Grigory V. Zyryanov

A decade update on solvent and catalyst-free neat organic reactions: a step forward towards sustainability

Particular success has been achieved in the synthesis of new products and in processes since the twelve principles of “green chemistry” were formulated in the 1990s. These products and processes are more compatible with human health, society, and the environment. In this review, a collection of research reports have been documented from the viewpoint of green chemistry. The main theme of this review is neat reactions, which are solvent and catalyst-free reactions. Neat reactions in the absence of any solvent or catalyst with concise summaries of microwave, ball milling, and neat reactions have been described.

Organocatalysis by an aprotic imidazolium zwitterion: regioselective ring-opening of aziridines and applicable to gram scale synthesis

An imidazole-based zwitterionic-salt, 4-(3-methylimidazolium)butane sulfonate (MBS), has been found to be an efficient organocatalyst for aziridine ring-opening regioselectively by various nucleophiles like indoles, pyrroles, methanol, ethanol, acetic acid and di-iso-propylamine. The reactions are highly regioselective and they always afford the products resulting from benzylic attack. The present methodology is applicable to gram scale synthesis.

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.

Brønsted acidic ionic liquid-catalyzed tandem reaction: an efficient approach towards regioselective synthesis of pyrano[3,2-c]coumarins under solvent-free conditions bearing lower E-factors

1-Butane sulfonic acid-3-methylimidazolium tosylate, [BSMIM]OTs, is found to be a remarkable catalyst for the tandem cyclization of 4-hydroxycoumarin with chalcones for the syntheses of pyrano[3,2-c]coumarins under solvent-free conditions. The developed protocol is applicable for the construction of biologically important pyranocoumarins from easily accessible chalcones having various substituents. This reaction possibly proceeds through Michael addition followed by cyclization. The feasibility of catalyst recycling is also demonstrated. This method produces only water as the byproduct and represents a green synthetic protocol. The catalytic reaction proceeded very smoothly under solvent-free conditions and showed high regioselectivity. Clean reaction, non-chromatographic purification technique, easily accessible reactants, and metal and solvent-free and environmentally friendly reaction conditions are the notable advantages of this procedure. In addition, this method shows lower E-factors.

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.

Combination of NH2OH·HCl and NaIO4: an effective reagent for molecular iodine-free regioselective 1,2-difunctionalization of olefins and easy access of terminal acetals

We have demonstrated a new application of our oxidizing reagent, a combination of NH2OH·HCl and NaIO4, in the first generalized regioselective 1,2-difunctionalization of olefins. It is a general method for the preparation of β-iodo-β′-hydroxy ethers, β-iodo ethers, β-iodohydrin, and β-iodo acetoxy compounds using different reaction media. The reactions are highly regioselective, always affording Markovnikovs type addition products. The methodology is also applicable for the easy access of terminal acetals. Molecular iodine-free synthesis, room temperature reaction conditions, high yields, use of less expensive reagents, mild reaction conditions, broad applicability of nucleophiles, and applicability for gram-scale synthesis are the notable advantages of this present protocol.

Direct diastereoselective addition of l-menthol to activated 1,2,4-triazin-5(4H)-one

Abstract For the first time in a triazine series it has been found that addition of a chiral O -nucleophile, l -menthol, to the C 6 -unsubstituted atom of 3-phenyl-1,2,4-triazin-5(4 H )-one 1 activated by aliphatic acid anhydrides proceeds diastereoselectively to form a mixture of 1-acyl-6-[(1′ R ,3′ R ,4′ S )-menthyl-3′)]-3-phenyl-(6 S )-1,6-dihydro-1,2,4-triazin-5(4 H )-ones 2 and 1-acyl-6-[(1′ R ,3′ R ,4′ S )-menthyl-3′)]-3-phenyl-(6 R )-1,6-dihydro-1,2,4-triazin-5(4 H )-ones 3 in which the diastereomers 2 predominate. The diastereoselectivity of the process improves as the size of the N 1 -acyl substituent increases.