Synthesis of condensed quinoxalines

A novel efficient synthesis of fluorescent, fused quinoxalines was achieved. 6-Triazolylthiazolo[4,5-b]quinoxalines were synthesized by the diazotisation of 6-amino-2-methylthiazolo[4,5-b]quinoxaline and coupling with selected aromatic amines followed by air oxidation. Diazotised aryl amines were coupled with 6-amino-2-methylthiazolo[4,5-d]quinoxaline followed by subsequent air oxidation afforded 1,2,3-triazolo[5,4-f]quinoxalino[2,3-d]thiazoles. 6-Amino-2-methylthiazolo[4,5-b]quinoxaline was condensed with conjugated enol ethers followed by cyclization in dowtherm resulted in thiazolo[4,5-b]quinoxalino[6,5-b]pyridine.     

3-Amino-2-quinoxalinecarbonitrile. New fused quinoxalines with potential cytotoxic activity

Starting with 3-amino-2-quinoxalinecarbonitrile 1,4-dioxide 1 , a new series of quinoxaline derivatives was prepared through chemical modifications of the 2-cyano and 3-amino groups. Nitration of 3-amino-2-quin-oxalinecarbonitrile 3 afforded the 7-nitro derivative 6 . Diazotation of 3 gave the 3-chloro compound 9 . 2,3-Quinoxalinedicarbonitrile 14 was obtained from 9 . Pyridazino[4,5-b]quinoxalines 15 and 16 were prepared by condensing 14 with hydrazine hydrate. A triazolo[4,5-b]quinoxaline 18 , a isothiazolo[4,5-b]quinoxaline 20 and two pyrazolo[3,4-b]quinoxalines 21 and 22 were identified. Compounds were tested as cytotoxic agents both in oxic and in hypoxic cells.     

Synthesis of 1-hydrazinopyridazino[4,5-b]quinoxaline and related compounds

This paper describes the synthesis of 1-hydrazinopyridazino[4,5-b]quinoxaline ( 10 ), tetrazolo[4,3-b]pyridazino[4,5-b]quinoxaline ( 11 ) and some 1,2,4-triazolo[4,3-b]pyridazino[4,5-b]quinoxalines 13 . Starting with 2-ethoxycarbonyl-3-methylquinoxaline 1,4-dioxide ( 1 ), 1,2-dihydro-1-oxopyridazino[4,5-b]quinoxaline ( 5 ) was prepared by three different ways: (a) chlorination of 1 in acetic acid gave 2-ethoxycarbonyl-3-dichloromethylquinoxaline 1,4-dioxide, which reacts with an excess of hydrazine to give about 60% of 5 ; (b) oxidation of 1 with selenium dioxide gave 90% of 2-ethoxycarbonyl-3-formylquinoxaline 1,4-dioxide ( 3 ), which reacts with hydrazine to give 5 (63%); (c) compound 3 was treated with hydrazine to give 1,2-dihydro-1-oxopyridazino-[4,5-b]quinoxaline 1,4-dioxide ( 4 ) (70%), which by reduction with sodium dithionite gave 5 (80%). Compound 5 reacts with phosphorus pentasulfide or the Lawesson reagent to give 1,2-dihydro-1-thiocarbonylpyridazino[4,5-b]quinoxaline ( 9 ), which treated with hydrazine gave 5 (80%). This last compound reacts with nitrous acid to give 11 . Some hydrazones 12 from 10 are described. Heating the aldehyde hydrazones 12a,c,d with dimethylsulfoxide some 1,2,4-triazolo[4,3-b]pyridazino[4,5-b]quinoxalines 13 were obtained. Compound 13a was also obtained in the reaction of 10 with benzoyl chloride. Reaction of 3 with phenylhydrazine gave 1,2-dihydro-1-oxo-2-phenylpyridazino[4,5-b]quinoxaline ( 6 ). Reactions of 5 with acetic anhydride and dimethylsulfate gave, respectively, 1-acetoxypyridazino[4,5-b]quinoxaline ( 8 ) and 1,2-dihydro-1-oxo-2-methylpyridazino-[4,5-b]quinoxaline ( 7 ). All the compounds were characterized by elemental analysis and ¹H-nmr spectra. Compounds 5 and 10 showed antihypertensive activity in rats.     

Synthesis of novel pyridazino[3,4-b]quinoxalines

The pyridazino[3,4-b]quinoxaline 12 was synthesized by the cyclization of the α-arylhydrazonoacyl-hydrazide 11. The reaction of compound 12 with phosphoryl chloride gave pyridazino[3,4-b]quinoxaline 13, whose reactions with sodium azide or cyclic secondary amines provided pyridazino[3,4-b]quinoxalines 14,17 and 18, respectively. The acylhydrazide 15 was also cyclized to pyridazino[3,4-b]quinoxaline 16.     

A convenient synthesis of 5,14-methano-16-oxo-1,5,6-benzoxadiazonino[3,4-b]quinoxalines utilizing a 1,3-dipolar cycloaddition reaction and an intramolecular alcoholysis

The reaction of the hydrazones 5a-c with 2-chloroacrylonitrile produced the 1,2-diazepino[3,4-b]quinoxaline hydrochlorides 6a-c , which were transformed into the 5,6,7,13-tetrahydro-5,14-methano-16-oxo-1,5,6-benzoxadiazonino[3,4-b]quinoxalines 7a-c , respectively. The oxidation of 7a-c with diethyl azodicarboxylate afforded the 7,13-dihydro-5,14-methano-16-oxo-1,5,6-benzoxadiazonino[3,4-b]quinoxalines 8a-c , respectively. Compounds 7a-c and 8a-c were also obtained by a one-pot synthesis from 5a-c and 6a-c , respectively.     

A facile synthesis of novel 1,2-diazepino[3,4-b]quinoxalines by a 1,3-dipolar cycloaddition reaction

The 1,3-dipolar cycloaddition reaction of the quinoxaline 4-oxides 4a,b with 2-chloroacrylonitrile gave the 2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxalines 5a,b , respectively, which were converted into the 2,3,4,6-tetrahydro-1H-1,2-diazepino[3,4-b]quinoxalines 7a,b and 8a,b , respectively.     

Reactions of furoxano[3,4-b]quinoxaline with alkynes and alkenes. Synthesis of pyrazino[2,3-b]quinoxaline 1,4-dioxides

Pyrazino[2,3-b]quinoxaline 1,4-dioxides 3a-e were prepared by reacting Furoxano[3,4-b]quinoxaline with alkynes and alkenes.     

New quinoxalines with nitrogen functions in the side chain. Potential inhibitors of 5-HT3

Starting with benzofuroxane 1 , 2-ethoxy-carbonyl-3-methylquinoxaline 1,4-dioxide 7 is obtained. From this compound different amides 5a-q and amino esters 6a-c are obtained. From 2-amino-3-cyanoquinoxaline 1,4-dioxide 7 , new amidines 9 , [5,4-b]pyrimido 10 and [6,5-b]diazepinoquinoxalines 11 were prepared.     

Synthesis of 2-N-(benzo[b]thiophen-2-yl)benzo and heterofused-1,2,3-triazoles

A novel efficient synthesis of 2-N-(benzo[b]thiophen-2-yl)benzo and heterofused-1,2,3-triazoles was achieved by the diazotisation of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile and ethyl-2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate and coupling with selected aromatic and heterocyclic amines followed by air oxidation in the presence of cupric acetate.     

Synthesis and biological activity of 1,5-dihydropyridazino-[3,4-b]quinoxalines and a new class of quinolones

A new class of quinolones, 1,4-dihydro-4-oxopyridazino[3,4-b]quinoxaline-3-carboxylic acids and related compounds, were synthesized via oxidation of 1,5-dihydropyridazino[3,4-b]quinoxalines obtained from 2-hydrazinoquinoxaline 4-oxides. Some of the 1,5-dihydropyridazino[3,4-b]quinoxalines, 1,4-dihydro-4-oxopyridazino[3,4-b]quinoxaline-3-carboxylic acids, and related compounds showed biological activity.     

Mono- and diadducts and bicyclic adducts in reactions of 2,3-dicyano-1-ethylpyrazinium cation with C- and O-nucleophiles

Products of diaddition of O- and C-nucleophiles to the 2,3-dicyano-1-ethylpyrazinium cation were isolated for the first time. The tandem A_N—A_N reactions of 2,3-dicyano-1-ethylpyrazinium tetrafluoroborate with 1,3-diketone enolates or keto esters afforded tetrahydrofuro[2,3-b]pyrazine derivatives, whereas cyclization with ethylene glycol gave tetrahydro-1,4-dioxino[2,3-b]pyrazine. Crystallographic data on the three-dimensional structures of these compounds were reported.     

Synthesis and application of ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate

Synthesis of ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate was achieved by diazotization of ethyl 2-amino-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate and coupling with selected N,N-dialkylanilines. The key intermediate ethyl 2-amino-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate was synthesized by the condensation of sodium salt of ethyl cyanoacetate with 2,3-dichloro-1,4-naphthoquinone. Ethyl 2-arylazo-4,9-dioxonaphtho[2,3-b]thiophene-3-carboxylate were applied on polyester fibers as disperse dyes and their dyeing properties were studied.     

Synthesis and Antimicrobial Activity of Novel Furothienoquinoxalines,Pyranothienoquinoxalines and Pyrimidopyranothienoquinoxalines

The reaction of ethyl‐3‐mercaptoquinoxaline‐2‐carboxylate with phenacyl bromide, ethyl chloroacetate, chloroacetonitrile or chloroacetone furnished the corresponding 3‐hydroxy thieno[2,3‐b]quinoxaline. 2‐Cyano‐3‐hydroxythieno[2,3‐b]quinoxaline and 2‐acetyl‐3‐hydroxythieno[2,3‐b]quinoxa line were employed as precursors in the synthesis of some novel furo[2′,3′:4,5]thieno[2,3‐b]quinoxaline, pyrano[2′,3′:4,5]thieno[2,3‐b]quinoxaline and other heterocyclic systems fused with thieno[2,3‐b]quinoxalines. The antibacterial and antifungal activities of some the synthesised compounds were studied.     

Acyl Indoles. III. The synthesis of [1,4] diazcpino [6,5-b ] indoles

The synthesis of 1,3,4,6-letrahydro-6-metliy]-2H,5H-[1,4]diazepino[6,5-b] indole-2,5-diones and 5-phenyl-3,6-dihydro[1,4]diazepino[6,5-b ]indole-2(lH)one is described. Also detailed is the, preparation of a 3-amino-2-benzoylindole.     

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 and properties of [1,4]diazepino[6,5-b]indoles

1-Aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxides were synthesized based on 3-(N"-aryl-N"-chloroacetyl)amino-2-formylindoles. Deoxidation of 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxide afforded 1,2,3,6-tetrahydro- and 1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole derivatives. A new approach to the synthesis of pyrido[3,2-b]indole and pyrimido[5,4-b]indole derivatives was developed.     

On the reduction of 1-aryl-2-oxo-1,2,3,6-tetra-hydro[1,4]diazepino[6,5-<Emphasis Type="Italic">b</Emphasis>]indole 4-oxides

Electrochemical reduction of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides, 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole, and 2-oxo-1-phenyl-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole was studied. The results obtained were compared with previous data for the reduction of 4-oxides with formamidinesulfinic acid.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2715–2718, December, 2004.     

Reduction of indolo[2,3-b]quinoxalines

Reduction of indolo[2,3-b]quinoxalines with zinc in the presence of an anhydride gave N,N-diacyl trapped 6,11-dihydroindolo[2,3-b]quinoxalines in 43-92% yields. When the reduction with zinc was performed in TFA/TFAA, an unexpected ring opened product was isolated in 49% yield. The structure of this product could be identified as 1,2-dihydro-1-trifluoroacetyl-3-[(2-trifluoroacetylamino)phenyl]quinoxaline.     

Synthesis and Transformations of 3-Ethoxycarbonyl-2-(N-R-thioureido)thiophenes

3-Ethoxycarbonyl-2-(N-R-thioureido)-4,5,6,7-tetrahydrobenzo[b]thiophenes were obtained by the reaction of 2-amino-3-ethoxycarbonyl-4,5,6,7-tetrahydrobenzo[b]thiophene with isothiocyanates and of 3-ethoxycarbonyl-2-isothiocyanato-4,5,6,7-tetrahydrobenzo[b]thiophene with primary and secondary amines. The cyclization paths of the products leading to derivatives of thieno[2,3-d]pyrimidine and thieno[2,3-d]-1,3-thiazine were studied. The corresponding S-substituted derivatives were obtained by the alkylation of 3-R-2-thioxo-3,4,5,6,7,8-hexahydrobenzo[b]thieno[2,3-d]pyrimidin-4-ones.     

13C-NMR study of 4H-1,3,4-thiadiazino[5,6-b]quinoxalines. A proof for the N5-deuteration in deuteriotrifluoroacetic acid

The carbon signals of the 2-acylamino-4H-1,3,4-thiadiazino[5,6-b]quinoxalines 1a,b , 2-acylamino-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 1,1-dioxides 2a,b , and 2-amino-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 3 in deuteriodimethyl sulfoxide and in deuteriotrifluoroacetic acid were assigned by the nmr (HMBC, HMQC) spectroscopy. The comparison of the carbon chemical shifts in deuteriodimethyl sulfoxide with those in deuteriotrifluoroacetic acid clarified that compounds 1a, 1b , and 3 were deuterized at the N₅-position in deuteriotrifluoroacetic acid, while the 1,1-dioxides 2a,b did not undergo the N₅-deuteration in deuteriotrifluoroacetic acid.