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.     

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.     

1,2,4-triazines. III. A convenient and general synthesis of 4H-[1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-4-ones

4H-[1,3,4]Thiadiazolo[2,3-c][1,2,4]triazin-4-ones were prepared by cyclization of 3-thio-4-amino-1,2,4-tri-azine-3,5(2H,4H)-diones with a variety of acids in the presence of concentrated sulfuric acid. The synthesis appears to be general.     

A CONVENIENT AND GENERAL SYNTHESIS OF A NOVEL HETEROCYCLIC SYSTEM; 5H-[1,3,4]THIADIAZOLO[2,3-d] [1,2,4]TRIAZIN-5-ONES

Abstract

5H-[1,3,4]Thiadiazolo[2,3-d][1,2,4]triazin-5-ones were synthesized by cyclocondensation of 4-amino-5-mercapto-1,2,4-triazin-3-ones with a variety of carboxylic acids in the presence of phosphorus oxychloride.     

Synthesis of heterocycles. Part VII Synthesis and antimicrobial activity of some 7H-s-triazolo[3,4-b][1,3,4]thiadiazine and s-triazolo[3,4-b][1,3,4]thiadiazole derivatives

The cyclization of 4-amino-5-aryl-3-cyanomethylthio-1,2,4-triazoles II in the presence of concentrated sulfuric acid yields 7H-6-amino-s-triazolo[3,4-b][1,3,4]thiadiazines III . Cyclization of 4-amino-5-aryl-1,2,4-tria-zole-3-thiones I with phenacyl chloride yields 7H-3-aryl-6-phenyl-s-triazolo[3,4-b][1,3,4]thiadiazines IV . Similarly, compounds I condensed with cyanogen bromide, phenyl isothiocyanate and carbon disulfide to give the corresponding cyclized products 6-amino-3-aryl-s-triazolo[3,4-b][1,3,4]thiadiazoles V , 3-aryl-6-phenyl-amino-s-triazolo[3,4-b][1,3,4]thiadiazoles VI and 3-aryl-striazolo[3,4-b][1,3,4]thiadiazol-6(5H)thiones VII , respectively. Also in the presence of phosphoryl chloride, compounds I underwent cyclization with monocarbo-xylic acids and oxalic acid to 3,6-diaryl-s-triazolo[3,4-b][1,3,4]thiadiazole VIII and 6,6′-bis(3-aryl-s-triazolo-[3,4-b][1,3,4]thiadiazoles) IX . The above compounds were screened for their antimicrobial activity.     

Synthesis of 3-Alkyl-6-aryl(arylamino)-7H-[1,2,4]triazolo- [3,4-b][1,3,4]thiadiazines

Starting from 5-alkyl-4-amino-4H-1,2,4-triazole-3-thiols and substituted chloroacetanilides, the corresponding (5-alkyl-4-amino-4H-1,2,4-triazol-3-ylsulfanyl)acetanilides were synthesized. The products underwent intramolecular cyclization in boiling phosphoryl chloride to afford 3-alkyl-6-arylamino-7H-[1,2,4]-triazolo[3,4-b][1,3,4]thiadiazines. 3-Alkyl-6-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine hydrobromides were obtained by reaction of 5-alkyl-4-amino-4H-1,2,4-triazole-3-thiols with substituted phenacyl bromides.     

Synthesis of Some 1,3-Thiazole, 1,3,4-Thiadiazole, Pyrazolo[5,1-c]-1,2,4-triazine, and 1,2,4-Triazolo[5,1-c]-1,2,4-triazine Derivatives Based on the Thiazolo[3,2-a]benzimidazole Moiety

3-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile was synthesized by refluxing ethyl 3-methylthiazolo[3,2-a]benzimidazole-2-carboxylate, acetonitrile, and sodium hydride. Treatment of 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile with phenyl isothiocyanate, in the presence of KOH, furnished the corresponding potassium salt which was converted into thioacetanilide derivative upon neutralization. The thioacetanilide derivative reacts with α-chloroacetylacetone and ethyl α-chloroacetoacetate to give the 1,3-thiazole derivatives, while the reaction of the'thioacetanilide derivative with hydrazonyl chlorides gave 1,3,4-thiadiazole derivatives. On the other hand, 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile reacted with the diazonium salt of both 3-phenyl-5-amino-(1H)-pyrazole and 5-amino-l,2,4-(1H)-triazole to afford the corresponding hydrazones. The latter hydrazones underwent an intramolecular cyclization upon boiling in pyridine to give pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives. Moreover, the behavior of thiazolo[3,2-a]benzimidazol-3(2H)-one towards phenyl isothiocyanate followed by the reaction with α-chloroketones or hydrazonyl chlorides was investigated. Some of the latter compounds exhibited moderate effects against some bacterial and fungal species.     

Condensed as-triazines. Synthesis of 7-aryl-8H-[1,4]thiazino[2,3-e]-1,2,4-triazin-3(2H)-one

Ring closure of 6-amino-3-oxo-as-triazine-5-thione with α-haloketones provides the thiazino[2,3-e]-1,2,4-triazines which dehydrate via an unusual pathway to give 7-aryl-8H[1,4]thiazino[2,3-e]-1,2,4-triazin-3(2H)-ones.     

Synthesis of Some 1,3-Thiazole, 1,3,4-Thiadiazole, Pyrazolo[5,1-c]-1,2,4-triazine, and 1,2,4-Triazolo[5,1-c]-1,2,4-triazine Derivatives Based on the Thiazolo[3,2-a]benzimidazole Moiety

Summary. 3-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile was synthesized by refluxing ethyl 3-methylthiazolo[3,2-a]benzimidazole-2-carboxylate, acetonitrile, and sodium hydride. Treatment of 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile with phenyl isothiocyanate, in the presence of KOH, furnished the corresponding potassium salt which was converted into thioacetanilide derivative upon neutralization. The thioacetanilide derivative reacts with α-chloroacetylacetone and ethyl α-chloroacetoacetate to give the 1,3-thiazole derivatives, while the reaction of the'thioacetanilide derivative with hydrazonyl chlorides gave 1,3,4-thiadiazole derivatives. On the other hand, 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile reacted with the diazonium salt of both 3-phenyl-5-amino-(1H)-pyrazole and 5-amino-l,2,4-(1H)-triazole to afford the corresponding hydrazones. The latter hydrazones underwent an intramolecular cyclization upon boiling in pyridine to give pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives. Moreover, the behavior of thiazolo[3,2-a]benzimidazol-3(2H)-one towards phenyl isothiocyanate followed by the reaction with α-chloroketones or hydrazonyl chlorides was investigated. Some of the latter compounds exhibited moderate effects against some bacterial and fungal species.     

Studies on condensed heterocyclic compounds II.Synthesis and antibacterial activity of 3-(4''''-pyridyl)-6-aroylamino/arylamino-S-triazolo[3,4-b]-1,3,4-thiadiazoles

3-(4′-Pyridyl)-4-amino-5-mercapto-1,2,4-triazole(1)reacted with aroyl isothiocyanates2a-1 to yield twelve novel 3-(4′-pyridyl)-6-aroylamino-S-triazolo[3,4-b]-1,3,4-thiadiazoles,4a-1.Triethylamine was necessary for the condensation of 1 with phenyl isothiocyanate(3)to give 3-(4′-pyridyl)-6-phenylamino-S-triazolo[3,4-b]-1,3,4-thiadiazole(6).The structures were confirmed bythe elemental and spectral analyses.Their antibacterial activity against B.Subtilis,E.Coli,E.aerogenes and S.aureus was observed preliminary.     

Synthesis of 1,2,4-triazole, 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives of benzotriazole

A novel series of 1-(1-carbonylmethyl-1H-benzotriazole) thiosemicarbazides 3a-e was synthesized and then cyclized with sodium hydroxide to afford 1-(4-substituted-4H-1,2,4-triazole-3-thion-5-yl)methyl-1H-benzotriazoles 4a-e , which were alkylated with ethyl iodide to l-(3-ethylthio-4-substituted-4H-1,2,4-triazol-5-yl)-methyl-1H-benzotriazoles 5b-e . The reaction of 1H-benzotriazol-1-acetic acid hydrazide ( 2 ) with carbon disulphide and potassium hydroxide followed by hydrazine hydrate gave 1-(4-amino-4H-1,2,4-triazole-3-thion-5-yl)methyl-1H-benzotriazole ( 6 ). Its subsequent condensation with carboxylic acids in the presence of phosphorus oxychloride or with phenacyl bromides afforded two series of fused heterocycles namely; 6-substituted-3-[1-(1H-benzotriazole)methyl]-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 7a-e and 6-substituted phenyl-3-[1-(1H-benzotriazole)methyl]-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines 8a-e respectively. The structure of the newly synthesized compounds was elucidated by elemental analyses, ir and nmr spectra.     

Regioselectivity of cyclization of 1-(6-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)-4-arylthiosemicarbazides by treating with methyl iodide and dicyclohexylcarbodiimide

1-(6-Methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)-4-arylthiosemicarbazides treated with methyl iodide in the presence of sodium acetate in ethanol convert into 6-methyl-3-arylamino[1,2,4]-triazolo[4,3-b][1,2,4]triazin-7(1H)-ones. In reaction with dicyclohexylcarbodiimide 6-methyl-3-arylamino[1,2,4]triazolo[3,4-c][1,2,4]triazin-5(1H)-ones were obtained which at heating in alcohol solution in the presence of sodium acetate or at 262–272°C underwent the Dimroth rearrangement to give 3-methyl-7-arylamino[1,2,4]triazolo[5,1-c][1,2,4]-triazin-4(8H)-ones.     

微波促进下3-(2-苯并呋喃基)-4-氨基-5-巯基-1,2,4-三唑

微波辐射条件下, 首先由2-苯并呋喃甲酰肼依次与二硫化碳和水合肼反应合成3-(2-苯并呋喃基)-4-氨基-5-巯基- 1,2,4-三唑, 进一步在微波辐射条件下由4-氨基-5-巯基-1,2,4-三唑分别与芳甲酸/芳氧基乙酸、α-溴代苯乙酮及芳醛反应以较高产率制得了相应的1,2,4-三唑并[3,4-b]-1,3,4-噻二唑、1,2,4-三唑并[3,4-b]-1,3,4-噻二嗪及4-芳亚甲基亚胺基-5-巯基-1,2,4-三唑. 产物结构经IR, ¹H NMR, MS及元素分析进行了表征.     

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).     

Reaction of 4-thioxo-1,3-benzothiazines with thiocarbohydrazine: Synthesis and reactivity of 1,3,4-triazolo[3,2-c]quinazoline derivatives

2-Aryl-4-thioxo-1,3-benzothiazines react with thiocarbohydrazide to give the new mesoionic compounds an-hydro 1-amino-5-aryl-2-mercapto-1,3,4-triazolo[3,2-c]quinazolin-4-ium hydroxides. These compounds react with methyl iodide, aldehydes and phenacyl bromides to give 1-amino-5-aryl-2-methylthio-1,3,4-triazolo-[3,2-c]quinazolin-4-ium iodides, 4-arylidenamino-3-(o-aroylamino)phenyl-1H-1,2,4-triazolin-5-thiones and 3-(o-aroylamino)phenyl-6-aryl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines, respectively. These latter compounds by sequential treatment with methyl trifluoromethanesulphonate and triethylamine lead to 3-(o-aroylamino)-phenyl-6-aryl-1-methyl-7-mercapto-1H-pyrazolo[5,1-c]-1,2,4-triazoles.     

1,2,4-Triazoles. Improved synthesis of 5-substituted 4-amino-3-mer-cato-(4H)-1,2,4-triazoles and a facile route to 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles

The reaction of thiocarbohydrazide with carboxylic acids at the melting temperature allows an improved preparation of the S-substituted 4-amino-3-mercapto-1,2,4-triazole heterocycles. The crude 4-amino-5-mercapto-1,2,4-triazoles react easily with carboxylic acids or carboxylic acid chlorides to afford the 1,2,4-triazolo[3,4-fc][1,3,4]thiadiazole ring system.     

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.     

Synthesis of 1,3-Bis[(3-aryl)-S-triazolo[3,4-b]-[1,3,4]thiadiazole-6-yl]benzenes

1,3-bis[(3-aryl)-s-triazolo[3,4-b]-[1,3,4]thiadiazole-6-yl]benzenes 2 were synthesized in high yields by the reaction of 3-aryl 4-amino-5-mercapto-1,2,4-triazole 1 with m-phthalic acid.     

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.     

Synthesis of 8-Aryl[1,2,4]triazolo[1,5-d][1,2,4]triazin-5(6H)-ones by S HN Reactions

A new procedure has been proposed for the synthesis of 8-aryl[1,2,4]triazolo[1,5-d][1,2,4]-triazin-5(6H)-ones by reaction of 6-aryl-1,2,4-triazin-3(2H)-ones with hydrazides derived from aliphatic, aromatic, and heterocyclic carboxylic acids. The process invloves nucleophilic substitution of hydrogen (S_N ^H)in aryltriazinones, oxidative closure of azole ring, and Dimroth rearrangement.