Oxidations of 3,6-diamino-1,2,4,5-tetrazine and 3,6-bis(s,s-dimethylsulfilimino)-1,2,4,5-tetrazine

Oxidation of 3,6-diamino-1,2,4,5-tetrazine ( 1 ) with most peracids gave 3,6-diamino-1,2,4,5-tetrazine 1,4-dioxide ( 3 ) as the major product; however, treatment of 1 with peroxytrifluoroacetic acid (PTFA) gave 3,6-diamino-1,2,4,5-tetrazine 1-oxide ( 4 ) as the major product along with a small amount of 3-amino-6-nitro-1,2,4,5-tetrazine 2,4-dioxide ( 5 ). Oxidation of 3,6-bis(S,S-dimethylsulfilimino)-1,2,4,5-tetrazine ( 6 ) with 3-chloroperoxybenzoic acid (MCPBA) gave 3-S,S-(dimethylsulfilimino)-6-nitroso-1,2,4,5-tetrazine ( 7 ), which was oxidized further with dimethyldioxirane to 3-(S,S-dimethylsulfoximino)-6-nitro-1,2,4,5-tetrazine ( 8 ). All attempts to obtain 3,6-dinitro-1,2,4,5-tetrazine ( 2 ) by further oxidation of 7 or 8 failed.     

Synthesis of peroxide compounds by the BF3-catalyzed reaction of acetals and enol ethers with H2O2

Aliphatic and alicyclic gem-bis-hydroperoxides and their derivatives, bis(1-hydroperoxycycloalkyl) and bis(1-hydroperoxyalkyl) peroxides, dispiro- and tetraalkyl-1,2,4,5-tetroxanes were synthesized by the reaction of aliphatic and alicyclic acetals and enol ethers with H₂O₂ in the presence of BF₃ in anhydrous Et₂O.     

Nucleophilic substitution with amines: dihydro-1,2,4,5-tetrazines are more useful precursors than 1,2,4,5-tetrazines

A one step synthesis of (di)alkylamino-substituted 1,2,4,5-tetrazines direct from 3,6-disubstituted-1,2-dihydro-1,2,4,5-tetrazine precursors is described. A comparative study revealed that the described method not only avoids the up-to-now required oxidation step but also lower reaction times and/or temperatures compared to usual protocols. The efficiency of the reaction was highlighted by a practical synthesis of 3,6-bis(methylamino)-1,2,4,5-tetrazine using aqueous methylamine. Other primary and secondary amines were also found to give disubstitution products when reacted with 3,6-bis(methylsulfanyl)-1,2,4,5-dihydrotetrazine.     

Synthesis of 1,2,4,5-Tetrakis(1,2,4-Triazolyl) Benzene and 1,2,4,5-Tetrakis(1,3,4-Oxadiazolyl) Benzene Derivatives

Abstract

A series of 1,2,4,5-tetrakis(1,2,4-triazolyl)benzenes and 1,2,4,5-tetrakis(1,3,4-oxadiazolyl)benzenes was synthesized by nucleophilic addition of sodium salts of 4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thiones and 1,3,4-oxadiazole-2(3H)-thiones to 1,2,4,5-tetrakis(bromomethyl)benzene. The structure of the newly synthesized compounds was confirmed by elemental analysis, IR and ¹H and ¹³C NMR spectra.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: 1H and 13C NMR spectra of products (Figures S1-S24).     

Energetic Trinitro‐ and Fluorodinitroethyl Ethers of 1,2,4,5‐Tetrazines

Several new energetic ethyl ethers of 1,2,4,5‐tetrazine have been synthesized. These molecules display good thermal stability, good oxygen balance, and high densities. Included in these studies are a 2,2,2‐trinitroethoxy 1,2,4,5‐tetrazine and two fluorodinitroethoxy 1,2,4,5‐tetrazines. One of these compounds was converted into the di‐N‐oxide derivative. The sensitivity of these materials towards destructive stimuli was determined, and overall the materials show promising energetic performance properties.     

Azido and Tetrazolo 1,2,4,5‐Tetrazine N‐Oxides

This study presents the synthesis and characterization of the oxidation products of 3,6‐diazido‐1,2,4,5‐tetrazine ( 1 ) and 6‐amino‐[1,5‐b ]tetrazolo‐1,2,4,5‐tetrazine ( 2 ). 3,6‐Diazido‐1,2,4,5‐tetrazine‐1,4‐dioxide was produced from oxidation with peroxytrifluoroacetic acid, and more effectively using hypofluorous acid, and 2 can be oxidized to two different products, 6‐amino‐[1,5‐b]tetrazolo‐1,2,4,5‐tetrazine mono‐N‐oxide and di‐N‐oxide. These N‐oxide compounds display promising performance properties as energetic materials.     

The chemistry of hexahydro-1,2,4,5-tetrazines—II: Mass spectra of 1,4-dialkylhexahydro-1,2,4,5-tetrazines and 1,4-dialkyl-2,5-diacylhexahydro-1,2,4,5-tetrazines

The mass spectra of twenty-eight 1,4-dialkylhexahydro-1,2,4,5-tetrazines and 1,4-dialkyl-2,5-diacylhexahydro-1,2,4,5-tetrazines (1) have been recorded and interpreted with the aid of deu-terium labelling, high resolution measurements, and the metastable defocusing technique. The principal fragmentations involve initial scission of ring bonds, particularly C-N bonds, leading to characteristic ions of mass M/2 and M/2± 1, and to 2,3-diaza-1,3-butadienyl ions (II). In the spectra of acylated compounds, acyl migration occurs within the molecular ion. The elimination of formaldehyde from the principal fragment ion is discussed.     

A N NMR study of tautomerism in dimethyl dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate

Dimethyl dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate can exist either in 1,2- or 1,4-dihydro tautomeric forms. The ¹⁵N NMR spectra of dimethyl dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate were measured at the ¹⁵N natural abundance level as well as in ¹⁵N doubly labelled selectively and in ¹⁵N completely labelled compounds (20% ¹⁵N). The J(¹⁵N,¹⁵N) value was determined in ¹⁵N completely labelled compounds (20% ¹⁵N) using 1D ¹⁵N INADEQUATE and was found to be 12.2 ± 0.2 Hz in deuteriochloroform, acetonitrile-d₃, DMSO-d₆ and CD₃OH. Very similar ¹⁵N chemical shifts and ¹J(¹⁵N,¹H) values were also observed in all the solvents. This indicates that compound 1 exists completely in the 1,4-dihydro tautomeric form (i.e., as dimethyl 1,4-dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate) in all the solvents tested.     

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.     

Reactions of 1,2,4,5-tetrazines with S-nucleophiles

The reactions of 3,6-disubstituted and azoloannulated 1,2,4,5-tetrazines containing heterocyclic leaving groups with S-nucleophiles were studied. The methods of introduction of functionalized thiols, including thiol derivatives of 1,7- and 1,2-dicarba-closo-dodecaboranes, into the tetrazine ring were developed. It was established for the first time that, instead of replacement of a leaving group in the tetrazine ring, the attack of S-nucleophile at the unsubstituted carbon atom occurs in the case of imidazo[1,2-b][1,2,4,5]tetrazines to form previously unknown products of nucleophilic substitution of the hydrogen atom.

     

Synthesis of 6-(arylthio)- and 6-[(arylmethyl)thio] -1,2,4,5-tetrazin-3-amines and n-phenyl- and n-(phenylmethyl)-1,2,4,5-tetrazine-3,6-diamines as potential antimalarial agents

Alkylation of tetrahydro-1,2,4,5-tetrazine-3,6-dithione with iodomethane and 1,2-dichloro-4-(chloromethyl)benzene, respectively (Scheme 1, 4 ) followed by oxidation afforded 3,6-bis(methylthio)- and 3,6-bis[[(3,4-dichlorophenyl)methyl]thio]-1,2,4,5-tetrazines ( 6, 15 ). The reaction of 15 with amines provided the 6-[(arylmethyl)thio]-1,2,4,5-tetrazin-3-amines ( 16) while sequential displacement of both methylthio groups in 6 afforded the tetrazine-diamines 8 and 10 . Hydrolysis of N,N-dimethyl-6-(methylthio)-1,2,4,5-tetrazin-3-amine ( 11 ) with potassium hydroxide afforded the tetrazin-3-ol ( 12 ) which was chlorinated and then treated with 4-chlorobenzenethiol to provide 13 . The target 6-substituted-1,2,4,5-tetrazin-3-amines displayed negligible antimalarial activity.     

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.

     

Low-frequency vibrational modes and temperature dependence of NQR frequencies in 1,2,4,5-tetrabromobenzene

A temperature variation study of the nuclear quadrupole resonance (NQR) frequencies for the two resonance lines in 1,2,4,5-tetrabromobenzene was carried out in the range 77–300 K. The far-infrared spectrum of 1,2,4,5-tetrabromobenzene was recorded and the low-frequency vibrational modes noted. From the nine observed frequencies, the torsional modes contributing to the change in NQR frequencies with temperature are identified by correlating the calculated values of the NQR frequencies at different temperatures with the observed values.     

Stereoselective one-pot preparation of 1,2,4,5-tetraalkylidene- and 1,4-dialkylidenecyclohexanes

1,2,4,5-Tetraalkylidene- and 1,4-dialkylidenecyclohexanes were prepared by the regio- and stereoselective homocoupling of skip-type diynes and enynes, and their Diels-Alder reaction to form a polycyclic compound was demonstrated.     

Synthesis of 5-trifluoromethylpyrazol-1-yl-substituted 1,2,4,5-tetrazines

Previously unknown products of the cyclocondensation of 1,1,1-trifluoro-2,4-pentanedione with triaminoguanidine and hydrazine derivatives of 1,2,4,5-tetrazine have been obtained. 5-Hydroxy-5-tri-fluoromethylpyrazoline substituents formed on the tetrazine ring were dehydrated under the action of trifluoroacetic anhydride. A comparison has been carried out of the reactivity of 5-trifluoro-methylpyrazolyl-substituted 1,2,4,5-tetrazines and their unfluorinated analogs in nucleophilic substitution and [4 + 2] cycloaddition reactions.     

N-Alkylation of Unsymmetrical 1,6-Dihydro-1,2,4,5-tetrazine Under Alkali Condition

6-Methyl-3-phenyl-1,6-dihydro-1,2,4,5-tetrazine was stable in alkali solution at room temperature and decomposed gradually to form 1,2-dibenzylidenehydrazine. The plausible mechanism of the reaction is discussed. Because it was stable for a period of time, a convenient and effective method for synthesis of 1-alkyl-1,6-dihydro-1,2,4,5-tetrazines has been developed. The starting 1,6-dihydro-1,2,4,5-tetrazine can be alkylated with alkyl halides in methanol and lithium hydroxide monohydrate as a base at room temperature.     

An improved synthesis of 3,6-diamino-1,2,4,5-tetrazine. II. From triaminoguanidine and 2,4-pentanedione

A new synthesis for the title compound that gives an 80% overall yield was developed. Treatment of triaminoguanidine monohydrochloride ( 1 ) with 2,4-pentanedione ( 2 ) gave 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine ( 3 ) in 80–85% yield. Oxidation of 3 with nitric oxide or nitrogen dioxide to 3,6-bis(3,5-dimethyylpyrazol-1-yl)-1,2,4,5-tetrazine ( 4 ) followed by ammonolysis of 4 gave 3,6-diamino-1,2,4,5-tetrazine ( 5 ) in guantitatively yields.     

Synthesis and reactions of 7-phenylimidazo[1,2-b][1,2,4,5]tetrazines with nucleophiles

Russian Chemical Bulletin - A series of novel 3-substituted 7-phenylimidazo[1,2-b][1,2,4,5]tetrazines was synthesized via the reaction of 3-R-amino-1,2,4,5-tetrazines with 2-aminoacetophenone. The...     

The coordination chemistry of 1,2,4,5-tetrazines

1,2,4,5-Tetrazine and its 3,6-disubstituted derivatives exhibit a particular coordination chemistry, characterized by electron and charge transfer phenomena and by the ability of these heteroatom-rich ligands to bridge metal centers in various ways. A very low-lying π* orbital localized at the four nitrogen atoms is responsible for intense low-energy charge transfer absorptions, electrical conductivity of coordination polymers, unusual stability of paramagnetic radical or mixed-valent intermediates and for often well-resolved EPR hyperfine structure in the radical complexes. Substituted 1,4-dihydro-1,2,4,5-tetrazines have also been used as bridging ligands. The structural consequences of electron transfer as well as the capability for efficient and variable metal–metal bridging render the tetrazines as valuable components of supramolecular materials.     

Vapour pressures of crystalline 1,2,4,5-tetrachlorobenzene,and crystalline and liquid 1,3,5-trichlorobenzene and 1,2,4,5-tetramethylbenzene

Vapour pressures as a function of temperature for 1,3,5-trichlorobenzene [CA 108-70-3] (crystalline and liquid), 1,2,4,5-tetrachlorobenzene [CA 95-94-3] (crystalline), and 1,2,4,5-tetramethylbenzene [CA 95-93-2] (crystalline and liquid) were determined by means of a diaphragm manometer and simultaneous torsion, mass-loss effusion. An unconventional but simple method is used for the representation and the assessment of the present experimental results, together with results from other authors. The method is physical in nature, and at the same time reveals the quality of the experimental results in terms of random and systematic errors. The thermodynamic properties at p^o =  1 Pa were evaluated, the results being (the uncertainties are standard deviations, and T_tdenotes triple point):