Regioselectivity of Alkylation of 3-Substituted 5-Amino-1,2,4-thiadiazoles

We have synthesized 3-substituted 4-alkyl-5-imino-4,5-dihydro-1,2,4-thiadiazoles by reaction of 3-alkyl(benzyl)thio-5-amino-1,2,4-thiadiazoles with methyl iodide or ethylene chlorohydrin. In the reaction with epichlorohydrin, addition of an oxirane molecule occurs with formation of tetrahydropyrimido[2,1-b]-1,2,4-thiadiazoles.     

1,2,4-三嗪类化合物的研究XXI.3-甲硫基-5-氧代-2.5-二氧-1,2,4-三嗪的取代苯磺铣化反应及6- 碳的亲电特性

3-甲硫基-5-氧代-2.5-二氧-1,2,4-三嗪(Ic)与取代的苯磺铣氯反应,在无水吡啶中生成N-[6-(3-甲硫基-5-负氧基)-1,2,4-三嗪基]吡啶内嗡盐(4);在NaOH-H~2O-Ch~3COCH~3中生成3-甲硫基-4-(取代苯磺铣基)-5-氧化-6-羟基-1,4,5,6-四氢- 12,4-(6);资Naoh-Ch~3O中则生成1-(对甲苯磺铣基)-3-甲硫基-6-甲氧基-1,4,5,6-四氢-三嗪(7)显示了其6-C具有不寻常的亲电特性.     

Base-induced rearrangement of 4-amidino-3-R-furoxans into 1-substituted 3-(1-nitroalkyl)-5-R-1H-1,2,4-triazoles

A new base-induced rearrangement of furoxans, viz., a recyclization of 4-amidino-3-Rfuroxans into 1-substituted 3-(1-nitroalkyl)-5-R-1H-1,2,4-triazoles in the presence of alkali metal alkoxides and into 3-acyl-5-R-1H-1,2,4-triazoles in aqueous alkaline solutions, was found.     

Reaction of 3-oxo-N-phenylbutanethioamide with 5-amino-1H-1,2,4-triazoles

Reactions of 3-oxo-N-phenylbutanethioamide with 3-substituted 5-amino-1H-1,2,4-triazoles in acetic acid led to the formation of 5-methyl-7,8-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-thiones, 7-methyl-5,8-dihydrol[1,2,4]triazolo[1,5-a]pyrimidine-5-thiones and 7-methyl-5-phenylamino[1,2,4]triazolo[1,5-a]pyrimidines. The structure of the products was proved by the ¹H and ¹³C NMR spectra, X-ray diffraction data, and chemical transformations.     

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.     

Diphenylmethyl and tetrahydropyranyl protecting groups in the synthesis of 3-substituted 5-amino- and 5-hydrazino-1,2,4-triazoles

The use of hydrazine as reagent in nucleophilic substitution and reduction in the 1,2,4-triazole series in combination with introduction of labile protecting groups makes it possible to synthesize 5-hydrazino-3-nitro-1H-1,2,4-triazole and 3-chloro-5-hydrazino-1H-1,2,4-triazol-5-ylhydrazine which were difficultly accessible previously, as well as to extend the series of 3-substituted 5-amino-1H-1,2,4-triazoles. Original Russian Text V.V. Tolstyakov, I.V. Tselinskii, N.A. Dreving, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 12, pp. 2034-2040.     

New syntheses on the basis of ethyl 2-oxotetrahydrofuran-3-carboxylates

Alkylation of 5-substituted ethyl 5-methyl-2-oxotetrahydrofuran-3-carboxylates with alkyl halides in the presence of sodium ethoxide gave the corresponding 3-alkyl derivatives which were converted into 3,5-substituted 5-methyl-N-(4-nitrophenyl)-2-oxotetrahydrofuran-3-carboxamides and 5-methyltetrahydrofuran-2-ones. Reactions of the latter with hydrazine hydrate led to the formation of 4-hydroxypentanoic acid hydrazides which were treated with isothiocyanates to obtain the corresponding thiosemicarbazides whose intramolecular cyclization in the presence of aqueous alkali gave previously unknown 1,2,4-triazole-3-thiol derivatives.     

Synthesis of some new 4,5-substituted-4H-1,2,4-triazole-3-thiol derivatives

In this study appropriate hydrazide compounds, furan-2-carboxylic acid hydrazide (1) and phenylacetic acid hydrazide (2) were converted into 1,4-substituted thiosemicarbazides 4a-e and 5a-e and 4-amino-5-(furan-2-yl or benzyl)-4H-1,2,4-triazole-3-thiols 7 and 10. The 1,4-substituted thiosemicarbazides were then converted into 5-(furan-2-yl or benzyl)-4-(aryl)-4H-1,2,4-triazole-3-thiols 8a-e and 9a-e. In addition, the azomethines 11a-d and 12a-d were prepared from the corresponding arylaldehydes and the 4-amino-5-(furan-2-yl or benzyl)-4H-1,2,4-triazole-3-thiols 7 and 10. The structures of all the synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR and(13) C-NMR spectra.     

Domino synthesis of novel series of 4-substituted 5-thioxo-1,2,4-triazolidin-3-one derivatives

The efficient synthesis of 4-substituted 5-thioxo-1,2,4-triazolidin-3-one derivatives (4-substituted thiourazoles) via domino combination of thiophosgene, aliphatic or aromatic amines, and ethyl carbazate is presented.     

A green one-pot synthesis of 3(5)-substituted 1,2,4-triazol-5(3)-amines as potential antimicrobial agents

Journal of the Iranian Chemical Society - An efficient procedure was proposed for the synthesis of 3(5)-substituted 1,2,4-triazol-5(3)-amines via a one-pot reaction of thiourea, dimethyl sulfate...     

3-Nitro-1,2,4-triazol-5-one derivatives

3-Nitro-1,2,4-triazol-5-one and its monomethyl derivatives react with methyl vinyl ketone to give products of addition to the ring N₁ and N₄ atoms. The reaction with formaldehyde and N-methylolacetamide proceeds only at the N₁ atom. The keto derivatives of 3-nitro-1,2,4-triazol-5-one undergo the Schmidt reaction to give the corresponding acetamides. A number of compounds that include functional groups in the N₁-alkyl substituent of the 3-nitro ring were obtained by treatment of the bases of N₁-substituted 3,5-dinitro-1,2,4-triazoles in aprotic media.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 552–558, April, 1981.     

1,2,4-triazines. 1. A convenient synthesis of 4,5-dihydro-1,2,4-triazin-3-(2H)one and its 6-substituted derivatives

A facile synthesis of 4,5-dihydro-1,2,4-triazin-3-(2H)one (2a) from 5-methylthio-1,2,4-triazin-3-(2H)one (1a) with sodium borohydride is described. The reaction provides a convenient method for its 6-substituted derivatives (2b-h).     

Synthese de s-triazolo[4,3-d] et [1,5-d] triazines-1,2,4

2-substituted s-triazolo[1,5-d] and 3-substituted s-triazolo [4,3-d]-1,2-4-triazine 8-ones were obtained starting from 5-(3)-alkyl-3(5)-carboxyhydrazino-1,2,4 triazoles and ethyl orthoformate. However, the same reaction was not found to be an efficient one in the case of 5(3)-β-D-ribofuranosyl-3(5)-carboxyhydrazino-1,2,4 triazole.     

Tandem oxidation processes for the regioselective preparation of 5-substituted and 6-substituted 1,2,4-triazines

α-Hydroxyketones undergo MnO₂-mediated oxidation, followed by in situ trapping with 2-pyridylamidrazone, to give 3-pyridyl-5-substituted 1,2,4-triazines in a one-pot procedure, which avoids the need to isolate the reactive α-ketoaldehyde intermediates. By modifying this procedure to allow condensation prior to oxidation, the corresponding 6-substituted 1,2,4-triazines were obtained. The preparation of a novel unsymmetrical 2,2′-bipyridine using one of the pyridyl 1,2,4-triazines prepared herein is also described.     

Synthesis of 5-(3,4,5-trimethoxyphenyl)-4-substituted aryl-3-hydrazino-carbonylmethylthio-4H-1,2,4-triazoles as possible antiinflammatory agents

A series of 5-(3,4,5-trimethoxyphenyl)-4-substituted aryl-3-hydrazinocarbonylmethylthio-4H-1,2,4-triazoles were synthesized and evaluated for their antiprotolytic and antiinflammatory activities.     

A new method for the synthesis of novel 3-substituted 4-amino-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazines and pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepines

Novel 3-substituted 4-amino-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazines 7,8 were synthesized by the reactions of malononitrile and ethyl cyanoacetate with the pyrazole-5-diazonium salt 3 . Moreover, compounds 7,8 were converted into the pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepines 9, 10 .     

5-Substituted 3-Nitro-1-vinyl-1,2,4-triazoles

A series of 5-substituted 3-nitro-1-vinyl-1,2,4-triazoles were synthesized by alkaline treatment of the corresponding 1-(2-haloethyl- or 2-nitroxyethyl)-3-nitro-1,2,4-triazoles and by transvinylation of NH acids of the same series with vinyl acetate. The scope of applicability of the transvinylation procedure was established with respect to the azole pK _a value. The vinylic double bond on the nitrogen was shown to be inactive toward both nucleophilic and electrophilic reagents, whereas the halogen atom in position 5 exhibits enhanced reactivity. The latter factor provides the possibility for versatile structural modification via nucleophilic replacement of the 5-halogen atom by various groups, including triazolate ion.     

Pyrazolo[4,3-e][1,2,4]triazines: purine analogues with electronic absorption in the visible region

Synthesis of several pryrazolo[4,3-e][1,2,4]-triazines is described. The absorption spectrum of some 5-substituted derivatives was found to extend to the visible region. These compounds were found to inhibit some enzymes of purine metabolism, like xanthine oxidase or bacterial purine-nucleoside phosphorylase with Ki values in the 10(-3) -10(-5) M range.     

Synthesis of 4-(pyrazol-5-yl)-1,2,4-triazole-3-thiones

Condensation of pyrazolyl isothiocyanates 2 with N-substituted hydrazines provided the 2-methyl/phenyl-4-(pyrazol-5-yl)thiosemicarbazides 3 . Cyclization of 3 with formic acid-acetic anhydride or with triethyl orthoacetate-acetic anhydride provided 4-(pyrazol-5-yl)-l,2,4-triazole-3-thiones 4a-f and 5-methyl-4-(pyrazol-5-yl)-1,2,4-triazole-3-thiones 4g-I respectively.     

A convenient synthesis of 3-substituted 5-guanidino-1,2,4-oxadiazoles

The reaction of amidoximes with cyanoguanidine in the presence of Lewis acids affords 3-substituted 5-guanidino-1,2,4-oxadiazoles. A study of the reaction of¹⁵N-labeled chloroacetamidoxime with cyanoguanidine showed that the formation of the oxadiazole ring occursvia the elimination of the amino group from the amidoxime fragment. 1,2,4-Oxadiazoles bearing the imidazole or pyrimidine moiety were synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 118–121, January, 1994.