Enamine Bond Research Articles

A magnetic nanocatalyst based on Bronsted acid and Lewis acid centers for the efficient synthesis of polycyclic melting 1,5-benzodiazepines

In this study, 3-(Triethoxysilyl)propyl chloride (CPTES) was used to modify the surface of magnetic nanoparticles Fe3O4@SiO2, and aminomethylphosphonic acid (AMPA) was further anchored on the surface. Then, Ce (III) was used as the ligand to immobilize the surface of the modified material with N/O as the donor. Magnetic nanocatalysts (Fe3O4@SiO2@CPTES@AMPA@CeCl3) were successfully prepared. The prepared catalysts were characterized by infrared spectroscopy (FT-IR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen absorption-desorption experiment (BET), vibrating sample magnetometer (VSM), energy dispersive spectroscopy (EDS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). A synergetic effect of Brønsted and Lewis acid (AMPA and CeCl3) of the magnetic nanocatalyst was examined to active carbonyl, imine or enamine bonds for the synthesis of polycyclic fused 1,5-benzodiazepine with quaternary carbon centers or quinoxaline ring in a one-pot method. It was found that this catalyst exhibited excellent catalytic activities (TON up to 111368, TOF up to 110232 h−1) and high selectivities in the synthesis of fused 1,5-benzodiazepine compounds (22 examples, 85–96 % yields). The mechanism for the synthesis of polycyclic fused 1,5-benzodiazepine catalyzed by Fe3O4@SiO2@CPTES@AMPA@CeCl3 was proposed. The nanocatalyst was readily recovered by simple magnetic decantation and can be recyclable without obviously reducing catalytic activity up to seven times.

Formation of Zwitterionic and Self-Healable Hydrogels via Amino-yne Click Chemistry for Development of Cellular Scaffold and Tumor Spheroid Phantom for MRI.

In situ-forming biocompatible hydrogels have great potential in various medical applications. Here, we introduce a pH-responsive, self-healable, and biocompatible hydrogel for cell scaffolds and the development of a tumor spheroid phantom for magnetic resonance imaging. The hydrogel (pMAD) was synthesized via amino-yne click chemistry between poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethylmethacrylamide) and dialkyne polyethylene glycol. Rheology analysis, compressive mechanical testing, and gravimetric analysis were employed to investigate the gelation time, mechanical properties, equilibrium swelling, and degradability of pMAD hydrogels. The reversible enamine and imine bond mechanisms leading to the sol-to-gel transition in acidic conditions (pH ≤ 5) were observed. The pMAD hydrogel demonstrated potential as a cellular scaffold, exhibiting high viability and NIH-3T3 fibroblast cell encapsulation under mild conditions (37 °C, pH 7.4). Additionally, the pMAD hydrogel also demonstrated the capability for in vitro magnetic resonance imaging of glioblastoma tumor spheroids based on the chemical exchange saturation transfer effect. Given its advantages, the pMAD hydrogel emerges as a promising material for diverse biomedical applications, including cell carriers, bioimaging, and therapeutic agent delivery.

Cellulose-based film with stable fluorescent, antibacterial, and UV-shielding performance fabricated via Biginelli reaction and enamine functionalization

Cellulosic multifunctional films offer extensive versatility and hold potential for diverse applications across multiple domains. However, the majority of cellulose-based multifunctional film studies have indicated issues with inadequate stability and consistency. Herein, a cellulose-based multifunctional film with exceptional stability was fabricated using multiple chemical modifications. Firstly, the solvent exchange method was used to prepare a cellulose acetoacetate (CAA) hydrogel film. Then, the fluorescent group and gentamicin sulfate (antibacterial group) were bonded to the CAA hydrogel film through Biginelli reaction and the formation of enamine bond, respectively. The resulting film exhibited photoluminescent, high transparency (above 80%), UV-shielding (blocking 90.9% UVA), and antibacterial properties, which are also very stable to external solvents. Hence, the multifaceted films made from cellulose displayed immense promise in various areas including eco-friendly packaging for perishables, ensuring authenticity, and in manufacturing unique types of films.

PH-activated antibacterial coating switching from polyzwitterion to polycation

Stimuli-responsive surfaces have the potentials to solve the trade-off between biocompatibility and antibacterial performance by switching specific function on-demand, which makes them a promising option for developing biocompatible antibacterial surfaces. In this study, a pH-responsive antibacterial surface was created by grafting polycationic brushes and forming an acid-sensitive zwitterionic structure through a spontaneous amino-yne click reaction. Under physiological conditions, the zwitterionic structure provided the surface with good biocompatibility, as confirmed by lower hemolysis and cytotoxicity, as well as low adhesion and activation of platelets. When bacteria begin to colonize on the biomaterial surface, the decrease in local pH can break the acid-sensitive enamine bond and expose the polycations, activating the bactericidal activity. The good and on demand bactericidal activity was verified by the stimulated and authentic bacterial infection conditions. This study highlights the potential of stimuli-responsive zwitterionic surfaces as a valuable option for infection-resistant medical devices.

Photostimulated Covalent Linkage Transformation Isomerizing Covalent Organic Frameworks for Improved Photocatalytic Performances.

Covalent organic frameworks (COFs) offer a desirable platform to explore multichoromophoric arrays for photocatalytic conversion. Symmetric arrangement of choromophoric modules over π-extended frameworks enhances exciton delocalization while impairing excitation density and accordingly photochemical reactivity. Herein, a photoisomerization-driven strategy is proposed to break the excited-state symmetry of ketoenamine-linked COFs with multichoromophoric arrays. Incorporating electron-withdrawing benzothiadiazole facilitates the ultrafast excited-state intramolecular proton transfer (ESIPT) from enamine to keto within 140 fs, resulting in partially enolized COF isomers. The hybrid linkages containing imine and enamine bonds at the node of framework alter the symmetry of electronic structure and enforce the photoinduced charge separation. Increasing the imine-to-enamine ratio further promotes the electron transferred number in a long range, thereby affording the optimum photocatalytic hydrogen evolution rate. This work put forward an ESIPT-induced photoisomerization to build a symmetry-breaking COF with weakened exciton effect and enhanced photochemical reactivity.

A novel crosslinking strategy on functional cellulose-based aerogel for effective and selective removal of dye

Motivated by sustainable development, the huge pressure of harmful dyes wastewater treatment has highlighted an urgent need to develop more effective biomass adsorbents for selective removal and separation of dyes. Herein, cellulose-based aerogel adsorbent (CPB) is successfully prepared through a novel crosslinking strategy for static and dynamic dye removal, starting with the fabrication of cellulose acetoacetate (CAA) and β-cyclodextrin acetoacetate (β-CDAA) through transesterification process, followed by the crosslinking of polymer chains using polyethyleneimine (PEI) through the formation of dynamic enamine bonds and the freeze-drying treatment of three-dimensional (3D) network structures. A maximum adsorption capacity toward methyl orange (MO) up to 1013.11 mg g−1 is achieved at 25 °C. Besides, the CPB aerogel has abundant surface positive charge, which can be employed to selectively remove anions dyes from ternary mixed systems and has additional antibacterial activity. More importantly, the CPB material based on the dynamic crosslinking strategy can be regulated by adjusting pH, which greatly facilitates the reprocessing and utilization of the adsorbent. The cellulose-based aerogel presented in this work could be an extremely promising material for dye wastewater treatment.

Cellulose-based fluorescent films with anti-counterfeiting and UV shielding capabilities enabled by enamine bonds

Based on the enamine reaction, the cellulose-based (CAA-PEA) UV shielding film was prepared by solvent pouring.

Enantioselective Michael Addition/Cyclization/Desymmetrization Sequence of Prochiral Cyclic Hemiacetals and Nitroolefins: Synthesis of Chiral Oxygen-Bridged Bicyclic Compounds.

The organocatalytic enantioselective Michael addition of functionalized prochiral cyclic hemiacetals and nitroolefins has been developed under cooperative enamine and hydrogen bond catalysis. The obtained chiral hemiacetal intermediates could be used in the subsequent diastereocontrolled cyclization/desymmetrization divergent process to access (1) 9-oxabicyclo[3.3.1]nonane or 8-oxabicyclo[3.2.1]octane frameworks via oxocarbenium ion-mediated Friedel-Crafts cyclization, and (2) 2,9-dioxabicyclo[3.3.1]nonane frameworks via intramolecular nucleophilic cyclization. Experimental results suggest that there is neighboring group participation controlling the diastereoselectivities of the desymmetrization process.

Environmentally Stable, Stretchable, Adhesive, and Conductive Organohydrogels with Multiple Dynamic Interactions as High-Performance Strain and Temperature Sensors.

Nowadays, with the rapid development of artificial intelligence, conductive hydrogel-based sensors play an increasingly vital role in health monitoring and temperature sensing. However, the perfect integration of the environmental stability and applied performance of the hydrogel has always been a challenging and significant problem. Herein, we report an environmentally tolerant, stretchable, adhesive, self-healing conductive gel through multiple dynamic interactions in the water/glycerol/ionic liquids medium, which can be used as a high-performance strain and temperature sensor. The random copolymer poly(acrylic acid-co-acetoacetoxyethyl methacrylate) interacts with the branched poly(ethylene imine) (PEI) and Zr4+ ions via the dynamic covalent enamine bonds, coordinations, and electrostatic interactions to improve stretchable (1300%), compressible, fatigue-resistant (1000 cycles at 50% strain), and self-healing performance (95%, 24 h). The combination of water/glycerol/ionic liquids imparts the resulting gel with excellent electrical conductivity, anti-drying, and anti-freezing performance. By means of the above excellent performance, the gel could be used as the flexible strain or pressure sensor with high sensitivity and stability for the detection of the movement, expression, handwriting, pronouncing, and electrocardiogram (ECG) signals in various models. Meanwhile, the resulting gel can be assembled as the temperature sensor to trace the change of temperature accurately and steadily, which has a wide operating window (0 to 100 °C), an ultralow detection limit (0.2 °C), and high sensitivity (2.1% °C-1). It is believed that the strategy for the multifunction and high-performance gel will blaze a new trail for the smart device in health management, temperature detection, and information transmission under various environmental conditions.

Novel multifunctional papers based on chemical modified cellulose fibers derived from waste bagasse

Most technologies to produce multifunctional paper involved the defect of poor uniformity and stability. Herein, a high stability multi-functional cellulose-based paper was developed via a multiple chemical modification derived from waste bagasse. Firstly, the acetoacetyl groups was anchored on the surface of bagasse cellulose fibers by a heterogeneous transesterification. Then, paper was made based on these modified fibers. The fluorophore and gentamicin sulfate (Gen) were bonded in-situ to the paper through Hantzsch reaction and the form of enamine bond, respectively. The resulting paper exhibited excellent multifunctional properties, such as fluorescence property, antibacterial property and hydrophobic property. These properties are very stable to external environments. In addition, relatively mild surface modification has no obvious effect on fibers and shows similar whiteness and stiffness properties as that of the CAA paper. Thus, these novel functional papers held great potential for many fields such as food packaging, anti-counterfeiting, and other specialty papers.

A Degenerate Metal-Templated Catalytic System with Redundant Functional Groups for the Asymmetric Aldol Reaction.

A degenerate zinc-templated catalytic system containing two bipyridine ligands with redundant functional groups for either enamine or hydrogen bond formation was applied to the asymmetric aldol reaction. This concept led to both a higher probability of reaction and rate acceleration. Thus, the catalyst loading could be decreased to a remarkable 2 mol % in what we think is a general approach.

Hajos-Parrish-Eder-Sauer-Wiechert reaction: The definitive reaction mechanism deciphered by DFT calculations

The use of (S)-proline as a catalyst for intramolecular aldol reactions pioneered by Hajos, Parrish, Eder, Sauer and Wiechert paved the way for modern organocatalysis, which earned MacMillan and List the Nobel Prize in Chemistry in 2021. The work reported herein shed light on mechanistic aspects regarding the “prototypal” H-P-E-S-W reaction that, up to date, are unclear. The DFT calculations determined i) the mechanism of the dehydration step of the ketol intermediate that proceeds via an E1cB (elimination, unimolecular, conjugate base) mechanism; ii) the rate-determining steps (RDS) of the H-P-E-S-W reaction that correspond to enamine formation and dehydration; iii) the catalytic role of the water molecule formed during the reaction, that behaves as a proton shuttle during the enamine and CC bond formation and determines a significant lowering of the activation barriers.

Multifunctional Dynamic Enamine‐Based Hydrogels with On‐Demand Removability for Wound Healing

AbstractTo meet the urgent requirement in complex wound treatment, the injectable self‐healing biocompatible hydrogel with tunable mechanical properties, adhesion, on‐demanding removability, antibacterial properties, and hemostasis is designed. For the first time, hydrogels are fabricated through dynamic enamine bonds among dodecane grafted quaternized chitosan (DQCS) and ketone group functionalized polyvinyl alcohol (PVA‐Ket) to achieve efficient wound closure. Owing to the dynamic enamine bond, the hydrogel exhibits self‐healing, injectability and suitable mechanical properties. It can be easily injected into wound, adhere tightly, and bear deformation damage. Dodecyl groups and quaternary amine groups endow the biocompatible hydrogels outstanding antibacterial feature, hemostatic performance, and tissue adhesiveness (40.05 ± 3.21 kPa), which greatly facilitate the wound healing process. Owing to interaction between the amino acid and PVA‐Ket, the hydrogel exhibits painless on‐demand dissolution behavior, causing uninjurious separation from wound sites. Furthermore, in vivo study demonstrates that the hydrogel promotes wound healing by upregulating growth factors, alleviating the inflammation and promoting angiogenesis, collagen deposition, and the growth of granulation tissue, leading to a better curative effect than the commercial gauze and Atrauman. Ag in infected and uninfected wounds. Thus, the multifunctional dynamic enamine‐based hydrogel with on‐demand removability has great potential in clinical applications.

Fabrication of durable fluorescent and hydrophobic cotton fabrics by multiple surface modifications

The functionalization of cotton fabrics with fluorescent and hydrophobic performances are widely used in our daily life. However, most technologies to produce such cotton fabrics involved the defect of poor uniformity and stability. Herein, novel hydrophobic and fluorescent cotton fabrics were developed via a multiple chemical modification. Acetoacetyl groups were firstly introduced on the surface of cotton fibers by transesterification. The 1,4-dihydropyridine (DHP) fluorescent ring and octadecylamine (ODA) were then bonded to the modified fibers through Hantzsch reaction and the form of dynamic enamine bond, respectively. The functional modification process can be accomplished through a one-pot method under room temperature. The resulting modified fabrics exhibited bright fluorescent and good hydrophobic performances, which were very stable to solvents and washing. In addition, the surface modification has no obvious effect on the mechanical performance, whiteness, and thermal stability of cotton fabrics. Such a unique fluorescent and hydrophobic cotton fabrics held great potential for many fields such as anti-counterfeit and functional textiles.

Nickel(II)-Catalyzed [3 + 2] Cycloaddition of Nitrones and Allenoates to Access N-Vinylindoles and N-Vinylpyrroles.

A variety of N-vinylindoles and N-vinylpyrroles were prepared in moderate to good yields through the nickel(II)-catalyzed [3 + 2] cycloaddition of α,β-unsaturated nitrones with allenoates under mild reaction conditions. A rational mechanism for the formation of N-vinylindoles was proposed based on the 18O-labeled experiments and key intermediates detected by high-resolution mass spectrometry trace experiments. The present method highlights a nickel(II)-controlled cyclization, atom-economical reaction, broad substrate scope, good functional group tolerance, and high Z-stereoselectivity for the enamine bond.

Synthesis of Indolo[1,2-a]quinoxalinones through Palladium/Copper-Cocatalyzed Oxidative Isocyanide-Insertion Cyclization of Indoles and Hydrolysis of Enamines

AbstractA novel Pd/Cu-cocatalyzed isocyanide-insertion cyclization of indoles and hydrolysis of enamines has been developed for the construction of indolo[1,2-a]quinoxalinones. A secondary amine group on the N-phenylindole skeleton acts as an important directing groups that participates in activation of the C(2)-position of the indole and the subsequent isocyanide-insertion cyclization. The fragile generated enamine bond is easily hydrolyzed by the acid medium to give the corresponding quinoxalinone skeleton. This regioselective and high-yielding transformation, which avoids the use of hazardous CO gas, might be extendable to syntheses of natural polycyclic products.

The Study on Chlorination by Sulfuryl Chloride of Benzene/Pyridine Carboxamides and Carbonitriles

In the chlorination of N-[2-aryl-1-(1-piperidinylcarbonyl)ethenyl]arenecarboxamides, it has been found that a derivative having two methoxy substituents on the arenecarbonyl ring undergoes chlorination on the same ring rather than converting into the expected enamine bond chlorination product. Based on the above results, the chlorination of benzamides/nicotinamides by sulfuryl chloride (SO2Cl2) has been studied. We developed a method of synthesizing aromatic chlorinated compounds by treating aromatic amides or nitriles with SO2Cl2 in dichloromethane at 0oC without catalyst. This is a new mild method and gives good yields, especially when benzene ring is substituted by amide or cyano group together with the alkoxy group.

A Facile Strategy to Fabricate Polysaccharide‐Based Magnetic Hydrogel Based on Enamine Bond†

Summary of main observation and conclusionMagnetic hydrogels have found extensive applications in fields such as soft robotics, drug delivery and shape morphing. Here a facile method was fabricated to prepare polysaccharide‐based magnetic hydrogels. The chitosan‐Fe3O4 ferrofluid was obtained by dispersing carboxyl groups modified Fe3O4 nanoparticles uniformly in chitosan matrix. Subsequently, the magnetic polysaccharide hydrogel was obtained by simply mixing cellulose acetoacetate solution with chitosan‐Fe3O4 ferrofluid. The structures and properties of the magnetic hydrogel were analyzed using Fourier‐transform infrared spectroscopy, rheological recovery, responsiveness, and stability measurements. The results indicated that magnetic polysaccharide hydrogel showed pH responsiveness and excellent self‐healing properties, and the hydrogel manifested outstanding stability under physiological conditions (37 °C) for 72 h. In addition, the injectable polysaccharide‐based hydrogel exhibited sensitive magnetic responsive and shape‐shifting ability under an external magnetic field. Therefore, the strategy for the facile preparation of the magnetic polysaccharide‐based hydrogel in this work could provide a benign and versatile method for achieving self‐healing, responsive, injectable properties for the application in biomedical fields.

Durable and Effective Antibacterial Cotton Fabric Collaborated with Polypropylene Tissue Mesh for Abdominal Wall Defect Repair.

A feasible, efficient antibacterial and anti-infective mesh for clinical abdominal wall defect repair is significant, but challenging due to the complexity of the postoperative wound environment. Herein, a simple strategy was provided to construct woven cotton fabric modified with gentamicin (Gem) via the enamine bonds. The obtained cotton fabric possessed favorable antibacterial properties against E. coli and S. aureus with the bactericidal rate of over 99.99% and could be combined with a commercial polypropylene (PP) mesh to serve as a two-layer composite mesh for abdominal wall defect repair. The antibacterial cotton layer was systematically characterized by FTIR, XPS, SEM, EDS, and mechanical measurements. The C2C12 cells and human fibroblasts were employed to assess the cytocompatibility of the composite mesh in vitro. Furthermore, the rat abdominal wall defect model was used to evaluate the efficacy of antibacterial and anti-infection properties. It was demonstrated that the two-layer composite mesh possessed favorable biocompatibility and satisfactory anti-infection properties involved in abdominal wall defect repair. Therefore, this synergetic two-layer composite mesh would out-perform surgical PP meshes in preventing infectious complications.

Imine or Enamine? Insights and Predictive Guidelines from the Electronic Effect of Substituents in H-Bonded Salicylimines.

Imine and enamine bonds decorate the skeleton of numerous reagents, catalysts, and organic materials. However, it is difficult to isolate at will a single tautomer, as dynamic equilibria occur easily, even in the solid state, and are sensitive to electronic and steric effect, including π-conjugation and H-bonding. Here, using as model Schiff bases generated from salicylaldehydes and TRIS in a set of linear free energy relationships (LFER), we disclose how the formation of either imines or enamines can be controlled and provide a comprehensive framework that captures the structural underpinning of this prediction. This work highlights the potentiality of tailor-made designs en route to compounds with desirable functionality.