Huisgen Reaction Research Articles

Synthesis, Thermal, and Optical Properties of Tris(5‐aryl‐1,3,4‐oxadiazol‐2‐yl)‐1,3,5‐triazines, New Star‐Shaped Fluorescent Discotic Liquid Crystals

The synthesis of tris(aryloxadiazolyl)triazines (TOTs), C 3‐symmetrical star‐shaped mesogenes with a 1,3,5‐triazine center, 5‐phenyl‐1,3,4‐oxadiazole arms, and various peripheral alkoxy side chains is reported. Threefold Huisgen reaction on a central triazine tricarboxylic acid and suitable aryltetrazoles yields the title compounds. Selected analogues with a benzene center are included in this study and allow for an evaluation of the impact of the central unit on the physical properties. Thermal (differential scanning calorimetry, DSC; polarization optical microscopy, POM), optical (UV/Vis, fluorescence), electric (time of flight, TOF), and structural (single crystal; wide‐angle X‐ray scattering, WAXS) properties of these compounds were investigated. The modification of alkoxy chain length and substitution pattern allows for a tuning of the physical properties. TOTs emit blue to yellow light, depending on conjugation length, donor–acceptor substitution, and solvent polarity, whereas concentration quenches and aggregation enhances the emission. The width of the mesophases is typically around ΔT=100–150 K but can even exceed 220 K. Polarization optical microscopy and X‐ray diffraction on oriented filaments reveal that TOTs are highly ordered liquid crystals (LCs) with long‐range hexagonal columnar structure.

3D, covalent and noncovalent hybrid materials based on 3-phenylcoumarin derivatives and single walled carbon nanotubes as gas sensing layers

In this work, the effect of different types of functionalization of single walled carbon nanotubes (SWCNT) with 3-phenylcoumarin derivatives on the chemiresistive sensor response to ammonia (10–50 ppm) was studied. Covalent functionalization of SWCNT was performed according to the Huisgen reaction of azide-alkyne 1,3-dipolar cycloaddition between mono alkyne-substituted 3-phenylcoumarin and single walled nanotubes modified by azide groups. Covalent functionalization was shown by IR- and X-ray photoelectron spectroscopy. To obtain the 3D hybrid material, the dialkyne functionalized 3-phenylcoumarin molecules were used as linkers between nanotubes. Third hybrid material was prepared by noncovalent functionalization of SWCNT, namely by adsorption of 7-propinyloxy-3-(p-propinyloxyphenyl)coumarin on SWCNT surface. It was shown that the 3D hybrid and the hybrid obtained by covalent functionalization exhibit 2 and 4 times higher sensor responses to ammonia compared to noncovalently functionalized SWCNT. The value of sensor response is in good correlation with the degree of functionalization of SWCNTs with coumarin molecules.

Synthesis and study of sorption properties of polyvinyl alcohol (PVA)-based hybrid materials

The present contribution aims at reporting the synthesis and the preliminary evaluation of hybrid materials combining polyvinyl alcohol (PVA) functionalized with ethylenediaminetetraacetic acid (EDTA) as complexing groups, and alumina that, together, were able to efficiently complex and remove metallic cations from aqueous effluents. For such purpose, well-defined PVA homopolymers bearing an azide (PVA-N3) or an alkyne function (PVA-alkyne) were functionalized via chemical modification by either phosphoric acid (PPVA-N3), to promote adhesion to alumina, or ethylenediaminetetraacetic acid (PVA(EDTA)-alkyne), able to efficiently complex metallic cations. Modified PVA chains were coupled by Huisgen reaction using copper catalysis (CuAAC) leading to the formation of bifunctional diblock copolymers. Then, hybrid materials were produced via the grafting of PVA-based copolymers onto alumina particles. Finally, the sorption capacity of these materials towards Co(II), Ni(II) and Sr(II) was determined to evaluate their removal efficiency. Such hybrid materials could be efficiently used in the context of nuclear effluents treatment.

1,3,4-Oxadiazoles by Ugi-Tetrazole and Huisgen Reaction.

Easy to perform, functional group tolerant, and short syntheses of the privileged scaffold oxadiazole are highly desired. Here, a metal-free protocol for MCR-based synthesis of 2,5-disubstituted 1,3,4-oxadiazoles via a Ugi-tetrazole/Huisgen sequence was developed. Optimization and scope and limitations of this short and general sequence are described. The reaction was also successfully performed on a gram scale.

Water as a solvent for Ru‐catalyzed click reaction: Highly efficient recyclable catalytic system for triazolocoumarins synthesis

A new family of Ru (III) complexes has been synthesized, characterized and their catalytic performance has been tested for alkyne–azide cycloaddition (AAC) in water under ultrasonic irradiation conditions. These complexes are found to be effective heterogeneous catalysts for the regioselective synthesis of 1,4‐disubstituted‐1,2,3‐triazoles giving access to these products in excellent yields. The catalyst system is equally active for one‐pot multi‐component protocol of the AAC reactions. Also, successive sequencing of Huisgen reaction with Knoevenagel condensation reaction results in the effective assembly of a diversified hitherto unreported 1,2,3‐triazolyl coumarin frameworks. In present strategy, the catalyst could be easily isolated by simple filtration and reused up to eight consecutive cycles without significant drop in the reaction yields. During the leaching experiment, there is no leaching amount of the catalyst was detected, suggesting true heterogeneity in the catalytic system. The results of gram‐scale reaction and green metrics calculations also confirmed the sustainability and industrial applicability of the current catalytic protocol.

Preparation of multifunctional glycopolymers using double orthogonal reactions and the effect of electrostatic groups on the glycopolymer–lectin interaction

We investigated synthetic biomacromolecules to control molecular interactions. Multifunctional glycopolymers for molecular recognition were prepared via living radical polymerization and post-click chemistry with orthogonal Huisgen and thiol-epoxy reactions. The synthesis of the polymer backbone and the subsequent side-chain introduction successfully proceeded in high yield. The multifunctional glycopolymers had a tri-block structure: the first and third blocks contained mannose, and the second block contained either a positively or negatively charged group or a neutral hydrophilic group. The molecular recognition of the glycopolymers toward lectin was evaluated via fluorescence quenching measurements. Because of the electrostatic interaction, the binding constant varied in the following order: positively charged glycopolymer (PT110) > negatively charged glycopolymer (NT110). The effect of the electrostatic interactions was modest compared with the effect of the carbohydrate–lectin binding. These results suggested that the carbohydrate–lectin interaction was an important factor in the molecular recognition of glycopolymers. This study provides guidelines for the preparation of multifunctional polymers, such as biomaterials. The block glycopolymers with specific arrangement of sugar ligand and electric charges were synthesized via RAFT living radical polymerization, where the block polymers were efficiently obtained using two orthogonal reactions of Huisgen and thiol-epoxy ring opening reactions. The molecular recognition abilities of the block glycopolymers was examined.

Network regulation and properties optimization of glycidyl azide polymer‐based materials as a candidate of solid propellant binder via alternating the functionality of propargyl‐terminated polyether

ABSTRACTA kind of glycidyl azide polymer (GAP)‐based composite has been fabricated using propargyl‐terminated ethylene oxide‐tetrahydrofuran copolymer (PPET) with two (p‐) and three (t‐) alkyne functionalities via Huisgen reaction. Independent upon the PPET functionality, both crosslink densities and mechanical properties for two GAP/PPET systems showed a positive‐interrelation changes of initial increase and subsequent decrease with an increase of azide/alkyne molar ratios. At equivalent of azide/alkyne molar ratios, the composites containing t‐PPET with higher alkyne functionality exhibited better mechanical properties, while those with two alkyne functionality presented lower glass transition. Under the regulation of alkyne functionality as 3 and azide/alkyne molar ratio as 3:1, the tensile strength, Young's modulus and breaking elongation could simultaneously reach the maximum values of 1.38 MPa, 4.07 MPa, and 122.5%, which was ascribed to optimal participation of azide/alkyne reaction into network construction. Overall, this study provides an additional optimization route for network‐structured binders in solid propellant system. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48016.

Asymmetric syntheses and applications of planar chiral hypervalent iodine(V) reagents with crown ether backbones

Novel optically active hypervalent iodine(V) reagents with planar chiral crown ether backbones were synthesized using the intramolecular Huisgen reaction as a key step and l-methyl lactate as the source of chirality. The relative configurations of these reagents and stabilities of planar chiralities were determined by DFT calculations. These planar chiral reagents were applied to the hydroxylative dearomatization/[4 + 2]-dimerization reactions of phenols to afford bisthymol and biscarvacrol, a natural product, with moderate enantioselectivities.

Multicomponent click reaction catalyzed by organic surfactant-free copper sulfide (sf-CuS) nano/micro flowers

The azide-alkyne cycloaddition (Huisgen reaction) is one of the most powerful and widely used copper-mediated reactions. In many such reactions, use of metal or metal oxide nanoparticles as the catalyst is more appealing because of the increased catalytic activity attributed to the large surface to volume ratio. However, the nano/micro particles are synthesized often in the presence of long chain organic molecules as capping or stabilizing agents. These organic molecules cover the active centers and restrict or reduce their catalytic activity. Therefore, we have synthesized the copper sulfide (sf-CuS) nano/micro particles without having organic surfactant molecules as the capping agent. These particles with a flower-like architecture (micro flowers, mf) were obtained readily under the supersaturated condition at room temperature. In these particles, the surface was freely available for adsorption and desorption reactions. When utilized as a catalyst in multicomponent cycloaddition reactions, the sf-CuS mf exhibited excellent catalytic activity compared with some other nanoparticles with surfactants. This sf-CuS mf catalyzed the one-pot synthesis of 1,2,3-triazole and β-hydroxy-1,2,3-triazole effectively from a variety of benzyl bromide derivatives epoxides respectively. Both these reactions proceeded in the presence of azide and phenylacetylene in the water at room temperature. The catalyst was reusable, and there was no catalyst leaching observed during reactions. Synthesis of β-hydroxy triazoles and 1,2,3-triazoles under exceptionally mild conditions with high yields proved the sf-CuS mf as the catalyst as a robust and recyclable catalyst.

Tetrakis(oxadiazolylphenyl)pyrazines: New St. Andrew's Cross-Shaped Liquid Crystals.

π-Conjugated molecules with the shape of St. Andrew's cross have been synthesized via fourfold Huisgen reaction. Four 2,5-diaryl-1,3,4-oxadiazol arms are attached to a central pyrazine nucleus. These fluorescent stars, when decorated with a rim of eight alkoxy side chains are discotic liquid crystals. Depending on the substitution pattern, the width of the liquid phase varies within a broad range of 25 °C to 250 °C. In their liquid crystalline phase, the molecules assemble in a typical hexagonal columnar supramolecular arrangement.

Synthesis of new polymers containing 1,2,3-triazole units from poly(vinylchloride) via "click” chemistry catalyzed by copper iodide and its application in extraction of nitrates and metals contained in wastewater

New polymers with potential application in a waste water purification from inorganic contaminants were synthesized via a chemical modification of poly(vinyl chloride) by "click” method based on copper(I)-catalyzed Huisgen reaction. The structure of the resulting polymers containing 1,4-disubstituted triazole units was confirmed by infrared spectroscopy (ATR-FTIR), nitrogen elemental analysis and differential thermal analysis (DTA). The obtained polymers were subsequently used in the elimination of nitrate ions and metalions from the wastewater of Beja region (Tunisia). It was found that new polymers were most efficient in capturing of zinc ions, the average extraction percentage of Zn2+ was 28%, while the average extraction percentage of nitrates did not exceed 12.5%. The selectivity of the binding of investigated ions can be arranged in the following order: Zn2+> NO3–> Ca2+> Mg2+.

Synthesis and antibacterial activity of new 1,2,3-triazolylmethyl-2H-1,4-benzothiazin-3(4H)-one derivatives

BackgroundA novel series of 1,2,3-triazole derivatives containing 1,4-benzothiazin-3-one ring (7a–9a, 7b–9b), (10a–12a, 10b–12b) and (13–15) were synthesized by 1,3-dipolar cycloaddition reactions of azides α-d-galactopyranoside azide F, 2,3,4,6-tetra-O-acetyl-(d)-glucopyranosyl azide G and methyl-N-benzoyl-α-azidoglycinate H with compounds 4–6.FindingsInitially, the reactions were conducted under thermal conditions in ethanol. The reaction leads, each time, to the formation of two regioisomers: (Schemes 2, 3) with yields of 17 to 21% for 1,5-disubstituted 1,2,3-triazole-regioisomers (7b–12b) and yields ranging from 61 to 65% for the 1,4-disubstituted regioisomers (7a–12a). In order to report an unequivocal synthesis of the 1,4-regioisomers and confirm the structures of the two regioisomers obtained in thermal conditions (Huisgen reactions), the method click chemistry (Copper-Catalyzed Azide-Alkyne Cycloaddition) has been used.ConclusionsThe newly synthesized compounds using cycloaddition reactions were evaluated in vitro for their antibacterial activities against some Gram positive and Gram negative microbial strains. Among the compounds tested, the compound 8a showed excellent antibacterial activities against PA ATCC and Acin ESBL (MIC = 31.2 μg/ml).

Huisgen Reaction Catalyzed by Silica-Coated Magnetic Copper Nanoparticles

Huisgen Reaction Catalyzed by Silica-Coated Magnetic Copper Nanoparticles

Synthesis and anticancer activity of novel rapamycin C‐28 containing triazole moiety compounds

Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Its C-43 semi-synthetic derivatives temsirolimus and everolimus have been used as mTOR targeting anticancer drugs in the clinic. Following our previous research on antitumor rapalogs modified on the C-43 position, 13 novel rapamycin triazole hybrids (6a-g, 7a-f) were designed and synthesized on the C-28 position of rapamycin via Huisgen's reaction. Anticancer assays indicated that the targeted derivatives containing phenyl and 4-methylphenyl groups showed an obvious raise in anticancer activity. On the contrary, the compounds with methoxyl, amine, and halogen groups on the benzene ring displayed lower anticancer activity. Compound 6c, as the most active compound, showed a stronger inhibition effect as compared with rapamycin for almost all of the tested cell lines (p < 0.01), except PC-3. Meanwhile, the effect of 6c on inducing apoptosis and cell cycle arrest in A549 cells was more powerful than that of rapamycin. In addition, 6c inhibited the phosphorylation of mTOR and its downstream key kinases 4EBP1 and p70S6K1 in A549 cells, indicating that 6c also effectively inhibits the mTORC1 signaling pathway as rapamycin. On the basis of these findings, 6c may have the potential to be developed as a new mTOR inhibitor against specific cancers.

Optically Functionalized Grid-Type Complexes by a Post-Assembly Strategy.

Bisterpyridine-based grid complexes can serve as supramolecular three-dimensional scaffolds for the construction of larger molecular assemblies. Through functionalization of the ligand with azide groups, followed by self-assembly and metal-free Huisgen reactions, eight pyrene molecules can be attached to the grid structure in a single reaction step. The orientation and proximity provided by the scaffold allows for tuning the fluorescence properties of the dye molecules.

Tristriazolotriazines: Luminescent Discotic Liquid Crystals

Tristriazolotriazines (TTT) are new tetracyclic and planar cores for discotic liquid crystals. Two symmetrical isomers are known, paddle‐wheel type t‐TTTs and r‐TTTs with the shape of a propeller. Cyclocondensation of chlorotriazoles gives r‐TTTs, Huisgen reaction of tetrazoles and cyanuric chloride yields t‐TTTs with tangentially attached substituents. Many alkoxyphenyl‐substituted t‐TTTs form broad mesophases, typically with a hexagonal columnar structure. These luminescent molecules, when heated above 200 °C, suffer a thermal isomerization. A threefold ring opening/ring closing mechanism transforms t‐TTTs via unsymmetrical isomers to r‐TTTs. Thermotropic properties are largely influenced by planarization and increase of molecular diameter. Increased melting points, even the complete loss of liquid crystallinity have been observed, but also the gain of mesomorphism.

Massively Multiplexed Tip-Based Photochemical Lithography under Continuous Capillary Flow

Summary Multiplexed microarrays—where different biological probes are spatially encoded onto a surface into spots with micrometer-scale diameters—have facilitated the rapid advancement of "omics" research. Further miniaturization of feature diameters could increase the number of probes in a microarray, reduce the sample required for analysis, and decrease costs. Tip-based lithography (TBL) has gained popularity for patterning delicate, biologically active materials, but no versatile TBL-based multiplexing strategy has been devised. Here, we combine microfluidics, beam pen lithography, and photochemical surface reactions to create multiplexed arrays. For proof of concept, the thiol-ene reaction was optimized, and the reaction kinetics were analyzed. Subsequently, we created several patterns containing multiple fluorescent alkenes, where each pattern was designed to demonstrate a different capability of this instrument. This patterning strategy is a powerful approach to studying and optimizing organic reactions on surfaces and creating massively multiplexed arrays and, as such, could provide an entirely new approach for miniaturizing biochips or understanding interfacial reactivity.

Batch and Continuous-Flow Huisgen Reactions on Dendrimer-Supported CuSO4

Key words copper catalysis - Huisgen reaction - alkynes - azides - aqueous reaction - heterogeneous catalysis

Synthesis of novel perillyl-dihydropyrimidinone hybrids designed for antiproliferative activity.

A series of fifteen novel dihydropyrimidinone hybrid compounds were synthesized in good yields via a multicomponent reaction combined with the Huisgen reaction. The antiproliferative activity was investigated against nine tumor cell lines, and four hybrid compounds (TGI < 10 μM) showed promising antiproliferative activity against the tumor cell lines OVCAR-3 (ovarian), UACC-62 (melanoma) and U251 (glioma). Several hybrid compounds assayed have high TGI values (TGI 147.92-507.82) for the human keratinocyte cell line (HaCat), which reveals selectivity to cancer cells.

Isomerisation of Liquid-Crystalline Tristriazolotriazines.

Star-shaped discotic liquid crystals with columnar superstructures constitute a highly interesting class of organic materials. Phenyl-substituted tris[1,2,4]triazolo-[1,3,5]triazine, prepared by a Huisgen reaction of phenyltetrazole and cyanuric chloride, represents an excellent core for discotic liquid crystals (DLCs). The thermal stability is not perfect, at temperatures above the clearing point, a successive threefold isomerization leads to a highly planar, C3 -symmetrical isomer, which mainly differs in the orientation of the aryl substituents to the centre of the molecule. A new class of discotic liquid crystals has been obtained: Equipped with peripheral alkoxy chains both isomers can form broad thermotropic mesophases. The optical, thermal, and physical properties were investigated by polarized optical microscopy, differential scanning calorimetry, wide-angle X-ray scattering, UV/Vis absorption and fluorescence spectroscopic measurements. The thermotropic properties are decisively affected by the molecular structure of the isomers, isomerisation leads to higher melting points but also the loss or even gain of mesomorphism is observed.