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Please login or sign up for a free trial to access the full content. Variation 1: Halogenation of 1,3-Disubstituted 1H-Pyrazol-5-ols at Position 4

DOI: 10.1055/sos-SD-012-00002

Stanovnik, B.; Svete, J.Science of Synthesis, (200212174.

Electrophilic halogenation of pyrazoles unsubstituted at 1-position affords unstable 1-halopyrazoles that readily rearrange into C-halogenated products. In 1-substituted pyrazoles the halogen is introduced at the 4-position followed by the 3-position and the 5-position. The 3- and 5-positions are deactivated by quarternization. Chlorine and bromine are the reagents that are most widely used for halogenation, for example, halogenation of 4-unsubstituted pyrazoles with chlorine or bromine gives 4-chloro- 415 (X=Cl) or 4-bromopyrazoles 415 (X=Br), respectively (Scheme 231).[‌247‌,‌749‌‌752‌] Chlorination is usually carried out in carbon tetrachloride, with an equivalent amount of chlorine passed through the solution. For bromination, carbon tetrachloride, chloroform, or acetic acid with or without sodium acetate are used. In addition, N-halosuccinimides,[‌753‌,‌754‌] alkali hypohalites,[‌755‌‌758‌] tert-butyl hypochlorite,[‌538‌,‌759‌] sulfuryl chloride,[‌149‌,‌760‌‌762‌] and phosphorus pentachloride can be used.[‌763‌]

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