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.     

A facile synthetic approach to novel spiro-oxindoles/acenaphthylen-1-ones containing benzo[1,4]thiazin-3-one ring via 1,3-dipolar cycloaddition

A series of spiro-oxindole derivatives containing spirobenzo[1,4]thiazin-3-one ring were synthesized regioselectively via a multicomponent 1,3-dipolar cycloaddition of isatin, 2-(4-methyl-benzylidene)-4H-benzo[1,4]thiazin-3-one and sarcosine or l-proline in toluene under reflux condition. Also spiro-acenaphthylen-1-ones containing spirobenzo[1,4]thiazin-3-one ring have been synthesized using 2-(4-methyl-benzylidene)-4H-benzo[1,4]thiazin-3-one as dipolarophile. The methodology affords high yields of products in short reaction time.     

A Facile and Rapid Method for Preparation of Thiazine and Thiadiazine Derivatives by Sonication Technique

Ultrasound accelerated synthesis of 2,3-(substituted)benzo-1,4-thiazino[5,6-b]-4H-9H-7- methyl-10-oxoquinolines (4), 7-substituted-2,2-dimethyl-2,3-dihydro-1H,10H-phenothiazin- 4-one (5), 4-substituted-3,9, 10-trihydro-11-oxo-quinolino[2,3-b]-1,3,4-thiadiazino[2,3-d]- 1,2,4-triazole (6), and 7,7-dimethyl-7,8-dihydro-3H,5H,6H-1,2,4-triazolo[3,4-b][1,3,4] benzothiadiazin-9-one (7) from carbostyril and dimedone using sulfur powder and iodine as a catalyst in THF is reported. The structures of the compounds have been elucidated on the basis of spectral and elemental analysis.     

Reaction of 2,3-Dihydro-1,5-benzothiazepines and Phenylacetyl Chloride in the Presence of Triethylamine： A New Aspect on the Formation Mechanism of Dihydro-1,3-oxazin-4-one Derivatives

2a,4-Disubstituted 2,2a,3,4-tetrahydro-2-phenyl-1H-azeto[2,1-d][ 1,5]benzothiazepin-1-ones, as well as 2-substi-tuted 2,3-dihydro-3-phenylacetyl-2-styryl-benzothiazoles and 4a,6-disubstituted 3- .benzyl-4a,5-d/hydro-2-phenyl-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, were obtained from the reaction of 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepines with phenylacetyl chloride in the presence of triethylamine. The mechanism for the formation of 4a,5-dihydro-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, 2,3-dihydro-1,3-oxazin-4-one derivatives, was suggested.     

Synthesis of diversely functionalized hexahydropyrrolo[2,3-b]indoles using domino reactions, olefination, isomerization and Claisen rearrangement followed by reductive cyclization

Hexahydropyrrolo[2,3-b]indoles 6 were synthesized in five steps from indolin-3-one 8 by a general and efficient method, in which elements of molecular diversity were readily added onto the 3a-position of the pyrrolo[2,3-b]indole ring system. Horner-Wadsworth-Emmons reaction of 2-allyloxyindolin-3-ones 7, derived from indolin-3-one 8 and a variety of allylic alcohols, smoothly proceeded with successive Claisen rearrangement to give the corresponding 3-allyl-3-cyanomethylindolin-2-ones 15. Indolin-2-ones 15 were converted into pyrrolo[2,3-b]indoles 6 using partial hydrolysis followed by reductive cyclization with LiAlH(4). Synthesis of N-methylated pyrrolo[2,3-b]indole derivatives 23 and 26 is also described.     

A tandem multi-component synthesis of 5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones

The five-component reaction of ethyl 2-[(2-oxopropyl)sulfanyl]acetate, aromatic aldehydes, and ammonium acetate affords two diastereomers of 5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones via a novel tandem Mannich-enamine-substitution sequence. Presumably, they are generated from ethyl 2-[(4-oxo-2,6-diaryl-3-piperidinyl)sulfanyl]acetates. During the formation of the trans-5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]-thiazin-2(3H)-ones from ethyl 2-[(4-oxo-2,6-diaryl-3-piperidinyl)sulfanyl]acetates, the configuration at the carbon bearing an aryl group adjacent to the enamide CC double bond is inverted via ring opening and closure. When o-substituted benzaldehydes were employed in this reaction, 5,7-diaryl-5,6-dihydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones were obtained via air oxidation, along with trans-5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]-thiazin-2(3H)-ones.     

Condensed isoquinolines. 37.* Heterocyclization using 3-(arylamino)- and 3-(hetarylamino)isoquinolin-1(2H)-ones

The reaction of 3-NHR-isoquinolin-1(2H)-ones (R = Ar) with aromatic aldehydes in the presence of Me3SiCl or in acetic acid leads to the formation of derivatives of dibenzo[b,f][1, 8]naphthyridin-5(6H)- one and benzo[f]isoquino[3,4-b][1, 8]naphthyridine-5,9(6H,7H)-dione. The reaction for R = Het in the presence of Me3SiCl gives derivatives of 5H-pyrido[1',2':1,2]pyrimido[4,5-c]isoquinolin-5-one, benzo[f]isoquinoline[3,4-b][1,8]naphthyridine-5,9[6H,7H]-dione, and derivatives of new heterocyclic systems, 5H-pyrazino[1',2':1,2]pyrimido[4,5-c]isoquinolin-5-one, 5H-[1,3]thiazolo[3',2':1,2]pyrimido- [4,5-c]isoquinolin-5-one, 5-H-benzo[f]pyrazolo[3,4-b][1,8]naphthyridin-5-one, and isoquino[3,4-b]- [1,5]naphthyridin-5(6H)-one. The effect of the structure of substituent R and nature of the substituent in the benzaldehydes on the structure of the reaction products was studied.     

Ionic Liquid-Mediated Facile Synthesis and Antimicrobial Study of Thiazolo [2,3-b]Benzo[h]Quinazolines and Thiazino[2,3-b] Benzo-[h]Quinazolines

Abstract

8-Methoxy-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione, obtained by the condensation of 2-benzylidene-6-methoxy-3,4-dihydronapthalene-1(2H)-one with thiourea, on reaction with chloroacetic acid and 3-chloropropanoic acid in the presence of the ionic liquid N-methylpyridinium tosylate furnishes 3-methoxy-7-phenyl-7,10-dihydro-5H- benzo[h]thiazolo[2,3-b]quinazoline-9(6H)-one and 3-methoxy-7-phenyl-5,6,10,11-tetrahydro- benzo[h][1,3]thiazino[2,3-b]quinazoline-9(7H)-one. Further, condensation of the thione with 1,2-dibromoethane and 1,3-dibromopropane yields 3-methoxy-7-phenyl-6,7,9,10-tetrahydro-5 H-benzo[h]thiazolo[2,3-b]quinazoline and 3-methoxy-7-phenyl-5,6,7,9,10,11-hexahydrobenzo [h][1,3]thiazino[2,3-b]quinazoline respectively. Arylidene derivatives have been obtained by two routes. The structures of the cyclized compounds have been established on the basis of elemental analysis and spectroscopic data. The synthesized compounds were screened for antimicrobial activity. Some of the compounds showed promising antimicrobial activities.     

Condensed isoquinolines 23. Reaction of <Emphasis Type="Italic">o</Emphasis>-bromomethylphenyl-acetonitrile with anthranilic acids: Synthesis of 6H, 12H,17H-dibenzo[3,4:6,7][1,8]-naphthyridino[1,8-<Emphasis Type="Italic">ab</Emphasis>]quinazoline-6,17-diones

The direction of the reaction of anthranilic acids with o-bromomethylphenylacetonitrile upon fusion depends on the temperature and nature of the substituent in the anthranilic acid. The reaction may lead to three types of products: Derivatives of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones below 150°C and to 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one or derivatives of 6H,12H,17H-dibenzo[3,4:6,7][1,8]naphthyridino[1,8-ab]quinazoline-6,17-diones above 150°C depending on the nature of the substituent in the anthranilic acid. A study was carried out on the mechanism for the formation of 6H,12H,17H-dibenzo[3,4:6,7][1,8]naphthyridino[1,8-ab]quinazoline-6,17-diones, which permitted the preparation of 6-(4-methylphenyl)-6,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1059–1067, July, 2007.     

A facile synthesis of novel 2-amino-6-arylmethyl-7-carboxamido-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5-ones

A facile synthesis of novel 2-amino-6-arylmethyl-7-carboxamido-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5-ones is described. The synthesis was developed on solid phase and was applied to provide a series of analogs in good yield. The key reactions are acylation of a cysteine derivative with 2,4-dichloropyrimidine-5-carbonyl chloride followed by cyclization to generate a 6-arylmethyl-7-carboxamido-2-chloro-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5-one, which is further derivatized with an amine to give the desired 2-amino-6-arylmethyl-7-carboxamido-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5-one.     

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.     

New heterocyclic structures. [1,2,5]Thiadiazolo[3′,4′:4,5]pyrimido-[2,1-b][1,3]thiazine and thiazolo[3,2a][1,2,5]thiadiazolo[3,4-d]pyrimidine

Derivatives of two new molecular structures, namely, 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one and 6,7-dihydro-9H-thiazolo[3,2-a][1,2,5]thiadiazolo[3,4-d][pyrimidin-9-one, and derivatives of N-substituted sulfamic acid, namely, (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-on-7-yl)sulfamic acid and (7-amino-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-on-6-yl)sulfamic acid, were separated out as by-products in the reduction reaction of 8-amino-3,4-dihydro-7-nitroso-2H,6H-pyrimido[2,1- b][1,3]thiazin-6-one and 7-amino-2,3-dihydro-6-nitroso-5H-thiazolo[3,2-a]pyrimidin-5-one derivatives, respectively, with sodium hydrosulfite. A mechanism of reaction, which hypothesizes the action of sodium hydrosulfite in an asymmetic form, is proposed. The results of single-crystal X-ray investigation on 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one (R = 0.032 for 863 reflections) and (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b]- [1,3]thiazin-6-on-7-yl)sulfamic acid, sodium salt (R = 0.028 for 3507 reflections) are reported.     

Synthesis of substituted 4H-thieno[2,3-b][1]benzothiopyran-4-ones as possible schistosomicidal agents

Summary A new series of thiophenic isosters of thioxanthones, namely: 2-substituted-4H-thieno[2,3-b][1]benzothiopyran-4-ones and 5-substituted-2-nitro-8-methyl-4H-thieno[2,3-b][1]benzothiopyran-4-ones were synthesized as potential schistosomicidal agents. The synthesized compounds were characterized by their¹H-NMR data.

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Synthese von substituierten 4H-Thieno[2,3-b][1]benzothiopyran-4-onen als mögliche schistosomicide Wirkstoffe

Zusammenfassung Es wurde eine neue Serie von thiophenischen Isosteren des Thioxanthons, nämlich 2-substituierte 4H-Thieno[2,3-b][1]benzothiopyran-4-one und 5-substituierte 2-Nitro-8-methyl-4H-thieno[2,3-b][1]benzothiopyran-4-one als potentielle schistosomicide Wirkstoffe synthetisiert. Die synthetisierten Verbindungen wurden mittels ihrer¹H-NMR Daten charakterisiert.

     

Synthesis of some new spiroindoline derivatives incorporated with pyrazoloheterocycles

Indole-2,3-dione ( 1 ) was treated with malonic acid ( 2 ) in a mixture of ethanol/pyridine to afford 1-[3-(2-oxoindolinylidene)]acetic acid ( 3 ). Compound 3 reacted with thionyl chloride to give the corresponding acid chloride ( 4 ). The acid chloride 4 reacted with arenes in the presence of AlCl₃ to yield 3-(2-oxoindolinylidene)acetophenones 5a–c . Compounds 5a–c reacted with 3-methylpyrazolin-5-one derivatives 6a , b to give 3-aracyl-3-[4′-(3′-methylpyrazolin-5-onyl)]-indoline-2-one derivatives 7a–f . Compounds 7a–f were treated with phosphorus pentoxide in phosphoric acid, with ammonium acetate or methanolic methylamine and with phosphorus pentasulfide to give spiro[indoline-3,4′-(pyrazolo[4,5-b]pyran)]-2-ones 8a–f , spiro[indoline-3,4′-(pyrazolo[4,5-b]-dihydropyridine)]-2-ones 9a–f , 10a–f and spiro[indoline-3,4′-(pyrazolo[4,5-b]thiopyran)]-2-ones 10a–f , respectively. All of the synthesized spiroheterocycle derivatives were identified by conventional spectroscopic methods (IR, ¹H NMR) and elemental analyses. © John Wiley & Sons, Inc.     

Investigation of nitrogen- and sulfur-containing heterocycles

The corresponding N-(3-pyridyl)hydroxamic acid derivatives were obtained by reductive desulfuration of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid amide, benzylamide, and morpholide. The amides were synthesized by reaction of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid ester with diethylaminoethylamine and pyrrolidine. Heating of the ester and morpholide of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid with H₂SO₄ gives 2-chloropyrido[2,3-b] [1,4]thiazin-6-one.See [1] for communication XXVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 676–678, May, 1973.     

Reactions of 2-sulfanylethanol with mucochloric acid and its derivatives

Mucochloric acid reacted with 2-sulfanylethanol in the presence of triethylamine to give 3-chloro-5-hydroxy-4-(2-hydroxyethylsulfanyl)furan-2(5H)-one which underwent acid-catalyzed cyclization to 7-chloro-2,3,4a,6-tetrahydrofuro[2,3-b][1,4]oxathiin-6-one. Likewise, reactions of 5-alkoxy-3,4-dichlorofuran-2(5H)-ones with 2-sulfanylethanol in the presence of triethylamine involved replacement of chlorine in position 4 of the furan ring with formation of the corresponding 4-(2-hydroxyethylsulfanyl) derivatives. The reaction of mucochloric acid with 2-sulfanylethanol in excess aqueous potassium hydroxide resulted in the formation of an acyclic product, 3-(2-hydroxyethylsulfanyl)-2-chloroprop-2-enoic acid. The structure of 7-chloro-2,3,4a,6-tetrahydrofuro[2,3-b][1,4]oxathiin-6-one and 3-(2-hydroxyethylsulfanyl)-2-chloroprop-2-enoic acid was proved by X-ray analysis.     

Chemistry of dioxine-annelated cycloheptatriene endoperoxides and their conversion into tropolone derivatives: an unusual non-benzenoid singlet oxygen source

The chemistry of two bicyclic endoperoxides, obtained by photooxygenation of 2,3-dihydro-7H-cyclohepta[1,4]dioxine and 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one was investigated with the aim of synthesizing the respective tropolone derivatives. The reaction of these endoperoxides with base, thiourea and their thermolysis provided the desired tropolone derivatives in high yield. On the other hand, the thermolysis of the endoperoxide derived from 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one underwent an unprecedented route and formed parent molecule and singlet oxygen instead of the expected troponoids. The formation mechanisms of all products are discussed.     

Cyclization reactions of 1,3-dibromopropan-2-ol, 2,3-dibromopropan-1-ol and 1-bromomethyloxirane with 6-amino-2,3-dihydro-2-thioxo-4(1H)-pyrimidinone

The cyclization reactions, carried out in strongly- or weakly-basic media, are described. Sometimes, 7-amino-2,3-dihydro-3-hydroxymethyl-5H-thiazolo[3,2-a]pyrimidin-5-one is separated out, together with 8-amino-3,4-dihydro-3-hydroxy-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one, as the principal product. A mechanism of reaction, during which the cyclizating agents are changed into oxirane derivatives, is proposed. The results of single-crystal X-ray investigations on 8-amino-3,4-dihydro-3-hydroxy-7-nitroso-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one (R = 0.035 for 1013 reflections), and on 7-hydroxymethyl-6,7-dihydrothiazolo[3,2-a][1,2,3]triazolo[4,5-d]pyrimidin-9(1H)-one (R = 0.027 for 1607 reflections) are reported.     

Synthesis of 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

The reaction of methyl 2-bromo-6-(trifluoromethyl)-3-pyridinecarboxylate ( 1 ) with methanesulfonamide gave methyl 2-[(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridine-carboxylate ( 2 ). Alkylation of compound 2 with methyl iodide followed by cyclization of the resulting methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate ( 3 ) yielded 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 4 ). The reaction of compound 4 with α,2,4-trichlorotoluene, methyl bromopropionate, methyl iodide, 3-trifluoromethylphenyl isocyanate, phenyl isocyanate and 2,4-dichloro-5-(2-propynyloxy)phenyl isothiocyanate gave, respectively, 4-[(2,4-dichlorophenyl)methoxy]-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazine 2,2-dioxide ( 5 ), methyl 2-[[1-methyl-2,2-dioxido-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4-yl]oxy]propanoate ( 6 ), 1,3,3-trimethyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 7 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 8 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-phenyl-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 9 ) and N-[2,4-dichloro-5-(2-propynyloxy)phenyl]-4-hydroxy-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2] thiazine-3-carboxamide 2,2-dioxide ( 10 ).     

Parallel solution-phase synthesis of 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one derivatives from 1,5-difluoro-2,4-dinitrobenzene

This paper discusses the synthesis of privileged structures 4H-benzo[1,4]thiazin-3-one and 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one derivatives in a parallel solution-phase manner using 1,5-difluoro-2,4-dinitrobenzene. Each scaffold possesses four diversity points. A cheap and efficient oxidant, urea-hydrogen peroxide (UHP), was applied for the introduction of the sulfone group. The intramolecular cyclization to 1,1-dioxo-1,4-dihydro-2H-1lambda6-benzo[1,4]thiazin-3-one was achieved by microwave assistance or the use of an inorganic base.