Synthesis and reactions of 1-(4-chloro-, 3-chloro-, 2-chloro-, 2,4-dichloro-, and 2,4-difluorophenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles

Abstract

Keywords: 2.6-diaryl-4,4-dimethyl-4,5-dihydro-1H(3H)-indazolo [4,5-g]imidazoles. 4.5-dioxo-and 4-oxo-I -halophenyl-6.6-dimethyl-4,5.6.7-tetrahydroindazoles.Bearing in mind the importance of modifying a number of indazoles with the objective of preparing biologically active compounds 11-10], in continuation of work [111 we synthesized a series of I-halophenyl-4-oxo-4.5,6,7-tetrahydroindazoles and prepared some of their derivatives.We obtained the corresponding 2-hydrazinomethylene derivatives of dimedone (3) from the reaction of the potassium salt of 2-fomlyldimedone (1) with the hydrochlorides of 4-chloro-, 3-chloro-. 2-chloro-, 2,4-dichloro-, and 2.4-difluorophenylhydrazines (2). These compounds were converted into l-substituted 4-oxo-6,6-dimethyl-4.5.6.7-tetrahydroindazoles (4) on boiling in ethanol in the presence of hydrochloric acid. Oxidation of these ketones with selenious acid by a method 111, 12] gave the corresponding 4,5-dioxo-4.5,6,7-tetrahydroindazoles only with compounds 4a and 4b. Oxidation of the indazoles 4c-e by this method gave resinous products from which it was not possible to isolate pure products. Therefore we boiled the compounds in dioxane with selenious acid to oxidize the indazoles 4c-e. Resinous materials were fomled again but the individual products, separated by thin-layer chromatography, were shown to be the hydrated forms of the 4,5-dioxo derivatives by IR spectroscopy (two carbonyl frequencies in the 1730-1670 cm' region, absorptions at 3400-3100 cm '). Heating these for a short time at 160-170~ gave the individual cL-diketones 5c-e. Reaction of the 4,5-dioxo compounds 5a,c,e with equimolar anaounts of hydroxylamine, isonicotinic and salicylic acid hydrazides gave the corresponding carbonyl derivatives at the more electrophilic C,,,-carbonyl [11]. Reaction of the same c~-diketones 5a,c,e with o-phenylenediamine gave pyrazolo [4,3-alphenazines 7a,c,d. Reaction of the diketone 5a with 2.3-diaminopyridine gave a single reaction product which we ascribe the structure 3-(4-chlorophenyl)-5.5-dimethyl-4.5-dihydro-3H- lOazapyrazolo[4,phenazine (7b), since the amino group at C,,, in 2.3-diaminopyridine is the better nucleophile.

Reactions of 1-aryl- and 2,3-diaryl- 5-diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetra- hydroindazoles with N-ethyl- and N-phenyl-substituted maleimides

“…Among them have been discovered agonists and antagonists of estrogen receptors [9, 10], dopamine D-3 [11,12], corticotropin [13], and adenosine [14]; derivatives have been found with antitumor [15], antiinflammatory [16], and antimicrobial [17] action; inhibitors of HIV proteases [18] and membrane-active substances [19] have been discovered. Indazole derivatives have also been used as ligands [20].Previously, based on 4,5-dioxo-, 4-chloro-5-formyl-, and 5-diazo-4-oxo derivatives of 4,5,6,7-tetrahydroindazoles obtained by us, we synthesized a series of derivatives of them annelated with heterocycles [21][22][23][24].The interaction of 1-aryl-and 2,3-diaryl-5-diazo-4-oxo-4,5,6,7-tetrahydroindazoles of types 1 and 2 with maleic anhydride and acetylenedicarboxylic acid ester has been carried out. This led to the formation of the corresponding 3-spiropyrazoline and pyrazole derivatives of 4,5,6,7-tetrahydroindazole [25].…”

“…Previously, based on 4,5-dioxo-, 4-chloro-5-formyl-, and 5-diazo-4-oxo derivatives of 4,5,6,7-tetrahydroindazoles obtained by us, we synthesized a series of derivatives of them annelated with heterocycles [21][22][23][24].…”