A convenient synthesis of new pyrido[3,2-e][1,4]diazepine-2,5-diones and pyrido[2,3-e][1,4]diazepine-2,5-diones

A convenient synthesis of a series of pyrido[3,2-e][1,4]-diazepine-2,5-diones 8 and pyrido[2,3-e][1,4]diazepine-2,5-diones 9, is reported using the condensation of α-amino acid methyl ester derivatives with 1H-pyrido[3,2-d][1,3]oxazine-2,4-dione and 1H-pyrido[2,3-d][1,3]oxazine-2,4-dione. Compounds 8 and 9 were also synthesized by peptide coupling of α-amino acid methyl ester derivatives with β-amino acids (2 or 3) followed by the cyclisation in tetrahydrofuran with sodium hydride (NaH).     

New application of heterocyclic diazonium salts. Synthesis of pyrazolo[3,4-d][1,2,3]triazin-4-ones and imidazo[4,5-d][1,2,3]triazin-4-ones

The pyrazolo[3,4-d][1,2,3]triazin-4-ones 3 and imidazo[4,5-d][1,2,3]triazin-4-ones 4 are analogs structurally related to purines that have showed a wide and significant variety of biological activity. These compounds were synthesized by one-pot diazotization of 5-amino-1H-pyrazole-4-carbonitriles 1 and 5-amino-1H-imidazole-4-carbonitriles 2, respectively.     

Synthesis and antimicrobial of some new substituted tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives using 1H-benzo[d][1,2,3]triazole as starting material

A series of tetrazolomethylbenzo[d][1,2,3]triazole derivatives (2–14) have been synthesized and evaluated as antimicrobial agents from 1H-benzo[d][1,2,3]triazole (1) as starting material. The reaction of benzotriazole 1 with chloroacetonitrile afforded 2-(1H-benzo[d][1,2,3]-triazol-1-yl)acetonitrile 2, which was reacted with sodium azide to give tetrazole derivative 3. Esterification of benzotriazole 1 with ethyl bromoacetate in the presence of anhydrous potassium carbonate afforded ester 4, which was treated with hydrazine hydrate to afford the corresponding hydrazide 5. Reaction of 3 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide afforded the nitro-glycoside derivative 6, which was deacetylated using methanolic ammonia to deprotected nitroglycoside 7. The hydrazide 5 was reacted with 4,5,6,7-tetrachlorophthalic anhydride or 1,2,4,5-benzenetetracarboxylic dianhydride in refluxing glacial acetic acid to give the corresponding imides 8 and 9, respectively. Also, the hydrazide 5 was reacted with carbon disulphide in ethanol to give potassium salt 10, which was reacted with hydrazine hydrate to afford aminotriazole derivative 11. The latter compound was reacted with carbon disulphide to afford thiadiazole derivative 12, which was treated with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide to give the thioglycoside derivative 13. Deacetylation of the thioglycoside 13 using methanolic ammonia solution at room temperature afforded the deprotected thioglycoside 14. The antimicrobial screening of some synthesized compounds showed that many of these compounds have good antimicrobial activities comparable to streptomycin and fusidic acid as reference drugs.     

Synthesis of 6-hydrazino-3,4-dimethyl-1H-pyrazolo[3,4-d]pyrimidine and its application for the construction of a pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidine system

A new representative of heterocyclic hydrazines, viz., 6-hydrazino-3,4-dimethyl-1H-pyrazolo[3,4-d]pyrimidine (3) was synthesized from diacetyl ketene N,S-acetal. A condensation of hydrazine 3 with amide acetals or aldehydes and subsequent cyclization furnished pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidines, whose structure was confirmed by ¹H, ¹³C, and ¹H/¹⁵N HMBC NMR spectroscopy. Reactions of hydrazine 3 with acetylacetone, ethyl acetoacetate, diethyl malonate, and acetic anhydride were studied.     

Synthese von Thiazolo[3,2−a]thieno[2,3−d]pyrimidin-Derivaten

Derivatives of 5H-thiazolo[3.2?a]thieno[2.3?d]pyrimidine(A), 5H-[1]benzothieno[2.3?d]thiazolo[3.2?a]pyrimidine (B), 4H-thiazolo[3.2?a]thieno[3.2?e]pyrimidine (C) and 5H-[1]benzo-thieno[3.2?e]thiazolo[3.2?a]pyrimidine (D) were synthesized by various methods. Similar reactions are leading to derivatives of thieno[2′.3′∶4.5]pyrimido[2.1?b][1.3]thiazine (E) and [1]benzothieno[2′.3′∶4.5]pyrimido[2.1?b][1.3]thiazine (F).C, D, E, andF are new heterocyclic ring systems. Detailed papers will appear soon.     

Behavior of [1,2,5]oxadiazolo[3,4-<Emphasis Type="Italic">e</Emphasis>][1,2,3,4]tetrazine 4,6-dioxide in various media

A behavior of [1,2,5]oxadiazolo[3,4-e][1,2,3,4]tetrazine 4,6-dioxide (1) in organic solvents and aqueous solutions of various acidity has been studied by UV spectrophotometry. Kinetic laws for the N,N′-dioxide 1 hydrolysis have been established and decomposition process constants at various temperatures in the media with pH 6.86 have been determined. A product of the reaction with water, viz., 5H-[1,2,3]triazolo[4,5-c][1,2,5]oxadiazole, has been isolated. 5-(tert-Butyl)-5H-[1,2,3]triazolo[4,5-c][1,2,5]oxadiazole has been synthesized as the model compound. Decomposition of N,N′-dioxide 1 occurs in basic media. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1358–1363, July, 2008.     

Triazolo[4′,3′:4,5] [1,3,4]thiadiazolo[2,3-b]quinazolin-6-one

3-Methyl-6H-[1,2,4]triazolo[4′,3′: 4,5] [1,3,4]thiadiazolo[2,3-b]quinazolin-6-one (6) has been synthesized by the condensation of isatoic anhydride (1) with 4-amino-5-mercapto-3-methyl-[1,2,4]triazole (2) and final cyclisation of the intermediate3 with POCl₃ and PCl₃. Alternatively6 could also be synthesized by the condensation of 3-amino-2-mercapto-3H-quinazolin-4-one (7) withN-carbethoxy hydrazine in presence of hydrochloric acid and final cyclisation of the intermediate8 with acetic acid. The structures have been confirmed on the basis of IR, PMR and analytical results.     

Triazolopyridines. Part 24: New polynitrogenated potential helicating ligands

The synthesis of novel 7-{[1,2,3]triazolo[1,5-a]pyridin-3-yl}-[1,2,3]triazolo[1,5-a]pyridines 7, 2-pyridyl-[1,2,3]triazolo[1,5-a]pyrid-7-ylmethanols 11, 3-(6-substituted-2-pyridyl)-[1,2,3]triazolo[1,5-a]pyridines 12, and 7,7′-disubstituted-3,3′-[1,2,3]triazolo[1,5-a]pyridine 20, interesting polynitrogenated ligands as potential helicating compounds or luminescent sensors, from [1,2,3]triazolo[1,5-a]pyridines is described.     

Synthesis of novel 2-phenoxybenzo[<Emphasis Type="Italic">g</Emphasis>][1,2,4]triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]quinazoline and its derivatives starting with diphenyl-<Emphasis Type="Italic">N</Emphasis>-cyanoimidocarbonate

Cyclocondensation reaction of 3-hydrazinyl-2-naphthoic acid with diphenyl-N-cyanoimidocarbonate furnished the target 2-phenoxy-benzo[g][1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one (1) in high yield. Alkylation, thionation and chlorination of the lactam group in the compound 1 produced a variety of derivatives 2–17. Their structures were characterized by NMR and HREI-MS analyses.     

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.     

Imidazo- und Diazino-Anellierungen an das [1]Benzothieno[2,3—d]pyrimidin-System

Derivatives of the following six ring systems were synthesized:

1. 3,10-Dihydro-[1]benzothieno[2,3-d]imidazo[1,5-a]-pyrimidine (I)
2. 6H-[1]Benzothieno[2,3-d]pyrazino[1,2-a]pyrimidine (II)
3. 1,5-Dihydro-[1]benzothieno[2,3-d]imidazo[1,2-a]-pyrimidine (III)
4. 6H-[1]Benzothieno[2,3-d]pyrimido[1,2-a]pyrimidine (IV)
5. 1,5-Dihydro-imidazo[1,2-a]thieno[2,3-d]pyrimidine (V)
6. 4H-Pyrimido[1,2-a]thieno[2,3-d]pyrimidine (VI)

The first four types are new heterocyclic systems. 2-Aminomethyl-5,6,7,8-tetrahydro-[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (5), which was used as intermediate for typesI andII, was synthesized by various methods. TypesIII andIV were prepared from 2-methylthio-5,6,7,8-tetrahydro-[1]-benzothieno[2,3-d]pyrimidin-4(3H)-one via the corresponding 2-benzylamino derivatives, followed by ring closure.     

Synthese von Thieno-[2′,3′∶4,5]pyrimido[1,2—b][1,2]benzisothiazolderivaten

Cyclization of N-(3-carbamoyl-2-thienyl)-pseudosaccharinic amides gave derivatives of 4H-thieno[2′.3′∶4.5]pyrimido-[1.2-b][1.2]benzisothiazole (A) and 13H[1]benzothieno[2′.3′∶4.5]-pyrimido[1.2-b][1.2]benzisothiazole (B), two new heterocyclic ring systems.     

Synthesis of new condensed nitrogen heterocyclic systems

A cotarnine alkaloid-based synthesis was developed for new heptacyclic condensed diisoquinolines via the double intramolecular pseudosalt bis[1,3]dioxolo[4,5-g;4′,5′-g′][1,3,4]oxadiazolo[2,3-a;5,4-a′]diisoquinoline 6. Substitution of the central O atom in 6 by C, S, or N nucleophiles afforded the first representatives of the new ring systems bis[1,3]dioxolo[4,5-g:4,5-g′]pyrazolo[3,2-a:5,1-a′]diisoquinoline (7a-d), bis[1,3]dioxolo[4,5-g:4,5-g′][1,3,4]thiadiazolo[2,3-a:5,4-a′]diisoquinoline (8), and bis[1,3]dioxolo[4,5-g:4,5-g′][1,2,4]triazolo[3,2-a:5,1-a′]diisoquinoline (9a-d) under simple reaction conditions.     

Unexpected valence bond isomerization of [1,2,4]triazolo[3,4-c][1,2,4]benzotriazines under flash vacuum pyrolytic (fvp) conditions

Flash vacuum pyrolysis (fvp) of some substituted [1,2,4]triazolo[3,4-c][1,2,4]benzotriazine derivatives (1a-d) has been studied between 450 and 600 °C. The only transformation observed up to 525 °C was the unexpected valence bond isomerization of the angularly fused starting compounds to the isomeric linearly fused [1,2,4]triazolo[4,3-b][1,2,4]benzotriazine derivatives (9a-d), whereas at higher temperatures fragmentation products such as aromatic nitriles were also formed. Kinetic measurements revealed negative entropies of activation in the isomerization process, which suggest a concerted ring closure reaction to an intermediate antiaromatic diazirine. Reversibiblity of the title isomerization reaction was also proved by FVP experiments.     

A convenient synthesis of benzofuro[3,2-c]isoquinolines and naphtho[1′,2′:4,5]furo[3,2-c]isoquinolines

A convenient method for the preparation of benzofuro[3,2-c]isoquinoline derivatives is described. The condensation reaction of methyl 2-(chloromethyl)-benzoate with substituted salicylonitriles 7a-c and intramolecular cyclization of the resulting substituted methyl 2-[(2-cyanobenzyl)oxy]benzoates 10a-c using potassium tert-butoxide results in the substituted benzofuro[3,2-c]isoquinolin-5(6H)-ones 1a-c. The same sequence of reactions starting from 2-(chloromethyl)benzonitrile and compounds 7a-c gave substituted 5-aminobenzofuro[3,2-c]isoquinolines 13a-c. In addition, this method is useful for the synthesis of other heterocycles. For example, using 1-cyano-2-naphthol 16, instead of the salicylonitriles 7a-c, gives naphtho[1′,2′:4,5]furo[3,2-c]isoquinolines.     

Synthesis and reactivity of pyrrolo[3,2-d][1,3]oxazine-2,4-dione. Access to new pyrrolo[3,2-e][1,4]diazepine-2,5-diones

A convenient synthesis of pyrrolo[3,2-d][1,3]oxazine-2,4-dione 4 is described and its reactivity towards various nucleophiles studied. The regioselective ring opening of anhydride 4 or its N-alkylated analog 25 in the presence of alanine or proline afforded, respectively, imidazolidinedione 22 and N-protected pyrrolo[3,2-e][1,4]diazepines 30 and 31 in a one-pot process. In a last part of this study, an alternative route to produce a library of eight non protected pyrrolo[3,2-e][1,4]diazepine-2,5-diones 35a–h is described to overcome the limited reactivity of anhydride 4.     

Synthesis and structure of benzimidazo[1,2-c][1,2,3]thiadiazoles: first examples of a novel ring system

(1-Amino-1H-benzimidazol-2-yl)methanol 1 with thionyl chloride at reflux afforded 3-chlorobenzimidazo[1,2-c][1,2,3]thiadiazole 4, which reacted with various nucleophiles to give different products depending on the nature of the solvent. The structures of 4 and di(benzimidazo[1,2-c][1,2,3]thiadiazol-3-yl)sulfide 8 were confirmed by single-crystal X-ray analysis.     

Pyrazoles as building blocks in heterocyclic synthesis: Synthesis of pyrazolo [3,4-d]pyrimidine, pyrazolo[3,4-e][1,4]diazepine, pyrazolo [3,4-d][1,2,3]triazine and pyrolo [4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives

Several new pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-e][1,4]diazepine, pyrazolo[3,4-d][1,2,3]triazine and pyrolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives were prepared by the reaction of the corresponding 5-amino-pyrazole-4-carbonitrile derivative with different organic reagents under different reaction conditions. Using IR, ¹H NMR, and mass spectra we have characterized all new compounds.     

Methyl 3,3,3-trifluoro-2-(thiazol-2-ylimino)propionate in cycloaddition and cyclocondensation reactions

The behavior of methyl 3,3,3-trifluoro-2-(thiazol-2-ylimino)propionate (1) in cycloaddition and cyclocondensation reactions was studied. Cycloaddition of dimethylcyanamide to imine 1 gave a thiazolo[3,2-a][1,3,5]triazine derivative. Cyclocondensations of imine 1 with 2-aminothiazoline, N-cyclohexylbenzamidine, methyl (Z)-3-aminobut-2-enoate, and 6-amino-1-benzyluracil yielded dihydroimidazo[2,1-b]thiazol-5(6H)-one, 4,5-dihydroimidazol-5-one, 4,5-dihydro-1H-pyrrol-5-one, and dihydro-1H-pyrrolo[2,3-d]pyrimidine-2,4,6-trione derivatives, respectively.     

Synthesis of 1-hydroxybenzotriazoles angularly annulated by furazan or furoxan rings

Synthesis of 6-hydroxy-6H-[1,2,3]triazolo[4,5-e][2,1,3]benzoxadiazole and a mixture of isomeric 6-hydroxy-6H-[1,2,3]triazolo[4,5-e][2,1,3]benzoxadiazole-1(3)-oxides is carried out starting from 2,4-dinitrosoresorcinol. Total assignment of the signals in the ¹³C NMR spectra of O-methylated products of these compounds is performed.