Keywords: 3,8-substituted 1-methyl-4,5-dihydropyrazolo [5,4-h]quinazolines, 1-(2-pyridyl)-and l-phenyl-4-chloro-5-formyl-3-methyl-6,7-dihydroindazoles.We continue work [1][2][3][4] describing the synthetic uses of l-phenyl-(1) and l-(2-pyridyl)-(2) 4-chloro-5-formyl-3-methyl-6,7-dihydroindazoles in their reaction with a series of amidines and their cyclic analogs (2-aminobenzimidazole and 5-aminotetrazole). In addition to C-carbamidines 2-carbamidino-5-trifluoromethylpyridine and 2-carbamidinopyrazinc, N-carbamidines carbamidinopyrrolidinc, 4-carbamidinomorpholine, and creatine were also used. In all cases, the single reaction products were the 3,8-substituted 1-methyl-4,5-dihydropyrazolo[5,4-h]quinazolincs (3)(4)(5)(6)(7)(8)(9).Reaction of chlorovinylaldehydes 1 and 2 with salts of carbamidinopyrrolidine and morpholine was carried out with prolonged (10-I 5 h) refluxing in absolute ethanol in the presence of two equivalents of KOH or, in the case of creatine hydrate, two hour refluxing in the presence of an equimolar amount of KOH. The reaction with 2-carbamidino-5-trifluoromethylpyridine and 2-carbamidinopyrazine salts also needed prolonged heating. In the first example it was best to use an equimolar amount of alcoholate and in the second KOH.The reaction with the tree bases of cyclic amidine analogs (5-aminotetrazole and 2-aminobenzimidazole)" was also carried out in the presence of an equimolar amount of alcoholate. Moreover, for the reaction of phenylindazole 1 with 5-aminotetrazole, the single reaction product is tetrazolo [l,5-a]pyrazolo [5,4-h] quinazoline10 and with 2-aminobenzimidazole benzimidazolo[l,2-a]pyrazolo[5,4-h]quinazoline 11. Treatment of l-(2-pyridyt)indazole 2 with 2-aminobenzimidazole leads to formation of both compound 12 and 5-aminomethyleneindazole 13. In contrast, the reaction of enol ether 14 (prepared from the chloro derivative 2 and sodium ethylate) with 2-aminobenzimidazole gave only compound 12.IR and ~H NMR spectroscopic data are fully in agreement with the proposed structures. Hence the JH NMR spectra confirm the presence in compound 13 ofa trans orientated aminomethylene group, identified by the doublet signals at 7.67 ppm (J = 13 Hz) for CH and at 11.34 ppm for NH (J = 13 Hz), together with the signal for the NH proton of the imidazole fragment at 11.56 ppm. In the IR spectrum, the NH bond frequency is seen in the range 3200-3050 cm t. In the spectra of compounds 3-12 no NH bonds were observed but for compound 9 the presence of the carboxylic hydroxyl function was established by vcoo. at 2650-2450 cm t and 8cc~orl at 10.5 ppm.

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Derivatives of indazole and other pyrazole-containing condensed systems are attracting attention because of their biological activity and the possibilities of further conversions [1][2][3][4][5][6][7]. Therefore, continuing the work reported in [8][9][10][11][12][13][14], we have obtained a number of derivatives of 1-(2-pyridyl)-4,5,6,7-tetrahydroindazole.The oxidation of 1-(2-pyridyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazole by selenious acid, l:bllowing the procedure used in [9], gives the ~-diketone lb. In the IR spectrum of the 4,5-dioxo derivative lb, intense absorption bands of carbonyl groups are observed at 1725 and 1676 cm -1, and in the PMR spectrum a signal of protons of the C(7)-methylene group at 3.73 ppm. Oxidation of the diketone Ib with hydrogen peroxide in a mixture of formic acid and acetic anhydride, in accordance with [9, 15], gives the dicarboxylic acid II. Boiling of the acid II with acetic anhydride leads to the formation of an anhydride -the oxepinopyrazole III, the structure of which is confirmed specifically by the presence of characteristic IR absorption bands of anhydrides at 1777 and 1730 cm -1, and also the corresponding signals of protons in the PMR spectrum (corresponding in number and character).In reactions of the 4,5-dioxo derivative Ib with hydrazides of nicotinic, isonicotinic, salicylic, and 3-bromobenzoic acids, the corresponding 4-oxo-5-acylhydrazonoindazoles IVa-d are obtained; their PMR spectra exhibit downfield signals of NH protons involved in an H-chelate ring (6NH 14.33-14.61 ppm).We also obtained the tosylhydrazone IVe, which, when subjected to the action of alkali, is converted to the 4-oxo-5-diazo derivative Ic. Bromination of the indazole Ia by N-bromosuccininlide (NBS) affords the 7-bromo derivative Va, even with excess of the brominating agent; but bromination of Ia by pyridinium bromide-perbromide (PBP), depending on the mole ratio of reagents, gives the 4-oxo-5-bromo derivative (Id) and the 4-oxo-5,5-dibromo derivative (Ie), respectively. This is consistent with the relationships in the bromination of 4-oxo-4,5,6,7-tetrahydroindazoles that were noted in [9, 11]. The 5,7-dibromo derivative Vb was obtained by the action of PBP on the 7-bromoindazole Va. The 4,5-dioxo-7-bromoindazole Vc was obtained from the 4,5-dioxoindazole Ib by the action of either N-bromosuccinimide or pyridinium bromide-perbromide, which is observed for the first time in the 6,6-dimethyl-4,5,6,7-tetrahydroindazole series.As a result of the introduction of a bulky substituent -bromine -into position 5 or 7, the C(6)-methyl groups become magnetically nonequivalent and are observed in the PMR spectrum, in contrast to 5,7-unsubstituted 6,6-dimethyl~,5,6,7-tetrahydroindazoles and their 5-oxo (Ib), 5-diazo (Id), and 5-hydrazono (IV) derivatives, in the form of two signals. The signal of the remaining C(7 ) proton in compounds Va-c undergoes a considerable downfield shift to 6.36 ppm (Va), 6.53 ppm (Vb), and 6.58 ppm (Vc).

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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.

Continuing our study of the synthesis of 3-acyl-l,5-diazepines through reaction of 2-acyicyclane-l,3diones with 1,2-diamines [I, 2] we have examined the reaction of 2-formyl-5,5-dimethylcyclohexane-l,3-diones (I) with 4-methyl-(lib), 4-benzoyi-(IIc), and 1,2-diamino-4-nitrobenzenes (IId). As shown in [2], the formylcyclanedione I and o-phenylenediamine (IIa) react in a molar ratio of 1 : 1 to give enamine IIIa. The presence of two non-equivalent amino groups in the starting diamines IIb-d makes the possible formation of two isomers in these reactions.Under experimental conditions for similar reactions (mixing of hot ethanolic solutions of the starting materials and subsequent recrystallization of the obtained product) only in the reaction of diamine lid is a single isomer formed and this is 2-(2-amino-5-nitrophenylaminomethylene)-5,5-dimethylcyclohexane-l,3-dione (IIId). In the case of diamines lib,c, a mixture is formed consisting of the main product which is enamine IIIb or IIIc and also the product of reaction at the second amino group, i.e., 2-(2-amino-5-methylphenylaminomethylene)-5,5dimethylcyclohexane-l,3-dione and 2-(2-amino-4-benzoylphenylaminomethylene)-5,5-dimethyicyclohexane-l,3dione respectively. The pure isomers IIIb,c could be prepared by treating formylcyclanedione I with diamines IIb,c at -20~ and precipitation of the products by aqueous potassium chloride solution.The structure of the obtained products was established through the analysis of spectral data. As has been shown in [1], in compounds of type III the most informative aspect of their PMR spectra is the chemical shift of the signal assigned to the aromatic proton situated in a meta position relative to the substituent (R or RZ). The shift of this signal depends on the way the amino groups in diamine II takes part in reaction with compound I. If the reacted amino group is situated meta to the substituent (R or R 1) the signal for this proton is shifted to high field relative to the signals of the other aromatic protons and is found in the region 6.84-6.86 ppm. In the opposite case, the signal is shifted to lower field (7.27 ppm) and does not differ significantly from those of the other aromatic protons. The observed shifts for the signals of compounds IIIc,d (6.79 and 6.80 ppm) unambiguously show that the