A new method for the synthesis of 4H-1,3,4-thiadiazino[5,6-b]quinoxalines

The reaction of 6-chloro-2-[1-methyl-2-(Mmemylthiocarbamoyl)hydrazino]quinoxaline 4-oxide 5 with acetic anhydride or trifluoroacetic anhydride resulted in dehydrative cyclization to give 2-(N-acetyl)-memylamino-8-chloro-4-methyl-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 6 or 8-chloro-2-(N-trifluoroacetyl)methylamino-4-methyl-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 9 , respectively. The oxidation of compound 6 or 9 with 2-fold molar amount of m-chloroperbenzoic acid afforded the 4H-1,3,4-thiadiazino-[5,6-b]quinoxaline 1,1-dioxide 8 or 13 , respectively. The acetyl group of compound 6 was hardly hydrolyzed, but the trifluoroacetyl group of compound 9 was easily hydrolyzed to change into 8-chloro-4-methyl-2-memylamino-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 10 . The acylation of compound 10 with acetic anhydride, trifluoroacetic anhydride, phenyl isocyanate, and chloroacetyl chloride furnished the 2-(N-acetyl)methylamino 6 , 2-(N-trifluoroacetyl)methylamino 9 , 2-(1-methyl-3-phenylureido) 11 , and 2-(N-chloroacetyl)methylamino 12 derivatives, respectively.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 15. Isomerization of thiazolo[4,5-b]quinoxalines in the presence of acids

4-Alkyl-2-phenyl-3a,4,9,9a-tetrahydrothiazolo[4,5-b]quinoxalines undergo isomerization in chloroform in the presence of acids to the regioisomeric (with respect to them) 9-alkyl-substituted derivatives. Under the same conditions 2,4-dimethyl-3a,4-9,9a-tetrahydrothiazolo [4,5-b]quinoxaline undergoes isomerization to 4-methyl-1H-2,3,3a,4,9,9a-hexahydropyrrolo[2,3-b]quinoxaline-2-thione. It was demonstrated by means of deuterium labels that in both cases the isomerization proceeds through a step involving dissociation to a quinoxalinium cation and the corresponding thioamide.See [1] for Communication 14.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 396–403, March, 1985.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 10. Isomeric thiazolo[4,5-b]quinoxalines in reactions of N-methylquinoxalinium ions with dithiocarbamates

The cyclization of N-methylquinoxalinium iodide with ammonium salts of N-alkyl-dithiocarbamic acids in DMSO leads to 4-methyl-2,3,3a,4,9,9a-hexahydrothiazolo-[4,5-b]quinoxalines, whereas regioisomeric cycloadducts with a reversed orientation of the thiazole ring are formed in ethanol in the presence of diethylamine.See [1] for communication 9.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 680–685, May, 1984.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 24. Synthesis of condensed 1,2,4-triazino- and 1,2,4-oxadiazino[5,6-b]quinoxaline systems

Cyclization of quinoxalinium salts with amidoximes and amidhydrazones yields partially hydrogenated derivatives of new 1,2,4-oxadiazino- and 1,2,4-triazino[5,6-b]quinoxaline heterocyclic systems.For Communication 23, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1118–1121, August, 1987.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 11. Reactions of quinoxalinium salts with thioamides — Simple method for the synthesis of hydrogenated thiazolo[4,5-b]quinoxalines

Thioacetamides and thiobenzamides undergo cyclization with N-alkylquinoxalinium salts in the presence of bases to give 4-alkyl-3a,4,9,9a-tetrahydrothiazolo[4,5-b]quinoxalines.See [1] for communication 10.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 686–690, May, 1984.     

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.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 29. Synthesis of a novel 1,3,4-thiadiazolo-[2,3-a]quinoxalino[2,3-d]pyrrole heterocyclic system

1,4,4a,5,10,10a-Hexahydro-1,3,4-thiadiazino[5,6-b]quinoxalines react with acetylacetone and acetoacetate esters upon heating in ethanol to give derivatives of a novel heterocyclic system, hexahydro-1,3,4-thiadiazolo[2,3-a]quinoxalino[2,3-d]pyrrole.For Communication 28, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 697–702, May, 1990.     

Cyclization of azinium cations with bifunctional nucleophiles. 27. Actoacetamides in synthesis of derivatives of a new heterocyclic system of pyrrolo[3,2-E]-1,2,4-triazine

Conclusions A new approach to the synthesis of condensed pyrrolo-1,2,4-triazines was carried out, based on the nucleophilic diaddition of acetoacetoamides to 1,2,4-triazine derivatives.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1637–1644, July, 1989.     

A selective synthesis of 2-arylamino-4H-1,3,4-thiadiazino[5,6-b]-quinoxalines and mesoionic triazolo[4,3-a]quinoxaline

The reaction of the 6-chloro-2-(1-methyl-2-thiocarbamoylhydrazino)quinoxaline 4-oxides 3a-d with trifluoroacetic anhydride gave the 2-(N-aryl)trifluoroacetamido-8-chloro-4-methyl-4H-1,3,4-thiadiazino-[5,6-b]quinoxalines 7a-d , respectively, while the reflux of compounds 3a-c in N,N-dimethylformamide afforded the mesoionic triazolo[4,3-a]quinoxaline 4 . Hydrolysis of compounds 7a-d with triethylamine/water provided the 2-arylamino-8-chloro-4-methyl-4H-1,3,4-thiadiazino[5,6-b)]quinoxalines 8a-d , respectively.     

Synthesis of 4H-1,3,4-oxadiazino[5,6-b]quinoxalines from 2-substituted quinoxaline 4-oxides

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 8 with acetic anhydride resulted in the intramolecular cyclization to give 8-chloro-2,4-dimethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline 7a , while the reaction of compound 8 with acetic anhydride/pyridine or acetic anhydride/acetic acid afforded 3-(2,2-diacetyl-1-memymydrazmo)-7-chloro-2-oxo-1,2-dihydroquinoxaline 9 , effecting no intramolecular cyclization. The reaction of 2-(2-acetyl-1-methylhydrazino)-6-chloroquinoxaline 4-oxide 10a or 6-chloro-2-(1-methyl-2-trifluoroacetylhydrazino)quinoxaline 4-oxide 10b with phosphoryl chloride provided compound 7a or 8-chloro-4-memyl-2-trifluoromethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline 7b , respectively. The reaction of compound 7b with phosphorus pentasulfide gave 7-chloro-3-(1-methyl-2-trifluoroacetylhydrazino)-2-thioxo-1,2-dihydroquinoxaline 11 , whose dehydration with sulfuric acid in acetic acid afforded 8-chloro-4-methyl-2-trifluoromemyl-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 12 .     

Cyclization of N-alkylazinium cations with bisnucleophiles. 6. Cycloelimination of tetrahydro-endo-furo[2,3-b]quinoxalines leading to 2,3-disubstituted tetrahydroquinoxalines

The reaction of an N-methylquinoxalinium salt with a -diketone under thermodynamic-control conditions leads to 2,3-disubstituted tetrahydroquinoxaline via cycloelimination of the initially formed tetrahydro-endo-furo[2,3-b]quinoxaline.See [1] for communication 5.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1410–1416, October, 1982.     

A new tautomeric zwitterion form of 2-acylamino-4H-1,3,4-oxadiazino[5,6-b]quinoxalines in solution

The reaction of 2-acyiamino-8-chloro-4-methyl-4H-1,3,4-oxadiazino[5,6-b]quinoxalines 2a-d with methyl iodide/base gave the 8-chloro-4,10-dimethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxalin-10-ium-2-acylamidates 4a-d , respectively. Comparison of the nmr spectral data between compounds 2a-d and 4a-d in deuteriodimethyl sulfoxide or in deuteriotrifluoroacetic acid established that compounds 2a-d existed as the zwitterionic tautomers 2′a-d in solution.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 22. Crystal and molecular structure of tetrahydroquinoxaline condensed with the six-membered 1,3,4-thiadiazine ring

X-ray diffraction examination of 4-acetyl-10-methyl-2-phenyl-1,4,4a,5,10,10a-hexahydro-1,3,4-thiadiazino[5,6-b]quinoxaline has shown that the 4a-H and 10a-H hydrogens attached to the carbon atoms common to both heterocycles are cis-oriented, as in the annelation of five-membered heterocycles to the tetrahydropyrazine ring, but in this case the torsion angle H_(4a)C_(4a)C_(10a)H_(10a) is much greater, having a value of 60.For Communication 21, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 701–706, May, 1987.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 25. Oxidation of tetrahydroquinoxalines condensed with six-membered ring heterocycles

Reaction of six-membered ring heterocycle-annulated tetrahydroquinoxalines with potassium permanganate in acetone results in the formation of oxidation products containing a common system of conjugated double bonds.For Communication 24, see Ref. [1].Translated from Khimiya Geterotsklicheskikh Soedinenii, No. 9, pp. 1260–1263, September, 1987.     

Cyclizations of N-alkyl-substituted azinium cations with bifunctional nucleophiles. 28. Orientation of the nucleophile in the reaction of quinoxalinium salts with indan-1,3-dione

In reactions with quinoxalinium salts in alcoholic-base media indan-1,3-dione acts as a C nucleophile, adding at the 2 or 3 position of the heterocycle to give the corresponding ylidene derivatives; attack by the nucleophile at the C₍₃₎ atom (the position relative to the quaternary nitrogen atom) is preceded by addition of alcohol at the a position. Dissociative substitution at the C₍₂₎ atom in 2-alkoxy-3-(1,3-dioxoindan-2-ylidene)-1,2,3,4-tetrahydroquinoxalines by another nucleophile makes it possible to regard lyate complexes as probable intermediates in cyclizations of 1,4-diazinium salts with dinucleophiles.See [1] for Communication 27.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 667–674, May, 1990.     

N-oxides of imidazo[4,5-b]quinoxalines and imidazo[4,5-b]pyrazines

The N-oxides and N,N-dioxides of methyl derivatives of imidazo[4,5-b]quinoxaline and imidazo[4,5-b]pyrazine were synthesized. The higher reactivity of the 2-methyl group in the N-oxides of 2-methylimidazo[4,5-b]quinoxaline as compared with the corresponding unoxidized derivatives was demonstrated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1266–1270, September, 1972.     

Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 23. Electrochemical criteria for electrophilicity in 1,4-diazinium cations and their participation in cyclizations with acetoacetamide

The polarographic reduction potentials E_1/2 of the pyrazinium, quinoxalinium, benzoquinoxalinium, pyrido[2,3-b]pyrazinium, and pteridinium cations were determined. Annellation of a benzene ring increases the electrophilicity of the diazinium cations to a greater degree than the introduction of such electron acceptors as aza, aminocarbonyl, or methoxycarbonyl groups. The boundary between the active and inactive 1,4-diazinium salts was determined; cations with E_1/2 values more negative than –0.50 V do not form either stable covalent adducts or cyclic diadducts through annellation of the dinucleophiles to the pyrazine ring.For Communication 22, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1110–1117, August, 1987.     

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.     

The chemistry of furazano-[3,4-b]pyrazine. 7. Properties of 5,6-diamino- and 5,6-dihydrazino-furazano[3,4-b]pyrazine

The reactions of 5,6-diamino- and 5,6-dihydrazinofurazano[3,4-b][yrazine that produce polycyclic or highly reactive compounds are reviewed. The furazan ring has a deactivating effect on the amine functions of these compounds. Dedicated to Professor Henk van der Plas on his 70th birthday. For No. 6, see [1]. Latvian Institute of Organic Synthesis, Riga LV-1006 Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 564–573, April, 1999.