Pyrazoles Vilsmeier-Haack reaction

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

Substituted pyrazoles are formylated (Vilsmeier-Haack reaction) and acetylated (Friedel-Crafts reaction) at C-4 (B-76MI40402). Both hydroxy and amino substituents in positions 3 and 5 facilitate the reaction (80ACH(105) 127,80CHE1), but the heteroatoms compete with the C-substitution. For instance, when the amino derivative (91 R = =Ph, R = H) was submitted to the Vilsmeier-Haack reaction, the 4-formyl-5-dimethylaminomethylene derivative was isolated. 

The Vilsmeier-Haack reaction of the benzazepinone 306 gives the en-aminone 307, which, upon treatment with 4-chlorophenyl hydrazine, gives the pyrazole 308. Pyrazolothiazines and pyrazolo-[4,3-6][l,4]-benzothia zines were similarly prepared (72CPB1325). 

Reactions of Other Derivatives.—Condensation of 2-methyl-benzothiazoles with aromatic aldehydes may be carried out in 50% aqueous sodium hydroxide at room temperature in the presence of triethylbenzylammonium chloride. In some cases the intermediate carbinols are isolable under these conditions. 2-Methylbenzothiazoles undergo the Vilsmeier-Haack reaction to give products [1 R = C( CHOH)CHO] that can be converted into other heterocycles e.g., alkyl- or aryl-hydrazines furnish pyrazoles. ... 

The corresponding 4-halopyrazoles are produced by the action of chlorine or bromine in acetic acid. Nitrating acid yields 4-nitropyrazoles and, dependent on the substituents in the pyrazole ring, reaction takes place either with pyrazole itself or the pyrazolium ion. Sulfonation involves the pyrazolium ion. For this reason, heating in oleum is necessary, which leads to pyrazole-4-sulfonic acid. Pyrazoles with substituents in the 1-position yield pyrazole-4-carbaldehyde in the Vilsmeier-Haack formylation and are amenable to Friedel-Crafts acylation. 4- and 5-aminopyrazoles can be diazotized. 

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