Highly active,thermo‐responsive polymeric catalytic system for reuse in aqueous and organic CuAAC reactions

Tris‐(benzyltriazolylmethyl)amine (TBTA) has been immobilized onto a styrenic monomer and subsequently copolymerized with N‐isopropyl acrylamide (NIPAM) to afford catalytically active thermo‐responsive copolymers for copper assisted click chemistry. P(TBTA‐co‐NIPAM) copolymers were synthesized with incorporation of between 2 and 10 ligand units per chain and tuneable molecular weight (28–148 kDa). A combination of ¹H NMR spectroscopy, size exclusion chromatography (SEC) and elemental analysis (EA) confirmed the controlled synthesis of these polymers and allowed for quantification of the degree of TBTA‐functionalized monomer incorporation. After loading with copper(I) bromide, this homogeneous catalyst system was added to a water/ethyl acetate two‐phase system. Using this biphasic system aqueous click reactions could be performed at room temperature, while organic click chemistry could be performed above the cloud point temperature of the catalyst system. The polymer catalyst system could be regenerated via extraction by making use of its lower critical solution temperature (LCST)‐behavior, and then reused for further copper(I) catalyzed azide‐alkyne cycloaddition (CuAAC) reactions. While a reduced catalytic activity is observed as a result of copper leaching in aqueous click reactions, the recycling experiments in the organic phase demonstrated that this copolymer supported system allows for efficient recycling and reuse. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Recyclable Cu nanoparticle catalyzed azide-alkyne click polymerization

The Cu(I)-catalyzed alkyne-azide cycloaddition(CuAAC) has been developed into a powerful polymerization reaction for the synthesis of new polytriazoles with versatile properties. However, research on recyclable and reusable copper catalyst for click polymerization to meet the requirement of green chemistry was rarely reported. Copper nanoparticles were reported to be capable catalysts for CuAAC. Replacing conventional copper catalyst with copper nanoparticles may realize the recycle and reuse of the copper catalyst in click polymerization. In this paper, copper nanoparticles were prepared and used as an effective catalyst for click polymerization, and soluble polytriazoles with high molecular weights were obtained in excellent yields under optimized reaction conditions. Importantly, the copper nanoparticles can be recycled and reused for up to 11 times for the click polymerization. Moreover, introducing aggregation-induced emission(AIE)-active moiety of tetraphenylethylene into the monomers makes the resultant polymers retain the AIE feature. This work not only provides an efficient recyclable catalytic system for the azide-alkyne click polymerization, but also might inspire polymer chemists to use recyclable copper species to catalyze other polymerizations.     

Copper + nickel-in-charcoal (Cu-Ni/C): a bimetallic, heterogeneous catalyst for cross-couplings

A new heterogeneous catalyst composed of copper and nickel oxide particles supported within charcoal has been developed. It catalyzes cross-couplings that traditionally use palladium, nickel, or copper, including Suzuki-Miyaura reactions, Buchwald-Hartwig aminations, vinylalane alkylations, etherifications of aryl halides, aryl halide reductions, asymmetric conjugate reductions of activated olefins, and azide-alkyne "click" reactions.     

点击化学在食品安全检测中的应用研究进展

点击化学因具有反应模块化、无有毒有害副产物、反应效率高等出色的反应性能备受关注,是继组合化学之后又一新型合成技术,在材料表面功能化、大分子聚合物的合成、生物标记等领域得到了广泛应用.点击反应试剂的活性基团易于修饰在其他化学基团上,表明点击反应有望作为中间反应介导特定反应的信号转换或放大.近几年出现了大量基于点击化学构建...     

Assessment of the Full Compatibility of Copper(I)-Catalyzed Alkyne-Azide Cycloaddition and Oxime Click Reactions for bis-Labelling of Oligonucleotides

The conjugation of oligonucleotides with reporters is of great interest for improving their intrinsic properties or endowing new ones. In this context, we report herein a new procedure for the bis-labelling of oligonucleotides through oxime ligation (Click-O) and copper(I)-catalyzed alkyne–azide cycloaddition (Click-H). 5′-Azido and 3′-aldehyde precursors were incorporated into oligonucleotides, and subsequent coupling reactions through Click-O and Click-H (or vice versa) were successfully achieved. In particular, we exhaustively investigated the full compatibility of each required step for both tethering strategies. The results demonstrate that click Huisgen and click oxime reactions are fully compatible. However, whilst both approaches can deliver the targeted doubly conjugated oligonucleotide, the route involving click oxime ligation prior to click Huisgen is significantly more successful. Thus the reactions investigated here can be considered to be key elements of the chemical toolbox for the synthesis of highly sophisticated bioconjugates.     

Optimization of Click Chemistry of Ferrocene Derivatives on Acetylene‐Functionalized Silicon(100) Surfaces

The optimization of the reaction conditions for copper‐catalyzed azide‐alkyne ‘click’ cyclo‐addition reactions used to covalently confine substituted ferrocene derivatives on passivated silicon(100) surfaces is reported. Variations in the observed reaction yields and the extent of surface contamination as a function of the source of the copper catalyst and the solvent system used in the ‘click’ procedure were evaluated spectroscopically. The electronic communication between the ferrocene centre and the underlying semiconductor surface was investigated by means of cyclic voltammetry and found to be consistent with that expected for a well‐behaved and robust redox interface.     

Star polymers by photoinduced copper‐catalyzed azide–alkyne cycloaddition click chemistry

Well‐defined star polymers consisting of tri‐, tetra‐, or octa‐arms have been prepared via coupling‐onto strategy using photoinduced copper(I)‐catalyzed 1,3‐dipolar cycloaddition click reaction. An azide end‐functionalized polystyrene and poly(methyl methacrylate), and an alkyne end‐functionalized poly(ε‐caprolactone) as the integrating arms of the star polymers are prepared by the combination of controlled polymerization and nucleophilic substitution reactions; whereas, multifunctional cores containing either azide or alkyne functionalities were synthesized in quantitatively via etherification and ring‐opening reactions. By using photoinduced copper‐catalyzed azide–alkyne cycloaddition (CuAAC) click reaction, reactive linear polymers are simply attached onto multifunctional cores to form corresponding star polymers via coupling‐onto methodology. The chromatographic, spectroscopic, and thermal analyses have clearly demonstrated that successful star formations can be obtained via photoinduced CuAAC click reaction. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1687–1695     

Synthesis of glycopolymers via click reactions

This mini-review describes recent work in the field of glycopolymer synthesis, with a focus on methods that have employed “click chemistry” and controlled polymerization methodology. A variety of carbohydrates with clickable groups such as azide, alkyne, and thiol moieties provide new routes to glycopolymers. Several studies use copper catalyzed azide-alkyne cycloaddition (CuAAC) reactions to synthesize glycomonomers or to incorporate carbohydrates into a clickable polymeric backbone. Alternatively, there are many thiol based click reactions which provide metal-free synthesis, which are discussed in details.     

Click Chemistry Route to the Synthesis of Unusual Amino Acids,Peptides, Triazole‐Fused Heterocycles and Pseudodisaccharides

Conjugation of different molecular species using copper(I)‐catalyzed click reaction between azides and terminal alkynes is among the best available methods to prepare multifunctional compounds. The effectiveness of this method has provided wider acceptance to the concept of click chemistry, which is now widely employed to synthesize densely functionalized organic molecules. This article summarizes the contributions from our group in the development of new methods for the synthesis of functional molecules using copper(I)‐catalyzed click reactions. We have developed very efficient methods for the synthesis of peptides and amino acids conjugated with carbohydrates, thymidine and ferrocene. We have also developed an efficient strategy to synthesize triazole‐fused heterocycles from primary amines, amino alochols and diols. Finally, an interesting method for the synthesis of pseudodisaccharides linked through triazoles, starting from carbohydrate‐derived donor‐acceptor cyclopropanes is discussed.     

Polymer end group modifications and polymer conjugations via “click” chemistry employing microreactor technology

This study presents the development of microreactor protocols for the successful continuous flow end group modification of atom transfer radical polymerization precursor polymers into azide end‐capped materials and the subsequent copper‐catalyzed azide alkyne click reactions with alkyne polymers, in flow. By using a microreactor, the reaction speed of the azidation of poly(butyl acrylate), poly(methyl acrylate), and polystyrene can be accelerated from hours to seconds and full end group conversion is obtained. Subsequently, copper‐catalyzed click reactions are executed in a flow reactor at 80 °C. Good coupling efficiencies are observed and various block copolymer combinations are prepared. Furthermore, the flow reaction can be carried out in only 40 min, while a batch procedure takes several hours to reach completion. The results indicate that the use of a continuous flow reactor for end group modifications as well as click reactions has clear benefits towards the development and improvement of well‐defined polymer materials. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1263–1274     

Destabilizing Predictive Copper-Catalyzed Click Reactions by Remote Interactions with a Zinc-Porphyrin Backbone

In order to obtain new supramolecular ligands that build up around a zinc-porphyrin scaffold, we envisioned to access sulfonyl triazole intermediates by well-known copper-catalyzed click reactions. Unexpectedly, these triazole intermediates do not form due to the presence of the zinc-porphyrin moiety at close proximity of the active copper species. Indeed, the copper catalyst undergoes a different chemo-selective reaction pathway reacting with traces of alcohols or water from the media that behave as effective nucleophiles leading to sulfonyl imidates or sulfonyl amides covalently connected to the zinc-porphyrin. We show that copper-catalyzed click reactions can follow different reaction mechanisms when the catalytic events occur at close proximity of a zinc-porphyrin unit which likely acts as a Lewis acid to stabilize otherwise inaccessible reaction intermediates.     

Discrete macromolecular constructs via the Diels–Alder “Click” reaction

Functional polymeric materials with desired properties can be designed by precise control of macromolecular architectures. Over the recent years, click reactions have enabled efficient synthesis of a variety of polymers with different topologies via efficient polymer–polymer conjugations. While the copper catalyzed Huisgen type (3+2) dipolar cycloaddition between azide and alkyne has been widely used toward this goal, the Diels–Alder (DA) reaction offers an alternative click reaction that allow efficient macromolecular conjugations, oftentimes without the need of any additional reagent or catalyst. This article highlights, with illustrative examples, the power of the DA “click” reaction to efficiently synthesize a variety of different well‐defined macromolecular constructs in a modular fashion. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Novel approach to the design of potential bioactive alkaloid anabasine conjugates using click chemistry methodology

Anabasine‐containing azides and acetylenes were used as building blocks in copper(I)‐catalyzed 1,3‐dipolar cycloaddition reactions with a series of acetylenes and azides via click methodology to provide a range of anabasine conjugates being potential ligands for neuronal nicotinic acetylcholine receptors.     

Synthesis and Catalytic Studies of Thermoresponsive Copper (I) Complex towards Click Reactions

Click reaction or copper-assisted azide–alkyne cycloaddition (CuAAC) reaction can conveniently synthesize desired organic molecules or functionalize biological macromolecules. In many cases, trace amounts of residual copper from the reaction mixture are not trivial to remove when the exhaustive purification step is avoided to fulfill the essential criteria of a click reaction. It is often detrimental, particularly for biochemical applications or when it involves biological macromolecules. Herein, we have reported the synthesis of a new type of copper (I) complex as a smart catalyst for click reaction, which can be separated from the reaction mixture very easily by the slight elevation of temperature, thanks to its thermoresponsive behavior. The click reactions using a thermoresponsive catalyst were first studied in an aqueous medium using various organic molecules containing alkyne and azide functional groups. Later, the strategy was extended to biological macromolecules like collagen.     

Klick‐Chemie. Synthesen,die gelingen

Click‐Chemistry is a concept in organic synthesis that uses a limited amount of very reliable reactions on a broad variety of substrates. This leads within a few steps to molecules of high diversity which is important to accelerate drug‐discovery. Besides favourable thermodynamic requirements, the criteria for a click‐reaction include also simple reaction conditions and a quick and easy (almost unnecessary) workup. The most successful of these click‐reactions is the copper catalysed 1, 3‐dipolar cycloaddition of azides and alkynes, which in the meantime is used in most diverse areas of chemistry. The mechanistic ideas of this reaction is looked at in more detail.     

Copper(I)‐Catalyzed Interrupted Click Reaction: Synthesis of Diverse 5‐Hetero‐Functionalized Triazoles

The 5‐heterofunctionalized triazoles are important scaffolds in bioactive compounds, but current click reactions (CuAAC) cannot produce these core structures. A copper(I)‐catalyzed interrupted click reaction to access diverse 5‐functionalized triazoles is reported. Various 5‐amino‐, thio‐, and selenotriazoles were readily assembled in one step in high yields. The reaction proceeds under mild conditions with complete regioselectivity. It also features a broad substrate scope and good functional group compatibility.     

A Mechanochemically Triggered “Click” Catalyst

“Click” chemistry represents one of the most powerful approaches for linking molecules in chemistry and materials science. Triggering this reaction by mechanical force would enable site‐ and stress‐specific “click” reactions—a hitherto unreported observation. We introduce the design and realization of a homogeneous Cu catalyst able to activate through mechanical force when attached to suitable polymer chains, acting as a lever to transmit the force to the central catalytic system. Activation of the subsequent copper‐catalyzed “click” reaction (CuAAC) is achieved either by ultrasonication or mechanical pressing of a polymeric material, using a fluorogenic dye to detect the activation of the catalyst. Based on an N‐heterocyclic copper(I) carbene with attached polymeric chains of different flexibility, the force is transmitted to the central catalyst, thereby activating a CuAAC in solution and in the solid state.     

Copper(I) 1,2,3-triazol-5-ylidene complexes as efficient catalysts for click reactions of azides with alkynes

Complexes of copper with 1,4-diphenyl, 1,4-dimesityl, and 1-(2,6-diisopropylphenyl)-4-(3,5-xylyl)-1,2,3-triazol-5-ylidene (abnormal NHC = N-heterocyclic carbene) were prepared by consecutive treatment of the corresponding azolium salts with silver oxide and copper chloride. The new CuCl(aNHC) complexes efficiently catalyzed click reactions of azides with alkynes to give 1,4-substituted 1,2,3-triazoles in excellent yields at room temperature with short reaction times. CuCl(TPh) was particularly effective for the reaction between sterically hindered azides and alkynes.     

Dosage colorimétrique du cuivre dans les aciers par l'acide rubéanique

The rapid colorimetric determination of copper has been studied by means of the coloured reactions of copper salts with dithio-oxamide or rubeanic acid. This method can be used for the determination of copper, contained in an impure state in steels, in the presence of iron and some alloy elements without first extracting in an acetic buffer medium, the iron being made complex by citric acid. The method can equally be applied to the determination of small quantities of copper in different metals and alloys. The accuracy obtained is about ± 2.5 % of the quantity of copper.