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AbstractRecently, there has been an increased interest in developing new antibacterial agents that target the MurB inhibition, which is necessary for bacterial survival. We developed a two-step tandem protocol to synthesize 15 new bis(pyrazolo[1,5-a]pyrimidines), which are attached to alkane cores by amide linkages. The protocol involved reacting the appropriate bis(2-cyanoacetamides) with dimethylformamide-dimethylacetal in toluene at 80 °C for 3-4 h. The crude bis(2-cyano-3-(dimethylamino)acrylamides) was collected, then reacted with 3,5-diamino-1H-pyrazoles. The reaction gave the desired products in 82-92% yields after 5-6 h of heating at reflux in pyridine. Bis(2,7-diamino-3-(4-methoxybenzyl)pyrazolo[1,5-a]pyrimidine-6-carboxamides) demonstrated comparable efficacy to ciprofloxacin. Their MIC and MBC ranged from 2.8-3.0 and 5.7-6.0 µM, respectively, against S. aureus and E. coli. Moreover, these products displayed promising MurB inhibitory activity with IC50 ranging from 7.8 to 8.0 µM. [ABSTRACT FROM AUTHOR]

The aza-Michael addition reaction of primary and secondary amines to α,β-unsaturated olefins viz; acrylonitrile, phenyl vinyl sulfone and dimethyl maleate has been carried out using 5–10 mol% Co(NO3)2.6H2O as a catalyst in t-BuOMe at 80–100 °C, giving rise to the desired β-aminocarbonyl compounds or sulfones in moderate to good yields. A wide range of aromatic amines, even those bearing electron withdrawing groups could be added to activated olefins via this strategy. Addition of (hetero)aromatic amines were also feasible, while in case of 2-aminopyridine the reaction was found to be effective only when AgOTf was added along with the catalyst. The aliphatic amines; benzylamine, dibenzylamine, di-n-butylamine were also smoothly added to acrylonitrile and phenyl vinyl sulfone. The methodology describes cobalt(II) nitrate as an eco-friendly, cheap and shelf available catalyst suitable for performing the Michael-type hydroamination reactions. [ABSTRACT FROM AUTHOR]

The synthesis and biosynthesis of the complex saxitoxin (STX) structure have garnered significant interest. Previously, we hypothesized that the tricyclic skeleton of STX originates from the monocyclic precursor 11‐hydroxy‐IntC’2 during biosynthesis, although direct evidence has been lacking. In this study, we identified conditions to synthesize a proposed tricyclic biosynthetic intermediate, 12,12‐dideoxy‐decarbamoyloxySTX (dd‐doSTX), along with its 6‐epimer (6‐epi‐dd‐doSTX) and a bicyclic compound, in a single step from di‐Boc protected 11‐hydroxy‐IntC’2. The reaction mechanism involves successive aza‐Michael addition of a guanidino amine to the conjugated olefin. Notably, both dd‐doSTX and 6‐epi‐dd‐doSTX were detected in a toxin‐producing cyanobacterium, suggesting that the biosynthetic enzymes may generate these compounds via similar mechanisms. [ABSTRACT FROM AUTHOR]

The present study provided an efficient synthesis pathway to the azepino[5,4,3‐cd]indoles using N‐sulfonyl‐1,2,3‐triazoles and 4‐vinylindoles through a cascade carbene insertion and intramolecular aza‐Michael addition. This method is distinguished by mild reaction conditions, straightforward operational steps, accessible starting materials and broad substrate compatibility. Furthermore, the versatility of this reaction with various Michael acceptors significantly broadens the scope of potential substrates. The ability to further transform the resulting multifunctional products underscores the promising applications of this approach in indole nitrogen heterocyclic synthesis. [ABSTRACT FROM AUTHOR]

This document provides information on the synthesis and characterization of various compounds, including β-aminonitriles, β-amino sulfones, and dimethyl aspartates. The compounds were synthesized using lanthanoid triflates Yb(OTf)3 and Tb(OTf)3 as catalysts and the reactions were optimized for yield. The document also includes spectroscopic data, such as melting points and NMR spectra, for the compounds. The data presented in the document match those previously reported in the literature. The document acknowledges the facilities used for the research and dedicates the work to the late Prof. Ibrahim Ibnusaud. [Extracted from the article]

This works documents a new silica gel-supported nanocatalyst (Si@NSBPdNPs 3) with low Pd loadings for n-alkylation reactions at room temperature. Post synthesis characterisation using SEM-EDX and ICP techniques provided a quantitative assessment of palladium species. Additionally, TEM analysis unveiled an average palladium nanoparticle size of 5.87 ± 0.2 nm. In-depth X-ray Photoelectron Spectroscopy (XPS) analysis revealed its predominant composition as Pd(0) complexed to a Schiff base ligand on low cost silica matrix. The nanocatalyst exhibited high efficacy in the catalysis of n-alkylation (Michael addition) reactions with various α,β-unsaturated Michael acceptors, yielding the corresponding n-alkyl products at room temperature with exceptional yields. Notably, the catalyst exhibited good stability and could be easily separated from the reaction mixture. Moreover, the catalyst displayed recyclability potential, maintaining its original catalytic efficacy for up to seven cycles without any discernible loss.

Acidic ionic liquids are a subset of ionic liquids where the cation or anion possess acidic properties with huge applications in various fields. Here we describe environmentally safe and highly efficient conjugate addition of aromatic and aliphatic amines to α, β-unsaturated compounds in the presence of novel acidic ionic liquids. The acidic ionic liquid catalyst was prepared by combining benzyl chloride with 2-(dimethylamino) ethanol and SnCl2 in a simpler manner. The resulting acidic ionic liquid was characterized using SEM, EDS and FTIR spectroscopy. In the presence of ionic liquids, a wide variety of amines undergo facile conjugate addition to α, β-unsaturated compounds affording the corresponding β-amino compounds in good to excellent yields (72–97 %), shorter reaction times (1–4 h) and mild reaction conditions (60 °C). Furthermore, the study demonstrated the sustainability of the process by showcasing that the acidic ionic liquids could be reclaimed and reused for up to five cycles without compromising their catalytic effectiveness.

A novel approach has been developed for the synthesis of bicyclic β, γ‐fused bicyclic γ‐ureasultams containing two consecutive chiral centers through an intramolecular Mannich and aza‐Michael addition cascade of alkenyl sulfamides. The straightforward practical procedure and readily available starting materials enable the synthesis of variously substituted ureasultams. In addition, bicyclic γ‐ureasultams is a class of potential biotin analogues. [ABSTRACT FROM AUTHOR]

In this paper, we present the synthesis of poly(β‐amino ester)‐based solid polymer electrolytes (SPE) from off‐stoichiometric acrylate‐amine formulations using one‐step, catalyst and solvent free aza‐Michael addition. By varying the monomers, the pendant functionality of the polymer chain structure could be altered. All synthesized polymers yield freestanding and easy to handle electrolyte films and hence are evaluated as a new class of SPEs. The SPE with 1,4‐butanediol diacrylate and propylamine showed the highest conductivity of 1.15 × 10−7 S cm−1 at 30°C with 10 wt% lithium bis(trifluoromethanesulfonyl)imide. Because of the presence of the various functional groups in the structure, the polymer chain aids in the movement of both the anion and the cation. [ABSTRACT FROM AUTHOR]

The area of combining an enzyme and transition metals to catalyse the sequence of reactions in one-pot which improve total conversion and operational stability has seen tremendous growth in recent years. Herein, we describe the synthesis and substrate controlled modification of β-aminocarbonyl using α-amylase enzyme and Pd-based catalyst in the one-pot. Moreover, the chemo-enzymatic approach provides substituted indole derivatives unprecedentedly when isocyanide was used in the reaction. In the second phase, isocyanide was replaced by phenyl boronic acid which in turn provides the substituted amino biaryls in good yield. Next, the feasibility of one-pot chemo-enzymatic approach was proved by employing substituted 2-bromo aniline along with different isocyanide/phenyl boronic acid and obtained the corresponding products in 56–84% isolated yield. [ABSTRACT FROM AUTHOR]

A chemoenzymatic approach that combines chemical and bio‐catalyst has proven very useful in synthetic chemistry, however, mutual deactivation of chemical and bio‐catalyst when employed in the same pot is still a challenge. In this context, the development of nanobiohybrid catalysts has played an important role and overcoming the issue of mutual deactivation between catalysts to a certain extent. Herein, we design and synthesize a novel heterogeneous recyclable nanobiohybrid catalyst comprising palladium nanoparticles and α‐amylase from Aspergillus oryzae immobilized onto halloysite nanotubes as a solid heterogeneous support. Further, the wider applicability of the developed nanobiohybrid catalyst is revealed in the one‐pot chemoenzymatic synthesis of functionalized biphenyls and bis(indolyl)methanes which consists of Pd‐catalyzed Suzuki‐Miyaura coupling and α‐amylase mediated aza‐Michael addition or electrophilic substitution reactions respectively. Further, the robustness and generality of the developed one‐pot chemoenzymatic synthesis are demonstrated by incorporating different substitutions at the starting materials and obtaining the corresponding products in moderate to good yields. [ABSTRACT FROM AUTHOR]

BACKGROUND: The enzymes involved in the 2‐C‐methyl‐d‐erythritol 4‐phosphate (MEP) pathway are attractive targets of a new mode of action for developing anti‐infective drugs and herbicides, and inhibitors against 1‐deoxy‐d‐xylulose 5‐phosphate reductoisomerase (IspC), the second key enzyme in the pathway, have been intensively investigated; however, few works are reported regarding IspC inhibitors designed for new herbicide discovery. RESULTS: A series of fosmidomycin (FOS) analogs were designed with nitrogen‐containing linkers replacing the trimethylene linker between the two active substructures of FOS, phosphonic acid and hydroxamic acid. Synthesis followed a facile three‐step route of sequential aza‐Michael addition of α‐amino acids to dibenzyl vinylphosphonate, amidation of the amino acid carboxyl with O‐benzyl hydroxylamine, and simultaneous removal of the benzyl protective groups. Biological activity evaluation of IspC and model plants revealed that some compounds had moderate enzyme and model plant growth inhibition effects. In particular, compound 10g, which has a N‐(4‐fluorophenylethyl) nitrogen‐containing linker, exhibited the best plant inhibition activities, superior to the control FOS against the model plants Arabidopsis thaliana, Brassica napus L., Amaranthus retroflexus and Echinochloa crus‐galli. A dimethylallyl pyrophosphate rescue assay on A. thaliana confirmed that both 10g and FOS exert their herbicidal activity by blocking the MEP pathway. This result consistent with molecular docking, which confirmed 10g and FOS binding to the IspC active site in a similar way. CONCLUSION: Compound 10g has excellent herbicidal activity and represents the first herbicide lead structure of a new mode of action that targets IspC enzyme in the MEP pathway. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In recent years, the use of solvent-free reactions represents a challenge for organic chemists, since it would help to optimize methodologies and contribute to the development of sustainable chemistry. In this regard, our research group has intensified efforts in the search for reactions that can be carried out in the absence of a solvent. In this paper, we present a protocol for the aza-Michael addition of benzylamine to α,β-unsaturated esters to prepare N-benzylated β-amino esters in the presence of catalytic amounts of DBU (0.2 eq) via solvent-free reaction. Depending on the α,β-unsaturated esters, we observed a reduction in reaction times, with good to excellent yields for aza-Michael addition. [ABSTRACT FROM AUTHOR]

Despite the continued efforts and advancements in anti‐cancer drug discovery, cancer is still considered as one of the leading causes of mortality globally. Hence, the discovery of novel chemotherapeutic agents that displayed a prominent effect against cancer is a pressing need. In this study, an expeditious cascade was used to access a pilot library of indolopyrazine fused to imidazole and pyrimidinone heterocyclic scaffolds. The synthetic strategy utilized a cascade reaction that combined Mannich with aza‐Michael addition reactions followed by coupling with a variety of amines. Phenotypic screening of the developed library against HCT116 colon and MCF‐7 breast cancer cell lines identified chemotypes that formed the basis for hit‐to‐lead development of anti‐cancer agents. The intriguing architecture and scope of functional variability of these types of pentacyclic molecules made them appropriate motifs for the development of lead drug candidates. [ABSTRACT FROM AUTHOR]

A highly α-regioselective N-nucleophilic allylic substitution of cyclic MBH alcohols and acetates with imidazole or benzimidazole, in toluene at reflux with an azeotropic distillation, was successfully carried out with no catalysts or additives, affording the corresponding N-substituted imidazole derivatives in good yields. On the other hand, in refluxing toluene or methanol, the aza-Michael addition of imidazole onto acyclic MBH alcohols was performed using DABCO as an additive, leading to the corresponding 1,4-adducts in 70–84% yields.

Starting from acid chlorides, alkynes, tryptamines, and acryloyl chloride, 21 densely substituted tetrahydro-β-carbolines were prepared in a four-component, one-pot reaction. In this study, the aza-Michael addition step to generate intermediate enaminones was optimized in the presence of ytterbium triflate. Moreover, apart from acryloyl chloride, all reactants could be deployed in almost equimolar ratios, which increases the atom economy of the sequence. For mechanistic rationalization, the concluding aza-anellation was investigated by DFT calculations on potential intermediates and corresponding activation energies, revealing that the aza-anellation proceeds via ene reaction rather than via electrocyclization.

A novel series of 1,2-dihydroquinolinhydrazonopropanoate have been synthesized via a convenient aza-Michael addition reaction between hydrazinylquinolinones and ethyl propiolate in ethanol under refluxing temperature. The structures for all obtained products were confirmed with FTIR, NMR spectrums, as well as mass spectrometry. In addition, the monoclinic structure for compounds 8a, 8c, and 8d was also confirmed via X-ray crystallography analyses. The E-configuration for the obtained products was confirmed form the X-ray analysis. On the other hand, the crystal packing shows that the intermolecular and hydrogen bonds between atoms are parallel to the bc plan.

A series of 3-aminopyrrolidine-2,5-dione derivatives was synthesized and tested for anticonvulsant activity. Succinimide derivatives were obtained from a simple solvent-based reaction and a mechanochemical aza-Michael reaction of maleimide or its N-substituted derivatives with selected amines. The structure of the compounds was confirmed by spectroscopic methods (NMR, FT-IR, HPLC, ESI-MS, EA and XRD for four compounds). The cytotoxic activity of the succinimide derivatives was evaluated using HepG2 cells for hepatocytotoxicity and SH-SY5Y cells for neurocytotoxicity. None of the studied compounds showed hepatocytotoxicity and two showed neurocytotoxicity. Initial anticonvulsant screening was performed in mice using the psychomotor seizure test (6 Hz, 32 mA). The selected compounds were evaluated in the following acute models of epilepsy: the maximal electroshock test, psychomotor seizure test (6 Hz, 44 mA), subcutaneous pentylenetetrazole seizure test, and acute neurotoxicity (rotarod test). The most active compound 3-((4-chlorophenyl)amino)pyrrolidine-2,5-dione revealed antiseizure activity in all seizure models (including pharmacoresistant seizures) and showed better median effective doses (ED50) and protective index values than the reference compound, ethosuximide. Furthermore, 3-(benzylamino)pyrrolidine-2,5-dione and 3-(phenylamino)pyrrolidine-2,5-dione exhibited antiseizure activity in the 6 Hz and MES tests, and 3-(butylamino)−1-phenylpyrrolidine-2,5-dione and 3-(benzylamino)−1-phenylpyrrolidine-2,5-dione exhibited antiseizure activity in the 6 Hz test. All active compounds demonstrated low in vivo neurotoxicity in the rotarod test and yielded favourable protective indices.

The objective of this study is to present a promising route to design a series of new poly(vinyl chloride) (PVC) films cross-linked with polyetheramine (PEA), namely jeffamine, by combining copper (I)-catalyzed azide-alkyne cycloaddition "click" reaction (CuAAC) and aza-Michael addition (PVC-Jeffs). In the first step, the clickable azido‐functional PVC is prepared easily by displacement reaction between chlorine groups and sodium azide (PVC-N3) and then reacted with propargyl acrylate by CuAAC (PVC-acr). The second step is aza-Michael addition of PVC-acr and Jeffamine to achieve the desired PVC-Jeffs. Transparent and uniform films are prepared by casting from dichloromethane solvent. The effect of loading ratio by weight (PVC/Jeffamine (w/w) = 9:1; 8:2 and 7:3) on the thermal properties of final PVC-Jeffs is systematically explored. The chemical structure of PVC-Jeffs and their intermediates is characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H-NMR) spectroscopies, whereas thermal characteristics of the samples are investigated by thermogravimetric (TGA) and differential scanning calorimetry (DSC) analyses. The higher Jeffamine loaded PVC-Jeff exhibit enhanced thermostability and glass transition temperature with the Tg of 69.9 °C. Hence, this kind of strategy to achieve the PVC based films with good characteristics is expected to be applied in the preparation of biomedical materials. [ABSTRACT FROM AUTHOR]

The catalyst Y(NO3)3, 6H2O exhibited remarkable activity in the aza-Michael addition of various aromatic and aliphatic amines with acrylonitrile at ambient temperature in a protic solvent. The method is selective for the monocyanoethylation of primary aromatic amines, aliphatic secondary amines, and sterically hindered aliphatic amines. Phenols and active methylene compounds do not undergo cyanoethylation. Thiophenol, in the presence of yttrium nitrate, promotes the polymerization of acrylonitrile. The water solubility and high catalyst stability make the process of removing the catalyst from the product easy. Direct aqueous workup of the reaction mixture could lead to the isolation of cyanoethylation products up to 99.9% purity. Selective mono-cyanoethylation at the primary aromatic amine, especially electron-rich aromatic amines Excellent regio-selectivity in the presence of Carbon and Oxygen nucleophiles The reported condition could be used to polymerize acrylonitrile in the presence of thiophenol. Reaction is facile for electron-rich aromatic amine. Highly sensitive to the steric effect at the nitrogen center [ABSTRACT FROM AUTHOR]

The preparation and characterization of a new multi-functionalized terpyridine molecule featuring a pyrrole heterocycle and a cyano group is described. This new compound was obtained via a KF/alumina-catalyzed Michael addition of 4′-(pyrrol-2-yl)-2,2′:6′,2″-terpyridine into acrylonitrile. The mild reaction conditions leave the nitrile group unaltered. The title compound was fully characterized via NMR spectroscopy (1H and 13C) as well as via high resolution mass spectrometry and infrared spectroscopy. [ABSTRACT FROM AUTHOR]

[Display omitted] A new efficient synthesis of racemic (R *, R *)-Pyrphos ligand based on aza-Michael addition reaction of 2,3-bis(di- phenylphosphoryl)buta-1,3-diene with ammonia followed by the reduction of resulting 3,4-bis(diphenylphosphoryl)- pyrrolidine is proposed. The starting reactants are available but-2-yne-1,4-diol and chloro(diphenyl)phosphine. [ABSTRACT FROM AUTHOR]

A catalyst-free aza-Michael addition/C(sp3)-O bond formation tandem reaction of substituted amino ferrocenes with quinone esters was developed, which provided a green and efficient strategy for the construction of a C(sp3)-O bond from C(sp3)-H, and a series of N-ferrocene-substituted benzodihydrooxazoles were smoothly produced in moderate to excellent yields (up to >99% yield). The mechanism experiments showed that quinone esters performed as both substrate and oxidant. The salient features of this transformation include good functional group tolerance, broad substrate scope and mild conditions. [ABSTRACT FROM AUTHOR]

The 1,4‐conjugated addition of nitrogen centered nucleophiles to electron‐deficient alkenes, historically called the aza‐Michael addition, is one of the most significant and widely used reactions in modern synthetic organic chemistry. In the last decade, great progress has been made in this field namely in the development of various catalytic systems. Fundamental advances involve the use of transition metal catalysts, organocatalysts, enzymes, ionic liquids, Brønsted and Lewis acids and bases. This Review aims to critically analyze the results of research into the reactions of aliphatic and aromatic amines with Michael acceptors. [ABSTRACT FROM AUTHOR]

The high incidence of osteochondral defects has increased the interest in the development of improved repairing alternatives, with tissue engineering being considered a promising approach. The hierarchical, complex structure of osteochondral tissue requires the design of a biomimetic multilayered scaffold. Here, a multilayered and multiphasic 3D macroporous structure was achieved at subzero temperature by the Michael addition reaction of amino functionalities of collagen with acryloyl groups of a bifunctionalized poly(ε-caprolactone). This green approach has been successfully applied to crosslink layers of different composition, both for their efficient sequential formation and connection. Polyethylenimine functionalized nano-hydroxyapatite (nHApLPEI) was added to the bottom layer. The resulting hybrid cryogels were characterized by morphology, equilibrium swelling ratios, compressive strength analysis, and MTS assay. They presented good stability, integrity, and biocompatibility. The results revealed that the properties of the prepared constructs may be tuned by varying the composition, number, and thickness of the layers. The Young modulus values were between 3.5 ± 0.02 and 10.5 ± 0.6 kPa for the component layers, while for the multilayered structures they were more than 7.3 ± 0.2 kPa. The equilibrium swelling ratio varied between 4.6 and 14.2, with a value of ~10.5 for the trilayered structure, correlated with the mean pore sizes (74–230 µm). [ABSTRACT FROM AUTHOR]

Azepino[3,4,5‐cd]indole derivatives represent the core scaffold of important natural products and biologically relevant compounds. Therefore, the establishment of step‐ and atom‐economic strategies to access this class of compounds is of paramount importance. To this end, complexity‐to‐diversity (CtD) strategy has become one of the most important tools that transforms complex molecules into diverse skeleta. However, many of the reactions that could be employed in CtD are restricted by the functional handles exist in these molecules. This limits the achievement of the desired skeletal diversity. Herein, an efficient and step‐economic strategy to access a diverse collection of azepino‐[3,4,5‐cd]indole architectures through a cascade that combines Pictet‐Spengler with Michael addition, is described. This was achieved by reacting cyclohexadienone acetaldehydes 2 a–2 d with indolyl‐4‐ethyl amine 1. Employing a CtD strategy on the developed azepino‐[3,4,5‐cd]indoles, a rapid rearrangement reaction that provided a modular, chemo‐ and diastereoselective access to diverse collection of spiro azepinocarbazole nature‐inspired frameworks, was encountered. [ABSTRACT FROM AUTHOR]

A proposed mechanism of the reaction of guanidinium chlorides with dimethyl acetylenedicarboxylate in a tandem aza-Michael addition reaction/intramolecular cyclization was investigated by DFT M06-2X and B3LYP computational approaches. The energies of the products were compared against the G3, M08-HX, M11, and wB97xD data or experimentally obtained product ratios. The structural diversity of the products was interpreted by the concurrent formation of different tautomers formed in situ upon deprotonation with a 2-chlorofumarate anion. A comparison of relative energies of the characteristic stationary points along the examined reaction paths indicated that the initial nucleophilic addition is energetically the most demanding process. The overall reaction is strongly exergonic, as predicted by both methods, which is primarily due to methanol elimination during the intramolecular cyclization step producing cyclic amide structures. Formation of a five-membered ring upon intramolecular cyclization is highly favored for the acyclic guanidine, while optimal product structure for the cyclic guanidines is based on a 1,5,7-triaza [4.3.0]-bicyclononane skeleton. Relative stabilities of the possible products calculated by the employed DFT methods were compared against the experimental product ratio. The best agreement was obtained for the M08-HX approach while the B3LYP approach provided somewhat better results than the M06-2X and M11 methods. [ABSTRACT FROM AUTHOR]

(S)-N1,N3-dibenzyl-1-cyclohexyl-N1,N3-bis((R)-1-phenylethyl)propane-1,3-diamine was prepared in good yield by the reduction of the corresponding amide, which was obtained by the addition of a chiral lithium amide to an α,β-unsaturated ester. The target compound was fully characterized by NMR (1H and 13C), high-resolution mass spectrometry and polarimetry. [ABSTRACT FROM AUTHOR]

The preparation and characterization of a new multi-functionalized terpyridine molecule featuring a pyrrole heterocycle and a cyano group is described. This new compound was obtained via a KF/alumina-catalyzed Michael addition of 4′-(pyrrol-2-yl)-2,2′:6′,2″-terpyridine into acrylonitrile. The mild reaction conditions leave the nitrile group unaltered. The title compound was fully characterized via NMR spectroscopy (1H and 13C) as well as via high resolution mass spectrometry and infrared spectroscopy.

In this paper, a simple and efficient synthetic route for the preparation of new heterocyclic amino acid derivatives containing azetidine and oxetane rings was described. The starting (N-Boc-azetidin-3-ylidene)acetate was obtained from (N-Boc)azetidin-3-one by the DBU-catalysed Horner–Wadsworth–Emmons reaction, followed by aza-Michael addition with NH-heterocycles to yield the target functionalised 3-substituted 3-(acetoxymethyl)azetidines. Methyl 2-(oxetan-3-ylidene)acetate was obtained in a similar manner, which was further treated with various (N-Boc-cycloaminyl)amines to yield the target 3-substituted 3-(acetoxymethyl)oxetane compounds. The synthesis and diversification of novel heterocyclic amino acid derivatives were achieved through the Suzuki–Miyaura cross-coupling from the corresponding brominated pyrazole–azetidine hybrid with boronic acids. The structures of the novel heterocyclic compounds were confirmed via 1H-, 13C-, 15N-, and 19F-NMR spectroscopy, as well as HRMS investigations. [ABSTRACT FROM AUTHOR]

The sulfur fluoride exchange (SuFEx) reaction is significant in drug discovery, materials science, and chemical biology. Conventionally, it involves installation of SO2F followed by fluoride exchange by a catalyst. We report catalyst‐free Aza‐Michael addition to install SO2F and then SuFEx reaction with amines, both occurring in concert, in microdroplets under ambient conditions. The microdroplet reaction is accelerated by a factor of ∼104 relative to the corresponding bulk reaction. We suggest that the superacidic microdroplet surface assists SuFEx reaction by protonating fluorine to create a good leaving group. The reaction scope was established by performing individual reactions in microdroplets of 18 amines in four solvents and confirmed using high‐throughput desorption electrospray ionization experiments. The study demonstrates the value of microdroplet‐assisted accelerated reactions in combination with high‐throughput experimentation for characterization of reaction scope. [ABSTRACT FROM AUTHOR]

Benzimidazole scaffolds became an attractive subject due to their broad spectrum of pharmacological activities. In this work, a methodology was developed for the synthesis of N-substituted benzimidazole derivatives from benzimidazoles and α, β-unsaturated compounds (acrylonitriles, acrylate esters, phenyl vinyl sulfone) catalyzed by lipase TL IM from Thermomyces lanuginosus in continuous-flow microreactors. Investigations were conducted on reaction parameters such as solvent, substrate ratio, reaction temperature, reactant donor/acceptor structures, and reaction time. The transformation is promoted by inexpensive and readily available lipase in methanol at 45 °C for 35 min. A wide range of β-amino sulfone, β-amino nitrile, and β-amino carbonyl compounds were efficiently and selectively synthesized in high yields (76–97%). All in all, a microfluidic biocatalysis system was applied to the synthesis of N-substituted benzimidazole derivatives, and could serve as a promising fast synthesis strategy for further research to develop novel and highly potent active drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aza-Michael addition reaction improves compatibility in PU/polysaccharide aerogels. • Dynamic covalent bonding grants good self-healing and recyclability performances. • Flame-retardant alginate enhances gels' thermal insulation and biodegradability. Bio-based waterborne polyurethane (PU) has garnered significant attention as a sustainable alternative petroleum-derived counterpart, offering environmentally friendly alternatives. In this work, a new approach is proposed to fabricate two kinds of composite aerogels of lowly/highly melamine-modified sodium alginate (SAML/SAMH) with methacrylate-terminated PU (SAML-PU and SAMH-PU) through dynamic covalent cross-linking via Aza-Michael addition reactions. We aim to improve the poor compatibility of polysaccharide and PU associated with traditional blending methods and impart the resulting aerogels with good biodegradability, compressive strength, thermal insulation, flame-retardant, and self-healing. Comprehensive characterizations, including Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy collectively demonstrate the successful derivatization of alginate and the effective synthesis of the Aza-Michael addition copolymer involving derivate alginate and PU. Substantial improvements in compressive strength and thermal properties are realized at comparable densities. Higher compressive strength, higher decomposition temperature and lower thermal conductivity are significantly achieved for SAML-PU (0.35 MPa, 410 °C and 0.024 W/m/K at 0.13 g/cm3) and SAMH-PU (0.58 MPa, 427 °C and 0.022 W/m/K at 0.12 g/cm3) compared to pristine PU foams (0.15 MPa, 330 °C and 0.031 W/m/K at 0.15 g/cm3). Additionally, molecular simulations of the Aza-Michael addition reaction and finite element simulations of aerogel thermal-insulation properties are conducted to corroborate experimental results. Notably, the dynamic polymers of SAML-PU and SAMH-PU exhibited excellent self-healing, recycling, biodegradability, and flame-retardant attributes. The elucidated preparation methodology and the exceptional performance and versatile applications of sodium alginate-based PU aerogels suggest a promising trajectory for future research endeavors and industrial implementation. [ABSTRACT FROM AUTHOR]

• A new flame-retardant curing agent was prepared via aza-michael addition. • The prepared flame-retardant compound was successfully integrated into an epoxy resin matrix. • The thermal stability, fire reaction and mechanical properties of the epoxy resin were improved. • Peak of Heat Release Rate is closely related to the delay to intumescence • The fire performances depend not only on phosphorus content but also on crosslinking. A novel reactive flame-retardant (FR), phosphorus-modified tetraethylenepentamine (TEPA-m-MVP), was prepared via aza-Michael addition process, using dimethyl vinylphosphonate (MVP). TEPA-m-MVP was successfully covalently introduced into the structure of the epoxy system, into the epoxy resin matrix synthesised from tetraethylenepentamine (TEPA) and diglycidyl ether bisphenol A (DGEBA) reaction, leading to the development of a flame-retardant epoxy resin (FR-EP). The curing behaviour, mechanical properties, thermal stability and flame-retardant behaviour of FR-EP samples were investigated and compared to the behaviour of the neat epoxy resin (EP). FR-EPs showed an increase in glass transition temperature (T g), from 120 to 147 °C upon integrating TEPA-m-MVP into the epoxy resin structure, while the value of the E modulus remained unaffected. Furthermore, FR-EP-2%P sample with the optimal P content, approximately 2 wt%, displayed excellent flame-retardant properties. In comparison to EP, total heat release (THR) and peak heat release rate (pHRR) for FR-EP-2%P decreased from 22.6 to 15.3 kJ.g−1 and from 1557 to 572 kW.m−2, respectively. In addition, an interesting impact of the crosslinking density of FR-EP samples on the fire behaviour was observed. This work presents a new strategy for the simultaneous modification of the flame retardancy and mechanical properties of epoxy systems. [Display omitted] [ABSTRACT FROM AUTHOR]

This works documents a new silica gel-supported nanocatalyst (Si@NSBPdNPs 3) with low Pd loadings for n -alkylation reactions at room temperature. Post synthesis characterisation using SEM-EDX and ICP techniques provided a quantitative assessment of palladium species. Additionally, TEM analysis unveiled an average palladium nanoparticle size of 5.87 ± 0.2 nm. In-depth X-ray Photoelectron Spectroscopy (XPS) analysis revealed its predominant composition as Pd(0) complexed to a Schiff base ligand on low cost silica matrix. The nanocatalyst exhibited high efficacy in the catalysis of n -alkylation (Michael addition) reactions with various α,β -unsaturated Michael acceptors, yielding the corresponding n -alkyl products at room temperature with exceptional yields. Notably, the catalyst exhibited good stability and could be easily separated from the reaction mixture. Moreover, the catalyst displayed recyclability potential, maintaining its original catalytic efficacy for up to seven cycles without any discernible loss. [ABSTRACT FROM AUTHOR]

(S)-N1,N3-dibenzyl-1-cyclohexyl-N1,N3-bis((R)-1-phenylethyl)propane-1,3-diamine was prepared in good yield by the reduction of the corresponding amide, which was obtained by the addition of a chiral lithium amide to an α,β-unsaturated ester. The target compound was fully characterized by NMR (1H and 13C), high-resolution mass spectrometry and polarimetry.

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. [ABSTRACT FROM AUTHOR]

A simple and general addition of aromatic amines to activated olefins viz; acrylonitrile, phenyl vinyl sulfone and dimethyl maleate were realized using a combination of 1–10 mol% of NiBr2 and 2–20 mol% of AgOTf at 27–100 °C in toluene as solvent. A variety of aromatic amines bearing both electron donating and electron withdrawing groups including sterically demanding ones, as well as heteroaromatic amines could be added to activated olefins giving rise to the desired β‐amino acid derivatives or β‐amino sulfones in good yields. Addition of anilines to acrylonitrile was also found to be progressing when AgOTf alone was used as catalyst but was far less effective when compared to catalysis in the presence of NiBr2. [ABSTRACT FROM AUTHOR]

Herein, a water‐accelerated, N‐heterocyclic carbene (NHC)‐catalyzed aza‐Michael addition reaction was reported to access β‐aminosulfonyl fluorides, which are key hubs of the sulfur(VI) fluoride exchange (SuFEx) reaction. As a crucial reaction medium, water considerably enhanced the reaction rate with excellent chemo‐ and site‐selectivity (up to >99 : 1) compared to conventional solvents. In addition, the late‐stage ligation of bioactive molecules with the aliphatic β‐amino SuFEx hub was demonstrated. Mechanistic studies on experimental, analytical, and computational approaches support noncovalent activation over NHC catalysis "on‐water". [ABSTRACT FROM AUTHOR]

Primary nitramines have been shown to react with a triple bond of methyl propiolate to form 3-(nitramino)acrylates, on the basis of which a number of bromine derivatives have been synthesized. [ABSTRACT FROM AUTHOR]

A catalyst-free aza-Michael addition/C(sp3)-O bond formation tandem reaction of substituted amino ferrocenes with quinone esters was developed, which provided a green and efficient strategy for the construction of a C(sp3)-O bond from C(sp3)-H, and a series of N-ferrocene-substituted benzodihydrooxazoles were smoothly produced in moderate to excellent yields (up to >99% yield). The mechanism experiments showed that quinone esters performed as both substrate and oxidant. The salient features of this transformation include good functional group tolerance, broad substrate scope and mild conditions.

In this research, a simple and chemoselective synthesis of highly fluorescent polysubstituted dihydro‐6H‐chromeno[4,3‐d]pyrazolo[1,5‐a]pyrimidin‐6‐ones containing one chiral stereocenter is presented by a sequential four‐component reaction of 4‐chloro‐3‐formylcoumarin, 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ5‐phosphanylidene)ethan‐1‐ones (Wittig reagent), benzoylacetonitriles and hydrazine hydrate as readily available starting materials, which includes base‐mediated 1,4‐addition/aza‐Michael addition/formation of two C−N bonds. The desired products were obtained with short reaction times, easy purification (products can be purified by washing with EtOH), and medium to high yields (up to 92 %) under relatively mild reaction conditions. Molecular structures were determined by IR spectrophotometry, mass spectrometry, NMR spectroscopy, and single‐crystal X‐ray analysis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This work first synthesized a series of linear polyesters by step-growth polycondensation, then an amino-terminated hydrophilic polyether was grafted to the polyester as side-chains through aza-Michael addition to prepare a self-dispersible, non-ionic waterborne comb-like polyester (NWCPE). In contrast to traditional functionalization methods that usually require harsh reaction conditions and complex catalysts, the aza-Michael addition proceeds efficiently at room temperature without a catalyst. In this facile and mild way, the NWCPE samples with number-average molecular weight (Mn) of about 8000 g mol−1 were obtained. All dispersions showed excellent storage stability, reflected by no delamination observed after 6 months of storage. The NWCPE dispersion displayed better hydrolysis resistance than an ionic waterborne polyester, as was indicated by a more slight change in pH value and Mn after a period of storage. In addition, the film obtained after the NWCPE dispersion was cross-linked with the curing agent, it exhibited good water resistance, adhesion, and mechanical properties. [ABSTRACT FROM AUTHOR]

A protocol has been developed that allows the synthesis of 2‐aryl/heteroaryl‐4‐quinolones from readily available, affordable starting materials. The reaction proceeds under microwave conditions with moderate to high yields in the presence of copper catalyst. Short reaction time, good functional group tolerance, high atom economy, non‐toxic byproduct and no use of special ligands emphasize the applicability of this method in organic synthesis. [ABSTRACT FROM AUTHOR]

Tropones are commercially available and extremely valuable non‐benzenoid aromatic compounds. Tropone and its derivatives are very important building blocks that are immensely used in synthetic organic chemistry and other mechanistic studies. In the broad realm of cycloaddition reactions, tropones behave as versatile cycloaddition partners. In these reactions, they act as 4π, 6π or, 8π synthons. The cycloaddition products derived from tropone play a noticeable role in the synthesis of bioactive molecules. Tropone is a veritable example as a precursor for the synthesis of natural products.. Tropones are one of the major scaffolds in pharmaceutical chemistry. This review is focused on a few protocols for the synthesis of substituted tropones, tropolones and the racemic, asymmetric reactions of tropones that occurred in the last decade (2012–2021). [ABSTRACT FROM AUTHOR]

[Display omitted] A three-component protocol was adopted to efficiently prepare new bis(pyrazolo[1,5- a ]pyrimidines) linked to different spacers in 80-92% yields from 1 H -pyrazole-3,5-diamines, malononitrile and bis(aldehydes). The p -xylene-linked bis(pyrimidine) bearing 3-positioned 4-methoxy-benzyl substituent had the best antibacterial activity with MIC / MBC values up to 2.2 / 4.4 µm. [ABSTRACT FROM AUTHOR]

With the aim of gaining understanding of the molecular basis of commercially available Candida antarctica lipase B (CALB) immobilized on polyacrylic resin catalyzed regioselective mono aza-Michael addition of Benzhydrazide to Diethyl maleate we decided to carry out molecular dynamics (MD) simulation studies in parallel with our experimental study. We found a correlation between the activity of CALB and the choice of solvent. Our study showed that solvent affects the performance of the enzyme due to the binding of solvent molecules to the enzyme active site region, and the solvation energy of substrates in the different solvents. We also found that CALB is only active in nonpolar solvent (i.e. Hexane), and therefore we investigated the influence of Hexane on the catalytic activity of CALB for the reaction. The results of this study and related experimental validation from our studies have been discussed here.

The high incidence of osteochondral defects has increased the interest in the development of improved repairing alternatives, with tissue engineering being considered a promising approach. The hierarchical, complex structure of osteochondral tissue requires the design of a biomimetic multilayered scaffold. Here, a multilayered and multiphasic 3D macroporous structure was achieved at subzero temperature by the Michael addition reaction of amino functionalities of collagen with acryloyl groups of a bifunctionalized poly(ε-caprolactone). This green approach has been successfully applied to crosslink layers of different composition, both for their efficient sequential formation and connection. Polyethylenimine functionalized nano-hydroxyapatite (nHApLPEI) was added to the bottom layer. The resulting hybrid cryogels were characterized by morphology, equilibrium swelling ratios, compressive strength analysis, and MTS assay. They presented good stability, integrity, and biocompatibility. The results revealed that the properties of the prepared constructs may be tuned by varying the composition, number, and thickness of the layers. The Young modulus values were between 3.5 ± 0.02 and 10.5 ± 0.6 kPa for the component layers, while for the multilayered structures they were more than 7.3 ± 0.2 kPa. The equilibrium swelling ratio varied between 4.6 and 14.2, with a value of ~10.5 for the trilayered structure, correlated with the mean pore sizes (74–230 µm).