Some novel heterocyclic systems derived from 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-α]benzimidazole and the corresponding diamine

The preparation of 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-a]benzimidazole from 1,4-diacetamido-2,3-dinitrobenzene is described. Reaction of this compound with 2,5-dimethoxytetrahydrofuran produces 2,3-dihydro-8-nitro-7-N-pyrrolo-1H-pyrrolo[1,2-a]benzimidazole, which can be cyclised to produce two new heterocyclic ring systems, 9,10-dihydro-8H-pyrrolo[1,2-a]pyrrolo(1′,2′:1,2]imidazo[5,4-f]quinoxaline and 9,10-dihydro-8H-pyrrolo[2,1-c]pyrrolo[1′,2′:1,2]imidazo[4,5-h][1,2,4]benzotriazine. The corresponding diamine, 7,8-diamino-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazole undergoes a variety of condensation reactions to produce several new heterocyclic systems, for example, with formic acid, 1,7,8,9-tetrahydroimidazo-[4,5-e]pyrrolo[2,1-6]benzimidazole is formed and with diacetyl, 9,10-dihydro-2,3-dimethyl-8H-pyrrolo-[1′,2′:1,2]imidazo[5,4-y]quinoxaline is obtained.     

A new method of preparation of 1H-1,2-benzodiazepines by the rearrangement of 2,4,6-trichlorophenylhydrazones

A new method for preparing 1H-1,2-benzodiazepines is described. Hydrazones of generalised structure 1 undergo base catalysed cyclisation to form 4-imidazolyl-4,5-dihydro-1H-1,2-benzodiazepines of general structure 2 . These compounds readily eliminate imidazole to form 1H-1,2-benzodiazepines of general structure 3 .     

Synthesis of 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

The reaction of methyl 2-bromo-6-(trifluoromethyl)-3-pyridinecarboxylate ( 1 ) with methanesulfonamide gave methyl 2-[(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridine-carboxylate ( 2 ). Alkylation of compound 2 with methyl iodide followed by cyclization of the resulting methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate ( 3 ) yielded 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 4 ). The reaction of compound 4 with α,2,4-trichlorotoluene, methyl bromopropionate, methyl iodide, 3-trifluoromethylphenyl isocyanate, phenyl isocyanate and 2,4-dichloro-5-(2-propynyloxy)phenyl isothiocyanate gave, respectively, 4-[(2,4-dichlorophenyl)methoxy]-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazine 2,2-dioxide ( 5 ), methyl 2-[[1-methyl-2,2-dioxido-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4-yl]oxy]propanoate ( 6 ), 1,3,3-trimethyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 7 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 8 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-phenyl-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 9 ) and N-[2,4-dichloro-5-(2-propynyloxy)phenyl]-4-hydroxy-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2] thiazine-3-carboxamide 2,2-dioxide ( 10 ).     

Benzimidazole condensed ring systems. 2. New synthesis of substituted 1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitriles and related derivatives

The synthesis of some 3-substituted and 2,3-disubstituted-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbo-nitriles 5,6 by fusing 1H-benzimidazole-2-acetonitrile 1 with some β-keto esters 2,4 in the presence of ammonium acetate or with ethyl β-aminocrotonate 3 is described. The tricyclic compounds were converted to their N-5 methyl of N-5 ethyl derivatives 8,9. Vilsmeir-Haack formylation of 3-methyl-1-oxo-1H,5H-pyrido[1,2-a]-benzimidazole-4-carbonitrile 5a afforded its 2-formyl derivative 10. Chlorination of 5 and 6 with phosphorus oxychloride yielded the respective 1-chloropyrido[1,2-a]benzimidazole-4-carbonitriles 11,12 which were utilized to prepare the 1-azido, 1-amino, 1-piperidino and 1-methoxy derivatives of the ring system. Compound 11a exhibited strong in vitro activity against S. aureus. Four compounds were screened against P-388 lymphocytic leukemia in mice but were inactive.     

The synthesis of 1H-benzimidazole derivatives containing a 9H-xanthene or 9H-thioxanthene ring

2-(9H-Xanthen-9-ylmethyl)-1H-benzimidazole ( 2a ) was prepared by condensing 9H-xanthene-9-acetic acid ( 1a ) with 1,2-benzenediamine. Similarly, 2-(9H-thioxanthen-9-ylmethyl)-1H-benzimidazole ( 2b ) and its S,S-dioxide ( 2d ) were obtained. Compound 2d was also prepared by oxidizing 2b with hydrogen peroxide in acetic acid. Heating of 9H-thioxanthene-9-acetic acid 10-oxide ( 1c ) with 1,2-benzenediamine gave 9-methylene-9H-thioxanthene ( 3 ). 2-(9H-Thioxanthen-9-ylmethyl)-1H-benzimidazole S-oxide ( 2c ) was obtained by oxidizing 2b with m-chloroperbenzoic acid in acetone.     

Photochemistry of 3-Substituted 1-Iminopyridinium Ylides. Regiospecific versus non-regiospecific photoisomerization patterns [1]

3-Substituted 1-iminopyridinium ylides 1 undergo photo-induced ring enlargement to 1H-1,2-diazepines. With strongly electron-withdrawing substituents the ring expansion process is regiospecific and leads exclusively to 4-substituted 1 H-1, 2-diazepines. Weak electron-donating substituents, like a methyl group and halogen atoms, do not have any directing effect since both 4- and 6-substituted 1 H -1,2-diazepines are obtained. With strong electron-donating substituents no diazepines are formed; instead one observes photo-induced isomerization to the 2-aminopyridine derivatives, the process being non-regiospecific. Regiospecific photo-induced ring expansion processes are explained in terms of a simple HMO model.     

1,2-fused pyrimidines. V. Synthesis of 1-alkyl or phenyl-2H-dipyrido-[1,2-a:2′,3′-d]pyrimidine-2,5(1H)-diones

The reaction of 2-[(N-acyl, N-alkyl or phenyl)amino]-4H-pyrido[1,2-a]pyrimidin-4-ones 8a-g with the N,N-dimethylformamide/phosphorus oxychloride Vilsmeier reagent 1 (95°, 90 minutes) afforded 1-alkyl or phenyl-2H-dipyrido[1,2-a:2′,3′-d]pyrimidine-2,5(1H)^?diones, 3-alkyl substituted or not, 10a-g . The starting compounds 8 were prepared by treating 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones N-alkyl substituted 7a,b or N-phenyl substituted 4 with excess anhydrides (130°, 7 hours) when the 2-(alkylamino) derivatives 7 were used in the reaction, compounds 8 were obtained along with very small amounts of 3-acyl-2-(alkylamino)-4H-pyrido[1,2-a]pyrimidin-4-ones 9 .     

A new method for the synthesis of novel 1-aryl-3-heteroaryl-1H-pyrazolo[3,4-b]quinoxalines

The reaction of 3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxaline 4 with o-chlorobenzenediazonium chloride gave 3-[α-(o-chlorophenylhydrazono)-2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-ylmethyl]-2-oxo-1,2-dihydroquinoxaline 6 , whose refluxing in phosphoryl chloride/pyridine afforded 1-(o-chlorophenyl)-3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-yl)-1H-pyrazolo[3,4-b]quinoxaline 7. The reactions of 6 and 7 with nitrous acid resulted in sulfur extrusion to provide 1-(o-chlorophenyl)-3-(4-methyl-4H-1,2,4-triazol-5-yl)1H-pyrazolo[3,4-b]quinoxaline 8 and 3-[α-(o-chlorophenylhydrazono)-4-methyl-4H-1,2,4-triazol-5-ylraethyl]-2-oxo-1,2-dihydroquinoxaline 9 , respectively.     

Synthesis and structure of novel 4-arylhexahydro-1H,3H-pyrido[1,2-c]pyrimidine derivatives

A series of new 4-aryl-hexahydro-1H,3H-pyrido[1,2-c]pyrirnidine-1,3-dione derivatives 4a-k were prepared by catalytic hydrogenation of 4-aryl-1H,2H-pyrido[1,2-c]pyrirnidine-1,3-diones 3a-k. The structures of compounds were determined by ¹H and ¹³C nmr spectroscopy in solution. Steric hindrance caused twisting of the phenyl ring with respect to the pyridopyrimidine system, the effect was confirmed by X-ray diffraction.     

Azacycloalkanes: XXXIX. New Syntheses of 1<Emphasis Type="Italic">H</Emphasis>-Pyrrole-1-carboxylic acid and 1,2-dihydropyrrolo-[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrazin-3(4<Emphasis Type="Italic">H</Emphasis>)-one derivatives

New procedures have been developed for the synthesis of α-(2-formyl-1H-pyrrol-1-yl)-substituted carboxylic acids, α-(2-R-aminomethyl-1H-pyrrol-1-yl)-substituted carboxylic acids, and 1,2-dihydropyrrolo-[1,2-a]pyrazin-3(4H)-ones on the basis of furfurol and α-amino acids.     

Cycloaddition of benzoheteroazepine III Reaction of 2,3-dihydro-1H-15benzodiazepines with dichlorocarbene and stereo-structures of products

Reaction of 2, 3-dihydro-1H-1. 5-benzodiazepines with dichlorocarbene generated in situ using benzyltriethylammonium chloride (TEBA) as a phase transfer catalyst in chloroform-aqueous sodium hydroxide mixture gave mainly 1,2-cycloadducts, cis and trans-1a, 3-disubstituted-1, 1-dichloro-1a, 2,3,4-tetrahydro-1H-azirino[1,2-a][1,5]benzodiazepines (2.3), and formylated 1,2-cycloadducts, trans-1a,3-disubstituted-1, 1-dichloro-4-formyl-1a, 2, 3, 4–1 H-azirino[1, 2-a][1, 5]benzodiacepines (4). The stereo-structures of cycloadducts and the mechanism are also discussed.     

Eine neue einfache Synthese spirocyclischer 1H-Chinolin-Derivate

A New and Simple Method for the Synthesis of Spirocyclic la-Quinolines The reaction of anilines with (+)-(R)-pulegone in toluene at temperatures between 125 and 150° with 4-toluenesulfonic acid or I₂ as catalysts leads to diastereoisomeric mixtures of spiro[cyclohexane-1,2′(1′H)-quinoline] derivatives (see 1–4 , Scheme 1; Table). The diastereoisomers are separated by column chromatography, and the structure of the single isomers is determined by NMR-spectroscopic methods. A reaction mechanism proceeding via several 6π-electrocyclic rearrangements and H-shifts is proposed for the formation of 1H-quinolines 1–4 (Scheme 2). This mechanism is in accordance with the results of the reaction of 2-isopropenylaniline with 3-methylcyclohexanone which leads to a stereoisomeric mixture of 3,4′-dimethylspiro[cyclohexane-1,2′(1H)-quinolines] (Scheme 3).     

Formation of fluorene and anthracene derivatives in reactions of perfluorinated 1-alkyl-1-phenyl- and 1-alkyl-2-phenyl-1,2-dihydrocylobutabenzenes with antimony pentafluoride

The reaction of perfluoro(1-methyl-1-phenyl-1,2-dihydrocyclobutabenzene) with SbF₅ at 50°C, followed by hydrolysis, gave perfluoro(1-phenylindan-1-ol), while analogous reaction at 90°C afforded perfluoro[10-methylanthracen-9(10H)-one]. Perfluoro(1-methyl-2-phenyl-1,2-dihydrocyclobutabenzene) did not undergo skeletal transformations under analogous conditions, whereas at 200°C it was converted mainly into perfluoro(9-methylfluoren-9-ol). Perfluoro(1-ethyl-2-phenyl-1,2-dihydrocyclobutabenzene) reacted with SbF5 at 200°C to form perfluoro(9-ethylfluoren-9-ol) together with perfluorinated 9,9-dimethyl- and 9-ethyl-9-methyl-1,2,3,4-tetrahydro-9H-fluorenes.     

The mass spectra of some 1H-imidazo[1,2-a]pyrrolo[3,2-e]pyridines

We report here the mass spectral fragmentations of some derivatives of a new heterocyclic system 1H-imidazo[1,2-a]pyrrolo[3,2-e]pyridine. These compounds combine structural features of 1H-pyrrolo[2,3-b]pyridines and imidazo[1,2-a]pyridines, but follow fragmentation pathways similar to the former.     

Crystal structure,dissociation and zwitterion formation in 2,6-diaryl-1(3)-oxo-3(1)-hydroxy-5(7)-imino-7(5)-amino-1 H,5H-(3-H,7H)-pyrazolo[1,2-a]pyrazoles

Single crystal X-ray analysis and quaternization of 2,6-diphenyl-1(3)-oxo-3(1)-hydroxy-5(7)-imino-7(5)-1H,-5H[3H,7H)-pyrazolo[1,2-a]pyrazole is described. The dissociation constants are determined and compared with those of 4-phenyl-1,2-dimethyl-3(5)-oxo-5(3)-hydroxypyrazole and 4-phenyl-3,5-diaminopyrazole. The quaternization of the latter compound is also described. The influence of electron donating substituents at the cationic moiety on the electronic spectra of such paraionic systems is discussed. The title products exist in the solid state as zwitterions and probably as covalent species in solution.     

Synthesis of 1R‐1H‐Imidazo[1,2‐a]pyridin‐4‐ium‐8‐olate Derivatives

A new method based on reaction of 4‐bromobut‐2‐enoates with N‐alkylimidazoles was proposed for obtaining 1R‐1H‐imidazo[1,2‐a]pyridin‐4‐ium‐8‐olate and 1‐R‐8‐methoxy‐1H‐imidazo[1,2‐a]pyridin‐4‐ium derivatives. The structures of synthesized compounds were confirmed by ¹H, ¹³C NMR, elemental analysis, and X‐ray data.     

A facile and novel synthesis of 1,6-naphthyridin-2(1H)-ones

A new and convenient procedure for the synthesis of 1,6-naphthyridin-2(1H)-ones and their derivatives is described. In the first scheme 5-acetyl-6-[2-(dimethylamino)ethenyl]-1,2-dihydro-2-oxo-3-pyridinecarbonitrile ( 4 ) obtained by the reaction of N,N-dimethylformamide dimethyl acetal with 5-acetyl-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile ( 3 ) was cyclized to 1,2-dihydro-5-methyl-2-oxo-1,6-naphthyridine-3-carbonitrile ( 5 ) by the action of ammonium acetate. Thermal decarboxylation of acid 7 obtained from the hydrolysis of nitrile 5 led to a mixture of 5-methyl-1,6-naphthyridin-2(1H)-one ( 8 ) and its dimer 9 . Hydrazide 11 obtained from nitrile 5 in two steps was converted to 3-amino-5-methyl-1,6-naphthyridin-2(1H)-one ( 12 ) by the Curtius rearrangement. The amino group of 12 was readily replaced by treatment with aqueous sodium hydroxide to yield 3-hydroxy-5-methyl-1,6-naphthyridin-2(1H)-one ( 13 ). In the second scheme, Michael reaction of enamines of type 20 with methyl propiolate, followed by ring closure gave 5-acyl(aroyl)-6-methyl-2(1H)-pyridinones ( 21 ) which in turn were treated with Bredereck's reagent to produce 5-acyl(aroyl)-6-[2-(dimethylamino)ethenyl]-2(1H)-pyridinones ( 22 ). Treatment of 22 with ammonium acetate led to the formation of 1,6-naphthyridin-2(1H)-ones 23 .     

A new two‐dimensional CdII coordination polymer based on 2‐(1H‐imidazol‐1‐ylmethyl)‐6‐methyl‐1H‐benzimidazole and benzene‐1,2‐dicarboxylate: synthesis,crystal structure and characterization

In the construction of coordination polymers, many factors can influence the formation of the final architectures, such as the nature of the metal centres, the organic ligands and the counter‐anions. In the coordination polymer poly[aqua(μ‐benzene‐1,2‐dicarboxylato‐κ⁴O ¹,O ^1′:O ²,O ^2′)[μ‐2‐(1H‐imidazol‐1‐ylmethyl)‐6‐methyl‐1H‐benzimidazole‐κ²N ²:N ³]cadmium(II)], [Cd(C₁₂H₁₂N₄)(C₈H₄O₄)(H₂O)]_n or [Cd(immb)(1,2‐bdic)(H₂O)]_n , each Cd^II ion is seven‐coordinated by two N atoms from two symmetry‐related 2‐(1H‐imidazol‐1‐ylmethyl)‐6‐methyl‐1H‐benzimidazole (immb) ligands, by four O atoms from two symmetry‐related benzene‐1,2‐dicarboxylate (1,2‐bdic²⁻) ligands and by one water molecule, leading to a CdN₂O₅ distorted pentagonal bipyramidal coordination environment. The immb and 1,2‐bdic²⁻ ligands bridge Cd^II ions and form a two‐dimensional network structure. O—H…O and N—H…O hydrogen bonds stabilize the structure. In addition, the IR spectroscopic properties, PXRD patterns, thermogravimetric behaviour and fluorescence properties of the title polymer have been investigated.     

Synthesis of 2-(p-R-benzoylmethylene)-3-(p-R-phenyl)-1H-quinoxalines

The reaction of 1,2-diaminobenzenes with substituted 1,2-dibenzoyl-1,2-dibromoethanes constitutes a convenient synthetic route to the hitherto 2-(p-R-benzoylmethylene)-3-(p-R-phenyl)-1H-quinoxalines. Structures of all products were elucidated by ir, ¹H and ¹³C-nmr, mass spectra data. X-Ray crystallography data confirm assigned structures.     

Synthesis of 7-substituted 1H-indolo[3,2-d][1,2]benzoxazepines

The synthesis of the novel 7-substituted 1H-indolo[3,2-d][1,2]benzoxazepine ring system is described. Fischer indolization of 2-fluoroacetophenone phenylhydrazone provided the starting material 2-(2-fluorophenyl)-1H-indole. An acyl group was then introduced at the 3-position of the indole nucleus and the resulting ketone was converted to the ketoxime. Upon treatment with sodium hydride to form the oxanion of the ketoxime, an intramolecular cyclization took place via displacement of fluoride from the adjacent 2-fluorophenylsubstituent. This ring closure completed the construction of the 1H-indolo[3,2-d][1,2]benzoxazepine ring system.