Pyrazole 1-phenyl-, ring synthesis

Bielectrophiles have found appreciable applications in the synthesis of ring-fused systems, especially those involving [5,6] fused systems. The following serve to illustrate these applications. Reaction of pyrazole with (chlorocarbonyl)phenyl ketene (214) (Type 1, Scheme 6) readily formed the zwitterionic pyrazolo[l,2-a]pyrazole derivative (215) (80JA3971). With l-methylimidazole-2-thione (216), anhydro-2-hydroxy-8-methyl-4-oxo-3-phenyl-4//-imidazo[2,l-6][l,3]thiazinium hydroxide (217) was obtained (80JOC2474). 

The synthesis of tripyrazolylmethane and similar reactions of N-magnesium bromide derivatives of pyrazoles (see below) show that the reactive center cannot be transferred from nitrogen to the a-position of the ring as with pyrrole.719-722 Unlike the CH-group of triphenyl-methane, that in tri-l-pyrazolylmethane is not labile.719 The 1-pyrazolyl group is presumably a weaker electron acceptor than a phenyl group because the electron pair of the 1-nitrogen atom is not completely withdrawn into the aromatic system. 

Diazonium intermediates have also been employed in the synthesis of pyrazoles. A convenient one-pot procedure for the preparation of 3-phenyl- or 3-pyridylpyrazoles 27 from the 1,3-dipolar cycloadditions of phenylacetylene or 3-(pyridyl)acetylene with diazo compounds 26 generated in situ from aldehydes 25 has been reported <03JOC5381>. Cyclization of ortho-(arylethynyl)benzene diazonium salts 28 having substituents at the para-position of the aryl ring furnished indazoles 29 <03TL5453>. 

The most frequently adopted approach to the synthesis of this ring system involves condensation of appropriately substituted 4,5-diaminopyrazoles 21 with a-dicarbonyl compounds such as benzil, diacetyl, and glyoxal. Such condensations have given pyrazolo[3,4-hjpyrazines unsubstituted in the pyrazole ring. Similarly, 1-methyl compounds,1-phenyl-3-methyl derivatives, and 3-hydroxy compounds, both unsubstituted in the 1-position and substituted by methyl or phenyl groups, ° have been obtained by this approach. 

A remarkable ring closure reaction was elaborated for the synthesis of 3-cyano-l-(phenyl)pyrazoles [5]. 2,6-Dichloro-4-trifluoromethylaniline (7) is diazotized and then coupled with 2,3-dicyanopropionate to obtain phenyl-diazoester 8, which is cyclized and decarboxylated to 5-amino-3-cyano-l-(2,6-dichloro-4-trichloromethy-phenyl)pyrazole (9) [67] (Scheme 29.5.1). 

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