Micellar Catalysis Research Articles

Reactions of In Situ-Generated Difluorocarbene (:CF2) with Aromatic/Heteroaromatic Alcohols, Thiols, Olefins, and Alkynes under Environmentally Responsible Conditions.

Environmentally respectful methods for generating and utilizing difluorocarbene (:CF2) in the synthesis of a wide array of valuable difluoromethylated compounds are disclosed. In particular, the insertion of the CF2 moiety into aromatic/heteroaromatic alcohols, thiols, olefins, and alkynes under neat or aqueous micellar catalysis conditions is demonstrated. These methods yield both satisfactory results and significantly lower E-Factors compared to traditional synthetic approaches. Key applications of these methodologies include optimization en route to a pantoprazole intermediate and development of a representative one-pot chemoenzymatic sequence. Additionally, analysis via calorimetry indicates no significant safety risk in the context of the developed solvent-free conditions.

Size and shape matter for micellar catalysis using light-responsive azobenzene surfactants.

The micellar catalysis of a model Claisen-Schmidt aldol condensation reaction using heterogeneous nanoreactors based on cationic azobenzene trimethylammonium bromide (AzoTAB) photosurfactants is investigated. Under UV irradiation, AzoTABs undergo a trans-cis photoisomerisation, which changes not only the critical micelle concentration, but also the shape and size of the micelle. The effect of surfactant structure (tail and spacer lengths), concentration and temperature on the reaction yield were investigated. Monitoring of the zeta potential during the reaction indicated that it proceeds at the micelle/water interface for AzoTABs, with the enolate intermediate stabilised in micelle/water interface (i.e. the Stern layer). The reaction yield was found to correlate directly to micellar shape and size, with smaller, more spherical micelles typical of cis-AzoTABs favouring higher reaction efficiencies.

Micelle-Assisted C(sp2)-H Functionalization for C-Se and C-X Bond Formation in the Aqueous Medium.

An environmentally sustainable, versatile, and cost-effective approach for C-Se and C-X (X = I, Br, and Cl) bond formation through C-H functionalization assisted by micellar catalysis in water is developed. The reaction utilizes a minimum amount of diorganyl diselenides and potassium halides for the respective functionalizations. The present protocol was suitable for scale-up synthesis, which directly provided the desired selenylated products without the need for chromatographic purification, in sufficient purity. The aqueous micellar catalysis system was reusable for up to 5 reaction cycles without compromising the reaction yield.

Micellar (Photo−)Catalysis Driven by IR‐Active Semiconductor Surfactants

AbstractIn micellar catalysis, one uses aggregates formed by surfactants as nanoreactors for performing chemical reactions. A special class of tailor‐made surfactants containing catalytically active sites opens new perspectives in micellar catalysis. Little is known about the combination of such surfactants with photocatalysis. Molecular semiconductors are presented, which simultaneously have amphiphilic properties and are made of a hydrophilic fullerenol head group attached to dye molecules as the hydrophobic entity. The first generation of those surfactants produces reactive oxygen species (ROS) when exposed to light in the UV/Vis range. The concept of the current paper is that one can drive the photocatalytic process also using low‐energy photons in the near‐infrared region. For this purpose, NIR‐active dye molecules were selected and attached to the fullerenol head. It is shown that a fullerenol ‐ aminostilbene compound representing the second generation of semiconductor surfactants fulfills all requirements. It forms aggregates in water that are catalytically active. Moreover, two‐photon experiments with λ=780 nm were performed, indicating successful ROS production and, thus, photocatalytic activity.

Probing the surfactant-constructed microenvironment of PtCu bimetallic nanoalloys to improve catalytic selectivity in aqueous micelles

Aqueous micellar catalysis has become recognized as an efficient, green and sustainable technology, yet is still challenging to improve the catalytic selectivity by manipulating the microenvironment of bimetallic nanoalloys. In this work, we present a water-based micelle-bimetal strategy to regulate effectively the selective hydrogenation of α,β-unsaturated aldehydes. This strategy employed surfactant GluM to stabilize PtCu bimetallic alloys and enrich the substrate to reinforce the contact with NPs. Importantly, the steric effect created by surfactant GluM can modulate the adsorption mode of α,β-unsaturated aldehydes on the alloy surface from planar configuration to linear configuration. The remarkable conversion (up to 98.5 %) and selectivity (up to 94.6 %) for the hydrogenation of α,β-unsaturated aldehydes to unsaturated alcohols were achieved, attributed to a synergy of favorable factors, such as alloy effect, multifunctionality of GluM and auxiliary effect of H2O. This work not only highlights the important role of the specific microenvironment surrounding the bimetal alloys in regulating the catalytic selectivity, but also provides a novel reference for improving catalytic selectivity in aqueous micelles.

Rediscovery of an Old Named Reaction: From Micellar Catalysis to Unusual Schotten–Baumann Conditions

Rediscovery of an Old Named Reaction: From Micellar Catalysis to Unusual Schotten–Baumann Conditions

Pd-Catalyzed C(sp2)-H/C(sp2)-H Coupling of Limonene.

Limonene undergoes a regioselective Pd(II)-catalyzed C(sp2)-H/C(sp2)-H coupling with acrylic acid esters and amides, α,β-unsaturated ketones, styrenes, and allyl acetate, affording novel 1,3-dienes. DFT computations gave results in accord with the experimental results and allowed for the formulation of a plausible mechanism. The postfunctionalization of one of the coupled products was achieved via a large-scale Sonogashira reaction conducted under micellar catalysis.

Synthesis and In vitro evaluation of bichalcones as novel anti-toxoplasma agents.

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, an apicomplexan parasite that infects approximately a third of the world's human population. This disease can cause serious complications during pregnancy and can be fatal in immunocompromised hosts. The current treatment options for toxoplasmosis face several limitations. Thus, to address the urgent medical need for the discovery of novel anti-toxoplasma potential drug candidates, our research focused on exploring a series of monomeric and dimeric chalcones, polyphenolic molecules belonging to the class of flavonoids. Chalcones 1aa-1bg and axially chiral A-A'-connected bichalcones 2aa-2bg were evaluated in vitro against the proliferation of the parasite in a cell-based assay. A comparison of the efficacy demonstrated that, in several cases, bichalcones exhibited increased bioactivity compared to their corresponding monomeric counterparts. Among these compounds, a bichalcone with a phenyl substituent and a methyl moiety 2ab showed the most potent and selective inhibitory activity in the nanomolar range. Both enantiomers of this bichalcone were synthesized using an axially chiral biphenol building block. The biaryl bond was forged using Suzuki cross-coupling in water under micellar catalysis conditions. Separation of the atropisomers of this biphenol building block was conducted by chiral HPLC on a preparative scale. The biological evaluation of the enantiomers revealed that the (R a)-enantiomer (R a)-2ab is the eutomer. These studies suggest that bichalcones may be important drug candidates for further in vivo evaluations for the discovery of anti-toxoplasma drugs.

Polymer and micellar catalysis in d-fructose oxidation by imidazolium fluorochromate: A kinetic and mechanistic study

This work investigated the oxidation of d-fructose using imidazolium fluorochromate (IFC) as an oxidant and analyzed how sodium dodecyl sulfate (SDS) and polyethylene glycol (PEG-400) affected the reaction kinetics. The process exhibited a unit-order dependence on IFC, d-fructose, and perchloric acid concentration. Perchloric acid was the primary source of hydrogen ions in the reaction mixture. The stoichiometry of the reaction indicated that 3 mol of d-fructose requires 4 mol of IFC. Acrylonitrile, a radical-generating species, did not impact the reaction rate, indicating the absence of a free radical intermediate. The reaction rate decreases as the Mn (II) ions concentration increases, suggesting the involvement of Cr (IV) species in the reaction. The dielectric value of the reaction medium (D) had an inverse effect on the rate, and the outcomes were consistent with the Amis (log k1 and 1/D) and Kirkwood plots (log k1 and (D-1/2D+1)), indicating the presence of dipole-dipole interactions in the process. SDS and PEG-400 catalyzed the reaction. The reaction showed significant catalysis before reaching the critical micelle concentration (CMC). However, the observed rate constants stabilized at higher SDS concentrations exceeding the CMC. Piszkiewicz's cooperativity model was employed to describe the surfactant catalysis, while the Benesi-Hildebrand equation was utilized to explain polymer catalysis. The activation parameters are ΔH† = 44.3 ± 1.3 kJ mol−1, and ΔS† = −133.4 ± 4.3 J K−1 mol−1. The products of the reaction have been identified by spectral analysis as d-arabinoniclactone and formic acid. The formation of an ester complex followed by its decomposition was proposed as the rate-limiting step in the proposed mechanistic reaction pathway.

Efficient Copper‐Free Sonogashira Coupling in Water and under Ambient Atmosphere

AbstractSonogashira coupling is one of the cornerstone Palladium mediated cross coupling reactions, giving a direct and high yield access to symmetric and non‐symmetric alkynes with high tolerance of substituents. The method generally requires the use of CuI as a cocatalyst, an inert atmosphere to protect palladium catalyst, somewhat harsh conditions like prolonged heating and the use of organic solvents due to the hydrophobicity of reagents and products. Leveraging on the opportunities offered by micellar catalysis, we here present a general methodology to perform Sonogashira coupling in water, with moderate or no heating, under air, without copper co‐catalysts and at very low catalyst loading. The method offers the same generality and scope of organic solvents based couplings, but strongly improves sustainability while offering excellent yields.

Effect of diphenylalanine on the functional activity of porphyrin and non-porphyrin photosensitizers solubilized by Pluronic F127

The effect of the diphenylalanine (Phe-Phe) amino acid on the rate of tryptophan photooxidation catalyzed by photosensitizers (PS) of different natures: dimegin (DMG), fluorinated tetraphenylporphyrin (FTPP), photoditazine (PD) and methylene blue (MB) was studied. It was shown that in the presence of Phe-Phe, the effective constant of photooxidation of the substrate catalyzed by DMG, PD and MB in the aqueous phase decreases. However, the introduction of the amphiphilic polymer Pluronic F127 into the systems allows not only to restore, but also to increase the activity of the PS in the processes of photosensitized oxidation. In particular, the activity of dimegin solubilized by Pluronic F127 in the presence of Phe-Phe is higher than the activity of both pure porphyrin and solubilized DMG. In addition, the activity of the hydrophobic FTPP solubilized by Pluronic also increases. At the same time, a study of the luminescence of singlet oxygen generated by solubilized FTPP in the absence and presence of Phe-Phe revealed that the dipeptide does not influence the processes of 1О2 generation. It was suggested that micellar catalysis influences the activity of solubilized PS in the presence of a biologically active dipeptide.

Aqueous Micelles as Solvent, Ligand, and Reaction Promoter in Catalysis.

Water is considered to be the most sustainable and safest solvent. Micellar catalysis is a significant contributor to the chemistry in water. It promotes pathways involving water-sensitive intermediates and transient catalytic species under micelles' shielding effect while also replacing costly ligands and dipolar-aprotic solvents. However, there is a lack of critical information about micellar catalysis. This includes why it works better than traditional catalysis in organic solvents, why specific rules in micellar catalysis differ from those of conventional catalysis, and how the limitations of micellar catalysis can be addressed in the future. This Perspective aims to highlight the current gaps in our understanding of micellar catalysis and provide an analysis of designer surfactants' origin and essential components. This will also provide a fundamental understanding of micellar catalysis, including how aqueous micelles can simultaneously perform multiple functions such as solvent, ligand, and reaction promoter.

Molecular Dynamic Simulations of Aqueous Micellar Organometallic Catalysis: Methane Functionalization as a Case Study.

Molecular Dynamics (MD) simulations constitute a powerful tool that provides a 3D perspective of the dynamical behavior of chemical systems. Herein the first MD study of the dynamics of a catalytic organometallic system, in micellar media, is presented. The challenging methane catalytic functionalization into ethyl propionate through a silver-catalyzed process has been targeted as the case study. The intimate nature of the micelles formed with the surfactants sodium dodecylsulfate (SDS) and potassium perfluorooctane sulfonate (PFOS) has been ascertained, as well as the relative distribution of the main actors in this transformation, namely methane, the diazo reagent and the silver catalyst, the latter in two different forms: the initial compound and a silver-carbene intermediate. Catalyst deactivation occurs with halide containing surfactants dodecyltrimethylammonium chloride (DTAC) and Triton X-100. Computed simulations allow explaining the experimental results, indicating that micelles behave differently regarding the degree of accumulation and the local distribution of the reactants and their effect in the molecular collisions leading to net reaction.

Molecular Dynamic Simulations of Aqueous Micellar Organometallic Catalysis: Methane Functionalization as a Case Study

AbstractMolecular Dynamics (MD) simulations constitute a powerful tool that provides a 3D perspective of the dynamical behavior of chemical systems. Herein the first MD study of the dynamics of a catalytic organometallic system, in micellar media, is presented. The challenging methane catalytic functionalization into ethyl propionate through a silver‐catalyzed process has been targeted as the case study. The intimate nature of the micelles formed with the surfactants sodium dodecylsulfate (SDS) and potassium perfluorooctane sulfonate (PFOS) has been ascertained, as well as the relative distribution of the main actors in this transformation, namely methane, the diazo reagent and the silver catalyst, the latter in two different forms: the initial compound and a silver‐carbene intermediate. Catalyst deactivation occurs with halide containing surfactants dodecyltrimethylammonium chloride (DTAC) and Triton X‐100. Computed simulations allow explaining the experimental results, indicating that micelles behave differently regarding the degree of accumulation and the local distribution of the reactants and their effect in the molecular collisions leading to net reaction.

Cross-Coupling Reaction of Hydrophobic Substrates in Water: Micellar Catalysis with Macromolecular Surfactants

Cross-Coupling Reaction of Hydrophobic Substrates in Water: Micellar Catalysis with Macromolecular Surfactants

Green imine synthesis from amines using transition metal and micellar catalysis.

Imines are a versatile class of chemicals with applications in pharmaceuticals and as synthetic intermediates. While imines are conventionally synthesized via aldehyde-amine condensation, their direct preparation from amines can avoid the need for the independent preparation of the aldehyde coupling partner and associated constraints with regard to aldehyde storage and purification. The direct preparation of imines from amines typically utilizes transition metal catalysis and is often well-aligned with green chemistry principles. This review provides a comprehensive overview of transition metal catalysed imine synthesis, with a particular focus on the copper-catalyzed oxidative coupling of amines. The emerging application of micellar catalysis for imine synthesis is also surveyed due to its potential to avoid the use of hazardous solvents and intensify these reactions through reduced catalyst loadings and locally increased reactant concentrations. Future directions relating to the confluence of these two areas are proposed towards the more sustainable preparation of imines.

Harboring organocatalysts in a star-shaped block copolymer for micellar catalysis and emulsion catalysis

Conducting an asymmetric aldol reaction in both micelles and emulsions with high interfacial reactivity and stereoselectivity is achieved by incorporating an organocatalyst in the inherently hydrophobic center of a star-shaped polymer.

Micellar catalysis: Polymer bound palladium catalyst for carbon-carbon coupling reactions in water.

Metallosurfactants, defined here as hydrophobic metal-containing groups embedded in hydrophilic units when dispersed in water, emanate in the formation of metallomicelles. This approach continues to attract great interest for its ability to serve as micellar catalysts for various metal-mediated chemical transformations in water. Indeed, relevant to green chemistry, micellar catalysis plays a preeminent function as a replacement for organic solvents in a variety of chemical reactions. There are several methods for the interaction of metal complexes (catalysts or catalyst precursors) and surfactants for producing micellar aggregates. A very effective manner for achieving this involves the direct bonding of the metal center to the amphiphilic polymeric materials. Herein, we describe the synthesis of a metallosurfactant containing a palladium complex covalently incorporated into a CO2-based triblock polycarbonate derived using a dicarboxylic acid chain-transfer agent. This amphiphilic polycarbonate was shown to self-assemble in water to provide uniform and spherical micelles, where the catalytic metal center is located in the hydrophobic portion of the micelle. The resulting metallosurfactant was demonstrated to effectively catalyze carbon-carbon coupling reactions at very low catalyst loadings.

Kilogram‐Scale Synthesis of 4‐Chloro‐6‐(6‐methoxypyridin‐ 3‐yl)pyrimidine through a Suzuki–Miyaura Cross‐Coupling Using Micellar Catalysis

AbstractA scalable and environmentally benign protocol for a Suzuki–Miyaura cross‐coupling in water using vitamin E derived surfactant TPGS‐750‐M is reported. The protocol is the most simple and standard for such transformations under micellar catalysis that has been amply utilized within our own research and development portfolio over the last decade. The impact of the synthetic procedure is reenforced by green Process Mass Intensity and Total Carbon Release metrics.

Micellar Catalysis for a Sustainable Hydroaminomethylation Process in Water

Micellar Catalysis for a Sustainable Hydroaminomethylation Process in Water