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. 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. A series of 1,2,3triazole derivatives was synthesized from. Synthesis of 3,5disubstituted 1,2,4triazoles containing.
The 1,2,3triazoles can be divided in three main groups. They have been reported to be inhibitors of glycogen. The introduction of more diversified substituents into the s. 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. E 8d, pp305405 1,2,3triazoles1 and pp 406478 benzotriazoles. The coppercatalyzed azidealkyne cycloaddition cuaac is a highly effective method for the selective incorporation of deuterium atom into the c5 position of the 1,2,3 triazole structure. The mildness of the method renders it applicable to substrates of. All the synthesized triazoles were characterized by ir, 1h, c, 19f nmr, and hrms. The synthesis of the 1,2,4triazole has a wide range of biological functions. Synthesis of some new substituted 1,2,4triazole and 1,3,4. Vijaya kumarc and dhurke kashinatha adepartment of chemistry, national institute of technology, warangal506 004, india. Lakshmiviveka osmania university, department of chemistry, hyderabad, india abstract. 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. The reaction has been widely used in bioorthogonal chemistry and in organic synthesis.
The coppercatalyzed 1,3dipolar cycloaddition reactions were carried out without nitrogen protection and in a mecnh 2 o mixture. Triazoles and their derivatives are of great importance in medicinal chemistry and can be used for the synthesis of numerous heterocyclic compounds with different biological activities such as antiviral, antibacterial, antifungal, antituberculosis, anticonvulsant, antidepressant, antiinflammatory, anticancer activities, etc. European journal of organic chemistry 2014, 2014 30, 66536657. The reader is then introduced to the people and the research behind 1,2,4triazole synthesis aswell as the synthetic methods used. Synthesis of nheterocycles synthesis of 1,2,4triazoles. Nineteen 1,5disubstituted 1,2,3triazoles were successfully obtained by merely washing the ionic liquid phase with ether, thus avoiding the need for intermediate purification. Synthesis of new 1, 2, 4triazole compounds containing schiff and.
Efficient regioselective synthesis of 3,4,5trisubstituted 1,2,4triazoles on the basis of a lithiationtrapping sequence. Fluorescence properties via merging metalfree domino reactions. One disubstituted and two trisubstituted 1,2,4triazoles were prepared and characterised by physical and spectroscopic properties. The synthesis of 4vinyl1,2,4triazoles springerlink. Preparation and antibacterial properties of substituted 1. The chemistry of mercapto and thione substituted 1,2,4. Like the azoles, triazoles are used in many antifungal drugs and fungicides, and the triazolebased drugs are more selective for fungi than mammalian cells.
Along with successful model compound synthesis, a thorough spectroscopic investigation of the 1,2,4triazoles by 1hnmr is described. Introduction 4amino5mercapto1,2,4triazole derivative is a readymade building block for construction of various organic heterocycles since they contain two nucleophilic groups, amino and thiol groups. The synthesis of 1monosubstituted aryl 1,2,3triazoles was achieved in good yields using calcium carbide as a source of acetylene. Nmr is available, free of charge, at as a pdf file. The reaction of 1,2,4triazole and 5methyl1,2,4triazole with acetylene gives 4vinyl 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. Frerichs and beckurts 26 isolated the phenylhydrazone of 1phenyl5hydroxy1,2,4. In the last few decades, the chemistry of 1, 2, 4triazoles has received considerable attention owing to their synthetic and effective biological importance.
Ionic liquidphase synthesis of 1,5disubstituted 1,2,3. Synthesis and evaluation of biological activities of triazoles. They were investigated as inhibitors of src kinase. 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. Synthesis of fused mercaptothione1,2,4triazole heterocycles 3. 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. In view of the biological impovtance of these 1,2,4triazoles, several methods have been developed for the synthesis of this class of compounds. N n n so2ch3 ch3 4 5methyl14methylsulfonylphenyl1h1,2,3. Triazoles are amongst the most important and most intensively stud. Although the condensation is stepwise, the reaction is usually regiospecific, and most useful for the preparation of 5amino or 5hydroxy1,2,3triazoles with an. Synthesis of 1,5disubstituted 1,2,3triazoles from 4trimethylsilyl5iodo1,2,3triazole. For these reasons, the synthesis of chalcones and their functionalized derivatives is a primary objective.
I have examined the final electronic copy of this thesis for form and content and recommend that it be accepted in partial fulfillment of the requirements for the. Biological evaluation and conformational analysis studies. Physical and characterization data of compound 3ae are given in table1. Among the newly synthesized triazole derivatives, the schiff base. Synthesis of nsubstituted phthalimidoalkyl 1h1,2,3triazoles. Request pdf synthesis of 2h1,2,3triazoles this chapter gives an overview of methods for the synthesis of nh and n2substituted 1,2,3triazoles, their. Pdf synthesis and evaluation of some 1, 2, 4triazole derivatives. Synthesis of novel 1,2,4triazole derivatives containing the.
Synthesis of disubstituted triazoles synform thieme. Triazoles, sulfonamides, benzimidazoles, click synthesis, antimicrobial activity. Synthesis of functionalized 1,2,3triazoles using bi2wo6. Synthesis of 1,4disubstituted 1,2,3triazole derivatives. Pdf synthesis of novel sulfonamide1,2,4triazoles, 1,3. They are aromatic ring compounds similar to the azoles pyrazole and imidazole, but with an additional nitrogen atom in the ring structure.
Synthesis and biological assessment of new 1,2,4triazole. The azidealkyne huisgen cycloaddition is a mild and selective reaction that gives 1,2,3triazoles as products. 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. 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 5iodo1, 2, 3triazoles from organic azides and. Synthesis of 3phenylazo1,2,4triazoles by a nucleophilic reaction of primary amines with 5chloro2,3diphenyltetrazolium salt via mesoionic 2,3diphenyltetrazolium5aminides shuki araki, satoshi hirose, yoshikazu konishi, masatoshi nogura and tsunehisa hirashita. 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 view of the biological importance of these 1,2,4triazoles, several methods have been developed for the synthesis of this class of compounds. Platinumii complexes comprising 1,2,4triazoles as ligands show antitumor activity similar to cisplatin. Design and synthesis of antifungal compounds from 1,2,3. Our study aimed to prepare three substituted 1,2,4triazoles and to evaluate their antibacterial properties. The azide alkyne huisgen cycloaddition is a mild and selective reaction that gives 1,2,3triazoles as products.
Experimental melting points was determined using an electrothermal digital melting point apparatus and are uncorrected. Triazoles are relatively stable functional groups and linkages can be used in replacing the phosphate backbone of dna. Introduction, triazole refers to either one of a pair of isomeric chemical compounds with molecular formula c2h3n3, having a five membered ring of two carbon atoms and three nitrogen atoms. Synthesis of 1,2,3triazole derivatives and evaluation of. The next logical step in the process was to produce model compounds. Synthesis of novel sulfonamide1,2,4 triazoles, 1,3,4thiadiazoles and 1,3,4oxadiazoles, as potential antibacterial and antifungal agents. 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. Synthesis of deuterated 1,2,3triazoles the journal of. General papers arkivoc 2010 ii 127147 issn 15517012 page 129 arkat usa, inc. The main aim of the work submitted in this thesis was the synthesis of such 1,2,4triazolecaldehydes. Organocatalytic routes toward substituted 1,2,3triazoles.
Synthesis of some substituted 1,2,3triazole derivatives. Synthesis and biological evaluation of novel3, 5disubstituted 4h1, 2, 4triazoles l. In conclusion, we have developed an efficient and convergent method to synthesize differently substituted 3amino1,2,4triazoles 1 from readily available starting materials. Synthesis and antimicrobial activity of 1,2,4triazoles. Flow chemistry as a versatile tool for the synthesis of. Synthesis and antimicrobial activity of 1,2,4triazoles 3 aceticacid. Synthesis of novel glycerolderived 1,2,3 triazoles and evaluation of organic and medicinal chemistry international journal how to cite this article. Medicinal and biological importance of 1,2,3triazoles in. Pdf a new series of substituted 1,2,4triazoles as substituted 4,5diphenyl 4h1, 2,4triazole3thiols 3a1a6 3d1d6 have been synthesized. In 2001, sharpless and meldal came across with a copperi catalyzed regioselective synthesis of 1,4disubstituted 1,2,3triazoles by cycloaddition between azides and terminal alkynes. This has the practical advantage of giving the researcher experience in the reactions required in the synthesis. The triazoles are two isomers, namely 1,2,3triazole or 1,2,4triazole, with the formula c 2 h 3 n 3. The synthesis of 3acylaminoalkyl5alkyloxycarbonyl 1,2,4triazoles, designed as rgd peptidomimetics, is described and the reactivity of 1,2,4triazoles under conditions of peptide chemistry is. A general method was developed for the synthesis of novel unsymmetrical 3, 5disubstituted 4h1, 2, 4triazoles with benzyl group in the 4ring position.
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. Synthesis of new triazolebased trifluoromethyl scaffolds. Compounds containing quinazoline and triazole heterocyclic rings play a significant. Tom general introduction previously published information regarding this product class can be found in houben weyl, vol.
Ir and 1h nmr spectral data of compound 3ae are given in table2. The synthesis of triazoles from organic azides and active methylene compounds under basic conditions is well known. A simplified ionic liquidphase synthesis of 1,5disubstituted 1,2,3triazole was developed. Triazoles exhibit biological activity, notably as antifungals, antimicrobials, and enzymatic inhibitors. Pdf both 1,2,3triazoles and nucleosides have proved to be useful pharmacophores for antiviral and anticancer agents. The synthesis of the first representatives of these compounds was reported in the late 19th century by pechmann. Synthesis of 2h1,2,3triazoles request pdf researchgate. Chapter ii synthesis of 1,2,4triazole derivatives and. 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. There has been considerable interest in the development of novel heterocyclic compounds with varied biological activities.
Both 1,2,3 and 1,2,4triazoles are nowadays incorporated in numerous antibacterial pharmaceutical formulations. Synthesis of novel 1, 2, 4triazole derivatives containing the. To vary the 3amino substitutents, the synthesis of. Synthesis and biological screening of 1,2,4triazole. Reactions of alkynes and azides can be conveniently carried out in a biphasic medium of ch2cl2d2o, using the cuso4na ascorbate system. A method to prepare 5iodo1,2,3triazole directly from organic azide. Efficient methodology for the synthesis of 3amino1,2,4. Triazoles heterocyclic building blocks sigmaaldrich. This is reflected in the abundance of examples of ih and 2ftriazoles and the rarity of 4triazoles. Pdf synthesis of 1,2,3 triazole nucleoside analogues. The store bought potatoes contain retardants such as triazole or tetcyclacis, which play an important role in agriculture and chemical synthesis. Synthesis of enamine 1 from methyl propiolate and morpholine ii. While 1 h and 2 1,2,3triazoles are aromatic compounds their 4h.