Recent Developments in Azide‐Free Synthesis of 1,2,3‐Triazoles

1,2,3‐Triazoles, as one of the most significant nitrogen‐containing heterocycles due to their extensive use in biology, material science and organic synthesis, have aroused great interest. 1,2,3‐Triazoles are commonly synthesized by metal‐catalyzed azide–alkyne cycloaddition and organocatalytic azide–carbonyl cycloaddition, which indispensably employ the toxic and potentially explosive azides. The azide‐free synthetic approaches provide a powerful and straightforward alternative to the assembly of diverse 1,2,3‐triazoles without the use of azides. In this review, we summarize the recent development of the construction of 1,2,3‐triazoles under azide‐free conditions.     

Rhodium(II)‐Catalyzed Intramolecular Annulation of 1‐Sulfonyl‐1,2,3‐Triazoles with Pyrrole and Indole Rings: Facile Synthesis of N‐Bridgehead Azepine Skeletons

A convenient and efficient synthetic method has been developed to construct highly functionalized N‐bridgehead azepine skeletons, which are of great importance in biological and pharmaceutical industry. The reaction proceeds through a rhodium(II) azavinyl carbene intermediate, which initiated the intramolecular C? H functionalization with pyrrolyl and indolyl rings. A variety of azepine derivatives were obtained in moderate to good yields under mild reaction conditions with high chemoselectivity. Several interesting derivatizations of the resulting products demonstrate that this method is synthetically valuable and useful.     

Copper Supported on the SiO2 Nanoparticle in Click Chemistry: An Alternative Catalytic System for Regioselective and One‐Pot Synthesis of 1,2,3‐Triazoles and β‐Hydroxytriazoles

In this work, readily prepared copper supported on the SiO₂ nanoparticles has been found to effectively catalyze the 1,3‐dipolar cycloaddition of a variety of azides, alkynes, epoxides and sodium azide, furnishing the corresponding 1,2,3‐triazoles and β‐hydroxytriazoles. Click reaction proceeds in short reaction times and under mild reaction conditions, and the resulting products are obtained in good yields at ambient temperature.     

Synthesis and Insecticidal Evaluation of Novel Phthalic Diamides Containing 1,2,3‐Triazoles via Click Reaction

A series of novel phthalic diamide derivatives containing 1,2,3‐triazole moiety were synthesized using one‐pot click chemistry approach and characterized by ¹H NMR and HRMS. The insecticidal activity against armyworm (Mythimna separata), Tetranychu scinnabarinus and cowpea aphid (Aphis craccivora) was evaluated. Compounds 4II‐a and 4II‐i showed 50% insecticidal activity against armyworm (Mythimna separata) at the concentration of 4 mg/L and one‐third of the compounds had moderate activity against Tetranychus cinnabarinus at 500 mg/L.     

A Metal‐Free Three‐Component Reaction for the Regioselective Synthesis of 1,4,5‐Trisubstituted 1,2,3‐Triazoles

A metal‐free three‐component reaction to synthesize 1,4,5‐trisubstituted 1,2,3‐triazoles from readily available building blocks, such as aldehydes, nitroalkanes, and organic azides, is described. The process is enabled by an organocatalyzed Knoevenagel condensation of the formyl group with the nitro compound, which is followed by the 1,3‐dipolar cycloaddition of the azide to the activated alkene. The reaction features an excellent substrate scope, and the products are obtained with high yield and regioselectivity. This method can be utilized for the synthesis of fused triazole heterocycles and materials with several triazole moieties.     

Ferromagnetic nanoparticle‐supported copper complex: A highly efficient and reusable catalyst for three‐component syntheses of 1,4‐disubstituted 1,2,3‐triazoles and C–S coupling of aryl halides

A new nanocatalyst was synthesized by immobilization of 4′‐(4‐hydroxyphenyl)‐2,2′:6′,2″‐terpyridine/CuI complex on ferromagnetic nanoparticles through a surface modification (FMNPs@SiO₂‐TPy‐Cu). This heterogeneous catalyst was characterized using various techniques including Fourier transform infrared and energy‐dispersive X‐ray spectroscopies, transmission and scanning electron microscopies, X‐ray diffraction, vibrating sample magnetometry and thermogravimetric analysis. The resulting nanocatalyst presented excellent catalytic activity for the regioselective syntheses of 1,4‐disubstituted 1,2,3‐triazoles and thioethers. The thermally and chemically stable, benign and economical catalyst was easily recovered using an external magnet and reused in at least five successive runs without an appreciable loss of activity.     

Microwave‐Assisted Palladium‐Catalyzed Direct Arylation of 1,4‐Disubstituted 1,2,3‐Triazoles with Aryl Chlorides

Treatment of 1,4‐disubstituted 1,2,3‐triazoles with aryl chlorides in the presence of potassium carbonate under palladium catalysis and microwave irradiation at 250 °C for 15 min leads to arylation of the triazole at the 5‐position. A variety of functional groups, including ester and hydroxy groups, are compatible. The procedure is suitable for the regioselective preparation of trisubstituted triazoles. Microwave irradiation accelerates the reaction, thus allowing the rapid synthesis of trisubstituted triazoles, which are difficult to synthesize selectively.     

The Syntheses of 4‐Arylamino‐1,2,3‐Triazoles and Stable 6‐Sydnonyl Verdazyls from Sydnone Derivatives and Their Fragments

α‐Chloroformylarylhydrazones 1 and α‐chloroformylarylhydrazones of sydnonecarbaldehydes 3 have been prepared by a new synthetic route: α‐chloroformylarylhydrazines hydrochlorides 2 reacted with corresponding carbonyl compounds. Reactions of compounds 3 with various hydrazines to give 6‐sydnonyl‐1,2,4,5‐tetrazinan‐3‐ones 7 and/or carbazones 8 were also investigated. By oxidization with lead dioxide, compounds 7 were trans formed to stable 6‐sydnonyl‐3,4‐dihydro‐3‐oxo‐1,2,4,5‐tetrazin‐1(2H)‐yl radical derivatives 9 (sydnonyl verdazyls). Furthermore, sydnonecarbaldehydes arylhydrazones 5 through acidic conditions could be transferred to 4‐arylamino‐1,2,3‐triazoles 6 which were also obtained by means of acidic decompositions of 4‐formylsydnones 10 .     

Easy One‐Pot Synthesis of 1‐Monosubstituted Aliphatic 1,2,3‐Triazoles from Aliphatic Halides,Sodium Azide and Propiolic Acid by a Click Cycloaddition/Decarboxylation Process

1‐Monosubstituted aliphatic 1,2,3‐triazoles were synthesized by a one‐pot reaction from aliphatic halides (Cl and Br), sodium azide and propiolic acid. The yields ranged from moderate to good. The reaction was easily carried out in DMF with Cs₂CO₃ at 100°C by copper‐catalyzed click cycloaddition/decarboxylation.     

Pd‐NHC‐Catalyzed Direct Arylation of 1,4‐Disubstituted 1,2,3‐Triazoles with Aryl Halides

A highly efficient method for the synthesis of unsymmetrical multi‐substituted 1,2,3‐triazoles via a direct Pd‐NHC system catalyzed C(5)‐arylation of 1,4‐disubstituted triazoles, which are readily accessible via "click" chemistry has been developed. It is important to note that C? H bond functionalizations of 1,2,3‐triazoles with a variety of differently substituted aryl iodides and bromides as electrophiles can be conveniently achieved through this catalytic system at significantly milder reaction temperatures of 100°C under air.     

Synthesis and reactivity ratios of regioisomeric vinyl‐1,2,3‐triazoles with styrene

The free radical reactivity ratios between styrene and different vinyl‐1,2,3‐triazole regioisomeric monomers in 1,4‐dioxane at 65 °C have been established using nonlinear least square method. The results obtained for the reactivity ratio between regioisomers show exceptionally different polymerization behavior, highlighting the effects of the electronic and steric factors of these regioisomeric monomers. The experimental results highlight the effects of the electronic and sterics on the copolymerization behavior. In case of 1,4‐vinyl‐triazoles, it was found that without the steric effects, the reactivity is very similar to that of styrene and forms random copolymers. However, it was found that 1,5‐vinyl‐triazoles are more reactive than 1,4‐vinyl triazoles. In the case of styrene‐co‐1,4‐vinyl‐1,2,3‐triazoles, the reactivity ratios were calculated to be r_styrene: r_{1‐octyl‐4‐vinyl‐triazole} = 1.97:0.54, r_styrene : r_{1‐benzyl‐4‐vinyl‐triazole} = 1.62:0.50, and r_styrene: r_{1‐methyl‐4‐vinyl‐triazole} = 0.90:0.87. On the other hand, reactivity ratios for styrene‐co‐1,5‐vinyl‐1,2,3‐triazoles were found to be r_styrene: r_{1‐octyl‐5‐vinyl‐triazole} = 0.13:0.66 and r_styrene: r_{1‐benzyl‐5‐vinyl‐triazole} = 0.34:0.49. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3359–3364     

Energetic Materials with Promising Properties: Synthesis and Characterization of 4,4′‐Bis(5‐nitro‐1,2,3‐2H‐triazole) Derivatives

Using a variety of functionalization strategies, derivatives of 4, 4′‐bis(5‐nitro‐1,2,3‐2H‐triazole) were designed, synthesized, and characterized. The isomers were separated, their structures were confirmed with single‐crystal X‐ray analysis, and their properties were determined by differential scanning calorimetry, density, impact sensitivity, heat of formation, and detonation velocity and pressure (calculated by EXPLO5 V6.01). Those materials were found to exhibit superior detonation performance when compared with the other fully carbon‐nitrated bis(azoles).     

One‐Pot Synthesis of 4‐Aryl‐NH‐1,2,3‐Triazoles through Three‐Component Reaction of Aldehydes,Nitroalkanes and NaN3

A one‐pot three‐component reaction of aldehydes, nitroalkanes and NaN₃ for the synthesis of NH ‐1,2,3‐triazoles has been developed. The reaction provides a safe, efficient and step‐economic approach for the synthesis of various NH ‐1,2,3‐triazoles in good to excellent yields.     

Synthesis of 2(5H)‐Furanone Derivatives with Bis‐1,2,3‐triazole Structure

A series of new chiral 2(5H)‐furanone derivatives containing bis‐1,2,3‐triazole moiety were designed and synthesized from (5S)‐5‐alkoxy‐3,4‐dihalo‐2(5H)‐furanones 1 , dicarboxyl amino acids 2 , propargyl bromide, and organic azides 5 under mild conditions via the sequential three steps, including asymmetric Michael addition‐elimination, substitution and no‐ligand click reaction. Twelve new intermediates, including N‐[5‐alkoxy‐2(5H)‐furanonyl] dicarboxyl amino acids 3 and their corresponding propargyl esters 4 , and twelve target molecules 6 were characterized by FTIR, ¹H NMR, ¹³C NMR, MS and elemental analysis. The influences of different synthetic conditions and substrates in each step were investigated. The research provides a new method and idea for the synthesis of 2(5H)‐furanone compounds with polyheterocyclic structure due to the diversities of four basic unit molecules.     

Bimetal‐Catalyzed Cascade Reaction for Efficient Synthesis of N‐Isopropenyl 1,2,3‐Triazoles via In‐Situ Generated 2‐Azidopropenes

A bimetal‐catalyzed cascade reaction for the synthesis of N‐isopropenyl 1,2,3‐triazoles in high yield is reported. This reaction involves the generation of 2‐azidopropenes in situ by C(sp³)‐OAr bond cleavage for click reaction and features a broad substrate scope, good functional group tolerance and readily available substrates.     

Synthesis, Crystal Structure and Biological Activities of O, O-Dialkyl α-[1-（2-Chlorothiazol-5-ylmethyl）-5-methyl- 1 H-1,2,3-triazol-4-ylcarbonyloxy]alkylphosphonates

In order to search for novel agrochemicals with high activity and low toxicity, a series of phosphonate derivatives containing 1,2,3-triazole and thiazole rings were designed and synthesized using 2-chloro-5-（chloromethyl）- thiazole as the starting material. Their structures were confirmed by IR, ^1H NMR, ^31p NMR, EI-MS or ESI-MS and elemental analyses. The crystal structure of 7a was determined by single crystal X-ray diffraction. Preliminary bioassays indicated that most of the target compounds did not display insecticidal activities, but a fraction of them possessed herbicidal and fungicidal activities to some extent.     

Efficient Synthesis of Substituted 3‐Azabicyclo[3.1.0]hexan‐2‐ones from 2‐Iodocyclopropanecarboxamides Using a Copper‐Free Sonogashira Coupling

The copper‐free Sonogashira coupling between N‐substituted cis‐ 2‐iodocyclopropanecarboxamides and terminal aryl‐, heteroaryl‐alkynes or enynes, followed by 5‐exo‐dig cyclization of the nitrogen amide onto the carbon–carbon triple bond, provides a remarkably efficient access to a variety of substituted 4‐methylene‐3‐azabicyclo[3.1.0]hexan‐2‐ones in excellent yields. Protonation of these latter enamides generates bicyclic N‐acyliminium ions that can be involved in Pictet–Spengler cyclizations leading to new 3‐azabicyclo[3.1.0]hexan‐2‐ones, possessing a quaternary stereocenter at C4, with high diastereoselectivities. This strategy constitutes an attractive complementary alternative to the classical route that relies on the addition of organometallic reagents to cyclopropyl imides.     

Copper Catalysis and Organocatalysis Showing the Way: Synthesis of Selenium‐Containing Highly Functionalized 1,2,3‐Triazoles

This article provides a comprehensive overview of reported methods ‐ particularly copper‐ and organocatalyzed reactions ‐ for the regioselective syntheses of selenium‐containing 1,2,3‐triazoles systems. These chemical entities are prevalent cores in biologically active compounds and functional materials. In view of their unique properties, substantial efforts have been paid for the design and development of practical approaches for the synthesis of these scaffolds.     

Stereoselective Synthesis of 1,2,3‐Triazolooxazine and Fused 1,2,3‐Triazolo‐δ‐Lactone Derivatives

The stereoselective synthesis of 1,2,3‐triazolooxazine and fused 1,2,3‐triazolo‐δ‐lactone by applying chemoenzymatic methods is described. trans‐2‐Azidocyclohexanol was successfully resolved by Novozyme 435 with an ee value of 99%. Installation of the alkyne moiety on the enantiomerically enriched azidoalcohol by O‐alkylation, followed by intramolecular azide? alkyne [3+2] cycloaddition resulted in the desired 1,2,3‐triazolooxazine derivative. Enantiomerically pure azidocyclohexanol was also subjected to the Huisgen 1,3‐dipolar cycloaddition reaction with dimethylacetylene dicarboxylate, followed by intramolecular cyclization of the corresponding cycloadduct, to furnish a fused 1,2,3‐triazolo‐δ‐lactone.