Triazole Formation Research Articles

Azole‐Substituted Triazole Formation through Organocatalytic Cycloaddition of β‐keto Azoles and Aryl Azides

AbstractA highly efficient metal free regioselective approach for the synthesis of a novel azole substituted triazoles via organocatalytic [3+2] cycloaddition between β‐keto azoles and aryl azides at room temperature is reported. The proposed methodology is well tolerated with range of substituents in the β‐keto azoles and aryl azides with good to excellent yield (81–94 %) without column chromatography as purification technique under ambient reaction conditions.

Emerging Aspects of Triazole in Organic Synthesis: Exploring its Potential as a Gelator.

Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) - commonly known as the "click reaction" - serves as the most effective and highly reliable tool for facile construction of simple to complex designs at the molecular level. It relates to the formation of carbon heteroatomic systems by joining or clicking small molecular pieces together with the help of various organic reactions such as cycloaddition, conjugate addition, ring-opening, etc. Such dynamic strategy results in the generation of triazole and its derivatives from azides and alkynes with three nitrogen atoms in the five-membered aromatic azole ring that often forms gel-assembled structures having gelating properties. These scaffolds have led to prominent applications in designing advanced soft materials, 3D printing, ion sensing, drug delivery, photonics, separation, and purification. In this review, we mainly emphasize the different mechanistic aspects of triazole formation, which includes the synthesis of sugar-based and non-sugar-based triazoles, and their gel applications reported in the literature for the past ten years, as well as the upcoming scope in different branches of applied sciences.

Formation and catalytic potential of sheet like nanostructured amino functionalized graphene oxide Schiff's base immobilized by Cu nanoparticles in Click reaction, oxidation of fluorene and in photodegradation of methylene blue

A heterogeneous catalyst, environmentally benign, containing copper immobilized over amino functionalized Schiff's base graphene oxide was prepared. The prepared nanocatalyst was explored in various organic transformations such as in tri-azoles formation, in oxidation and the degradation of methylene blue. Click chemistry was employed in the formation of triazoles for the construction of carbon-heteroatom bonds which have many applications ranging from drug discovery to material science. Our present work focused on graphene-based nanocatalyst (Cu @NH2GO) which provided excellent efficiency and catalytic activity in carrying out organic transformations. The prepared nanocatalyst was characterized and examined by various spectroscopic techniques such as X-ray diffraction (PXRD), thermo gravimetric analysis (TGA), field emission-scanning electron microscopy (FE-SEM), EDX, high-resolution transmission electron microscopy (HR-TEM), Fourier transformer infrared spectroscopy (FT-IR), and X-ray Photoelectron Spectroscopy (XPS). TEM images showed the light grey sheets of silane functionalized Schiff's base on which Cu nanoparticles were immobilized. The catalyst was also explored for the degradation of methylene blue which provided an effective path for the treatment of wastewater. Methylene Blue is one of the environmentally persistent, carcinogenic and mutagenic cationic dyes. A large volume of methylene blue containing wastewater is discharged into groundwater or surface water. So it becomes necessary to degrade the toxic dye by the use of a prepared nanocatalyst (Cu @NH2GO). Moreover, the catalyst possesses excellent stability and reusability.

Synthesis and Photolysis Properties of a New Chloroquine Photoaffinity Probe.

A new chloroquine-derived photoaffinity probe has been prepared by a convergent synthesis from derivative of 4,7-dichloroquinoline and N1,N1-diethyl-N4-methylpentane. The features of this probe are a unique 3-azido photolabel, the pyridine ring of the quinoline, and the presence of a secondary amine at the 4-position of the quinoline. These features, particularly the 4-amino methylation, prevent triazole formation through combination of the 3-azide and the 4-amine. This undergoes facile cleavage with exposure to a medium-pressure mercury lamp with a 254 nm excitation wavelength. Trapping of the nitrene byproduct is accomplished with its reaction with N-phenylmaleimide as its cycloazidation product. The structure of a ring-opened DBU amine has been structurally characterized.

Click assembly through selective azaylide formation.

An efficient triple-click assembly using a newly designed trivalent platform is disclosed. We achieved the selective azaylide formation of 2,3,5,6-tetrafluorophenyl azides with o-ester-substituted triarylphosphines leaving 2,6-dichlorophenyl azides untouched. Further rapid Staudinger reaction of dichlorophenyl azides and subsequent triazole formation allowed us to prepare trifunctionalized molecules in three steps.

Rapid diazotransfer for selective lysine labelling.

Azide functionalization of protein and peptide lysine residues allows selective bioorthogonal labeling to introduce new, site selective functionaltiy into proteins. Optimised diazotransfer reactions under mild conditions allow aqueous diazotransfer to occur in just 20 min at pH 8.5 on amino acid, peptide and protein targets. In addition, conditons can be modified to selectively label a single lysine residue in both protein targets investigated. Finally, we demonstrate selective modification of proteins containing a single azidolysine using copper(I)-catalyzed triazole formation.

1,3-Butadiynyl sulfide-based compact trialkyne platform molecule for sequential assembly of three azides.

A compact trialkyne platform with a silyl-protected 1,3-butadiynyl sulfide moiety and a terminal alkyne group has been developed for sequential regioselective transition metal-catalyzed triazole formation reactions with three azides. This method enabled the facile construction of a low-molecular-weight triazole library and the synthesis of middle-molecular-weight trifunctional probes for protein modification.

CycloSiFA: Die nächste Generation von Silicium‐basierten Fluoridakzeptoren für die Positronenemissionstomographie (PET)

AbstractDie ringöffnende Si‐Fluorierung einer Vielzahl von Azasilolderivaten Cyclo‐1‐(iPr2Si)−4‐X−C6H3−2‐CH2NR (4: R=2,6‐iPr2C6H3, X=H; 4 a: R=2,4,6‐Me3C6H2, X=H; 9: R=2,6‐iPr2C6H3, X=tBuMe2SiO; 10: R=2,6‐iPr2C6H3, X=OH; 13: R=2,6‐iPr2C6H3, X=HCCCH2O; 22: R=2,6‐iPr2C6H3, X=tBuMe2SiCH2O) mit verschiedenen 19F‐Fluoridquellen untersucht, optimiert und die gewonnenen Erfahrungen in einem translationalen Ansatz genutzt, um ein einfaches 18F‐Markierungsprotokoll für die Azasilolderivate [18F]6 und [18F]14 zu erstellen. Letzteres stellt eine potenziell klickbare CycloSiFA‐prothetische Gruppe dar, die bei der Entwicklung von PET‐Tracern unter Verwendung der Cu‐katalysierten Triazolbildung eingesetzt werden könnte. Auf der Grundlage unserer Ergebnisse hat CycloSiFA das Potenzial, ein neuer Einstieg in nicht‐kanonische Markierungsmethoden für die Entwicklung radioaktiver PET‐Tracer zu werden.

CycloSiFA: The Next Generation of Silicon-Based Fluoride Acceptors for Positron Emission Tomography (PET).

The ring-opening Si-fluorination of a variety of azasilole derivatives cyclo-1-(iPr2 Si)-4-X-C6 H3 -2-CH2 NR (4: R=2,6-iPr2 C6 H3 , X=H; 4 a: R=2,4,6-Me3 C6 H2 , X=H; 9: R=2,6-iPr2 C6 H3 , X=tBuMe2 SiO; 10: R=2,6-iPr2 C6 H3 , X=OH; 13: R=2,6-iPr2 C6 H3 , X=HCCCH2 O; 22: R=2,6-iPr2 C6 H3 , X=tBuMe2 SiCH2 O) with different 19 F-fluoride sources was studied, optimized and the experience gained was used in a translational approach to create a straightforward 18 F-labelling protocol for the azasilole derivatives [18 F]6 and [18 F]14. The latter constitutes a potential clickable CycloSiFA prosthetic group which might be used in PET tracer development using Cu-catalysed triazole formation. Based on our findings, CycloSiFA has the potential to become a new entry into non-canonical labelling methodologies for radioactive PET tracer development.

Organocatalytic Synthesis of Furan-Embedded Styrene Atropisomers.

Herein, we report the first synthesis of furan-embedded styrene atropisomers via the reaction between 1-(aryl-ethynyl)-naphthalen-2-ol and γ-hydroxyenone. The reaction proceeds through in situ furan formation from γ-hydroxyenone. The styrene derivatives were obtained in moderate to good yields with high diastereoselectivities with a catalytic amount of PTSA. Few applications such as triazole formation and cross-coupling reactions have been demonstrated. A preliminary catalytic asymmetric version was also reported.

4-azido-7-nitrobenzoxadiazole as Innovative Clickable Fluorescence Probe for Trace and Selective Quantification of Ethinylestradiol in Human Plasma.

Quantification of Ethinylestradiol (EE) in biological matrices is challenging since it is a very potent drug with a very low Cmax (75 pg.mL-1 ). Despite the high sensitivity of fluorometric methods, detection of EE by them is confined because its structure exhibited very limited fluorescence. Therefore, it must be derivatized first using a fluorogenic agent to produce more potent fluorescent derivative to achieve the desired ultra-sensitive bioanalysis. Herein, For the first time, we proposed a promising click fluorescent probe, 4-azido-7-nitrobenzoxadiazole (NBD-AZ) to react with the alkyne group of EE, by the help of copper sulphate and L-ascorbic acid to give a highly fluorescent and stable 1,2,3- triazole derivative. Density functional theory calculation revealed how the triazole formation affects the quantum yield and fluorescence of click reaction product when comparing to NBD-AZ. The resulting triazole exhibited strong signal at wavelength of 540 nm after excitation at 470 nm. Reaction parameters impacting the intensity of fluorescence were cautiously studied and optimized. The suggested approach has shown outstanding performance, high linearity (25-300 pg.mL-1 ) and low detection limit of 7.5 pg.mL-1 . The enhanced sensitivity and selectivity were exploited for analysing EE in plasma using liquid-liquid extraction for samples cleaning up without interference from any biological components and with mean % recovery of 100.13±0.39. Accuracy, sensitivity, selectivity, simplicity, and cost-effectiveness make this approach a convincing, promising, and appealing alternative over the reported analytical methods for EE bioanalysis in different matrices.

An Efficient Catalyst-Free Direct Approach to 5-Polyfluoroalkyl-1,2,4-triazole-3-thiones

AbstractAn easy to handle high-efficient approach to 5-polyfluoroalkyl-1,2,4-triazole-3-thiones (11 examples, up to 91% yield) is reported. The tautomerism of thione and thiol forms for the obtained products is discussed. A one step procedure for 6,6-dimethyl-3-(trifluoromethyl)-5,6-dihydro[1,3]thiazolo[2,3-c][1,2,4]triazole formation from trifluoroacetic acid and 4-methallylthiosemicarbazide has been developed. The structures of the products were unambiguously determined by complex NMR investigation and by single crystal X-ray diffraction.

Convenient syntheses of phthalocyanine and tetrabenzotriazaporphyrin (TBTAP) mono-alkynes; unhindered building blocks for click chemistry and beyond

Unsymmetrical phthalocyanines and related macrocycles are often desirable for covalent construction or the self-assembly of more complex architectures. Terminal alkynes are versatile in this regard because they are amenable to cross-coupling via Sonogashira-type reactions, alkyne-alkyne coupling via Glaser-type couplings, and triazole formation via Click reaction with azides. Here we describe two complementary syntheses to conveniently add a single alkyne onto the phthalocyanine peripheral position and onto the meso-phenyl group of an (aryl)tetrabenzotriazaporphyrin, here providing a remote link point that is insulated from the macrocycle.

Expedient synthesis of imino-C-nucleoside fleximers featuring a one-pot procedure to prepare aryl triazoles.

Nucleoside analogues such as the antiviral agents galidesivir and ribavirin are of synthetic interest. This work reports a "one-pot" preparation of similar fleximers using a bifunctional copper catalyst that generates the aryl azide in situ, which is captured by a terminal alkyne to effect triazole formation.

Stimuli-Responsive Catenane-Based Catalysts.

Rotaxanes and molecular knots exhibit particular properties resulting from the presence of a mechanical bond within their structure that maintains the molecular components interlocked in a permanent manner. On the other hand, the disassembly of the interlocked architecture through the breakdown of the mechanical bond can activate properties which are masked in the parent compound. Herein, we present the development of stimuli-responsive CuI -complexed [2]catenanes as OFF/ON catalysts for the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The encapsulation of the CuI ion inside the [2]catenanes inhibits its ability to catalyze the formation of triazoles. In contrast, the controlled opening of the two macrocycles induces the breaking of the mechanical bond, thereby restoring the catalytic activity of the CuI ion for the CuAAC reaction. Such OFF/ON catalysts can be involved in signal amplification processes with various potential applications.

Stimuli‐Responsive Catenane‐Based Catalysts

AbstractRotaxanes and molecular knots exhibit particular properties resulting from the presence of a mechanical bond within their structure that maintains the molecular components interlocked in a permanent manner. On the other hand, the disassembly of the interlocked architecture through the breakdown of the mechanical bond can activate properties which are masked in the parent compound. Herein, we present the development of stimuli‐responsive CuI‐complexed [2]catenanes as OFF/ON catalysts for the copper‐catalyzed alkyne‐azide cycloaddition (CuAAC) reaction. The encapsulation of the CuI ion inside the [2]catenanes inhibits its ability to catalyze the formation of triazoles. In contrast, the controlled opening of the two macrocycles induces the breaking of the mechanical bond, thereby restoring the catalytic activity of the CuI ion for the CuAAC reaction. Such OFF/ON catalysts can be involved in signal amplification processes with various potential applications.

SCuNPs‐Catalyzed Solventless Oxidative [3+2] Azide‐Olefin Cycloaddition: An Efficient Protocol For Di‐ And Trisubstituted 1,2,3‐Triazole Synthesis

AbstractA starch capped copper nanoparticles (SCuNPs) promoted solvent free methodology has been developed for oxidative [3+2] azide‐olefin cycloaddition reaction. The reactions employ atmospheric O2/DMSO as oxidant to furnish an assortment of disubstituted and trisubstituted 1,2,3‐triazoles. This method is well‐suited not only with acyclic terminal olefins, but also with cyclic and open chain internal olefins. The proposed mechanism was validated with the help of DFT calculations. The triazole formation proceeds through exergonic pathway and the activation barriers are not very high which helps in the easy formation of triazole derivative.

Improvement strategies on metal–organic frameworks (IFMC-1) as adsorbent and its kinetic study for dye pollutant removal and wastewater treatment

Green application of a high-nitrogen, zeolite-like, porous metal–organic framework, IFMC-1 (Institute of Functional Material Chemistry), is reported for dye pollutant removal and wastewater treatment. The IFMC-1 contained a high-nitrogen-content ligand without an NH2 group (H3dttz), dimethylacetamide, and Zn ion. The synthesis of H3dttz from diaminomaleonitrile was initiated after closure of the triazole ring and formation of 4,5-dicyano-2H-1,2,3-triazole as an intermediate material; thus, two tetrazole rings were obtained in a 1,3-dipolar cycloadditionn. Only four nitrogens of the IFMC-1 ligand coordinate with zinc, and 63.6% of the nitrogens are free. The IFMC-1-based tetrazole without an NH2 group was investigated for removal of methylene blue (MB) and basic red 46 (BR-46) pollutants. The results indicated that the IFMC-1 adsorbent effectively removed the MB and BR-46 dyes from solution. The contaminant adsorption capacity of IFMC-1 for MB and BR-46 was 293.9 and 135.2 mg g–1, respectively. Investigation of isotherm and kinetic data of dye removal using the synthesized absorbent indicated that it follows the Langmuir isotherm and pseudo-second-order kinetics.

In Situ Cellular Localization of Nonfluorescent [60]Fullerene Nanomaterial in MCF-7 Breast Cancer Cells.

Cellular localization of carbon nanomaterials in cancer cells is essential information for better understanding their interaction with biological targets and a crucial factor for further evaluating their biological properties as nanovehicles or nanotherapeutics. Recently, increasing efforts to develop promising fullerene nanotherapeutics for cancer nanotechnology have been made. However, the main challenge regarding studying their cellular effects is the lack of effective methods for their visualization and determining their cellular fate due to the limited fluorescence of buckyball scaffolds. Herein, we developed a method for cellular localization of nonfluorescent and water-soluble fullerene nanomaterials using the in vitro click chemistry approach. First, we synthesized a triple-bonded fullerene probe (TBC60ser), which was further used as a starting material for 1,3-dipolar cycloaddition using 3-azido-7-hydroxycoumarin and sulfo-cyanine5 azide fluorophores to create fluorescent fullerene triazoles. In this work, we characterized the structurally triple-bonded [60]fullerene derivative and confirmed its high symmetry (Th) and the successful formation of fullerene triazoles by spectroscopic techniques (i.e., ultraviolet–visible, fluorescence, and Fourier transform infrared spectroscopies) and mass spectrometry. The created fluorescent fullerene triazoles were successfully localized in the MCF-7 breast cancer cell line using fluorescent microscopy. Overall, our findings demonstrate that TBC60ser localizes in the lysosomes of MCF-7 cells, with only a small affinity to mitochondria.

Real-Time High-Sensitivity Reaction Monitoring of Important Nitrogen-Cycle Synthons by 15N Hyperpolarized Nuclear Magnetic Resonance.

Here, we show how signal amplification by reversible exchange hyperpolarization of a range of 15N-containing synthons can be used to enable studies of their reactivity by 15N nuclear magnetic resonance (NO2– (28% polarization), ND3 (3%), PhCH2NH2 (5%), NaN3 (3%), and NO3– (0.1%)). A range of iridium-based spin-polarization transfer catalysts are used, which for NO2– work optimally as an amino-derived carbene-containing complex with a DMAP-d2 coligand. We harness long 15N spin-order lifetimes to probe in situ reactivity out to 3 × T1. In the case of NO2– (T1 17.7 s at 9.4 T), we monitor PhNH2 diazotization in acidic solution. The resulting diazonium salt (15N-T1 38 s) forms within 30 s, and its subsequent reaction with NaN3 leads to the detection of hyperpolarized PhN3 (T1 192 s) in a second step via the formation of an identified cyclic pentazole intermediate. The role of PhN3 and NaN3 in copper-free click chemistry is exemplified for hyperpolarized triazole (T1 < 10 s) formation when they react with a strained alkyne. We also demonstrate simple routes to hyperpolarized N2 in addition to showing how utilization of 15N-polarized PhCH2NH2 enables the probing of amidation, sulfonamidation, and imine formation. Hyperpolarized ND3 is used to probe imine and ND4+ (T1 33.6 s) formation. Furthermore, for NO2–, we also demonstrate how the 15N-magnetic resonance imaging monitoring of biphasic catalysis confirms the successful preparation of an aqueous bolus of hyperpolarized 15NO2– in seconds with 8% polarization. Hence, we create a versatile tool to probe organic transformations that has significant relevance for the synthesis of future hyperpolarized pharmaceuticals.