Adamantylazoles: IX. Acid-catalyzed Adamantylation of 1,2,4-Triazol-3-thione

1,2,4-Triazole-3-thione reacts with 1-adamantanol in sulfuric acid to form 1-(1-adamantyl)-3- [(1-adamantyl)sulfanyl]-1,2,4-triazole and 3,3′-disulfandiylbis[1-(1-adamantyl)-1,2,4-triazole].__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 1, 2005, pp. 142–145.Original Russian Text Copyright © 2005 by Amandurdyev, Saraev, Polyakova, Golod.     

Tautomerism of azacycles: III. Molecular and crystal structures of 3<Emphasis Type="Italic">H</Emphasis>-and 2-phenyl-1<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>-4,5-dihydro-1,2,4-triazole-5-thiones

Compounds capable of tautomerism: sulfanyl-1,2,4-triazole, its C-phenyl derivative, and the crystal hydrate of the latter, were studied by single crystal X-ray diffraction. In the crystals they exist in the form of 3-R-1(H),4(H)-4,5-dihydro-1,2,4-triazole-5-thione with a considerable contribution of the bipolar structure. Published data on the tautomerism of sulfanyl-1,2,4-triazoles and their N-substituted analogs and on the correlation between the spectral characteristics and structures of sulfanyl-1,2,4-triazoles capable of tautomerism are discussed.     

Synthesis and single-crystal X-ray diffraction studies of 1-β-D-ribofuranosyl-1,2,4-triazole-3-sulfonamide and certain related nucleosides

1-β-D-Ribofuranosyl- 21 , 1-(2-deoxy-β-D-erytftro-pento fur anosyl)- 27 and 1-β-D-arabinofuranosyl- 29 derivatives of 1,2,4-triazole-3-sulfonamide ( 19 ) have been prepared. Glycosylation of the silylated 19 with 1,2,3,5-tetra-0-acetyl-β-D-ribofuranose ( 5 ) in the presence of trimethylsilyl triflate gave the corresponding blocked nucleoside ( 20 ), which on ammonolysis afforded 1-β-D-ribofuranosyl-1,2,4-triazole-3-sulfonamide ( 21 ). Stereospecific glycosylation of the sodium salt of 19 with either 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose ( 22 ) or 1-chloro-2,3,5-tri-0-benzyl-α-D-arabinofuranose ( 23 ) provided the corresponding protected nucleosides 26 and 28. Deprotection of 26 and 28 furnished 1-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,4-triazole-3-sulfonamide ( 27 ) and 1-β-D-arabinofuranosyl-1,2,4-triazole-3-sulfonamide ( 29 ), respectively. 2-0-D-Ribofuranosyl-1,2,4-triazole-3(4H)-thione ( 7 ) and 4-β-D-ribofuranosyl-1,2,4-triazole-3(2H)-thione ( 9 ) were also prepared utilizing either an acid catalyzed fusion of 1,2,4-triazole-3(1H,2H)-thione ( 4 ) with 5 , the reaction of 5 with silylated 4 in the presence of trimethylsilyl triflate, or by ring closure of 4-(2,3,5-tri-0-benzoyl-β-D-ribofuranosyl)thiosemicarbazide ( 10 ) with mixed anhydride and subsequent deacylation. The synthesis of 1-β-D-ribofuranosyl-3-benzylthio-1,2,4-triazole ( 15 ) has also been accomplished by the silylation procedure employing 3-benzylthio-1,2,4-triazole ( 13 ) and 5 to give 1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)-3-benzylthio-1,2,4-triazole ( 14 ). Deacetylation of 14 furnished 15 . The structural assignments of 7, 14 and 21 were made by single-crystal X-ray diffraction analysis and their hydrogen bonding characteristics have been studied. The sulfonamido-1,2,4-triazole nucleosides are devoid of any significant antiviral or antitumor activity in cell culture.     

Reaction of azolethiones with diacetylene

Reactions of 2,3-dihydro-1H-benzimidazole-2-thione, 2,3-dihydro-1H-1,2,4-triazole-3-thione, 4-amino-5-phenyl-3,4-dihydro-2H-1,2,4-triazole, and 6-aminopurine-2-thiol with diacetylene in DMSO gave the corresponding 1-(azolylsulfanyl)but-1-en-3-ynes having Z configuration of the double bond.     

Synthesis of 3-methyl-6-r-6h-thiazolo-[4,3-<Emphasis Type="Italic">b</Emphasis>]-1,2,4-triazolo[4,3-<Emphasis Type="Italic">d</Emphasis>]-1,3,4-thiadiazoles

A one-reactor method has been developed for the synthesis of 3-methyl-6-R-6H-thiazolo[4,3-b]-1,2,4-triazolo[4,3-d]-1,3,4-thiadiazoles by the condensation of aromatic aldehydes, thioglycolic acid, and 4-amino-5-methyl-1,2,4-triazole-3(2H)-thione in a sulfuric acid medium.     

Adamantylazoles: XI. Reaction of 1-phenyltetrazole-5-thione with adamantan-1-ol in strong acids

The reaction of 1-phenyltetrazole-5-thione with adamantan-1-ol in sulfuric acid gave 3-(1-adamantyl)-1-phenyltetrazole-5-thione having a mesoionic structure, 5-(1-adamantylsulfanyl)-1-phenyltetrazole, and 3-(1-adamantyl)-5-(1-adamantylsulfanyl)-1-phenyltetrazolium hydrogen sulfate. Hydrolysis of 5-(1-adamantylsulfanyl)-1-phenyltetrazole led to the formation of 1-phenyltetrazol-5-one. The adamantylation process is reversible.     

3-取代苯氧甲基-4-氨基-1,2,4-三唑-5-硫酮席夫碱的合成、结构表征和生物活性研究

以醋酸为反应溶剂和催化剂,用自制的4-氨基-4,5-二氢-3-取代苯氧甲基-1,2,4-三唑-5-硫酮与4-氟苯甲醛反应合成了5个4-氨基-4,5-二氢-3-取代苯氧甲基-1,2,4-三唑-5-硫酮席夫碱化合物,通过1HNMR、IR和元素分析对所有化合物进行了结构表征.初步生物活性测试结果表明所有化合物具有优良的杀菌活性,并对席夫碱结构与活性的关系进行了探讨.     

Adamantylazoles: XIII. Specificity of acid-catalyzed alkylation of 1-(1-adamantyl)-4,5-dihydro-1H-tetrazole-5-thione

Russian Journal of General Chemistry - In the reaction of 1-(1-adamantyl)-4,5-dihydro-1H-tetrazole-5-thione with 1-adamantyl in sulfuric acid 2-(1-adamantyl)-5-(1-adamantylsulfanyl)-2H-tetrazole...     

Adamantylazoles: XII. Alkylation of 1-R-tetrazole-5-thiones and 1-R-tetrazol-5-ones with tertiary alcohols in sulfuric acid

In the reaction of 1-(1-adamantyl)-4,5-dihydro-1H-tetrazole-5-thione with 1-adamantyl in sulfuric acid 2-(1-adamantyl)-5-(1-adamantylsulfanyl)-2H-tetrazole and 1,3-bis(1-adamantyl)-5-(1-adamantylsulfanyl)-1H-tetrazolium salt are formed. Methylation of 1-(1-adamantyl)-4,5-dihydro-1H-tetrazole-5-thione in alkaline medium affords 1-(1-adamantyl)-5-methylsulfanyl-1H-tetrazole while its interaction with formaldehyde affoeds 1-(1-adamanttl)-4-(hydroxymethyl)-4,5-dihydro-1H-tetrazole-5-thione.     

Synthesis and biological evaluation of some novel Schiff's bases from 1,2,4-triazole

We have synthesized a number of novel Schiff's bases from 4-amino-3-(D-glucoheptonic-hexitol-1-yl)-1H-1,2,4-triazole-5-thione. By attaching D-glucoheptonic-hexitol-1-yl residues to 1,2,4-triazole at the 3-position, the solubility of the title compounds has been improved greatly. All the products have been characterized by elemental analysis, IR, 1H-NMR, 13C-NMR and MS. The plant-growth regulating effects of the title compounds were examined. From the biological activity results, we found that most compounds showed weak to moderate activities.     

Study of the Products of Iodocyclization of 4-Allyl-5-phenyl-1,2,4-triazole-3-thione

The interaction of 4-allyl-5-phenyl-1,2,4-triazole-3-thione with iodine proceeds with the formation of a mixture of 6-iodomethyl-3-phenyl-5,6-dihydrothiazolo[2,3-c]-1,2,4-triazole and 6-iodo-3-phenyl-6,7-dihydro-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine. The structures of the cyclization products obtained were established on the basis of the ¹H NMR spectra of their dehydroiodinated derivatives. 6-Methyl-3-phenylthiazolo[2,3-c]-1,2,4-triazole, 3-phenyl-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine, and 3-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3-thiazine are formed on eliminating HI from the cyclization products.     

Synthesis of derivatives of 1, 2, 4-triazole-3, 5-dicarboxylic acid

By oxidation of 3,5-dimethyl-1,2,4-triazole the monopotassium salt of 1,2,4-triazole-3,5-dicarboxylic acid was obtained. The mononitryl of 1,2,4-triazole-3,5-dicarboxylic acid was isolated during the reaction between 3-diazo-1,2,4-triazole-5-carboxylic acid and potassium cyanide in the presence of copper cyanide. Acid hydrolysis of 3-cyano-1,2,4-triazole-5-carboxylic acid leads to the formation of 3-carbamido-5-carboxy-1,2,4-trlazole, which on esterification with methanol gives rise to 3-carbamido-5-carbomethoxy-1,2,4-triazole.     

Preparation of aminotriazole-thione derivatives from n-aryl-n-carboxyethyl-β-alanines

Depending on the substituents in the aryl moiety, the fusion of N-aryl-N-ethoxycarbonyl-β-alanines with thiocarbohydrazide gives di- or monotriazole derivatives, namely, 4-amino-(2-{[2-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones, 1-[2-(4-amino- 5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]-2,3-dihydroquinolin-4(1H)-ones, 4-amino-3-[2-(4-methylanilino))ethyl]-4,5-dihydro-1H-1,2,4-triazole-5-thione and 4-amino-3-[2-(4-ethoxyanilino)-ethyl]-4,5-dihydro-1H-1,2,4-triazole-5-thione. A ditriazolethione derivative was also obtained from the diethyl ester of N-ethoxycarbonyl-N-(4-ethoxyphenyl)- β-alanine.     

Adamantylazoles. Acid-catalyzed adamantylation of 1,2,4-triazoles

The reaction of 1-adamantanol with 1,2,4-triazole in sulfuric acid forms 1-adamantyl derivatives. In boiling chloroform containing traces of sulfuric acid, a mixture of isomeric N-adamantyl-1, 2, 4-triazoles is obtained. It is shown that 1-adamantyl carbocation is formed at a sulfuric acid concentration above 70%.St. Petersburg State Technological Institute, St. Petersburg 198013. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Khimiya Geterotsklicheskii Soedinenii, No. 8, pp. 1078–1087, August, 1996. Original article submitted June 7, 1996.     

Adamantylation of 3-Nitro- and 3-Ethoxycarbonyl-1,2,4-triazolo[5,1-c]-1,2,4-triazin-4-ones

Reaction of 3-nitro- and 3-ethoxycarbonyl-1,2,4-triazolo[5,1-c]-1,2,4-triazin-4-ones with 1-adamantanol (or 1-adamantyl nitrate) in concentrated sulfuric acid or with 1-bromoadamantane in sulfolane affords N-adamantyl derivatives. The adamantylation of 3-nitro-1,4-dihydro-7H-1,2,4-triazolo[5,1-c]-1,2,4-triazin-4-one yields a mixture of N⁸- and N¹-isomers that undergo interconversion in concentrated sulfuric acid along intermolecular mechanism.     

3-(N-取代苯基-2-乙酰胺基)硫基-4-N-取代邻羟苯基亚胺基-5-甲基-1,2,4-三唑类化合物的合成及生物活性研究

以对称二氨基硫脲为原料,与冰醋酸反应生成5-甲基-4-氨基-1,2,4-三唑-3-硫酮(1);在弱酸性条件下,1与取代水杨醛反应生成席夫碱中间体5-甲基-4-(N-取代邻羟苯基)亚胺基-1,2,4-三唑-3-硫酮(2a～2c);最后在碱性条件下分别与N-取代苯基-2-氯乙酰胺发生烷基化反应生成15种未见报道的目标化合物3-(N-取代苯基-2-乙酰胺基)硫基-4-(N-取代邻羟苯基)亚胺基-5-甲基-1,2,4-三唑(3a～3o),其结构经IR,1H NMR,13C NMR确证.初步生物测试表明,质量分数为0.01%时,3a～3o对白色念珠菌的抑菌率均达90%以上,具有很强的抑菌活性;对金黄色葡萄球菌、大肠杆菌的抑菌率达80%以上,具有较强的抑菌活性.     

Synthesis of 5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-amino-1,2,4-triazole-3-thione and its Reactions with Polyfunctional Electrophiles

Summary.  In the reaction of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazole-2-thione with hydrazine hydrate, 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-amino-1,2,4-triazole-3-thione was formed. The reactions of the latter with ethyl bromoacetate and chloroacetonitrile in the presence of triethylamine proceeded under formation of the corresponding S-alkylated derivatives, whereas from its reaction with ω-bromoacetophenone and ethyl 4-chloroacetoacetate triazolothiadiazines were obtained. Treatment of the title compound with ethyl 2-chloroacetoacetate led to the formation of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-4-N-acetylamino-(3-ethoxy-carbonylmethylthio)-1,2,4-triazole. Performing of the latter reaction without basic catalyst gave a triazolothiadiazine. Treatment of the S-alkylated derivatives with sodium methoxide resulted in triazolothiadiazines via a cyclocondensation reaction. Received November 20, 2000. Accepted January 15, 2001     

2-Nitroguanidine Derivatives: IX. Reaction of 1-Amino-2-nitroguanidine with Oxalic Acid as a Method of Synthesis of 3(5)-Nitroamino-1,2,4-triazole-5(3)-carboxylic Acid and 5,5′-Bi(3-nitroamino-1,2,4-triazole) Salts

A new procedure for the synthesis of 5(3)-nitroamino-1,2,4-triazole-3(5)-carboxylic acid and 5,5′ -bi(3-nitroamino-1,2,4-triazole) potassium salt has been developed. It includes cyclization of [2-(N²-nitro-carbamimidoyl) hydrazino]oxoacetic acid and 2,2′-bis(N ²-itrocarbamimidoyl)oxalohydrazide, respectively, which are prepared by reaction of 1-amino-2-nitroguanidine with oxalic acid. The reaction of 5(3)-nitroamino-1,2,4-triazole-3(5)-carbohydrazide with 1-methyl-2-nitro-1-nitrosoguanidine leads to N′ -(N ²-nitrocarbamimidoyl)-5(3)-nitroamino-1,2,4-triazole-3(5)-carbohydrazide whose intramolecular cyclization in the presence of bases may be regarded as a new method of synthesis of 5,5′-bi(3-nitroamino-1,2,4-triazole) salts.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 3, 2005, pp. 447–450.Original Russian Text Copyright © 2005 by Metelkina, Novikova, Berdonosova, Berdonosov.For communication VIII, see [1].     

Synthesis and anti-inflammatory properties of novel 1,2,4-triazole derivatives

This research is based on the pharmacological activity of the triazole ring. In the last decade much work has been conducted on the triazole ring. Scientists have developed many new compounds based on this structure and screened them to obtain molecules with good pharmacological activity. In this research starting from 4-amino-5-(4-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione, a series of new 1,2,4-triazole derivatives were prepared. Results revealed that two compounds had anti-inflammatory potency after 4 h greater than that of indomethacin whereas another derivative had less potency than indomethacin.     

Synthesis and pancreatic lipase inhibitory activities of some 1,2,4-triazol-5(3)-one derivatives

In this study, starting from 4-amino-5-(4-chlorobenzyl)-2,4-dihydro-3H-1,2,4-triazole-3-one ( 1 ), the 4-Amino-5-(4-chlorobenzyl)-2-undecyl-2,4-dihydro-3H-1,2,4-triazol-3-one ( 2 ) was first synthesized and this compound was converted to Schiff base derivatives ( 3a-e ). In the second step of the study, the 2-[3-(4-chlorobenzyl)-5-oxo-1-undecyl-1,5-dihydro-4H-1,2,4-triazole-4-yl]-acetohydrazide ( 6 ), which was used as a key product in the synthesis of many heterocyclic compounds was synthesized in four steps, and then this compound was converted into methylidene acetohydrazide ( 7a-e ), thiosemicarbazide ( 8a-e ), and 1,2,4-triazole-5-thione ( 9a-e ) derivatives. Also, in the last part of the study, 1,2,4-triazole-5-thione derivatives were changed into Mannich bases ( 10a-b ) bearing a 4-phenylpiperazine ring. These new compounds were tested with regard to pancreatic lipase (PL) inhibition activity, and compound 3b , 3d , 7d , 8d , and 9d showed a considerable anti-lipase activity at various concentrations. The activity of compounds 7b (IC₅₀ = 1.45 ± 0.12 μM) was the highest in terms of IC₅₀, comparable to that of orlistat, a well-known PL inhibitor used as an antiobesity drug.