Dmitry S. Kopchuk

Preparation of 3-Cyano-1-(2-Pyridyl)Isoquinolines by Using Aryne Intermediates

While the isoquinoline system serves as a structural foundation of many natural product molecules, such as certain alkaloids [1], isoquinolines also have intrinsic biological activity [2] and play an important role as fragments in natural and synthetic drugs. Besides that, 1-(2-pyridyl)isoquinolines present interest as ligands for transition metal cations [3]. The introduction of a cyano group at position 3 of isoquinoline ring in such compounds opens a broad range of possibilities for obtaining various derivatives through subsequent functionalization. Unfortunately, no effective methods are currently known for the synthesis of 3-cyanoisoquinolines. For example, direct cyanation of isoquinoline N-oxides occurs exclusively at position 1, while the few cases of direct 3-cyanation of isoquinolines gave low yields [4] or required special reaction conditions [5]. Besides, 3-cyanoisoquinolines can be obtained through various variants of heterocyclization [6, 7] and by the decomposition of 2,3-substituted diazidonaphthaline – in that case 3-cyanoisoquinoline was formed in mixture with by-products [8]. Finally, the 3-cyano group in isoquinoline may be created by chemical transformations of other functional groups, such as substitution of a chlorine atom [9]. In this report, we propose a convenient method for the synthesis of 3-cyano-1-(2-pyridyl)isoquinolines based on the available 5-cyano-3-(2-pyridyl)-1,2,4-triazines 1а-с [10] by using a known effective method for the synthesis of various pyridine derivatives from 1,2,4-triazine analogs [11]. It has been established that the interaction of 1,2,4-triazines with enamines followed by oxidation [12], or with in situ generated arynes [13] allows to obtain substituted isoquinolines effectively, even avoiding the aromatization step in the case of arynes [14]. We have previously demonstrated that 3-(2-pyridyl)-1,2,4-triazines substituted with aryl groups at positions 5 and/or 6 [15] react with 1,2-dehydrobenzene forming 10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indoles. However, 5-cyano-3-(2-pyridyl)-1,2,4-triazines have never before been used as starting materials in these reactions. _______ *To whom correspondence should be addressed, e-mail: gvzyryanov@gmail.com.

Preparation of Pyridyl-substituted Monoazatriphenylenes

Azatriphenylene derivatives are of considerable interest due to their promising photophysical and coordinating properties [1] and to their presence in the composition of natural compounds [2, 3]. Azatriphenylenes are important in inorganic biochemistry thanks to their use as intercalating ligands [4, 5]. In addition, azatriphenylenes have shown promise as luminescent chemosensors of organic anions and nitroaromatic compounds [6]. The most frequently used method for preparing azatriphenylenes is the Skraup synthesis [7, 8] which demands the use of forcing conditions. Contemporary synthetic methods broadly use a cycloaddition reaction of hard to obtain alkenes or arylacetylenes with aromatic substrates catalyzed by transition metal salts [9, 10]. Finally, the cyclocondensation of phenanthrenequinone with hydrazones of (hetero)aromatic carboxylic acid amides leads to the corresponding aryl[11, 12] and hetaryl-substituted [13] triazatriphenylenes. In this report, we propose an efficient method for the synthesis of cycloalkene-annelated derivatives of monoazatriphenylenes based on an aza-Diels–Alder reaction of the previously uncharacterized 3-(pyridin2-yl)phenathro[9,10-e][1,2,4]triazine (1) [14] with 1-morpholinocycloalkenes. A method for preparing different pyridine derivatives through reaction of the corresponding mononuclear 1,2,4-triazines has been known for some time [15-17]. In our work, we have used this method for the first time in a single-stage synthesis of the poorly available pyridyl-substituted monoazatriphenylenes 2a,b.

Aryne intermediates in the synthesis of polynuclear heterocyclic systems (Review)

Published examples of the polynuclear fused heterocyclic systems production by cycloaddition reactions involving aryne intermediates generated in situ are reviewed.

Solvent-free synthesis of pillar[6]arenes

An efficient solvent-free procedure for the synthesis of pillar[6]arenes has been developed. The procedure involves the solid-state condensation of finely milled 1,4-dialkoxybenzene and paraformaldehyde by grinding in the presence of a catalytic amount of H2SO4. The use of organic solvents for the extraction of products has also been avoided. Operational simplicity, compatibility with various 1,4-dialkoxybenzenes, non-chromatographic purification technique, high yields and mild reaction conditions are the notable advantages of this procedure. A large scale reaction demonstrated the practical applicability of this methodology.

(Benzo[h])Quinolinyl-Substituted Monoazatriphenylenes: Synthesis and Photophysical Properties

We propose a method for the synthesis of quinolinyl- and benzo[h]quinolinylmonoazatriphenylenes through 1,2,4-triazine intermediates with subsequent transformations in aza-Diels–Alder reaction. The photophysical properties of these new compounds were examined, and the effects due to additional fused aromatic rings were explored.

Solvent-free synthesis of 5-(aryl/alkyl)amino-1,2,4-triazines and α-arylamino-2,2′-bipyridines with greener prospects

A green and highly efficient method has been developed for the synthesis of 5-(aryl/alkyl)amino-1,2,4-triazines and α-arylamino-2,2′-bipyridines according to the principles of atom economy. It has been performed by two consecutive solvent-free reaction pathways: the ipso-substitution of a cyano-group in 5-cyano-1,2,4-triazines and the aza-Diels-Alder reaction of the resulting 5-arylamino-1,2,4-triazines with 1-morpholinocyclopentene used as a dienophile. Solvent and catalyst-free conditions, operational simplicity, the compatibility with various functional groups, nonchromatographic purification technique, and high yields are the notable advantages of this procedure. The present methodology possesses a low E-factor.

Reaction of 4,5-dimethoxy-1,2-dehydrobenzene with 3-(Pyridin-2-yl)-1,2,4-triazines

Reaction of 3-(pyridin-2-yl)-1,2,4-triazines with aryne intermediate, 4,5-dimethoxy-1,2-dehydrobenzene generated in situ, was investigated. As a result of the interaction products of the 1,2,4-triazine transformation are produced: 2,3-dimethoxy-10-(1H-1,2,3-triazol-1-yl)-pyrido[1,2-a]indoles, and also the products of Diels-Alder aza-reaction, 6,7-dimethoxy-1-(pyridin-2-yl)isoquinolines.

The Extension of Conjugated System in Pyridyl-Substituted Monoazatriphenylenes for the Tuning of Photophysical Properties

We propose a method for the synthesis of diaryl-substituted pyridylmonoazatriphenylenes by the heterocyclization reaction of dihalosubstituted phenanthrenequinones with pyridine-2-carboxylic acid amidrazone, followed by aza-Diels–Alder reaction and Suzuki cross coupling. The obtained compounds showed more promising photophysical properties, compared to non-arylated analogs.

Extended cavity pyrene-based iptycenes for the turn-off fluorescence detection of RDX and common nitroaromatic explosives

Extended cavity pyrene-based iptycenes have been synthesized by using the Diels–Alder reaction between in situ generated dehydropyrenes and anthracene. The photophysical properties and the interaction of these iptycenes with nitro-explosive components were studied both in solution and in the solid state by using fluorescence spectroscopy and X-ray crystallography, respectively. Due to the presence of both the large iptycene cavity and the central pyrene core, an unprecedently high fluorescence-quenching response towards non-aromatic and non-planar 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) has been observed both in solution (with an apparent Stern–Volmer constant value aKSV up to 1.53 × 103 M−1) and in the vapor phase (50–75% fluorescence quenching of the PU films doped with chemosensors). In the case of nitroaromatic explosives, nitrobenzene (NB), 2,4-DNT, TNT, and 2,4,6-trinitrophenol (TNP or picric acid, PA), pyrene-based iptycenes also demonstrate a good fluorescence-quenching response both in solutions (with apparent Stern–Volmer constant values aKSV = 0.4–8.0 × 103 M−1) and in the vapor phase (up to 90% fluorescence quenching of the PU films doped with chemosensors). The “sphere of action” fluorescence quenching model was suggested.

Effective synthetic approach to 4′,5-Diaryl-2,2′:6′,2″-terpyridines

By applying a combination of Kröhnke method and “1,2,4-triazine” method (Sauer method) 2,2′:6′,2″-terpyridines were prepared bearing various aromatic substituents in the positions 4′ and 5 of the oligopyridine scaffold.