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.     

Inhibitors of platelet aggregation. 4. [1,2,5]Thiadiazolo[3,4-c]acridines, 7,8,9,10-Tetrahydro[1,2,5] thiadiazolo[3,4-c]acridities,and 8,9-Dihydro-7H-cyclopenta[b][1,2,5] thiadiazolo[3,4-H]quinolines

The condensation of 4-amino-2,1,3-benzothiadiazole (IV) with diphenyliodonium-2-earboxylate gave N-(2,1,3-benzothiadiazoI-4-yl)anthranilic acid (V) (28%), which was cyclized with phosphorus oxychloride to 6-chloro[1,2,5]thiadiazolo[3,4-c]acridine (VI) (84%). Treatment of VI with 3-(dimethylamino)-1-propanethiol hydrochloride in phenol afforded 6-[ [3-(dimethylamino)-propyl]thio] [1,2,5]thiadiazolo[3,4-c]acridine (VII) (65%). The reaction of IV with a mixture of methyl and ethyl 2-oxocyclohexanecarboxylate gave the adduct, which was ring closed in Dowtherm to 7,9,10,1 1-tetrahydro[1,2,5] thiadiazolo[3,4-c]acridin-6(8H)one (VIII) (70%). Chlorination of VIII with phosphorus oxychloride gave 6-chloro-7,8,9,10-tetrahydro[1,2,5]thiadiazolo[3,4-c]acridine (IX) (84%), which was condensed with 3-(dimethylamino)-1-propanethiol hydrochloride in phenol yielding 6-[ [3-(dimethylamino)propyl]thio]-7,8,9,10-tetrahydrof 1,2,5]-thiadiazolo[3,4-c]acridine (X) (27%). 6-[ [3(1)imethylamino)propyl]thio]-8,9-dihydro-7H-cyclopenta[b] [1,2,5]thiadiazolo[3,4-h]quinoline (XIII) (25%) was prepared similarly from IV and a mixture of methyl and ethyl 2-oxocyclopentanecarboxylate via 7,8,9,10-tetrahydro-6H-cyclopenta[b][1,2,5]thiadiazolo[3,4-h]quinolin-6-one (XI) (85%) and 6-chloro-8,9-dihydro-7H-cyclopenta[b][1,2,5]thiadiazolof3,4-h]quinoline (XII) (56%). The effects of compounds VII-XIII as inhibitors of platelet aggregation are discussed.     

New syntheses of [1,2,5]oxadiazolo[3,4-e][1,2,3,4]tetrazine 4,6-dioxide

New methods were developed for the synthesis of [1,2,5]oxadiazolo[3,4-e][1,2,3,4]tetrazine 4,6-dioxide from 4-(tert-butyl-NNO-azoxy)-N-nitro-1,2,5-oxadiazol-3-amine or its alkali metal salts and acid anhydrides (or chlorides) in the presence of strong acids. The yield of [1,2,5]oxadiazolo[3,4-e][1,2,3,4]tetrazine 4,6-dioxide in acetic anhydride in the presence of sulfuric acid or sulfuric anhydride at 20°C in 20 min attained 83%. A general mechanism was proposed for the reactions under study. Acetyl group behaved for the first time as departing group in the synthesis 1,2,3,4-tetrazine 1,3-dioxides, and [1,2,5]oxadiazolo[3,4-e][1,2,3,4]tetrazine 4,6-dioxide was obtained in 47% yield from N-[4-(acetyl-NNO-azoxy)-1,2,5-oxadiazol-3-yl]acetamide.     

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 and structures of 5(3H)-oxotetrahydro-1H-imidazo[4,5-c][1,2,5]thiadiazole 2,2-dioxides

The reactions of sulfamides with 4,5-dihydroxyimidazolidin-2-ones were studied at ambient and high pressure. The previously unknown derivatives of 5(3H)-oxotetrahydro-1H-imidazo-[4,5-c][1,2,5]thiadiazole 2,2-dioxide, viz., sulfo analogs of tetrahydroimidazo[4,5-d]imidazole-2,5-(1H,3H) diones (glycolurils), were synthesized. The structures of some of these compounds were established by X-ray diffraction. The high-pressure reactions performed under conditions of solvent phase transitions afforded also N-(1,3-diethyl-5-hydroxy-2-oxoimidazolidin-4-yl)-N,N′-dialkylsulfamides. Among these compounds, a new conglomerate was found. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1711–1719, May, 2008.     

Generation of oxodiazonium ions 2. Synthesis of benzotetrazine-1,3-dioxides from 2-(tert-butyl-NNO-azoxy)-N-nitroanilines

A new method for the synthesis of benzotetrazine-1,3-dioxides was developed, which involves the reaction of 2-(tert-butyl-NNO-azoxy)-N-nitroanilines with the Ac₂O/H₂SO₄ system. This method was also used for the synthesis of [1,2,5]oxadiazolo[3,4-c]cinnoline-5-oxide from 3-nitramino-4-phenylfurazan. The suggested mechanism of these reactions involves the formation of the intermediate oxodiazonium ion, resulting from acetylation of the oxygen atom of the nitramine group, followed by protonation and ionic dissociation. Then the oxodiazonium ion enters the intramolecular reaction with the neighboring tert-butyl-NNO-azoxy or phenyl group to form the corresponding heterocyclic systems.     

Synthesis of thieno [3,4-c ]- and selenopheno[3,4-c] pyrylium salts

Acylation of 3-acetonyl- and 3-phenacyl-2,5-dimethylthiophenes with aliphatic acid anhydrides in the presence of perchloric acid gives thieno[3,4-c]pyrylium perchlorates. Reaction of the latter with ammonia gives the corresponding thieno[3,4-c]pyridines or diketones of the thiophene series. Selenopheno[3,4-c]pyrylium salts could not be isolated in the acylation of 3-acetonyl- and 3-phenacyl-2,5-dimethylselenophenes.     

Generation of oxodiazonium ions 4. Nitramine O-alkyl derivatives in the synthesis of benzotetrazine-1,3-dioxides

A new method for the synthesis of benzotetrazine-1,3-dioxides was developed from the 2-(tert-butyl-NNO-azoxy)-N-nitroaniline O-alkyl derivatives upon the action of strong acids (H₂SO₄, MeSO₃H, CF₃CO₂H) or BF₃·Et₂O. A mechanism suggested for these reactions includes transformation of the N=N(O)OR group (R = Me, Prⁱ) to the oxodiazonium ion (N=N=O)⁺, which intramolecularly reacts with the neighboring tert-butyl-NNO-azoxy group, furnishing the tetrazine-1,3-dioxide ring.     

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.     

A new derivative of 1,5-dihydropyrazolo[4,3-c][1,2,5]benzotriazepine

A new compound, 1,5-dihydro-3-methyl-7-nitro-propylpyrazolo[4,3-c][1,2,5]benzotriazepine, was synthesized by intramolecular cyclization of 5-amino-4-[(2-bromo-5-nitrophenyl) azo]-3-methyl-1-isopropylpyrazole, and it was established on the basis of the spectral data that the triazepine ring in the synthesized compound exists in two tautomeric forms — amino-azo- and hydrazone. The structure of the compound synthesized was confirmed by the data of the PMR, IR, electronic, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1136–1139, August, 1984.     

Synthesis of pyrrolo[3,4-c]pyridazines

We have prepared the pyrrolopyridazines 7a-f starting from the diazo compounds 4 . The synthesis involves a tandem condensation-aza-Wittig reaction or a combination of Wittig and aza-Wittig reactions as key steps. Reaction of pyridazine 7d with diazomethane results in C-methylation to yield 7g . Sodium borohydride reduces 7d to either the dihydropyridazine 12 or the hydroxylactam 13b depending of the reaction conditions.     

Synthesis, characterization and DNA-binding studies of ruthenium(II) mixed-ligand complexes containing dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline

A novel ligand dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline (dpoq) and its complexes [Ru(bpy)₂(dpoq)]²⁺ and [Ru(phen)₂(dpoq)]²⁺ (bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline) have been synthesized and characterized by elemental analysis, electrospray mass spectra and ¹H NMR. The interaction of Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption spectroscopy, fluorescence spectroscopy, thermal denaturation and viscosity measurements. Results suggest that two Ru(II) complexes bind to DNA via an intercalative mode.     

Synthesis and structure of 3-oxopyrano[3,4-c]pyridines

Acylation of the enamine of 2,2-dimethyltetrahydropyran-4-one with acid chlorides produced -acylpyran-4-ones which give 3-oxopyrano[3,4-c]pyridines when treated with cyanoacetamide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1137–1142, August, 1989.     

Properties of 4H-[1]benzopyrano[3,4-c]-[1,2,5]-selenodiazol-4-one

4H-[1]benzopyrano[3,4-c][1,2,5]selenodiazol-4-one has been synthesized by the reaction of 3,4-diaminocoumarin with selenous acid and its reaction with several nucleophiles (alkali, ammonia, amines, hydrazine hydrate) and its nitration have been studied. Using PMR spectroscopy, a comparative kinetic study of the opening of the lactone ring in 6,8-dinitro-4H-[1]benzopyrano[3,4-c][1,2,5]seleno- and thiadiazol-4-ones has been carried out.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 128–133, January, 1991.     

5-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物的合成新方法

以2,6-二氯吡啶为起始原料, 经肼基化、还原、硝化、Nietzki-Dietschy环合4步反应得到5-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物。 结合反应机理讨论了还原、硝化、Nietzki-Dietschy环合反应的影响因素,获得了合成5-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物的最佳工艺条件,目标产物的总收率为59.2%。 用1H NMR、MS和IR谱对5-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物的结构进行了表征。     

5-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物的新法合成

以2,6-二氯吡啶为起始原料,经肼基化、还原、硝化、Nietzki-Dietschy环合4步反应得到5-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物.结合反应机理讨论了还原、硝化、Nietzki-Dietschy环合反应的影响因素,获得了合成-.氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物的最佳工艺条件,目标产物的总收率为59.2%.用1H NMR、MS和IR谱对5-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物的结构进行了表征.     

Annulated benzotetrazine 1,3-dioxides 1. [1,2,5]Oxadiazolo[3,4-f][1,2,3,4]benzotetrazine 2,4,7-and 2,4,9-trioxides

Thermolysis of 6-azido-5-nitro-7-R-benzotetrazine 1,3-dioxides (R = H and Br) gave benzotetrazine 1,3-dioxides annulated with the furoxan ring at the C(5)-C(6) bond. According to the NMR data, these compounds at 297 K are equilibrium mixtures of two isomers with different positions of the N-oxide oxygen atom in the furoxan ring. Full assignment of signals in the ¹³C NMR spectra of the compounds obtained was accomplished. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 133–136, January, 2006.