aza-Michael Reaction Research Articles

Facile fabrication of superhydrophobic porous materials using the water-based aza-Michael reaction for high-efficiency oil-water separation

Superhydrophobic porous materials are widely used in oil-water separation due to their water-blocking and oil-passing properties. However, the preparation of most superhydrophobic porous materials is generally energy-intensive and must be performed using organic solvents. In this study, we describe a straightforward and cost-effective strategy for fabricating superhydrophobic coatings on nanosized soil particle-modified stainless steel mesh (SSM). The coating is prepared via the aza-Michael reaction of stearyl acrylate and melamine-urea–formaldehyde (MUF) resin catalysed by methyl cyclodextrin in water. Superhydrophobic meshes with water contact angles (WCAs) exceeding 150° are obtained, exhibiting extraordinary water repellency. The superhydrophobic mesh also effectively prevents surface contamination, creating a self-cleaning surface that is both waterproof and dustproof. Most importantly, the superhydrophobic mesh presents excellent oil separation performance for oil-water mixtures of various compositions, maintaining extremely high separation efficiency (>98%) even after 80 cycles. Additionally, we successfully apply this strategy to the preparation of superhydrophobic melamine sponges with excellent oil adsorption capacity (17.6–44.2 g/g). This innovative study provides an effective strategy for designing biomimetic superhydrophobic surfaces and is a promising development in the field of environmentally friendly oil-water separators.

K2CO3/TBAB, a Composite of Inorganic and Organic Salts, a Novel and Powerful Media for Regioselective Michael Addition of Dihydropyrimidinones to Acrylic Esters Under and Without Solvent Conditions

Aims: Synthesis of dihydropyrimidinones derivatives. Background: carrying out reactions in the green route and organic solvent-free conditions. Objective: Regioselective Michael addition of dihydropyrimidinones to acrylic esters. Methods: The reaction proceeded in the presence of K2CO3/TBAB, a media of inorganic base K2CO3 and organic ionic salt TBAB (tetrabutylammonium bromide) at 100oC. Results: A series of new dihydropyrimidinone derivatives using aza-Michael addition reaction were synthesized under solvent-free conditions. Conclusion: The reaction is characterized by high efficiency, relatively short reaction time, high yields, simple environmentally friendly reaction conditions. Other: The reaction of acrylic esters with dihydropyrimidinones produced N3-substituted derivative of dihydropyrimidinones with 85-95% yields in 6 h.

Enantioselective Total Synthesis of Spirotryprostatin A.

In this paper, we disclosed a novel enantioselective total synthesis of spirotryprostatin A (1) in 15 steps with a 7.4% total yield from commercially available 2-iodo-5-methoxyaniline and γ-butyrolactone. The key step features of this synthesis include the copper-catalyzed cascade reaction of o-iodoaniline derivatives with alkynone to introduce the quaternary carbon stereocenter and an aza-Michael tandem reaction to construct the spiro[pyrrolidine-3,3'-oxindole] moiety.

Harnessing β-Hydroxyl Groups in Poly(β-Amino Esters) toward Robust and Fast Reprocessing Covalent Adaptable Networks

Poly(β-amino esters) (PBAEs), which include tertiary amines at the β-position of ester linkages, are promising in biomaterials due to their biodegradability and pH responsiveness. Such characteristics in the molecular structure are also appealing for designing catalyst-free covalent adaptable networks (CANs), but this has rarely been explored in the literature. Herein, we synthesize a series of PBAE-based CANs by aza-Michael addition, using diacrylate monomers with and without β-hydroxyl groups, and a triamine crosslinker. By leveraging hydrogen bonding, the thermal and mechanical properties of these PBAE-based CANs are effectively tuned through the monomer composition. Owing to the numerous tertiary amines serving as internal catalysts, these CANs undergo catalyst-free network exchange through a dynamic aza-Michael reaction. Interestingly, increasing the amount of β-hydroxyl groups accelerates overall stress relaxation from the synergistic effects of transesterification (associative type) at lower temperatures and dynamic aza-Michael reaction (dissociative type) at higher temperatures. Based on these features, we successfully demonstrate the reprocessing and healing at elevated temperatures under mild pressure, as well as shape memory and shape reconfiguration. Thus, controlling the β-hydroxyl group concentration in PBAE-based CANs is a useful strategy for enhancing both the mechanical strength and reprocessing rate.

Ascorbic Acid-Modified Silicones: Crosslinking and Antioxidant Delivery.

Vitamin C is widely used as an antioxidant in biological systems. The very high density of functional groups makes it challenging to selectively tether this molecule to other moieties. We report that, following protection of the enediol as benzyl ethers, the introduction of an acrylate ester at C1 is straightforward. Ascorbic acid-modified silicones were synthesized via aza-Michael reactions of aminoalkylsilicones with ascorbic acrylate. Viscous oils formed when the amine/acrylate ratios were <1. However, at higher amine/acrylate ratios with pendent silicones, a double reaction occurred to give robust elastomers whose modulus is readily tuned simply by controlling the ascorbic acid amine ratio that leads to crosslinks. Reduction with H2/Pd removed the benzyl ethers and led to increased crosslinking, and either liberated the antioxidant small molecule or produced antioxidant elastomers. These pro-antioxidant elastomers show the power of exploiting natural materials as co-constituents of silicone polymers.

Template-Less and Surfactant-Less Synthesis of CeO2 Nanostructures for Catalytic Application in Ipso-hydroxylation of Aryl Boronic Acids and the aza-Michael Reaction.

Due to its excellent physicochemical properties, CeO2 has found great importance as an electrochemical and in electronics, photocatalysis, sensing, and heterogeneous catalysis. Herein, we report the surfactant-less and template-less synthesis of CeO2 nanostructures by the hydrothermal method. The synthesized CeO2 nanostructures have been characterized in detail by electron microscopy, spectroscopy, diffractometry, and other analytical methods. The XRD studies revealed the formation of pure crystalline CeO2, possessing a cubic fluorite structure with an average crystallite size of 15.6 to 16.4 nm. Electron microscopy studies reveal the formation of cube-shaped CeO2 nanostructures with sizes below 25 nm. The cube-shaped CeO2 nanostructures exhibited a higher BET surface area compared to their bulk counterparts. The XPS analysis has confirmed the existence of Ce in the mixed oxidation states of +3 and +4, while O is present as O2- in the sample. The as-synthesized CeO2 nanostructures exhibit excellent catalytic activity in both the ipso-hydroxylation of aryl boronic acids and the aza-Michael reaction. The analysis of the used catalyst has confirmed its stability under the reported reaction conditions. The catalysts retain their catalytic activity up to the fifth run in both types of reactions, which is economically beneficial for industrial application.

Thia-Michael Reaction: The Route to Promising Covalent Adaptable Networks.

While the Michael addition has been employed for more than 130 years for the synthesis of a vast diversity of compounds, the reversibility of this reaction when heteronucleophiles are involved has been generally less considered. First applied to medicinal chemistry, the reversible character of the hetero-Michael reactions has recently been explored for the synthesis of Covalent Adaptable Networks (CANs), in particular the thia-Michael reaction and more recently the aza-Michael reaction. In these cross-linked networks, exchange reactions take place between two Michael adducts by successive dissociation and association steps. In order to understand and precisely control the exchange in these CANs, it is necessary to get an insight into the critical parameters influencing the Michael addition and the dissociation rates of Michael adducts by reconsidering previous studies on these matters. This review presents the progress in the understanding of the thia-Michael reaction over the years as well as the latest developments and plausible future directions to prepare CANs based on this reaction. The potential of aza-Michael reaction for CANs application is highlighted in a specific section with comparison with thia-Michael-based CANs.

Green synthesis of chitooligosaccharide-PEGDA derivatives through aza-Michael reaction for biomedical applications

Chitooligosaccharide (COS) as an emerging material carbohydrate polymer with huge potential in biomedical applications was prepared using a microwave-assisted process. The obtained COS exhibited reduced molecular weight (Mw) and higher water solubility in comparison to chitosan while preserving the main saccharide structure and same degree of deacetylation (DD). The optimized COS (13 kDa) was then used to synthesize a new family of COS-poly(ethylene glycol) diacrylate (PEGDA) derivatives based on aza-Michael addition of acrylate groups of PEGDA to the amine groups of COS in the absence of any exterior agents. The modulation of the reaction time, temperature, pH and NH2:acrylate molar ratio, had a strong influence on the Michael reaction progress. At higher degrees of conversion of acrylate groups, COS-PEGDA derivative formed gel with high biocompatibility towards human bone mesenchymal stem cells (hBMSCs). These COS-PEGDA hydrogels synthesized at mild conditions through a green chemistry are, therefore, an innovative system combining adequate biological performance, ease of preparation, and an environmentally friendly concept of production.

Synthesis, stereochemistry and in vitro STD NMR and in silico HIV-1 PR enzyme-binding potential of MBH-derived inhibitors

Aza-Michael reactions of a pyridine-3-carbaldehyde-derived Morita-Baylis-Hillman (MBH) adduct with various amines have afforded a series of 10 diastereomeric products, stereochemical analysis of which has been achieved using a combination of NMR (1D, 2D and NOESY) and computer modelling methods. Saturation Transfer Difference (STD) 1H NMR spectroscopy and in silico molecular docking studies have been used to explore the HIV-1 protease sub-type C enzyme binding potential of these compounds in five different HIV-1 PR enzyme receptors.

Green Synthesis of Biobased Soft Foams by the Aza-Michael Reaction

Green Synthesis of Biobased Soft Foams by the Aza-Michael Reaction

Liriogerphines A-D, a Class of Sesquiterpene-Alkaloid Hybrids from the Rare Chinese Tulip Tree Plant.

Liriogerphines A-D (1-4, respectively), an unprecedented class of hybrids of germacranolide-type sesquiterpenoids and aporphine-type alkaloids, were isolated from the rare medicinal plant Liriodendron chinense. Their structures were elucidated by comprehensive spectroscopic analyses combined with electronic circular dichroism calculations and X-ray crystallographic data. Biosynthetically, an aza-Michael addition reaction is proposed to be involved in the assemblies of this class of hybrids. Compound 4 exhibited cytotoxicity against leukemia cells via inducing apoptosis and inhibiting Bcl-2 expression.

Stereochemical switch driven by crystallization: Interplay between stoichiometry and configuration of the products.

An intriguing example of a crystallization-induced stereochemical switch in the configuration of aza-Michael reaction products is described. Depending on both the stereochemical purity and stoichiometric ratio of the chiral amine used, the reaction delivers crystalline diastereomers of a different stereochemistry. The optically pure diastereomer smoothly converts to its racemic epimer salt upon the addition of a complementary chiral amine.

Catalyst and base free aza-Michael addition reaction: Synthesis of poly-substituted 4-pyrazole based benzopyrans

An efficient and catalyst free protocol has been disclosed for aza-Michael addition reaction of pyrazoles with 2-aryl-3-nitro-2H-chromene derivatives, which provides synthetically important 4-pyrazole-3-nitrobenzopyrans at room temperature. In this one-pot transformation, good to excellent yield of the products up to 84% were obtained and generated a new CN bond. The relative configuration of the product was characterized by a single crystal X-ray crystallography. This protocol is extensively applicable for the wide substrate scope, high yields, easy accessibility, as well as base and catalyst free condition.

One-pot solvent-free microwave-assisted aza-Michael addition reaction of acrylonitrile

A novel and highly effective one-pot microwave-assisted aza-Michael addition reaction of acrylonitrile, as Michael acceptor with various primary aliphatic and aromatic amines, as Michael donor has been reported. The reaction was catalyzed by a cost-effective, highly efficient and eco-friendly catalyst, molecular sieve of 4 A0 size, under solvent-free conditions. A detail investigation on reaction controlling parameters like reaction timing and amount of catalyst was studied. The plausible mechanistic pathway has been proposed for the formation of acrylonitrile adducts. The identity of the synthesized products was established by conventional spectroscopic techniques FT-IR, 1H and 13C{1H} NMR, ESI-MS and DLS measurements. DLS result shows hydrodynamic diameter of lower alkyl chain in the range of 200–300 nm and for higher alkyl chain around 1 μm. Sheldon's hot filtration test confirms the significance of the catalyst and their heterogeneity was also confirmed by recycling it for five consecutive cycles without any noticeable change in the yield.

NIPAm-Based Modification of Poly(L-lysine): A pH-Dependent LCST-Type Thermo-Responsive Biodegradable Polymer.

Polylysine is a biocompatible, biodegradable, water soluble polypeptide. Thanks to the pendant primary amines it bears, it is susceptible to modification reactions. In this work Poly(L-lysine) (PLL) was partially modified via the effortless free-catalysed aza-Michael addition reaction at room temperature by grafting N-isopropylacrylamide (NIPAm) moieties onto the amines. The resulting PLL-g-NIPAm exhibited LCST-type thermosensitivity. The LCST can be tuned by the NIPAm content incorporated in the macromolecules. Importantly, depending on the NIPAm content, LCST is highly dependent on pH and ionic strength due to ionization capability of the remaining free lysine residues. PLL-g-NIPAm constitutes a novel biodegradable LCST polymer that could be used as “smart” block in block copolymers and/or terpolymers, of any macromolecular architecture, to design pH/Temperature-responsive self-assemblies (nanocarriers and/or networks) for potential bio-applications.

Asymmetric Phase-Transfer Catalytic aza-Michael Addition to Cyclic Enone: Highly Enantioselective and Diastereoselective Synthesis of Cyclic 1,3-Aminoalcohols.

The highly enantioselective aza-Michael reaction of tert-butyl β-naphthylmethoxycarbamate to cyclic enones has been accomplished by using a new cinchona alkaloid derived C(9)-urea ammonium catalyst under phase-transfer catalysis conditions with up to 98% ee at 0 °C. The resulting aza-Michael adducts can be converted to versatile intermediates by selective deprotection and the cyclic 1,3-aminoalcohols by diastereoselective reduction with up to 32:1, which have been widely used as important pharmacophores in pharmaceutical development.

Antibacterial Activity of Small Molecules Which Eradicate Methicillin-Resistant Staphylococcus aureus Persisters.

The serious challenge posed by multidrug-resistant bacterial infections with concomitant treatment failure and high mortality rates presents an urgent threat to the global health. We herein report the discovery of a new class of potent antimicrobial compounds that are highly effective against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The compounds were efficiently synthesized in one-pot employing a cascade of Groebke–Blackburn–Bienaymé and aza-Michael addition reactions. Phenotypic screening of the pilot library against various bacterial species including methicillin-sensitive and MRSA strains, has identified potent chemotypes with minimal inhibitory concentrations (MIC) of 3.125–6.25 μg/ml. The most potent compounds were fast-acting at eradicating exponentially growing MRSA, with killing achieved after 30 min of exposure to the compounds. They were also able to kill MRSA persister cells which are tolerant to most available medications. Microscopic analysis using fluorescence microscope and atomic force microscope indicate that these compounds lead to disruption of bacterial cell envelopes. Most notably, bacterial resistance toward these compounds was not observed after 20 serial passages in stark contrast to the significant resistance developed rapidly upon exposure to a clinically relevant antibiotic. Furthermore, the compounds did not induce significant hemolysis to human red blood cells. In vivo safety studies revealed a high safety profile of these motifs. These small molecules hold a promise for further studies and development as new antibacterial agents against MRSA infections.

Rapid synthesis of polyester based single-chain polymeric nanoparticles via an intra-molecular aza-Michael addition reaction

An alternative method to produce single-chain polymeric nanoparticles using the aza-Michael addition reaction of a linear polyester containing in-chain reactive triple bonds is introduced.

Introducing the aza-Michael addition reaction between acrylate and dihydropyrimidin-2(1H)-thione into polymer chemistry

The aza-Michael addition reaction between dihydropyrimidin-2(1H)-thione and acrylate has been used to fabricate new polymers through different synthesis routes.

Combined aza-Michael and radical photopolymerization reactions for enhanced mechanical properties of 3D printed shape memory polymers.

3D printed shape memory polymers (SMP) were formed by combining aza-Michael addition and light initiated radical polymerization. Amine consumption and acrylate conversion were monitored by 1H-NMR and Fourier transform infrared spectroscopies. Dynamic mechanical analysis and cyclic thermomechanical tensile tests enabled direct observation of the polymer network changes. Increased homogeneity of the 3D network and enhanced SMP properties were achieved after the reaction between residual acrylate functions trapped in the vitrified medium with the secondary amines formed during the process. This allows the fabrication of shape memory objects by 3D printing.