Mechanochemical approaches in an organic synthesis have received increased interest because of their wide applications in green methodologies.

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A general synthetic route for the synthesis of functionalized bi- and terpyridines is reported. Functionalized 1,2,4-triazene 4-oxides 7 and 8-obtained from the reaction of hydrazones 1 with pyridine aldehydes and followed by oxidation-are functionalized by introduction of a cyano group via nucleophilic aromatic substitution. The thus-obtained 5-cyano-1,2,4-triazines 9 and 10 undergo facile inverse-electron-demand Diels-Alder reactions with enamines and alkenes to yield functionalized bi- and terpyridines, respectively. The substituent at position 6 of the 1,2,4-triazene 4-oxides must be aromatic or heteroaromatic in order to allow their facile synthesis, but other substituents and reagents may vary. Each step of the synthetic route allows diversification, which makes the approach particularly useful for the facile synthesis of a large variety of functionalized bi- and terpyridines.

Azolo[5,1 c] 1,2,4 triazines as a new class of antiviral compoundsSynthetic methods, reactivity, and the properties of a new class of antiviral compounds, pyrazolo , imidazo , 1,2,4 triazolo[5,1 c] 1,2,4 triazinones, tetrazolo[5,1 b] 1,2,4 triazinones, and azoloannulated amino 1,2,4 triazines having structural similarity with biogenic purines and capable of mimicking them in metabolic processes are considered.Aza analogs and structural analogs of natural purine and pyrimidine bases are widely employed for the synthesis of abnormal nucleosides in the search for antiviral and antitumor agents. Abnormal nucleosides on the basis of azauracil, azathymine, and azacytosine have been prepared, 18-31 for example, antiviral compounds 6-9. Pyrrolo , 32 imidazo , 33-35 and 1,2,4 triazolo 1,2,4 tri azines 33,36,37 containing a ribosyl fragment in the azole ring, for example, compounds 10-12, have been described.This review considers the synthetic methods, reactiv ity, and properties of 1,2,4 triazinones annulated at the edge to pyrrole, pyrazole, imidazole, or 1,2,4 triazole frag ment; 7 aminoazolo 1,2,4 triazines and tetrazolo[5,1 b] 1,2,4 triazine 7(4H) ones, 7 aminotetrazolo[5,1 b] 1,2,4 triazines, and abnormal nucleosides based on them. The last section is devoted to the antiviral action of this class of compounds, which allows one to estimate the synthetic potential of the heterocyclic system in the search for anti viral agents.The considered azolotriazines have three types of num bering of the heterocyclic system. Thus the numbering of pyrrolo , pyrazolo , imidazo[5,1 c] 1,2,4 triazine, and imidazo[2,1 c] 1,2,4 triazine I starts with a triazine ni trogen, while in 1,2,4 triazolo[3,4 c] 1,2,4 triazine II, 1,2,3 triazolo , 1,2,4 triazolo , and tetrazolo[5,1 c] 1,2,4 triazines III, from azole nitrogens.Discussion of the methods of synthesis and chemical properties of the whole group of azolo[c] 1,2,4 triazines using their inherent numbering systems is inconvenient for the unified information perception; therefore, in the review we number the heterocyclic system as is usually done for 1,2,3 triazolo , 1,2,4 triazolo , and tetrazolo [5,1 c] 1,2,4 triazines III. Synthesis of azolo[5,1 c] 1,2,4 triazin 7(4H) ones and 7 aminoazolo[5,1 c] 1,2,4 triazinesThe azolo[5,1 c] 1,2,4 triazine system can be con structed by two strategic approaches: annulation of a 1,2,4 triazine ring to an azole ring or annulation of an azole ring to a 1,2,4 triazine ring. The annulation of a 1,2,4 triazine ring is mainly performed according to the [4+2] pattern, the N-C-N-N fragment of the 1,2,4 triazine ring be ing provided by the azole moiety, and the C-C fragment coming from the second reactant. According to the [3+3]Azolo[5.1 c] 1,2,4 triazine Russ.

Two general methods for the selective incorporation of an (15)N-label in the azole ring of tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines were developed. The first approach included treatment of azinylhydrazides with (15)N-labeled nitrous acid, and the second approach was based on fusion of the azine ring to [2-(15)N]-5-aminotetrazole. The synthesized compounds were studied by (1)H, (13)C, and (15)N NMR spectroscopy in both DMSO and TFA solution, in which the azide-tetrazole equilibrium is shifted to tetrazole and azide forms, respectively. Incorporation of the (15)N-label led to the appearance of (13)C-(15)N J coupling constants (J(CN)), which can be measured easily using either 1D (13)C spectra with selective (15)N decoupling or with amplitude modulated 1D (13)C spin-echo experiments with selective inversion of the (15)N nuclei. The observed J(CN) patterns permit unambiguous determination of the type of fusion between the azole and azine rings in tetrazolo[1,5-b][1,2,4]triazine derivatives. Joint analysis of J(CN) patterns and (15)N chemical shifts was found to be the most efficient way to study the azido-tetrazole equilibrium.

N‐(2‐Methoxybenzyl)‐2,5‐dimethoxyphenethylamines (NBOMes) are synthetic phenethylamine derivatives emerging on the global drug market and reported to be associated with untoward effects in people who use drugs. Its action involves agonism at serotonin 5‐HT2A receptors, affecting cognitive and behavioral processes. However, certain isomers of NBOMes may not show any psychoactive effects. They are not controlled by legislation and can be tested as pharmaceutical drugs. This study deals with the differentiation among positional isomers of 25H‐NBOMe differing in the position of the two methoxy groups in the phenylethyl moiety of the molecule, using chromatography–mass spectrometry methods. The gas chromatography analysis showed that the isothermal mode was more efficient than the usually applied temperature‐programming mode for the separation of the mentioned isomers. Electron ionization mass spectra of 25H‐NBOMe isomers were highly similar, often resulting in a high probability of erroneous identification. However, mass spectra of their trifluoroacetyl or pentafluoropropanoyl derivatives were easily identified as they contained fragments with many significant differences. The proposed analysis using liquid chromatography–tandem mass spectrometry could distinguish the isomers of 25H‐NBOMe without the need for any derivatization.

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