A new methodology of annelation of five- and seven-membered heterocycles to quinoxalines

Pyrazolo[3,4-b]-, isoxazolo[4,5-b]-, benzo[2,3]-1,4-diazepino-, and benzo[2,3]-1,4-oxazepinoquinoxalines were prepared by reactions of 2-quinoxalinecarboxaldehyde with 1,2-N,N-, 1,2-N,O and 1,4-N,N- and 1,4-N,O-dinucleophiles.     

Synthesis and reactivity of thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,3-diamines

It has been established that the interaction of N¹-(2-hydroxyphenylmethylthieno[2,3-b]pyrid-3-yl)arylamides with hydrazine hydrate leads to thieno[2,3-b]pyridine-2,3-diamines. It was shown that the reaction of the latter with acetylacetone and acetoacetic ester occurs regioselectively at the amino group in position 3 of the thiophene ring. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1400–1408, September, 2007.     

Facile synthesis of regio-isomeric naphthofurans and benzodifurans

Naphtho[1,2-b]furans 1a-f, naphtho[2,1-b]furans 2a-f, benzo[1,2-b:5,4-b′]difurans 3a-b, benzo[1,2-b:4,5-b′]difurans 4a-b, and benzo[1,2-b:4,3-b′]difurans 5a-b were synthesized by base-catalyzed cyclization reaction of the corresponding o-alkoxybenzoylarene derivatives. The o-alkoxybenzoylarenes were obtained from the etherification reaction of the o-hydroxybenzoylarenes, which were prepared either by the reaction of methoxyarenes with benzoyl chloride in the presence of aluminum chloride or by photo-Fries rearrangement of aryl benzoates.     

Photochromic Dihetarylethylenes. 21. Synthesis and Photochemical Properties of 1,2-Bis{5-(2-benzothiazolyl)-2-ethylthieno-[2,3-<Emphasis Type="Italic">b</Emphasis>]thiophen-3-yl}Hexafluorocyclopentene

1,2-Bis{5-(2-benzothiazolyl)-2-ethylthieno[2,3-b]thiophen-3-yl}hexafluorocyclopentene has been synthesized for the first time. It was shown that, unlike analogous derivatives of thieno[3,2-b]thiophene, on irradiation with UV light (λ = 313 nm) it did not display photochromic properties, but undergoes an irreversible photoconversion which is accompanied by the display of intense fluorescence. This raises the prospect of using this compound for creating an irreversible photoluminescent recording medium.Dedicated to V. I. Minkin on his 70th birthday.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 360–364, March, 2005.For Part 20 see [1].     

4-(3-Cyanopyridin-2-ylthio)acetoacetates in synthesis of heterocycles

Substituted 2-amino-4-aryl-3-cyano-5-oxo-5,6-dihydro-4H-pyrano[2,3-d]pyrido[3",2":4,5]thieno[3,2-b]pyridines were synthesized by the reactions of 4-hydroxy-1H-thieno[2,3-b;4,5-b]dipyridin-2-ones with arylidenemalononitriles or by the three-component reactions of hydroxythienodipyridinones with aldehydes and malononitrile in DMF in the presence of triethylamine. Methods for syntheses of substituted 3-alkoxycarbonyl-6-amino-4-aryl-2-(3-cyanopyridin-2-ylthiomethyl)-4H-pyrans were developed on the basis of the reactions of 4-(3-cyanopyridin-2-ylthio)acetoacetates and arylidenemalononitriles or aldehydes and malononitrile. Ethyl 4-(3-cyanopyridin-2-ylthio)acetoacetate and 4-methoxybenzylidenecyanothioacetamide were used for the synthesis of 6-(pyridin-2-ylthiomethyl)-3-cyanopyridine-2(1H)-thione.     

The use of 3-amino-4,6-dimethylpyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridine in the synthesis of novel heterocycles of pharmaceutical interest

3-Amino-4,6-dimethylpyrazolo[3,4-b]pyridine was used for the preparation of some novel heterocycles of pharmaceutical interest. The starting material reacted with 2-cyano-3,3-bis(methylthio)acrylate, chloroacetyl chloride, phenyl isothiocyanate, carbon disul-fide, and aromatic aldehydes to give the novel heterocycles. The structures of the hitherto unknown ring systems have been confirmed by analytical and spectral methods. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 891–898, June, 2008.     

Mechanism of the reaction of neutral and anionic N-nucleophiles with α-halocarbonyl compounds

N-Acylalkylation of neutral and anionic N-nucleophiles with α-halocarbonyl compounds was investigated by quantum chemical methods in terms of the density functional theory and by experimental methods for 2,3-dihydroimidazo[2,1-b]quinazolin-1(10)H-5-one, its N-anion, and simpler model structures. High reactivity of these reagents is determined primarily by stabilization of transition states (TS) by bridge bonds involving halogen or nitrogen atoms rather than by conjugation, as has been commonly accepted. Bridged TS are formed by both the substitution mechanism S _N 2 and the addition-elimination mechanism. α-Haloalkyl-substituted zwitterions, which are potential intermediates of stepwise N-acylalkylation of neutral N-nucleophiles, do not exist in the isolated state, but they are rather efficiently stabilized upon solvation. These zwitterions, as well as analogous O-anions generated from anionic N-nucleophiles, can serve as intermediates of N-acylalkylation, as was demonstrated by localization of the corresponding TS. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1150–1164, June, 2007.     

Synthesis of 3-alkyl-1,4-dihydrocyclopenta[b]indoles: unexpected formation of dimeric compounds

Acid-catalyzed dehydration of 3-alkyl(aryl)-4-methyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-ols gives dimeric derivatives of 3-alkyl(aryl)-4-methyl-1,4-dihydrocyclopenta[b]indole.     

Efficient synthesis of 2- and 3-substituted-2,3-dihydro [1,4]dioxino[2,3-b]pyridine derivatives

A versatile new approach for the synthesis in three steps of 2-substituted-2,3-dihydro[1,4]dioxino[2,3-b]pyridines B via a Smiles rearrangement using easily available reagents is described. A study illustrating the influence of experimental conditions on the progress of the reaction is reported.     

Cross reactions of cyanoacetic acid derivatives with carbonyl compounds 3. One-step synthesis of substituted 2-amino-5-oxo-4,5-dihydropyrano[3,2-c]chromenes

Three-component reactions of 4-hydroxycoumarin, carbonyl compounds, and malono-nitrile or alkyl cyanoacetates in ethanol in the presence of Et₃N as a catalyst give substituted 2-amino-5-oxo-4,5-dihydropyrano[3,2-c]chromenes. Dedicated to Academician V. I. Minkin on the occasion of his 70th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 968–972, April, 2005.     

2-Amidinylindole-3-carbaldehydes: synthesis of new tetracyclic compounds containing the pyrrolo[1,2-c]1,4-diazepine ring

2-Amidinylindol-3-carbaldehydes bearing an α-alkoxycarbonyl substituent on the cyclic-tertiary amine moiety were prepared. Pyrolysis of these amidines in diethylenglycol-monoethyl ether produced mainly a pyrrolo[1′,2′-1,2]-1,4-diazepino[5,6-b]indol-7,11-dione. A similar result was obtained starting from 2-amidinylbenzofuran-3-carbaldehyde.     

Synthesis of 6′-carbamoylmethylthio-5′-cyano-1′,4′-dihydro-3,4′-bipyridine-3′-carboxylic and 6′-carbamoylmethylthio-5′-cyano-1′,4′-dihydro-4,4′-bipyridine-3′-carboxylic esters and investigation of their stability. 2. Esters of 6′-carbamoylmethyl-thio-5′-cyano-1′,4′-dihydro-4,4′-bipyridine-3-carboxylic acids

The stability of solutions of esters of 6′-carbamoylmethylthio-5′-cyano-2′-methyl-1′,4′-dihydro-4,4′-bipyridine-3′-carboxylic acids was investigated by HPLC. The corresponding esters of 6′-carbamoylmethylthio-5′-cyano-4,4′-bipyridine-3′-carboxylic acids,esters of 8-cyano-5-methyl-3-oxo-7-(4-pyridyl)-2,3-dihydro-7H-thiazolo-[3,2-a]pyridine-6-carboxylic acids, methyl 3-amino-2-carbamoyl-6-methyl-4-(4-pyridyl)-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate, and methyl 3-amino-2-carbamoyl-6-methyl-4-(4-pyridyl)-thieno[2,3-b]pyridine-5-carboxylate were synthesized as standard compounds (typical impurities). Analysis by HPLC was realized under the conditions of reverse-phase chromatography. It was established that solutions of the investigated compounds (with mixtures of acetonitrile with phosphate buffer, having pH values of not less than 3 and not more than 5, as solvents) are stable for one month when the solutions are stored in a place protected against light. It is also necessary to use chromatographic systems in which the aqueous components have pH 3–5 during determination of the purity of the esters of 6′-carbamoylmethylthio-5′-cyano-2′-methyl-1′,4′-dihydro-4, 4′-bipyridine-3′-carboxylic acid by HPLC in order to separate the analyzed sorbates and their typical impurities more completely. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 841–848, June, 2007.     

Interaction of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methyl-thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine with Raney nickel

3-Amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methylthieno[2,3-b]pyridine was synthesized by the reaction of 2(1H)-thioxopyridine-3-carbonitrile with 3-chloromethylisoxazole in the presence of two equivalents of KOH. Boiling of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-meth-ylthieno[2,3-b]pyridine with Raney nickel results in 4-aminothieno[2,3-b;4,5-b′]dipyridine or 5-(4-amino-2-pyridyl)pyridine depending on the reaction conditions. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 669–670, March, 2008.