Perfluoroalkyl pyrazoles

Several 3-(perfluoroalkyl)pyrazoles can be brominated at position 4 under mild conditions, however, 5-(perfluoroalkyl)pyrazoles are unreactive [37] (equation 19). 

A solution of perfluoroalkyl iodide (0.4 mmol), a-chlorostyrene (1.2 mmol) and Bu3SnSnBu3 (0.44 mmol) in benzene (3 ml) was irradiated using a metal halide lamp (National Sky-beam MT-70) in Pyrex tube under 02 atmosphere for 5 h. After removal of the solvent, ethanol and hydrazine acetate were added. The resultant solution was stirred under refluxing conditions for 2 h. After removal of the solvent, the residue was chromatographed on silica gel using a mixture of hexane and dichloromethane as an eluent, to give perfluoroalkylated pyrazole in 59% yield [117]. 

Bouillon JP, Didier B, Dondy B, Doussot P, Plantier-Royon R, PorteUa C (2001) Efficient synthesis of 4-fluoro-5-(perfluoroalkyl)pyrazoles from organofluorosilicon building blocks. EurJOigChem 187-192... 

One-pot synthesis of pyrazole (112) bearing a perfluoroalkyl group is performed by the treatment of a-chlorostyrene (111), perfluoroalkyl iodide, and Bu3SnSnBu3, followed by reaction with hydrazine (eq. 4.38d). 

Based on the assumptions about the reaction mechanism, one can predict that this technique will be applicable to other binucleophiles for the synthesis of perfluoroalkylated heterocyclic compounds. For example, the reaction of arylhydrazine with perfluoro-2-methylpent-2-ene in the presence of triethylamine led to N-arylperfluoro-3-ethyl-4-methylpyrazole 58 and N-arylperfluoro-4-methyl-5-ethylpyrazole 59 in different ratios depending on the reaction conditions (89RP1456419, 87RP1456418, 90IZY2583 89JAP(K)01 22855 99JFC(98)29). Syn- and /-aminoimines are intermediates in syntheses of pyrazoles they were isolated individually. On heating in the presence of triethylamine they are transformed into mixtures of 58 and 59. 

Examples of the photoisomerization of pyrazoles to imidazoles have been reported by Nishiwaki et al. In the photoisomerization of perfluoroalkyl-pyridazines to the corresponding pyrazines, Chambers et al. have shown that an intermediate diaza Dewar-benzene is involved rather than a diazaprismane. Ogata and Takagi have observed a novel photoisomerization of 2-pyridylaceto-nitrile to u-aminobenzonitrile, possibly via a Dewar-intermediate. 

Introduction of a pyrazole ring is a popular choice for molecular modification in designing medicinal and agrochemical agents, and the use of fluorinated pyrazoles in particular has received much recent attention. The development of celecoxib provides a notable example. Many procedures have been developed for the preparation of fluorinated pyrazoles, but a majority of early work was concentrated on perfluoroalkyl groups substituted on the ring. However, in the past several years, new routes to 3-, 4-, and 5-fluoropyrazoles have been reported. 

Ttifluowmethylr and Perfluoroalkyl-Substituted Pyrazoles Trifluoromethyl-substituted pyrazoles are readily available through reactions of hydrazines with a,[3-unsaturated trifluoromethyl ketones and trifluoromethylated [3-dicarbonyl compounds. In addition, 1,3-dipoIar addition reactions can be applied. Such transformations have been... 

From these examples, the versatility of 1,3-cycloaddition reactions in the synthesis of 1,2,3-triazoles is apparent. Other strategies, however, are available. Greif and coworkers developed perfluoroalkyl-substituted p-chlorovinylaldehydes as new building blocks for a number of fluorinated heterocyclic systems such as thiazoles, pyridines, pyrazoles, and benzimidazoles. Reaction of the chlorovinylaldehydes with sodium azide leads to the formation of moderate to good yields of 4-perfluor-... 

A single report documents the study of perfluoroalkyl poly(pyrazolyl)borate cobalt complexes however, their breadth and significance is appreciable. The compounds H B(pz)4 CpCo(Rf) (x = 0, 1,2) were prepared by the interaction of the respective K[H B(pz)4 J salt with CpCo(Rf)(CO)I, and in each case exhibit bidentate coordination of the poly(pyrazolyl)borate ligand, regardless of the number of pyrazole donors potentially available. 

The Pechmann pyrazole synthesis has also found similar utility for the preparation of perfluoroalkylated heterocyclic phosphonates, as demonstrated by the Shen group. Reaction of EDAC (30) with trifluoromethyl alkynylphosphonate 32 resulted in the formation of regioisomers 33 and 34 in high yield. The two regioisomers, isolated in a ratio of 85 15 (33 34) could be separated by column chromatography. 

Ikeda I, Kogame Y, Okahara M (1985) Synthesis of novel pyrazoles containing perfluoroalkyl groups by reactions of perfluoro-2-methylpent-2-ene and hydrazones. J Org Chem 50 3640-3642... 

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