Preparation and characterization of 1,2,3‐triazole‐cured polymers from endcapped azides and alkynes

Fourteen commercial polyols have been characterized by GPC, NMR spectroscopy, and elemental analysis. From these, eight corresponding tosylates, six nitrate esters, seven mesylates, 13 alkynes, and 14 azides have been prepared and all these derivatives have been fully characterized. Five alkyne monomers and eight azide monomers were also prepared. Twelve alkynes and 13 azides (functionality 2–4) were combined in 1,3‐dipolar cycloaddition reactions under neat conditions to prepare triazole‐cured polymers, avoiding any heavy metal catalyst. Characterization by NMR spectroscopy, elemental analysis, and gel permeation chromatography indicated triazole polymers 14 , 22 , 23 , 28 , and 30 with degrees of polymerization of 17–28 to be the best candidates for future work. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 238–256, 2008     

Facile synthesis,characterization, and antimicrobial studies of some disubstituted 1,2,3-triazoles with sulfonamide functionality

An expedient synthesis of some 1,4-disubstituted 1,2,3-triazoles (3a–3x) having sulfonamide functionality from various terminal alkynes and aromatic azides through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition has been reported. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, high-resolution mass spectra and screened for in vitro antimicrobial activity against Staphylococcus aureus (Gram-positive bacteria), Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes (Gram-negative bacteria), Candida albicans, and Aspergillus niger (fungi). Some of the synthesized compounds were found to exhibit good potency against above-tested microbial strains. Moreover, to study the binding interactions, docking simulation of broadly active compound 3x was also performed against E. coli dihydropteroate synthase enzyme.     

Key Non‐Metal Ingredients for Cu‐catalyzed “Click” Reactions in Glycerol: Nanoparticles as Efficient Forwarders

The effect of long‐alkyl‐chain amines in CuI‐assisted azide–alkyne cycloadditions of terminal alkynes with organic azides in glycerol and other environmentally benign solvents (water, ethanol) has been examined. The presence of these additives favors the in situ formation of Cu^I‐based nanoparticles and results in an increase of the catalytic reactivity. In glycerol, liquid‐phase transmission electron microscopy (TEM) analyses, enabled by the negligible vapor pressure of this solvent, proved that Cu^I nanoparticles are responsible for the observed catalytic activity. The wide variety of alkynes and azides of which this effect has been investigated (14 combinations) confirms the role played by these additives in Cu‐catalyzed Huisgen cycloadditions.     

NHC copper complexes functionalized with sulfoxide and sulfone moieties

A series of N‐heterocyclic copper carbene complexes bearing sulfoxide and sulfone moieties have been prepared. In case of new copper compounds with sulfone ligand, the solid‐state structures were determined using X‐Ray crystallography. Obtained complexes were investigated as catalysts in such transformations as: 1,3‐dipolar cycloaddition of alkynes and azides (CuAAC), A³ coupling reaction and β‐hydroboration and compared with standard copper catalytic systems.     

Indoles from Alkynes and Aryl Azides: Scope and Theoretical Assessment of Ruthenium Porphyrin-Catalyzed Reactions

A symbiotic experimental/computational study analyzed the Ru(TPP)(NAr)₂-catalyzed one-pot formation of indoles from alkynes and aryl azides. Thirty different C₃-substituted indoles were synthesized and the best performance, in term of yields and regioselectivities, was observed when reacting ArC≡CH alkynes with 3,5-(EWG)₂C₆H₃N₃ azides, whereas the reaction was less efficient when using electron-rich aryl azides. A DFT analysis describes the reaction mechanism in terms of the energy costs and orbital/electronic evolutions; the limited reactivity of electron-rich azides was also justified. In summary, PhC≡CH alkyne interacts with one NAr imido ligand of Ru(TPP)(NAr)₂ to give a residually dangling C(Ph) group, which, by coupling with a C(H) unit of the N-aryl substituent, forms a 5+6 bicyclic molecule. In the process, two subsequent spin changes allow inverting the conformation of the sp² C(Ph) atom and its consequent electrophilic-like attack to the aromatic ring. The bicycle isomerizes to indole via a two-step outer sphere H-migration. Eventually, a ′Ru(TPP)(NAr)′ mono-imido active catalyst is reformed after each azide/alkyne reaction.     

Novel one pot synthesis of substituted quinazolin-4(3H)-ones and pyrazolo[4,3-d]pyrimidin-7(6H)-ones using copper iodide,azides and terminal alkynes

A simple and highly efficient copper iodide catalyzed one-pot synthesis of 2-substituted quinazolin-4(3H)-ones have been developed from anthranilamide, terminal alkynes and azides. A wide variety of alkynes were screened to understand the scope of this methodology. This method has been extended for the synthesis of 5-substituted pyrazolo[4,3-d]pyrimidin-7(6H)-ones which are having potential applications in medicinal chemistry.     

A Sequential Homologation of Alkynes and Aldehydes for Chain Elongation with Optional 13C‐Labeling

Terminal alkynes (RCCH) are homologated by a sequence of ruthenium‐catalyzed anti‐Markovnikov hydration of alkyne to aldehyde (RCH₂CHO), followed by Bestmann–Ohira alkynylation of aldehyde to chain‐elongated alkyne (RCH₂CCH). Inverting the sequence by starting from aldehyde brings about the reciprocal homologation of aldehydes instead. The use of ¹³C‐labeled Bestmann–Ohira reagent (dimethyl ((1‐¹³C)‐1‐diazo‐2‐oxopropyl)phosphonate) for alkynylation provides straightforward access to singly or, through additional homologation, multiply ¹³C‐labeled alkynes. The labeled alkynes serve as synthetic platform for accessing a multitude of specifically ¹³C‐labeled products. Terminal alkynes with one or two ¹³C‐labels in the alkyne unit have been submitted to alkyne–azide click reactions; the copper‐catalyzed version (CuAAC) was found to display a regioselectivity of >50 000:1 for the 1,4‐ over the 1,5‐triazine isomer, as shown analytically by ¹³C NMR spectroscopy.     

The “Click” Reaction Involving Metal Azides,Metal Alkynes,or Both: An Exploration into Multimetal Structures

Cu^I‐catalyzed 1,3‐cycloaddition of azides and alkynes (CuAAC) is one of the most powerful synthetic methodologies known. However, its use to prepare well‐defined multimetallic structures is underdeveloped. Apart from the applications of this reaction to anchor different organometallic reagents to surfaces, polymers, and dendrimers, only isolated examples of CuAAC with metal–η¹‐alkyne and metal–azide complexes to prepare multimetal entities have been reported. This concept sketches the potential of these reactions not only to prepare “a la carte” multimetal 1,2,3‐triazole derivatives, but also to discover new and unprecedented reactions.     

One‐pot synthesis of precise polyisoxazoles by click polymerization: Copper (I)‐catalyzed 1,3‐dipolar cycloaddition of nitrile oxides with alkynes

This article reports a new one‐pot method for polymer preparation, which involves double click chemistry. In one pot, two click reactions take place sequentially by adding the reactants step by step. The first click reaction is to produce the monomer for the second click reaction for polymerization. The click polymerization differs from the general click polymerization with the reaction of diazides and dialkynes. Nitrile oxides, produced in situ by the first click reaction of the formation of aldoxime, instead azides, avoiding the poisonousness and explosiveness of azides and being much safer and easy to operate. And 3,5‐disubstitute polyisoxazoles are produced by the copper(I)‐catalyzed the 1,3‐dipolar cycloaddition of nitrile oxides with alkynes in high yields by our one‐pot method. The resulting polyisoxazoles agree well with the structural assignment obtained by the ¹H NMR and IR analyses, with high molecular weights, narrow molecular weight distribution (M_w/M_n < 1.2) and high regioregularity. The poor solubility of these polymers is found to be caused by their crystallization. Improvement of solubility is achieved by modifying the structures of alkyne monomers. All the polymers are thermally stable, losing little of their weights when heated to ～350 °C. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Copper‐catalyzed Synthesis of N‐alkylated 2‐(4‐substituted‐1H‐1,2,3‐triazol‐1‐yl)‐1H‐indole‐3‐carbaldehyde by Step‐wise and One‐pot Three‐component Huisgen's 1,3‐dipolar Cycloaddition Reaction

An efficient method for the synthesis of N‐alkylated 2‐(4‐substituted‐1H‐1,2,3‐triazol‐1‐yl)‐1H‐indole‐3‐carbaldehyde has been developed starting from oxindole and indole using Huisgen's 1,3‐dipolar cycloaddition reaction of organic azides to alkynes. The effect of catalysts and solvent on these reactions has been investigated. Among all these conditions, while using CuSO₄·5H₂O, DMF was found to be the best system for this reaction. It could also be prepared in a one‐pot three‐component manner by treating equimolar quantities of halides, azides, and alkynes. The Huisgen's 1,3‐dipolar cycloaddition reaction was performed using CuSO₄·5H₂O in DMF with easy work‐up procedure.     

Synthesis and characterization of amphiphilic block–graft MPEG‐b‐(PαN3CL‐g‐alkyne) degradable copolymers by ring‐opening polymerization and click chemistry

A straightforward strategy is proposed for the synthesis of novel, amphiphilic block–graft MPEG‐b‐(PαN₃CL‐g‐alkyne) degradable copolymers. First, the ring‐opening polymerization of α‐chloro‐ε‐caprolactone (αClCL) was initiated by hydroxy‐terminated macroinitiator monomethoxy poly(ethylene glycol) (MPEG) with SnOct₂ as the catalyst. In a second step, pendent chlorides were converted into azides by the reaction with sodium azide. Finally, various kinds of terminal alkynes were reacted with pendent azides by copper‐catalyzed Huisgen's 1,3‐dipolar cycloaddition, and thus a “click” reaction. These copolymers were characterized by differential scanning calorimetry (DSC), ¹H NMR, IR, and gel permeation chromatography. By fixing the length of the MPEG block and increasing the length of PαClCL (or PαN₃CL) block, an increase tendency in T_gs was observed. However, the copolymers of MPEG‐b‐PαClCL and MPEG‐b‐PαN₃CL were semicrystalline when the M_n of MPEG was above 2000 g mol^?1. The block–graft copolymers formed micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range of 1.4–12.0 mg L^?1 depending on the composition of polymers. The lengths of hydrophilic segment influence the shape of the micelle. The mean hydrodynamic diameters of the micelles from dynamic light scattering were in the range of 90–160 nm. In vitro hydrolytic degradation of block–graft copolymers is faster than the corresponding block copolymers. The drug entrapment efficiency and the drug loading content of micelles depending on the composition of block–graft polymers were described. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4320–4331, 2008     

Cu(I)‐Catalyzed Efficient Synthesis of 2′‐Triazolo‐nucleoside Conjugates

A small library of thirty‐two 2′‐triazolyl uridine and 2′‐triazolyl‐5‐methyluridine has been synthesized by Cu(I)‐catalyzed condensation of 2′‐azido‐2′‐deoxyuridine and 2′‐azido‐2′‐deoxy‐5‐methyluridine with different alkynes and aryl propargyl ethers in almost quantitative yields. Triazolo‐nucleoside conjugates, which can be evaluated for different biological activity for suitable drug development, were unambiguously identified on the basis of ¹H NMR, ¹³C NMR, IR, and HRMS data analysis. These compounds have been synthesized for the first time and have not been reported in the literature earlier.     

The Synthesis of Fipronil Derivatives via Pd‐Catalyzed Direct Alkynylation of Phenylpyrazole with Terminal Alkynes in Green Solvents

The palladium‐catalyzed direct alkynylation of phenylpyrazole (5‐amino‐1‐[2, 6‐dichloro‐4‐trifluoromethylphenyl]‐lH‐pyrazole‐3‐carbonitrile) with terminal alkynes is being reported. The protocol utilizes EtOH/H₂O as the solvents and does not require the preactivation of phenylpyrazole with halide to form its halide substrate, which exemplifies the ideal condition of green chemistry. Various terminal alkynes such as arylacetylenes and aliphatic alkynes are used in the reaction to afford a series of fipronil derivatives of 4‐alkynyl‐1‐phenylpyrazoles with potential bioactivity in good yields. All the compounds were characterized by ¹H NMR, ¹³C NMR, and HRMS spectroscopic techniques.     

1,2,3‐Triazole derivatives of 3‐ferrocenylidene‐2‐oxindole: Synthesis,characterization, electrochemical and antimicrobial evaluation

A series of bioactive, triazole‐linked benzyl, aryl, sugar and aliphatic conjugates of 3‐ferrocenylidene‐oxindole have been synthesized. A facile 1,3‐dipolar‐Huisgen coupling reaction of the respective azides with the 3‐ferrocenylidene‐oxindole N‐propargyl moiety ( 3 ) gave the corresponding conjugates ( 5a–n ). All the newly synthesized compounds ( 5a–n ) were characterized by ¹H‐NMR, ¹³C‐NMR, HRMS, Fourier transform‐infrared spectroscopy and elemental analysis. The UV–Vis and electrochemical studies of these compounds were performed in dimethylsulfoxide solutions. The structure of compound ( 3 ) was determined by single crystal X‐ray diffraction study. These compounds exhibited moderate to good antimicrobial activity against Gram‐positive and Gram‐negative strains.     

Synthesis of New 1,2,3‐Triazole Derivatives Possessing 4H‐Pyran‐4‐one Moiety by 1,3‐Dipolar Cycloaddition Reaction of Azidomethyl Phenylpyrone with Various Alkynes

A series of new 1,2,3‐triazole derivatives were synthesized by 1,3‐dipolar cycloaddition reaction of 2‐(4‐azidomethylphenyl)‐6‐phenyl‐4H‐pyran‐4‐one with different alkynes in 40–71% yields. In the case of terminal alkynes, the reaction was proceeded in the presence of Cu(I) catalyst. The structure of the synthesized compounds were confirmed by FTIR, ¹H‐NMR, and ¹³C‐NMR spectroscopy and elemental analysis.     

Strain‐Promoted Double Azide Addition to Octadehydrodibenzo[12]annulene Derivatives

Octadehydrodibenzo[12]annulenes (DBAs), readily available by the oxidative acetylenic coupling of 1,2‐diethynylbenzene derivatives, were reacted with organic azides. As compared to the well‐known strain‐promoted azide‐alkyne cycloaddition (SpAAC) of 5,6,11,12‐tetradehydrodibenzo[a,e][8]annulene, the reactivity of the DBA alkynes was lower due to the lower strain energy. However, the regioselective double azide addition occurred without any side reactions under mild conditions, yielding bis‐triazole products. The structures of the products were confirmed by an X‐ray crystal structure analysis, and the reaction mechanism was studied by ¹H‐NMR spectroscopy and computational studies. It was also found that the DBAs were hardly fluorescent, while the bis‐triazole products showed a green fluorescence with quantum yields up to 5.1 %. Finally, the new strain‐promoted double azide addition to the DBAs was used for step‐growth polymerization, successfully producing a high molecular weight triazole polymer.     

Efficient Cu(I) acetate‐catalyzed cycloaddition of multifunctional alkynes and azides: From solution to bulk polymerization

“Click” chemistry is an effective and commonly used technique in polymer chemistry for the synthesis and modification of polymers. In this study, the bulk polymerization of multifunctional alkynes and azides was achieved by the copper(I)‐catalyzed alkyne–azide 1,3‐dipolar cycloaddition. The influence of different catalyst systems on the polymerization kinetics of the “click”reaction were evaluated by differential scanning calorimetry. Surprisingly, Cu(I) acetate showed the most efficient catalytic behavior among the applied Cu(I) salts. The polymerization kinetics in solution were investigated by 1H NMR spectroscopy and size exclusion chromatography. According to the 1H NMR investigation the copper(I)‐catalyzed cycloaddition follows a second‐order kinetics with external catalysis. Additionally, the mechanical properties of the resulting polymers were investigated by depth sensing indentation. Thereby the polymerizations of the alkyne tripropargylamine with the azides 1,3‐bis(azidomethyl)benzene and 1,4‐bis(azidomethyl)benzene resulted in mechanical hard materials. Furthermore, the combination of the alkynes tripropargylamine and di(prop‐2‐yn‐1‐yl) isophorone dicarbamate and polymerization with 1,2‐bis(2‐azidoethoxy)ethane resulted in high indentation moduli. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 239–247     

Copper(II) Acetylacetonate: An Efficient Catalyst for Huisgen‐Click Reaction for Synthesis of 1,2,3‐Triazoles in Water

An efficient and green copper(II ) acetylacetonate‐catalyzed protocol for the Huisgen‐click reaction in water at 100 °C has been established. The protocol was not only suitable for the reaction between organic azides and alkynes, but also suitable for one‐pot three‐component reaction among alkyl halides, NaN₃ and alkynes.     

Experimental Evidence for the Involvement of Dinuclear Alkynylcopper(I) Complexes in Alkyne–Azide Chemistry

Dinuclear alkynylcopper(I) ladderane complexes are prepared by a robust and simple protocol involving the reduction of Cu₂(OH)₃OAc or Cu(OAc)₂ by easily oxidised alcohols in the presence of terminal alkynes; they function as efficient catalysts in copper‐catalysed alkyne–azide cycloaddition reactions as predicted by the Ahlquist–Fokin calculations. The same copper(I) catalysts are formed during reactions by using the Sharpless–Fokin protocol. The experimental results also provide evidence that sodium ascorbate functions as a base to deprotonate terminal alkynes and additionally give a convincing alternative explanation for the fact that the Cu^I‐catalysed reactions of certain 1,3‐diazides with phenylacetylene give bis(triazoles) as the major products. The same dinuclear alkynylcopper(I) complexes also function as catalysts in cycloaddition reactions of azides with 1‐iodoalkynes.     

Syntheses of N-sulfonyl-N,N-disubstituted amidines via a three-component free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes

A facile and efficient synthesis of N-sulfonyl-N,N-disubstituted amidines has been achieved via a CuI-catalyzed three-component free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes in the presence of azodiisobutyronitrile(AIBN).The reaction mechanism of this reaction has also been studied.