肼类衍生物在五元唑类杂环合成中的应用进展

简要概述了肼类衍生物的结构及反应活性,总结了近十年来肼类衍生物分别在合成五元唑类杂环如吡唑、噻唑、1,3,4-噁二唑、1,3,4-噻二唑以及三唑类化合物,及其相关的稠杂环如吡唑并某环、s-三唑[3,4-b][1,3,4]-噻二唑、s-三唑[3,4-b][1,3,4]-噻二嗪,以及含有1,2,4-三唑的稠杂环化合物等合成中的应用进展.     

Synthesis of Benzo[4,5]thiazolo[2,3-c][1,2,4]triazole Derivatives via C-H Bond Functionalization of Disulfide Intermediates

Many nitrogen- and sulfur-containing heterocyclic compounds exhibit biological activity. Among these heterocycles are benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles for which two main synthetic approaches exist. Here we report a new synthetic protocol that allows the preparation of these tricyclic compounds via the oxidation of a mercaptophenyl moiety to its corresponding disulfide. Subsequent C-H bond functionalization is thought to enable an intramolecular ring closure, thus forming the desired benzo[4,5]thiazolo[2,3-c][1,2,4]triazole. This method combines a high functional group tolerance with short reaction times and good to excellent yields.     

Syntheses of Chiral Fused Heterocyclic Compounds Containing l,2,4-Triazole Ring

The chemistry of life is based considerably on chirality. Consequently, stereospecificity has to be regarded as an especially important characteristic of biological systems. The influence of stereospecificity of the biological activities of enzyme inhibitors or compounds binding to receptor is a well known fact in the field of drug action^[1]. s-Triazoles and l,3,4-thiadiazoles are reported to exhibit broad spectrum of biological and pesticidal activities^[2-3].In recent years, bridge head nitrogen heterocycles have received much attention as anthelmintic agents, however, it is not observed that the syntheses of chiral fused heterocyclic compounds containing s-triazoles and l,3,4-thiadiazoles. In order to study the relationship between stereochemistry and the performance of fungicides, we have synthesized a series of (s)-1,2-di(3-aryl-s-triazolo[3,4-b][1,3,4] thiadiazolo-6-yl) ethylamine and (s)-1-(3-aryl-s-triazolo[3,4-b][l,3,4] thiadiazolo-6-yl) ethylamine by the condensation of 3-aryl-4-amino-5-mercapto-1,2,4-triazoles with L-aspartic acid and L-alanine in the presence of phosphorusoxychloride.     

Ionic Liquid-Mediated Facile Synthesis and Antimicrobial Study of Thiazolo [2,3-b]Benzo[h]Quinazolines and Thiazino[2,3-b] Benzo-[h]Quinazolines

Abstract

8-Methoxy-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione, obtained by the condensation of 2-benzylidene-6-methoxy-3,4-dihydronapthalene-1(2H)-one with thiourea, on reaction with chloroacetic acid and 3-chloropropanoic acid in the presence of the ionic liquid N-methylpyridinium tosylate furnishes 3-methoxy-7-phenyl-7,10-dihydro-5H- benzo[h]thiazolo[2,3-b]quinazoline-9(6H)-one and 3-methoxy-7-phenyl-5,6,10,11-tetrahydro- benzo[h][1,3]thiazino[2,3-b]quinazoline-9(7H)-one. Further, condensation of the thione with 1,2-dibromoethane and 1,3-dibromopropane yields 3-methoxy-7-phenyl-6,7,9,10-tetrahydro-5 H-benzo[h]thiazolo[2,3-b]quinazoline and 3-methoxy-7-phenyl-5,6,7,9,10,11-hexahydrobenzo [h][1,3]thiazino[2,3-b]quinazoline respectively. Arylidene derivatives have been obtained by two routes. The structures of the cyclized compounds have been established on the basis of elemental analysis and spectroscopic data. The synthesized compounds were screened for antimicrobial activity. Some of the compounds showed promising antimicrobial activities.     

Synthesis and reactions of 3-aminothiazolidine-2-thion-4-one derivatives. 4. Thiazolo[3,4-b][1,2,4]treiazole derivatives

It is shown that derivatives of a new heterocyclic system, viz., thiazolo[3,4-b][1,2,4]triazole, the structure of which was established by means of their IR and PMR spectra, are formed in the reaction of 5-substituted 3-aminorhodanines with imidoyl chlorides.See [1] for Communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 331–333, March, 1982.     

Recent synthetic strategies of medicinally important imidazothiadiazoles

Imidazothiadiazole is a fundamental fused heterocyclic compound containing imidazole and thiadiazole ring systems. This versatile framework has significant applications in pharmaceutical chemistry and also possessed a remarkable biological profile. The derivatives of imidazo[2,1-b][1,3,4]thiadiazole have a broad spectrum of biological applications such as antitumor, tubulin inhibitor, anticancer, antifungal, anti-inflammatory, antimicrobial, antitubercular, anticonvulsant, antibacterial and as enzyme inhibitors. These derivatives also play a significant role in the development of non-linear optics and photo-electronics. Synthesis of this fused bicyclic compound mainly involved the reaction between 2-amino-1,3,4-thiadiazoles and α-haloketones, with different substitutions at the 2, 5, and 6 positions of the ring system. Moreover, microwave assisted multicomponent and C–C coupling reactions in the presence of catalysts or under solvent free reaction conditions were found to be reliable and valuable approaches. This review is a concerted approach to describe the synthesis and applications of imidazo[2,1-b][1,3,4] thiadiazole derivatives reported during 2015–2022.     

SYNTHESES AND BIOLOGICAL ACTIVITIES OF 1,2,4-TRIAZOLO-[3,4-B][1,3,4]THIADIAZOLE DITHIOPHOSPHATES

In this article, we incorporated the organic phosphorus group on to a triazolothiadiazole ring to prepare the title compounds fused 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole heterocyclic compounds. From the results on biological activities, we found that most compounds showed weak activities, and thus the structures need to be further optimized for improved activity.     

Synthesis of condensed heterocycles containing a pyrimido[5,4-e][1,3]-thiazine fragment

The cyclocondensation of 4,6-dichloro-2-methylthiopyridine-5-carbaldehyde and heterocyclic thiones such as 1,2,4-triazole-5-thione, imidazolidine-2-thione, imidazole-2-thione, and 4,5-diphenylimidazole-2-thione in dimethylformamide gave tricyclic heterocycles containing a pyrimido[5,4-e][1,3]thiazine fragment. The reaction of 6-chloro-8-methylthio-5H-pyrimido[5,4-e][1,2,4]triazolo[5,1-b][1,3]thiazin-5-ol with diethylamine, pyrrolidine, and morpholine gave the corresponding 6-dialkylaminopyrimidotriazolothiazines.Vilnius University, 2006 Vilnius, Lithuania; e-mail: sigitas.tumkevicius@chf.vu.lt. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 854–856, June, 2000.     

Microwave assisted synthesis of some new fused 1,2,4-triazines bearing thiophene moieties with expected pharmacological activity

Rapid and efficient solvent-free synthesis of 4-amino-3-mercapto-6-[2-(2-thienyl)vinyl]-1,2,4-triazin-5(4H)-one 1 under microwave irradiation is described. Some new fused heterobicyclic nitrogen systems such as 1,2,4-triazino[3,4-b][1,3,4]thiadiazinones, 1,3,4-thiadiazolo[2,3-c][1,2,4]triazinone and pyrazolo[5,1-c]-[1,2,4]triazine-7-carbonitrile, have been synthesized by treatment of 1 with bifunctional oxygen and halogen compounds, CS?/KOH and malononitrile via heterocyclization reactions, in addition to some uncondensed triazines. Structures of the products have been deduced from their elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR). Select new synthesized compounds were screened as anticancer agents, with some showing activity as cytotoxic agents against different cancer cell lines.     

Regioselectivity of cyclization of 3-allyl(propargyl)sulfanyl-5<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indoles

The interaction of 3-allylsulfanyl-5H-[1,2,4]triazino[5,6-b]indole with iodine led to 1-iodomethyl-1,2-dihydro[1,3]thiazolo[2',3':3,4][1,2,4]triazino[5,6-b]indol-11-ium pentaiodide with an angular structure, on the basis of which 1-iodomethyl-1,2-dihydro[1,3]thiazolo-, 1-methylidene-1,2-di-hydro[1,3]thiazolo, and 1-methyl[1,3]thiazolo derivatives were obtained. The intramolecular cyclization of 3-propargyl(allyl)sulfanyl-5H-[1,2,4]triazino[5,6-b]indoles under the influence of concentrated sulfuric acid led to linear annelated products:3-methyl[1,3]thiazolo[3',2':2,3][1,2,4]tri-azino[5,6-b]indole or its 2,3-dihydro derivative.     

Condensed heterocycles with a thiazole ring. 10. Thiazolo[3,4-b][1,2,4]triazines

Derivatives of a new heterocyclic system, viz., the thiazolo[3,4-b][1,2,4]triazinium ion, were obtained by condensation of cyanobenzyl benzenesulfonate with substituted N-dithiocarboxyhydrazones of 1,2-diketones and -isonitroso ketones.See [1] for communication 9.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 498–501, April, 1985.     

Halocyclization of 3-allylthio-5H-[1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indole

The synthesis of 3-allylthio-5H-[1,2,4]triazino[5,6-b]indole has been carried out by the reaction of 3-mercapto-5H-[1,2,4]triazino[5,6-b]indole with allyl bromide in the NaOH–H₂O–DMSO system and in a one-pot synthesis from isatin-β-thiosemicarbazide. Halocyclization of allylthio-5H-[1,2,4]-triazino[5,6-b]indole synthesized the 3-halomethyl-3,10-dihydro-2H-[1,3]thiazolo[3',2':2,3][1,2,4]-triazino[5,6-b]indolium halides.     

Synthesis of heterocyclic compounds possessing the 4H-thieno[3,2-b]pyrrole moiety

A series of novel heterocyclic combinatorial libraries containing 4H-thieno[3,2-b]pyrrole, thieno[2',3':4,5]-pyrrol[1,2-d][1,2,4]triazine and thieno[2',3':4,5]pyrrolo[1,2-a]pyrazine heterocyclic moieties were obtained by parallel solution-phase synthesis. Key steps include different reactions of initial alkyl 4H-thieno[3,2-b]-pyrrole-5-carboxylates, such as alkylation with alkylating agents; transformation of the carboxylate group into different reactive functionalities, followed by reactions with electrophilic species; intramolecular cyclizations; and amide bond formation. Simple manual techniques for parallel reactions were coupled with easy purification procedures to give high-purity final products.     

Fused 1,2,4-triazole heterocycles. IV. Synthesis of four new heterocyclic ring systems of [1,2,4]triazolo[1,3]thiazinoquinolines

Syntheses of 5H-[1,2,4]triazolo[5′,1′:2,3][1,3]thiazino[5,4-c]quinolines 8, 5H-[1,2,4]triazolo[3′,4′:2)3][1,3]thiazino[5,4-c]quinolines 9, 5H-[1,2,4]triazolo[5′,1′:2,3][1,3]thiazino[5,6-c]quinolines 14 and 5H-[1,2,4]triazolo[3′,4′:2,3][1,3]thiazino[5,6-c]quinolines 15 are described starting from 4-chloro-3-chloromethylquinaldine (4) and 1,2,4-triazole-5-thiols 5 taking advantage of different reactivity of the chlorine atoms of 4 under different reaction conditions. The structures of products 8, 9, 14 and 15 and the intermediates leading to them were confirmed by desulfurization, unequivocal syntheses and nmr spectroscopy as well.     

Design,Synthesis, and Anticancer Activity of Novel Fused Purine Analogues

6‐Mercaptopurine has been utilized for the synthesis of various fused purine analogues through different chemical reactions to yield [1,4]thiazino[4,3,2‐gh ]purines 2, 3, 10a,b, 14 , (8‐oxo‐[1,4]thiazino[4,3,2‐gh ]purin‐7(8H )‐ylidene) acetate 4 , [1,4]thiazepino[4,3,2‐gh ]purine 6 , thiazolo[3,4,5‐gh ]purine 7 , imidazo[1,5,4‐gh ]purin‐5‐amine 8 , 5‐methylimidazo[1,5,4‐gh ]purine 9 , [1,2,4]triazino[4,3‐i ]purines 16, 18, 21 , [1,2,4]triazino[4,5,6‐gh ]purine 20 , 5‐methyl‐2‐(7H ‐purin‐6‐yl)‐1H ‐pyrazol‐3(2H )‐one 22 , [1,2,4]triazolo[4,3‐i ]purine 23 , [1,2,5]triazepino[5,4,3‐gh ]purine 24 , and ethyl 6‐(2‐(ethoxycarbonyl)hydrazinyl)‐9H ‐purine‐9‐carboxylate 26 . Seventeen of the newly synthesized compounds were selected by the NCI, Maryland, USA, and were tested for their anticancer activity in an initial single high dose in the full NCI 60 cell line panel among which [1,4]thiazino[4,3,2‐gh ]purine‐7,8‐dione 2 , 7‐benzyl‐[1,4]thiazino[4,3,2‐gh ]purine 10b , and 3‐(2,4‐dimethoxyphenyl)‐7H ‐[1,2,4]triazolo[4,3‐i]purine 23 were found to possess very potent anticancer activity against most of the cancer cell lines.     

A novel approach to fused 1,2,4-triazines by intramolecular cyclization of 1,2-diaza-1,3-butadienes bearing allyl(propargyl)sulfanyl and cyclic tert-amino groups

3-Allyl- and 3-prop-1-ynylsulfanyl-2-arylazo-3-cycloalkylamino-acrylonitriles undergo cyclization under mild conditions to afford the novel heterocyclic systems 1,4,6,7,8,8a-hexahydropyrrolo[2,1-c][1,2,4]-triazine-4-thione, 1,4,6,7,9,9a-hexahydro-[1,4]oxazino[3,4-c][1,2,4]triazine and 1,6,7,8,9,9a-hexahydro-4H-pyrido[2,1-c][1,2,4]triazine via a number of consecutive pericyclic reactions.     

Syntheses of heterocyclic fused thiazolecarboxylic acids I

A number of thiazolo 5-carboxylic acid derivatives were prepared which were fused to other heterocycles such as 1,2,4-benzothiadiazine, quinazoline, and pyrimidine rings at the 2,3-position of the thiazole ring. In several instances unexpected products were obtained, depending on the reaction conditions. The chemistry of these reactions and the identification of the products are discussed.     

Synthesis of 6‐Aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐Aryl‐thiazolo[3,2‐b][1,2,4]triazoles

The cyclization of the derivatives of 3‐aminotriazole, 2‐(5‐substituted 4H‐1,2,4‐triazol‐3‐ylamino)‐1‐arylethanones and 2‐(4H‐1,2,4‐triazol‐3‐ylthio)‐1‐arylethanones to yield 6‐aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐aryl‐thiazolo[3,2‐b][1,2,4]triazoles has been described.     

Synthesis of Some New Fused and Polyfused [1,2,4]Triazolo-[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazepines

7-[1,3-Dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6,8-dione and 7-[5-oxo-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]-thiadiazepine-6,8-diones were obtained by treating 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazepine-6,8-diones with CS₂ and chloroacetyl chloride, respectively. Treatment of the above compounds with mercaptoacetic acid gave 1,2-dibromoethane or the corresponding spiro polyfused heterocycles. Some other triazolothiadiazepine derivatives including spiro polyfused compounds were also synthesized. __________ Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1256–1264, August, 2005.     

Microwave Assisted Synthesis of 6-Aryl-3-substituted-5H-[1,2,4]-triazolo[4,3-b][1,2,4]triazoles: A Case for a Comparative Study

A simple and fast synthesis of 6-aryl-3-substituted-5H-[1,2,4]-triazolo[4,3-b][1,2,4]triazoles 4 in high yields has been developed by microwave assisted heterocyclization of N-(3-methylthio-5-substituted-4H-1,2,4-triazol-4-yl)benzenecarboximidamides 3 . The effectiveness of the microwave irradiation and conventional heating for the formation of compounds 4 has been investigated.