4-Azidocinnoline—Cinnoline-4-amine Pair as a New Fluorogenic and Fluorochromic Environment-Sensitive Probe

A new type of fluorogenic and fluorochromic probe based on the reduction of weakly fluorescent 4-azido-6-(4-cyanophenyl)cinnoline to the corresponding fluorescent cinnoline-4-amine was developed. We found that the fluorescence of 6-(4-cyanophenyl)cinnoline-4-amine is strongly affected by the nature of the solvent. The fluorogenic effect for the amine was detected in polar solvents with the strongest fluorescence increase in water. The environment-sensitive fluorogenic properties of cinnoline-4-amine in water were explained as a combination of two types of fluorescence mechanisms: aggregation-induced emission (AIE) and excited state intermolecular proton transfer (ESPT). The suitability of an azide–amine pair as a fluorogenic probe was tested using a HepG2 hepatic cancer cell line with detection by fluorescent microscopy, flow cytometry, and HPLC analysis of cells lysates. The results obtained confirm the possibility of the transformation of the azide to amine in cells and the potential applicability of the discovered fluorogenic and fluorochromic probe for different analytical and biological applications in aqueous medium.     

Methods for the synthesis of cinnolines (review)

This review analyses the principal approaches to the synthesis of the cinnoline nucleus, used as synthetic precursors of arenediazonium salts, arylhydrazones, and arylhydrazines, and also reductive methods for the synthesis of polycondensed derivatives of cinnoline. The mechanisms of the transformations and the possibilities and limitations of the various methods are discussed. Special attention is paid to methods based on the cyclization of derivatives of arenediazonium salts, which have been developed substantially in recent years. In memory of A. A. Potekhin __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 643–667, May, 2008.     

A TDDFT study of the low-lying excitation energies of polycyclic cinnolines and their carbocyclic analogues

The low-lying excited states of 21 compounds of polycyclic cinnoline, monoaza-hydrocarbon and their corresponding polycyclic aromatic hydrocarbon (PAH) analogues have been investigated in the framework of time-dependent density functional theory (TDDFT). The gradient corrected BLYP, hybrid B3LYP and B3P86 functionals together with 6-31G (d) basis set have been used. The hybrid-type B3LYP and B3P86 systematically overestimate the excitation energies for states with dominating ionic character (corresponding to group III band), with a mean absolute deviation (MAD) of 0.33 eV (B3LYP) and 0.34 eV (B3P86), respectively. However, they can accurately predict the excitation energies for states with covalent character (corresponding to group II and I bands). The MAD for group II (B3LYP: 0.05 eV; B3P86: 0.05 eV) and I bands (B3LYP: 0.12 eV; B3P86: 0.12 eV) are significantly smaller. The BLYP outperforms B3LYP and B3P86 for group III band (MAD: 0.09 eV), but has a worse performance for group II (MAD: 0.15 eV) and I (MAD: 0.13 eV) bands. Comparison of the lowest-lying excited states for polycyclic cinnolines with those of the corresponding PAH analogues, the first excited states of polycyclic cinnolines mainly result from n→π₀* transitions. Therefore, in non-polar solvents, the spectra of some polycyclic cinnolines exhibit an additional absorption band at longer wavelengths.     

A short route to 3-alkynyl-4-bromo(chloro)cinnolines by Richter-type cyclization of ortho-(dodeca-1,3-diynyl)aryltriaz-1-enes

Cleavage of ortho-(dodeca-1,3-diynyl)triazenes in HCl or HBr medium and subsequent cyclization of the resulting diazonium salts is investigated. In the absence of a strong electron-withdrawing substituent, the reaction affords 3-alkynyl-4-bromo(chloro)cinnolines as the only product. A methoxycarbonyl group promotes hydrolysis of 4-halocinnolines which results in the formation of by-products: furo[3,2-c]cinnoline and cinnolinone. Substitution of bromine in 3-(alk-1-ynyl)-4-bromocinnolines is achieved with methylamine, Na₂S and ethynylbenzene affording pyrrolo[3,2-c]cinnoline, thieno[3,2-c]cinnoline and 3,4-diethynylcinnoline, respectively.     

Formation of the pyrroline N-oxide ring by interaction of α-isonitrosoketones — derivatives of tetrahydrobenzofurazan and -furoxan with aldehydes and morpholine and some of the reactions of these compounds

-Isonitroso ketones, derivatives of tetrahydrobenzofurazan and furoxan, react with aldehydes (acetaldehyde and propionaldehyde) and morpholine to form derivatives of tetrahydropyrrolo[2,3-e]-2,1,3-benzoxadiazole 6-oxide. Treatment of the latter with hydrazine hydrate gave derivatives of 4,5-dihydro-1,2,5-oxadiazolo[3,4-f]cinnoline which are readily dehydrogenated with tetrachloro-benzoquinone to derivatives of 1,2,5-oxadiazolo[3,4-f]cinnoline. Reduction of tetrahydropyrrolo[2,3-e]-2,1,3-benzoxadiazole 6-oxides with sodium borohydride gave derivatives of N-hydroxyhexahydro-pyrrolo[2,3-e]-2,1,3-benzoxazole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, 1558–1563. October, 2004.     

Studies on cyclization of o-(alka-1,3-diynyl)arenediazonium salts

The Richter reaction of o-(alka-1,3-diynyl)arenediazonium salts, obtained by diazotization of diacetylenic derivatives of anilines, leads to 3-alkynyl-4-chloro- or 3-alkynyl-4-bromocinnolines and/or 3-alkynyl-4-hydroxycinnolines (the latter cyclize into furo[3,2-c]-cinnolines under the reaction conditions). 3-Alkynyl-4-chlorocinnolines undergo solvolysis in methanol giving rise to 3-alkynyl-4-methoxycinnolines, the subsequent hydrolysis of which also gives furo[3,2-c]cinnolines. Effects of the nature of substituents in the aromatic ring and of the reaction conditions on the product composition and yields have been established. The reaction course has been studied by spectrophotometry. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1693–1700, August, 2008.     

Aluminium Chloride–Catalyzed Synthesis of 4-Benzyl Cinnolines from Aryl Hydrazones

An efficient synthesis of 4-benzyl cinnolines from aryl phenylallylidene hydrazone is described. In this report aluminium chloride as a Lewis acid catalyst and toluene as a solvent are used for the synthesis. This method is expected to more advantageous than the other reported methods of synthesis of the cinnoline rings because of its low cost, better yield, and benign reaction conditions.

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