Synthesis and study of thermal stability of 3-nitro-1,2,4-triazole N-nitroxy-and N-azidomethyl derivatives

A method for the preparation of new 3-nitro-1,2,4-triazole derivatives has been suggested based on modification of the N-hydroxymethyl group by nitration and nucleophilic substitution reactions. Thermal stability of 3-nitro-1,2,4-triazole N-nitroxy- and N-azidomethyl derivatives, as well as of dinitrates, 5,5′-dinitro-2,2 ′-bisnitroxymethyl-2 H,2′H-3,3 ′-bi(1,2,4-triazole) and -(nitromethylene)bis(1,2,4-triazole), has been studied.     

Reactions of 3-nitro-1,2,4-triazoles with alkylating agents. 6*. Alkylation of a neutral heterocycle by alcohols in acid media*

Reaction of 3-nitro-1,2,4-triazole and 5-methyl-3-nitro-1,2,4-triazole with secondary and tertiary alcohols in conc. H₂SO₄ takes place at the N(2) atom. Alkylation by 2-propanol occurs regioselectively to form the 1-isopropyl-3-nitro-and 1-isopropyl-3-methyl-5-nitro-1,2,4-triazoles. As a consequence of isomerization the alkylation using cyclohexyl or tert-butyl alcohols gives respectively a mixture of regioisomers substituted at atom N(1) (1-cyclohexyl-3-nitro-and 1-cyclohexyl-5-methyl-3-nitro-1,2,4-triazoles) and at atom N(2) (5-nitro-1-cyclohexyl-and 1-cyclohexyl-3-methyl-5-nitro-1,2,4-triazoles) and, in the second case, to 1-tert-butyl-3-nitro-1,2,4-triazole. * For Communication 5 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1680–1687, November, 2008.     

Picryl derivatives of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one

Treatment of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one ( 1 ) with picryl fluoride (PkF) in 1-methyl-2-pyrrolidinone (NMP) gave a mixture of a monopicryl and a dipicryl derivative of 1 in a ratio of 2 :1 , respectively, regardless of the initial concentrations of 1 and PkF. The products were identified as 5-nitro-2-picryl-2,4-dihydro-3H-1,2,4-triazol-3-one ( 2 ) by X-ray crystallography and 5-nitro-2,4-dipicryl-2,4-dihydro-3H-1,2,4-triazol-3-one ( 4 ) by ¹⁵N labeling experiments.     

Reactions of 3-Nitro-1,2,4-Triazole Derivatives with Alkylating Agents. 2. Alkylation of a Neutral Heterocycle by Dimethyl Sulfate

The reaction of 3-nitro-1,2,4-triazole and 5-methyl-3-nitro-1,2,4-triazole with dimethyl sulfate leads to mixtures of N-mono- and N,N-dimethylnitrotriazolium compounds and products of the subsequent conversion of the latter, namely, N,N-dimethyl-1,2,4-triazol-5-ones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1168–1173, August, 2005.     

Reaction Of 3-Nitro-1,2,4-triazolederivatives with Alkylating Agents. 1. Alkylation in the Presence of Alkali

Alkylation of 3-nitro-1,2,4-triazole and 5-methyl-3-nitro-1,2,4-triazole with dialkyl sulfates or alkyl halides in the presence of alkali proceeds with a low selectivity for the alkylating agent with the formation of two regioisomers at the N₍₁₎ and N₍₂₎ atoms of the heterocycle. Depending on the reaction conditions the proportion of the N₍₂₎ isomer was 14.6-33.8%. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1020–1025, July, 2005.     

Crystal and Molecular Structure of 5-Acetylamino-3-nitro-1,2,4-triazole

This paper reports on an X-ray diffraction study of 5-acetylamino-3-nitro-1,2,4-triazole. Monoclinic crystals, space group P2_1/c; a=8.2079(7), b=13.096(1), c=13.650(1) , =100.64(1)°. Two independent molecules are identical in conformation and both have an N–H···sO intramolecular hydrogen bond; the difference lies in their interactions with neighbors. In molecule A, the acetyl oxygen atom and all nitrogen atoms (except those of the amino group) are involved in the intermolecular hydrogen bonds; in molecule B, these hydrogen bonds are formed by only two NH groups in addition to the above oxygen. The crystal structure of the title compound is compared with that of 5-amino-3-nitro-1,2,4-triazole.     

Heterocyclic nitro compounds. 26. Reaction of 1-substituted 3,5-dinitro-1,2,4-triazoles with anions of heterocyclic NH acids

1-Substituted 3-nitro-5-(N-azolyl)-1,2,4-triazoles mixed with 1-substituted 3-nitro-1,2,4-triazol-5-ones are obtained in the reaction of 1-substituted 3,5-dinitro-1,2,4-triazoles with anions of heterocyclic NH acids (1,2,4-triazole, 1,2,3-triazole, pyrazole, benzotriazole, benzimidazole, and indazole derivatives). 1-Methyl-3-nitro-5-amino-1,2,4-triazole is formed instead of the expected 5-tetrazolyl derivative in the reaction of 1-methyl-3,5-dinitro-1,2,4-triazole with tetrazole in alkaline media. See [1] for communication 25. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 257–261, February, 1980.     

Reactions of 3-nitro-1,2,4-triazole derivatives with alkylating agents. 5. Selective synthesis of 1,4-dialkyl-and 1,4,5-trialkyl-3-nitro-1,2,4-triazolium salts from 1-alkyl-and 4,5-dialkyl-3-nitro-1,2,4-triazoles and dialkyl sulfates

Interaction of N₍₁₎-alkyl-substituted 3-nitro-5-R-1,2,4-triazoles with dialkyl sulphates proceeds selectively and results in the respective salts of 1,4-dialkyl-, 1,4,5-trialkyl-3-nitro-1,2,4-triazoliums. The reaction of N₍₄₎-alkyl-substituted 3-nitro-5-R-1,2,4-triazoles yields the mixtures of the salts of 1,4-dialkyl-, 1,4,5-trialkyl-3-nitro-1,2,4-triazoliums and 1,4-dialkyl-, 1,3,4-trialkyl-1,2,4-triazol-5-ones with predominance of quaternary salts. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 927–934, June, 2007.     

Reactions of 3-nitro-1,2,4-triazoles with alkylating agents. 3. Alkylation of a neutral heterocycle by diethyl sulfate

The reaction of 3-nitro-5-R-1,2,4-triazoles with diethyl sulfate gives 1-ethyl-3-R-5-nitro-, 4-ethyl-3-nitro-5-R-1,2,4-triazoles, 1,4-diethyl-, 1,4-diethyl-3-methyl-1,2,4-triazol-5-ones, and 1,4-diethyl-3-nitro-5-R-1,2,4-triazolium salts. When compared with the use of dimethyl sulfate as alkylating agent the ethylation products have a markedly increased fraction of triazolones (up to 30–37%) and a somewhat lowered yield of nitrotriazolium salts (up to 6–10%). The reaction time is increased by an order. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1378–1381, September, 2006.     

Vibrational spectra and structure of 1,2,4-triazole derivatives

The frequencies and forms of the normal vibrations of 3-nitro-1,2,4-triazole, its 1-deuteroand 1-methyl derivatives, and 1-methyl-3-nitro-5-chloro(bromo)-1,2,4-triazole, which are classified as having C_S group symmetry, were calculated. The potential energy constants were refined by solution of the reciprocal spectral problem, and the frequencies in the experimental spectra were assigned to the principal types of vibrations.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 707–712, May, 1973.     

Synthesis of certain 1,2,4-triazole nucleoside derivatives

The syntheses of 3-amino-4-methyl-1-(β-D-ribofuranosyl)-1,2,4-triazolin-5-one ( 8a ) and its 2′-deoxy analog 8b as well as 5-amino-2-methyl-1-(β-D-ribofuranosyl)-1,2,4-triazolin-3-one ( 12 ) have been accomplished. Compounds 8a and 8b were synthesized via glycosylation of 3-bromo-5-nitro-1,2,4-triazole which was followed by replacement in three steps of the 3-bromo function to yield 3-nitro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1,2,4-triazolin-5-one ( 4a ) and its 2′-deoxy analog 4b . Compounds 4a and 4b were methylated at N², hydrogenated and deblocked to give 3-amino-4-methyl-1-(β-D-ribofuranosyl)-1,2,4-triazolin-5-one ( 8a ) and the 2′-deoxy analog 8b . Compound 12 was synthesized by glycosylation of 3-amino-1-methyl-1,2,4-triazolin-5(2H)-one ( 10 ). The structures of 8b and 12 were confirmed by single crystal X-ray diffraction analysis.     

Synthesis and structure of new ditopic ligands containing tetrazole and 3-nitro-1,2,4-triazole fragments

Alkylation of 3-nitro-1,2,4-triazole with haloalkyltetrazoles has afforded in high yields previously unknown 1-[2-(3-nitro-1H-1,2,4-triazol-1-yl)ethyl]-1H-tetrazole and 2-tert-butyl-5-(3-nitro-1H-1,2,4-triazol-1-ylmethyl)-2H-tetrazole. The molecular and crystal structure of these compounds has been established by X-ray diffraction analysis (XRD).     

Radiosensitizing hypoxic cells with new 3-nitro-1,2,4-triazole derivatives in vitro and in vivo

The new regioisomer derivatives 4a-f and 5a-f of 3-nitro-1,2,4-triazole (3-NTR) were synthesized for the development of new radiosensitizers of hypoxic cancer cells for radiotherapy. N(2)-Substituted 3-NTR derivatives 5a-f were stronger radiosensitizers of hypoxic cells in vitro (Chinese hamster V79 cells) than N(1)-substituted 3-NTR derivatives 4a-f, but in vivo they were weaker (SCCVII carcinoma cells inoculated into C3H/He mouse).     

Heterocyclic nitro compounds. 25. 1-Hydroxymethyl-3-nitro-1,2,4-triazoles and their derivatives

1-Hydroxymethyl derivatives of tetrazoles were obtained by the reaction of 1,2,4-triazole and 3-nitro-5-substituted triazoles with formaldehyde in water. The hydroxy groups were replaced by chlorine, and the hydroxymethyltriazoles were acetylated and tosylated. The chloro and tosyl groups are readily replaced by iodine by the action of potassium and ammonium iodide in acetone. See [1] for communication 24. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 251–256, February, 1980.     

Iodocyclization of S-allyl derivatives of 3-mercapto-4-methyl-1,2,4-triazole

It has been established that iodocyclization of 3-(2-methyl-2-propenyl)thio-4-methyl-1,2,4-triazole occurs regioselectively with annelation of the thiazole ring, 3-(3-methyl-2-butenyl)thio-4-methyl-1,2,4-thiazole with annelation of the thiazine ring, and 3-allylthio-4-methyl-1,2,4-triazole with annelation of both rings to form derivatives of [1,3]thiazolo[3,2-b][1,2,4]triazolium and [1,2,4]triazole[5,1-b][1,3]thiazinium iodides.     

Alkylation of 4(5)-nitro-1,2,3-triazole with alcohols in strongly acidic media

Alkylation of 4(5)-nitro-1,2,3-triazole with alcohols in concentrated H₂SO₄ occurs at all three endocyclic N atoms, giving a mixture of isomeric N(1)-, N(2)-, and N(3)-alkyl-4-nitro-1,2,3-triazoles (alkyl is isopropyl, sec-butyl, and cyclohexyl). The selectivity of the alkylation depends on the alcohol used. The most selective alkylation is provided at the N(2) atom when isopropyl (81%) and sec-butyl alcohols are used (67%). With an increase in the reaction time, also in the order isopropyl-, sec-butyl-, and cyclohexyl-4-nitro-1,2,3-triazoles, the N(2)-isomers undergo isomerization into N(1)-alkyl-4-nitro-1,2,3-triazoles. In all the cases, the fraction of the N(3)-substitution products in the mixtures is 6–30%.     

Heterocyclic nitro compounds. 27. Methods for the synthesis of 3-nitro-5-R-1,2,4-triazoles

A method for the preparation of 3-nitro-5-R-1,2,4-triazoles by reaction of 1-(3'-oxobutyl)-3,5-dinitro-1,2,4-triazole with nucleophilic reagents with various structures with replacement of the nitro group in the 5 position of the triazole ring during subsequent elimination of the oxobutyl fragment in an alkaline medium is examined. A number of previously undescribed NH acids, viz., 1,2,4-triazole derivatives, including 3-nitro-5-azolyl-1,2,4-triazoles, were obtained, and the ionization constants were determined for some of them.See [1] for Communication 26.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp, 1553–1557, November, 1980.     

N-Alkylation of 4-nitro-1,2,3-triazole revisited. Detection and characterization of the N3-ethylation product, 1-ethyl-5-nitro-1,2,3-triazole

The products of the alkylation of sodium 4-nitro-1,2,3-triazolate with ethyl bromide were investigated using ¹H, ¹³C, and ¹⁵N NMR spectroscopy. It was found that alkylation proceeds on the triazole nitrogen atoms giving a mixture of three isomeric N-ethyl-4-nitro-1,2,3-triazoles. The molar ratio of N1, N2, and N3-alkylation products was 4:8:1. The formation of a minor N3-isomer, namely 1-ethyl-5-nitro-1,2,3-triazole was confirmed by X-ray structural analysis of single crystals of its tetranuclear copper(II) complex obtained by reaction of copper(II) chloride dihydrate with a mixture of the N2 and N3-isomers.     

Selective synthesis of 1,3-dialkyl-4-nitro-1,2,3-triazolium salts from 1-alkyl-4-nitro-1,2,3-triazoles and dialkyl sulfates

The process of alkylation of 1-alkyl-substituted 4-nitro-1,2,3-triazoles with dimethyl and diethyl sulfates has been studied. The structures of the N,N’-dialkyl-C-nitro-1,2,3-triazolium alkylsulfates and perchlorates has been confirmed by IR, ¹H and ¹³C NMR spectroscopy. Alkylation with an excess of dialkyl sulfate occurred regioselectively at N-3 with the formation of 1,3-dialkyl-4-nitro-1,2,3-triazolium salts, which is in agreement quantum-chemical calculations of the relative stability of the corresponding isomeric cations. The molecular and crystal structures of the first example of this type of salt – 1,3-diethyl-4-nitro-1,2,3-triazolium perchlorate – have been determined by X-ray crystallo-graphy. Nitrotriazolium salts with mixed alkyl substituents – 3-ethyl-1-methyl- and 1-ethyl-3-methyl-4-nitro-1,2,3-triazolium salts – have been synthesized an studied for the first time.     

Theoretical studies on a series of 1,2,3-triazoles derivatives as potential high energy density compounds

Based on the full-optimized molecular geometric structures at B3LYP/6-31G* and B3P86/6-31G* levels, the densities (ρ), detonation velocities (D), and pressures (P) for a series of 1,2,3-triazole derivatives, as well as their thermal stabilities, were investigated to look for high energy density compounds (HEDCs). The heats of formation (HOFs) are also calculated via designed isodesmic reactions. The calculations on the bond dissociation energies (BDEs) indicate that the BDEs of the initial scission step are between 53 and 70 kcal/mol, and 4-nitro-1,2,3-triazole is the most reactive compound, while 1-(2′,4′-dinitrophenyl)-5-nitro-1,2,3-triazole is the least reactive compound for 1,2,3-triazole derivatives studied. The condensed phase heats of formation are also calculated for the title compounds. These results would provide basic information for the further studies of HEDCs. The detonation data of 1-(3′,4′-dinitrophenyl)-4-nitro-1,2,3-triazole and 1-(2′,4′-dinitrophenyl)-4-nitro-1,2,3-triazole show that they meet the requirement for HEDCs.