Aromatic Azides Research Articles

A simple one-pot preparation of 3,3a-dihydro-5H-pyrano[3,3a-c]isoxazol-5-ylideneethanal from 4-vinyloxyphenyl azide: an example of aromatic azide photooxidation for the synthesis of nitrogen-containing heterocyclic compounds

Photolysis of 4-vinyloxyphenyl azide in the presence of oxygen in acetonitrile leads to the formation of a fused heterocyclic compound due to the ability of the intermediates of this reaction to undergo a unique domino reaction sequence. The rate constants and activation parameters of some elementary stages of the process are measured by flash photolysis.

Synthesis of 1,5-regioregular polytriazoles by efficient NMe4OH-mediated azide–alkyne click polymerization

The efficient and regioselective NMe4OH-mediated aromatic azide and alkyne click polymerization to generate 1,5-regioregular polytriazoles was successfully established.

On the photonics of aromatic azide molecules

Energies of electronically excited states of a number of aromatic azides have been calculated using ab initio quantum-chemical methods. It has been shown that the relative arrangement of the singlet and triplet states of the A′ and A″ types changes with an increase in the number of π electrons in the system. As in the case of other classes of heteroaromatic molecules, five relative locations of these states are possible. On this basis, the dependence of the luminescent and photochemical properties of molecules of aromatic azides on their chemical structure has been rationalized.

O-Fluorination of aromatic azides yields improved azido-based fluorescent probes for hydrogen sulfide: synthesis, spectra, and bioimaging.

Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule with multiple biological functions. To visualize the endogenous in situ production of H2S in real time, new coumarin- and boron-dipyrromethene-based fluorescent turn-on probes were developed for fast sensing of H2S in aqueous buffer and in living cells. Introduction of a fluoro group in the ortho position of the aromatic azide can lead to a greater than twofold increase in the rate of reaction with H2S. On the basis of o-fluorinated aromatic azides, fluorescent probes with high sensitivity and selectivity toward H2S over other biologically relevant species were designed and synthesized. The probes can be used to in situ to visualize exogenous H2S and D-cysteine-dependent endogenously produced H2S in living cells, which makes them promising tools for potential applications in H2S biology.

Synthesis and antiproliferative activity of 8-hydroxyquinoline derivatives containing a 1,2,3-triazole moiety

Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by performing copper-catalyzed Huisgen 1,3-dipolar cycloaddition (“click” reaction) between an 8-O-alkylated-quinoline containing a terminal alkyne and various aromatic or protected sugar azides. These compounds were evaluated in vitro for their antiproliferative activity on various cancer cell types. Protected sugar derivative 16 was the most active compound in the series, exhibiting potent antiproliferative activity and high selectivity toward ovarian cancer cells (OVCAR-03, GI50 < 0.25 μg mL−1); this derivative was more active than the reference drug doxorubicin (OVCAR-03, GI50 = 0.43 μg mL−1). In structure–activity relationship (SAR) studies, the physico-chemical parameters of the compounds were evaluated and docking calculations were performed for the α-glucosidase active site to predict the possible mechanism of action of this series of compounds.

Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid

Dehydroabietic acid (DHA) is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid), and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol), four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells. Better antiproliferative effect was found for compound 5, with an IC50 of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC50 of etoposide, was 1.83 µM.

ChemInform Abstract: Facile Synthesis of Unsymmetrical Acridines and Phenazines by a Rh(III)‐Catalyzed Amination/Cyclization/Aromatization Cascade.

We report formal [3 + 3] annulations of aromatic azides with aromatic imines and azobenzenes to give acridines and phenazines, respectively. These transformations proceed through a cascade process of Rh(III)-catalyzed amination followed by intramolecular electrophilic aromatic substitution and aromatization. Acridines can be directly prepared from aromatic aldehydes by in situ imine formation using catalytic benzylamine.

ChemInform Abstract: A Simple and Effective Synthesis of Aryl Azides via Arenediazonium Tosylates.

Aromatic azides are formed in high yield from arenediazonium tosylates and sodium azide in water at room temperature or from aromatic amines via diazotization in the presence of p-TsOH. Besides being experimentally simple, these methods do not require any metal catalysis and provide clean products without purification.

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.

Thermolysis of 3-Azido-N-Phenylthieno-[2,3-b]pyridine-2-Carboxamides

Annelated 1,4-diazepines are of interest as they are often compounds possessing different forms of biological and pharmacological activity [1]. Many methods for the synthesis of diazepines have been reported up until now, but the search for novel methods still of interest for scientific community. One of the known methods for closing a diazepine ring is the intramolecular transformation of aromatic azides. The formation of the diazepine ring occurs via photolysis of azides [2] or by an intramolecular cycloaddition of the azide group at a carbon–carbon multiple bond [3-6]. Continuing our study on the synthesis of 1,4-diazepines condensed with a thienopyridine fragment [7] we have developed a method for the preparation of polycyclic 1,4-diazepine derivatives based on the thermal decomposition of thieno[2,3-b]pyridine azides 2a-c. We have selected the N-phenyl-substituted tertiary 3-aminothieno[2,3-b]pyridine-2-carboxamides 1a-c as starting materials and carried out successive diazotization and azide formation reactions to give the corresponding azides 2a-c.

Facile synthesis of unsymmetrical acridines and phenazines by a Rh(III)-catalyzed amination/cyclization/aromatization cascade.

We report formal [3 + 3] annulations of aromatic azides with aromatic imines and azobenzenes to give acridines and phenazines, respectively. These transformations proceed through a cascade process of Rh(III)-catalyzed amination followed by intramolecular electrophilic aromatic substitution and aromatization. Acridines can be directly prepared from aromatic aldehydes by in situ imine formation using catalytic benzylamine.

A Simple and Effective Synthesis of Aryl Azides via Arenediazonium Tosylates

Aromatic azides are formed in high yield from arenediazonium tosylates and sodium azide in water at room temperature or from aromatic amines via diazotization in the presence of p-TsOH. Besides being experimentally simple, these methods do not require any metal catalysis and provide clean products without purification.

1,2,3-triazole-substituted oleanolic Acid derivatives: synthesis and antiproliferative activity.

Hybrid compounds are relevant products when searching for structure-activity relationships of natural products. Starting from the naturally occurring triterpene oleanolic acid, alkyl esters were prepared and treated with different aromatic azides using click chemistry to produce hybrid compounds. Some 18 new oleanolic acid derivatives were synthesized and the structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new derivatives was evaluated towards normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), promyelocytic leukemia (HL-60), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells. The alkyne esters 1 and 3 showed activity on all cell lines but without selectivity (19.6–23.1 μM and 14.1–56.2 μM, respectively), their respective methyl esters were inactive. Compounds with a benzene and p-anisole attached to the triazole ring, showed no antiproliferative effect. Introduction of a chlorine atom into the benzene ring (compound 9) elicited a selective effect against AGS cells (IC50 value: 8.9 μM). The activity was lost when the COOH function at C-28 was methylated. Better antiproliferative effect was found for compounds 11 and 15 bearing a p-toluenesulphonyl group, with values in the range of 10.8–47.1 μM and 11.5–22.2 μM, respectively. The effect, however, was not associated with selectivity.

Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents

A series of ursolic acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethylester congeners have been designed and synthesized in an attempt to develop potent antitumor agents. A regioselective approach using Huisgen 1,3-dipolar cycloaddition reaction of ursolic acid-alkyne derivative with various aromatic azides was employed to target an array of triazolyl derivatives in an efficient manner. Their structures were confirmed by using 1H NMR, 13C NMR, IR and MS analysis. All the compounds were evaluated for anti-cancer activity against a panel of four human cancer cell lines including A-549 (lung), MCF-7 (breast), HCT-116 (colon), THP-1 (leukemia) and a normal human epithelial cell line (FR-2) using sulforhodamine-B assay. The pharmacological results showed that most of the compounds displayed high level of antitumor activities against the tested cancer cell lines compared with ursolic acid. Compounds 7b, 7g, 7p and 7r were found to be the most potent compounds in this study.

Efficient synthesis of solid-emissive Boron–Fluorine derivatives

A highly solid-emissive Boron–Fluorine scaffold with two conjugated alkyne groups (BOPIM-S) is facilely synthesized, which shows enhanced fluorescent intensity compared to the BOPIM dye without alkyne units. According to X-ray single crystal analysis, the terminal alkyne groups interact with atoms B, F, C and N on neighbouring molecules, producing a rigid rectangular structure, which helps to avoid energy loss via non-irradiative decay. Furthermore, BOPIM-S can undergo copper catalysed alkyne–azide-cycloaddition (CuAAC) chemistry with aromatic azides to produce conjugated molecules with high yields. According to absorption and fluorescent measurements, all these compounds synthesized by CuAAC emit large Stokes shift (over 100 nm) both in solution and in solid state. But the electronic environments of terminal aromatic rings slightly affect their photophysical properties.

3D photografting with aromatic azides: A comparison between three-photon and two-photon case

Photografting is a method utilizing light activation for covalent incorporation of functional molecules into a polymer surface or polymer matrix. It has been widely applied as a simple and versatile method for tailoring physical–chemical properties of various surfaces. Grafting induced via multi-photon absorption provides additional advantages of spatial and temporal control of the process. Here, a novel fluoroaryl azide photografting compound (AFA) was synthesized and compared with the commercially available azide BAC-M. Using Z-scan technique, it was determined that AFA is a two-photon absorber at 798nm, whereas BAC-M is a three-photon absorber at this wavelength. Both azides were employed for 3D photografting within a PEG-based matrix using femtosecond laser pulses. Both Z-scan measurements and 3D photografting tests indicated that, the intensity threshold for nonlinear absorption and photografting process is lower for AFA. As a result the processing window of AFA is much broader than that of BAC-M. But on the other hand, since BAC-M is characterized by the three-photon absorption (3PA) process, patterns with finer features can be produced using this molecule. The choice of the appropriate compound for 3D grafting will depend on the final application and the requirements associated with the resolution and post-modification protocol.

Synthesis and Properties of Porous Organic Polymers from a Rigid Macrocyclic Building Block

AbstractTwo rigid macrocyclic CTV‐based porous organic polymers, Click‐POP‐1 and Click‐POP‐2, have been synthesized by Click reaction of a cyclotriveratrylene analogue with alkyne groups and aromatic azides in one pot. FTIR, solid 13C NMR and elemental analysis confirmed the formation of the polymers. Both of them possess high thermo‐stability which is up to 410 and 900°C, respectively, and moderate hydrogen storage properties with 0.46 wt% at 77 K. Their nitrogen uptake showed type‐I isotherm with BET surface areas up to 342 and 317 m2·g−1.

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.

Continuous process for click reactions using glass micro-reactor functionalized with β-cyclodextrin

A micro-reactor based on glass micro-chip functionalized with β-cyclodextrin was prepared and used to develop a flow process for click reactions of aromatic azides and acetylenes. Products with 97–99% yield were obtained within a few minutes. Modified surface remained stable and almost no degradation was observed after 50h of continuous use.

Synthesis of nitrogen-containing heterocyclic compounds by photooxidation of aromatic azides

It is shown that the photolysis of certain aromatic azides in the presence of oxygen leads to the formation of nitrogen-containing heterocyclic compounds via a domino reaction sequence.