Synthesis and biological screening of 1,2,4triazole. Cu nanoparticles immobilized on modified magnetic zeolite for the synthesis of 1,2,3. Herein we turn our attention to the synthesis of new triazoles. The compound 25 was highly active on the leukemia k562 cell line gp 21. Synthesis of disubstituted triazoles synform thieme. The reaction is efficiently promoted by trichloroisocyanuric acid to afford the desired products mostly in high yields and in relatively short time. The reaction has been widely used in bioorthogonal chemistry and in organic synthesis. Supplementary data are available free of charge at as pdf file. The store bought potatoes contain retardants such as triazole or tetcyclacis, which play an important role in agriculture and chemical synthesis. Synthesis of new triazolebased trifluoromethyl scaffolds.
Triazoles are relatively stable functional groups and triazole linkages can be used in a variety of applications for example, replacing the phosphate backbone of dna. Further by means of intermolecular cyclization bis1,2,4triazoles were obtained, structure of heterocyclic rings were. So, a facile preparation 1,2,4 triazoles for lead discovery is highly desirable. Synthesis of nheterocycles synthesis of 1,2,4triazoles. Original signatures are on file with official student records. Synthesis of some sderivatives of 1,2,4triazoles ysu. The 1,2,4triazole nucleus is associated with diverse pharmacological activities such as antibacterial, antifungal, hypoglycemic, antihypertensive and analgesic. Cu nanoparticles immobilized on modified magnetic zeolite. Continuousflow processing offers unprecedented opportunities to accelerate, integrate, simplify, scaleup and automatize chemical reactions, in combination with an inherently safer and greener nature over traditional batchbased syntheses. Synthesis of 1,2,3triazole derivatives and evaluation of. The use of thiosemicarbazide in organic synthesis has become a classical strategy for the synthesis of several heterocycles. One disubstituted and two trisubstituted 1,2,4triazoles were prepared and characterised by physical and spectroscopic properties. Synthesis and evaluation of functionalized imidazole and. It was found that the reaction of aliphatic ketones with alkyl or aryl azides in the presence of potassium tbutoxide yielded 5phenyl hydroxyl1,2,3triazoles27.
In this context we have foreseen that the use of new solid phase. Synthesis of mono and bis1,2,3triazole derivatives containing 4h. Pdf recent advances in the synthesis of triazole derivatives. Synthesis of some substituted 1,2,3triazole derivatives. Synthesis of 1,2benzisoxazole tethered 1,2,3triazoles.
Synthesis of 1,4disubstituted 1,2,3triazole derivatives. The synthesis of 1,4disubstitited triazole analogues were performed with the regiospecific coppercatalyzed aac, which is a. Synthesis of nheterocycles synthesis of 1,2,4 triazoles. The synthesis of 1monosubstituted aryl 1,2,3triazoles was achieved in good yields using calcium carbide as a source of acetylene. Triazoles are amongst the most important and most intensively stud. Synthesis of 1,2,4 triazole derivatives through potassium salt of hydrazinecarbodithioates syntheti ic layout of f novel 1,3,5 5trisubstituted1,2,4tr riazoles 109 figure 29. However, there was a selective influence observed in some of the compounds on several cancer cell lines table 1. Triazoles are relatively stable functional groups and linkages can be used in replacing the phosphate backbone of dna. The li terature reveals that substituted1,2,4triazole has diverse biological potential, and the easy synthetic routes for synthesis have taken attention of the chemists, pharma. In this paper, a small library of baylishillman reactionderived imidazole and triazoles are synthesized and characterized.
All the synthesized triazoles were characterized by ir, 1h, c, 19f nmr, and hrms. The synthesis of new 1,2,3triazoles has been actualized by means of the reaction of dipolar1,3cycloaddition of organic azides to the. Synthesis of 1,2,3triazoles linked into chains with other carbo and heterocycles by a reaction between. The levels of triazole pyruvic acid and triazole lactic acid found in metabolism studies are low, and no toxicological data on these compounds were available, therefore, they were not considered by the present meeting. Request pdf synthesis of 1,2,3 triazoles in our study we have obtained a series of triazoles in moderate yields 3355% using alphamonohalogenated acetophenones as starting material. The azidealkyne huisgen cycloaddition is a mild and selective reaction that gives 1,2,3triazoles as products. Furthermore, their antifungal activities are evaluated against candida albicans and cryptococcus neoformans. The synthesized 1,2,3 triazoles displayed slight 15a, 6b, 25 or low activity in the in vitro screen on the tested cell lines. View the article pdf and any associated supplements and figures for a period of 48 hours. Triazoles 26 were then alkylated with the corresponding alkylbromide under basic conditions using the phase transfer catalyst bu 4 nbr26 to afford the desired nsubstituted1,2,3triazoles 717 scheme 2. Synthesis and in vitro biological activities of 4,5. Synthesis of enamine 1 from methyl propiolate and morpholine ii. Reported here is a straightforward and scalable click.
During model synthesis, one of the stages of triazole synthesis, namely amidrazone formation, produced a bipyridyl dihydrazide molecule from which we obtained a never before reported crystal structure. There has been considerable interest in the development of novel heterocyclic compounds with varied biological activities. Triazoles 32, 33 are important fivemember nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. Studies of the synthesis and reactivity of bridgehead pdf fileabstract studies of the synthesis, structure and reactivity of bridgehead fused 1,2,3triazoles provide the subject material for the following thesis. An efficient regioselective coppercatalyzed approach to. Chemistry of heterocyclic compounds 2018, 54 2, 167172. Triazoles are a special class of heterocyclic compounds with a broad spectrum of biological activities such as antimicrobial, cytotoxic, antihistaminic, anticonvulsant, analgesic, antiinflammatory, insecticidal, antimycotic, antimycobacterial, anticancer. In conclusion, we have developed an efficient and convergent method to synthesize differently substituted 3amino1,2,4triazoles 1 from readily available starting materials. Triazole and its derivatives belong to a class of exceptionally active compounds possessing a wide spectrum of chemotherapeutic activities, including anticonvulsant, antimicrobial, antihypertensive, analgesic, antiviral, antioxidant, antiinflammatory, antitumor and antihiv activity. Nevertheless, there are only a few reports in the literature concerning solid phase synthesis for 1,2,4triazoles 3840.
In view of the biological importance of these 1,2,4triazoles, several methods have been developed for the synthesis of this class of compounds. An efficient regioselective coppercatalyzed strategy for the synthesis of 1,2,3triazoles from ntosylhydrazones and azides has been reported. The chemistry of mercapto and thione substituted 1,2,4. E 8d, pp305405 1,2,3triazoles1 and pp 406478 benzotriazoles. The diversity of chemical structures of the triazoles family and their useful biological activities made these compounds attractive targets in synthetic organic chemistry.
This is a pdf file of an unedited manuscript that has been accepted for publication. Synthesis of 4amidomethyl1glucosyl1,2,3triazoles and. According to the acquired results, satisfactory tolerance of this watermediated, catalystfree protocol was verified by the smooth synthesis of the 4acylnh1,2,3triazoles 3at containing versatile substructures. Isothiazoles in the design and synthesis of biologically active substances and ligands for metal complexes. Presented here is a preliminary exploration of the synthesis.
Preparation and antibacterial properties of substituted 1. Synthesis and evaluation of biological activities of triazoles. As indicated in scheme 1, for monocyclic 1,2,3triazoles three subclasses can be recognized, depending on the position of the substituents in the ring. Triazoles exhibit biological activity, notably as antifungals, antimicrobials, and enzymatic inhibitors. Synthesis of 1,2,4triazolines and triazoles utilizing.
Pdf synthesis of some new 1,2,4triazole derivatives. The investigation of synthetic methods involving 5substituted 1,2,3triazoles began several years ago when lingjun li was a phd candidate at peking university more than ten years ago. The azide alkyne huisgen cycloaddition is a mild and selective reaction that gives 1,2,3triazoles as products. This transformation opened a new route to synthesize 1,2,3triazoles which is a common structural motif in natural products and pharmaceuticals. As shown in figure 3, the c nmr of compounds 9a and 9k revealed the absence of the signals of the c3 or c4 for the triazoles ii or iii,23 25 which are. This thesis approaches the synthesis of new combretastatin derivatives through triazole formation by azidealkyne cycloadditions aac. With this background, the synthesis of seleniumcontaining 1,2,3triazoles. Flow chemistry as a versatile tool for the synthesis of.
Several methods for synthesis of 1,2,4triazole are available in literature, which involve conventional one pot, multicomponents, microwave assisted, under solvent free condition, regioselective and signification method. Synthesis of 1,2benzisoxazole tethered 1,2,3triazoles that exhibit anti. In view of the biological impovtance of these 1,2,4triazoles, several methods have been developed for the synthesis of this class of compounds. Pdf triazole was first synthesized over a century ago, but still attracts attention of chemists, biologists, technologists and other specialists. To vary the 3amino substitutents, the synthesis of. Synthesis of fused mercaptothione1,2,4triazole heterocycles 3. Regioselective synthesis of 4fluoro1,5substituted1,2,3triazoles from synthetic surrogates of. Efficient methodology for the synthesis of 3amino1,2,4. Pdf anticancer screening of several 1,2,3triazoles with heterocyclic fragments has been performed. To vary the substitution at the n1 position, the synthesis of aniline derived sulfonic acid intermediate 5 is followed by addition of hydrazine and then cyclization.
Both 1,2,3 and 1,2,4triazoles are nowadays incorporated in numerous antibacterial pharmaceutical formulations. Efficient synthesis of 5trifluoromethylthio1,2,3triazoles. In the present study, we report the design and the synthesis of a series of 1,4disubstituted 1,2,3triazoles involving one pot condensation of methyl 2azidoacetate and different terminal alkynes. Yet the synthesis of relatively simple, albeit important, 1. Chapter ii synthesis of 1,2,4triazole derivatives and. They were investigated as inhibitors of src kinase. Investigation of alternative methods for the synthesis of. Synthesis and characterization of substituted 1,2,3triazoles. A simple, efficient, and mild method for the synthesis of substituted 1,2,4triazoles from hydrazines and formamide proceeds smoothly under microwave irradiation in the absence of a catalyst and shows excellent functionalgroup tolerance. While 1 h and 2 1,2,3triazoles are aromatic compounds their 4h. Catalystfree synthesis of 4acylnh1,2,3triazoles by. Tom general introduction previously published information regarding this product class can be found in houben weyl, vol. The initial imido esters have been synthesized by the pinner reaction, as well as by reaction of nitriles with methanol in the presence of a catalytic amount of. Their reactions with compounds containing co and cn groups is an elegant method for the preparation of biologically active compounds viz.
We describe herein a convenient method for the synthesis of 1,2,4triazolines using oxazolones and azodicarboxylates. Synthesis of 1,5disubstituted 1,2,3triazoles from 4trimethylsilyl5iodo1,2,3triazole. Subsequent treatment of these 1,2,4triazolines with naoh provides efficient access to the corresponding triazoles. Pdf we describe herein the synthesis of new macrocycles and podants derived from the 3alkyl phenyl1,2,4triazole5 thiones 1ac in a. Regioselective synthesis of 4fluoro1,5substituted1,2,3triazoles. Nalkylation of unsymmetrical 4,5disubstituted1,2,3triazoles.
Synthesis, antibacterial and antifungal activity of 4substituted5. Recent advances in the synthesis of triazole derivatives. To examine the scope of this watermediated 1,2,3triazole synthesis, a broad range of enaminones 1 was then employed to react with tosyl azide under the optimal conditions. The 1,2,3triazoles can be divided in three main groups. Organocatalytic routes toward substituted 1,2,3triazoles. The coppercatalyzed 1,3dipolar cycloaddition reactions were carried out without nitrogen protection and in a mecnh 2 o mixture. The cover feature shows a reaction plate where many reactions employing mixture of reagents successfully enable the identification of the most suitable reaction conditions highlighted in green in a straightforward manner.
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