An investigation of nitrogen- and sulfur-containing heterocycles

The reaction of 3-amino-6-chloro-2-mercaptopyridine with ortho-substituted phenacyl halides has been investigated. Two types of intermediate compounds have been isolated: 3-amino-6-chloro-2-(phenacylthio)pyridines and 2-aryl-2-hydroxy-1,2-dihydro-3H-pyrido[2,3-b][1,4]thiazines. Boiling 3-amino-6-chloro-2-mercaptopyridine with ortho-substituted phenacyl halides in ethanol has given 2-aryl-3H-pyrido[2,3-b][1,4]thiazines.For Communication XXVII, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1262–1265, September, 1973. Original article submitted March 15, 1972,     

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.     

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.     

Synthesis and some heterocyclization reactions of new diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate and ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate

A new CF₂X-analogue of 1,1-bis(trifluoromethyl)-2,2-dicyanoethylene (X = P(O)(OEt)₂), diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate, has been synthesized from diethoxyphosphoryl pentafluoroacetone 1. A similar phosphoryl analogue of ethyl 3,3-dicyano-2-trifluoromethylacrylate, ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate, has been obtained from ethyl 3-(diethoxyphosphoryl)-3,3-difluoro-2-oxopropionate 2. By heterocyclization of these new ethylenes with 3-methyl-2-pyrazoline-5-ones, 3(5)-aminopyrazoles, dimedone, 2-aminopyridines, 1-aryl-3-methyl-5-aminopyrazoles, 1,3,3-trimethylisoquinolines, as well as by condensation with anilines and ketones, the difluoromethylphosphonate-substituted derivatives of 1,4-dihydropyrano[2,3-c]pyrazole, 4,5-dihydropyrazolo[1,5-a]pyrimidine, 5,6,7,8-tetrahydro-4H-chromene, 2H-pyrido[1,2-a]pyrimidine, 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine, 1,4-dihydropyridine, 4,5,6,7-tetrahydro-1H-[1]pyrindine, 1,4,5,6,7,8-hexahydroquinoline, and 6,7-dihydro-2H-pyrido[2,1-a]isoquinoline have been obtained in one stage.     

Synthesis and Properties of 1,3-Diaryl-5,6-dihydro-8H-imidazo[2,1-c]-1,4-oxazinium Bromides

It has been established that the condensation of 3-(4-methoxyphenylamino)-5,6-dihydro-2H-1,4-oxazine with substituted phenacyl bromides occurs at the exocyclic nitrogen atom with formation of 3-aryl-3-hydroxy-1-(4-methoxyphenyl)-2,5,6,8-tetrahydro-3H-imidazo[2,1-c]-1,4-oxazinium bromides. By treatment of the latter with acetic anhydride 3-aryl-1-(4-methoxyphenyl)-5,6-dihydro-8H-imidazo[2,1-c]-1,4-oxazinium bromides are formed. The structures of the compounds synthesized were determined via ¹H NMR spectroscopy and X-ray diffraction.     

Reaction of diketene with cyanothioacetamide: A convenient and regioselective method for the preparation of new 4(1H)-pyridone derivatives

The reaction of diketene with cyanothioacetamide in dry dioxane in the presence of triethylamine gives triethylammonium 3-cyano-6-methyl-4-oxo-1,4-dihydro-2-pyridinethiolate. The regioselective S-alkylation of this thiolate is a convenient method for the preparation of substituted 4(1H)-pyridones and also derivatives of thiazolo[3,2-a]pyridine and thieno[2,3-b]pyridine. The action of 2-amino-1,1,3-tricyanopropene on this thiolate leads to its transformation into a new heterocyclic system, namely, 5H-pyrido[2′,3′:4,5]thiopyrano[2,3-b]pyridine; treatment with iodine yields the oxidation product, namely, the corresponding bis(2-pyridyl) disulfide. The structure of isopropyl (3-cyano-6-methyl-4-oxo-1,4-dihydro-2-pyridinyl)thioacetate was confirmed by X-ray diffraction structural analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 716–725, May, 2007.     

Chemistry of Acyl(imidoyl)ketenes: IX. Synthesis and Thermolysis of 3-Aroyl-8-chloro-1,2-dihydro-4<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">c</Emphasis>][1,4]benzoxazine-1,2,4-triones

Reactions of 3-Z-aroylmethylene-6-chloro-3,4-dihydro-2H-1,4-benzoxazine-2-ones with oxalyl chloride afford 3-aroyl-8-chloro-1,2-dihydro-4H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones and Z-3-(2-aryl-2-chlorovinyl)-6-chloro-2H-1,4-benzoxazine-2-ones. Aroyl(imidoyl)ketenes generated by decarbonylation of pyrrolobenzoxazinetriones undergo dimerization through [4+2]-cycloaddition to form 4-aroyl-3-aroyloxy-2-(2-oxo-2H-1,4-benzoxazin-3-yl)-1H, 5H-pyrido[2,1-c][1,4]benzoxazine-1,5-diones.     

The Mannich reaction in the synthesis of N,S-containing heterocycles 3. Unexpected direction of the aminomethylation reaction of N-methylmorpholinium 1-amino-2,4-dicyano-4-ethoxycarbonyl-1,3-butadienethiolate. One stage cascade synthesis of new derivatives of pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>][1,3,5]triazine

The interaction of N-methylmorpholinium 1-amino-2,4-dicyano-4-ethoxycarbonyl-1,3-butadienethiolate with primary amines and formaldehyde leads to the formation of ethyl esters of 7-cyano-6-thioxo-1,3,4,6-2H-pyrido[1,2-a][1,3,5]triazine-9-carboxylic acid in place of the expected derivatives of pyrido[2,1-b][1,3,5]thiadiazine. The structure of the ethyl ester of 7-cyano-3-phenyl-6-thioxo-1,3,4,6-2H-pyrido[1,2-a][1,3,5]triazine-9-carboxylic acid was demonstrated by X-ray structural analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1075–1081, July, 2007.     

Synthesis and molecular structure of 4-nitro-9-phenyl-1H-and 9-hydroxy-3-oxo-9-phenyl-2,3-dihydro-9H-indeno-[2,1- c ]pyridines and 3,7-diphenyl-3a, 4,5,6-tetrahydroindeno[2,1- c ]isoxazolo[5,4- d ]pyridine

The 4-nitro derivatives and an oxidation by-product, 9-hydroxy-2-methyl-3-oxo-9-phenyl-2,3-dihydro-9H-indeno[2,1-c]pyridine were obtained by the nitration of N-alkyl-9-phenyl-2,3-dihydro-1H-indeno-[2,1-c]pyridines with sodium nitrite in acetic acid. Their molecular structures were studied by X-ray structural analysis. The product of [2+3] cycloaddition, 5-methyl-3,7-diphenyl-3a, 4,5,6-tetrahydroindeno[2,1-c]isoxazolo[5,4-d]pyridine, was obtained by the interaction of 2-chloro-1-hydroxy-2-phenylazomethine with 2-methyl-9-phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1390–1399, September, 2007.     

A simple and effective synthetic approach to pyrido[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazines

The reaction of partially hydrogenated 2-pyridinethiols with 1,3-dibromopropane gives substituted pyrido[2,1-b][1,3]thiazines. The structure of 7,9-dicyano-6-oxo-3,4,6,7-tetrahydro-2H-spirocyclohexane-1′,8-pyrido[2,1-b][1,3]thiazine was solved by X-ray diffraction structural analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1428–1433, September, 2007.     

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.     

Five-membered 2,3-dioxoheterocycles: LVIII. Reaction of methyl 1-Aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrol-2-carboxylates with substituted 1-methyl-3,4-dihydroisoquinolines. New approach to the synthesis of steroid 13-azaanalogs

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with substituted 1-methyl-3,4-dihydroisoquinolines with the formation of substituted 3-oxo-2,3,5,6-tetra-hydropyrrolo[2,1-a]-isoquinoline-2-spiro-2′-(1-aryl-3-aroyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrroles). A new approach was developed to the synthesis of 13-azagonanes, substituted benzo[f]pyrrolo[2,1-a]isoquinoline-9-spiro-2′-pyrroles.     

Bromination and diazo-coupling of pyridinethiones; microwave assisted synthesis of isothiazolopyridine, pyridothiazine and pyridothiazepines

Isothiazolopyridines, pyridothiazines and pyridothiazepines are important compounds that possess valuable biological activities. This paper reports on the synthesis of these compounds using both conventional chemical methods and modern microwave techniques. 3-Bromo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide, 5-arylazo-6-hydroxy-4-methyl-2-thioxo-1,2-dihydropyridine-3-carboxamides, 3,5-bis-arylazo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-caboxamide, 4-methyl-2,3,6,7-tetra-hydroisothiazolo[5,4-b]-pyridine-3,6-dione, 2,2'-(methylene-bis-(sulfanediyl))bis(4-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide), 2-hydroxy-5-methyl-4H-pyrido[3,2-e][1,3]-thiazine-4,7(8H)-dione and 2-arylmethylene-8-hydroxy-6-methyl-2,3,4,5-tetrahydropyrido-[3,2-f][1,4]thiazepine-3,5-diones have been prepared from 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide. Some of these compounds were prepared using microwave-assisted reaction conditions, that provided higher yields in shorter times than the conventional methods.     

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].     

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.     

5-Cyano-6-aryluracil and 2-thiouracil derivatives as potential chemotherapeutic agents. IV

A series of 5-cyano-6-aryluracils and 2-thiouracils 1a-h has been prepared and alkylated to 1,3-dialkyluracils 2a-d and 2-alkylthiouracils, 3, 4 and 6 , by electrophilic substitution with alkyl halides. Reaction of 1b with dibromoethane and 1,3-dibromopropane gave the corresponding bicyclic products, 7-aryl-6-cyano-2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones 5a,b and 8-aryl-7-cyano-3,4-dihydro-2H-pyrimido[2,3-b][1,3]thiazin-6-ones 5c-g . Nucleophilic substitution on 6 with hydrazine led to 7 which on refluxing with formic acid gave 5-aryl-6-cyano-8-methyl-s-triazolo[3,4-b]pyrimidin-7-ones ( 9 ), while with acetic and propionic acids only 2-acylhydrazino-3-methyl-4-oxo-5-cyano-6-arylpyrimidines 8a,b were isolated. The hydrazine 7 undergoes cyclization with acetylacetone and methyl dimethylmercaptoacrylate providing 2-(pyrazol-1-yl)-3-methyl-4-oxo-5-cyano-6-substituted pyrimidines 10 , and 11 . Some of the compounds were screened for antibacterial-, antifungal- and antiviral activities and a few of them showed significant chemotherapeutical activities.     

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].     

Synthesis of 1,2-diazepino[3,4-b]quinoxalines and pyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4-b]quinoxalines via a 1,3-dipolar cycloaddition reaction

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 8 with furfural, 3-methyl-2-thiophene-carbaldehyde, 2-pyrrolecarbaldehyde, 4-pyridinecarbaldehyde and pyridoxal hydrochloride gave 6-chloro-2-[2-(2-furylmethylene)-1-methylhydrazino]quinoxaline 4-oxide 5a , 6-chloro-2-[1-methyl-2-(3-methyl-2-thienyl-methylene)hydrazino]quinoxaline 4-oxide 5b , 6-chloro-2-[1-methyl-2-(2-pyrrolylmethylene)hydrazino]quinoxa-line 4-oxide 5c , 6-chloro-2-[1-methyl-2-(4-pyridylmethylene)hydrazino]quinoxaline 4-oxide 5d and 6-chloro-2-[2-(3-hydroxy-5-hydroxymethyl-2-methyl-4-pyridylmethylene)-1-methylhydrazino]quinoxalme 4-oxide 5e , respectively. The reaction of compound 5a or 5b with 2-chloroacrylonitrile afforded 8-chloro-3-(2-furyl)-4-hydroxy-1-methyl-2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxaline-5-carbonitrile 6a or 8-chloro-4-hydroxy-1-methyl-3-(3-methyl-2-thienyl)-2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxaline-5-carbonitrile 6b , respectively, while the reaction of compound 5e with 2-chloroacrylonitrile furnished 11-chloro-7,13-dihydro-4-hydroxy-methyl-5,14-methano-1,7-dimethyl-16-oxopyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4-b]quinoxaline 7.     

4-Hydroxy-2-quinolones. 108. N-R-amides of 9-fluoro-1-hydroxy-5-methyl-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid and their antitubercular activity

The reaction of 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline with triethylmethanetricarboxylate gives di(9-fluoro-1-hydroxy-5-methyl-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-ij]quinolin-2-yl)methane and ethyl 9-fluoro-1-hydroxy-5-methyl-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylate from which alkyl-, dialkylaminoalkyl-, and hetarylamides as well as hydrazides were prepared. The structure and antitubercular properties of the compounds synthesized are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1391–1407, September, 2006.