Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 11. Reactions of quinoxalinium salts with thioamides — Simple method for the synthesis of hydrogenated thiazolo[4,5-b]quinoxalines

Thioacetamides and thiobenzamides undergo cyclization with N-alkylquinoxalinium salts in the presence of bases to give 4-alkyl-3a,4,9,9a-tetrahydrothiazolo[4,5-b]quinoxalines.See [1] for communication 10.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 686–690, May, 1984.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 14. Reaction of quinoxalinium salts with mono- and N,N′-disubstituted amidines

Monosubstituted benzamidines undergo cyclization with quinoxalinum salts to give 1,2-disubstituted 3a,4,9,9a-tetrahydroimidazo[4,5-b]quinoxalines. The participation in similar cyclizations of N,N-disubstituted amidines with a CH-active group in the a position leads to 3a,4,9,9a-tetrahydropyrrolo[2,3-b]quinoxalines.See [1] for Communication 13.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 390–395, March, 1985.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 10. Isomeric thiazolo[4,5-b]quinoxalines in reactions of N-methylquinoxalinium ions with dithiocarbamates

The cyclization of N-methylquinoxalinium iodide with ammonium salts of N-alkyl-dithiocarbamic acids in DMSO leads to 4-methyl-2,3,3a,4,9,9a-hexahydrothiazolo-[4,5-b]quinoxalines, whereas regioisomeric cycloadducts with a reversed orientation of the thiazole ring are formed in ethanol in the presence of diethylamine.See [1] for communication 9.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 680–685, May, 1984.     

Cyclizations of N-alkylazinium cations with bifunctional nucleophiles. 19. Crystal structure of the kinetic product of the reaction of N-methylquinoxalinium iodide with thioacetamide

The mutual orientation of the heterorings and the three-dimensional structure of the kinetic product of the reaction of N-methylquinoxalinium iodide with thioacetamide were established by x-ray diffraction analysis of 2,4-dimethyl-9-acetyl-3a,4,9,9a-tetrahydrothiazolo [4,5-b]quinoxaline.See [1] for communication 18.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1417–1421, October, 1985.     

Structure and properties of 1- and 3-hydroxytriazolo [4,5-b] pyridines

It is shown that 1-hydroxytriazolo[4,5-b]pyridine exists in alcohol solution primarily in the N-oxide form, whereas 3-hydroxytriazolo[4,5-b]pyridine exists in the hydroxy form. 4-Methyl-triazolo[4,5-b]pyridine 1-oxide is formed in the methylation of 1-hydroxytriazolo[4,5-b]pyridine, whereas 3-methoxytriazolo[4,5-b]pyridine is formed in the methylation of 3-hydroxytriazolo[4,-5-b]pyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1418–1421, October, 1976.     

An efficient synthesis of novel benzo[b]pyrido[3',2':4,5] thieno[2,3-e][1,6]naphthy-ridine-8-ones

An efficient method for the synthesis of novel benzo[b]pyrido[3',2':4,5] thieno[2,3-e][1,6] naphthyridine-8-one derivatives has been developed using a Pictet-Spengler reaction between 4-(3-aminothieno[2,3-b]pyridin-2-yl)quinoline-2-ones, which could be obtained from the alkylation of 4-bromomethylquinoline-2-ones with 3-cyanopyridine-2-thione followed by a Thorpe-Ziegler isomerization, and aromatic aldehydes under p-TsOH as catalysis in good yields.     

An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction

An efficient method for the synthesis of novel pyrido[3',2':4',5']thieno[3',2':2,3]pyrido [4,5:d][1,3]thiazolo[3,2-a]pyrimidine-4-one derivatives (5) has been developed using a Pictet-Spengler reaction between 2-(3-aminothieno[2,3-b]pyridin-2-yl)thiazolo[3,2-a] pyrimidin-5-one (3), which could be obtained from the condensation of 7-(chloromethyl)-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with 3-cyanopyridine-2-thione (2) via Thorpe-Ziegler isomerization, and aromatic aldehydes under NH₂SO₃H as catalysis in good yields.     

Quantitation of mutagenic/carcinogenic heterocyclic aromatic amines in food products.

A method for screening genotoxic heterocyclic aromatic amines in cooked foods using solid-phase extraction and high-performance liquid chromatography with ultraviolet and fluorescence detection is described. Solid-phase extraction includes basic extraction on diatomaceous earth (Extrelut) and subsequent purification on propylsulphonic acid silica gel. This convenient procedure separates the analytes into a polar group and an apolar group. We have identified the following components in the two groups. The polar group contains aminoimidazoazaarenes i.e. 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, and glutamic acid pyrolysates, i.e. 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole and 2-aminodipyrido[1,2-a:3',2'-d]-imidazole. The apolar group consists of five carbolines: 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, 2-amino-9H-pyrido[2,3-b]indole, 9H-pyrido[3,4-b]indole and 1-methyl-9H-pyrido[3,4-b]indole. The extraction efficiencies range from 45 to 90%, and the detection limits are in the low nanogram per gram range. The method was applied to the analysis of heterocyclic aromatic amines in pan-fried, oven-cooked and barbecued salmon.     

Acetylation of pyridazino[4, 5-b]indoles and their dihydro and tetrahydro derivatives. III

Acetylation of pyridazino[4,5-b]indol-4-ones with acetic anhydride gives the O-acetyl derivatives, and acetylation of 1,2-dihydropyridazino[4,5-b]indol-4-ones leads to the 2-acetyl and 2,4-diacetyl derivatives. Tetrahydropyridazino[4,5-b]indoles, obtained by reduction of the dihydro derivatives, undergo substitution by an acetyl group at the 2 position.See [1] for communication II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1218–1222, September, 1976.     

Chemistry of Thienopyridines. XXIV. Two Transformations of Thieno[ 2,3-b] pyridine 7-Oxide

Refluxing thieno[2,3-b ]pyridine 7-oxide ( 1 ) with aeetic anhydride plus subsequent hydrolysis produced a mixture of thieno[2,3-b]pyrid-6(7H)one ( 2 ) (13%) and 5-hydroxythieno[2,3-b]-pyridine ( 4 ) (4%). Refluxing 1 with phosphorus oxychloride yielded a mixture of 4- and 6-chloro-thieno[2,3-b]pyridines, ( 5 ) (54%) and ( 6 ) (31%), respectively. Compound 6 was also obtained directly from 2 (31%). A mechanistic rationalization for the isomerization of 1 to form 2 and 4 is presented. Marked differences in the mass spectral fragmentations of these three isomeric compounds are noted.     

Cyclization of N-alkylammonium cations with bifunctional nucleophiles. 17. Annelation of imidazole and 1,2,4-triazine rings with pyrazines via the reactions of thiosemicarbazides with pyrazinium salts

1- and 4-mono- as well as 1,4-disubstituted thiosemicarbazies undergo cyclization reactions upon treatment with N-alkylpyrazinium and quinoxalinium salts to give N-aminosubstituted imidazo[4,5-b]pyrazines and imidazo[4,5-b]quinoxalines, respectively. Thiosemicarbazides containing substituents in the 2-position react with N-alkylquinoxaline salts to give 1,2,4-triazino[5,6-b]quinoxalines after cyclization.For communication No, 16, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 960–966, July, 1985.     

2,6-Dithiodecahydro-1H,5H-Diimidazo[4,5,-b:4′,5′-e]Pyrazine and related dioxo- and diimino-decahydrodiimidazopyrazines

Thiourea condensed with 1,4-diformyl-2,3,5,6-tetrahydroxypiperazine 2 in the presence of hydrochloric acid to give 2,6-dithiodecahydro-1 H,5H-diimidazo[4,5,-b:4′,5′-e]pyrazine 5 isolated as the dihydrochloride salt. The salt 5 . 2HCl was converted to the free base 5 by lithium hydroxide, to the dinitrate salt 5 . 2HNO₃ by silver nitrate, degraded to 2-thio-2,3,4,7-tetrahydro-1 H-imidazo[4,5-b]pyrazine 6 in a reaction with tert-butyl amine, and converted to 4,8-dihydro-4,8-dinitro-1H,5H-diimidazo[4,5-b:4′,5′-e]pyrazine-2,6- disulfonic acid 9 by nitric acid (100%) at −40°C. Denitration of the dinitramine 9 to give 4,8-dihydro-1H,5H-diimidazo[4,5-b:4′,5′-e]pyrazine 11 was brought about by methanolic hydrogen chloride in ether. In one run nitration without oxidation converted the salt 5 · 2HCl to the dinitrate salt of the 4,8-dinitro derivative 10 ; treatment with triethyl amine liberated the free base 10 from the salt. Degradation of 2,6-dioxo-1,3,4,5,7,8-hexanitrodecahydro-1H,5H-diimidazo[4,5-b:4′,5′-e]pyrazine 12 to 2-oxo-2,3-dihydro-1,3-dinitro-1H-imidazo[4,5-b] pyrazine 13 was brought about by hydrochloric acid. Treatment with lithium hydroxide also liberated 2,6-dioxodecahydro-1H,5H-diimidazo [4,5-b:4′,5′-e]pyrazine 3 from its dihydrochloride salt. Attempts to liberate 2,6-diiminodecahydro-1H, 5H-diimidazo[4,5-b:4′,5′-e]pyrazine 4 from its tetrahydrochloride salt led instead to intractable mixtures. The tetrahydrochloride salt 4 · 4HCl was converted to the dihydrochloride salt 4 · 2HCl in a reaction with tert-butyl amine.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 16. σ-adducts of quinoxalinium salts with amines,alcohols, and enolates and their role in cyclizations with β-dicarbonyl compounds

In the reaction of N-methylquinoxalinium iodide with acetylacetone at –30 °C, the formation of 3-acetyl-2,4-dimethyl-3a,4,9,9a-tetrahydrofuro[2,3-b]quinoxaline has been recorded by ¹H NMR spectroscopy, this being a regioisomer of the 3-acetyl-2,9-dimethyl-3a,4,9,9a-tetrahydro[2,3-b]quinoxaline formed in this reaction at temperatures above –10 °C. -Adducts of the N-methylquinoxalinium cation with alcohols, amines, and -diketones have also been identified, and their role in cyclizations leading to the annelation of a furan ring is discussed.For Communication 15, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 669–677, May, 1985.     

Thermolysis of benzannulated enyne-carbodiimides. Application in the synthesis of pyrido[1',2':1,2]pyrimido[4,5-b]indoles and related heteroaromatic compounds

Several derivatives of the pyrido[1',2':1,2]pyrimido[4,5-b]indoles 4 and the pyrazino[1',2':1,2]pyrimido[4,5-b]indoles 14 were synthesized by treatment of the benzannulated enyne-isocyanates 8 with the iminophosphoranes 9 and 13, respectively, for the aza-Wittig reaction followed by thermolysis. The reaction presumably proceeds through an initial formation of the corresponding benzannulated enyne-carbodiimides, such as 10, followed by a formal intramolecular hetero Diels-Alder reaction. Surprisingly, when the iminophosphorane 17 was used for condensation with 8, the expected pyrimido[1',6':1,2]pyrimido[4,5-b]indoles 16 were not obtained. Instead, the isomeric pyrimido[6',1':2,3]pyrimido[4,5-b]indoles 21 were isolated. Presumably, an alternative reaction pathway involving an initial [2 + 2] cycloaddition reaction to form 19 followed by ring opening could lead to 20 and, after an intramolecular radical-radical coupling, 21. Treatment of the urea derivatives 24 with dibromotriphenylphosphorane also produced in situ the benzannulated enyne-carbodiimides 25, which on thermolysis gave the isoquinolino[2',1':1,2]pyrimido[4,5-b]indoles 26. Methylation of 4a, 14a, and 26a with methyl iodide occurred exclusively at the site of the indolo nitrogen. The planar geometry of those novel heteroaromatic compounds, resembling many DNA-binding agents, makes them potential candidates as DNA intercalators.     

Heterocycles containing nitrogen and sulfur. Part 49. Synthesis of derivatives of new heterocyclic systems: 1,2-Dioxocyclopenta(hexa)[g]oxazolidino-[3,2-f] pyrimido[4,5-b][1,4]thiazine, 1,2-dioxocyclopenta(hexa)-[g] imidazolidino[3,2-f]pyrimido[4,5-b][1,4]thiazine, and 1,2-oxazino[5,4-g]pyrimidino[4,5-b][1,4]thiazine

The reaction of 4-methoxy-5-amino-6-mercaptopyrimidine with 2-oxo-1-chlorocyclopentyl(hexyl)glyoxalate esters gave derivatives of the previously unknown tetracyclic systems 1,2-dioxocyclopenta (hexa)[g]oxazolidino[3,2-f]pyrimido[4,5-b][1,4]thiazines, which are transformed by ammonium acetate into derivatives of 1,2-dioxocyclopenta(hexa) [g]imidazolidino[3,2-f]pyrimido[4,5-b]-[1,4] thiazines. Derivatives of the new tricyclic 1-oxazino [5,4-g]pyrimido[4,5-b][1,4]thiazine system were obrtained by reaction of 6-carbethoxy-7-acetylpyrimido [4,5-b] [1,4] thiazines with hydroxylamine.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Synthesis of 5H-pyridazo[4,5-b]indoles by condensation of 2-acylindole-3-carboxylic acids with hydrazine

5H-Pyridazo[4,5-b]indol-1-ones were obtained by heating 2-acetylindole-3- or 2-aroylindole-3-carboxylic acids with hydrazine hydrate in ethylene glycol or alcohol. 1-Chloro-5H-pyridazo[4,5-b]indoles are formed by treatment of 5H-pyridazo[4,5-b]indol-1-ones with phosphorus oxychloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1064–1066, August, 1982.     

A concise synthesis of all four possible benzo[4,5]furopyridines via palladium-mediated reactions

[reaction: see text] By taking advantage of the alpha- and gamma-activation of chloropyridines as well as palladium-mediated reactions, all four possible benzo[4,5]furopyridine tricyclic heterocycles, benzo[4,5]furo[2,3-b]pyridine, benzo[4,5]furo[2,3-c]pyridine, benzo[4,5]furo[3,2-c]pyridine, and benzo[4,5]furo[3,2-b]pyridine, are efficiently synthesized from 2-chloro-3-iodopyridine, 3-chloro-4-stannylpyridine, 4-chloro-3-iodopyridine, and 2-chloro-3-hydroxypyridine, respectively.     

Pyridyl-substituted [1,3]Dithiolo-[4,5-<Emphasis Type="Italic">b</Emphasis>][1,4]dithiine-2-thiones

We have obtained 5-(2-pyridyl)[1,3]dithiolo[4,5-b][1,4]dithiine-2-thione for the first time by cycloaddition of 2-ethynylpyridine to 4,5-dihydro-1,3-dithioltrithione (isotrithionedithiol). We have studied this thione, 5-(2-pyridyl)- and 5-(4-pyridyl)-5,6-dihydro[1,3]dithiolo[4,5-b][1,4]dithiine-2-thiones by mass spectroscopy and also IR, UV, ¹H and ¹³C NMR spectra. We have determined the crystal and molecular structure of 5-(2-pyridyl)-5,6-dihydro[1,3]dithiolo[4,5-b][1,4]dithiine-2-thione.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 429–434, March, 2005.     

4-(10-Methyl-10H-phenothiazin-3-yl)-1,4-dihydropyridines, 4,5-dihydroindeno[1,2-<Emphasis Type="Italic">b</Emphasis>]-and 5,5-dioxo-4,5-dihydrobenzo-thieno[3,2-<Emphasis Type="Italic">b</Emphasis>]pyridines

Different modifications of the Hantzsch synthesis using 10-methyl-10H-phenothiazine-3-carbaldehyde gave 4-(10-methyl-10H-phenothiazin-3-yl)-substituted 1,4-dihydropyridine-3,5-di-, 5-oxo-4,5-dihydro-1H-indeno[1,2-b]pyridine-, and 5,5-dioxo-4,5-dihydro-1H-5λ⁶-benzo[4,5]thieno[3,2-b]pyridine-3-carboxylic esters. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 280–288, February, 2007.