Benzyl Azide Research Articles

Orthogonal functionalization of a fullerene building block through copper-catalyzed alkyne–azide and thiol–maleimide click reactions

In this study, the synthesis of an orthogonally clickable fullerene building block mono-adduct bearing on one side an alkyne unit and a maleimide moiety on the other side is presented. This derivative has been involved in CuAAC and thiol–maleimide click reactions using stepwise or one-pot processes with benzyl azide and 1-octanethiol. The one-pot process involving the CuAAC reaction followed by the thiol–maleimide conjugation gives the highest yield. This new platform could pave the way for the synthesis of a wide range of fullerene derivatives exploiting this set of orthogonal reactions.

Fine‐Tunable Tris(triazolyl)methane Ligands for Copper(I)‐ Catalyzed Azide–Alkyne Cycloaddition Reactions

AbstractThe preparation of a small library of modular tris(triazolyl)methane ligands for copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reactions is reported. The synthesis of the first generation ligand, tris(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methanol (1a), suitable for work in aqueous systems, is reported at the 50–100 mmol scale through a one‐stage, environmentally benign procedure. One‐stage procedures for the synthesis of tris(aryltriazolyl)methanol structures (1b, phenyl; 1c, para‐trifluoromethylphenyl; 1d, para‐methoxyphenyl) designed for electronic fine‐tuning of catalytic properties, and of 1a‐derived ethers 2c (OBn) and 2d (OMe), designed for CuAAC reactions in organic solvents, are also reported. The complete set of ligands (1a–d, 2c–d) has been tested in the reaction of phenylacetylene with benzyl azide in six different solvents (water, hexane, toluene, dichloromethane, tetrahydrofuran, and acetonitrile), and this has allowed the identification of 1b, 1c and 2c as the ligands depicting the highest tolerance to changes in solvent polarity within the considered family. The comparative performance of ligands 1b–d and 2c in the cycloaddition of a small family of alkynes with benzyl azide in two very different reaction media (1:1 t‐BuOH/H2O and toluene) has been studied as a guide for catalyst selection in specific applications. The applicability of 1c in CuAAC reactions involving functional substrates in toluene has been explored under thermal and microwave‐accelerated (tandem azide formation plus CuAAC reaction) reaction conditions.magnified image

A Highly Active and Magnetically Recoverable Tris(triazolyl)–CuI Catalyst for Alkyne–Azide Cycloaddition Reactions

Nanoparticle-supported tris(triazolyl)-CuBr, with a diameter of approximately 25 nm measured by TEM spectroscopy, has been easily prepared, and its catalytic activity was evaluated in the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. In initial experiments, 0.5 mol % loading successfully promoted the CuAAC reaction between benzyl azide and phenylacetylene, in water at room temperature (25 °C). During this process, the iron oxide nanoparticle-supported tris(triazolyl)-CuBr displayed good monodispersity, excellent recoverability, and outstanding reusability. Indeed, it was simply collected and separated from the reaction medium by using an external magnet, then used for another five catalytic cycles without significant loss of catalytic activity. Inductively coupled plasma (ICP) analysis for the first cycle revealed that the amount of copper leached from the catalyst into the reaction medium is negligible (1.5 ppm). The substrate scope has been examined, and it was found that the procedure can be successfully extended to various organic azides and alkynes and can also be applied to the one-pot synthesis of triazoles, through a cascade reaction involving benzyl bromides, alkynes, and sodium azide. In addition, the catalyst was shown to be an efficient CuAAC catalyst for the synthesis of allyl- and TEG-ended (TEG=triethylene glycol) 27-branch dendrimers.

ChemInform Abstract: A Strategy to Access Fused Triazoloquinoline and Related Nucleoside Analogues.

Abstract Fused triazoloquinolines have been prepared starting from ( E )-3-(2-nitrophenyl)-1-aryl-prop-2-en-1-ones and sugar or benzyl azides in a sequential [3+2] cycloaddition reaction, followed by one pot Pd–C assisted reduction, cyclization and aromatization. The triazolyl fused quinolines with N 1 -glycosyl substituents as unnatural nucleosides have inherent potential to generate a library of compounds for bioevaluations.

ChemInform Abstract: Probing the Reactivity of o‐Phthalaldehydic Acid/Methyl Ester: Synthesis of N‐Isoindolinones and 3‐Arylaminophthalides.

A new method for the synthesis of N-substituted isoindolinones and 3-arylaminophthalides was developed through aza-Wittig/cyclisation. The reaction of o-phthalaldehydic acid methyl ester with benzylic, aromatic and aliphatic azides gave N-isoindolinones whereas reaction of o-phthalaldehydic acid with the aromatic azides gave 3-arylaminophthalides.

Multi-component Vaporization Model for Hexadecane-benzyl Azide Droplets without Liquid Phase Reaction

To study the mechanisms of the reduced combustion duration of diesel- benzyl azide blend, a rapid mixing multi-component vaporization model for hexadecane-benzyl azide droplets without liquid phase reaction was built and validated. Hexadecane was used as a representative for diesel to eliminate its multi-component effect. Comparisons of normalized squared droplet diameter and droplet temperature between numerical and experimental results were presented and discussed. The results show that the model gives an acceptable approximate prediction, and the difference between the vaporization rate of benzyl azide and hexadecane results in the slope variation of normalized squared droplet diameter curve, while the variation of the heat penetrated into droplet interior results in the slope variation of droplet temperature curve.

Synthesis of Open-cage Fullerenes with 4-Alkynylphenyl Groups on the Rim of the Orifice

Alkynyl anilines react with a diketo open-cage fullerene derivative and expand the orifice size from 11- to 18-membered rings. Benzyl azide reacts with the terminal alkynyl group under Click conditions. Single crystal X-ray structure of the C s symmetric bis-3-alkynylaniline derivative showed the formation of a head to tail dimer due to strong H-bonding and π-π interactions.

Synthesis of Conjugated Polymers Containing DIBAC-Derived Triazole Monomers

2,7-Dibromoazadibenzocyclooctyne (DIBAC-Br2) was prepared as a pro-monomer unit that could be modified by the metal-free strain-promoted azide–alkyne cycloaddition (SPAAC). Click cyclization of DIBAC-Br2 with five different benzyl azides produced a homologous series of monomers with different functionality on the resulting triazole ring, ranging from electron-withdrawing to electron-donating substituents. Using this series of monomers, in combination with 2,7-dialkylfluorene as a comonomer, five different conjugated polymers were prepared via Suzuki polycondensation, each having different electronic properties. The resulting copolymers exhibited Mw values ranging from 5 to 10 kDa and PDI values in the 1.5–2 range. These polymers were characterized by 1H NMR spectroscopy, optical spectroscopy, and cyclic voltammetry. Finally, a coumarin-containing oligomer was synthesized and used to demonstrate a photo-cross-linking scheme via [2 + 2] cycloaddition.

ChemInform Abstract: Direct C—H Amination of Arenes with Alkyl Azides under Rhodium Catalysis.

AbstractThe Rh‐catalyzed treatment of arenes bearing chelating groups with benzyl and alkyl azides provides a new and straightforward approach to diverse aromatic amines.

“Click” and Olefin Metathesis Chemistry in Water at Room Temperature Enabled by Biodegradable Micelles

The two laboratory reactions focus on teaching several concepts associated with green chemistry. Each uses a commercial, nontoxic, and biodegradable surfactant, TPGS-750-M, to promote organic reactions within the lipophilic cores of nanoscale micelles in water. These experiments are based on work by K. Barry Sharpless (an azide-alkyne "click" reaction) and Robert Grubbs (an olefin cross-metathesis reaction); both are suitable for an undergraduate organic laboratory. The copper-catalyzed azide-alkyne [3+2] cycloaddition of benzyl azide and 4-tolylacetylene is very rapid: the triazole product is readily isolated by filtration and is characterized by thin-layer chromatography and melting point analysis. The ruthenium-catalyzed olefin cross-metathesis reaction of benzyl acrylate with 1-hexene is readily monitored by thin-layer chromatography and gas chromatography. The metathesis experiment comparatively evaluates the efficacy of a TPGS-750-M/water medium relative to a traditional reaction performed in dichloromethane (a common solvent used for olefin metathesis).

An Abnormal N‐Heterocyclic Carbene–Copper(I) Complex in Click Chemistry

AbstractHerein we report the synthesis of a copper(I) chloro complex using an abnormal N‐heterocyclic carbene (aNHC) salt, 1,3‐bis(2,6‐diisopropylphenyl)‐2,4‐diphenylimidazolium. The CuCl(aNHC) complex efficiently catalyzed Huisgen 1,3‐dipolar cycloaddition reactions (click reactions) of azides with alkynes to give 1,4‐substituted 1,2,3‐triazoles in excellent yields at room temperature within short reaction time under solvent‐free conditions. The catalyst successfully activated benzyl azide and phenylacetylene under the low catalyst loading of 0.005 mol% resulting in a nearly quantitative yield of the product at room temperature with the high TON value of 19,800. The catalyst also exhibits high efficiency in the reaction between sterically hindered azides and alkynes under solvent‐free conditions at room temperature. Furthermore, a number of internal alkynes was successfully tested in this copper‐catalyzed cycloaddition reaction for synthesis of 4,5‐disubstituted triazoles.magnified image

A Selective Synthesis of 4-Bromoisoquinoline and 4-Bromoisquinolone

2-Alkynyl benzyl azides smoothly underwent an electrocyclic reaction catalysed by palladium to selectively afford either 4-bromoisoquinoline and 4-bromoisquinolones under different conditions. 4-Bromoisoquinoline was synthesised in the presence of PdBr2/CuBr2/LiBr in MeCN, and 4-bromoisoquinolone was selectively produced with PdBr2/CuBr2/HOAc in CH2ClCH2Cl. A bromine was introduced into the products which makes the methodology more attractive for organic synthesis.

A strategy to access fused triazoloquinoline and related nucleoside analogues

Fused triazoloquinolines have been prepared starting from (E)-3-(2-nitrophenyl)-1-aryl-prop-2-en-1-ones and sugar or benzyl azides in a sequential [3+2] cycloaddition reaction, followed by one pot Pd–C assisted reduction, cyclization and aromatization. The triazolyl fused quinolines with N1-glycosyl substituents as unnatural nucleosides have inherent potential to generate a library of compounds for bioevaluations.

Propargyl‐Functional Aliphatic Polycarbonate Obtained from Carbon Dioxide and Glycidyl Propargyl Ether

The synthesis of propargyl-functional poly(carbonate)s with different content of glycidyl propargyl ether (GPE) units is achieved via the copolymerization of propargyl glycidyl ether and carbon dioxide. A new type of functional poly(carbonate) synthesized directly from CO(2) and the glycidyl ether is obtained. The resulting polymers show moderate polydispersities in the range of 1.6-2.5 and molecular weights in the range of 7000-10 500 g mol(-1). The synthesized copolymers with varying number of alkyne functionalities and benzyl azide are used for the copper-catalyzed Huisgen-1,3-dipolar addition. Moreover, the presence of vicinal alkyne groups opens a general pathway to produce functional aliphatic poly(carbonate)s from a single polymer scaffold.

Recyclable Porous Polymer‐Supported Copper Catalysts for Glaser and Huisgen 1,3‐Diolar Cycloaddition Reactions

A family of polymer-attached phenanthrolines was prepared from solvothermal copolymerization of divinylbenzene with N-(1,10-phenanthroline-5-yl)acrylamide in different ratios. The polymer-supported copper catalysts were obtained through typical impregnation with copper(II) salts. The polymers and supported copper catalysts have been characterized by N2 adsortion, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermogravimetric analysis (TG); they exhibit a high surface area, hierarchical porosity, large pore volume, and high thermal and chemical stabilities. The copper catalyst has proved to be highly active for Glaser homocoupling of alkynes and Huisgen 1,3-diolar cycloaddition of alkynes with benzyl azide under mild conditions at low catalyst loading. The heterogeneous copper catalyst is more active than commonly used homogeneous and nonporous polystyrene-supported copper catalysts. In particular, the catalyst is easily recovered and can be recycled at least ten times without any obvious loss in catalytic activity. Metal leaching was prevented due to the strong binding ability of phenanthroline and products were not contaminated with copper, as determined by ICP analysis.

The triazolyl analogue of the trityl cation

Abstract The formation of the tris(3-benzyl-triazol-5-yl)carbenium cation, a heterocyclic analogue of the trityl cation, from tris(3-benzyl-triazol-5-yl)methanol, itself generated by Cu(I)-catalyzed Huisgen reaction of benzyl azide with triethynylmethanol, in the presence of trifluoroacetic anhydride is evidenced through a selective S N 1 reactivity with various O -, N -, S -, and C -nucleophiles, giving the corresponding triazolylmethane derivatives in moderate to high yields.

Synthesis and reactivity of dibenzoselenacycloheptynes.

Dibenzoselenacycloheptynes were prepared in three steps from commercially available reagents and trapped in situ with benzyl azide to form the corresponding triazoles. Surprisingly, the dibenzoselenacycloheptynes also abstracted hydrogen atoms from solvents such as THF or toluene, forming dibenzoselenacycloheptene products. These alkenyl compounds arise from a hydrogen transfer reaction from solvent to the unisolable intermediate, and we postulate that the reaction proceeds via a radical mechanism originating from the strained alkynyl bond that has unusually high radical character.

A Rapid Click Chemistry Using Beta-Cyclodextrin Immobilized on Glass Micro-Particles

The surface of glass micro-particle (GMP) was functionalized with β-cyclodextrin (→ GMP-β-CD) and was characterized by X-ray photoelectron spectroscopy (XPS). GMP-β-CD was used as a phase transfer catalyst for click reactions of aromatic azides with terminal acetylenes. For click reaction of benzyl azide and phenyl acetylene, reaction time was decreased from 5.8 h to 10 min when 0.8g GMP-β-CD /mmol of benzyl azide was added. The modified surface of GMP-β-CD showed no change or degradation after repeated use as confirmed from XPS analysis after 10 cycles.

On the Unique Reactivity of Pd(OAc)2 with Organic Azides: Expedient Synthesis of Nitriles and Imines

On the Unique Reactivity of Pd(OAc)₂ with Organic Azides: Expedient Synthesis of Nitriles and Imines

Synthesis of Penicillenol C1 and of a Bis-Azide Analogue for Photoaffinity Labeling

Two diasteroisomers of the Penicillium metabolite penicillenol C1 were synthesized for the first time by 3-acylation of an L-threonine-derived tetramic acid with enantiopure 2-methyloct-(6E)-enoic acids. The 5S,6R,9S isomer has NMR spectra and optical rotation identical with those of the natural compound. A bis-azide-tagged penicillenol analogue was also synthesized for photoaffinity labeling of target proteins. The photolysis of the bis-azide in the presence of methanol as a protein-mimicking nucleophile led to reaction only of the aryl azide, while leaving the benzyl azide available for pull-downs or the attachment of fluorescent tracers. As a proof of concept, the distribution of this bis-azide-tagged tetramic acid in living cells was visualized via a Staudinger ligation between the azide tag and a phosphane fluorophore.