A study of nitrogen- and sulfur- containing heterocycles

The reaction of 3-amino-6-chloro-2-mercaptopyridine with phenacyl halides has been studied, and a number of 3-aryl-7-chloro-2H-pyrido-[2,3-b]-1,4-thiazines have been synthesized. Two types of intermediate compounds have been isolated: 2-amino-6-chloro-2-phenacyl-thiopyridines and 3-aryl-7-chloro-3-hydroxy-1,2-dihydropyrido[2,3-b]-1,4-thiazines.     

A study of nitrogen- and sulfur- containing heterocycles

The reaction of 3-amino-6-chloro-2-mercaptopyridine with phenacyl halides has been studied, and a number of 3-aryl-7-chloro-2H-pyrido-[2,3-b]-1,4-thiazines have been synthesized. Two types of intermediate compounds have been isolated: 2-amino-6-chloro-2-phenacyl-thiopyridines and 3-aryl-7-chloro-3-hydroxy-1,2-dihydropyrido[2,3-b]-1,4-thiazines.For part VI, see [3].     

Research on nitrogen and sulfur-containing heterocycles

2-Mercapto-3-amino-5-chloropyridine reacts with phenacyl halides to yield 2-phenacylmercapto-3-amino-5-chloropyridines and 2-aryl-7-chloro-3H-pyrido[2, 3-b][1, 4]thiazines.For part V, See [11].     

Nitrogen- and sulfur-containing heterocycles

4-Chloro-5-amino- and 4-chloro-5-methylamino-6-phenacylmercaptopyrimidines (II–V and XVI–XX) were obtained by the reaction of 4-chloro-5-amino- and 4-chloro-5-methylamino-6-mercaptopyrimidines (I and XV) with phenacyl halides. It is shown that II–V are cyclized by alkalis to 4-chloro-6-aryl-6-hydroxy-5,6-dihydropyrimido[4,5-b][1,4]thiazines (VI–IXa), while both II–IXa and XVI–XIX, respectively, are converted to 7H-4-chloro-6-aryl- (X–XIII) and 5H-4-chloro-5-methyl-6-arylpyrimido[4,5-b][1,4]thiazines (XX–XXIII) under the influence of acidic reagents.See [5] for communication XVIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 73–77, January, 1971.     

Synthesis and Properties of 7-Acetyl-8-aryl-9-cyano-3-hydroxy-6-methyl-3,4-dihydro-2H,8H-pyrido[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazines

7-Acetyl-8-aryl-2-(1-chloro-2-hydroxy-3-propyl)thio-9-cyano-6-methyl-1,4-dihydropyridines were obtained by treatment of 1,4-dihydropyridine-2(3H)-thiones with epichlorohydrin in the presence of sodium bicarbonate. When treated with NaOMe, these compounds are readily intramolecularly alkylated with formation of 7-acetyl-8-aryl-3-hydroxy-9-cyano-6-methyl-3,4-dihydro-2H,8H-pyrido[2,1-b]-[1,3]thiazines. We have studied amination of 2-(1-chloro-2-hydroxy-3-propyl)thio-1,4-dihydropyridines and acylation of 3-hydroxy-3,4-dihydro-2H,8H-pyrido[2,1-b][1,3]thiazines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1394–1399, September, 2005.     

Investigation of nitrogen- and sulfur-containing heterocycles

2-Mercapto-3-ureido-6-chloropyridine reacts with the ortho, meta, and para derivatives of phenacyl halides to give 2-phenacylthio-3-ureido-6-chloropyridines, which are readily cyclized to 6-arylpyrido[2,3-b][1,4]thiazines regardless of the presence or absence of a substituent in the meta and para positions of the benzene ring.See [1] for communication XXIX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 798–800, June, 1974.     

Derivatives of condensed pyrimidine,pyrazine, and pyridine systems

Reaction of 2-mercapto-3-amino-5,6-dimethyl- and 2-mercapto-3-amino-5,6-diphenylpyrazines withα-halo acid esters gave 2-carbethoxy-3-aminopyrazines, which are converted by the action of sodium ethoxide to 5,6-dimethyl- and 5,6-diphenylpyrazino[2,3-b]-[1,4]thiazin-6-ones. The latter are more conveniently obtained from 2-chloro-3-amino-5,6-dimethyl- and 2-chloro-3-amino-5,6-diphenylpyrazines and thioglycolic acid. 5,6-Dihydropyrazinothiazine is formed by reduction of 5,6-dimethyl pyrazino[2,3-b][1,4]thiazin-6-one, whereas the 2,3-dimethyl-5-amino-6-sulfonic acid and its N-oxide are formed by oxidation.     

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.     

NOVEL SYNTHESIS OF CONDENSED HETEROCYCLIC SYSTEMS CONTAINING 1,2,4-TRIAZOLE RING

3-Aryl-6,7-dihydro-s-triazolo[3,4-b][1,3]thiazines and 3-aryl-5,6-dihydro-thiazolo[2,3-c]-s-triazoles were synthesized by nucleophilic substitution of 3-aryl-5-mercapto-1,2,4-triazoles with 1,3-dibromopropane and 1,2-dichloroethane. And the bis-Mannich reaction of 3-aryl-5-mercapto-1,2,4-triazoles with formaldehyde has been studied.     

Facile synthesis of some novel pyrido[3',2':4,5]thieno[2,3-b][1,4]thiazine-8-carboxylic acids

Model tetrahydropyrido[3',2':4,5]thieno[2,3-b][1,4]thiazines 9a-c were synthesized via reductive lactamization, using sodium dithionite, of the respective 2-[(carboxyalkyl)thio]-3-nitro-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acids 7a-c. The latter derivatives were made via interaction of 2-chloro-7-cyclopropyl-3-nitro-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid (6) with each of alpha-mercaptoacetic, alpha-mercaptopropionic, and alpha-mercaptosuccinic acids and triethylamine in aqueous acetone at room temperature. The structures of 7a-7c and 9a-9c are supported by microanalytical and spectral (IR, MS, NMR) data. Compounds 9a and 9c showed potent inhibitory activity against the IGROV1 (Ovarian Cancer) cell line.     

4H-dithieno[2,3-b:3',2'-e][1,4]thiazines--synthesis and electronic properties of a novel class of electron rich redox systems

Quantum chemical screening reveals that 4H-dithieno[2,3-b:3',2'-e][1,4]thiazines possess the highest HOMO among four constitutional isomers, even 0.27 eV higher in energy than the well established 10H-phenothiazine. N-Substituted 4H-dithieno[2,3-b:3',2'-e][1,4]thiazines are readily accessible by twofold Pd-catalyzed amination. According to cyclic voltammetry dithienothiazines are reversibly oxidized and can be considered as new donors for functional π-systems.     

Synthesis of 6-acetylhomopterin. A naturally occurring pyrimido[4,5-b][1,4]diazepine

2-amino-4-oxo-6-acetyl-3,4,7,8-tetrahydro-3H,9H-pyrimido- [4,5-b][1,4]diazepine (or 6-acetylhomopterin), has been synthesised from 1-amino-4,4-diethoxy-3-pentanol and 2-amino-4-chloro-5-nitro-6(1H)-pyrimidinone.     

10-Aryl-7,7-dimethyl-5,6,7,8,9,10-hexahydro-11H-pyrido[3,2-b][1,4]benzodiazepin-9-ones

In reactions of 3-(2-amino-3-pyridyl)amino-5,5-dimethylcyclohex-2-en-1-one with aromatic aldehydes (2- and 4-hydroxy-, 2-hydroxy-3-methoxy-, 4-dimethylamino-, 4-methoxy-, 2,4- and 3,4-dimethoxy-, 3,4-methylenedioxy-, 4-bromo-, 4-fluoro-, 4-chloro-, 2-nitro- and 3-nitrobenzaldehydes, furfural, and 2-thiophenecarbaldehyde), we have obtained the corresponding 10-aryl-7,7-dimethyl-5,6,7,8,9,10-hexahydro-11H-pyrido[3,2-b][1,4]benzodiazepin-9-ones.     

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.     

Investigation of nitrogen- and sulfur-containing heterocyclic compounds

The halogenation of 2,3-dimethylpyrazino[2,3-b][1,4]thiazin-6-one with bromine or 1 mole of sulfuryl chloride gives 7-bromo-and 7-chloropyrazino[2,3-b][1,4]thiazin-6-ones, while 2 moles of sulfuryl chloride give 7,7-dichloropyrazino[2,3-b][1,4]thiazin-6-one. A number of 7-amino-and 7,7-diaminopyrazino[2,3-b][1,4]thiazin-6-ones were obtained by the reaction of the appropriate halo derivatives with amines. Some of the pyrazino[2,3-b][1,4]thiazin-6-one derivatives inhibit the growth of interweavable tumors in animals.See [3] for communication XX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1498–1501, November, 1971.     

Researches on nitrogen and sulfur heterocyclic rings

A number of 7H-pyrimido[4, 5-b]thiazines are obtained by reacting 5-amino-6-mercaptopyrimidines with -halogeno ketones. It is established that the reaction takes place in three stages: formation of 5-amino-6-[-ketoalkyl(aralkyl)-mercapto]pyrimidines, cyclization of these to 6-hydroxy-5, 6-dihydropyrimido[4, 5-b][1, 4]thiazines, and dehydration of the latter to 7H-pyrimido[4, 5-b][1, 4]thiazines.For Part III see [5].     

Synthesis of novel heteroaromatics structurally related to ellipticine alkaloids via thermolysis of pyridannulated enyne-carbodiimides

New synthetic pathways to the 5H-pyrido[3',4':4,5]pyrrolo[2,3-b]quinolines 6, the 6H-pyrido[3',4':4,5]pyrrolo[2,3-b][1,6]naphthyridines 7, and the 11H-pyrido[4',3':4,5]pyrrolo[2,3-b]quinolines 8 via thermolysis of the pyridannulated enyne-carbodiimides 14, 19, and 23 were established. These novel heteroaromatic systems are structurally related to ellipticine alkaloids and could serve as DNA-intercalating agents.     

Synthesis of Derivatives of 4,6-Dioxo-1,4,6,7,8,9-hexahydropyrimido[4,5-<Emphasis Type="Italic">b</Emphasis>][1,6]naphthyridines

It has been shown that 1-aryl-8-(4-bromophenyl)-4,6-dioxo-2H(phenyl)-7-phenyl-1,4,6,7,8,9-hexahydropyrimido[4,5-b][1,6]naphthyridines are formed on heating anilides of 1-aryl-7-(4-bromostyryl)-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acids in PPA.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 597–600, April, 2005.     

Investigation of nitrogen- and sulfur-containing heterocycles. 38. Reactions of 2-mercapto-3-ureidopyridines with halo β-diketones

The reaction of 2-mercapto-3-ureido-6-chloropyridine with chlorodibenzoylmethane in the presence of alkali leads to 2-(benzoylmethylthio)-3-benzamido-6-chloropyridine, whereas the reaction in the absence of alkali leads to 2-chloro-6-phenyl-7-benzoylpyrido[2,3-b] [1,4]thiazine. Under similar conditions 2-(diacetylmethylthio)-3-ureido-6-chloropyridine, 2-(acetylmethylthio)-3-ureido-6-chloropyridine, and 2-chloro-6-methyl-7-acetylpyrido[2,3-b][1,4]thiazine were obtained from 2-mercapto-3-ureido-6-chloropyridine and chloroacetylacetone. Treatment of 2-(diacetylmethylthio)-3-ureido-6-chloropyridine with alcoholic alkali leads to 2-(acetylmethylthio)-3-ureido-6-chloropyridine. 2-Chloro-6-phenyl-7-acetylpyrido-[2,3-b] [1,4]thiazine and 2-(benzoylmethylthio)-3-ureido-6-chloropyridine are formed in the reaction of 2-mercapto-3-ureido-6-chloropyridine with chlorobenzoylacetone in the presence of an equimolar amount of alkali, while 2-(benzoylmethylthio)-3-acetamido-6-chloropyridine is formed when excess alkali is used. See [1] for communication 37. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 787–790, June, 1980.     

The reaction of 2-hetarylacetonitriles with heterocyclic haloaldehydes

The reaction of 4-oxo-3,4-dihydroquinazolyl-and benzimidazolylacetonitriles with 2-chloro-2-quinolinecarbaldehydes and 1-aryl-5-chloro-3-methyl-1H-pyrazole-4-carbaldehydes gave the corresponding 3-(2-chloro-3-quinolyl)-2-(4-oxo-3,4-dihydro-2-quinazolyl)-2-propenenitriles and 3-(1-aryl-5-chloro-3-methyl-1H-4-pyrazolyl)-2-hetaryl-2-propenenitriles. Intramolecular cyclization of these compounds gives 15-oxo-15H-benzo[6,7][1,8]naphthyridino[2,1-b]quinazoline-6-carbonitriles, 1-aryl-3-methyl-11-oxo-1,11-dihydropyrazolo[4′,3′:5,6]pyrido[2,1-b]quinazoline-5-carbonitriles, and 1-aryl-3-methyl-1H-benzo[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyridine-5-carbonitriles.