The chemistry of 1,2,5-thiadiazoles V. Synthesis of 3,4-diamino-1,2,5-thiadiazole and [1,2,5] thiadiazolo[3,4-b]pyrazines

The o-diamine, 3,4-diamino-1,2,5-thiadiazole ( 2 ), was synthesized from 3,4-dichloro-1,2,5-thiadiazole ( 3 ) hy three methods. Aqueous glyoxal cyclized 2 into [1,2,5]thiadiazolo[3,4–6]-pyrazine ( 14 ). 3,4-Dichloro-1,2,5-thiadiazole 1,1-dioxide ( 18 ) reaeted with 2 to give 1,3-dihydro-bis[1,2,5]thiadiazolo[3,4-b:3′,4′-e]pyrazine 2,2-dioxide ( 19 ). The reaction of 2 with selenium oxyehloride led to [1,2,5]selenadiazolo[3,4-c] [1,2,5]thiadiazole ( 12 ). Ring closure of 2,3-diaminoquinoxaline ( 4 ) with thionyl chloride or selenium oxychloride gave [1,2,5]thiadiazolo-[3,4-b]quinoxaline ( 21 ) and [1,2,5]selenadiazolo[3,4-b]quinoxaline ( 22 ), respectively. Sulfurous acid reduced 21 to the 4,9-dihydro derivative 23 , which was reoxidized to 21 with chloranil. Aqueous hase hydrolyzed 21 to 4 via the hydrated intermediate 24 . Aqueous glyoxal cyclized 4 to the covalent hydrate of pyrazino[2,3-b]quinoxaline ( 26 ), 27 , which was dehydrated to 26 . Compound 26 underwent rapid addition of two alcohols in a process analogous to covalent hydration.     

Synthesis of [1,2,5]selena(or thia)diazolo[3,4‐e][1,4]diazepines, [1,2,5]selena(or thia)diazolo[3,4‐e][1,4]oxazepines and [1,2,5]selena(or thia)diazolo[3,4‐c] [1,2,6]thiadiazines

Novel heterocycles [1,2,5]selenadiazolo[3,4‐e][1,4]diazepines 3a‐c , [1,2,5]thiadiazolo[3,4‐e]‐[1,4]diazepines 7a‐c , [1,2,5]selenadiazolo[3,4‐e][1,4]oxaepines 4a,b , [1,2,5]thiadiazolo[3,4‐e]‐[1,4]oxazepines 9a‐c and [1,2,5]selena(or thia)diazolo[3,4‐c][1,2,6]thiadiazines 10a,b were synthesized starting form 4,6‐dimethyl[1,2,5]se]enadiazolo[3,4‐d]pyrimidine‐5,7(4H,6H)‐dione 1 or 4,6‐dimethyl‐[1,2,5]thiadiazolo[3,4‐d]pyrimidine‐5,7(4H,6H)‐dione 5 .     

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.     

Generation of oxodiazonium ions 1. Synthesis of [1,2,5]oxadiazolo[3,4-c]cinnoline 5-oxides

Methods for the synthesis of [1,2,5]oxadiazolo[3,4-c]cinnoline 5-oxides, which include the reaction of 3-nitramino-4-(R-phenyl)furazans or their O-methyl derivatives with electrophilic agents, have been developed. Unsubstituted [1,2,5]oxadiazolo[3,4-c]cinnoline 5-oxide was synthesized from 3-nitramino-4-phenylfurazan upon the action of phosphorus anhydride or oleum, as well as from O-methyl derivative of 3-nitramino-4-phenylfurazan upon the action of H₂SO₄, MeSO₃H, CF₃CO₂H and BF₃·Et₂O, while 6-, 7-, 8-, and 9-nitro-substituted [1,2,5]oxadiazolo[3,4-c]cinnoline 5-oxides — from the corresponding 3-nitramino-4-(nitrophenyl)furazans upon the action of the H₂SO₄-HNO₃ nitrating mixture. A suggestion has been made that an oxodiazonium ion is formed in these reactions from nitramines or their O-methyl derivatives upon the action of electrophilic agents, which is further involved into the intra-molecular reaction of electrophilic aromatic substitution (S _EAr) with the aryl group. The structure of [1,2,5]oxadiazolo[3,4-c]cinnoline 5-N-oxides was confirmed by ¹H, ¹³C, and ¹⁴N NMR spectra. Theoretical studies by the B3LYP/6-311G(d,p) method of combined molecular system (O-methylated 3-nitramino-4-phenylfurazan + [H₃SO₄]⁺) resulted in calculation of thermodynamic parameters of the sequence of cascade elementary reactions leading to the formation of [1,2,5]oxadiazolo[3,4-c]cinnoline 5-oxide.     

Reduction of 4,7-diphenyl-1,2,5-thia(oxa)diazolo[3,4-c]pyridines affording 2,5-diphenyl-3,4-diaminopyridines and ring closure of the diamines to fluorescent azaheterocycles

Reduction of 4,7-diphenyl-1,2,5-thia- ( 1a-i ) and 1,2,5-oxadiazolo[3,4-c]pyridines ( 3a and c-e ) gave 3,4-diamino-2,5-diphenylpyridines ( 2a-g ), which were converted into the fluorescent triazolo[4,5-c]-( 5 ), 1,2,5-selenadiazolo[3,4-c]- ( 6 ), imidazolo[4,5-c]pyridines ( 8 ), and pyrido[5,6-c]pyridines ( 11 ). In the reduction of 3a, c and e , 4,5-dihydro[1,2,5]oxadiazolo[3,4-c]pyridines ( 4a-c ) were obtained.     

New D–A–D luminophores of the [1,2,5]thiadiazolo[3,4-d]pyridazine series

Three [1,2,5]thiadiazolo[3,4-d]pyridazines containing 4,7-positioned indole-type substituents were synthesized from the corresponding 4,7-dibromo precursor employing the SNAr aromatic nucleophilic substitution. Photophysical properties and DFT calculations showed that the D–A–D dyes based on [1,2,5]thiadiazolo[3,4-d]pyridazine core exhibited fluorescence in the near infrared region of the spectrum, which makes them promising for use as an active emitting layer in NIR-OLEDs as well as for other possible applications as an IR luminophore.     

The chemistry of 1,2,5-thiadiazoles,IV. Benzo[1,2-c:3,4-c′:5,6-c″] tris [1,2,5] thiadiazole

Benzo [1,2-c:3,4-c′:5,6-c″] tris [1,2,5] thiadiazole (1) was synthesized from benzo [1,2-c:3,4-c′] - bis [1,2,5] thiadiazole (11) . Nitration of 11 gave compound 15 , which on direct amination gave nitroamine 17 . Reduction of 17 gave diamine 18 , and cyclization of 18 with thionyl chloride gave 1 . Diamine 18 was also cyclized with selenium oxychloride, glyoxal, 9,10-phenanthrene-quinone, and formic acid to give the compounds 4, 5, 19 , and 6 , respectively. A new procedure for the preparation of 2,1,3-benzothiadiazole (7) from o-phenylenediamine was used.     

Electron ionization mass spectra and crystal structures of some [1,2,4]triazolo[1,2-b]- and [1,3,4]thiadiazolo[3,4-b]phthalazines

The mass spectra of ten 1,3-dithioxo[1,2,4]triazolo[1,2,-b]phthalazines, five 3-iminosubstituted 1-thioxo-[1,3,4]thiadiazolo[3,4-b]phthalazines, three 3-iminosubstituted-1-thioxo[1,2,4]triazolo[1,2-b]phthalazines, and 1,3-dithioxo-5,10-dihydro[1,3,4]thiadiazolo[3,4-b]phthalazine were recorded under electron ionization. The fragmentation pathways were elucidated by metastable ion analysis and exact mass measurements. The changes in the ring-system had little effect on the fragmentation mechanism, but the effect on peak intensities was considerable. The most important fragmentations began with the opening of the triazole ring. Substituents at nitrogen atoms also had a marked effect on the mass spectral behavior. The aryl substituents prompted a whole new fragmentation. The X-ray crystal structure was determined for a few compounds. Two of the three structures of the 1,3-dithioxo[1,2,4]triazolo[1,2-b]phthalazines that were studied proved to be relatively planar, whereas the structure of 1,3-dithioxo-5,10-dihydro[1,3,4]thiadiazolo[3,4-b]phthalazine was considerably bent similarly to the 2-(4-chlorophenyl)-1,3-dithioxo-2,3,5,10-tetrahydro[1,2,4]triazolo[1,2-b]-phthalazine. The triazole and the thiadiazole rings had a strong double bond nature.     

Synthesis of 1H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazines, 8H-pyrazolo[3,4-e]tetrazolo[5,1-c]-as-triazine and 1,7-dihydro-8H-pyrazolo[3,4-e]-as-triazine derivatives

3-Hydrazino-7-methyl-5-phenyl-5H-pyrazolo[3,4-c]-as-triazine 1 underwent ring closure and/or condensation reaction with formic acid, acetic acid, acetic anhydride and benzoyl chloride to afford 1H-pyrazolo-[3,4-d]-s-triazolo[3,4-c]-as-triazines 2, 5 and 7a and/or N-acyl derivatives 3, 4 and 6 . N-Acyl derivatives 3 and 6 underwent cyclisation reaction on treatment with phosphoryl chloride to give 5 and 7a . 3-Methyl-1-phenyl-8-aryl-1H-pyrazolo[3,4-e]-s-triazolo[34,-c]-as-triazines 7 were also prepared by the reaction of the hydrazono derivatives 8 wit thionyl chloride. On treatment of 1 with nitrous acid gave the 8H-pyrazolo[3,4-e]tetrazolo-[5,1-c]-as-triazine 9 . Compound 1 underwent ring closure with carbon disulphide or ethyl chloroformate to 1,7-dihydro-8H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazine derivatives 10 and 12 . Reaction of 1 with ethyl acetoacetate or acetylacetone gave 3-pyrazolo derivatives 13 and 14 .     

Microwave-assisted synthesis of 1,3-dihydro-[1,2,5]thiadiazolo[3,4-b]pyrazine-2,2-dioxides

1,3-Dihydro[1,2,5]thiadiazolo[3,4-b]pyrazine-2,2-dioxides are obtained in a good yield from the reaction of 2,3-diamino pyrazines with sulfamide under microwave conditions.     

Condensation reaction of 3,4-dibenzoyl-1-methyl-2,5-diphenylpyrrole and -1-phenylpyrazole with methylamine derivatives affording pyrrolo [3,4-c]pyridine and 2H-pyrazolo[3,4-c]- and [4,3-c]pyridines

The reaction of 3,4-dibenzoyl-1-methyl-2,5-diphenylpyrrole ( 1 ) and -1-phenylpyrazole ( 2 ) with methylamines ( 3a-c ) afforded pyrrolo[3,4-c]pyridine ( 4 ), and isomeric 2H-pyrazolo[3,4-c]pyridines ( 5a-c ) and [4,3-c]pyridines ( 6a-c ), respectively.     

Syntheses and properties of 4,6-dimelhyl[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7(4H,6H)dione 1-oxide

New convenient syntheses of 4,6-dimethyl[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7(4H,6H)-dione 1-oxide (I) from 1,3-dimethyl-6-hydroxylaminouracil by means of nitrosative and nitrative cyclizations are described. Compound I was converted into 4,6-dimethyl[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7(4H,6H)dione [4,6-dimethyl-5,7(4H,6H)furazano[3,4-d]pyrimidinedione] by refluxing in dimethylformamide. Transformation of I to 1,3,7,9-tetramethyl-2,4,6,8(1H,3H,7H,9H)pyrimido[5,4-g]pteridinetetrone and/or 1,3,6,8-tetramethyl-2,4,7,9(1H,3H,6H,8H)pyrimido[4,5-g]pteridinetetrone is described.     

Synthesis of 1H-thieno[3,4-c]pyrazoles,thieno[3,4-b]furans,selenolo[3,4-b]furans and pyrrolo[3,4-d]thiazoles

Starting from the readily available aryl 2-methyl-5-phenyl-3-furyl ketones, 5-methyl-1H-1-phenylpyrazole-4-yl ketones and 4-methyl-2-phenyl-5-thiazolylcarboxaldehyde, a series of 2-phenyl-4-arylthieno[3,4-b]-furan, 2-phenyl-4-(p-methoxyphenyl)selenolo[3,4-b]furan, 4-aryl-1H-1-phenylthieno[3,4-c]pyrazole and 5-benzyl-2-phenylpyrrolo[3,4-d]thiazole were prepared in high yield.     

A Re‐Examination of the Reaction of 3,4‐Diamino[1,2,5]oxadiazole with Glyoxal

Reaction coordinate mapping was used to study the reaction of 3,4‐diamino[1,2,5]oxadiazole (3,4‐diaminofurazan) and 3,4‐diamino[1,2,5]thiadiazole with glyoxal. The thiadiazole was known to give a good yield of [1,2,5]thiadiazolo[3,4‐b]pyrazine, whereas the oxadiazole had not yielded, until now, [1,2,5]oxadiazolo[3,4‐b]pyrazine (or furazano[2,3‐b]pyrazine). The calculations suggested that the diols, 5,6‐dihydroxy‐4,5,6,7‐tetrahydro[1,2,5]oxadiazolo[3,4‐b]pyrazine and 5,6‐dihydroxy‐4,5,6,7‐tetrahydro[1,2,5]thiadiazolo[3,4‐b]pyrazine should be stable intermediates, and once formed, should provide a pathway to the target compounds via two dehydration steps, under forcing conditions. With this information in mind, the reactions of 3,4‐diamino[1,2,5]oxadiazole with glyoxal and pyruvic aldehyde were re‐examined. The reaction of 3,4‐diamino[1,2,5]oxadiazole with glyoxal and pyruvic aldehyde produced, under slightly basic conditions, a near quantitative yield of the expected initial products, 5,6‐dihydroxy‐4,5,6,7‐tetrahydro[1,2,5]oxadiazolo[3,4‐b]pyrazine and the 5‐methyl analog, respectively. The diols were easily isolated by lyophilizing the aqueous reaction mixture. The diols were pyrolized on silica gel at 160°C to give the desired [1,2,5]oxadiazolo[3,4‐b]pyrazine and the 5‐methyl analog. Both compounds were easily reduced to the corresponding 4,5,6,7‐tetrahydro‐derivative using sodium borohydride in THF/methanol. The [1,2,5]oxadiazolo[3,4‐b]pyrazine also displayed other interesting chemistry.     

Synthesis and carbon-13 NMR study of 2-benzyl, 2-methyl, 2-aryloctahydropyrrolo [3,4-c] pyrroles and the 1,2,3,5-tetrahydropyrrolo [3,4-c] pyrrole ring system

2-Benzyl, 2-phenyl, 2- (3-methoxyphenyl) and 2-(3-trifluoromethylphenyl) octahydropyrrolo[3,4-c]pyrrole ( 9a, 9b, 9c , and 9d , respectively) were prepared in five steps from 1-benzylpyrrole-3,4-dicarboxylic acid ( 2 ). 2-Methyloctahydropyrrolo [3,4-c]pyrrole ( 9′a ) was prepared analogously in six steps from 1-methylpyrrole-3,4-dicarboxylic acid ( 3 ). Diborane reduction of 1-benzyl-N-methyl-1H-pyrrole-3,4-dicarboximide ( 7′a ) and 1, N-dibenzyl-1H-pyrrole-3,4-dicarboximide ( 7a ) gave 5-benzyl-2-methyl and 2, 5-dibenzyl-1,2,3,5-tetrahydropyrrolo [3,4-c]pyrrole ( 19 ′ and 19 , respectively); the first reported members of the 1,2,3,5-tetrahydropyrrolo[3,4-c]pyrrole ring system. A detailed study of the carbon-13 nmr shifts permitted a complete assignment for all compounds. Mono and disubstituted products produce a systematic effect on the shifts for the bicyclic ring systems which can be readily interpreted in terms of substituent chemical shifts. The effect of protonation at nitrogen is also shown to produce a series of well defined chemical shifts for the octahydropyrrolo [3,4-c] pyrrole ring system.     

Synthesis and alkylation of pyrazolo[3,4-c]isoquinolines and hexahydrocyclohepta[d]pyrazolo[3,4-b]pyridines

The condensation of 1-acyl-2-(morpholin-4-yl)cycloalkenes with 3-amino-1-phenyl-1H-pyrazol-5(4H)-ones gave the corresponding 2,3,6,7,8,9-hexahydropyrazolo[3,4-c]isoquinoline and 3,6,7,8,9,10-hexahydrocyclohepta[ d]pyrazolo[3,4-b]pyridine derivatives. Alkylation of 2,3,6,7,8,9-hexahydropyrazolo[3,4-c]-isoquinolines with alkyl halides occurred at the nitrogen atom in the 3-position. The structure of 7-methyl-2,5-diphenyl-2,3,6,7,8,9-hexahydro-1H-pyrazolo[3,4-c]isoquinolin-1-one was proved by X-ray analysis.     

Reactions of 4,7-dibromo[1,2,5]thiadiazolo[3,4-d]pyridazine with alcohols

Russian Chemical Bulletin - The reaction of 4,7-dibromo[1,2,5]thiadiazolo[3,4-d]pyridazine with alcohols and sodium alkoxides was evaluated under various conditions. Depending on the reaction...     

1,4-Cyeloaddition reactions. IV. preparation of Cyclopenta[g]furo[3,2-c]quinolines,Cyclopenta- [f]furo[3,2-c]quinolines,Benzo[H]furo[3,2-c]quinolines,and Furo- [3,2-c]indeno[1,7-gh] quinolines from 2,3-Dihydro-5-methylfuran and schiff bases

The boron trifluoride catalyzed 1,4-addition of 2,3-dihydro-5-methylfuran to N-(p-methoxybenzylidene)-5-indanamine (VI) gave 2 pairs of epimers, dl-3,3a,4,5,7,8,9,10b-octahydro-4-(p-methoxyphenyl)-10b-methyl-2H-cyclopenta[g]furo[3,2-c]quinoline (VIIa and b) and dl-3,3a, 4,-5,8,9,10,10c-octahydro-4-(p-methoxyphenyl)-10c-methyl-2H-cyclopenta[f]furo[3,2-c]quinoline (VIIIa and b). When 4-(benzylideneamino)-1-naphthol (IXa) was condensed with 2,3-dihydro-5-methylfuran in an analogous manner, a mixture of two isomers of dl-1,2,2a,3,4,5a-hexahydro-5a-methyl-2-phenylbenzo[h]furo[3,2-c]quinolin-7-ol [Xa and b (R ? H)] was obtained. Likewise, 4-[(p-hydroxybenzylidene)amino]-1-naphthol (IXb) and 4-(p-methoxybenzylidene)amino]-1-naphthol (IXc) gave a mixture of two isomers of dl-1,2,2a,3,4,5a-hexahydro-2-(p-hydroxyphenyl)-5a-methylbenzo[h]furo[3,2-c]quinolin-7-ol [Xa and b (R ? OH)] and dl-1,2,2a,3,4,5a-hexahydro-2-(p-methoxyphenyl)-5a-methylbenzo [h]furo[3,2-c]quinolin-7-ol [Xa and b (R ? OCH₃)], respectively. The condensation of N-(p-methoxybenzylidene)-5-acenaphthenamine (XI) with 2,3-dihydro-5-methylfuran afforded a mixture of two isomers of dl-2,3,3a,4,5,9,10,-11b-octahydro-4-(p-methoxyphenyl)-11b-methylfuro[3,2-c]indeno[1,7-gh]quinoline (XIIa and b). Structural assignments for all of the products were made from NMR spectra. None of these compounds possessed appreciable biological activity.     

1,2,5]Thiadiazolo[3,4-c][1,2,5]thiadiazolidyl: a long-lived radical anion and its stable salts

[1,2,5]Thiadiazolo[3,4-c][1,2,5]thiadiazole (1) is synthesized in 62% yield by fluoride ion-induced condensation of 3,4-difluoro-1,2,5-thiadiazole with (Me(3)SiN=)(2)S. The reversible electrochemical reduction of 1 leads to the long-lived [1,2,5]thiadiazolo[3,4-c][1,2,5]thiadiazolidyl radical anion (2) and further to the dianion (3). The radical anion 2 is also obtained by the chemical reduction of the precursor 1 with t-BuOK in MeCN. The radical anion 2 is characterized by ESR spectroscopy in solution and in the crystalline state. The stable salts [K(18-crown-6)][2] and [K(18-crown-6)][2].MeCN (8 and 9, respectively) are isolated from the spontaneous decomposition of the [K(18-crown-6)][PhXNSN] (6, X = S; 7, X = Se) salts in MeCN solution followed by XRD characterization. The radical anion 2 acts as a bridging ligand in 8 and as chelating ligand in 9. The structural changes observed by XRD in going from 1 to 2 are explained by means of DFT/(U)B3LYP/6-311+G calculations.     

Facile synthesis of 6-hetaryl[1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazoles and 7-hetaryl[1,3,4]thiadiazolo[2,3-<Emphasis Type="Italic">c</Emphasis>][1,2,4]triazines with fungicidal activity

Condensation of 4-amino-4H-1,2,4-triazole-3-thiol and 4-amino-6-methyl-3-sulfanyl-1,2,4-triazin-5(4H)-one with ethyl cyanoacetate gave ethyl [1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-ylacetate and ethyl 3-methyl-4-oxo-4H-[1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-7-ylacetate, respectively. Reactions of the condensation products with 1,3-diphenylprop-2-en-1-one, aromatic aldehydes, and carbon disulfide or N,N-dimethylformamide dimethyl acetal (followed by treatment with hydrazine hydrate) gave the corresponding 6-hetaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 7-hetaryl-3-methyl-4H-[1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-4-ones. Preliminary tests revealed fungicidal activity of the pyrazolyl-substituted derivatives. Published in Russian in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 12, pp. 1813–1818. The text was submitted by the authors in English.