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.     

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.     

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.     

Acyl and Sulfonyl Derivatives of 3,5-Diamino-1-R-1,2,4-triazoles

3-Acylamino-5-amino-1-R-1,2,4-triazoles are formed regioselectively on acylating 3,5-diamino-1-R-1,2,4-triazoles with an equimolar amount of anhydrides, carboxylic acid chlorides, and sulfonyl chlorides. With an excess of anhydride and carboxylic acid chloride 3,5-diacylamino-1-R-1,2,4-triazoles are formed. 3-Acylamino-5-amino-1-R-1,2,4-triazoles do not interact with sulfonyl chlorides. The higher reactivity of the 3-amino group towards acylating agents is determined by electronic and not steric factors. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1342–1350, September, 2005.     

5-substituted 3-nitro-1-trinitromethyl-1,2,4-triazoles

A number of 5-R-substituted 3-nitro-1-trinitromethyl-1H-1,2,4-triazoles (R = Me, Cl, Br, N₃, NH₂, NO₂) were synthesized by nitration of the corresponding ω-(5-R-3-nitro-1H-1,2,4-triazol-1-yl)alkan-2-ones with mixtures of concentrated sulfuric and nitric acids.     

Acidic N-dealkylation in nitrotriazolium salts

New selective synthesis of 1-alkyl-5-nitro-1,2,3-triazoles and 1-alkyl-4-nitro-1,2,3-triazoles has been developed, involving acid N-dealkylation of the relative 4-nitro-1,2,3- and 3-nitro- 5-R-1,2,4-triazolium salts. The assortment of novel 1-alkyl- 4(5)-nitro-1,2,3-triazoles has been thus essentially expanded. Treatment of relative 3-nitro-1,2,4-triazolium salts with HCl or HBr proceeds mostly as S_N^ipso-substitution of the nitro group.     

Alkylation of acyl and sulfonyl derivatives of 3,5-diamino-1-phenyl-1,2,4-triazole

Alkylation of 3-acylamino-, 5-amino-1-phenyl-3-tosylamino-1,2,4-triazoles and 3,5-diacetylamino-1-phenyl-1,2,4-triazole in the presence of an equimolar amount of sodium methylate in DMSO occurs regioselectively at the amide (sulfamide) group nitrogen atom. The benzylation of 3-acetylamino-5-amino-1-phenyl-1,2,4-triazole with excess base and benzyl chloride also alkylates the amino group at position 5. Alkylamino-1-R-1,2,4-triazoles can be conveniently prepared by alkylation of the corresponding acetylamino-1,2,4-triazoles in the presence of base and subsequent acid hydrolysis of the N-acetyl-N-alkyl derivatives. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 557–567, April, 2009.     

Synthesis and properties of 1-dinitromethyl-3-R-1,2,4-triazoles

Reductive denitration of 1-trinitromethyl-3-R-1,2,4-triazoles by KI or NH₂OH followed by the treatment of the formed 1-dinitromethyl-3-R-1,2,4-triazoles salts with sulfuric acid yielded dinitromethyl compounds (R = H, N₃, Cl, NO₂), sufficiently strong CH-acids (pK_a 1.37–0.12) whose typical reactions are similar to those of gem-dinitrocompounds from the aliphatic series. The spectral data and the analysis of correlation relations between pK_a of 1-dinitromethyl-3-R-1,2,4-triazoles and the substituent constants confirm that their structure is analogous to that of the majority of compounds belonging to the mentioned series.     

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.     

Thermal decomposition mechanisms of nitro-1,2,4-triazoles: A theoretical study

Possible decomposition mechanisms of C-nitro-and N-nitro-1,2,4-triazoles were simulated. We showed that in addition to the experimentally detected thermolysis products including N₂, N₂O, NO, CO₂, HCN, HNCO, 1,2,4-triazole, 3(5)-nitroso-1,2,4-triazole, and 1,2,4-triazolone, some other decompositon products (H₂O, CO, NO₂, cyanamide, cyanuric acid, and melamine) can be formed. Using the density functional approach (B3LYP/6-31G* approximation), we assessed the most favorable thermal decomposition pathways of nitrotriazoles and studied the relationships between the thermolysis pathways of these substances and their molecular and electronic structures. We found a correlation between the energy gap width (energy difference between the frontier molecular orbitals) and the stabilities of the C-nitro-1,2,4-triazole tautomers to thermal decomposition. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1338–1358, August, 2006.     

2-R-7-methyl[1,2,4]triazolo[2,3-a]pyrimidines: synthesis and structures

Reactions of 5-R-3-amino-1,2,4-triazoles with ethoxymethylideneacetylacetone and ethyl ethoxymethylideneacetoacetate proceeded regioselectively, giving 2-R-7-methyl[1,2,4]triazolo[2,3-a]-pyrimidines in good yields. The compounds obtained were characterized by elemental analysis, ¹H NMR spectroscopy, and X-ray diffraction analysis (for ethyl 2-ethylthio-7-methyl[1,2,4]triazolo[2,3-a]pyrimidine-6-carboxylate). The frontier orbitals, the molecular electrostatic potential, and the geometries of the reagent molecules were calculated by the DFT method (B3LYP/6-31G**). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1244–1248, June, 2008.     

Heterocyclic nitro compounds. 28. 1-(Oxoalkyl)-3-nitro-5-r-1,2,4-triazoles in reactions with hydrazine and hydroxylamine

The reaction of 1-(oxoalkyl)-3-nitro-5-R-1,2,4-triazoles with hydroxylainine and hydrazine takes place at the keto group to give azines and oximes (R = H, CH₃), with reduction of the nitro group (R = NO₂, hydroxylamine), or with participation of both reaction centers with annelation and conversion to triazolo[3,2-c]-1,2,4-triazines and -1,2,4-triazepines, depending on the character of the substituent in the 5 position of the triazole ring and the type of reagent.See [1] for Communication 27.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1113–1117, August, 1982.     

Synthesis of 4-Amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones and 8H-3-R-7-Aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones

A study was carried out on the reaction of 4-amino-6-R-2,3,4,5-tetrahydro-3-thioxo-1,2,4-triazin-5-ones with halo ketones in alkaline media to yield 4-amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones, which then convert to 8H-3-R-7-aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones.     

Reaction of 4-Amino-3-methylthio-5-oxo-6-R-4,5-dihydro-1,2,4-triazines with Sulfonylacetic Acid Nitriles

The reactions of 4-amino-3-methylthio-5-oxo-6-R-4,5-dihydro-1,2,4-triazines with arylsulfonylacetonitriles and with dinitriles of sulfonyldiacetic acid and methylenebis(sulfonylacetic) acid have been studied. 7-Amino-3-R-8-(R'-sulfonyl)-1,4-dihydropyrazolo[5,1-c][1,2,4]triazin-4-ones have been synthesized and these are the first representatives of geminal sulfones in which the heterocyclic ring is bound directly to the sulfur atoms of the sulfonyl groups.     

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.     

Heterylation of 3-R1-5-R2-1,2,4-Triazoles with Derivatives of 3,5-Dinitro-1,2,4-Triazole

Heterylation of 3-R¹-5-R²-1'2'4-triazoles (pK _a 3-12) with N-alkyl-, N-alkenyl-, N-alkoxy-carbonyl-, N-oxoalkyl-, N-nitroxyalkyl, N-nitroaminoalkyl-3'5-dinitro-1'2'4-triazoles results insubstitution of a nitro group in 5 position of the dinitro compound yielding 1-R-methyl-3-nitro-5-(3-R¹-5-R²-1,2,4-triazolyl)-1,2,4-triazoles. The side processes: Hydroxide-ion attack on C⁵ and (or) N¹ of the ring both in the substrate and in the target compound afford 1-R-methyl3-nitro-1,2,4-triazol-5-ones, 3,5-dinitro-1,2,4-triazole and NH-acids of N-C-bitriazole series. Optimal reaction media are aprotic dipolar substances, and for compounds prone to heterolysis ethyl acetate-water systems. The azole pK _a is the decisive factor controlling the composition and the ratio of reaction products. The process is promising for azoles with pK _a > 5, and the optimal range of pK _a is 8-10.     

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.     

Synthese de 5-Aryl-3-[(1-dialcoxyphosphonyl)methyl]-1,2,4-triazoles a Partir d'Imidates N-Chloroacyles

A variety of 5-aryl-3-[(1-dialcoxyphosphonyl)methyl]-1,2,4-triazoles 3 has been synthesized efficiently by treatment of trialkylphosphites with 5-aryl-3-chlorométhyl-1,2,4-triazoles 2 . Compound 2 has been prepared by action of N-chloroacylimidates 1 with hydrazines. The structure of triazoles 2 and 3 have been unequivocally confirmed by means of IR, 1 H, 13 C, 31 P NMR spectroscopy and mass spectra.     

Synthesis of 5-alkoxy-3-amino-7-nitro-1,2,4-benzotriazine 1-oxides from 1,3,5-trinitrobenzene

1-Alkoxy-3,5-dinitrobenzenes were nitrated to give 1-alkoxy-2,3,5-trinitrobenzenes. The reaction of the latter with guanidine affordsN-(2-alkoxy-4,6-dinitrophenyl)guanidines, which undergo cyclization under the action of KOH to form 5-alkoxy-3-amino-7-nitro-1,2,4-benzotriazine 1-oxides. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1650–1652, September, 2000.     

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.