Indazolinones

The pyrazolinones (11) (pyrazolinethiones and iminopyrazolines) correspond to the replacement of R or R in (22) by 0 , and are normally represented by their neutral structure, but it is important to bear in mind their dipolar formula (26) when discussing their reactivity. Similarly, the indazolinones (12) (27) result from the indazolium salts (23). 

Of four possible tautomeric forms of indazolinone-3 109, evidence for the existence of solely the nonaromatic isomer 109b in the solid state has been obtained (Scheme 42) [76AHC(Sl),p. 352 96CHEC-II(3)1,96JCS(P2) 2263]. 

A recent SAR report [275] indicated that unsubstituted indazolinones inhibited 5-LO (2 //M), but without oral activity or selectivity (with respect to CO). Substitution on the 1-nitrogen had no effect, while substitution on... 

Indazolinone exists as such (227) in the solid state but only as a minor isomer (15%) in DMSO solution, where the 3-hydroxy-17/-indazole tautomer (228) predominates (85%) (86JCS(P2)1677). No evidence for the existence of 3-hydroxy-2 f-indazole (229) has been found. 

Indazolinones by Ugi-4CR with N-deprotection and Aromatic Nucleophilic Substitution... 

An interesting route to indazolinones was reported by Tempest and co-workers [58]. The reaction between 2-fluoro-5-nitrobenzoic acid, aldehydes, isocyanides,... 

For 3-indazolinone (XXIV) it is necessary to estimate the enthalpy of formation of CH3CONHNHCH3. A value of -130 kJ mol 1 is obtained if we assume thermoneutrality for the next reaction (using a value from [49] for the enthalpy of formation of CH3CONHCH3) ... 

We also note a comparison of acyclic and heterocyclic amides with the corresponding imines in which it was asserted that 3-indazolinone has considerably less... 

The 3-amino derivatives have been converted into alky], acyl, and benzylidene derivatives.327 332 Sulfonamides have been prepared,100,328 320 and further reactions (alkylation and acylation328 and condensation with a-naphthoquinones333) performed upon these. The 3-amino compound is converted by hydrazine into tetrahydro-indazolinone (190).334... 

Reaction of aryl azides with hydrazine hydrate can result in reductive cleavage of the azido group. Azidobenzene gives a mixture of benzene and aniline when heated with an excess of hydrazine hydrate in ethanol. If there is an acyl or an alkoxycarbonyl group at the ortho position, cyclization products are formed instead for example, methyl 2-azidobenzoate gave indazolinone (13 90%). 

The structure of indazolinone and some of its derivatives was determined by the combined used of crystallography, C CPMAS NMR, and N NMR <86JCS(P2)1677>. It was concluded that indazolinone exists as such (67a) in the solid state but only as a minor isomer (15%) in DMSO solution, where the 3-hydroxy-l//-indazole tautomer (67b) predominates (85%). The 3-hydroxy-2//-indazole tautomer (67c) has never been observed. The equilibrium between 2-hydroxy-3-methyl-indazole and 1/f-3-methylindazole-2-oxide has been studied in DMSO, methanol, and trifluoro-methanol by C and N NMR spectroscopy <87MRC721>. The position of the equilibrium was found to be dependent on the acidity of the solvent, the hydroxy form being predominant in weakly acidic media. 

Aran has studied the reactivity of 1,1-disubstituted indazol-3-ylio oxides <93JCS(Pl)ill9>, for instance, treatment of these compounds with hydrochloric acid affords the corresponding 3-hyd-roxyindazoles the Wawzonek rearrangement (formation of 1,2-disubstituted indazolinones) was also observed. 

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