Azide Precursor Research Articles

Nitrene-functionalized ruthenium nanoparticles

Ruthenium nanoparticles protected by ruthenium–nitrene π bonds were prepared by refluxing “bare” ruthenium colloids (2.12 ± 0.72 nm in diameter) and 4-dodecylbenezenesulfonyl azide in sec-butylbenzene. Thermogravimetric analysis (TGA) of the resulting nanoparticles showed that on average there were about 84.1 ligands on the nanoparticle surface. XPS studies showed a 1:1 atomic ratio between nitrogen and sulfur, consistent with the formation of nitrene fragments by the thermal decomposition of the azide precursors. In addition, the binding energies of Ru3d and N1s electrons suggested a covalent nature of the RuN interfacial linkage which appeared in FTIR measurements with a vibrational band at 1246 cm−1. Because of such conjugated bonding interactions, extensive intraparticle charge delocalization occurred, and the nanoparticle-bound nitrene moieties behaved analogously to azo derivatives, as manifested in UV-vis and fluorescence measurements. Further testimony of the formation of RuN interfacial linkages was highlighted in the unique reactivity of the nanoparticles with alkenes by imido transfer, which was evidenced in spectroscopic and electrochemical studies.

Fast dye salts provide fast access to azidoarene synthons in multi-step one-pot tandem click transformations

This study examined whether commercially available diazonium salts could be used as efficient aromatic azide precursors in one-pot multi-step click transformations. Seven different diazonium salts, including Fast Red RC, Fast Blue B, Fast Corinth V and Variamine Blue B were surveyed under aqueous click reaction conditions of CuSO 4/Na ascorbate catalyst with 1:1 t-BuOH/H 2O solvent. Two-step tandem reactions with terminal alkyne and diyne co-reactants led to 1,2,3-triazole products in 66–88% yields, while three-step tandem reactions with trimethylsilyl-protected alkyne and diyne co-reactants led to 1,2,3-triazole products in 61–78% yields.

Tridentate complexes of 2,6-bis(4-substituted-1,2,3-triazol-1-ylmethyl)pyridine and its organic azide precursors: an application of the copper(ii) acetate-accelerated azide–alkyne cycloaddition

Rapid coupling reactions between 2,6-bis(azidomethyl)pyridine and terminal alkynes in the presence of 5 mol% Cu(OAc)(2)·H(2)O without the addition of a reducing agent afford tridentate ligands for first-row transition-metal ions. The chelation between Cu(II) and alkylated nitrogen atoms of the azido groups of 2,6-bis(azidomethyl)pyridine, as observed in the solid state, is credited for the acceleration of the azide-alkyne cycloaddition reactions.

Multicomponent Synthesis of 1,2,3‐Triazoles in Water Catalyzed by Copper Nanoparticles on Activated Carbon

AbstractCopper nanoparticles on activated carbon have been found to effectively catalyze the multicomponent synthesis of 1,2,3‐triazoles from different azide precursors, such as organic halides, diazonium salts, anilines and epoxides in water. The first one‐pot transformation of an olefin into a triazole is also described. The catalyst is easy to prepare, very versatile and reusable at a low copper loading.

Exploring Drug Target Flexibility Using in Situ Click Chemistry: Application to a Mycobacterial Transcriptional Regulator

In situ click chemistry has been successfully applied to probe the ligand binding domain of EthR, a mycobacterial transcriptional regulator known to control the sensitivity of Mycobacterium tuberculosis to several antibiotics. Specific protein-templated ligands were generated in situ from one azide and six clusters of 10 acetylenic fragments. Comparative X-ray structures of EthR complexed with either clicked ligand BDM14950 or its azide precursor showed ligand-dependent conformational impacts on the protein architecture. This approach revealed two mobile phenylalanine residues that control the access to a previously hidden hydrophobic pocket that can be further exploited for the development of structurally diverse EthR inhibitors. This report shows that protein-directed in situ chemistry allows medicinal chemists to explore the conformational space of a ligand-binding pocket and is thus a valuable tool to guide drug design in the complex path of hit-to-lead processes.

Building Upon Patterned Organic Monolayers Produced via Catalytic Stamp Lithography

Soft lithographic sub-100 nm chemical patterning was demonstrated on organic monolayer surfaces using poly(dimethylsiloxane)-based stamps decorated with Pd nanostructures, structures termed "catalytic stamps". Chemically reactive azide or alkene functionalities were incorporated on oxide-capped silicon surfaces and utilized for patterning via Pd-catalyzed hydrogenation or Heck reactions. The catalytic stamps were soft lithographic stamps based on PDMS with embedded nanoscale palladium catalysts, prepared via block copolymer-based templating. Nanoscale chemical patterns were readily generated on the azide or alkene precursor surfaces simply by applying the Pd catalytic stamps and the reactive molecule, the molecular ink, to the surface, thanks to the highly localized catalytic transformations induced by the patterned, immobilized solid Pd catalysts. A series of successful postfunctionalization reactions on the resulting patterned surfaces further demonstrated the utility of this approach to construct novel designs of nanoarchitectures, with potentially unique and innovative properties.

Uranium azide photolysis results in C–H bond activation and provides evidence for a terminal uranium nitride

Uranium nitride [U[triple bond]N](x) is an alternative nuclear fuel that has great potential in the expanding future of nuclear power; however, very little is known about the U[triple bond]N functionality. We show, for the first time, that a terminal uranium nitride complex can be generated by photolysis of an azide (U-N=N=N) precursor. The transient U[triple bond]N fragment is reactive and undergoes insertion into a ligand C-H bond to generate new N-H and N-C bonds. The mechanism of this unprecedented reaction has been evaluated through computational and spectroscopic studies, which reveal that the photochemical azide activation pathway can be shut down through coordination of the terminal azide ligand to the Lewis acid B(C(6)F(5))(3). These studies demonstrate that photochemistry can be a powerful tool for inducing redox transformations for organometallic actinide complexes, and that the terminal uranium nitride fragment is reactive, cleaving strong C-H bonds.

A novel synthesis of 1,5-disubstituted fluorinated tetrazoles from 1,1-difluoroazides

A new one-step reaction between 1,1-difluoroazides and primary amines is reported as an efficient synthetic approach for tetrazole formation. Examples include the syntheses of fluorine-containing 1,5-substituted tetrazoles from three fluorinated azide precursors and various amines. Greater substituent diversity in comparison with conventional methods is achieved.

Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000

Several l-fucoglycolipids are associated with diseases such as cancer, cystic fibrosis and rheumatoid arthritis. Activation of iNKT cells is known to lead to the production of cytokines that can help alleviate or exacerbate these conditions. α-Galactosyl ceramide (α-GalCer) is a known agonist of iNKT cells and it is believed that its fucosyl counterpart might have similar immunogenic properties. We herein report the synthesis of α-l-fucosyl ceramide derivatives and describe their biological evaluation. The key challenge in the synthesis of the target molecules involved the stereoselective synthesis of the α-glycosidic linkage. Of the methods examined, the per-TMS-protected glycosyl iodide donor was completely α-selective, and could be scaled up to provide gram quantities of the azide precursor 11, from which a range of N-acylated α-l-fucosyl ceramides were readily obtained and evaluated for ex vivo expansion of human iNKT cells.

Tris(triazolyl)triazine via Click-Chemistry: A C3 Electron-Deficient Core with Liquid Crystalline and Luminescent Properties

The synthesis of a novel core based on tris(triazolyl)triazine has been accomplished by a one-pot procedure that combines a 3-fold deprotection of alkyne groups and "click chemistry" of the aromatic alkyne and azide precursors. The procedure is straightforward for the preparation of functional materials for organic electronics. Indeed, compounds with low reduction potential are obtained. These compounds also show liquid crystalline behavior, displaying columnar mesophases at room temperature, and are luminescent in the visible region both in solution and in thin films.

Synthesis of Amino‐Bridged Oligosaccharide Mimetics

AbstractSynthesis of amino‐bridged oligosaccharides using reductive amination opens rapid access to novel glycomimetic target structures as potential ligands for the receptor protein NKR P1 of natural killer cells. Emphasis was laid on fast and facile synthetic routes. The carbonyl building blocks were easily obtained by oxidation with Dess–Martin periodinane or iodoxybenzoic acid (IBX). For the required amino‐functionalized units, reduction of azide precursors was advantageous, and generation of the novel oligosaccharides was achieved by subsequent reductive amination. The target saccharide structures feature a bridging nitrogen atom inserted between two non‐anomeric positions as well as including one anomeric position.

“Four-Potential” Ferrocene Labeling of PNA Oligomers via Click Chemistry

The scope of the Cu(I)-catalyzed [2 + 3] azide/alkyne cycloaddition (CuAAC, click chemistry) as a key reaction for the conjugation of ferrocene derivatives to N-terminal functionalized PNA oligomers is explored herein (PNA: peptide nucleic acid). The facile solid-phase synthesis of N-terminal azide or alkyne-functionalized PNA oligomer precursors and their cycloaddition with azidoferrocene, ethynylferrocene, and N-(3-ethylpent-1-yn-3-yl)ferrocene-carboxamide (DEPA-ferrocene) on the solid phase are presented. While the click reaction with azidomethylferrocene worked equally well, the ferrocenylmethyl group is lost from the conjugate upon acid cleavage. However, the desired product was obtained via a post-SPPS conversion of the alkyne-PNA oligomer with azidomethylferrocene in solution. The synthesis of all ferrocene-PNA conjugates (trimer t(3)-PNA, 3, 4, 5, 6; 12mer PNA, 10 - t c t a c a a g a c t c, 11 - t c t a c c g t a c t c) succeeded with excellent yields and purities, as determined by mass spectrometry and HPLC. Electrochemical studies of the trimer Fc-PNA conjugates 3, 4, 5, and 6 with four different ferrocene moieties revealed quasi-reversible redox processes of the ferrocenyl redox couple Fc(0/+) and electrochemical half-wave potentials in a range of E(1/2) = -20 mV to +270 mV vs FcH(0/+) (Fc: ferrocenyl, C(10)H(9)Fe). The observed potential differences ΔE(1/2)(min) are always greater than 60 mV for any given pair of Fc-PNA conjugates, thus allowing a reliable differentiation with sensitive electrochemical methods like e.g. square wave voltammetry (SWV). This is the electrochemical equivalent of "four-color" detection and is hence denoted "four-potential" labeling. Preparation and electrochemical investigation of the set of four structurally different and electrochemically distinguishable ferrocenyl groups conjugated to PNA oligomers, as exemplified by the conjugates 3, 4, 5, and 6, demonstrates the scope of the azide/alkyne cycloaddition for the labeling of PNA with electrochemically active ferrocenyl groups. Furthermore, it provides a PNA-based system for the electrochemical detection of single-nucleotide polymorphism (SNP) in DNA/RNA.

Monosubstituted 1,2,3-triazoles from two-step one-pot deprotection/click additions of trimethylsilylacetylene

Two-step one-pot reaction conditions have been developed for synthesizing 1-substituted-1,2,3-triazoles. This transformation involves the base-catalyzed deprotection of trimethylsilylacetylene followed by Cu-catalyzed Huisgen 1,3-dipolar cycloaddition under aqueous reaction conditions. Utilization of potassium carbonate as the base and methanol as the alcoholic aqueous co-solvent resulted in optimal yields of the desired products. The reaction conditions were found to be successful for both alkyl and aryl azide reactants, including analogs with electron-donating and electron-withdrawing functionality. This procedure stands as a simple and regioselective means by which to prepare 1-substituted-1,2,3-triazole compounds directly from azide precursors.

Synthesis of a xylo-Puromycin Analogue

N 6 -Bis-demethylated xylo-puromycin analogue 2 was synthesized over six steps in 56% yield from adenosine 3, involving a Mattocks bromoacetylation, a regio- and stereoselective ribo-epoxide ring opening with sodium azide and an efficient Staudinger-Vilarrasa reaction to couple the amino acid to an azide precursor.

Selective Formation of Triplet Alkyl Nitrenes from Photolysis of β-Azido-Propiophenone and Their Reactivity

Photolysis of beta-azido propiophenone derivatives, 1, with built-in sensitizer units, leads to selective formation of triplet alkyl nitrenes 2 that were detected directly with laser flash photolysis (lambdamax = 325 nm, tau = 27 ms) and ESR spectroscopy (|D/hc| = 1.64 cm-1, |E/hc| = 0.004 cm-1). Nitrenes 2 were further characterized with argon matrix isolation, isotope labeling, and molecular modeling. The triplet alkyl nitrenes are persistent intermediates that do not abstract H-atoms from the solvent but do decay by dimerizing with another triplet nitrene to form azo products, rather than reacting with an azide precursor. The azo dimer tautomerizes and rearranges to form heterocyclic compound 3. Nitrene 2a, with an n,pi* configuration as the lowest triplet excited state of the its ketone sensitizer moiety, undergoes intramolecular 1,4-H-atom abstraction to form biradical 6, which was identified by argon matrix isolation, isotope labeling, and molecular modeling. beta-Azido-p-methoxy-propiophenone, with a pi,pi* lowest excited state of its triplet sensitizer moiety, does not undergo any secondary photoreactions but selectively yields only triplet alkyl nitrene intermediates that dimerize to form 3b.

Characterization of a Genuine Iron(V)−Nitrido Species by Nuclear Resonant Vibrational Spectroscopy Coupled to Density Functional Calculations

The characterization of high-valent iron species is of interest due to their relevance to biological reaction mechanisms. Recently, we have synthesized and characterized an [Fe(V)-nitrido-cyclam-acetato]+ complex, which has been characterized by Mössbauer, magnetic susceptibility data, and XAS spectroscopies combined with DFT calculations (Aliaga-Alcade, N.; DeBeer George, S.; Bill, E.; Wieghardt, K.; Neese, F. Angew. Chem., Int. Ed. 2005, 44, 2908-2912). The results of this study indicated that the [Fe(V)-nitrido-cyclam-acetato]+ complex is an unusual d3 system with a nearly orbitally degenerate S=1/2 ground state. Although the calculations predicted fairly different Fe-N stretching frequencies for the S=1/2 and the competing S=3/2 ground states, a direct experimental determination of this important fingerprint quantity was missing. Here we apply synchrotron-based nuclear resonance vibrational scattering (NRVS) to characterize the Fe-N stretching frequency of an Fe(V)-nitrido complex and its Fe(III)-azide precursor. The NRVS data show a new isolated band at 864 cm(-1) in the Fe(V)-nitrido complex that is absent in the precursor. The NRVS spectra are fit and simulated using a DFT approach, and the new feature is unambiguously assigned to a Fe(V)-N stretch. The calculated Fe-N stretching frequency is too high by approximately 75 cm(-1). Anharmonic contributions to the Fe-N stretching frequency have been evaluated and have been found to be small (-5.5 cm(-1)). The NRVS data provided a unique opportunity to obtain this vibrational information, which had eluded characterization by more traditional vibrational spectroscopies.

Crystal structure of 1-(2,3:5,6-Di-O-isopropylidene-β-D-mannofuranosyl)-1H-[1,2,3]triazol-4,5-dicarboxylic acid diethyl ester

The synthesis and X-ray crystal structure of 1-(2,3:5,6-di-O-isopropylidene-β-D-mannofuranosyl)-1H-[1,2,3]triazol-4,5-dicarboxylic acid diethyl ester are reported. It crystallizes in the orthorhombic system with space group P212121 (No. 19); a=8.6148(5), b=10.4793(6), c=24.6873(15) A and Z=4. The solid state structure verifies the β-anomeric form of the title compound and provides evidence for the structures of the azide and chloride precursors.

Solution−Liquid−Solid-Induced Tip-Growth of Filled-GaN Nanotubes on MCM-48 Microspheres

Using MCM-48 microspheres (MMS) as the support, GaN nanotubes, with branched tubules and encapsulated crystalline GaN nanoparticles, have been prepared by the reaction of GaCl3 with excess NaN3 in dry benzene solution. The key steps in our approach are as follows: (1) by stirring at low-temperature of 40 °C for 12 h, the starting materials are adsorbed on the MMS surface with the occurrence of in-situ gallium azide precursor; (2) at higher temperature, under the reduction of active sodium atoms (Na*) derived from the decomposition of surplus NaN3, liquid Ga droplets occur acting as catalytic centers for the growth of GaN nanotubes; (3) at the same time, small GaN nanoparticles, accompanying tube growth, are captured into the tube due to the capillarity-induced filling. Based on the solution−liquid−solid (SLS) model and hodograph concept, a SLS-induced tip-growth mechanism for the formation of filled-GaN nanotubes on MMS is proposed. The new nanostructures presented here enrich the nanoscale community with structural complexity and enable greater potential applications.

Spacer-separated sialyl LewisX cyclopeptide conjugates as potential E-selectin ligands

Completely protected sialyl LewisX azide was synthesized from a neolactosamine azide precursor carrying a 3- O-allyloxycarbonyl group as the temporary protecting group. After its Pd(0)-catalyzed deprotection and stereoselective α-fucosylation, the obtained LewisX azide was subjected to O-deacetylation in the galactose unit and subsequent regio- and stereoselective sialylation. Reduction of the anomeric azido group afforded the sialyl LewisX amine building block. Two molecules of this tetrasaccharide ligand were conjugated to a preformed cyclooctapeptide containing two equidistant l-asparagine units equipped with carboxy-terminated tetraethyleneglycol side chains to give, after deprotection, the target glycopeptide conjugate. Preliminary biological evaluation of the synthesized bivalent sialyl LewisX cyclopeptide conjugate showed only slightly enhanced inhibition of E-selectin binding in spite of the given flexibility of the two linked saccharide determinants.

Comparison of IR and UV cavity ring-down spectroscopy detection of transient intermediates: Pyrolysis of methyl azide to form methyleneimine

Mid-infrared cavity ring-down spectroscopy (CRDS) has been employed in this study to examine the hydride stretching region of methyl azide and its pyrolysis product methyleneimine. The absorption spectrum of methyl azide over 2835–3085 cm −1 was recorded, and the integrated absorption cross section was determined. The pyrolysis of methyl azide and subsequent production of methyleneimine was observed at various wavenumbers. Using IR CRDS, we were able to observe vibrational transitions of methyleneimine without interference from the methyl azide precursor. Our previous UV CRDS study showed that electronic transitions of methyleneimine overlapped with those of methyl azide. IR CRDS should thus be useful for the detection of polyatomic transient intermediates without interference from precursors.