An efficient electrochemical method for synthesis of (1h‐1,2,4‐triazol‐3‐ylthio)benzen‐1,2‐diol derivatives

Electrochemical oxidation of catechols ( 1a–c ) has been studied in the presence of 3‐mercapto‐1,2,4‐triazole ( 3 ) as a nucleophile in water/acetonitrile (90/10) solutions. The results revealed that the quinones derived from catechols ( 1a–c ) participate in the Michael addition reactions with anion of 3‐mercapto‐1,2,4‐triazole ( 3 ) and are converted to the corresponding (1H‐1,2,4‐triazol‐3‐ylthio)benzen‐1,2‐diol derivatives ( 4a–c ). © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:644–649, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20359     

Electrochemical Behavior of Some Thiotriazoles in Aqueous‐Alcoholic Media at GCE

An electrochemical study related to the electrooxidation of 4‐amino‐3‐thio‐5‐methyl‐1,2,4‐triazole (I), 4‐amino‐3‐thio‐5‐phenyl‐1,2,4‐triazole (II) and 3‐thio‐5‐phenyl‐1,2,4‐triazole (III), in 10% v/v methanol‐acetate buffer pH 4.6 has been performed. A variety of electrochemical techniques such as differential pulse voltammetry, cyclic voltammetry, double‐potential step chronoamperometry, rotating‐disk electrode voltammetry and coulometry, were employed to clarify that the mechanism of the electrode process follows the oxidation of thiol compounds. All the compounds exhibit similar redox behavior under the given conditions. They display one irreversible oxidation peak, which is diffusion controlled. From the plot of current function in cyclic voltammetry and the ratio of i_c/i_a less than one in double‐potential step chronoamperometry, it was established that these compounds undergo an one electron oxidation followed by a dimerization process involving the formation of disulfide derivative (EC mechanism). The pK_a values were obtained by the dependence of limiting current and potential with in the wide pH interval. The transfer coefficients, the diffusion coefficients and rate constant of coupled chemical reaction were also reported. The substituent effects were also investigated.     

Synthesis and antimicrobial evaluation of some 1,2,4‐triazole, 1,3,4‐oxa(thia)diazole,and 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives

3‐Methyl‐2‐benzofurancarboxylic acid hydrazide ( 2 ) reacts with carbon disulfide and pota‐ ssium hydroxide to give the corresponding potassium carbodithioate salt 3 . Treatment of the latter salt with hydrochloric acid, hydrazine hydrate, and with phen‐ acyl bromide afforded the corresponding 1,3,4‐oxadia‐ zole‐5‐thione 4 , 4‐amino‐1,2,4‐triazole‐5‐thione 5 , and thiazolidine‐2‐thione 9 derivatives, respectively. The reaction of either 1,3,4‐oxadiazole‐5‐thione 4 or 4‐amino‐1,2,4‐triazole‐5‐thione 5 with phenacyl bromide resulted in the formation of 1,2,4‐triazolo[3, 4‐b]‐1,3,4‐thiadiazine derivative 8 . Treatment of compounds 3 or 4 with hydrazonoyl halides 10a–d furn‐ ished the same 1,3,4‐thiadiazol‐2‐ylidene derivatives 11a–d . The 7‐arylhydrazono‐1,2,4‐triazolo[3,4‐ b ]‐1, 3,4‐thiadiazine derivatives 12a–d were obtained either by treatment of 4‐amino‐1,2,4‐triazole‐5‐thione 5 with hydrazonoyl halides 10a–d or by coupling of the 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivative 8 with diazonium salts. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:621–627, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20162     

Synthesis,characterization and studies of new 3‐benzyl‐4H‐1,2,4‐triazole‐5‐thiol and thiazolo[3,2‐b][1,2,4]triazole‐5(6H)‐one heterocycles

3‐Benzyl‐4‐phenyl‐1,2,4‐triazole‐5‐thiol ( 1 ) was synthesized and used as starting material for preparation of 1,2,4‐triazole bearing substituted thiosemicarbazides moiety ( 4a‐d ) in high yields. The thiosemicarbazides 4a‐d were cyclized in basic medium to give two triazole rings linked by thiomethylene group ( 5a‐d ), while cyclization of thiosemicarbazides 4a‐d with chloroacetyl chloride in the presence of CHCl₃ and K₂CO₃ afforded the thiazolidinone derivatives 6a‐d . The reaction of thiosemicarbazides 4a‐c with phenacyl bromide in the presence of EtOH and fused CH₃COONa gave the corresponding thiazoline ring systems 7a‐c . Condensation of the 3‐benzyl‐1,2,4‐triazole‐5(1H)‐thiol ( 1 ) with chloroacetic acid and aromatic aldehydes ( 8a‐ g) in boiling acetic acid/acetic anhydride mixture in the presence of fused sodium acetate gave one single isomer only, which might be 9a‐g or 10a‐g . Upon application of Micheal addition reaction on compounds 9a‐e with cyclic secondary amines such as piperidine or morpholine the 2‐benzyl‐6‐(α‐amino‐aryl/methyl)‐1,3‐thiazolo[3,2‐ b][1,2,4]‐triazol‐5‐ols ( 11a‐j ) were obtained in good yields The structure of all new compounds were determined using both spectral and elemental analyses.     

Hydrazononitriles as Precursors for 4‐aminotriazoles and 3‐aminoisoxazoles: One Pot Synthesis of triazolo[1,5‐a]quinazoline Derivatives

The reaction of various hydrazononitriles with hydroxylamine hydrochloride yielded various products, namely, 3‐aminoisoxazolone, 3‐amino‐1,2,4‐triazole and 4‐amino‐1,2,3‐triazole derivatives depending on the nature of substituents.     

4,5-二氢-1,2,4-三唑-5-硫酮席夫碱的合成和生物活性

以4-氨基-4,5-二氢-3-苯氧甲基-1氢-1,2,4-三唑-5-硫酮与取代苯甲醛为原料反应制得了9个新的三唑硫酮席夫碱类化合物,经IR、1H NMR和元素分析确定了各化合物结构。初步室内毒力测试结果表明该类化合物其具有较好的杀菌活性。     

水相中5-（嘌呤-6-巯基）邻苯二酚衍生物的电化学合成

本文报道了6-巯基嘌呤存在时在水相中通过阳极氧化邻苯二酚来电化学合成5-(嘌呤-6-巯基)邻苯二酚衍生物。循环伏安法和控制电位电解的结果表明该类化合物的形成为EC过程,即邻苯二酚衍生物原料先是被电化学氧化成对应的邻苯醌衍生物,该醌非常活泼,进一步与6-巯基嘌呤发生迈克尔加成反应,原位转化生成化合物3a-3d。该工作进一步证明了水相中邻苯醌衍生物的电化学合成与原位转化是合成邻苯二酚衍生物的重要方法。     

Synthesis of some novel pyrazolo[1,5‐a]pyrimidine, 1,2,4‐triazolo[1,5‐a]pyrimidine,pyrido[2,3‐d]pyrimidine,pyrazolo[5,1‐c]‐1,2,4‐triazine and 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine derivatives incorporating a thiazolo[3,2‐a]benzimidazole moiety

E‐3‐(N,N‐Dimethylamino)‐1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)prop‐2‐en‐1‐one ( 2 ) was synthesized by the reaction of 1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)ethanone ( 1 ) with dimethylformamide‐dimethylacetal. The reaction of 2 with 5‐amino‐3‐phenyl‐1H‐pyrazole ( 4a ) or 3‐amino‐1,2,4‐(1H)‐triazole ( 4b ) furnished pyrazolo[1,5‐a]pyrimidine and 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives 6a and 6b , while the reaction of enaminone 2 with 6‐aminopyrimidine derivatives 7a,b afforded pyrido[2,3‐d]pyrimidine derivatives 9a,b , respectively. The diazonium salts 11a or 11b coupled with compound 2 to yield the pyrazolo[5,1‐c]‐1,2,4‐triazine and 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine derivatives 13a and 13b . Some of the newly synthesized compounds exhibited a moderate effect against some bacterial and fungal species.     

Synthesis and Characterization of Novel Arylaldehyde (Arylketone)‐(4‐Substituted phenyl‐5‐Substituted phenoxy‐Methyl‐4H‐1,2,4‐Triazole‐3‐yl)‐Thiol Acetyl Hydrazones

Fourteen novel arylaldehyde (arylketone)‐(4‐substituted phenyl‐5‐substituted phenoxy‐methyl‐4H‐1,2,4‐triazole‐3‐yl)‐thiol acetyl hydrazone derivatives ( 5a‐5g, 6a‐6g ) were synthesized by 4‐substituted phenyl‐5‐substituted phenoxy‐methyl‐1,2,4‐triazole‐3‐thione as starting material according to substructure link principle, followed by thioetherification, hydrazide hydrazone reaction. The structures of these compounds were confirmed by IR, ¹H NMR and elemental analysis. Crystal structure of compounds 1b and 6d were determined by the X‐ray diffraction.     

Synthesis of Novel 3‐(3‐(5‐Methylisoxazol‐3‐yl)‐7H‐[1,2,4]Triazolo [3,4‐b][1,3,4]Thiadiazin‐6‐yl)‐2H‐Chromen‐2‐Ones

A novel series of coumarin substituted triazolo‐thiadiazine derivatives were designed and synthesized by using 5‐methyl isoxazole‐3‐carboxylic acid ( 1 ), thiocarbohydrazide ( 2 ), and various substituted 3‐(2‐bromo acetyl) coumarins ( 4a , 4b , 4c , 4e , 4d , 4f , 4g , 4h , 4i , 4j ). Fusion of 5‐methyl isoxazole‐3‐carboxylic acid with thiocarbohydrazide resulted in the formation of the intermediate 4‐amino‐5‐(5‐methylisoxazol‐3‐yl)‐4H‐1,2,4‐triazole‐3‐thiol ( 3 ). This intermediate on further reaction with substituted 3‐(2‐bromo acetyl) coumarins under simple reaction conditions formed the title products 3‐(3‐(5‐methylisoxazol‐3‐yl)‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl‐2H‐chromen‐2‐ones ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j ) in good to excellent yields. All the synthesized compounds were well characterized by physical, analytical, and spectroscopic techniques.     

Synthesis and Characterization of Novel 1,2,4‐oxadiazoline Derivatives Containing Pyrazole Moiety by 1,3‐Dipolar Cycloaddition

A series of novel pyrazolyl‐oxadiazoline derivatives bearing 1,2,4‐triazole moiety 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m , 4n , 4o , 4p were synthesized by schiff bases of 3‐methyl‐1‐phenyl?5‐(1,2,4‐triazole‐1‐yl)‐4‐formylpyrazole 3a , 3b , 3c , 3d and various benzohydroximinoyl chlorides in the presence of Et₃N via 1,3‐dipolar cycloaddition reaction. The target products were confirmed by IR, ¹H‐NMR, MS, elemental analysis. In addition, the structure of compound 4d was defined by X‐ray crystallography.     

Synthesis of New Pyrimido[4,5‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine Derivatives via S/N Smiles Rearrangement

Several new pyrimido[4,5‐e ][1,2,4]triazolo[3,4‐b ][1,3,4]thiadiazine derivatives ( 5a , 5b , 5c , 5d , 5e , 5f , 5g ) were synthesized through the condensation reaction of 5‐bromo‐4,6‐dichloropyrimidine ( 1 ) and 4‐amino‐5‐methyl‐4H‐1,2,4‐triazole‐3‐thiol ( 2 ). The single crystal X‐ray data of one of the derivatives confirmed the occurrence of the S/N type Smiles rearrangement during the course of the reaction.     

A Novel Iron‐catalyzed One‐pot Synthesis of 3‐Amino‐1,2,4‐triazoles

A novel one‐pot synthesis of 3‐amino‐1,2,4‐triazole developed via iron (III) catalyzed route is reported. The new method is more efficient, simple, and convenient and presents a concise new strategy for the synthesis of 3‐amino‐1,2,4‐triazole derivatives. The iron (III) complex intermediate assisted in the intramolecular bond cyclization owing to its Lewis acidity or oxidizing properties. A series of aromatic nitriles bearing different electron‐donating and electron‐withdrawing groups substituted at para and/or ortho positions were also investigated. The position of the substituents affected the yield of the final compound, with the para‐substituted substrates giving relatively higher yields.     

Synthesis and crystal structure of novel schiff bases derived from 3‐(2‐ethoxyphenyl)‐4‐amino‐5‐mercapto‐4H‐1,2,4‐triazole

A series of novel 4‐(arylmethylidene)amino‐5‐(2‐ethoxyphenyl)‐3‐mercapto‐4H‐1,2,4‐triazoles ( 2a‐f ) were easily synthesized in high yields by means of the reactions of 3‐(2‐ethoxyphenyl)‐4‐amino‐5‐mercapto‐4H‐1,2,4‐triazole ( 1 ) with various aromatic aldehydes. The compound, 4‐(4‐methylbenzylidene)‐amino‐5‐(2‐ethoxyphenyl)‐3‐mercapto‐4H‐1,2,4‐triazole was investigated with X‐ray crystallography.     

Synthesis of novel 1,3‐substituted 1H‐[1,2,4]‐triazole‐3‐thiol derivatives

By means of regioselective S‐alkylation of 1H‐1,2,4‐triazole‐3‐thiol ( 1 ), a series of S‐substituted derivatives 2a‐j were synthesized. In certain conditions, the reaction of 2 with arylsulfochlorides, arylisocyanates, and quaternary ammonium salts of azines corresponding compounds were obtained 1‐arylsulfonyl‐ (3a‐d) , 1‐arylcarbonamido‐ ( 4a,b ), and 1‐azinyl‐1,2,4‐ ( 6a‐p ) triazoles. Structures of compounds were confirmed by ¹H NMR and elemental analyses. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 20:405–410, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20565     

Synthesis and Characterization of Bis(triaminoguanidinium) 5,5′‐Dinitrimino‐3,3′‐azo‐1H‐1,2,4‐triazolate – A Novel Insensitive Energetic Material

The synthesis of 5,5′‐diamino‐3,3′‐azo‐1H‐1,2,4‐triazole ( 3 ) by reaction of 5‐acetylamino‐3‐amino‐1H‐1,2,4‐triazole ( 2 ) with potassium permanganate is described. The application of the very straightforward and efficient acetyl protection of 3,5‐diamino‐1H‐1,2,4‐triazole allows selective reactions of the remaining free amino group to form the azo‐functionality. Compound 3 is used as starting material for the synthesis of 5,5′‐dinitrimino‐3,3′‐azo‐1H‐1,2,4‐triazole ( 4 ), which subsequently reacted with organic bases (ammonia, hydrazine, guanidine, aminoguanidine, triaminoguanidine) to form the corresponding nitrogen‐rich triazolate salts ( 5 – 9 ). All substances were fully characterized by IR and Raman as well as multinuclear NMR spectroscopy, mass spectrometry, and differential scanning calorimetry. Selected compounds were additionally characterized by low temperature single‐crystal X‐ray diffraction measurements. The heats of formation of 4 – 9 were calculated by the CBS‐4M method to be 647.7 ( 4 ), 401.2 ( 5 ), 700.4 ( 6 ), 398.4 ( 7 ), 676.5 ( 8 ), and 1089.2 ( 9 ) kJ · mol^–1. With these values as well as the experimentally determined densities several detonation parameters were calculated using both computer codes EXPLO5.03 and EXPLO5.04. In addition, the sensitivities of 5 – 9 were determined by the BAM drophammer and friction tester as well as a small scale electrical discharge device.     

GIAO/DFT studies on 1,2,4‐triazole‐5‐thiones and their propargyl derivatives

Density functional theory (DFT)/Becke–Lee–Yang–Parr (B3LYP) and gauge‐including atomic orbital (GIAO) calculations were performed on a number of 1,2,4‐triazole derivatives, and the optimized structural parameters were employed to ascertain the nature of their predominant tautomers. ¹³C and ¹⁵N NMR chemical shifts of 3‐substituted 1,2,4‐triazole‐5‐thiones and their propargylated derivatives were calculated via GIAO/DFT approach at the B3LYP level of theory with geometry optimization using a 6‐311++G** basis set. A good agreement between theoretical and experimental ¹³C and ¹⁵N NMR chemical shifts could be found for the systems investigated. The data generated were useful in predicting ¹⁵N chemical shifts of all the nitrogen atoms of the triazole ring, some of which could not be obtained in solution state ¹⁵N HMBC/HSQC NMR measurements. The energy profile computed for the dipropargylated derivatives was found to follow the product distribution profile of regioisomers formed during propargylation of 1,2,4‐triazole thiones. Copyright © 2013 John Wiley & Sons, Ltd.     

A Facile One‐Pot Three‐Component Synthesis of 5‐(Trifluoromethyl)‐4,7‐dihydro‐[1,2,4]‐triazolo[1,5‐a]pyrimidine Derivatives in Ionic Liquid

An efficient one‐pot synthesis of 5‐(trifluoromethyl)‐4,7‐dihydro‐7‐aryl‐[1,2,4]triazolo[1,5‐a]pyrimidine derivatives was performed via the reaction of aryl aldehyde, 3‐amino‐1,2,4‐triazole and ethyl 4,4,4‐trifluoro‐3‐oxobutanoate or 4,4,4‐trifluoro‐1‐phenylbutane‐1,3‐dione in ionic liquid. This method has the advantages of short synthetic route, operational simplicities, mild reaction conditions, high yields and eco‐friendliness.     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

Nickel‐catalyzed Buchwald–Hartwig amination of pyrimidin‐2‐yl tosylates with indole,benzimidazole and 1,2,4‐triazole

Nickel‐catalyzed Buchwald–Hartwig amination of pyrimidin‐2‐yl tosylates with indole and benzimidazole was achieved using Ni(dppp)Cl₂ as catalyst, yielding a variety of novel C2‐substituted pyrimidine derivatives in good yields. This reaction proved to be tolerant of various pyrimidin‐2‐yl tosylates bearing either electron‐donating or electron‐withdrawing groups as well as nucleophiles including indole, benzimidazole and 1,2,4‐triazole. Copyright © 2016 John Wiley & Sons, Ltd.