Ethyl 1,4-dihydropyridinecarbodithioates and the electronic effects of sulfur-containing ester substituents

Methods have been developed for the synthesis of the ethyl esters of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis(carbodithioic) and 4-ary1-2-methyl-5-oxo-4,5-dihydro-1H-indeno[1,2-b]pyridine-3-carbodithioic acids. From the physicochemical properties (acid dissociation constants and electrochemical oxidation potentials of the 1,4-dihydropyridines with sulfur-containing substituents in the -positions, the electronic effects of these groups in the 1,4-dihydropyridine system have been determined. The inductive and resonance constants of these substituents in aromatic compounds have been found by ¹³C and ¹⁹F NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 491–500, April, 1986.     

Effect of substituents in the dihydropyridine ring on the reactivity of the ester group of 3,5-dialkoxycarbonyl-1,4-dihydropyridines

The reactivity of the ester group of 3,5-dialkoxycarbonyl-1,4-dihydropyridines upon reaction with nucleophilic reagents increases when substituents are absent in the ortho positions relative to the ester group and also in the case of steric disruption of the coplanarity of the -aminovinylcarbonyl system when substituents are introduced at the nitrogen atom in 2,6-dimethyl derivatives. Mono- and dicarboxylic acids were obtained by hydrolysis of such esters. Thus use of esters of propiolic acid esters and arylamines in the Hantzsch synthesis made it possible to obtain 1-aryl-2,6-unsubstituted derivatives of 1,4-dihydropyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1072–1077, August, 1982.     

2-Aryl-3,5-dinitro-1,2-dihydropyridines

The reaction of -nitroacetaldehyde with paraformaldehyde or aromatic aldehydes and ammonium acetate in acetic acid yielded 2-aryl-3,5-dinitro-1,2-dihydropyridines. Aromatic aldehydes, in an ethanol and acetic acid mixture, gave isomeric 3,5-dinitro-1,4-dihydropyridines in addition to 1,2-dihydropyridines. Physicochemical properties and reactivities of the compounds have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 64–70, January, 1993.     

Electrochemical Oxidation of Compounds Containing 1,4-Dihydropyridine and Pyridinium Rings — Analogs of Gene Transfection Agents

A study was carried out on the electrochemical oxidation of 1,4-dihydropyridines, found as substituents in pyridinium salts, which are strong electron acceptors. The potentials for their oxidation in acetonitrile were determined. NMR spectroscopy was used to find the relative acidity of the N–H and C–H protons and the oxidation potentials were determined for the anionic products of the ionization of the N–H bond in dihydropyridine. The only product of the preparative electrolysis, in contrast to chemical oxidation, is the corresponding pyridine, namely, the oxidized dihydropyridine form.     

Analysis of influence of substituents on electrochemical oxidation and reduction potentials of aromatic and heterocyclic compounds,on the basis of the dependence of electronic effects of the substituents in π-systems on the character of the π-molecular orbitals

The influence of substituents on the electrochemical potentials of aromatic and heterocyclic -systems has been analyzed from the standpoint of the relationship between the electronic effects of the substituents and the structure of the -molecular orbitals. The proposed calculational schemes and parametrization can be used for quantitative estimates of the magnitudes of the electrochemical oxidation and reduction potentials of substituted aromatic and heterocyclic compounds.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 31, No. 3, pp. 153–165, May–June, 1995.     

1,4-Dihydrobenzothieno[3,2-b]pyridine-5,5-dioxides

A series of polycyclic 1,4-dihydropyridines has been synthesized, viz., 1,4-dihydrobenzothieno[3,2-b]pyridine-5,5-dioxides with electron-acceptor substituents at position 3. Their alkylation, chemical oxidation, and reactivity in electrochemical oxidation have been studied. The effect of a sulfonyl group in the indene segment on properties (pK, electrochemical oxidation potential) of the dihydrobenzothienopyridine system is considered.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1563–1567, November, 1986.     

Some substitution and heterocyclization reactions based on 1,4-dihydropyridines

Data on the bromination, chlorination, and bromolactonization of 4-aryl-1,4-dihydropyridines are correlated. The reactions of the products of bromination of 4-aryl-1,4-dihydropyridines with various nucleophilic agents (amines and iodide, azide, and thiocyanate ions) and reactions involving the heterocyclization of the products of substitution of the 2,6-methyl groups of 4-aryl-1,4-dihydropyridines, which lead to condensed furo-, difuro-, pyrrolo-, dipyrrolo-, furopyrrolo-, and furothiazolopyridines and thiazolopyridothiadiazines are examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 781–791, June, 1992.     

Synthesis, Cardiovascular Activity, and Electrochemical Oxidation of Nitriles of 5-Ethoxycarbonyl-2-methylthio-1,4-dihydropyridine-3-carboxylic Acid

Nitriles of 4-aryl-5-ethoxycarbonyl-2-methylthio-1,4-dihydropyridine-3-carboxylic acid have been obtained by the methylation of 1,4-dihydropyridine-2-thiolates; of 1,4-dihydropyridine-2(3H)-thiones in the presence of a stoichiometric amount of piperidine, and of a mixture of 1,4,5,6-tetrahydro- and 1,4-dihydropyridine-2-thiolates with methyl iodide. One-pot multicomponent synthesis has also been used in the condensation of ethyl 2-arylmethyleneacetoacetate, 2-cyanothioacetamide, piperidine, and methyl iodide; of ethyl acetoacetate, 3-aryl-2-cyanothioacrylamide, piperidine, and methyl iodide; and of ethyl acetoacetate, an aromatic aldehyde, 2-cyanothioacetamide, piperidine, and methyl iodide. The latter, a five-component method, takes place rapidly and under mild conditions, it is efficient (yields of 75-96%, economy of time, labour, and resources) and green (there is no need to synthesize lachrymators, such as 3-aryl-2-cyanothioacrylamides).The cardiovascular activity and the electrochemical oxidation of the synthesized 2-methylthio-1,4-dihydropyridines have been investigated. A comparative analysis has been carried out of the ability towards electrochemical oxidation as a function of the electronic properties of the substituent at position 4 of the heterocycle.     

N-alkylation of 1,4-dihydropyridine-3,5-dicarboxylic acid esters

Alkylation of the anions of 1,4-dihydropyridines (1,4-DHP) formed by treatment of sodium hydride in aprotic solvents gave 1-alkyl(up to C₆H₁₃)-3,5-bis(ethoxycarbonyl)- and 1-alkyl-3,5-bis(aryloxycarbonyl)-1,4-DHP. The presence of a substituent in the 4 position increases the reactivity of the 1,4-DHP anion in the alkylation reaction. The absorption maximum in the UV spectra of the 1,4-DHP anion is shifted 100 nm bathochromically as compared with the neutral molecule. The longwave absorption maximum in the UV spectra of 1-alkyl-1,4-DHP is shifted hypsochromically as compared with the 1-unsubstituted compounds; this is explained by steric hindrance of the conjugation of the C=O groups with the -electron system of the ring. The introduction of an alkyl group at the nitrogen atom facilitates the electrical oxidation of 1,4-DHP.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1508–1513, November, 1978.     

Bromination of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(2′-difluoromethoxyphenyl)-1,4-dihydropyridine (foridone)

The action of mild brominating agents (pyridinium bromide-perbromide, dioxan dibromide N-bromosuccinimide, and N-bromoacetamide) on 2,6-dimethyl-3,5-dimethoxy-carbonyl-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine (Foridone) has been studied. Depending on reaction conditions, furo-, difuro-, and dibromomethyl-1,4-dihydropyridines are obtained together with certain oxidized forms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 948–952, July, 1989.     

1-aryl- and 1-benzyl-3,5-diethoxycarbonyl-1,4-dihydropyridines

The possibility has been studied of using anilines in the Hantzsch synthesis. It has been shown that, with the exception of those containing strong electron-accepting substituents, they take part in this reaction with the formation of 1-aryl-1,4-dihydropyridines. The reaction largely depends on the nature of the substituents in the aniline and in the benzaldehyde and is promoted by electron-accepting substituents in the aldehyde and electron-donating substituents in the amine. The mechanism of the reaction is discussed. A number of 1-benzyl-1,4-dihydropyridines have been synthesized. The UV, IR, and PMR spectra and the electro-oxidation of the compounds obtained have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 493–501, April, 1980.     

Synthesis of 1,4-dihydropyridine derivatives having an oxy-, alkoxy-, or dimethylaminophenyl substituent in the 4 position,their antioxidant activity,and their binding to phospholipid membranes

The method of Hantzsch was used to synthesize esters and amides of 2,6-dimethyl-4-aryl-1,4-dihydropyridine-3,5-dicarboxylic acid, containing electron donor substituents in the phenyl ring. It was found that in addition to their antioxidant properties, 3,5-diamides and 4-(3,4-dioxyphenyl) derivatives have an affinity for model phospholipid membranes.Latvian Institute of Organic Synthesis, Riga, LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp, 1358–1365, October, 1996. Original article submitted June 20, 1996.     

Preparation of pyridinium ylids, 1,4-dihydropyridines,and indolizines from γ-nitrophenyl- and γ-nitrobenzyl-pyridines

The transformations of N-phenacyl(p-nitrophenacyl, benzyl)-2,5-dimethyl-4-nitrophenyl (nitrobenzyl, benzyl)pyridinium bromides under the influence of potassium carbonate solution were studied. Stable pyridinium ylids were obtained in the case of -phenylpyridines that contain a nitro group in the benzene ring and in the case of -benzylpyridines with an N-nitrosubstituted phenacyl group. The conclusion that electron-acceptor substituents have a stabilizing effect on the stability of the ylids was confirmed. Under these conditions -nitrobenzyl derivatives are converted to substituted 1,4-dihydropyridines. The positions at which deprotonation of the starting quaternary pyridinium salts occurs and the formation of 1,4- and 1,2-dihydropyridines were established by PMR spectroscopy. The corresponding pyridinium salts were converted to a new group of indolizines containing a p-nitrophenyl (p-nitrobenzyl) substituent in the 2 or 7 position by the Chichibabin method. It was established that substituted dihydropyridines are converted to indolizines; ideas that confirm the scheme of the previously proposed mechanism for the formation of indolizines through a step involving ylids are expressed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 384–389, March, 1979.     

Fluorescence of 3,5-diethoxycarbonyl-1,4-dihydropyridine derivatives and their anions

The fluorescence spectra of a group of 3,5-diethoxycarbonyl-1,4-dihydropyridine (1,4-DHP) derivatives were investigated. The introduction of electron-acceptor N-substituents and 2,6-methyl groups decreases Q markedly. The fluorescence spectra of 1,4-DHP anions are shifted bathofluorically, and the Q values are higher than for the corresponding 1,4-DHP. The fluorescence spectra have large Stokesian shifts, which are decreased for 1,4-DHP anions. A good correlation exists between the _max values of the fluorescence bands of 1,4-DHP anions and the Hammett _p ⁺ constants of the 4-R-aryl substituents.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 67–70, January, 1988.     

Reactions of 2(3′-oxoalkyl)-1,3-cyclohexanediones with nitrogenous reagents

Condensed 1,4-dihydropyridines, which do not contain a substituent in position 4 and which are formed in the reaction of 2-(3-oxoalkyl)-1,3-cycohexanediones with ammonium acetate in acetic acid, undergo disproportionation. Pyridine bases are formed as the result of two competing reactions: disproportionation and oxidation of 1,4-dihydropyridines, intermediates in the heterocyclization of oxo-1,3-diketones with participation of the nitrogen atom, by air oxygen.N. G. Chernyshevskii Saratov State University Saratov 410026. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 647–651, May, 1994. Original article submitted April 22, 1994.     

Synthesis of flexible ligands for assembling two metals in close proximity. Magnetic,electrochemical and spectral properties of binuclear copper (II) complexes with different exogenous bridging motifs

Binuclear Cu^II complexes having new flexible heptadentate ligands 2,6-bis{[bis(3,3-N,N-dimethylaminopropyl)amino]methyl}-4-bromophenol [HL¹], 2,6-bis(3,3-N,N-dimethylaminopropyl)amino]methyl}-4-methylphenol [HL²], and 2,6-bis{[bis(3,3-N,N-dimethylaminopropyl)amino]methyl}-4-methoxyphenol [HL³], capable of assembling two copper ions in close proximity have been synthesized. Comparisons of the charge-transfer (CT) features, observed in electronic spectra of these complexes, are correlated with the electronic effect on the aromatic ring of the ligand systems. Cyclic voltammetry has revealed the existence of two reduction couples,

Reaction of 3,3-dichloropentane-2,4-dione with aromatic aldehydes under the conditions of Darzens reaction

3,3-Dichloropentane-2,4-dione reacts with aromatic aldehydes under the conditions of Darzens reaction to give 4-acetoxy-4-aryl-3,3-dichlorobutan-2-ones, the products of insertion into the -C-C bond. The reaction of ethyl dichloroacetylacetate with benzaldehyde yields a derivative of tricyclo[5.1.0.0^3,5]octane, rather than 2,6-bis(1-chlorobenzylidene)cyclohexane-1,4-dione, as the by-product.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1294–1298, July, 1995.     

Electrocatalytic Properties and Voltammetric Determination of Melatonin at a Nanostructured Film Electrode

A multi-wall carbon nanotube (MWNT) film coated glassy carbon electrode (GCE) was fabricated, and the electrochemical behavior of melatonin on the MWNT film coated GCE was investigated. The oxidation peak current of melatonin increases significantly and the oxidation peak position shifts positively at the MWNT film modified GCE compared to that at a bare GCE. This indicates that MWNTs feature highly effective catalysis to the electrochemical oxidation of melatonin. A simple and sensitive electroanalytical method was developed for the determination of melatonin. The oxidation peak current is proportional to the concentration of melatonin from 8×10^–8 to 1×10^–5molL^–1. The detection limit is about 2×10^–8molL^–1 for 3min accumulation. The proposed method was demonstrated to work satisfactorily with commercial capsules.     

Voltamperometry of 1,4-dihydropyridine derivatives

Thirty-nine -substituted 1,4-dihydropyridine derivatives were subjected to electrochemical oxidation on a rotating platinum microelectrode in acetonitrile, and the E_p (E_1/2) values were measured. A satisfactory linear correlation between the E_p and Taft. ^* constants of the substituents in the position was observed. A linear correlation of the E_p values with the ⁰, - and ^– constants also exists.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1525–1529, November. 1975.     

Synthesis and Electrochemical Oxidation of Nitriles of 4-Aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic Acids

Nitriles of 4-aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-6-hydroxy-1,4,5,6-tetrahydropyridine-3-carboxylic acids were obtained by the alkylation of 1,4,5,6-tetrahydropyridine-2-thiolate with iodoacetamide or by a three-component synthesis by condensing 2-arylmethylene-1,3-dicarbonyl compounds with 2-cyanothioacetamide in the presence of piperidine with subsequent reaction with iodoacetamide. Nitriles of 4-aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic acids were obtained by the dehydration of 6-hydroxy-1,4,5,6-tetrahydropyridines or with a one-reactor three-component system from 2-cyano-3-(4-methoxyphenyl)thioacrylamide, 1,3-dicarbonyl compounds, and iodoacetamide. The electrochemical oxidation of the synthesized nitriles was investigated and it was established that derivatives of 1,4,5,6-tetrahydropyridine as a rule are oxidized readily to the corresponding 1,4-dihydropyridines. A comparative analysis has been carried out of the ability of hydrogenated pyridines to be oxidized electrochemically depending on the electron-withdrawing properties of the substituents in the heterocycle.