Aromatic Azides Research Articles

O,o-Difluorination of aromatic azide yields a fast-response fluorescent probe for H2S detection and for improved bioorthogonal reactions.

The development of efficient bioorthogonal reactions for sensing of endogenous biomolecules and for bioconjugation should be of paramount importance in the field of chemical biology. In this work, the o,o'-difluorinated aromatic azide was firstly employed to develop a new fast-response fluorescent probe 1 for H2S detection and for bioorthogonal reactions. Compared with non- and mono-fluorinated probes, 1 showed faster reaction toward H2S, the third gasotransmitter, in buffer (pH 7.4), implying that the reaction rate could be enhanced by the dual-fluorine groups. Furthermore, such enhanced reaction rates of 1 were also observed in the Staudinger reaction and strain-promoted azide-alkyne cycloaddition (SPAAC) based on the comparison studies of the non-fluorinated probe. Our results firstly highlight that the o,o'-difluorinated aromatic azide group should be useful for fast bioorthogonal reactions and H2S detection.

ChemInform Abstract: Synthesis of 3,4,5‐Trimethoxybenzene Derivatives with Substituted Triazole Group by Huisgen 1,3‐Cycloaddition and Their Inhibitory Effects on 3T3‐L1 Adipocyte Differentiation.

AbstractTriazole derivatives are synthesized by Huisgen 1,3‐cycloaddition of aromatic azides with various alkynes.

Synthesis and antimicrobial evaluation of ester-linked 1,4-disubstituted 1,2,3-triazoles with a furyl/thienyl moiety.

Twenty ester-linked 1,4-disubstituted 1,2,3-triazoles having a furyl/thienyl moiety have been synthesized from heteroaryl prop-2-yn-1-yl carboxylate and aromatic azides via a Cu(I) catalyzed 1,3-dipolar cycloaddition. All the synthesized compounds were characterized by FTIR, [Formula: see text]H NMR, [Formula: see text]C NMR spectroscopy and HRMS. Synthesized triazoles were tested in vitro for antimicrobial evaluation against Gram-negative bacteria-Escherichia coli, Enterobacter aerogenes and Klebsiella pneumoniae; Gram-positive bacteria-Staphylococcus aureus and two fungal strains-Candida albicans and Aspergillus niger, reflecting moderate to good activity. The structure of compound 6f was also confirmed by X-ray crystallography (CCDC 1469326).

Thermal decomposition of 2,4,6-triazidopyridine

The thermal decomposition of 2,4,6-triazidopyridine in the melt is studied using thermogravimetry, manometry, mass spectrometry, and IR spectroscopy. In the temperature range of 120–160°C, the process obeys the first-order kinetic law, being described by the Arrhenius equation k [s–1] = 1012.8 ± 0.4exp[–(31200 ± 1500)]/RT with values of the parameters typical of the thermal decomposition of aromatic and heterocyclic azides. The reaction produces nitrogen, as the only gaseous product. Unlike the other heterocyclic azides, the decomposition of which is characterized by anomalously high values of the Arrhenius parameters, the thermal decomposition of 2,4,6-triazidopyridine yields a condensed product having a system of polyconjugated bonds with higher force characteristics. It is concluded that the decomposition of 2,4,6-triazidopyridine proceeds by a mechanism in which the rate-limiting step is the dissociation of the nitrogen molecule from the azide group to form a nitrene.

ChemInform Abstract: A Novel Copper‐Catalyzed Preparation of Pyrido[1,2‐a]pyrimidine Derivatives

Abstractstarting from aminopropynylpyridinium bromide derivatives and aromatic sulfonyl azides involving a novel application of ketenimines

Efficient chemoselective hydrogenation of organic azides catalyzed by palladium nanoparticles with alkyne-derived homogeneous supports

Catalytic chemoselective hydrogenation of organic azides using palladium nanoparticles stabilized by alkyne derivatives was studied. A broad range of aromatic and aliphatic azides were smoothly reduced to the corresponding amines in excellent yields with a quite small amount of the catalyst. Hydrogenation of 3-phenylpropylazide gave 3-phenylpropylamine almost quantitatively with a substrate-to-palladium molar ratio (S/Pd) of 12,900 under 8atm of H2. The reaction under 1atm of H2 also proceeded smoothly with an S/Pd of 1000. Several reduction-sensitive functional groups, such as carbonyl, halide, benzylic OH, and aliphatic nitro were well tolerated under the reaction conditions.

ChemInform Abstract: Photochemical Synthesis of Azaheterocycles

AbstractReview: [66 refs.

Microwave-assisted synthesis, anti-inflammatory and anti-proliferative activities of new maslinic acid derivatives bearing 1,5- and 1,4-disubstituted triazoles

In this work, 40 analogs with a natural maslinic acid core (from Olea europaea L.) and various aromatic azides were synthesized. A regiospecific, facile and practical synthesis of 1,5-triazolyl derivatives by Ru(II)-catalyzed azide-alkyne cycloaddition (RuAAC), and mono-, bis- and tri-1,4-triazolyl derivatives by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) was described. All the reactions were assisted by microwave irradiation avoiding toxic reagents and solvents. The new products were obtained from the reaction mixture by simple purification in almost quantitative yields and the reaction times were in general shorter than those reported in the literature. Their chemical structures were elucidated on the basis of extensive spectroscopic methods including ESI-HRMS, 1D and 2D-NMR. Most of the compounds were evaluated for their anti-inflammatory activity using LPS-stimulated human peripheral blood mononuclear cells (PBMCs) and antiproliferative effects towards cultured murine EMT-6 (Breast) and human SW480 (colon) cancer cell lines.

Photochemical Synthesis of Azaheterocycles

Synthetic organic photochemistry is a field that continues to offer unique routes to organic structures not typically accessed from thermal reactions. In this review, the photochemical synthesis of five-, six-, seven-, and eight-membered-ring azaheterocycles, as well as some aza-macrocycles, is discussed. The discussion will focus on methods where heterocycle formation occurs during or as a result of a photochemical event. Reaction mechanisms will be discussed also, as these provide a rationale for understanding the synthetic results. 1 Introduction 2 Five-Membered Rings 2.1 Cyclization Reactions 2.2 Cycloadditions 2.3 From Aromatic and Vinyl Azides 2.4 earrangements 2.5 Other Individual Methods 3 Six-Membered Rings 3.1 Cyclization Reactions 3.2 Isocyanide Insertions 3.3 Cycloadditions 4 Seven-Membered Rings and Larger 5 Conclusion

Pd/C Catalyzed Carbonylation of Azides in the Presence of Amines.

A facile and efficient Pd/C-catalyzed carbonylation of both aliphatic and aromatic azides in the presence of amines is reported. Serving as the widely existed fragments in an array of biological pharmaceuticals, functionalized unsymmetrical ureas were straightforwardly synthesized by using readily available and cheap azides with amines under CO atmosphere, with the extrusion of N2 as the only byproduct. It was found that not only aryl azides but also benzyl and alkyl azides were suited for this methodology. Another feature of this procedure was the employment of a highly efficient palladium charcoal catalytic system.

A Novel Copper-Catalyzed Preparation of Pyrido[1,2-a]pyrimidine Derivatives

A copper-catalyzed reaction of 2-amino-1-(prop-2-yn-1-yl)pyridinium bromide derivatives and aromatic sulfonyl azides has been demonstrated under mild condition.

Regiospecific synthesis by copper- and ruthenium-catalyzed azide–alkyne 1,3-dipolar cycloaddition, anticancer and anti-inflammatory activities of oleanolic acid triazole derivatives

The oleanolic acid (1), a natural pentacyclic triterpenoid, was quantitatively isolated from pomace olive (Olea europaea L.) under ultra-sonication conditions (6.8g (3.4mg/gDW)). Two series of oleanolic acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethylester 6a–g and new oleanolic acid-1-phenyl-1H-[1,2,3]triazol-5-ylmethylester 7a–g congeners have been designed and synthesized in an attempt to develop potent anticancer and anti-inflammatory agents. A facile and regiospecific synthesis of 1,2,3-triazoles catalyzed by Cu(I) (CuAAC) or Ru(II) (RuAAC) and conducted under microwave conditions of oleanolic acid–alkyne derivative 5 with various aromatic azides 2a–g afforded a series of 1,4- and 1,5-triazolyl derivatives, respectively. Their structures were confirmed by using 1H NMR, 13C NMR, NOESY and HRMS analysis. Most of the compounds were evaluated for their anticancer and anti-inflammatory activities. Oleanolic acid 1 exhibited promising anticancer activity against murine breast (EMT-6) and human colon (SW480) cancer cells. Its derivatives 6b and 6c (1,4-regioisomers) and 7b (1,5-regioisomer) were found to be anti-cancer agents. On the other hand, only 6b displays anti-inflammatory activity.

Efficient synthesis of novel 1,2,3-triazole-linked quinoxaline scaffold via copper-catalyzed click reactions

New 1,2,3-triazoles-linked quinoxaline, were prepared by the reaction of 2-chloro-3-(prop-2-ynyloxy)quinoxaline or 2,3-bis(prop-2-ynyloxy)quinoxaline with aromatic azides via copper-catalyzed click reactions in the presence of the Schiff base ligands.

Anticancer Evaluation of Tris(triazolyl)triazine Derivatives Generated via Click Chemistry

Click chemistry has been utilised for the preparation of new tris(triazolyl)triazines containing aliphatic and polar side chains through coupling of 2,4,6-triethynyl-[1,3,5]triazines, which possess free terminal alkyne moieties with substituted aromatic azides. The cytotoxic activity and in vitro anticancer potential of the newly synthesised compounds have been evaluated against seven human cancer cell lines including liver HepG2, breast MCF-7, lung A549, acute myeloid leukemia HL-60, colon HCT116, and prostate PC3 cancer cell lines in addition to human normal melanocyte, HFB4. The results revealed that all the compounds did not exhibit any activity against A549, HL-60, and PC3. However compound G2 was effective against MCF-7 and HepG2 cancer cell lines. On the other hand, compound G1a exhibited higher potency against MCF-7 and HepG2 cells with no toxicity on normal cells in comparison with the standard drug doxorubicin.

Alkaloids of the Flora of Siberia and Altai. XXI.* 5′-(1,2,3-Triazolyl)-Substituted Lappaconitine Derivatives

New derivatives of the diterpene alkaloid lappaconitine containing a 1H-substituted 1,2,3-triazol-4-yl substituent in the anthranilate C-5 ′ -position were synthesized via the reaction of 5 ′ -ethynyllappaconitine with aromatic or aliphatic azides in the presence of aqueous CuSO4 and sodium ascorbate in DMF. The yields of the 1,4-disubstituted 1,2,3-triazoles were 40–73% and depended on the nature of the azide.

Synthesis and antimicrobial evaluation of 1,4-disubstituted 1,2,3-triazoles containing benzofused N-heteroaromatic moieties

Synthesis of a small library of 1,4-disubstituted 1,2,3-triazoles containing benzofused N-heteroaromatic moieties was carried out through click reaction of various benzofused N-heteroaromatic alkynes with aromatic azides. All the synthesized compounds were characterized by spectroscopic techniques like IR, 1H NMR, 13C NMR, mass spectrometry and evaluated in vitro for antimicrobial activity against two Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus), one Gram-negative bacteria (Escherichia coli) and two fungi (Candida albicans, Aspergillus niger). Most of the synthesized 1,4-disubstituted 1,2,3-triazoles were found to possess significant antibacterial and antifungal activity against tested microbial species. Moreover, docking simulation of the compound 1-[(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl]-1H-benzo[d]imidazole was also carried out against E. coli topoisomerase II DNA gyrase B enzyme to study the binding modes and mechanism of action.

CuO nanoparticles: synthesis and application as an efficient reusable catalyst for the preparation of xanthene substituted 1,2,3-triazoles via click chemistry

Copper(II) oxide (CuO) nanoparticles have been found to be an efficient catalyst for 1,3-dipolar cycloaddition (CuAAC) of aromatic azides and acetylenic xanthenes furnishing the corresponding xanthene substituted triazoles in excellent yields. CuO nanoparticles have been synthesized from copper acetate by simple co-precipitation method and characterized by scanning electron microscope, energy dispersive X-ray analysis, transmission electron microscope, and X-ray diffraction analysis. The salient features of the present protocol are mild reaction conditions, shorter reaction time, reusability of the catalyst, and applicability to a wide range of substrates.

Highly Conductive Aromatic Functionalized Multi-Walled Carbon Nanotube for Inkjet Printable High Performance Supercapacitor Electrodes.

We report the functionalization of multiwalled carbon nanotubes (MWCNT) via the 1,3-dipolar [3+2] cycloaddition of aromatic azides, which resulted in a detangled CNT as shown by transmission electron microscopy (TEM). Carboxylic moieties (-COOH) on aromatic azide result in highly stable aqueous dispersion (max. conc. ~ 10 mg/mL H2O), making the suitable for inkjet printing. Printed patterns on polyethylene terephthalate (PET) flexible substrate exhibit low sheet resistivity ~65 Ω. cm, which is attributed to enhanced conductivity. Fabricated Supercapacitors (SC) assembled using these printed substrates exhibit good electrochemical performance in organic as well as aqueous electrolytes. High energy and power density (57.8 Wh/kg and 0.85 kW/kg) in 1M H2SO4 aqueous electrolyte demonstrate the excellent performance of the proposed supercapacitor. Capacitive retention varies from ~85–94% with columbic efficiency ~95% after 1000 charge/discharge cycles in different electrolytes, demonstrating the excellent potential of the device for futuristic power applications.

Application of the Thioacid‐Azide Ligation (TAL) for the Preparation of Glycosylated and Fluorescently Labeled Amino Acids

AbstractThe reaction of thiocarboxylic acids with azides (thioacid‐azide ligation, TAL) is a chemoselective transformation, leading to the formation of amide bonds. Especially in the case of electron‐deficient sulfonyl azides, the reaction occurs in excellent yields, within minutes at room temperature, in a broad range of solvents. In this article, the application of TAL for the synthesis of glycosylated and dansylated amino acids is reported. 2‐Azidosulfonylethyl glycosides were prepared from peracetylated monosaccharides and reacted with thioacid‐containing derivatives of aspartic acid and glutamic acid. Likewise, aromatic sulfonyl azides were employed. Ligation products were obtained in yields of up to 96 %. Different conditions for the generation of the thioacids were compared. Whereas reaction of succinimidyl esters with sodium hydrogen sulfide led to concomitant formation of diacyl disulfides, trityl thioesters turned out to be suitable precursors for the in situ preparation of thioacids by mild acidolysis.

Design, Synthesis and Biological Evaluation of Novel Fluorinated Heterocyclic Hybrid Molecules Based on Triazole & Quinoxaline Scaffolds Lead to Highly Potent Antimalarials and Antibacterials

A series of novel fluorinated heterocyclic hybrid molecules based on triazole & quinoxaline scaffold were designed, synthesized and evaluated for inhibition of Plasmodium falciparum, a virulent human malaria parasite. Mono and bis triazole tagged quinoxaline analogs were synthesized by propargylation of 6-amino quinoxaline followed by click reaction with various substituted aromatic azides under uncertain reaction conditions. The newly synthesized molecules were assessed for antimalarial activity and three of the analogs were identified as promising leads which killed parasites with IC50 values <10 μM and showed 27-70 selective indices. Keywords: Antimalarials, click reaction, hybrid molecules, plasmodium, quinoxalines, triazoles.