N. K. Ignatenko

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

Abstract6-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 and transformations of cyanomethyl-1,2,4,5-tetrazines

Derivatives of s-tetrazine containing malonodinitrile, ethyl cyanoacetate, and 1,3-indanedione fragments were synthesized by the nucleophilic substitution of heterocyclic groups in 3,6-diazolyl-1,2,4,5-tetrazines. Coordination compounds of the cyanomethyltetrazine anion with Cu+, Mn2+, and the tetrathiafulvalene radical cation were obtained, and their structures were determined. A transformation of cyanomethyltetrazines to pyrrolo[1,2-b][1, 2, 4, 5]tetrazines catalyzed by metal cations was discovered.

Replacement of dimethylpyrazolyl group in 1,2,4,5-tetrazines by aliphatic alcohols and water

Reactions of 3,6-bis(4-R-3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazines and 3-amino-6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazines with aliphatic alcohols and water in the presence of a base involved replacement of the dimethylpyrazolyl group and resulted in the formation of mono- and dialkoxy-1,2,4,5-tetrazines and 6-substituted 3-hydroxy-1,2,4,5-tetrazines. Dissociation constants of the latter were determined by potentiometric titration.

Study of the supramolecular structures of complexes of carborane-containing pyridazines with 2,3,5,6-tetrachloro-1,4-dihydroxybenzene

The structures and characteristic features of the molecular packing patterns of complexes of pyridazines containing heterocyclic substituents and the carborane moiety with 2,3,5,6-tetrachlorohydroquinone (TCHQ) were investigated. It was shown that TCHQ can form supramolecular assemblies with carborane-containing substituted pyridazines. The stoichiometry and three-dimensional structures of these assemblies depend on the substituents in the pyridazine ring and are formed via O-H…N hydrogen bonding between TCHQ and heterocyclic molecules.

Reactions of 3,6-bis(3,5-dimethyl-4-R-pyrazol-1-yl)-1,2,4,5-tetrazines with indole and 1,3,3-trimethyl-2-methyleneindoline

It has been found that 3,6-bis(3,5-dimethyl-4-R-pyrazol-1-yl)-1,2,4,5- tetrazines react with indole and 1,3,3-trimethyl-2-methyleneindoline to give pyridazines as (4+2)cycloaddition products. 1,3,3-Trimethyl-2-methyleneindoline has been shown to act as C-nucleophile in the substitution of pyrazolyl group as well as in the reactions of tetrazine ring expansion in

Synthesis and antifungal activity of 3-substituted imidazo[1,2-b][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.

Synthesis and tuberculostatic activity of amine-substituted 1,2,4,5-tetrazines and pyridazines

A series of novel 3,6-disubstituted 1,2,4,5-tetrazines and pyridazines bearing aminopyridyl, hydrazono, or aminoalkyl substituents were synthesized. Ten of these compounds showed marked tuberculostatic activity (MIC ≤ 12.5 mkg mL−1).

Synthesis and Tuberculostatic Activity of 2-Alkyl-5-Aryltetrazoles

2-Substituted 5-aryltetrazoles containing alkyl and aminoalkyl fragments were synthesized using alkylation and Mannich reactions. The tuberculostatic activity of the synthesized compounds against strain M. tuberculosis H37Rv was studied. Pronounced tuberculostatic activity (MIC ≤ 1.5 ìg/mL) was found for tetrazoles containing N(2) dimethyl- and diethylaminoethyl fragments.

Electrophilic heterocyclization reactions of allylamino- and propargylamino-substituted sym-tetrazines in the presence of HgI2

A range of 3-azolyl-6-methylimidazo[1,2-b][1, 2, 4, 5]tetrazines was obtained for the first time by electrophilic heterocyclization of 6-allylamino-3-azolyl- and 3-azolyl-6-propargylamino-1,2,4,5-tetrazines in the presence of HgI2. The structures of the starting materials and final products were confirmed by 1H and 13C NMR spectroscopy, elemental analysis, and X-ray structural analysis.

Terminal bis-acetylenes derived from 1,2-bis(1H-tetrazol-5-yl)ethane

The N(1)—N(1), N(2)—N(2), and N(1)—N(2) regioisomers of 1,2-bis[(prop-2-yn-1-yl)-1H-tetrazol-5-yl]ethane were first synthesized by alkylation of 1,2-bis(1H-tetrazol-5-yl)ethane with propargyl bromide. The peculiarities of the crystal structure of 1,2-bis[1-(prop-2-yn-1-yl)-1H-tetrazol-5-yl]ethane were evaluated by X-ray diffraction analysis. This compound is readily underwent Cu-catalyzed [3+2] cycloaddition with p-tolyl azide, p-nitrophenyl azide, and benzyl azide to give heterocyclic assembles bearing 1,2,3-triazole and tetrazole cycles. Catalyst-free [3+2] cycloadditions of 1,2-bis[1-(prop-2-yn-1-yl)-1H-tetrazol-5-yl]ethane and the mixtures of the N(1)—N(1), N(2)—N(2), N(1)—N(2) regioisomers with poly(glycidyl azide) oligomers resulted in 1,2,3-triazole cycles and crosslinking of the polymer chains.