Efficient,One-Pot Synthesis of Triazolothiadiazinyl-pyrazolone and Pyrazolyl-triazolothiadiazine Derivatives via Multicomponent Reaction

A one-pot, multicomponent reaction of 3-(2-bromo acetyl)coumarins, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and different derivatives of ethyl 2-(2-(aryl)hydrazono)-3-oxobutanoates provide an efficient and direct method for the synthesis of 4-(arylydrazono)-3-methyl-1-(6-(coumarin-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)-1H-pyrazol-5(4H)-ones (4a–h). A similar methodology was also developed for the synthesis of pyrazolyl-triazolothiadiazines (9a–f) using acetyl acetone, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and different derivatives of phenacylbromide. The resulting products were characterized by analytical and spectral data.     

Synthesis and antiviral evaluation of some novel [1,2,4]triazolo[4,3-β][1,2,4]triazole nucleoside analogs

Ribosylation of 3-amino-5H-[1,2,4]triazolo[4,3-b][1,2,4]triazole ( 1 ) with l-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose and stannic chloride resulted in the following protected nucleoside analogs: 3-amino-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 4 ), 3-amino-1-(2,3,5-tri-O-benzoyl-α-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 5 ), 3-amino-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 5 ), and 3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl) amino-5H-[1,2,4]triazolo[4,3-b]-[1,2,4]triazole ( 7 ). Compounds 4–6 were deprotected to 3-amino-1-β-D-ribofuranosyl[1,2,4]triazolo[4,3-b][1,2,4]-triazole ( 3 ), 3-amino-1-α-D-ribofuranosyl[1,2,4]triazolo[4,5-b][1,2,4]triazole ( 8 ), and 3-imino-2H-2-β-D-ribo-furanosyl[1,2,4]triazolo[4,3-b][1,2,4]triazole ( 9 ), while 7 could not be deprotected without decomposition. Compounds 1, 4, 6, 7 , and 9 were screened and found to have no antiviral activity.     

Novel One-Pot Multicomponent Synthesis of Substituted 2,3-Dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones and Substituted 3-[3-(N′-Benzylidene-hydrazino)-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones

A one-pot procedure has been developed for the synthesis of substituted 2,3-dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones by reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and phthalic anhydrides in acetic acid medium. Similarly, a one-pot, three-component synthetic procedure has been developed for substituted 3-[3-(N¹-benzylidene-hydrazino)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones from 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and various aromatic aldehydes in absolute ethanol and a few drops of glacial acetic acid.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Cyclocondensation of 3-amino-2-iminonaphtho[1,2-d]thiazole with oxalic acid derivatives

Refluxing 3-amino-2-iminonaphtho[1,2-d]thiazole ( 1 ) with diethyl oxalate ( 2a ) in a 2:1 molar ratio in dry pyridine provided 2,2′-binaphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazole ( 3 ). On the other hand, when 1 was treated with excess amount of 2a in dimethylformamide, it afforded ethyl naphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazole-2-carboxylate ( 4a ) on heating and ethyl N-(2-iminonaphtho[1,2-d]thiazol-3-yl)oxamate ( 5 ) by stirring at room temperature. Cyclization of 5 upon fusion led to the formation of 3-hydroxy-2H-naphtho-[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazin-2-one ( 6 ). Compound 6 could also be prepared directly from 1 by refluxing either with 2a neatly, in glacial acetic acid or with oxalic acid ( 2b ) in the same medium. The acid form of 4a might be obtained from 1 and 2b on heating in dimethylformamide, but it was decarboxylated to naphtho-[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazole ( 4b ) during the reaction.     

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.     

Synthesis of 3-aminochroman derivatives by radical cyclization

[reaction: see text] Enantiomerically pure 5-acetyl-3-amino-3,4-dihydro-2H-1-benzopyran and methyl 3-amino-3,4-dihydro-2H-1-benzopyran-5-carboxylate were successfully synthesized starting from d- or l-serine. The formation of the benzopyran ring involved a radical cyclization step. The enantiomeric purities of the final aminochroman derivatives were determined by capillary electrophoresis using beta-cyclodextrins as a chiral selector.     

Synthesis and Crystal Structure of 5-[（1H-1,2,4-Triazol-1- yl）methyl]-4-（2,3-dimethoxybenzylideneamino）-2- 2H-1,2,4-triazole-3（4H）-thione Monohydrate

1 INTRODUCTION Heterocyclic compounds bearing the 1,2,4-tri- azole moiety have attracted considerable attention over the past few decades since they exhibit some fungicidal activities against Puccinia recondite and applications in the field of root-growth regu- lation[1~3]. Meanwhile, 4-amino-5-mercapto-1,2, 4-triazole moiety has great versatility in fusing tovarious ring systems and possesses a broad spec- trum of biological activities[4, 5]. In our con- tinuous work directed towards the…     

Synthesis and study of 3-(pyrimidin-2-yl)amino-1(2)H-1,2,4-triazole derivatives

The previously unknown 3-[4(3H)-pyrimidinon-2-yl]amino-1H-1,2,4-triazoles, which were converted to 3-[4-chloro-, 3-(4-ethoxy)-, 3-(4-hydrazinopyrimidin-2-yl)]-amino-2(4)H-1,2,4-triazoles, were obtained by the reaction of 2-nitroamino-4(3H)-pyrimidinones with 3-amino-5-hexyl-1H-1,2,4-triazole. The condensation of the initial products with -diketones gave 3-[4-(1H-pyrazol-1-yl)pyrimidin-2-yl]-amino-2(4)H-1,2,4-triazoles. The IR, UV, and PMR spectra of the synthesized compounds were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1678–1681, December, 1980.     

Synthesis and Tautomeric Structure of 7-Arylhydrazono-7H-[1,2,4]Triazolo[3,4-b][1,3,4]Thiadiazines

Two synthetic approaches were developed for the title compounds 8a-g via coupling of diazotized anilines with 7-acetyl-6-methyl-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine 7 , and reaction of N-aryl 2-oxopropanehydrazonoyl chlorides 9 with 4-amino-3-mercapto-5-phenyl-1,2,4-triazole 1 . The tautomeric structures of 8 were elucidated by their spectral analyses and correlation of their acid dissociation constants with Hammett equation.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

含吡唑1,2,4-三唑噻二嗪衍生物的合成及抑菌活性

1-苯基-3-甲基-5-氯-4-吡唑甲醛与4-氨基-5-取代苯基-1,2,4-三唑-3-硫酮缩合生成4-(1-苯基-3-甲基-5-氯吡唑次甲亚胺基)-5-(取代苯基)-2H-1,2,4-三唑-3(4H)-硫酮,再烷基加成化为新型含吡唑基5,6-2H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪衍生物。 化合物结构经¹H NMR、IR以及元素分析确认。 初步生物活性测试结果表明,在100 mg/L浓度下,化合物8a(3-(2-甲基苯基)-6-(5-氯-2-甲基-4-苯基吡唑)-7-(4-硝基苯基)-5H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪)对黄瓜炭疽病的抑制率达90%。     

一步法合成噻唑并[3,2-b](1,2,4)-三唑类衍生物的研究

以3-芳基-5-巯基-1,2,4-三唑为原料, 在酸性条件下与乙酰丙酮和乙酰乙酸乙酯一步成环, 制备得到12种新的2-芳基-5-取代-6-甲基噻唑并[3,2-b](1,2,4)-三唑类衍生物. 所有化合物结构经IR, 1H NMR, 13C NMR 和MS及元素分析确证.     

Pyrimidine acyclo-C-nucleosides by ring transformations of 2-formyl-L-arabinal

The protected 2-formyl-L-arabinal 2 reacted with thiourea and cyanamide in the presence of sodium hydride to afford via ring transformations the 5-[1R,2S-1,2- bis(benzyloxy)-3-hydroxypropyl]-1,2-dihydropyrimidines 3 and 4, respectively. Similarly, treatment of 2 with 3-amino-2H-1,2,4-triazole yielded 6-[1R,2S-1,2- bis(benzyloxy)-3-hydroxypropyl][1,2,4]-triazolo[1,5-a]pyrimidine (5).     

5,6-2H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪衍生物的合成及抗癌活性测定

取代苯甲醛与4-氨基-5-(3,4,5-三甲氧基苯基)-1,2,4-三唑-3-硫酮(2)缩合生成5-(3,4,5-三甲氧基苯基)-4-取代苯基亚胺基-1,2,4-三唑-3-硫酮(3),再烷基加成化为新型5,6-2H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪衍生物4.化合物结构经1HNMR 13C NMR,IR以及元素分析确认.采用噻唑兰(MTT)比色法进行化合物抑制人体前列腺癌细胞(PC3)体外活性测试,结果表明所合成的化合物具有不同程度的抑制PC3活性,其中化合物4a在10μmol·L-1浓度下对PC3的抑制率为75.9%.     

The efficient synthesis of 3-[6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole

This study presents an efficient synthesis of 3-[6-(substituted-phenyl)-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazol-3-yl]-1H-indazole via dehydrative condensation with cyclization of 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]triazole-3-thiol and fluorinated or nonfluorinated carboxylic acids in presence of phosphorous oxychloride. The multistep reaction pathway proceeds through different compounds. Present synthesis has the advantages of easily accessible starting materials, convenient synthesis, simple reaction condition, wider substrate scope, and higher yield (75% to 90% isolated).     

One-pot synthesis of imidazo[1,2-b]pyrazole,imidazo[1,2-b]-1,2,4-triazole,imidazo[1,2-a]pyridine,imidazo[1,2-a]pyrimidine,imidazo[1,2-a]benzimidazole,and 1,2,4-triazolo[4,3-a]benzimidazole derivatives

Hydrazonoyl bromides 1a-c react with 5-amino-3-phenyl-1H-pyrazole, 5-amino-1H-1,2,4-triazole, 2-aminopyridine, and 2-aminobenzimidazole to afford the corresponding imidazol[1,2-b]pyrazoles 10, imidazo[1,2-b]-1,2,4-triazoles 11, imidazo[1,2-a]pyridines 16, imidazo[1,2-a]pyrimidines 17, and imidazo[1,2-a]benzimidazoles 20, respectively. Compounds 1a-c reacted also with 2-methylthiobenzimidazole to give 1,2,4-triazolo[4,3-a]benzimidazole derivatives 21. © 1997 John Wiley & Sons, Inc.     

High and low spin mononuclear and dinuclear iron(II) complexes of 4-amino and 4-pyrrolyl-3,5-di(2-pyridyl)-4H-1,2,4-triazoles

The first dinuclear iron(II) complexes of any 4-substituted 3,5-di(2-pyridyl)-4H-1,2,4-triazole ligands, [Fe(II)2(adpt)2(H2O)1.5(CH3CN)2.5](BF4)4 and [Fe(II)2(pldpt)2(H2O)2(CH3CN)2](BF4)4, are presented [where adpt is 4-amino-3,5-di(2-pyridyl)-4H-1,2,4-triazole and pldpt is 4-pyrrolyl-3,5-di(2-pyridyl)-4H-1,2,4-triazole]. Both dinuclear complexes feature doubly triazole bridged iron(II) centers that are found to be [high spin-high spin] at all temperatures, 4-300 K, and to exhibit weak antiferromagnetic coupling. In the analogous monometallic complexes, [Fe(II)(Rdpt)2(X)2](n+), the spin state of the iron(II) center was controlled by appropriate selection of the axial ligands X. Specifically, both of the chloride complexes, [Fe(II)(adpt)2(Cl)2] x 2 MeOH and [Fe(II)(pldpt)2(Cl)2] x 2 MeOH x H2O, were found to be high spin whereas the pyridine adduct [Fe(II)(adpt)2(py)2](BF4)2 was low spin. Attempts to prepare [Fe(II)(pldpt)2(py)2](BF4)2 and the dinuclear analogues [Fe(II)2(Rdpt)2(py)4](BF4)4 failed, illustrating the significant challenges faced in attempts to develop control over the nature of the product obtained from reactions of iron(II) and these bis-bidentate ligands.     

Syntheses and Characterization of Two New Alkaline Earth Metal-organic Topological Frameworks with 3-Amino-1H-1,2,4-triazole-5-carboxylate

Two new alkaline earth metal coordination polymers constructed from the deriva-tive of 1,2,4-triazole are presented herein,namely,{[Sr(AmTAZAc)2(H2O)]}(1) and {[Ba(AmTAZAc)2(H2O)]}(2)(AmTAZAc = 3-amino-1H-1,2,4-triazole-5-carboxylate),which have been synthesized by using the layering method and structurally characterized by elemental analysis,IR,and single-crystal X-ray diffraction.Complexes 1 and 2 are isostructural,and both crystallize in the orthorhombic system,space group Fdd2.X-ray structural analysis shows that 1 or 2 has an intriguing 3-D infinite network of(318.438.510) topology based on a 2-D sheet structure of(4,4) net.The result shows that noncovalent interactions play an important role in strengthening the whole structures of the compounds.     

The synthesis, structure and properties of N-acetylated derivatives of ethyl 3-amino-1H-pyrazole-4-carboxylate

Ethyl 3-amino-1H-pyrazole-4-carboxylate (1) was yielded through total synthesis and reacted with acetic anhydride to give the acetylated products 2-6. Compounds 1-6 were studied with HPLC, X-ray, FT-IR, (1)H-NMR, (13)C-NMR and MS. Acetylation was carried out in solvents of various polarity, namely; chloroform; dioxane; DMF; acetic anhydride, at room temperature and at boiling points; and in the presence and absence of DMAP. The acetylated products are mainly nitrogen atoms in the ring. The position of the ring proton in the solution was based on NOESY; multinuclear HMBC, HSQC spectra and calculations. For equivalent amounts (1-1.5 mol) of acetic anhydride at room temperature two products of monoacetylation are produced in the ring: 2 and 3, ca. 2 : 1 and at the same time only small amount of the third product of monoacetylated, 5 in DMF, as well the product diacetylated, 4. The greatest amount of the product 4 is produced during the reaction with chloroform. However, in this solvent and in dioxane no product 5 is produced. Compound 2 is, largely, formed in dimethylformamide, in the presence DMAP, 0.2 eq. In the presence of this catalytic base, for the first hour, there is a mixture 2 and 3 to the ratio ca. 95 : 5. With 8 eq of Ac(2)O at reflux, after another hour, the compounds 3, 4 and 6 appear about equal amounts. After a longer time, the compound, which appears most in this mixture is triacetylated derivative 6. The structural and spectroscopic characteristics of compounds 1-6 have been given and the methods for their preparation have been provided.     

Preparation and Crystal Structure of 3-（2-Hydroxyphenyl） -6- （4-nitrophenyl）-7H- 1,2,4-triazolo[3,4-b][1, 3,4]thiadiazine

Introduction3,6- Disubstituted- 7H- 1 ,2 ,4- triazolo[3,4- b][1 ,3,4]thiadiazines are amongst the various hete-rocycles that received considerable attention duringthe last two decades as potential biologically activeagents.This kind of N- bridged heterocycles hasbeen reported to possess the wide spectrum of bio-logical properties,such as antimicrobial[1] ,an-tibacterial,antifungal[2 ] ,antiinflammatory[3 ] ,di-uretic[4] ,anthelmintic,and analgesic properties[5] .They can be also used as plant…