Novel Aspects of the Reaction of 3-(Benzimidazol-2-yl)-2-iminocoumarins with Aromatic Aldehydes

The reaction of 3-(benzimidazol-2-yl)-2-iminocoumarins with aromatic aldehydes has been studied. The condensation products 7-aryl-7H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidines or 3-(benzimidazol-2-yl)coumarins are formed depending on the nature of the substituent in the starting 2-iminocoumarin and aldehyde. In DMF medium, 7-aryl-7H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidines isomerize to the corresponding 7-aryl-14H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidines. The effect of the substituent on the isomerization process has been studied and the reaction mechanisms are discussed.     

The Use of 4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one as “Masked” α-Bromo-α'-Hydroxy Ketone in the Synthesis of Heterocyclic Systems

4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one was obtained on the basis of the readily obtainable 4-methylene-5,5-dimethyl-1,3-dioxolan-2-one. It forms 2-imidazo[1,2-a]pyridin-2-yl-2-propanol with 2-aminopyridine, 11a-hydroxy-1,1-dimethyl-3-oxo-1,5,11,11a-tetrahydro[1,3]oxazolo[3,4-a]pyrido[1,2-d]-10-pyrazinium bromide with 2-(aminomethyl)pyridine, and the corresponding derivative of 4-hydroxyoxazolidin-2-one with 2-(3,4-dimethoxyphenyl)ethylamine. The last product was converted by intramolecular amidoalkylation without isolation into 10b-(bromomethyl)-8,9-dimethoxy-1,1-dimethyl-1,5,6,10b-tetrahydro[1,3]oxazolo[3,4-a]isoquinolin-3-one.     

Synthesis of 2-[3-(trifluoromethyl)phenyl]furo[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridine derivatives

2-[3-(Trifluoromethyl)phenyl]-4,5-dihydrofuro[3,2-c]pyridin-4-one (I) was prepared by a three-step synthesis. Its reaction with phosphorus sulfide rendered thione II which was methylated to 2-[3-(Trifluoromethyl)phenyl]-4-methylsulfanylfuro[3,2-c]pyridine (III). 5-Methyl-2-[3-(trifluoromethyl)phenyl]-4,5-dihydrofuro[3,2-c]pyridin-4-one (IV) was obtained by the reaction of I with methyl iodide in PTC conditions. The chlorine atom in derivate V was replaced with heterocyclic secondary amines via nucleophilic substitution and 4-substituted furopyridines VIa and VIb were thus prepared. 2-[3-(Trifluoromethyl)phenyl]furo[3,2-c]pyridine-4-carboxylic acid (VII) was obtained by hydrolysis of the corresponding carbonitrile Va.     

Synthesis and reactions of 2-[3-(trifluoromethyl)phenyl]furo[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridine

(E)-3-{5-[3-(Trifluoromethyl)phenyl]furan-2-yl}propenoic acid (I) was prepared from 5-[3-(tri-fluoromethyl)phenyl]furan-2-carbaldehyde under the Doebner’s conditions. The obtained acid was converted to the corresponding azide II, which was cyclized by heating in diphenyl ether to 2-[3-(trifluoromethyl)phenyl]-4,5-dihydrofuro[3,2-c]pyridin-4-one (III). This compound was aromatized with phosphorus oxychloride to chloroderivative IV which was reduced with H₂NNH₂-Pd/C to the title compound V. 2-[3-(Trifluoromethyl)phenyl]furo[3,2-c]pyridin-5-oxide (VI) was synthesized by reaction of V with 3-chloroperoxybenzoic acid in dichloromethane. On treatment of VI with benzoyl chloride and potassium cyanide (Reissert-Henze reaction), corresponding 2-[3-(trifluoromethyl)phenyl]furo[3,2-c]pyridine-1-carbonitrile (VII) resulted. 5-Amino-2-[3-(trifluoromethyl)phenyl]furo[3,2-c]pyridin-5-ium-4-methylbenzene sulfonate (VIII) was prepared by direct N-amination of the title compound V with 1-[(aminooxy)sulfonyl]-4-methylbenzene in dichloromethane. Then, VIII was transformed to a non-isolated zwitterionic N-imid IX which afforded the corresponding furo[3,2-c]pyrazolo[1,5-a]pyridine carboxylic acid esters X, XI by 1,3-dipolar cycloaddition reactions with dimethyl but-2-ynedionate (DBD) or ethyl propiolate. The structures of all compounds were confirmed by their IR and NMR spectra. Presented at the 1st International Conference “Applied Natural Sciences” on the occasion of 10th anniversary of the University of St. Cyril and Methodius, Trnava, 7–9 November 2007.     

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.     

Reaction of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazin-7-ones with Aryl Bromomethyl Ketones and Benzyl Bromide

The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles and 3-phenyl-2-propenoic acid, depending on the structure of R. The reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with benzyl bromide yields 5-aryl-3-benzylthio-4H-1,2,4-triazoles and 3-aryl-2-propenoyl bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 905–909, June, 2005.     

Synthesis of 8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine

8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine has been synthesized by the interaction of 6-tert-butyl-3-hydrazino-1,2,4-triazolo[3,4-c]-1,2,4-triazin-5-one with formic acid. The conditions of carrying out the reaction are discussed. Spectral characteristics are given.     

Oxidative Recyclization of 4,6,7-Trichloro-5-hydroxy-2-(2-pyrimidylamino)-2,3-dihydrobenzo[b]furan

When 4,6,7-trichloro-5-hydroxy-2-(2-pyrimidylamino)- 2,3-dihydrobenzo[b]furan reacted with phenyliodoso diacetate, an unexpected oxidative recyclization was observed to give 3-(3,5,6-trichloro-1,4-benzoquinon-2-yl)imidazo[1,2-a]pyrimidine. 2-[N-2-(3,5,6-Trichloro-1,4-benzoquinon-2-yl)ethenylamino]pyrimidine is the intermediate product in the conversion.     

2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones

A novel method for synthesis of 2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 3-R-4,5-dihydro-1H-1,2,4-triazole-5-thiones with 3-aryl(heteryl)-2-propenoyl chlorides is proposed.     

Synthesis and Properties of 6-Amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles

We have established that when 5-chloro-6-[cyano(2,3-dihydro-1-R-benzo[d]azol-2-yl)methyl]-2,3-pyrazinedicarbonitriles are reacted with nucleophilic reagents (aliphatic and aromatic amines, hydrogen sulfide), annelation of the five-membered ring occurs on the [b] face of the pyrazine with formation of 6-amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles and 6-amino-7-(1H-benzo[d]imidazol-2-yl)thieno[2,3-b]pyrazine-2,3-dicarbonitrile respectively. Further heating with excess of acylating reagent leads to formation of a novel heterocyclic system 1H-benzo[4,5]imidazo[1,2-c]pyrazino[2',3':4,5]pyrrolo[3,2-e]pyrimidine. Reaction of vicinal dinitriles with hydrazine hydrate leads to the novel system 1H-pyrrolo[2',3':5,6]pyrazino[2,3-d]pyridazine.     

Synthesis of 6-Amino-5-R2-7-(6-R1-4-oxo-3,4-dihydro-2-quinazolyl)-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles

It has been found that malonodinitrile and 2-(6-R¹-oxo-3,4-dihydro-2-quinazolyl)acetonitrile in the presence of triethylamine undergo hetarylation by 5,6-dichloro-2,3-pyrazinedicarbonitrile at the active methylene group to give the triethylammonium salt of 2-(3-chloro-5,6-dicyano-2-pyrazinyl)malononitrile or 5-chloro-6-cyano(6-R¹-4-oxo-1,2,3,4-tetrahydro-2-quinazolylidene)methyl-2,3-pyrazinedicarbonitriles. Reaction of these with primary amines leads to annelation of the pyrrole ring at the pyrazine [b] edge to give 6-amino-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3,7-tricarbonitriles and 6-amino-5-R²-7-(6-R¹-4-oxo-3,4-dihydro-2-quinazolyl)-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles respectively.     

The reaction of 2-amino-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]-pyrimidine with carbon disulfide and alkylation of its products

In the reaction with carbon disulfide, 2-amino-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine (1) forms the alkaline salts of substituted dithiocarbamic or iminodithiocarbonic acids depending on the molar ratio between1, CS₂, and the alkali. The alkylation of these salts leads to the esters ofN-(7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-2-yl)dithiocarbamic (2) and diesters of (7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-2-yl)iminodithiocarbonic acids (3). The synthesis of asymmetric diesters3 may be fulfilled based on monoesters2.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 14–14, August, 1994.     

Intramolecular Cyclization of 4-Isocyanato-3-(2-naphthyl)-1-phenylpyrazole Under Friedel-Crafts Reaction Conditions

4-Isocyanato-3-(2-naphthyl)-1-phenylpyrazole cyclized under the influence of AlCl₃ to give 2H-benzo[h]pyrazolo[4,3-c]isoquinoline.     

Reactions of 3-[N-chloroacetylamino-N-(4-nitrophenyl)]-2-formylindole with alkylamines

The reactions of 3-[N-chloracetylamino-N-(4-nitrophenyl)]-2-formylindole (1a) with 2-(N, N-dialkylamino)ethylamines afford complex condensation products 7b,c consisting of two similar but not identical diazepinoindole fragments. For the reaction of compound 1a with 3-(N,N-diethylamino)propylamine, the process occurs in a different manner, and the predominant product is 4-ethylaminopropyl-1-(4-nitrophenyl)-2-oxo-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole hydrocloride (14). Two routes of these unexpected transformations were proposed. The structures of the synthesized products were proved by the ¹sH and ¹³C NMR, HMBC, and HSQC (direct proton-carbon correlation) spectra. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1536–1542, August, 2007.     

Synthesis and Properties of Derivatives of the new Heterocyclic System Benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine

Derivatives of a new heterocyclic system - benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine have been obtained by successive reactions in three stages - alkylation of 3-cyanopyridine-2(1H)-thiones with 2-chloromethylbenzylimidazole to give 2-benzimidazolylmethylthio-3-cyanopyridines, closing the thiophene ring in the latter to form 3-amino-2-(benzimidazolyl-2)thieno[2,3-b]pyridines, and cyclization of the pyrimidine ring by acylation with carboxylic acid anhydrides or chlorides.     

Transformations of 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones in the presence of amines

When heated in piperidine, 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones undergo cyclization into 2-(1-hydroxyalkyl)naphtho[2,3-g]indole-6,11-diones. In contrast, 1-amino-2-(3-hydroxy-3-phenylpropynyl)-9,10-anthraquinone reacts with primary and secondary amines to give the corresponding 1-amino-2-(1-amino-2-benzoylvinyl)-9,10-anthraquinones, which undergo cyclization into 4-dialkylamino- or 4-alkylamino-2-phenylnaphtho[2,3-h]quinoline-7,12-diones. Heating of the starting phenylpropynol with Et₃N causes its dehydrogenation and isomerization.     

Synthesis of 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-Aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones

The reaction of 2-mercaptobenzimidazole, 5-ethoxy-2-mercaptobenzimidazole, and 2-mercaptoimidazoline with cinnamoyl chloride, its derivatives, and heteroanalogs was studied. Convenient methods were found for the synthesis of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones.     

Studien zur Chemie von thienoanellierten O,N- und S,N-haltigen Heterocyclen, 10. Mitt.: Synthese von 2- substituierten Thieno-Diltiazemderivaten

Summary The syntheses of 2-acetyl-, 2-benzyl-, and 2-ethyl-thieno-diltiazem derivatives are described starting from the corresponding 5-substituted 3-nitro-2-thiophenthiolvia reaction with racemic methyltrans-3-(4-methoxyphenyl)-glycidate under different conditions (solvent, catalyst, temperature) to obtain purethreo orerythro products. The nitro groups of these products were reduced and the resulting amino esters cyclized. The thieno[2,3-b][1,4]thiazepin-5(4H)-ones were N-alkylated and acetylated in position 3. The desired 2-substituted 4-(2-dimethylaminoethyl)-4,5,6,7-tetrahydro-7-(4-methoxyphenyl)-5-oxothieno[2,3-b][1,4]thiazepin-6-yl acetates were isolated in good yields.

     

Imidazo[1,5-a]- and Thiazolo[3,4-a]quinoxalines Based on 3-(a-Thiocyanobenzyl)quinoxalin-2(1H)-one

When 3-(a-thiocyanobenzyl-2(1H)-one is heated, competing processes of [a]-annelation of the imidazole or thiazole rings occurs with formation of imidazo[1,5-a]- and thiazolo[3,4-a]quinoxalin-4(5H)-ones.     

Reagents for new heteroannelation reactions III. 2-(Methylthio)-2-thiazoline

Summary A variety of partly novel tri- and tetracyclic hetero systems were obtained by reaction of heteroaromatic 2-aminoesters with 2-(methylthio)-2-thiazoline, yielding double-annelation of a thiazolo[2,3-b]pyrimido moiety in a one-pot process.On leave from University of Chittagong, Bangladesh