M. S. Tovbis

Catalytic hydrogenation of persubstituted p-nitrosophenols

Catalytic hydrogenation of dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosobenzene-1,3-dicarboxylates over Pd/C gave the corresponding previously unknown dialkyl 5-amino-2-hydroxy-4,6-dimethylbenzene-1,3-dicarboxylates. The first-order rate constants for the hydrogenation process were found to be linearly related to steric constants of the alkyl groups.

Synthesis of 5-(ethoxymethyl)-4-nitroso-1H-pyrazoles

In recent time, interest in new nitrosopyrazole derivatives has increased. Naphthyl-substituted nitrosopyrazoles have recently been synthesized by condensation of naphthyl-substituted 2-(hydroxyimino)-1,3-diketones with alkylhydrazines [1, 2]. We continued studies in the field of cycloaromatization of derivatives of β-dicarbonyl compounds with the goal of obtaining nitrosopyrazoles containing an ethoxymethyl group. Such derivatives attract interest since transformation of a hydroxy or carboxy group in medicinal agents into ether or ester moiety is known to change the polarity of their molecules and improve their pharmacological activity [3]. To achieve our goal, ethyl ethoxyacetate was reacted with acetone and acetophenone in the presence of sodium ethoxide in anhydrous diethyl ether according to the procedure described in [4]. As a result, we isolated 1-ethoxypentane-2,4-dione (1a) [4] and previously unknown diketone 1b. Nitrosation of diketones 1a and 1b with sodium nitrite in acid medium gave oximes 2a [5] and 2b, and the latter were treated with hydrazine hydrate in aqueous alkali. New nitrosopyrazoles 3a and 3b containing an ethoxymethyl group were isolated as green crystalline substances with sharp melting points.

Preparation of amine derivatives of persubstitued isophtalic acid arylamides and products of their chloroacetylation

p-Aminophenols and their derivatives are objects of practical interest, because they underlie popular pharmaceuticals (Paracetamol, Tylenol, Panadol) that are applied as antipyretics and analgesics [1]. Recently the persubstitued aminophenols containing ester substituents in ortho-positions to hydroxy group [2] were obtained. The derivatives of this kind aminophenols possess antiarrhythmic activity [3]. The introduction of arylamide groups into persubstitued aminophenols instead of ester groups followed by chloracetylating was the main goal of this study, because these transformations may considerably change the properties of the compounds.

Synthesis of salts of new arylamides of 2-hydroxy-5-nitroso-4,6-dimethylisophthalic acid

Completely substituted nitrosophenols containing methoxy-, ethoxy-, propoxy-, butoxycarbonyl substituents in the ortho-position with respect to the hydroxy group are obtained by the reactions of esters of acetonedicarboxylic acid with isonitrosacetylacetone [1–3]. Such nitrosophenols are readily reduced to persubstituted aminophenols [4] that at the modifi cation of the amino group afford the derivatives exhibiting the antiarrhythmic action [5]. The aim of this study was the preparation of persubstituted nitrosophenols of analogous structure containing arylamide groups instead of ester groups that would give an opportunity to synthesize new biologically active substances. The cyclization of arylamides of acetonedicarboxylic acid (I) dissolved in DMSO was carried out by the reaction with isonitrosoacetylacetone (II) in anhydrous ethanol containing potassium hydroxide. Nitrosophenols were isolated as potassium salts III. The initial arylamides of acetonedicarboxylic acid (I) were obtained by heating diethyl acetonedicarboxylate with the corresponding anilines in a sealed ampule for 24 h by the procedure [6]. Compounds IIIа–IIId were obtained by cyclization using the procedure applied in the reaction of isonitrosoacetylacetone with dialkyl acetonedicarboxylate [2]. In 2 ml of anhydrous ethanol was dissolved 0.25 mmol of potassium hydroxide and to the solution was added 0.25 mmol of isonitrosoacetylacetone (II) and 0.5 mmol of arylamide of acetonedicarboxylic acid Iа–Id dissolved in 0.5 ml of DMSO. The mixture was maintained for some time at 18–20°С, therewith the color of the solution changed from orange to green. Potassium phenolate was isolated by adding anhydrous ethyl ether till the solution turned turbid. The brght green crystals of precipitated phenolate III were fi ltered off, recrystallized from ethanol, and dried in a vacuum over Na2SO4. Potassium 2,6-bis(phenylcarbamoyl)-3,5-dimethyl4-nitrosophenolate (IIIа). Reaction duration 6 h. Yield 0.105 g (88%), green crystals. IR spectrum: 1642 cm–1 [ν(С=О)]. UV spectrum, λmax, nm (ε): 603 (73), 393 (16960). 1Н NMR spectrum, δ, ppm: 2.75 s (6H, 2CH3), 7.02 m (2Harom), 7.30 m (4Harom), 7.81 m (4Harom), 11.16 br.s (2H, NH). 13С NMR spectrum, δ, ppm: 17.2, 119.4,

Synthesis of potassium 2,6-di(alkoxycarbonyl)-3-methyl-4-nitroso-5-[pyridin-3(4)-yl]phenolates

Hexasubstituted nitrosophenols with methoxy-, ethoxy-, propoxy-, butoxycarbonyl substituents in the positions 2, 6 were obtained by the reaction of acetonedicarboxylic acid esters with isonitrosoacetylacetone [1–3]. Nitrosophenols are readily reduced into aminophenols [4] that at the modification of the amino group are transformed into compounds exhibiting the antiarrhythmic action [5]. The introduction of a pyridine residue into the molecule may enhance the biologic action and extend the range of useful applications since the substituted pyridines are already for a long time used as drugs [6].

New Synthesis of Diethyl-5-[(N,N-Diethylglycyl)Amino]-2-Hydroxy-4,6-Dimethylisophthalate

A new convenient synthesis of diethyl-5-[(N,N-diethylglycyl)amino]-2-hydroxy-4,6-dimethylisophthalate with anti-arrhythmic properties was developed.

Synthesis of new alkoxymethyl-substituted 4-amino-1H-pyrazoles and their acylation

Pyrazole derivatives exhibit various biological activities and are active components of some medicinals [1–3]. We previously synthesized 3-(ethoxymethyl)-4nitroso-5-phenyl(naphthyl)-1H-pyrazoles [4, 5] assuming that introduction of an alkoxy group into drug molecules should change their polarity and improve pharmacological activity [6]. In this communication we report for the first time the synthesis and acylation of 5-phenyland 5-(2-naphthyl)-4-amino-3-(ethoxymethyl)-1H-pyrazoles.

Preparation of new completely substituted 4-nitrosophenols with a pyridine residue

It is known that the completely substituted nitrosophenol may be easily converted in aminophenols and their derivatives exhibiting important pharmacologic properties [2]. Yet the nitrosophenols containing a pyridine fragment were not prepared up till now [3]. Therefore it seemed important to extend the range of synthesized salts of completely substituted nitrosophenols, to isolate and identify these compounds in a free state.

Acidity of new exhaustively substituted p-nitrosophenols

A number of exhaustively substituted p-nitrosophenols I having ester groups in the ortho positions with respect to the hydroxy group were reported in [1]. Ia, 5.33 ± 0.01; Ib, 5.35 ± 0.04; Ic, 5.35 ± 0.03; Id, 5.38 ± 0.04; Ie, 5.58 ± 0.03; If, 5.42 ± 0.03; Ig, 5.64 ± 0.06. These data show that the acidity constant almost does not depend on the alkyl group in the ester fragments of exhaustively substituted p-nitrosophenols. We can only note some tendency of pKa to increase with increase in the size of the alkyl group.