Henry Reaction Research Articles

Origin of selectivity in surface functionalized vinylpyridine mesoporous silica nanocomposites (VP/SBA) for Henry reaction

Origin of selectivity in surface functionalized vinylpyridine mesoporous silica nanocomposites (VP/SBA) for Henry reaction

Switch of Five Contiguous Chiral Centers in the Synthesis of Both Enantiomers of Hajos-Parrish Ketone Analogs via Diphenylprolinol Silyl Ether-Mediated Domino Reaction.

Both enantiomers of functionalized Hajos-Parrish ketone (HPK) analogs were prepared with excellent diastereoselectivities and enantioselectivities using the same chiral catalyst under two slightly different conditions. In condition A, dioxane was used as the solvent with 3 equivalents of water. In condition B, acetonitrile was used as the solvent with 30 equivalents of water, followed by epimerization with a base in a one-pot. The reaction consisted of a domino reaction including a diphenylprolinol silyl ether-mediated asymmetric Michael reaction and an intramolecular Henry reaction. In the Michael reaction, depending on the solvent and water amounts, syn- and anti-isomers were selectively synthesized with excellent enantioselectivity, in which the absolute configuration at C5 (indanone numbering) was opposite. The subsequent Henry reaction was diastereoselective, in which the C5 substituent controlled the three chiral centers in a highly diastereoselective manner. The final base treatment in condition B caused epimerization, changing the stereochemistry at C6. Switching more than two chiral centers with high enantioselectivity is extremely difficult using the same chiral catalyst; the present reaction is a very rare enantiodivergent reaction that switches five continuous chiral centers with high enantioselectivity.

Selectivity Control in Nitroaldol (Henry) Reaction by Changing the Basic Anion in a Chiral Copper(II) Complex Based on (S)-2-Aminomethylpyrrolidine and 3,5-Di-tert-butylsalicylaldehyde.

This article is a continuation of our previous research on the catalytic capability of a chiral copper complex based on commercially available (S)-2-aminomethylpyrrolidine and 3,5-di-tert-butylsalicylaldehyde with various counter-anions in the asymmetric Henry reaction. Our findings indicate that depending on the type of base used, chiral nitroalcohols with yields up to 98% and ee values up to 77%, as well as β-nitrostyrenes with yields up to 88%, can be produced. Additionally, it has been found that the outcome of the reaction and the catalytic properties of copper (II) complexes (S)-Cu1 and (S)-Cu2 are influenced by the structure of the aldehyde used.

Chiral amido-oxazoline functionalized MCM-41: A sustainable heterogeneous catalyst for enantioselective Kharasch–Sosnovsky and Henry reactions

In this study, a series of chiral amido-oxazoline ligands was synthesized with a primary focus on immobilizing the most effective ligands on MCM-41 mesoporous material. Following several attempts, the para-nitro group of the chiral amido-oxazoline ligands was successfully reduced to amino group, enabling their immobilization on MCM-41. The resulting chiral heterogeneous amido-oxazoline ligands were characterized using various techniques, including FT-IR, XRD, TGA, SEM, TEM, EDX, and BET-BJH, confirming the successful immobilization of the amido-oxazoline ligands. A comparison of the efficiency of the homogeneous and heterogeneous amido-oxazoline-based ligands in the Kharasch-Sosnovsky and Henry reactions revealed better performance of the heterogeneous ligand. The immobilized amido-oxazoline-copper complexes exhibited remarkable catalytic activity, achieving excellent yields and enantioselectivities (up to 88 % ee) in the Kharasch-Sosnovsky reaction, and delivering excellent yields with moderate enantioselectivities in the Henry reaction. Notably, the Henry reaction proceeded with moderate diastereoselectivity, favoring the syn diastereomer, under solvent-free conditions, highlighting the sustainability of the process. The heterogeneous nature of the catalysts facilitated effortless recovery and efficient reusability.

Structure Revision of Halisphingosine A via Total Synthesis and Bioactivity Studies.

Sphingoid bases are important bioactive lipids found in a variety of organisms, serving as the backbone of sphingolipids, which regulate essential physiological processes. Here we describe the total synthesis and structure revision of halisphingosine A, a sphingoid base initially isolated from marine sponges. To address inconsistencies in the NMR interpretation of this natural product, we developed a synthetic route involving a late-stage enantioselective Henry reaction that allows access to multiple stereoisomers of the proposed halisphingosine core structure. Our library of 32 fully characterized synthetic stereoisomers enabled us to rectify the structure of halisphingosine A as (2R,3R,8R,Z)-2-aminooctadec-9-ene-1,3,8-triol, and to pursue further structure-activity relation (SAR) studies regarding their antimicrobial and cytotoxic potential. In summary, our study offers a yet unreported compound library along with validated analytical datasets of marine sphingoid base derivatives, which significantly affects future ecometabolomic marine research and will facilitate the identification of inhibitors of sphingolipid metabolism or antagonists of sphingolipid base-sensing receptors.

Unveiling Heterogeneous Catalytic Potential of Distinctly Coordinated Polymers Toward Henry and Morita‐Baylis‐Hillman Reactions

AbstractThree 1D coordination polymers (CPs), {[CuL2(H2O)] ⋅ (H2O)3}n (1) {[CoL2(H2O)2] ⋅ (H2O)}n (2) and {[NiL2(H2O)] ⋅ (H2O)3}n (3), (L1=N‐nicotinoylglycinato) have been synthesized by adopting a solvothermal reaction strategy and characterized through several spectral techniques i. e., elemental analyses, FT‐IR, TGA, EDX, DSC, AAS, and PXRD. X‐ray single crystal analysis revealed the 5‐, 6‐ and 7‐coordinated structures respectively for CPs 1, 2 and 3 wherein, L1 connects the metal ions in a bridging mode. The CPs entail H‐bonding, π–π stacking along with other non‐covalent interactions and expand into 3D supramolecular networks. Further, FESEM and HRTEM provided morphological insight for 1–3 and aid in obtaining interplanar spacings. CPs 1–3 possessing distinct coordination numbers and good thermal stability have been subjected to catalysis after optimization and notably, these serve as efficient, easy to work up, and reusable porous heterogeneous catalysts for Henry and Morita‐Baylis‐Hillman (MBH) reactions with reasonably good yields (97–93 %). Remarkably, catalyzed by 1–3 can be reused at least seven times for the Henry reaction and six times for the MBH reaction, retaining their catalytic efficiency. Relative catalytic efficacy toward the Henry and MBH reactions follows the order 1>2>3. Present findings are based on a rational approach of varying coordination number (5, 6 and 7) and metal ions [Cu(II), Co(II) and Ni(II)] respectively in 1–3 having structural evidence and examine their catalytic performances for typical Henry and MBH reactions.

Structure-Directed Quaternary Ammonium Hydroxide Resins: High-Performance Heterogeneous Base Catalysts for Continuous-Flow Carbon-Carbon Bond-Forming Reactions.

Quaternary ammonium hydroxide resins are widely recognized for their effectiveness as immobilized bases and are frequently utilized as commodity chemicals for anion-exchange applications. However, despite their accessibility, chemically controlling their properties has proven challenging, hindering research and development efforts toward their use as solid base catalysts. This study investigates the synthetic factors that are crucial for achieving high functional performance in polystyrene resins. Using commercially available resin as a benchmark and the continuous-flow Henry reaction as a model system, we explore and evaluate newly synthesized resin catalysts to maximize their basic catalytic activity.

Construction of Co(II), Cu(II), and Zn(II) coordination compounds driven by a pyridine-dicarboxylic acid: Hydrothermal assembly, structural and topological versatility, and catalytic properties

A derivative of pyridine-dicarboxylic acid, 5-(3-carboxyphenyl)picolinic acid (H2cpic), was used as a versatile building block to synthesize a series of five novel coordination compounds under hydrothermal conditions and formulated as {[Cu2(μ-cpic)2(phen)]·H2O}n (1), [Co(μ-cpic)(phen)(H2O)]n (2), [Cu2(μ-cpic)2(2,2′-bipy)(H2O)2]·2H2O (3), {[Cu3(μ-cpic)3(μ-4,4′-bipy)1.5(H2O)3]·2H2O}n (4), and {[Zn2(μ-cpic)2(μ-dpe)0.5(H2O)3]·H2O}n (5). The auxiliary ligands used in the synthesis were 1,10-phenanthroline (phen), 2,2′-bipyridine (2,2′-bipy), 4,4′-bipyridine (4,4′-bipy), and 1,2-di(4-pyridyl)ethylene (dpe). The structures of the compounds 1–5 vary significantly, ranging from a 0D tetramer (3) to 1D metal–organic chains (1, 2, 4, and 5). Furthermore, these compounds were evaluated as heterogeneous catalysts for the Henry reaction, achieving high product yields under optimized conditions. We further investigated various reaction parameters, and substrate scope, and assessed the feasibility of catalyst recycling. This thorough investigation highlights the versatility of H2cpic as a dicarboxylate building block in the formation of functional coordination polymers.

An Overview of Various Applications of Cadmium Carboxylate Coordination Polymers.

This review highlights the most recent applications of Cd(II)-carboxylate-based coordination polymers (Cd(II)-CBCPs), such as sensors, catalysts, and storage materials, in comparison with those of Zn(II) counterparts. A wide range of species with luminescence properties were designed by using proper organic fluorophores, especially a carboxylate bridging ligand combined with an ancillary N-donor species, both with a rigid structure. These characteristics, combined with the arrangement in Cd(II)-CBCPs' structure and the intermolecular interaction, enable the sensing behavior of a plethora of various inorganic and organic pollutants. In addition, the Lewis acid behavior of Cd(II) was investigated either in developing valuable heterogeneous catalysts in acetalization, cyanosilylation, Henry or Strecker reactions, Knoevenagel condensation, or dyes or drug elimination from wastewater through photocatalysis. Furthermore, the pores structure of such derivatives induced the ability of some species to store gases or toxic dyes. Applications such as in herbicides, antibacterials, and electronic devices are also described together with their ability to generate nano-CdO species.

Development of Dual Cooperative Multi‐Urea Catalysts for Henry Reaction

AbstractA dual cooperative multi‐urea catalyst for Henry reaction was developed in which four urea groups were introduced into a rigid and rotatable framework. The tetraurea catalyst 1 showed higher activity for Henry reaction than its analogues, close‐bisurea 2 or distal‐bisurea 3 with two urea units, demonstrating additional cooperativity between the two substrate‐pinching catalytic sites of tetraurea 1. Addition of the reaction product to the reaction system resulted in a small amount of further activation. This work would provide a basis for new cooperative molecular catalysts, leading to a high degree of regulation based on allosteric cooperativity, e.g. with a distinct ON/OFF threshold for reactivity, or feedback activation by using the product as a reaction template.

Paracetamol Inclusion in Mechanically Interlocked Nanocages.

The solid-state synthesis and fast crystallization under kinetic control of poly-[n]-catenanes self-assembled of mechanically interlocked metal organic cages (MOCs) is virtually unexplored. This is in part, due to the lack of suitable crystals for single crystal X-ray diffraction (SC-XRD) analysis which limits their progress as advanced functional materials. Here we report the unprecedented inclusion of paracetamol in the cavities of amorphous materials constituted of M12L8, interlocked MOCs synthesized by mechanochemistry under kinetic control. Full structure determination of a low-crystallinity and low-resolution powders of the M12L8 poly-[n]-catenane including paracetamol has been carried out combining XRD data and Density Functional Theory (DFT) calculations using a multi-step approach. Each M12L8 cage contains six paracetamol guests which is confirmed by thermal analysis and NMR spectroscopy. The paracetamol loading has been also carried out by the instant synthesis method using a saturated paracetamol solution in which TPB and ZnI2 self-assemble immediately (i. e., 1-5 seconds) encapsulating ~7 paracetamol molecules in the M12L8 nanocages under kinetic control also giving a good selectivity. Benzaldehyde has been included in the M12L8 cages using amorphous M12L8 polycatenanes showing that the icosahedral cages can serve as potential nanoreactors for instance to study Henry reactions in the solid-state.

A Single Enzyme in Enantiocomplementary Synthesis of β-Nitroalcohols: Bidirectional Catalysis by Hydroxynitrile Lyase.

A single enzyme, Baliospermum montanum hydroxynitrile lyase (BmHNL), without alteration, enabled bidirectional catalysis in enantiocomplementary synthesis of chiral β-nitroalcohols. BmHNL catalyzed promiscuous Henry (24 examples) and retro-Henry reaction (22 examples) provided up to >99% and 50% conversion to (S)- and (R)-β-nitroalcohols respectively, while both cases displayed up to >99% ee. The broad substrate scope and high stereoselectivity of BmHNL represents its synthetic applications in sustainable production of diverse chiral β-nitroalcohols. Kinetic parameters of BmHNL was determined for Henry and retro-Henry reaction, which reveals poor catalytic efficiency for both the promiscuous transformations, however, the former has better efficiency than the latter. Practical applicability of the biocatalyst and transformation was illustrated by preparative scale synthesis of chiral intermediates of (S)-Tembamide, and (S)-Micanozole.

Multicomponent Synthesis of Novel Unsymmetric 6-Aryl Substituted 5-Nitropyridines

We have previously studied a multicomponent reaction for the synthesis of unsymmetrical 5-nitro-1,4-dihydropyridines using unsubstituted 2-nitroacetophenone, 1,3-dicarbonyl compounds, and various aldehydes such as formaldehyde, acetaldehyde, and furfural. This paper reports the use of unsymmetrical 3-acetyl-5-nitro-1,4-dihydropyridines containing aryl substituents at the 6-position in a multicomponent synthesis reaction. The starting aryl-substituted nitroacetophenones were prepared by two methods. The first method involved the two-step Katritzky method, which is described in the literature. This method consists of preparing N-acylbenzotriazoles from the corresponding substituted derivatives of benzoic acid and 1,2,3-benzotriazole in the presence of thionyl chloride. This is followed by C-acylation of nitromethane in supernatron medium (t-BuOK – DMSO). A number of 2-nitroacetophenone derivatives were prepared from more commercially available aromatic aldehydes by the Henry reaction with nitromethane followed by oxidation of the resulting secondary nitroalcohols. The multicomponent reaction of 6-aryl-substituted 5-nitro-1,4-dihydropyridines and their subsequent aromatization into 5-nitropyridines allowed us to reduce the overall reaction time by more than 40 times and to increase the total yield of 5-nitro-6-arylpyridines by an average of twofold compared to the method described in the literature. Furthermore, the 3-acetyl-5-nitropyridines we have obtained are significant intermediates in the synthesis of novel, more complex heterocyclic systems with potential biological activity. These systems include δ-carbolines and epoxybenzooxocyno[4,3-b]pyridines, which are currently of great interest for the study of their properties.

Henry reaction in WELAN: A Green Approach

Henry reaction in WELAN: A Green Approach

Organocatalytic Activation of Unsymmetrical 2,3‐Diketones towards Catalytic Asymmetric Domino Michael–Henry Reaction

In this study, we explored a method to distinguish between both enolizable regions of unsymmetrical 2,3‐diketones in organocatalytic domino reactions involving nitroalkenes. The selective formation of an enamine from only one side of the molecule was made possible by the use of optically pure 2‐(trifluoromethyl)pyrrolidine. This catalyst, remarkably enhancing the reaction, owes its efficacy to a unique interplay between basicity and nucleophilicity. These features caused the enolization of the substrate at the second possible site to be omitted. The approach resulted in excellent regio‐ diastereo‐ and enantioselectivity (91‐99% ee) across various nitroalkenes, leading to the synthesis of novel cyclopentanone derivatives with three contiguous stereogenic center.

Front Cover: Structure–Based Site–Directed Mutagenesis of Hydroxynitrile Lyase from Cyanogenic Millipede, Oxidus gracilis for Hydrocyanation and Henry Reactions (ChemBioChem 11/2024)

Front Cover: Structure–Based Site–Directed Mutagenesis of Hydroxynitrile Lyase from Cyanogenic Millipede, <i>Oxidus gracilis</i> for Hydrocyanation and Henry Reactions (ChemBioChem 11/2024)

Fabrication of an economical and environmentally friendly electrode utilizing fullerene modified with L-proline and coated with copper nanoparticles for enantioselective electro-organic henry reaction in the presence of NaCl electrolyte

This study focuses on the fabrication of an economical and environmentally friendly electrode for chiral electro-organic synthesis of (S)-2-Nitro-1-Phenylethanol derivatives 4(a-m) in good to excellent yields (90–96 %). The electrode is constructed using Fullerene modified with l-Proline and coated with copper nanoparticles (ox-Fullerene-Pro@Cu). The designed electrode aims to facilitate the synthesis of (S)-2-Nitro-1-Phenylethanol 4(a-m) derivatives efficiently. The utilization of sodium chloride as an electrolyte further enhances the electrochemical reaction. Following the electrode synthesis, comprehensive characterization and identification were conducted utilizing SEM, EDS, TEM, XPS, XRD, TGA, BET, CV and FT-IR analyses. The electrode's cost-effectiveness and eco-friendly nature make it a promising candidate for sustainable electro-organic synthesis processes. The synthesized (S)-2-Nitro-1-Phenylethanol derivatives 4(a-m) derivatives were identified and their properties reported through melting point, 1HNMR, Mass and CHN analyses.

Catalyzed Henry Reaction by Compartmentalized Copper‐Pyrazolyl‐Complex Modified Microgels

AbstractCompartmentalization of homogeneous catalysts enhances their catalytic performance and can even increase the selectivity. Microgels can serve as smart catalyst carrier systems offering the compartmentalization combined with good accessibility of the catalyst enabling the recyclability and re‐usability. Yet, the incorporation of coordination complexes into microgels has not been studied systematically, lacking in detailed insight in their structure and catalytic performance. Herein, microgels are synthesized with controlled number and localization of copper(II)‐pyrazolyl‐complexes. The catalytic activity of microgels in the Henry reactions is examined showing significantly higher yields compared to pure copper(II)‐pyrazolyl‐complexes. Furthermore, the localization of the copper(II)‐pyrazolyl‐complexes in the microgel core resulted in higher product yields than for microgel catalysts with copper(II) complexes in the shell. Microgel catalysts are demonstrated with copper(II) complexes that can be used in numerous reaction cycles, allow re‐loading of copper to recover catalytically active centers, and can be applicable in industrially‐relevant catalytic processes.

Absorption characteristics and molecular mechanism of a low viscosity iron-based ionic liquid for removing H2S

Aiming at the problem of by-product salt and volatile solvent component in industrial liquid redox process of H2S removal. A new absorbent, a 1-butyl-3-methylpyridine iron-based ionic liquid (rFeCl3/[BMP]Cl) with three iron-pyridine ratios (r=0.6, 0.8, and 1.0), was synthesized. The physicochemical properties and H2S solubility of rFeCl3/[BMP]Cl were measured and modeled. The molecular mechanism of chemical absorption of H2S by iron-based ionic liquids was explained from the interaction energy, reduced density gradient (RDG) and atoms in molecules (AIM) topology analysis, and standard reaction equilibrium constant by quantum chemical calculation. It was found that rFeCl3/[BMP]Cl have low viscosity, high solubility, and good thermal stability. Its Bronsted acidity avoids by-product salts produced in the absorption of H2S. The hydrophobicity makes the ionic liquid not diluted by the generated water during the absorption. The results of quantum chemical calculations show that rFeCl3/[BMP]Cl-H2S has moderate intermolecular interaction and large reactivity, which is consistent with the experimental results of the Henry's coefficient and reaction equilibrium constant.

Triton B Catalyzed Rapid and Mild Synthetic Protocol for both Henry Reaction of Isatin and Michael Reaction of Chalcone with Nitroalkane

AbstractA highly efficient and general synthetic protocol for both Henry and Michael reactions was developed using metal-free catalyst Triton B (benzyltrimethylammonium hydroxide) and isatins and chalcones, respectively. This methodology is inexpensive, the reagents are easy to handle, and the approach offers wide functional group tolerance of isatins and chalcones. The base catalyst Triton B is less toxic, recyclable, and reusable. This efficient method reduces reaction times, minimizes reagent excess, avoids chromatography, and is aligned with sustainable chemistry principles, offering eco-friendly applications in diverse industries.