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.     

Synthesis and Biological Evaluation of Some Novel N,N ′-Bis-(1,2,4-Triazin-4-Yl)Dicarboxylic Acid Amides and Some Fused Rings with 1,2,4-Triazine Ring

Some of novel N , N '-bis-(1,2,4-triazin-4-yl)dicarboxylic acid amides ( 2-5 ) and thiadiazolo[2,3- b ][1,2,4]triazin-7-yl carboxylic acid derivatives ( 6 , 7 ) were prepared by heating 4-amino-6-methyl-5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazine ( 1 ) with different dicarboxylic acids (oxalic, malonic, fumaric, maleic, succinic, and phthalic acids respectively) in POCl 3 . Refluxing 1 with 1-chloro-2,4-dinitrobenzene in DMF yielded 3-methyl-6-nitro-10 H -benzo[1,2,4]thiadiazino[2,3- c ][1,2,4]triazin-4-one ( 8 ). Condensation of 1 with 2,4-pentandione in refluxing acetic acid furnished 6-methyl-4-(1-methyl-3-oxobut-1-enylamino)-3-thioxo-3,4-dihydro-2 H -[1,2,4]triazin-5-one ( 9 ). 3,8-D imethyl[1,2,4] triazino[3,4- b ][1,3,4]thiadiazine-4,7-dione ( 11 ) was prepared by refluxing 1 with 2-bromopropionyl bromide in anhydrous benzene to afford the corresponding N -acetylated derivative 10 , which was cyclized by using triethylamine. Also, some triazinylquinazolinones 13a , b were obtained by fusion of 1 with 6-bromo(and/or 6,8-dibromo)-2-methyl-3,1-benzoxazin-4 H -ones.     

Facile synthesis of 6-hetaryl[1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazoles and 7-hetaryl[1,3,4]thiadiazolo[2,3-<Emphasis Type="Italic">c</Emphasis>][1,2,4]triazines with fungicidal activity

Condensation of 4-amino-4H-1,2,4-triazole-3-thiol and 4-amino-6-methyl-3-sulfanyl-1,2,4-triazin-5(4H)-one with ethyl cyanoacetate gave ethyl [1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-ylacetate and ethyl 3-methyl-4-oxo-4H-[1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-7-ylacetate, respectively. Reactions of the condensation products with 1,3-diphenylprop-2-en-1-one, aromatic aldehydes, and carbon disulfide or N,N-dimethylformamide dimethyl acetal (followed by treatment with hydrazine hydrate) gave the corresponding 6-hetaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 7-hetaryl-3-methyl-4H-[1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-4-ones. Preliminary tests revealed fungicidal activity of the pyrazolyl-substituted derivatives. Published in Russian in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 12, pp. 1813–1818. The text was submitted by the authors in English.     

New Synthesis of [1,3,4] Thiadiazolo [2,3-C][1,2,4] Triazinone; Transfer of Active Electron by Microwaves

Reaction of various aromatic aldehydes with 4-amino-6-methyl-1,2,4-triazin-5-one supported on to montmorillonite-K10 in the presence of nitrobenzene under microwaves irradiation, afforded the corresponding [1,3,4] thiadiazole [2,3-c][1,2,4]-triazinones.     

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%。     

Synthesis and molecular structure of 6-amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one

The title compound 6-amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]-triazin-8(7H)-one (4), molecular formula C(11)H(10)N(6)OS, was obtained by the reaction of 3-amino-2-benzyl-6-hydrazino-1,2,4-triazin-5(2H)-one (3) with carbon disulfide in a water/pyridine mixture. Compound 4 can also be synthesized by reacting 6-amino-3(2H)mercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (7) with benzyl bromide in methanolic ammonia water. The compound crystallizes in the monoclinic space group P2(1)/c with a = 7.2926(15), b = 14.456(2), c = 11.436(2) A, beta = 105.30(2) degrees , V= 1162.9(4) A(3) and Z = 4, resulting in a density Dcalc of 1.567 g/cm(3). Molecules of 4 are linked by extensive intermolecular N-H...N and N-H...O hydrogen bonding [graph set R(2)(2 )(9)]. The structure is further stabilized by pi-pi stacking interactions.     

Synthesis of 8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine

8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine has been synthesized by the interaction of 6-tert-butyl-3-hydrazino-1,2,4-triazolo[3,4-c]-1,2,4-triazin-5-one with formic acid. The conditions of carrying out the reaction are discussed. Spectral characteristics are given.     

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%.     

On the preparation of substituted 4H- 1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-4-ones and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles

The reaction of benzoyl isothiocyanates and methoxycarbonyl isothiocyanate with 4-amino-4,5-dihydro-3-(methylthio)-1,2,4-triazin-5-ones in acetonitrile gave several substituted 4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-4-ones VIa-h instead of the expected thioureas. In addition, benzoyl isothiocyanate reacted with 4-amino-3-(methylthio)-5-(trifluoromethyl)-4H-1,2,4-triazole to give the benzoyl thiourea IX and with 4-amino-3-mercapto-5-(trifluoromethyl)-4H-1,2,4-triazole to give the bicyclic compound N-[3-(trifluoromethyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol-6-yl]benzamide IX .     

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.     

Synthesis of [1,5-A]Pyrimidinone Ring Derivatives

Cyclodehydrogenation of the benzalhydrazino derivatives 5 and 6 gave 6-cyano-7-(4-methoxyphenyl)- 2-phenyl-5-oxo-1,2,4-triazolo[1,5-a]pyrimidine (8) and 6-cyano-7-(4-methoxyphenyl)-4-methyl-2-phenyl- 5-oxo-1,2,4-triazolo[1,5-a]pyrimidine (9) respectively. Melhylation, acetylation and benzylation of 8 gave the corresponding N-methyl, acetyl and benzyl derivatives 10-12 . Methylation of 5 with dimethylsulfate gave 2-benzalhydrazino-5-cyano-3-methyl-6-(4-methoxyphenyl)-3,4-dihydropyrimidin-4-one (6) , of which the reaction with acetic anhydride in pyridine afforded the N-acetylbenzalhydrazino derivative 15 . The latter was also prepared from acetylation of 5 followed by medthylation with iodomethane. Acetylation of 5 with boiling acetic anhydride afforded the diacetyl derivative 16 , whereas its benzylation gave the mono-N-benzyl derivative 14 .     

Condensed imidazo-1,2,4-azines. 14. Synthesis and reactivity of 3-chlorine-substituted imidazo[1,2-b]-1,2,4-triazines

When boiled with phosphorus pentachloride in phosphorus oxychloride, 2-methyl-6-phenyl-imidazo[1,2-b]1,2,4-triazin-4H-3-one gives a mixture of mono- and dichloro derivatives, whereas the action of thionyl chloride in chloroform with a catalytic amount of DMFA gives only the monosubstituted product 2-methyl-3-chloro-6-phenylimidazo[1,2-b]-1,2,4-triazine. The reactivity of the 3-chloro derivatives of imidazo[1,2-b]-1,2,4-triazine in reactions with diethylamine, piperidine, morpholine, aniline, hydrazine hydrate and thiourea was investigated.For Communication 13, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 981–985, July, 1986.     

Reactions of Hydrazonoyl Halides 41: 1 Synthesis of 1,2,4-Triazoles, 2,3-Dihydro-1,3,4-thiadiazoles,and Triazolo[4, 3-a]pyrimidines

Triazoles, thiadiazoles, and triazolo[4, 3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of 3-methyl-4-(methylthiothioxomethyl)-2-pyrazolin-5-one, 3-methyl-4-[methylthio(phenylamino)methyl]-2-pyrazolin-5-one, and pyrimidine-2-thiones. Structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative-methods synthesis whenever possible.     

6-Arylamino-3-methyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines: Novel N-Arylamidine Structures

We propose a method for obtaining derivatives of 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine by alkylation of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol by substituted -chloroacetanilides, followed by cyclization of the intermediate by phosphorus oxychloride.     

6-取代苄硫基-3-(3,4,5-三甲氧基苯基)-1,2,4-三唑[3,4-b][1,3,4]噻二唑类化合物的合成与抑菌活性

以4-氨基-5-(3,4,5-三甲氧基苯基)-3-巯基-1,2,4-三唑为原料,环化得到6-巯基-3-(3,4,5-三甲氧基苯基)-1,2,4-三唑[3,4-b][1,3,4]噻二唑再与取代苄氯反应,得到9个6-取代苄硫基-3-(3,4,5-三甲氧基苯基)-1,2,4-三唑[3,4-b][1,3,4]噻二唑类衍生物3a～3i.其结构经IR,1H NMR,MS和元素分析确证.初步生物活性测试结果表明部分化合物有一定的杀菌活性.     

3-Methyl-4H-[1,2,4]-oxadiazol-5-one: a versatile synthon for protecting monosubstituted acetamidines

The utilization of 3-methyl-4H-[1,2,4]-oxadiazol-5-one as a versatile protected acetamidine is demonstrated through employment in a variety of synthetic sequences. The potassium salt (2a) or the neutral form (2b) is alternatively shown to be superior for various synthetic reactions (i.e., alkylation, Michael addition, Mitsunobu) to incorporate side chains for further synthesis. The 3-methyl-4H-[1,2,4]-oxadiazol-5-one moiety was found to be stable to acid or base under non-aqueous conditions. It was also found to be stable to many reagents commonly used for organic synthesis. Despite this stability, the free acetamidine may be released by mild reduction including Lindlar hydrogenation or dissolving metal reductions. Alternatively, the hydroxyl amidine may be formed via alkaline hydrolysis.     

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

1,2,4-Triazines VIII. The synthesis of 1,2,4-triazino[2,3-e]pyrazolo[1,5-a]-1,3,5-triazines and 1,2,4-triazino[4,3-e]pyrazolo[],5-a] -1,3,5-triaziness

Substituted 2,5-dihydro-3[3-methyI(or phenyl)-5-aminopyrazolyl]-1,2,4-triazin-5-ones reacted with orthoesters to yield exclusively 1,2,4-triazino[2,3-e]pyrazolo[1,5-a]-1,3,5-triazin-5-ones. The structure elucidation was supported by independent synthesis of the isomeric 1,2,3-triazino-[4,3-e]pyrazolo[1,5-α]-1,3,5-triazin-7-one as well as by spectroscopical methods.     

含双-三唑并噻二唑环的庚烷类衍生物的合成及抗菌活性

The aroylhydrazides were prepared by esterification and hydrazinolysis of corresponding aromatic carboxylic acids.The reaction of aroylhydrazides with CS2/KOH in absolute ethanol gave potassium aroyldithiocarbazates and then hydrazinolysis of potassium aroyldithiocarbazates with hydrazine hydrate afforded 3-aryl-4-amino-5-mercapto-1,2,4-triazoles(1a～1g).New seven compounds of bis[(3-aryl)-s-triazolo[3,4-b]-[1,3,4]thiadiazole derivatives(2a～2g) were synthesized in high yields by cyclization of nonanedioic ac...     

Synthesis and anticancer activity of some new s-glycosyl and s-alkyl 1,2,4-triazinone derivatives

A series of S-glycosyl and S-alkyl derivatives of 4-amino-3-mercapto-6-(2-(2-thienyl)vinyl)-1,2,4-triazin-5(4H)-one (1) were synthesized using different halo compounds such as preacetylated sugar bromide, 4-bromobutylacetate, 2-acetoxyethoxy-methyl bromide, 3-chloropropanol, 1,3-dichloro-2-propanol, epichlorohydrin, allyl bromide, propargyl bromide, phthalic and succinic acids in POCl3. The structures of the synthesized compounds have been deduced from their elemental analysis and spectral (IR, 1H-NMR, and 13C-NMR) data. Some of the synthesized compounds were screened as anticancer agents. Significant anticancer activities were observed in vitro for some members of the series, and compounds 4-Amino-3-(3-hydroxypropylthio)-6-(2-(2-thienyl)vinyl)-1,2,4-triazin-5(4H)-one (12) and 3-(4-Oxo-3-(2-(2-thienyl)vinyl)-4H-[1,3,4]thiadiazolo-[2,3-c][1,2,4]tr-iazin-7-yl)propanoic acid (18) are active cytotoxic agents against different cancer cell lines.