Micellar Catalysis Research Articles

Synthesis of an ionic sugar-amino acid based surfactant in aqueous media

Micellar catalysis has been used to synthesis a sugar-amino acid based cationic surfactant (N,N,N-trimethyl-2-oxo-2-(((2R,3S,4S,5R)-3,4,5-trihydroxy-6-(tetradecyloxy)tetrahydro-2H-pyran-2-yl)methoxy)ethan-1-aminium iodide) with renewable raw materials in aqueous media. The micellar catalysis method was compared with the method that uses dimethylformamide (DMF) as solvent. The results confirm the superiority of micellar catalysis method in terms of efficiency, energy consumption and environmental issues. Common physicochemical properties of surfactants like critical micelle concentration (CMC), the minimum surface area per molecule (Amin) and Krafft temperature were determined to evaluate the behavior of synthesized surfactant properties at the air-water interface. Computational chemistry method (DFT (B3LYP/6-311g(d)) was conducted to calculate the dimensional properties of the surfactant to determine the shape, size and aggregation number of micelles at their CMC by an approach that uses Connolly solvent accessible area as the effective area of surfactant head groups. Dynamic light scattering method (DLS) was used to determine the size of micelles. The results of DLS tests show good agreement with the calculation method. Finally, the biodegradability of synthesized natural based cationic surfactant was studied by close bottle standard test to investigate the biodegradation of synthesized surfactant.

One-Pot Synthesis of Indoles and Pyrazoles via Pd-Catalyzed Couplings/Cyclizations Enabled by Aqueous Micellar Catalysis.

An effective one-pot synthesis of either indoles or pyrazoles can be achieved via Pd-catalyzed aminations followed by subsequent cyclizations facilitated by aqueous micellar catalysis. This new technology includes efficient couplings with low loadings of palladium, a more stable source of the required hydrazine moiety, greater atom economy for the initial coupling, and reduced reaction temperatures, all leading to environmentally responsible processes.

Sustainability as a Trigger for Innovation!

About a decade ago, prompted by regulatory pressure, we at Novartis entered the field of micellar catalysis. We were fortunate to discover some enabling techniques that rapidly allowed for application and deep impact of the technology within our development portfolio. In parallel, we endeavored to push the boundaries of science, building a powerful toolbox of chemistry, and gaining in the understanding of such systems. Of particular importance is the compartmentalization effect that needs to be well understood and mastered to access all the benefits of the technology. The following review article will illustrate our journey more specifically for Suzuki-Miyaura cross-couplings, with some detours that will further highlight the impact of the technology.

Sustainable Palladium-Catalyzed Tsuji-Trost Reactions Enabled by Aqueous Micellar Catalysis.

Palladium-catalyzed allylic substitution, or "Tsuji-Trost" reactions, can be run under micellar catalysis conditions featuring not only chemistry in water but also numerous combinations of reaction partners that require low levels of palladium, typically on the order of 1000 ppm (0.1 mol %). These couplings are further characterized by especially mild conditions, leading to a number of cases not previously reported in an aqueous micellar medium. Inclusion of diverse nucleophiles, such as N-H heterocycles, alcohols, dicarbonyl compounds, and sulfonamides is described. Intramolecular cyclizations further illustrate the broad utility of this process. In addition to recycling studies, a multigram scale example is reported, indicative of the prospects for scale up.

Iodine Promoted Efficient Synthesis of 2-Arylimidazo[1,2-a]pyridines in Aqueous Media: A Comparative Study between Micellar Catalysis and an “On-Water” Platform

In a new and environmentally sustainable approach, a series of 2-arylimidazo[1,2-a]pyridine derivatives were synthesized in aqueous media in the presence of iodine as a catalyst. The reaction proceeded by condensation of various aryl methyl ketones with 2-aminopyridines to afford 2-arylimidazo[1,2-a]pyridines in good overall yields. Although several of the reactions were efficiently performed “on water”, the addition of a surfactant, namely, sodium dodecyl sulphate , was found effective in terms of substrate scope and yield enhancement. Both methods were successfully used for the gram-scale synthesis of a marketed drug, zolimidine. The simple experimental setup, water as “green” media, and inexpensive catalyst are some of the merits of this protocol.

A Glimpse into Green Chemistry Practices in the Pharmaceutical Industry.

Invited for this month's cover is the research group of Sachin Handa at the University of Louisville and Wilfried Braje at AbbVie. The image shows how green chemistry in industry and micellar catalysis are contributing toward the environmental sustainability. The Minireview itself is available at 10.1002/cssc.202000317.

Micellar catalysis enabled synthesis of indolylbenzothiazoles and their functionalization via Mn(II)-catalyzed C2–H amination using pyridones

The sustainable synthesis of indolylbenzothiazloes is reported utilising TPGS-750-M enabled nanomicellar catalysis in water. The reactions do not require additional catalysts and/or oxidants and proceed at room temperature. Subsequently, the indole rings were functionalized to construct novel tris-heterocyclic scaffolds via benzothiazole directed Mn(II)-catalyzed C2–H amination utilizing pyridones as the amine partner.

Micelle-Catalyzed Synthesis of Arylmethylidene Derivatives of Malononitrile Trimer and Study of Their Optical Properties

Potassium salts of arylmethylidene derivatives of malononitrile trimer were obtained by the reactions of aromatic aldehydes with malononitrile trimer in an aqueous medium under micellar catalysis. The optical properties of the synthesized salts were studied to show they absorb in the range of 313–436 nm, depending on the substituent. Exchange reactions with various metal salts showed that the synthesized derivatives of malononitrile trimer form difficultly soluble compounds with silver salts.

Syntheses of Organic Semiconductors in Water. Recent Advancement in the Surfactants Enhanced Green Access to Polyconjugated Molecules

Organic semiconductors have been at the center of intense investigation for decades. The efficiencies of the most performing candidates, along with the compatibility with solution processing and printing led to relevant technological breakthrough. The development of market applications for Organic Light Emitting Devices (OLEDs), Organic Thin film transistors (OTFTs), and Organic Photovoltaics (OPVs) poses a relevant question regarding to the scaling up and overall sustainability of synthetic protocols employed for the preparation of active compounds. This review summarizes the role that the emerging field of micellar catalysis and surfactant enhanced chemistry can play in dramatically improving the sustainability of established and emerging performing organic semiconductors.

Amphiphilic PdII‐NHC Complexes on 1,3‐Alternate p‐tert‐Butylthiacalix[4]arene Platform: Synthesis and Catalytic Activities in Coupling and Hydrogenation Reactions

Herein we report the first example of amphiphilic PdII–NHC complexes on the thiacalix[4]arene backbone in 1,3‐alternate configuration. Relative catalytic activity of synthesized PdII–NHC complexes in Suzuki–Miyaura coupling of haloarenes with phenylboronic acid was studied. A combination of micellar and metallocomplex catalysis was observed in Suzuki–Miyaura coupling upon going from pure DMF to water/DMF 3:1: the 2‐fold increase of conversion of 4‐bromoanisole unlike pure DMF was found. Interesting feature was found using chloroarene in DMF/water: the reaction selectivity changed from heterocoupling to homo coupling of phenylboronic acid. PdII–NHC complexes demonstrated a high activity in model hydrogenation reaction of p‐nitrophenol using sodium borohydride. The most lipophilic PdII–NHC complex was found to be most active, which can be attributed with additional p‐nitrophenol preconcentration in the aggregates due to larger hydrophobic capacity of macrocycle.

Micellar catalyzed hydroxylation of 1,2,3-trichloro-4,6-dinitrobenzene: Role of cationic head group–π interaction

The micellar catalysis of the hydroxylation of 1,2,3-trichloro-4,6-dinitrobenzene (DNTCB) with aqueous NaOH, to synthesize 2-chloro-4,6-dinitroresorcinol (CDNR), was studied using cationic, anionic and non-ionic surfactants at different concentrations to promote the reaction kinetics. The micellar catalysis using cationic surfactants at optimum concentrations was effective giving highest conversion of DNTCB (92–100%), which was ascribed to high solubilization capacity of the micellar solutions for DNTCB, surface positive charges of micelles increasing OH– ions concentration near micellar surface, and the cation-π interaction of surfactant molecules (through cationic head group) with DNTCB molecules. The cation-π interaction plays important role in solubilization process, substrate activation and catalysis of the reaction. The higher surfactant concentrations retard the reaction owing to strong solubilization of DNTCB in micelles and reduced OH– ions concentration around the micelles. The cationic micellar solutions at optimum surfactant concentrations can be effective catalytic system for the aromatic nucleophilic substitution reactions.

Placing Single-Metal Complexes into the Backbone of CO2-Based Polycarbonate Chains, Construction of Nanostructures for Prospective Micellar Catalysis

The copolymerization of CO2 and epoxides in the presence of chain-transfer agents (CTAs) has provided a well-controlled route to polycarbonate polyols. Upon employing dicarboxylic acid CTAs which c...

Recent designer surfactants for catalysis in water

Recent development of new designer surfactants further spurs the development of micellar catalysis in water for chemical transformations and catalysis, providing reliable alternatives to the employment of organic solvents.

Cationic iron porphyrins with sodium dodecyl sulphate for micellar catalysis of cyclopropanation reactions.

Here, we report that the combination of cationic iron porphyrins with sodium dodecyl sulphate (SDS) gives rise to efficient micellar catalysis of cyclopropanation reactions of styrene derivatives, using diazoacetates as carbene precursors. This simple, yet effective approach for cyclopropanations illustrates the power of micellar catalysis.

Regioselective C–H hydroxylation of n-alkanes using Shilov-type Pt catalysis in perfluorinated micro-emulsions

In this work, the potential of combining Shilov-type PtII and micellar catalysis to realize the challenging terminal C–H hydroxylation of saturated n-alkanes using water as the reaction medium is demonstrated.

Surfactant Catalyzed Oxidation of Ethanolamines by Cerium(IV)

Effect of surfactant medium on the kinetics of oxidation of amino alcohol by cerium(IV) has been reported. Two amino alcohols namely, monoethanolamine (MEA) and triethanolamine (TEA) are chosen for kinetic study. Sizeable changes in reaction rate are noted only in presence of sodium lauryl sulphate (NaLS) as surfactant. Both the amino alcohols exhibit rate maxima at around the cmc of NaLS, beyond which the kψ-[NaLS] profile shows slow increase in rate constant with increasing NaLS concentration. Suitable model has been used to explain the kinetic pattern post CMC and from this the micelle-reactant binding constant values have been evaluated. From the temperature dependence study, the activation parameters for the oxidation reactions have been computed and these are compared against those obtained for aqueous medium. Based on all information, plausible mechanism for micellar catalysis has been presented.

Micellar Catalysis in Fischer Glycosidation: En Route to Diverse Functional Glycosides

AbstractWe have demonstrated that direct Fischer glycosidation of carbohydrates with selected alcohols, glycols and chloroalcohols to corresponding glucosides in micellar reaction system can be a promising and effective route for the selective synthesis of a number of functional glucosides. The use of specific catalyst combining both surfactant and acid catalyst functions enables formation of the reactive micellar system. The formation of corresponding glucosides with spectacular high selectivity to monoglucosides is one of the most important phenomena of the application of micellar catalysis to functional glucosides synthesis.

Micellar Catalysis Strategy of Cross-Condensation Reaction: The Effect of Polar Heads on the Catalytic Properties of Aminoalcohol-Based Surfactants

The effect of the polar head and the concentration of quaternary ammonium surfactants (C14EtOH, C14iPrOH, C14PrOH, where, 14 = carbon number iPrOH = iso-propanol, EtOH = ethanol, PrOH = propanol) in micellar catalysis for the cross-condensation reaction (Claisen–Schmidt) was investigated. The reaction in the Micellar-NaOH system with different concentrations of surfactants above the critical micelle concentration from 15 to 30 mmol between benzaldehyde and acetophenone was used as a model of reaction for this study. The examination of the effectiveness of the catalytic activity reveals that the compound C14EtOH has the best yield (80% of the desired product), followed by C14iPrOH and C14PrOH. The results were interpreted according to the solubilization capacity, droplet size analysis of reagents (benzaldehyde and acetophenone) in the micellar medium and stability of reaction intermediate (enolate) by the electrostatic interactions generated by positive charge of N+ quaternary ammonium atom. Therefore, the quantum calculations carried out by DFT method for surfactants in the aqueous medium, show that electrophilicity degree and the reaction yield% for three cationic surfactants varies in the same following order: C14PrOH < C14iPrOH < C14EtOH.

Visible-Light-Controlled Reaction-Separation for Asymmetric Sulfoxidation in Water with Photoresponsive Metallomicelles

Metallomicellar catalysis has gained increasing attention in recent years since it made water-incompatible organometallic catalysis highly efficient in water. However, a convenient approach to combine activity and recovery of metallomicelles from aqueous systems has remained challenging to date. Herein, we developed a series of nitrospiropyran-containing metallomicelles which possessed visible-light-responsivity, to realize the visible-light-controlled reaction and separation for asymmetric sulfoxidation in water. A series of nitrospiropyran-containing diblock chiral salen TiIV copolymers were thus prepared by copolymerizing photosensitive nitrospiropyran derivative with hydrophobic chiral salen TiIV monomer via free-radical polymerization. Characterization results suggested their visible-light-controlled self-assembly behavior in water due to the negative photochromism of nitrospiropyran block. The resultant light-responsive metallomicelles induced a micellar catalysis approach in the dark for asymmetric...

Discovery-Based SNAr Experiment in Water Using Micellar Catalysis

Micellar catalysis has become an important aspect of the chemical industry’s effort to “go green”. However, this chemistry has yet to be fully explored in educational settings such as second-year organic chemistry laboratories. Reported herein is a discovery-based nucleophilic aromatic substitution experiment that introduces chemistry students to micellar catalysis, green chemistry, and systems thinking. The students prepare tandem reactions in water to explore how the leaving group identity affects the rate of reaction and how the reaction incorporates principles of green chemistry. The product of the fastest reaction is isolated through recrystallization, and the product’s identity is verified through infrared spectroscopy and melting point analysis.