Synthesis of 1,2,4,5-tetrazines, symmetrically and unsymmetrically 3,6-disubstituted by N-nucleophiles

6-R-3-(3,5-Dimethylpyrazol-1-yl)-1,2,4,5-tetrazines with aliphatic, cycloaliphatic, and aromatic amines, and also with NH-heterocycles undergo a nucleophilic substitution of the dimethylpyrazole moiety yielding symmetrically and unsymmetrically substituted 1,2,4,5-tetrazines. In the 3,6-diimidazolyl-and 3,6-dibenzotriazolyl derivatives reactions of nucleophilic substitution of the heterocyclic moiety also occur. In some cases an ipsosubstitution of amino, hydrazino, and azido groups is observed.     

Synthesis,structures, and magnetic properties of crystals of dinuclear copper(II) and cobalt(II) complexes with 3-(3,5-dimethylpyrazol-1-yl)-6-R-1,2,4,5-tetrazines

Dinuclear complexes of Cu^II with 3-(3,5-dimethylpyrazol-1-yl)-6-(2-hydroxyethylami-no)-1,2,4,5-tetrazine (1) and CoII with 3-(3,5-dimethylpyrazol-1-yl)-6-(piperidin-1-yl)-1,2,4,5- tetrazine (2) were synthesized and structurally characterized, and the magnetic (SQUID) and resonance (EPR) properties of van der Waals crystals based on these complexes were studied. Unusual behavior of the effective magnetic moment μ_eff(T) is observed at T < 60 K. A nonmonotonic increase in μeff(?) for 1 (s~6 %) and a 20% reduction of μeff(?) for 2 have a common origin and are due to the influence of spin-orbital coupling on the character of the splitting between the t2g and eg levels of the central ion. Distortions of the coordination site “switch on” a positive (1) or negative (2) contribution of the orbital magnetic moment near 6 K. Irreversible temperature behavior of μeff(T) in the heating and cooling regimes in the vicinity of 60 K suggests that the character of structural distortions and the magnetic properties are related to ligand geometry. This factor plays a significant role in crystal engineering of magnetoactive structures with polynitrogen ligands.     

Synthesis and Cytotoxic Activity of 1,3,5-Triazinane Derivatives Based on Primary Amines and Amino Acids Esters

Russian Journal of General Chemistry - A series of 1,3,5-triazinane derivatives was synthesized and their cytotoxic activity was studied in vitro on normal cell line (HEK293) and tumor cell lines...     

Modeling of 1,2,4,5-tetrazine complexes with organic amines

Tetrazine complexes with organic ligands have been modeled. The composition and structure of the model complexes agree with experimental data. The structure and nature of the complexes affect a number of chemical reactions of 1,2,4,5-tetrazines with organic amines. It is shown that the possibility and route of nucleophilic substitution in the 3 and 6 positions of the tetrazine ring are provided by amine localization in the tetrazine complex and also by the orbital characteristics of the reagents. The route and possibility of cycloaddition reactions for tetrazines are dictated by the ability of the latter to form π-complexes with reagents and by the orbital characteristics of the complexes. The route of the cycloaddition reaction is also affected by the solvent.     

Cyclization of (1,2,4,5-tetrazin-3-yl)hydrazones to 3,7-dihydro-1,2,4-triazolo[4,3-b]-1,2,4,5-tetrazines

The intramolecular cyclization of (6-R-1,2,4,5-tetrazin-3-yl)hydrazones of ketones (R is 3,5-dimethylpyrazol-1-yl, 4-methylimidazol-1-yl, or 2-alkylidenehydrazino) giving rise to the previously unknown 3,7-dihydro-1,2,4-triazolo[4,3-b]-1,2,4,5-tetrazines, including spiro compounds, was studied. The reactivity and the yields of the reaction products depend on the structure of the alkylidene fragment and the nature of the substituent in the tetrazine ring.

     

Intermolecular interactions in heteromolecular crystals of tetrazine derivatives with azoles

Heteromolecular crystal structures formed by symmetrically and unsymmetrically 3,6-disubstituted tetrazine derivatives with NH donor azoles are investigated. The main crystal motifs and the intermolecular interactions responsible for their formation are identified.     

One-pot synthesis of 6H-pyrrolo[2,3-e[1,2,4]triazolo[1,5-a]pyrimidines on the basis of σH-adducts of 6-Nitro[1,2,4]triazolo[1,5-a]pyrimidine with carbonyl compounds

Aromatic, heteroaromatic, and aliphatic carbonyl compounds reacted with 6-nitro[1,2,4]triazolo[1,5-a]pyrimidine in the presence of a base to give stable σ^H-adducts at C⁷. Reduction of the nitro group in the latter is accompanied by tandem autoaromatization of the azine ring and intramolecular cyclocondensation with formation of the corresponding 6H-pyrrolo[2,3-e][1,2,4]triazolo[1,5-a]pyrimidines. Original Russian Text ? E.B. Gorbunov, G.L. Rusinov, R.I. Ishmetova, V.N. Charushin, O.N. Chupakhin, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 1, pp. 130–134. Dedicated to Full Member of the Russian Academy of Sciences G.A. Tolstikov on his 75th anniversary     

Synthesis and antifungal activity of 3-substituted imidazo[1,2-<Emphasis Type="Italic">b</Emphasis>][1,2,4,5]tetrazines

A number of new 3-substituted imidazo[1,2-b][1,2,4,5]tetrazines containing azolyl, aminopyridyl, and alkoxyl substituents was synthesized. These compounds were studied for the biological activity against mycelial anthropophilic and zoophilous dermatophyte fungi (Trichophyton, Microsporum and Epidermophyton), causing diseases of skin and its appendages (hair, nails), and yeast-like fungi Candida.     

[4+2]-Cycloaddition of 3,6-bis(3,5-dimethyl-4-R-pyrazol-1-yl)-1,2,4,5-tetrazines with alkenes

A number of 1,4-dihydropyridazines and pyridazines were prepared by the Diels-Alder reaction with an inverse electron demand from cyclic heterodiene systems, 3,6-bis(3,5-dimethyl-4-R-pyrazol-1-yl)-1,2,4,5-tetrazines, and some enamines as well as from 4-vinylpyridine, butyl vinyl ether, phenylacetylene, and acrylamide. The reaction of 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazine with styrene afforded 4,5-dihydropyridazine, which was readily oxidized by atmospheric oxygen to form the corresponding pyridazine. Electron-withdrawing substituents (Br or Cl) in the pyrazole rings accelerate [4+2]-cycloaddition. When heated, 1,4-dihydropyridazines, which were synthesized from tetrazines and enamines, eliminated amine to give pyridazines. The reactivities of tetrazines were evaluated by quantum-chemical methods. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 354–360, February, 2000.