Indazoles 2-hydroxy- from

In continuation of our efforts in the development of new synthetic methods for the synthesis of various heterocyclic compounds, we have developed a green and eco-friendly protocol for the synthesis of indazole derivatives from 0-hydroxy aromatic... 

Thermal cyclization was also the route employed to prepare 9-hydroxy-7-methyl-l/f-pyrazolo[3,4-/]quinoline (74) from the 6-aminoindazole/ethyl acetoacetate condensation adduct shown in Equation (41) <92JMC4595>. The hydroxyl substituent of compound (74) was then converted (POCl3, DMF) to a chloro, which in turn was displaced by treatment with aryl amines to give tricyclics with potent in vivo immunostimulatory activity like that noted for regioisomeric l//-imidazo[4,5-/]quinolines but unlike the inactive pyrazolo[4,3-/]quinolines. Although it was noted with some interest that none of the linear tricyclic isomer had been isolated, this finding actually parallels that reported earlier for the similar condensation of 1- and (V(6)-alkyl and unsubstituted 6-amino-indazoles with diethyl ethoxymethylenemalonate <83JHC1351>. 

The log P of 3-hydroxy-4-amino-5-trifluoromethylpyrazole has been determined <89JMC2il6>. The log P values of l-(l-adamantyl)pyrazole, 3.05 ( ), l-(l-adamantyl)indazole, 4.33 (59), and 2-(l-adamantyl)indazole, 3.68 (60) were determined by HPLC. From these values, the n value of the... 

Treatment of pyrazole derivatives with epihalohydrins yields the corresponding 2-hydroxy derivatives (326) (Equation (47)) <71JHC489,90UKZ1096>. This method can also be used for synthesis of the corresponding benzo derivatives from indazoles <71JHC489>. 

Hydrogen transfer from hydrazobenzene to benzofuroxan (622) results in azobenzene and o-benzoquinone dioxime (623). Compound (622) reacts with formaldehyde to yield the benzimidazolinone (624). Chlorobenzofuroxan aldehyde condenses with derivatives of hydroxylamine or hydrazine to yield oximes or hydrazones (625 R = OH, OMe, NHPh, NMe2, etc.), which rearrange thermally to indazoles (626). Treatment of 7-methoxy-4-nitro-benzofurazan 1-oxide with aqueous potassium hydroxide affords a mixture of the corresponding 7-hydroxy-compound (627) and the rearranged 5-hydroxy-4-nitrobenzofuroxan (628). ... 

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