Synthese von imidazo[1,5-a]- und pyrazino[1,2-a]benzimidazolen

1,2-Dihydro-3H-imidazo[1,5-a]benzimidazoles (6), 1-oxo-1,2-dihydro-3H-imidazo[ 1,5-a] benzimidazoles (8), 3H-imidazo[1,5-a]benzimidazoles (7), 3-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a] benzimidazoles (12), and 3,4-dioxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]benzinudazoles (13) were synthesized from 2-α-aminobenzyl (benzhydryl)-benzimidazoles (2).     

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.     

Transition-metal-free insertion of benzyl bromides into 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde: One-pot switchable syntheses of benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones and 3-arylquinolin-4-ones mediated by base

A transition-metal-free insertion of benzyl group between aldehyde and imidazole of 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde was achieved for the first time. Two diverse sets of quinolin-4-one derivatives: benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones (2) and 3-arylquinolin-4-ones (3) were synthesized based on identical starting materials 2-(1H-benzo[d]imidazol-1-yl)benzaldehydes (1) and benzyl bromides. In the preparations, two key intermediates I and II were involved and might be synthesized in situ through the reaction of an intra-Breslow intermediate with benzyl bromide via an enol attack in the presence of base or a NHC-based enamine attack in the absence of base, respectively, in which the intra-Breslow intermediate might function as a nucleophilic reagent by following two novel different pathways.     

Cyclisierungsbreaktionen von 2-aminobenzimidazolen zu s-triazino[1,2-a]benzimidazolen

2 - Aminobenzimidazolyl - 1 - phenylimidate 1; 1 - cyan - 2 - aminobenzimidazole 5 and 2 - aminobenzimidazolyl - 1 - amidines 8 were synthesized. 1 and 8 give with aromatic aldehydes or acids 1,2 - dihydro - 3 - aryl - 4 - phenoxy(or amino) - s - triazino[1,2-a]- or 2 - aryl - 4 - phenoxy(or amino) - s - triazino[1,2-a] - benzimidazoles 3, 3a, 4, 4a. 5 gives with isocyanates or azomethines tetrahydro - s - triazino[1,2-a] - benzimidazoles 6 and 7. The mass- and IR-spectres of the synthesized compounds are discussed.     

Reaction of azulene with 1,2-bis[4-(dimethylamino)phenyl]-1,2-ethanediol in a mixed solvent of methanol and acetonitrile in the presence of hydrochloric acid: a facile one-pot synthesis and properties of new triarylethylenes possessing an azulen-1-yl group

Reaction of azulene (1) with 1,2-bis[4-(dimethylamino)phenyl]-1,2-ethanediol (2) in a mixed solvent of methanol and acetonitrile in the presence of 36% hydrochloric acid at 60 °C for 3 h gives 2-(azulen-1-yl)-1,1-bis[4-(dimethylamino)phenyl]ethylene (3) (8% yield), 1-(azulen-1-yl)-(E)-1,2-bis[4-(dimethylamino)phenyl]ethylene (4) (28% yield), and 1,3-bis{2,2-bis[4-(dimethylamino)phenyl]ethenyl}azulene (5) (9% yield). Besides the above products, this reaction affords 1,1-di(azulen-1-yl)-2,2-bis[4-(dimethylamino)phenyl]ethane (6) (15% yield), a meso form (1R,2S)-1,2-di(azulen-1-yl)-1,2-bis[4-(dimethylamino)phenyl]ethane (7) (6% yield), and the two enantiomeric forms (1R,2R)- and (1S,2S)-1,2-di(azulen-1-yl)-1,2-bis[4-(dimethylamino)phenyl]ethanes (8) (6% yield). Furthermore, addition reaction of 3 with 1 under the same reaction conditions as the above provides 6, in 46% yield, which upon oxidation with DDQ (=2,3-dichloro-5,6-dicyano-1,4-benzoquinone) in dichloromethane at 25 °C for 24 h yields 1,1-di(azulen-1-yl)-2,2-bis[4-(dimethylamino)phenyl]ethylene (9) in 48% yield. Interestingly, reaction of 1,1-bis[4-(dimethylamino)phenyl]-2-(3-guaiazulenyl)ethylene (11) with 1 in a mixed solvent of methanol and acetonitrile in the presence of 36% hydrochloric acid at 60 °C for 3 h gives guaiazulene (10) and 3, owing to the replacement of a guaiazulen-3-yl group by an azulen-1-yl group, in 91 and 46% yields together with 5 (19% yield) and 6 (13% yield). Similarly, reactions of 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (12) and 1,1-bis{4-[2-(dimethylamino)ethoxy]phenyl}-2-(3-guaiazulenyl)ethylene (13) with 1 under the same reaction conditions as the above provide 10, 2-(azulen-1-yl)-1,1-bis(4-methoxyphenyl)ethylene (16), and 1,3-bis[2,2-bis(4-methoxyphenyl)ethenyl]azulene (17) (93, 34, and 19% yields) from 12 and 10 and 2-(azulen-1-yl)-1,1-bis{4-[2-(dimethylamino)ethoxy]phenyl}ethylene (18) (97 and 58% yields) from 13.     

A Convenient Synthesis of 2-Arylnaphtho[1,2-d]oxazole Derivatives Promoted by Triethylamine

A variety of 2-arylnaphtho[ 1,2-d]oxazole derivatives were efficiently synthesized in moderate to high yields by the reaction of aromatic aldehydes with 1-amino-2-naphthol derivatives in the presence of triethylamine in refluxing ethanol in air. Seven new 2-arylnaphtho[1,2-d]oxazole derivatives were obtained and characterized by the spectral data and elemental analysis. In addition, the X-ray crystal structures of 2-[4-（N,N-dimethylamino）phenyl]naphtho[ 1,2-d] oxzole （3d） and 1, 1＇-bis（naphtho[ 1,2-d]oxazol-2-yl）ferrocene （3n） have been determined.     

Condensed 1,3,5-triazepines—III : Derivatives of 4,5-dihydro-[1,3,5]triazepino[1,2-a]benzimidazole

Methods have been developed for the synthesis of 2-amino-1-(2-aminoethyl)-benzimidazoles 10. By ring closures with the aid of suitable C₁-components, derivatives 11a–c, 13–15 of the novel [1,3,5]triazepino[1,2-a] benzimidazole ring system have been obtained.     

Preparation and emission spectra of polymeric 1,2-diketones

Monomers of the methacrylate type, viz. 1-[4-(2-methacroyloxyethoxy)phenyl] propandione-1,2 (7a) and 1-phenyl-2-[4-(2-methacroyloxyethoxy)phenyl] ethandione-1,2 (7b) having the 1,2-dicarbonyl chromophore in the side-chain, were synthesized. The soluble homopolymer of monomer 76 and copolymers of both monomers 7a and 7b with styrene and methyl methacrylate were prepared by radical polymerization in solution. The absorption and emission spectra of a model compound and the homopolymer showed that the 1,2-dicarbonyl chromophore behaved as an isolated unit. No fluorescence was observed for the model compound or the homopolymer in emission spectra of poly(methyl methacrylate)-doped films. Phosphorescence of low- and high-molecular carbonyls was quenched by ferrocene in solution. Comparison of Stern-Volmer constants indicates partial steric hindrance of energy transfer for high-molecular donor.     

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 ).     

Synthesis and biological activity of fluorinated 2-amino-4-aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazoles

The heterocyclic nucleus s-triazino[1,2-a]benzimidazole has been reported to exhibit antibacterial activity. In this study, seven new 3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole derivatives were prepared via cyclocondensation between 2-guanidinobenzimidazole and fluorine substituted (including trifluoromethyl) benzaldehydes. The structures of all the compounds were confirmed by ¹H, ¹³C NMR and IR spectral data. Spectral data also suggested the existence of various tautomeric forms of the fluorine-containing s-triazino[1,2-a]benzimidazole compounds. The synthesized compounds were also screened for antibacterial and bovine dihydrofolate reductase (DHFR) inhibitory activities. The compound 3g substituted with a 3′,5′-bis(trifluoromethyl)phenyl moiety demonstrated the best antibacterial activity in the series. None of the tested compounds significantly inhibited bovine DHFR.     

Photobehaviour of 2- and 3-heteroaryl substituted o-divinylbenzenes; formation of fused 2,3- and 3,2-heteroareno-benzobicyclo[3.2.1]octadienes and 3-heteroaryl benzobicyclo[2.1.1]hexenes

New β-3-thienyl (8) and β-3-furyl derivatives of o-divinylbenzene (9) have been synthesised and their photochemical behaviour compared with 2-thienyl (7) and 2-furyl derivatives (2). Whereas the β-(2-heteroaryl) substituted o-divinylbenzenes (7 or 2) give only bicyclo[3.2.1]octadiene structure (14 or 1) by 1,6-ring closure of the biradical intermediate, β-(3-heteroaryl) substituted o-divinylbenzenes (8 or 9) give bicyclo[3.2.1]octadiene structure (23 or 24) and bicyclo[2.1.1]hexene structure (25 or 26) by 1,6- and 1,4-ring closure, respectively. This photochemical approach provides a simple method to 2,3- and 3,2-fused thiophene and furan polycyclic compounds.     

Synthesis and structure of a chiral areno-bridged [2.4]metacyclophane

The reductive coupling reaction of 1,4-bis(3-acetyl-5-tert-butyl-2-methoxyphenyl)butane 3 was carried out using TiCl₄-Zn in pyridine followed by a McMurry coupling reaction to afford the compounds anti and syn 1,2-dimethyl[2.4]MCP-1-ene 4. Bromination of 4 with BTMA-Br₃ in dry CH₂Cl₂ afforded the interesting compound 1,2-bis-(bromomethyl)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-1-ene 6 and consecutive debromination with Zn and AcOH in CH₂Cl₂ solution afforded the stable solid 5,15-di-tert-butyl-8,18-dimethoxy-1,2-dimethylene[2.4]MCP 7 in 89% yield. Compound 7 was conveniently employed in a Diels–Alder reaction with dimethyl acetylenedicarboxylate (DMAD) to provide 2-(3′,6′-dihydrobenzo)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-4′,5′-dimethylcarboxylate 8 in good yield. Diels–Alder adduct 8 was converted into a novel and inherently chiral areno-bridged compound [2.4]MCP 9 by aromatization. The chirality of the two conformers was characterized by circular dichroism (CD) spectra of the separated enantiomer which are perfect mirror images of each other.     

Synthesis and conformational analysis of new naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives

A new highly functionalized aminonaphthol derivative, 1-(amino(2-aminophenyl)methyl)-2-naphthol (4), was synthesized by the reaction of 2-naphthol, 2-nitrobenzaldehyde and tert-butyl carbamate or benzyl carbamate, followed by reduction and/or removal of the protecting group. The aminonaphthol derivative thus obtained was converted in ring-closure reactions with formaldehyde, benzaldehyde and/or phosgene to the corresponding naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives. The conformational analysis of some derivatives by NMR spectroscopy and accompanying molecular modelling are also reported.     

A facile synthesis of pyrrolo[1,2-a]benzimidazoles and pyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazole derivatives

Reaction of 2-cyanomethylbenzimidazole 1 with hydrazonoyl halides 2 led to formation of pyrrolo[1,2-a]benzimidazole derivatives 7. Similar reaction of 1 with halides 3 afforded 5-amino-4-(benzimidazol-2-yl)pyrazole derivatives 11 or 1-amino-2-arylpyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazol-4-one 14 depending on the reaction conditions. The mechanisms of the studied reactions are discussed.     

Synthesis of new 1,2,4-triazolo[4,3-b]pyridazines and related compounds

The synthesis of novel 6-[4-(1H-imidazol-1-yl)phenyl]-1,2,4-triazolo[4,3-b]pyridazines 8a-f and related compounds is described. Although the intermediate hydrazine derivatives 7 and 9 possess good positive inotropic activity, the fused bicyclic pyridazines 8a-f are significantly less potent than the 3(2H)-pyridazinone 5. Compounds 8a-f are potent but nonselective inhibitors of cardiac phosphodiesterase.     

Synthesis and in-vitro-antibacterial activity of [5-(furan-2-yl)-phenyl]-4,5-carbothioamide-pyrazolines

Cyclization of various different alkoxy [1-[2-(alkoxy)phenyl]-5-(furan-2-yl)-prop-2-en-1-one] chalcone with thiosemicarbazide in the presence of NaOH in ethanol afforded a series of novel 1-N-substituted cyclized pyrazoline analogues [5-(furan-2-yl)-3-[2-(alkoxy) phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2a–2d. The structures of these compounds were elucidated by IR, ¹H NMR, ¹³C NMR, Fab mass spectrometry and their purities were confirmed by elemental analyses. In vitro antibacterial activity of these compounds were evaluated by the disk diffusion assay and then the minimum inhibitory concentration (MIC) strain of two Gram-positive and two Gram-negative bacteria like Aeromonas hydrophila, Yersinia enterocolitica, Listeria monocytogenes, and Staphylococcus aureus, among all the compounds, alkoxy [5-(furan-2-yl)-2-(benzyloxy)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2b and 5-(furan-2-yl)-1-[2-(naphthalen-2-ylmethoxy) phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2d showed the most promising antibacterial agent when compared to gentamicin and tetracycline.     

Synthesis of novel pyrazolo[3,4‐d]pyridazine,pyrido[1,2‐a]benzimidazole,pyrimido[1,2‐a]benzimidazole and triazolo[4,3‐a]pyrimidine derivatives

4‐Acetyl‐5‐methyl‐1‐phenyl‐1H‐pyrazole reacts with dimethylformamide dimethylacetal (DMF‐DMA) to afford the corresponding (E)1‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐3‐(N,N‐dimethylamino)‐2‐propen‐1‐one. The latter product undergoes regioselective 1,3‐dipolar cycloaddition with nitrilimines and nitrile oxides to afford the novel 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)carbonyl‐1‐phenylpyrazole and 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)carbonyl isoxazole derivatives, respectively. It reacts also with 1H‐benzimidazole‐2‐acetonitrile, 2‐aminobenzimidazole and 3‐amino‐1,2,4‐triazole to afford the novel pyrido[1,2‐a]benzimidazole, pyrimido[1,2‐a]benzimidazole and the triazolo[4,3‐a]pyrimidine derivatives, respectively. The reaction of 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl) carbonyl‐1‐phenylpyrazole derivatives with hydrazine hydrate led to a new pyrazolo[3,4‐d]pyridazine derivatives.     

Synthesis and structure of mesomorphic 2-cyano-5-[p-alkyl(alkoxy)phenyl]-pyridines

Liquid-crystal 2-cyano-5-[p-alkyl(alkoxy)phenyl]pyridines were synthesized by the reaction of 1-dimethylamino-3-dimethylimmonia-2-[p-alkyl (alkoxy)phenyl]propene perchlorates with 2-acetylfuran and subsequently through 2-furyl-5-[p-alkyl(alkoxy)phenyl]pyrylium perchlorates and 2- (2-furyl)-5-[p-alkyl (alkoxy)phenyl]pyridines by conversion of the latter to 5-alkyl(alkoxy)phenylpyridine-2-carboxylic acids, from which the cyano derivatives were obtained by the usual scheme through the amides. The intermediate arylfurylpyridines and arylpyridine-2-carboxylic acid imides also display liquid-crystal properties.Translated from Khimiya Geterotskilicheskikh Soedinenii, No. 7, pp. 888–891, July, 1980.     

Efficient synthesis of novel dipyridoimidazoles and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives

Novel dipyrido[1,2-a;3′,4′-d]imidazoles 7a-d, dipyrido[1,2-a;4′,3′-d]imidazoles 8a,c and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives 9a-d were synthesized by two pathways: thermal electrocyclic reaction of 3-alkenylimidazopyridine-2-oximes 10 and direct condensation of ethyl glycinate (or hydrazine) with 2,3-dicarbonylimidazo[1,2-a]pyridines 11.     

Photodimerization of azaanthracene derivatives mediated by cucurbit[10]uril

Challenges of achieving efficient photodimerization of azaanthracene derivatives remain due to the low selectivity and slow reaction rate. In this paper, cucurbit[10]uril (CB[10]), with the largest rigid and hydrophobic cavity among CB[n]s, was used to affect the photodimerization reaction of four water-soluble 1-(2-)substituted azaanthracene derivatives (1-4). It revealed that 1-4 could form 1:2 host-guest complexes with CB[10] in aqueous solution. Irradiation of 1 in the presence of 0.5 equiv. of CB[10] selectively produced a head-to-tail (anti-HT) photodimer product. As for 2-4, CB[10] acted as a nanoreactor accelerating their photodimerization reaction in water. Our results suggest that photodimerization of azaanthracene derivatives could be promoted by the CB[10]-based host-guest strategy with high efficiency and selectivity.