives containing a difluoromethylene fragment directly on a nitrogen atom. Conditions have been found for introducing a cyano group into the nucleus of N-2-H-tetrafluoroethylpyrazole and converting it into carboxyl or tetrazole functions.Pyrazole derivatives enter into the composition of many compounds possessing high biological activity. Several of them, containing fluorinated groupings, are used as medicinal preparations [1] and pesticides [2].Compounds containing a difluoromethylene fragment linked directly with the nitrogen atom have been little studied up to the present. Trialkylamines containing the α-difluoromethylene fragment are hydrolytically unstable [3-5] as a result of the electron-donating influence of the unshared electron pair of nitrogen. However in the case of nitrogen heterocycles such compounds are significantly more stable, since the nitrogen electron pair is involved in the π−conjugation of the heterocyclic ring. Difluoromethyl and 2H-tetrafluoroethyl derivatives of pyrrole [5], imidazole, benzimidazole [6-8], triazole, 3,5-dimethyl-, and 3-carbethoxypyrazole [9, 10] have been synthesized previously.Recently we investigated [11] the chemical properties of N-2-H-tetrafluoroethyl derivatives of pyrrole and imidazole, and found conditions for nitrating, halogenating, and acylating such compounds. As a continuation of investigations in this area we have studied the chemical properties of N-difluoromethyl and N-2H-tetrafluoroethylpyrazoles 1a-d. N N R R (CF 2 ) n H 1a-d a R = H, b R = Me, с R = H, d R = Me; a, b n = 1, c, d n = 2Difluoromethylation of pyrazole, and of 3,5-dimethylpyrazole was carried out in aqueous dioxane medium by the action of chlorodifluoromethane and alkali. N-Difluoromethylpyrazole 1a proved to be an extremely volatile compound. It forms an azeotropically boiling mixture with water and diethyl ether. It is __________________________________________________________________________________________

Advances in the Synthesis and Application of Tetrafluoroethylene‐ and 1,1,2,2‐Tetrafluoroethyl‐Containing Compounds

“…Nitrogen heterocycles react with TFE in the sense of nucleophilic addition (Table ) , , . The corresponding products 16 are more stable to hydrolysis because of conjugation of the nitrogen electron pair with the heterocyclic ring …”

“…[51,52,[55][56][57] The corresponding products 16 are more stable to hydrolysis because of conjugation of the nitrogen electron pair with the heterocyclic ring. [56] Addition of nitrosyl bromide and nitrosyl chloride to TFE provides 1-bromotetrafluoro-2-nitroethane (17a) or 1-chlorotetrafluoro-2-nitroethane (17b), respectively, because the addition reaction is followed by oxidation of the nitrosyl group. [58] Compound 17b was also obtained by addition of nitryl chloride (Scheme 15).…”

Fluorinated Five‐Membered Nitrogen‐Containing Heterocycles

“…175 Recently, Yagupolskii and coworkers have undertaken an extensive investigation of nitrogen-containing heterocycles possessing perfluorinated alkyl groups directly attached to nitrogen. [176][177][178][179] Potassium salts of a set of heterocycles with different basicities, including imidazole, 2-methylebenzimidazle, 3,5-dimethylpyrazole, 1,2,4-triazole, and benzotriazole, were chosen for reactions with tetrafluoroethylene, chlorotrifluoroethylene, and 1,2-dichlorodifluoroethylene ( Fig. 3.102).…”

“…A related study of nitration and halogenation reactions of N-difluoromethyl-and N-2-H-tetrafluoroethylpyrazoles further extended the inventory of products. 177 The above are examples of research involving reaction of nitrogen-containing heterocyclic compounds with polyfluorinated hydrocarbons to produce N-perfluoroalkyl products. References to related work are found in the original papers.…”

Polyfluoroalkylation and alkenylation of 1-benzyl-1H-indazol-3-ol

“…In the spectrum of compound 2, the signal of the difluoromethyl group has a F-H coupling constant characteristic to difluoromethyl ethers [17], However in the spectrum of its isomer 3, it was characteristic to N-difluoromethyl derivatives [18]. In addition, one of the aromatic protons of the synthesized compounds was displayed as a doublet signal at more lower field (7.60-7.81 ppm) than the remaining (if the signals of the pyridyl fragment of compound 9c are discounted).…”