Organoiodine(III) Mediated Synthesis of Novel Symmetrical Bis([1,2,4]triazolo)[3,4‐a:4′,3′‐c]phthalazines as Antibacterial and Antifungal Agents

A series of new symmetrical 3,6‐bis(aryl)bis([1,2,4]triazolo)[3,4‐a:4′,3′‐c]phthalazines 9a‐l has been conveniently synthesized by oxidative cyclization of 1,4‐bis(substituted benzalhydrazino)phthalazines 8a‐l promoted by iodobenzene diacetate under mild conditions (12 examples, up to 93% yield). All the 12 compounds were tested in vitro for their antibacterial activity against two Gram‐positive bacteria, namely, Staphylococcus aureus, Bacillus subtilis and two Gram‐negative bacteria, namely, Escherichia coli and Pseudomonas aeruginosa. All the synthesized compounds were also tested for their antifungal action against two fungi, Aspergillus niger and Aspergillus flavus.     

Synthesis of 4,8-disubstituted 4H,8H-bis[1,2,5]oxadiazolo[3,4–6:3′,4′-e]pyrazines

The dilithio anion of 3,4-N,N′-disubstituted diamino[1,2,5]oxadiazole ( 4a R = benzyl, 4b R = p-methoxybenzyl, 4c R = isopropyl) and cyanogen oxide gave 4,7-disubstituted 5,6-dioximino[1,2,5]oxadiazolo[3,4-b]-pyrazines 5a,b,c. Ring closure to the title compound 1 was accomplished upon heating 5 with sodium hydroxide in ethylene glycol at 150°.     

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.     

Direct bromination of dithieno[3,4-b:3′,4′-d]pyridine and dithieno[2,3-b:3′,2′-d]pyridine

Bromination of dithieno[3,4-b:3′,4′-d]pyridine ( 1 ) and dithieno[2,3-b:3′,2′-d]pyridine ( 2 ) has been studied. Disubstitution occurred at both positions of the C ring. The substitution pattern is found to be similar to that of the nitration reaction. The structures of bromo derivatives were established by ¹H and ¹³C nmr spectroscopy.     

Nitration of dithieno[3,4-b:3′,2′-d]pyridine and dithieno[2,3-b:3′,2′-d]pyridine

The nitration of dithieno[3,4-b:3′,2′-d]pyridine ( 2 ) and dithieno[2,3-b:3′,2′-d]pyridine ( 3 ) has been studied. Nitration of 2 occurred in both positions of the c-fused thiophene ring, while 3 was predominantly substituted in the 2-position. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Synthesis of new guanidine derivatives from 2′,3′,4′,9′-tetrahydrospiro[piperidine-4,1′-[1H]pyrido[3,4-b]indole]

The reaction of the isothiourea derivative 2 with methylaminc or pyrrolidine resulted in guanidines 3a-3b . Using hydrazine under the same conditions the tetrazole derivative 4 was obtained. On reacting 2 with piperidine, morpholine, methylhydrazine, phenylhydrazine, hydroxylamine or sodium hydroxide, cycliza-tion took place leading to the novel 4-cyanimino-1,2,3,4,6,7,12,12b-octahydro-3,12b-ethanopyrim-ido[1′,6′:1,2]pyrido[3,4-b]indole ( 5 ). Some structural aspects of 5 and other model compounds were analysed mainly by ¹³C nmr spectroscopy.     

Compounds in the pyrrolo[3′,4′:4,5] pyrrolo[3,4-b]indole series

Compounds in the new pyrrolo[3′,4′:4,5]pyrrolo[3,4-b]indole series have been produced by an imide cyclization of appropriate derivatives of pyrrolo[3,4-b]indole.     

On the syntheses of 1,3-disubstituted dithieno[3,4-b:3′,2′-d]pyridines via halogen-metal exchange of 1,3-dibromodithieno[3,4-b:3′,2′-d]pyridine

Halogen-metal exchange of 1,3-dibromodithieno[3,4-b:3′,2′-d]pyridine with butyllithium under different conditions has been studied. Upon reaction with iodine, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl carbonate, dimethyl disulfide and thiuram disulfide, the 1,3-diiodo-, 1,3-diacetyl-, 1,3-diformyl-, 1,3-dicarbomethoxy, 1,3-di(thiomethyl)- and 1,3-di(N,N-dimethyldithiocarbamoyl)dithieno[3,4-b:3′,2′-d]-pyridines, respectively, were obtained in varying yields. 3-Monosubstituted derivatives were obtained in some cases. The formation of 3,7-disubstituted derivatives was sometimes also observed.     

Nitration of dithieno[3,2-b:3′,2′-d]pyridine and dithieno[3,2-b:3′,4′-d]pyridine

Nitration of dithieno[3,2-b:3′,2′-d]pyridine ( 4 ) and dithieno[3,2-b:3′,4′-d]pyridine ( 5 ) has been studied. Nitration of 4 occurred in both positions of the C ring, while 5 was predominantly substituted on the 3,4-fused ring. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyrimido[4′,5′:4,5]theino[2,3-b]quinoline and pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyriraido[4′,5′:4,5]theino[2,3-b]quinoline and 12-phenylpyrido[1′,2′:1,2[pyrimido[4,5-b]quinoline are described.     

The stereochemistry of 1,6,7,12b-Tetrahydro-2H,4H-[1,2] oxazino[3′,4′:1,2]-pyrido[3,4-b]indole and of 1,2,3,6,7,12b-Hexahydro-3-methyl-4H-pyrimido[3′,4′:1,2]pyrido[3,4-6] indole

From an analysis of nmr spectral data, 1,6,7,12b-tetrahydro-2H,4H-[1,3 ]oxazino[3′, 4′ :1,2]-pyrido[ 3,4-b ]indole is shown to exist in solution at room temperature almost entirely in the cis-fused ring conformation with the nitrogen lone pair bisecting the C4 methylene group whereas under the same conditions 1,2,3,6,7,12b-hexahydro-3-methyl-4H-pyrimido[3′,4′:1,2] pyrido-[3,4-b ]indole exists as an approximately 50:50 equilibrium mixture of the cis and trans-fused ring conformations.     

Syntheses and spectral properties of 2,3,7,8-tetracyano-5,10-dihydrodipyrazino[2,3-b:2′,3′-e]pyrazine

Base catalized intermolecular cyclization of 2-amino-3-chloro-5,6-dicyanopyrazines gave 5,10-disubsti-tuted-2,3,7,8-tetracyano-5,10-dihydrodipyrazino[2,3-b:2′,3′-c]pyrazines 11–20. These compounds have rather small molecular size but have strong intramolecular charge-transfer chromophoric system. They have strong fluorescence in solution and some have fluorescence even in the solid state which are very important to evaluate their electroluminescence property as an emitter for electroluminescence devices. The physical, structural, and electronic properties of these new 2,3,7,8-tetracyano-5,10-dihy-drodipyrazino[2,3-b:2′3′-e]pyrazines were studied using uv-visible spectroscopy and the Pariser-Parr-Pople molecular orbital calculation method.