5- Methyl-4-substituted pyrazol-3-ones, reaction

A new efficient procedure has been proposed for the synthesis of 3-aryl-5-amino-l//-pyrazoles by reaction of a-chloro-/ -arylacrylonitriles with hydrazine hydrate <2004RJ01518>. Reaction of 2-(3,3-dicyano-2-propenylidene)-4,4,5,5-tetra-methyl-l,3-dioxolane 641 with hydrazine afforded 3-(2-hydroxy-l,l,2-trimethylpropoxy)pyrazole 642 (Equation 134) <2003RJ01016>. Treatment of ethyl 3,3-dicyano-2-methoxyacrylate with alkyl, aryl, heterocyclic, and sulfonyl hydrazines led to the synthesis of N-l-substituted 3-acyM-cyano-5-aminopyrazoles, which are versatile intermediates for the synthesis of many biologically active scaffolds <2006TL5797>. 2-Hydrazinothiazol-4(5//)-one reacted with a variety of cinnamonitrile derivatives and activated acrylonitriles to yield annelated pyrazolopyrano[2,3-rf thiazole <1998JCM730>. 

The most common method for the preparation of pyrazoles from other heterocycles is from pyranone-type compounds. Condensation of 2,3-dihydro /7-pyran -ones 787 with various aryl hydrazines in the presence of montmorillonite KSF clay under mild conditions proceeded rapidly to afford enantiomerically pure 5-substituted pyrazoles 788 (Equation 172) <2004TL6033>. Comparable results were obtained when arylhydrazines were reacted with 2-formyl glycals under microwave irradiation <2004TL8587>. Phenylhydrazine and hydrazine were reacted with 3-acetyl-4-hydroxy-6-methyl-2/7-pyran-2-one to afford 4-acetoacetyl-3-methylpyrazolin-5-ones, which were employed in the synthesis of bipyrazoles and pyrazoloisoxazoles <1999JHC1291>. Reaction of 3,3-dialkyl-6-(trifluoromethyl)-2,3-dihy-dro -pyrones with hydrazine hydrate afforded 3-(trifluoromethyl)-5-substituted-pyrazoles <1998RCB1365>. 

The reaction of 5-methyl-4-substituted pyrazol-3-ones 740a d under similar conditions may be explained by an analogous mechanism (Scheme 218). After formation of intermediate 741, which due to C4 substitution of the pyrazol-3-one... 

Similar ring systems were prepared <97JHC1693> by Coppo and Fawzi from the reaction of substituted ethyl 5-[methyl(methylsulfonyl)amino]-l 7/-pyrazole-4-carboxylates 119 with sodium hydride. This gave the 7-substitued 1,7-dihydro-l-methylpyrazolo[3,4-c][l, 2]thiazin-4(37/)-one 2,2-dioxides 120 in fair to good yield (Scheme 30). They also extended this synthesis by treating methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate 121 with sodium hydride in dimethylformamide to yield l-methyl-7-(trifhioromethyl)-l//-pyrido[2,3-c][l,2]thiazin-4(3//)-one 2,2-dioxide 122 in 79% yield (Scheme 31) <98JHC499>. 

The fused pyrrole ring system (204) has been obtained by the reaction of 17/3-hydroxy-17-methylandrosta-l,4-dien-3-one with tosylmethyl isocyanide in the presence of sodium hydride in DMSO,92 and 17/3-hydroxy-17-methyl-7-oxa-5o -androstano-[3,2-c]- (205) or -[2,3-d]-isoxazoles (206 X = O) have been prepared by treating 7-oxa-2-(hydroxymethylene)-17/3 -hydroxy-17-methyl-5 a -androstan-3-one with hydroxylamine hydrochloride.93 In the presence of pyridine, the isox-azole (206 X = O) is formed, but when the reaction is catalysed by sodium acetate in acetic acid the isomeric steroid (205) results. Cycloaddition of hydrazine hydrate to the same 2-hydroxymethylene-7-oxa-steroid results in the [3,2-c]pyrazole (206 X = NH). A similar addition is encountered in the reactions between 3/3-hydroxy-16-(hydroxymethylene)-5a-androstan-17-one and the substituted hydrazines RNHNH2 (R = H, o-COC6H4NH2, or p-COQHUNH ,) when the corresponding [17,16-c]pyrazoles (207) are formed after cyclization of the intermediate hydrazones.94... 

Solid-phase synthesis of substituted pyrazolones 550 from polymer-bound /3-keto esters 549 has been described (Scheme 68) <2001EJ01631>. Trisubstituted pyrazole carboxylic acids were prepared by reaction of polymer-bound arylidene- or alkylidene-/3-oxo esters with phenylhydrazines <1999S1961>. 2-(Pyrazol-l-yl)pyrimi-dine derivatives were prepared by cyclocondensation of ethyl acetoacetate and (6-methyl-4-oxo-3,4-dihydropyrimi-din-2-yl)hydrazine with aromatic aldehydes <2004RJC423>. Reactions of acylated diethyl malonates with hydrazine monohydrochloride in ethanol afforded 3,4-disubstituted-pyrazolin-5-ones <2002T3639>. Reactions of hydrazines with A -acetoacetyl derivatives of (45 )-4-benzyloxazolidin-2-one (Evans oxazolidinone) and (2R)-bornane-10,2-sultam (Oppolzer sultam) in very acidic media gave pyrazoles retaining the 3(5)-chiral moiety <1999S157>. 

Structure 159 has been erroneously assigned to the product of the reaction between 3-benzoyl-3-methyl-47/-isoxazol-5-one 157 and SOCI2 (53GA192). In reality, the compound has the structure of isoxazolone 158 (74HCA1934). The reactions of chloro compound 158 with ammonia, phenylenediamine, and phenylhydrazine produce enamine 160, isoxazolo[5,4-e]1.4-diazepine 161, and isoxazolo[5,4-c]pyrazole 162, respectively (59ZOB3446). The formation of 161 and 162 represents examples of substitution at the keto group in position 5 (Scheme 71). 

A similar preference for cis- or emfo-products is generally observed in the reactions of thermally generated chloro(trichloroethenyl)carbene with a large variety of olefins (see Vol. E 19b, p 740)11. The alkynyl-substituted earbene 4 obtained by photolysis of 5-bromoethynyl-3,3-dimethyl-3//-pyrazole adds exo selectively to 3-cyclohexenone to give an 80 20 mixture of 7-bromo-7-(4-methyl-3-penten-l-ynyl)bicyclo[4.1.0]heptan-3-one (5/6)12. The reaction of chlorophenylcarbene and cyclohexene affords 7-chloro-7-phenylbicyclo[4.1.0]heptane with moderate endo preference (see Vol. E19b, p984), i. 

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