Synthesis of trifluoromethyl derivatives of pyrazolidine- and 2-pyrazoline-1-carboxamides and pyrazolidine- and 1-pyrazoline-carbothioamides

The reactions of enones containing trifluoromethyl groups with semicarbazide in basic media proceed unequivocally to give pyrazolidine-1-carboxamides. The direction of the reactions of these enones with thiosemicarbazide depends on their structure; the reaction products are pyrazolidine- and 2-pyrazoline-1-carbothioamides. An enone containing a CF₃ group and an ethoxy group capable of replacement reacts with semicarbazide to give 2-pyrazoline-1-carboxamide and with thiosemicarbazide to give the double addition product, 5-(1-thiosemicarbazido)-2-pyrazoline-1-carbothiamide.M. V. Lomonosov Moscow State University, 119899 Moscow, Russia, N. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 117907 Moscow, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 634–644, May, 1998.     

Aliphatic aldehydes in synthesis of 4-alkyl-5-carbamoyl-3-cyano-6-methylpyridine-2(1H)-thiones

Condensation of isovaleric or acetic aldehydes with cyanothioacetamide and acetoacetamide leads to formation of 4-isobutyl(methyl)-5-carbamoyl-3-cyano-6-methylpyridine-2(1H)-thiones. By alkylation of 5-carbamoyl-3-cyano-4,6-dimethylpyridine-2(1H)-thione with 4-methoxyphenacyl bromide, 5-carbamoyl-3-cyano-4,6-dimethyl-2-(4-methoxybenzoyl)methylthiopyridine has been obtained.Lugansk T. G. Shevchenko State Pedagogical Institute, Lugansk 348011, Ukraine. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 228–229, February, 1999.     

Heterocycles containing a bridge nitrogen atom. 11. Recyclization of 5-methyloxazolo[3,2-apyridinium cation under the action of nucleophiles containing NH2 group. Crystal structure of 3-(p-nitrophenyl)-1,4-dihydropyrido-[2,1-c]-as-triazinium perchlorate

Reactions of 5-methyl-2-(p-nitrophenyl)oxazolo[3,2-a]pyridinium perchlorate with ammonia and hydrazine, in contrast to the reaction with secondary amines, do not produce indolizines. The reaction with ammonia produces 5-methyl-2-(p-nitrophenyl)imidazo[1,2-a]pyridine; with hydrazine, 3-(p-nitrophenyl)-1,4-dihydropyrido[2,1-c]-as-triazinium semiperchlorate (2 moles of base per one mole of acid). The structure of the latter is solved by X-ray structural studies. Dedicated to Professor Henk van der Plas on his 70th birthday. For No. 9, see [1]. M. V. Lomonosov Moscow State University, Moscow 119899, Russia Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 550–556, April, 1999.     

Reactivities of 5-, 6-, and 7-(enamino)indoles in the synthesis of pyrroloquinolines

The concept of regioorientation is proposed for the annelation of the pyridine ring with the participation of 5-, 6-, and 7-aminoindoles. The conclusions based on the experimental data are supported by quantum-chemical calculations.Mordovian State Pedagogical Institute, Sarinks 430007, Russia. Mordovian State University, Sarinsk 430000, Russia. Moscow State University, Moscow 119899, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1223–1242, September, 1998.     

Reaction of trifluoromethyl-containing enones with thiophenol derivatives

The reaction of trifluoromethyl-containing enones with thiophenol derivatives has been studied. Reactions with 4-methylthiophenol proceed with the formation of either ketosulfides or a pyran derivative. Reactions of trifluoromethyl-containing enones with 2-mercaptobenzaldehyde lead to 3-trifluoroacetyl-substituted 2H-thiochromenes. M. V. Lomonosov Moscow State University, Moscow 119899, Russia N. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow 117907, Russia. Department of Chemistry, University of Durham, South Road, Durham, Great Britain, DH1 3LE. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 618–626, May, 1999.     

Investigation of the stereochemistry of the [3.3]-sigmatropic rearrangement of the sp-isomer of 2-allylthio-5-acetyl-6-methyl-4-(2-nitrophenyl)-3-cyano-1,4-dihydropyridine

The reaction of the syn-periplanar conformer (the sp-isomer) of morpholinium 5-acetyl-6-methyl-4-(2-nitrophenyl)-3-cyano-1,4-dihydropyridine-2-thiolate with allyl bromide proceeds regio- and stereoselectively with the formation of the sp-isomer of the substituted 2-allylthio-1,4-dihydropyridine. The [3.3]-sigmatropic rearrangement of the last leads to the sp-isomer of 3,4-trans-3-allyl-5-acetyl-6-methyl-4-(2-nitrophenyl)-3-cyano-1,2,3,4-tetrahydropyridine-2(1H)-thione.Deceased.A. N. Nesmeyanov Institute of Hetero-organic Compounds, Russian Academy of Sciences (RAN), Moscow 117813. N. D. Zelinskii Institute of Organic Chemistry, RAN, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 643–652, May, 1997.     

Heterocycles containing a bridge nitrogen atom. 10. Unexpected closure of oxazole ring during the reaction of 2-chloro-1-phenacylpyridinium salt with potassium cyanate. Crystal structure of 2-(p-nitrophenyl)oxazolo-[3,2-a]pyridinium bromide and N-(p-nitrophenacyl)pyrid-2-one

Reaction of 2-chloro-N-(p-nitrophenacyl)pyridinium bromide with potassium cyanate in acetonitrile produces 2-(p-nitrophenyl)oxazolopyridinium bromide. Performing the same reaction in methanol N-(p-nitrophenacyl)pyrid-2-one was isolated. The structures of the obtained products were proved by X-ray structural data. For No. 9, see [1]. M. V. Lomonosov Moscow State University, Moscow 119899, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 542–549, April, 1999.     

Saturated nitrogencontaining heterocycles. 19. Catalytic reduction of 10- and 9,10-substitutedsym-octahydroacridinium salts

10-Methyl(phenyl)- and 9,10-diphenylperhydroacridines have been obtained by the catalytic reduction of 10- and 9,10-substituted sym-octahydroacridinium salts. Selective reduction of the furan ring occurred in the case of 9-(2-furyl)-10-phenyl-sym-octahydroacridinium perchlorate. The stereoisomeric composition of the reaction products has been established and a probable scheme for their formation has been proposed.N. G. Chernyshevsky Saratov State University, Saratov 410600, Russia Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1108–1112, August, 2000.     

Lactam and amide acetals. 69. Synthesis and properties of 3-(aminomethylene)-2-indolinone derivatives

Oxindole derivatives reacted with the diethyl acetals of dimethylformamide and dimethylacetamide to give the corresponding derivatives of 3-(aminomethylene)-, (aminoethylidene)-, and (ethoxyethylidene)-2-indolinone. These products were then easily converted to N-aryl- and N-alkylaminomethyleneoxindoles upon treatment with aryl or alkyl amines. The alkylation of N,N-dimethylaminomethylene-2-indolinones by dimethyl sulfate and triethyloxonium tetrafluoroborate, and the reactions of the resulting methyl sulfates and tetrafluoroborates with nucleophilic reagents were studied. The configuration of the 3-(aminomethylene)-2-indolinone derivatives prepared at the enamine C=C double bond was investigated by NMR. The free energies of activation for the cis—trans isomerization were determined in a number of cases.For Communication 68, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1190–1198, September, 1991.     

Michael reaction in synthesis of 6-amino-4-(4-butoxyphenyl)-3,5-dicyanopyridine-2(1H)-thione

The reaction of 4-butoxybenzalcyanoacetic ester with cyanothioacetamide yielded 6-amino-4-(4-butoxyphenyl)-3,5-dicyanopyridine-2(1H)-thione, also synthesized by recyclization of 2,6-diamino-4-(4-butoxyphenyl)-3,5-dicyano-4H-thiopyran and condensation of 4-butyoxybenzaldehyde with a two-fold excess of cyanothioacetamide. Substituted 2-alkylthiopyridines and thieno[2,3-b]pyridines were obtained with the indicated pyridinethione. T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011. Ukraine, N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 213–219, February, 1998.     

Electrochemical interconversion of 1-(p-tolyl)-6-methyl-2,4-diphenylpyrimidinium perchlorate and 1-(p-tolyl)-6-methylene-2,4-diphenylpyrimidine

It is shown that reduction of the 6-methyl-1-(p-tolyl)-2,4-diphenylpyrimidinium cation proceeds in two one-electron stages. In the first stage, an unstable radical is formed, and in the second stage, an unstable anion. As a result of dehydrogenation of the radical, the anhydro base 6-methylene-1-p-tolyl-2,4-diphenyl-6H-pyrimidine is formed. Oxidation of this compound in a single one-electron stage forms an unstable cation radical, the hydrogenation of which leads to the original pyrimidinium cation. Data obtained by cyclic voltametry and electrosynthesis with subsequent identification of the products have shown that, the same as in the reaction with the hydroxide anion, the methyl-substituted pyrimidinium cation acts as a CH-acid.Rostov State University, Rostov-on-Don 344101, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 71–75, January, 1999.     

6-Cyclopropyl- and 6-(1-methylcyclopropyl) 1,4-benzodioxanes: synthesis and nitration. Rearrangement of nitro substituted 6-cyclopropyl-1, 4-benzodioxanes using concentrated sulfuric acid

6-Cyclopropyl- and 6-(1-methylcyclopropyl)-1,4-benzodioxanes have been synthesized as the first cyclopropyl 1,4-benzodioxanes. It was shown that nitration of these compounds occurs with retention of the three carbon ring. In contrast to simple ethers of cyclopropylphenols, nitration leads only to 7-nitro-6-cyclopropyl- and 7-nitro-6-(1-methylcyclopropyl)-1, 4-benzodioxanes,respectively. Nitration of 7-nitro-6-cyclopropyl-1,4-benzodioxane occurs regioselectively to give exclusively the 7 8-dinitro product. The structure of the nitration products was confirmed by their rearrangement to the corresponding nitrosopropionyl-1,4-benzodioxanes.M. V. Lomonosov State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 472–479, April, 1994. Original article submitted February 2, 1994.     

Reactions of hydroxyazolidines with π-donor heterocycles. 2. Reaction of 1-acetyl-5-hydroxypyrazolidines with pyrazol-5-ones on the surface of adsorbents

The reaction of 1-acetyl-2-phenyl-5-hydroxypyrazolidines with pyrazol-5-ones leads to the corresponding 4-(pyrazolidin-5-yl)pyrazolones, which exist mainly in the form of hydroxypyrazoles. The process proceeds on the surface of adsorbents in a nonpolar solvent. The structure and stereochemistry of the bisheterocycles obtained were studied.For Communication 1, see [1].M. V. Lomonosov Moscow State University, Moscow 119899, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1079–1087, August, 1998.     

Synthesis of 3-cyano-3-ethoxycarbonyl-4-methyl-6-phenylpyridine-2(1H)-thione and its alkylation

The condensation of acetaldehyde with cyanothioacetamide and ethyl benzoylacetate in the presence of N-methylmorpholine leads to the formation of 3-cyano-5-ethoxycarbonyl-4-methyl-6-phenylpyridine-2(1H)-thione. Alkylation of the last afforded the corresponding substituted 2-alkythiopyridines.T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011, Ukraine. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences (RAN),Moscow 117913, Russia.Translated from Khimiya Geterotsklicheskh Soedinenii, No. 12, pp. 1645–1646, December, 1999.     

Synthesis and properties of enaminoketohydrazides of the 1,2,3,4-tetrahydroisoquinoline series

It has been established that the reaction of 2,3-dioxopyrrolo[2,1-a]isoquinolines with hydrazine occurs at the lactam carbonyl with fission of the pyrroledione ring and the formation of enaminoketohydrazides, the structure of which was confirmed by x-ray crystallographic and spectral data on these compounds and their derivatives (hydrazones).Institute of Technical Chemistry, Urals Branch, Russian Academy of Sciences, Perm 614000, Russia. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1111–1117, August, 1998.     

On the regiospecificity of vanadium bromoperoxidase.

Vanadium haloperoxidase enzymes catalyze the oxidation of halide ions by hydrogen peroxide, producing an oxidized intermediate, which can halogenate an organic substrate or react with a second equivalent of hydrogen peroxide to produce dioxygen. Haloperoxidases are thought to be involved in the biogenesis of halogenated natural products isolated from marine organisms, including indoles and terpenes, of which many are selectively oxidized or halogenated. Little has been shown concerning the ability of the marine haloperoxidases to catalyze regioselective reactions. Here we report the regiospecific bromoperoxidative oxidation of 1,3-di-tert-butylindole by V-BrPO from the marine algae Ascophyllum nodosum and Corallina officinalis. Both enzymes catalyze the regiospecific oxidation of 1,3-di-tert-butylindole in a reaction requiring both H(2)O(2) and Br(-) as substrates, but which produce the unbrominated 1,3-di-tert-butyl-2-indolinone product exclusively, in near quantitative yield (i.e. one H(2)O(2) consumed per product). By contrast, reactions with the controlled addition of aqueous bromine solution (HOBr = Br(2) = Br(3)(-)) produce three monobromo and one dibromo-2-indolinone products, all of which differ from the V-BrPO-catalyzed product. Further, reactivities of 1,3-di-tert-butyl-2-indolinone with both aqueous bromine and V-BrPO differ significantly and shed light onto the possible nature of the oxidizing intermediate. This is the first example of a regiospecific bromination by a vanadium haloperoxidase and further extends their usefulness as catalysts.     

Synthesis and some properties of 6-(ω-aroylbutylthio)purines

A series of 6-(ω-aroylthio)purines, which have not been described in the literature, has been obtained by the reaction of 6-purinethione with ω-chlorovalerophenone and its substituted derivatives. Some properties of the compounds synthesized have been studied, viz. reaction at the carbonyl group, methylation, and hydrolysis. All-Russian Scientific Center for the Safety of Biologically Active Substances, Staraya Kupavna, Moscow region 142450. Zaporozhe State Medical University, Zaporozhe 330074, Ukraine. Center for Drug Chemistry, All-Russian Pharmaceutical Chemistry Research Institute, Moscow 119815. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1407–1411, October, 1999.     

Stereoselective Synthesis and Alkylation of N-Methylmorpholinium 4,5-trans-4-(2-chlorophenyl)-3-cyano-6-hydroxy-5-(2-thenoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine-2-thiolate. Molecular and Crystal Structure of 4,5-trans-4-(2-chlorophenyl)-3-cyano-6-hydroxy-2-methallylthio-5-(2-thenoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine

The condensation of 2-chlorobenzaldehyde with cyanothioacetamide and 2-thenoyltrifluoroacetone in the presence of N-methylmorpholine takes place stereoselectively and leads to the formation of N-methylmorpholinium 4,5-trans-4-(2-chlorophenyl)-3-cyano-6-hydroxy-5-(2-thenoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine-2-thiolate. The latter was used to synthesize the corresponding 2-alkylthiotetrahydropyridines. The structure of 4,5-trans-4-(2-chlorophenyl)-3-cyano-6-hydroxy-2-methallylthio-5-(2-thenoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine was determined by X-ray crystallographic analysis.     

Radical addition reaction of alcohols to 1-(4-nitrophenyl)-5H-pyrrolin-2-one

Quantum chemical calculations of the parameters of the 1-(4-nitrophenyl)-5H-pyrrolin-2-one molecule have been carried out by the MNDO method. The radical addition reaction of aliphatic, alicyclic, and aromatic alcohols to 1-(4-nitrophenyl)-5H-pyrrolin-2-one with the formation of 3- and 4-substituted pyrrolidones has been investigated.Kuban State Technological University, Krasnodar 350072, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 934–938, July, 1998.     

2,3,7-Trimethyl-5- and 2,3,7-trimethyl-6-aminoindoles in the synthesis of pyrroloquinolines

The possible utilization of 2,3,7-trimethyl-5- and 2,3,7-trimethyl-6-aminoindoles for different approaches to the synthesis of pyrroloquinolines was investigated. It was established that enamines, obtained from 2,3,7-trimethyl-6-aminoindole, undergo ready cyclization to substituted pyrrolo[3,2-g]quinolines, which is a convenient preparative method for their synthesis. It was shown that the peri-effect of the methyl group prevails over the ortho-effect of the methyl substituent at the position 7 with the ring binding of the pyridine nucleus to the benzene ring in the process of the cyclization of the corresponding 5-enaminoindoles.M. E. Evsev'ev Mordovo State Pedagogical Institute, Saransk 430007 Russia. M. V. Lomonosov Moscow State University, Moscow 119899, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 673–680, May, 1998.