Benzyl Azide Research Articles

Fluorinated Anions Promoted “on Water” Activity of Di- and Tetranuclear Copper(I) Catalysts for Functional Triazole Synthesis

A set of di- and tetra-copper(I) compounds [Cu2(L1H)2][BArF]2 (1) (L1H = bis(5,7-dimethyl-1,8-naphthyridin-2-yl)amine; BArF = [B{C6H3(CF3)2}4]) and [Cu4(L1)2(L2)2][BNBF]2 (2) (L2 = 5,7-dimethyl-1,8-naphthyridin-2-amine; BNBF = [NH2{B(C6F5)3}2]), stabilized by naphthyridine-based ligands and containing fluorinated anions, is synthesized. Their catalytic utility for copper(I)-catalyzed azide–alkyne coupling (CuAAC) reactions in organic solvents and “on water” is evaluated. The dimer analogue [Cu2(L1H)2][BPh4]2 (3) with nonfluorinated anion is synthesized for the purpose of comparison. All three compounds show CuAAC activity in organic solvents, although the performance of 3 is considerably lower. Remarkable rate enhancement is displayed by compounds containing fluorinated anions (1 and 2) under “on water” conditions for the model reaction involving benzyl azide, affording 98% conversions in 15–20 min, where compound 3 gives 76% conversions in 50 min. Kinetic experiments reveal the involvement of two coppers in the cycloaddition process. Employing a host of substrates, the usefulness of fluorinated anions to dramatically improve the catalytic activity of Cu(I) compounds under “on water” conditions is demonstrated.

ChemInform Abstract: A Novel Method for the Synthesis of Haloisoquinolines Involving an Electrophile‐Exchange Process.

A synthesis of haloisoquinolines through electrophilic cyclisation involving an electrophilic-exchange process has been developed. A variety of 2-alkynyl benzyl azides are cyclised in the presence ...

Evaporation characteristics of dual component droplet of benzyl azides-hexadecane mixtures at elevated temperatures

Abstract The evaporation characteristics of different dual component droplets are experimentally studied through a suspended droplet device and a high-speed video camera. The droplets of hexadecane, dodecane–hexadecane mixture and benzyl azides-hexadecane mixture are studied. The initial diameter of droplet is about 1.21–1.23 mm, and the elevated temperature environment in the range of 473 and 773 K is provided by an electric furnace. The results indicate that the evaporation trend of the dodecane–hexadecane blend droplet is the same as hexadecane at the different ambient temperatures, while the evaporation characteristics of the benzyl azides-hexadecane blend droplet are completely different from that of the dodecane–hexadecane at the high temperature of 673 K. The evaporation process of the benzyl azides-hexadecane blend droplet consists of three stages: transient heating, fluctuation evaporation and steady evaporation at the high ambient temperatures. The bubble formation and expansion, droplet distortion, puffing and incomplete micro-explosion are observed for benzyl azides-hexadecane droplet due to the reactivity of benzyl azides at liquid phase. Moreover, the reduction of the benzyl azides-hexadecane blend droplet lifetime is larger than that of the dodecane–hexadecane blend droplet with increasing ambient temperature. The increase of the liquid-phase reaction rate of benzyl azides is the main reason for improving the evaporation of the binary fuel droplet. In addition, with increasing benzyl azides mass fraction, the benzyl azides-hexadecane binary droplet lifetime decreases.

ChemInform Abstract: Synthesis and NMR Analysis of 1,4‐Disubstituted 1,2,3‐Triazoles Tethered to Pyridine, Pyrimidine, and Pyrazine Rings.

AbstractCopper catalyzed 1,3‐dipolar cycloaddition of terminal alkynes and aromatic or benzylic azides containing different six‐membered aromatic N‐heteroaryl substituents is examined to yield a variety of 1,2,3‐triazoles with the expected regioselectivity.

The Mechanism of Pyrolysis of Benzyl Azide: Spectroscopic Evidence for Benzenemethanimine Formation

We study the gas-phase pyrolysis of benzyl azide (BA, C6H5CH2N3) using ultraviolet photoelectron spectroscopy (UVPES) and matrix-isolation infrared (IR) spectroscopy, together with electronic structure calculations and Rice-Ramsperger-Kassel-Marcus (RRKM) calculations. It is found that BA decomposes via N2 elimination at ca. 615 K, primarily yielding benzenemethaninime. Other end products include HCN and C6H6. N-Methyleneaniline is not detected, although its formation at higher temperature is foreseen by RRKM calculations.

ChemInform Abstract: Synthesis of Piperidones from Benzyl Azides and Acetone.

AbstractTwo equivalents acetone (II) are annulated with N‐unsubstituted imines, in‐situ generated from benzyl azines (I), using a ruthenium catalyst leading to 2,2‐dimethyl‐6‐substituted‐4‐piperidones (III) under mild reaction conditions.

ChemInform Abstract: Preparation of Ruthenium Azido Complex Containing a Tp Ligand and Ruthenium‐Catalyzed Cycloaddition of Organic Azides with Alkynes in Organic and Aqueous Media: Experimental and Computational Studies.

AbstractNovel ruthenium complexes bearing an azido ligand are prepared and successfully applied as catalyst to the regioselective 1,3‐dipolar cycloaddition of benzyl azides to terminal alkynes.

ChemInform Abstract: Raney Ni Catalyzed Azide‐Alkyne Cycloaddition Reaction.

AbstractHuisgen‐type cycloaddition proceeds with excellent regioselectivity for phenyl azide (II) with aryl‐ and alkyl‐propargyl ethers (I) and alkynes (XI) and (XIII) while alkyl and benzyl azides (IV) in combination with alkyl propargylic ethers (Ib,c) as well as phenyl azide and propargylic alcohol (VIII) give regioisomeric mixtures with poor selectivity.

Transition metal-free generation of N-unsubstituted imines from benzyl azides: synthesis of N-unsubstituted homoallylic amines.

An efficient transition metal-free approach for the generation of N-unsubstituted imines from azides followed by trapping with allyl nucleophile to provide N-unsubstituted homoallylic amines has been described. Although catalytic KO(t)Bu in DMSO is sufficient to allow imine generation, stoichiometric KO(t)Bu is essential in THF. Further, an enantio- and diastereoselective synthesis of homoallylic amines from benzyl azide has also been exemplified.

Polyvinyl alcohol-stabilized cuprous oxide particles: efficient and recyclable heterogeneous catalyst for azide–alkyne cycloaddition in water at room temperature

The PVA-stabilized Cu2O particles were prepared using a novel and simple rout in aqueous medium at room temperature under aerobic conditions. Initially, Cu(II) ions were fixed in PVA matrix via complex formation with OH groups, subsequently this PVA–Cu(II) macromolecular complex as a precursor reacted with ascorbic acid as a reducing agent at pH = 12 to obtain the PVA–Cu2O composite. The products were characterized using XRD, FE-SEM, FTIR, and UV–Visible techniques. The as-prepared PVA–Cu2O composite was applied as an effective and recyclable heterogeneous catalyst for 1,3-dipolar cycloaddition reactions between terminal alkynes and azides to prepare 1,2,3-triazoles under an environmentally friendly reaction conditions. The substituted triazoles were produced of various aryl and benzyl azides using a catalytic amount of this composite as efficient, stable, and air- and moisture-tolerant catalyst in excellent yields in water at room temperature. These PVA-stabilized Cu2O particles could be recovered in a facile manner from the reaction mixture and reused several times without any loss of catalytic activity.

Rhenium(I) polypyridine dibenzocyclooctyne complexes as phosphorescent bioorthogonal probes: Synthesis, characterization, emissive behavior, and biolabeling properties

We report the development of rhenium(I) polypyridine complexes appended with a dibenzocyclooctyne (DIBO) moiety as bioorthogonal probes for azide-modified biomolecules. Three phosphorescent rhenium(I) polypyridine DIBO complexes [Re(N^N)(CO)3(py-C6-DIBO)][CF3SO3] (py-C6-DIBO=3-(N-(6-(3,4:7,8-dibenzocyclooctyne-5-oxycarbonylamino)hexyl)aminocarbonyl)pyridine; N^N=1,10-phenanthroline (phen) (1a), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen) (2a), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen) (3a)) and their DIBO-free counterparts [Re(N^N)(CO)3(py-C6-BOC)][CF3SO3] (py-C6-BOC=3-(N-(6-(tert-butoxycarbonylamino)hexyl)aminocarbonyl)pyridine; N^N=phen (1b), Me4-phen (2b), Ph2-phen (3b)) were synthesized and characterized. Upon photoexcitation, all the complexes displayed intense and long-lived yellow triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Re)→π*(N^N)) emission. The DIBO complexes underwent facile reactions with benzyl azide in methanol at 298K with second-order rate constants (k2) in the range of 0.077 to 0.091M−1s−1. As revealed from SDS-PAGE analysis, the DIBO complexes can selectively label azide-modified proteins and the resulting bioconjugates displayed strong phosphorescence upon photoexcitation. Results of inductively coupled plasma mass spectrometry (ICP-MS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that the DIBO complexes accumulated in Chinese Hamster Ovary (CHO) cells with considerable cytotoxic activity. Upon incubation of CHO cells with these complexes, relatively weak intracellular emission was observed. In contrast, upon pretreatment of the cells with 1,3,4,6-tetra-O-acetyl-N-azidoacetyl-d-mannosamine (Ac4ManNAz), intense emission was observed from the cell membrane and some internal compartments. The results suggest that the DIBO complexes are promising candidates for imaging azide-labeled biomolecules.

ChemInform Abstract: C—H Activation Guided by Aromatic N—H Ketimines: Synthesis of Functionalized Isoquinolines Using Benzyl Azides and Alkynes.

AbstractRu‐catalyzed generation of N—H ketimines [cf.(II)] followed by a Rh‐catalyzed anellation with alkynes allows the preparation of a broad spectrum of isoquinolines bearing various functionalities including 1‐alkoxy derivatives.

ChemInform Abstract: Efficient Synthesis and Antibacterial Activities of Some Novel 1,2,3‐Triazoles Prepared from Propargylic Alcohols and Benzyl Azides.

AbstractDerivative (IIIh) exhibits good antibacterial activities.

Synthesis, QSAR and anticandidal evaluation of 1,2,3-triazoles derived from naturally bioactive scaffolds

In the present study, we used eight natural precursors (1a-h) with most of them having promising antimicrobial activities and synthesised their novel 1,2,3-triazole derivatives (3a-h). In the reaction sequences, the precursor compounds (1a-h) were converted to their respective alkyne (2a-h) followed by addition of benzyl azide freshly prepared by the reaction of benzyl bromide with sodium azide using [3 + 2] azide-alkyne cycloaddition strategy. Structural elucidation of all the triazole derivatives was done using FT-IR, 1H, 13C NMR, mass and elemental analysis techniques. The single crystal X-ray diffraction for 3d was also recorded. The result of in vitro anticandidal activity performed against three different strains of Candida showed that compound 3e was found superior/comparable to fluconazole (FLC) with IC50 values of 0.044 μg/mL against Candida albicans (ATCC 90028), 12.022 μg/mL against Candida glabrata (ATCC 90030), and 3.60 μg/mL against Candida tropicalis (ATCC 750). Moreover, at their IC50 values, compounds 3e and 3h showed <5% hemolysis which indicates the non-toxic behaviour of these inhibitors. Cytotoxicity assay was also performed on VERO cell line and all the derivatives were found non-toxic up to the concentration of 10.0 μg/mL. The in silico technique of 3D-QSAR was applied to establish structure activity relationship of the synthesized compounds. The results reveal the molecular fragments that play an essential role in improving the anticandidal activity.

Regioselective Synthesis of 1,5-Disubstituted 1,2,3-Triazoles by Reusable AlCl3 Immobilized on γ-Al2O3

There is rapidly growing interest in the synthesis and use of substituted 1,2,3-triazoles. We report an easy and interesting procedure that demonstrates the effectiveness of surface-modified γ-Al2O3, which is reusable, efficient, catalytic, safe, and environmentally acceptable for the regioselective synthesis of 1,5-disubstituted-1,2,3-triazoles via [3 + 2] cycloaddition of phenyl and benzyl azides with a series of aryl nitroolefins in good yields. No adverse effect on substituents such as nitro, cyano, hydroxy, ether linkage, and halogens was observed. The catalyst could easily be recycled and was reused for nine runs without losing its activity.

Double [3,3]-sigmatropic rearrangement in the enzymatic dioxygenation of benzyl azide: preparation of novel synthetically valuable azido-diols.

Enzymatic dioxygenation of benzyl azide by toluene dioxygenase produces the expected enantiopure cis-cyclohexadienediol along with an exocyclic diene formed by a spontaneous sequence of two [3,3] sigmatropic shifts. This novel dienediol presents high synthetic potential for natural product synthesis. The sigmatropic rearrangements can be reversed by protection of the diol moiety. An optimized production protocol for either of these valuable diols is presented.

Copper promoted synthesis of substituted quinolines from benzylic azides and alkynes

A novel method for the synthesis of substituted quinolines from benzylic azides and internal alkynes using Cu(OTf)2is described. The reaction features a broad substrate scope, high product yields and excellent regioselectivity.

Ionic liquid-supported benzyl azide: an efficient soluble scavenger for alkynes

An ionic liquid functionalized with benzyl azide was synthesized and its synthetic utility was evaluated by scavenging excess alkynes in the synthesis of 2,4-disubstituted quinoline via the Povarov reaction.

On terminal alkynylcarbinols and derivatization thereof

The chemistry of three prototypes of secondary alkynylcarbinols (ACs), recently highlighted as challenging targets in anti-tumoral medicinal chemistry, is further documented by results on n-alkyl, alkynyl and alkenyl representatives. The N-naphthyl carbamate of an n-butyl-AC is thus characterized by X-ray crystallography. A novel dialkynylcarbinol (DAC) with synthetic potential is described, namely the highly dissymmetrical triisopropylsilyl-protected version of diethynylmethanol. The latter is shown to act as a dipolarophile in a selective Huisgen reaction with benzyl azide under CuAAC click conditions, giving an alkenyl-AC, where the alkene unsaturation is embedded in a 1,4-disubstituted 1,2,3-triazole ring, as confirmed by X-ray crystallography.

High pressure Raman scattering and synchrotron X-ray diffraction studies of benzyl azide.

Benzyl azide was investigated by high-pressure Raman scattering spectroscopy and X-ray diffraction technologies. A complete vibrational analysis of benzyl azide was performed by combining the experimental measurements and theoretical calculations using DFT-based scaled quantum chemical approach. The high-pressure Raman spectra and calculation results indicate that benzyl azide underwent a conformational change at 0.67 GPa accompanied by rotation of methylene group and azide group. The frequency of the CH2 bending mode decreases with increasing pressure due to the increase of the C-H···π interactions, which is similar to the role of the hydrogen bond. A liquid to solid phase transition occurred at 2.7 GPa, which was confirmed by the X-ray diffraction measurements. As the pressure reached 25.6 GPa, all the azide group vibrations vanished, indicating that the decomposition pressure of the molecular azide groups in organic azides is lower than that of the azide ions in inorganic azides.