Aqueous Micellar Media Research Articles

Development of In-Water Scalable Process for the Preparation of [2-(3-Bromo-2-methylphenyl)-7-chloro-1,3-benzoxazol-5-yl]methanol, a Key Intermediate in the Synthesis of Potent PD-1/PD-L1 Inhibitors

AbstractWe propose a synthetic process for the preparation of a benzoxazole building block for a programmed death-ligand 1 inhibitor that is a candidate currently under clinical investigation for cancer treatment. Our research focused on searching for mild, scalable, and ecofriendly conditions for the synthesis of benzoxazoles. To reduce the use of toxic reagents or solvents and to minimize the production of organic wastes, the cyclization reaction was performed in an aqueous micellar medium. This in-water benzoxazole synthesis gave comparable yields to previously reported processes, and was applied to a broad range of benzoxazoles with various substitution patterns, showcasing its effectiveness in ecofriendly benzoxazole cyclization reactions.

Characterization of Fipronil in Micellar Medium with Brij 35

Fipronil is a phenyl pyrazole used as an insecticide to combat termites, moths, and locusts. Its low solubility in water represents a problem with its commercial formulations. In this work, an aqueous micellar medium was formed with Brij 35, calculating the critical micellar concentration at 0.01% (w/v) by UV-visible spectrophotometry and conductimetry. In this medium, the apparent pka was estimated at 12.6 from spectrophotometric data by the graphical method and Partial Least Squares Regression. Finally, its degradation kinetics in this medium at pH 12 was studied, finding that it conforms to a first-order model, with a half-life of 3.3 h, higher than the 2.4 h reported by other authors for an aqueous medium. In conclusion, the micellar medium favored the solubility of the compound in aqueous medium, allowing the estimation of its pka and retarding its chemical degradation.

Chemo‐Enzymatic Synthesis of Navarixin by Using Aqueous Micellar Media: A Greener Approach

AbstractA mild and scalable chemo‐enzymatic procedure for the synthesis of the anticancer drug navarixin was developed in aqueous micellar media. We herein, report a greener methodology for the synthesis of a key chiral amine intermediate in the synthesis of navarixin using transaminases. This was obtained in high yields with an enantiomeric excess of >99.9 %. The current synthetic method represents a mild and sustainable procedure to afford the chiral amine intermediate in a single step without the use of expensive chiral ligands and auxiliaries. Furthermore, the chiral amine was used in the synthesis of navarixin which was obtained in high yield and an enantiomeric excess of >97.7 %.

UV‐Light Generation in Micelles via Triplet‐Triplet Annihilation Upconversion – Towards Synthetic Applications

AbstractOver the last century UV‐light mediated processes gave access to synthetically valuable products. Some of the disadvantages encountered when performing such UV‐light triggered synthetic reactions are the necessity for special glassware (quartz), the environmentally unfriendly irradiation sources and the need for oxygen removal, often via time consuming freeze‐pump‐thaw cycles. In addition, the penetration of UV‐light into the reaction mixture is a challenge due to absorption effects and scattering. A solution to these disadvantages could be triplet‐triplet annihilation upconversion performed under micellar reaction conditions. Hereby, UV‐light can be generated in the reaction mixture using visible light irradiation. In addition, the aqueous micellar medium can allow for the process to occur without the need for oxygen removal. This concept has been sporadically demonstrated and holds a great promise for the development of UV‐light promoted photochemical reactions under milder and more benign reaction conditions that may eventually allow for the development of scale up protocols.

An efficient, green and micellar catalyzed preparative-scale synthesis of 3,4-Disubstituted isoxazole-5(4H)-ones in the water

The one-pot three-component synthesis of 3,4-Disubstituted isoxazole-5(4H)-ones has been developed using an aqueous micellar medium as a catalyst under milder reaction conditions. The reaction was completed by using 25 mol% of sodium lauryl sulfate in an aqueous medium at room temperature. The reaction employs a green solvent, an eco-friendly reagent, and a non-chromatographic method for purification. The present reaction tolerates several substituted aldehydes and has proved to be efficient along with excellent yield. Moreover, the micellar catalyst was recovered and reused several times without significantly losing its catalytic activity.

Photochemical cyclopropanation in aqueous micellar media - experimental and theoretical studies.

While in nature, reactions occur in water-based confined compartments, for a long time, water has been often regarded as an unsuitable medium for organic reactions. We have, however, found that photochemical cyclopropanation of styrenes with diazo compounds or their precursors can be performed in micellar systems. COSMO-RS studies revealed that the reactivity correlates with the predicted critical micelle concentration (CMC), with higher CMC values delivering higher yields.

Twisted-intramolecular-charge-transfer based fluorogenic nano-probes for ultrafast cyanide sensing in water and micellar medium

Two pre-twisted TICT active probes with varying pi-acidic terminal substituents have been employed for CN− detection in water and in the aqueous micellar medium. Selectivity and sensitivity towards CN− improved substantially in aqueous medium with the assistance of CTAB.

Design and spectral-luminescent properties of a triad consisting of two BODIPY chromophores axially bound to a Sn(IV)-porphyrin in aqueous and aqueous micellar media

In this work, we designed and studied the emissive properties of a triad consisting of two BODIPY chromophores axially bound to a Sn(IV)-porphyrin via a methylphenolate bridge in aqueous and aqueous micellar media. It has been shown that the fluorescent properties of the porphyrin fragment of the triad, due to photoinduced energy transfer from the axial fragments to the macrocycle, are most sensitive to small changes in viscosity in the range from 3 to 6 cP, which corresponds to the viscosity of the blood of a healthy person (4–6 cP). The localization of the triad in the spherical CTAB micelles increases its emission in aqueous media. The structure–property dependencies established in the study can be applied to design molecular devices for sensing local viscosity of aqueous and aqueous micellar media, which could be of great interest for non-contact detection of physical properties of intracellular or lymphatic fluids.

Metal free synthesis of substituted 5-aryl/alkyl aminotetrazoles in water

The synthesis of tetrazoles is established under metal free conditions at room temperature in the presence of open air. The reaction of 2-bromoaryl isothiocyantes with amines gives thiourea that undergoes reaction in situ with NaN3 using Iodine in the presence of water medium to afford 1-(2-bromophenyl)-N-5-arylaminotetrazoles via substitution followed by electrocyclization processes at ambient temperature. All electron donating and withdrawing substituents readily underwent the reaction to get the corresponding final products 2a–2ab in moderate to good yield. This methodology has also applied for gram-scale quantity of tetrazoles. In addition, our aqueous micellar medium has shown good recyclability activity and it has exhibited good yield of the product up to four cycles.

Green One‐Pot Chemo‐Enzymatic Synthesis of a Key Chiral Amine Intermediate: Useful to Pralsetinib Synthesis

AbstractA facile, chemo‐enzymatic one‐pot and scalable procedure was developed for the synthesis of the key chiral intermediate of pralsetinib in an aqueous micellar medium. This method afforded the desired chiral intermediate with high enantioselectivity without the use of any expensive chiral ligands and toxic reagents that are difficult to handle. A green synthesis of chiral intermediate of pralsetinib was carried out using an enzyme ATA‐260 in an aqueous media with >99.9 % ee that was confirmed by a chiral reverse‐ phase HPLC. This study hence represents a mild and scalable procedure for the synthesis of the chiral intermediate of Pralsetinib with yields exceeding 80 %, which forms a crucial step in the synthesis of the anti‐ cancer drug.

A facile, one-pot reductive alkylation of aromatic and heteroaromatic amines in aqueous micellar media: a chemoenzymatic approach.

A facile, green, selective and practical method for the catalytic N-alkylation of amines using molecular hydrogen as the reductant was developed. This procedure involves a lipase-mediated one-pot chemoenzymatic cascade wherein an amine undergoes a reductive amination with an aldehyde generated in situ. The imine formed thereby is reduced to give the corresponding amine. This process represents a convenient, environmentally benign and scalable one-pot process for the synthesis of N-alkyl amines. We report for the first time chemoenzymatic reductive alkylation in aqueous micellar media with an E-factor of 0.68.

Cu-catalysed Chan–Lam synthesis of unsymmetrical aryl chalcogenides under aqueous micellar conditions

Herein, we report a green and sustainable Cu-catalysed Chan–Lam oxidative protocol for the synthesis of (hetero)aryl selenides/sulfides from diorganyl dichalcogenides and (hetero)aryl boronic acids in an aqueous micellar medium.

Kinetic studies of copper-catalyzed homocoupling reactions of arylboronic acids in aqueous micellar media

The kinetic studies for copper-catalyzed homocoupling phenylboronic acids (1a-d) have been successfully carried out in an aqueous micellar medium under environmentally benign conditions (water as a solvent, micelle to help solubilize hydrophobic adducts) in this study cetyl trimethyl ammonium bromide (CTAB ) is used as surfactant to produce micelle. Using different copper salts and copper complexes as catalysts under benign to mild conditions at a temperature range (40-65˚C, under air) without the addition of any additives (base, oxidant, and ligands). The reactions were followed using a UV-Vis spectrophotometer and the absorbances were measured at maximum wavelengths for the biphenyl production of each five selected (1a-d). The observed rate constants (kobs) were calculated using a pseudo-first-order equation and unsubstituted 1a was selected for optimization processes. The experimental results showed good to excellent curve fit (R2=0.9967-0.9998) to the pseudo-first-order equation and origin software was used for this purpose. Among all copper catalysts, the observed rate constant (kobs) for cupric acetate (Cu(OAc)2)is much higher than others, (kobs=0.1605 min-1), while CuCl2.2H2O has a minimum observed rate constant, kobs=0.0216min-1. The two copper complexes [Cu(4-mba)2(tmeda)], and [Cu(3-mba)2(H2O)2(tmeda)] require a mild condition (85˚C) which is higher than other copper catalysts when 1a is used as reactant the value of kobs is (0.0176, 0.0343 min-1) respectively, while using p-tolylboronic acid (1b) as reactant the value of kobs is (0.0173, 0.0147 min-1) respectively.

Hypervalent iodine(III) promoted synthesis of isothiocyanates in water

Here, we have established method for the synthesis of isothiocyanates using diacetoxyiodobenzene as a desulfurizing agent under micellar condition in water. We have explored functional group tolerance under optimized reaction conditions. All electron donating and withdrawing amines carried out the reaction to produce their corresponding desired isothiocyanates 1a–17a in moderate to good yield. This synthetic process in water can be applied to prepare isothiocyanates at gram-scale quantity. Our aqueous micellar medium also demonstrated high reusability as the reaction can be performed for several cycles without losing its efficiency. The reaction is metal-free, utilize water as solvent and practical at room temperature and open flask.

Synthesis of Tetrahydrobenzo[b]pyrans Promoted by Sodium Stearate as a Lewis Base-Surfactant Combined Catalyst in an Aqueous Micellar Medium

Synthesis of Tetrahydrobenzo[b]pyrans Promoted by Sodium Stearate as a Lewis Base-Surfactant Combined Catalyst in an Aqueous Micellar Medium

Synergistic reinforcement of CPC/TX-100 mixed micellar microenvironment for diperiodatocuprate(III) (DPC) oxidation of 1-propanol and 1,3-propanediol

The realization of employment of two surfactants in organic transformation comes from the intensity on achievement of better results with lower concentrations of individual surfactants than with single surfactants. In this work, the oxidations of 1-propanol and 1,3-propanediol by copper(III)-periodate (DPC) complex in aqueous micellar media were investigated, separately. The kinetic measurements were conducted by recording UV–visible absorbance spectra following the pseudo-first order condition. The isolated oxidized products were identified by assigning 1H NMR and FTIR studies. Both the oxidations were considerably promoted by the presence of micro-environment, constituted by CPC (cetylpyridinium chloride) and TX-100 (Triton-X 100) surfactants, individually. The maximum catalytic achievement was ascertained while both the surfactants were exist in equimolar amount in the reaction media. The aggregation of binary surfactants to produce a balanced mixed micelle is crucial to analyze the absolute kinetic results of present oxidation study. The electrostatic interaction between charged micelle and DPC facilitates to bring about the oxidizing species closest approach to the substrate (1-propanol and/or 1,3-propanediol) which are usually solubilized in micellar micro-environment.

Magnetically recoverable Fe3O4 nanocatalyst for the synthesis of biodynamically significant 1H-pyrazolo[1,2-b]phthalazine-5,10-diones derivatives and its DFT study.

An environmentally sustainable and proficient method is reported for the synthesis of medicinally important pyrazolo[1,2-b] phthalazine dione derivatives by aqueous micellar medium catalysed by Fe3O4 NPs. Dialkyl acetylenedicarboxylate with isocyanides in the presence of phthalhydrazide is used as starting material. The main advantages of this protocol are the availability of starting materials, short reaction times, green solvents and practical simplicity.

New PEDOT Derivatives Electrocoated on Silicon Nanowires Protected with ALD Nanometric Alumina for Ultrastable Microsupercapacitors.

This work deals with electroactive conducting polymers (ECPs) used as a complementary component on purely capacitive silicon nanowires protected by a 3 nm alumina layer. Accordingly, in this work, we use a fast and simple deposition method to create a pseudocapacitive material based on the electropolymerization in aqueous micellar media (SDS and SDBS 0.01 M) of hydroxymethyl-EDOT (EDOT-OH) onto 3 nm alumina-coated silicon nanowires (Al3@SiNWs). The composite material displays remarkable capacitive behavior with a specific capacitance of 4.75 mF·cm−2 at a current density of 19 µA·cm−2 in aqueous Na2SO4 electrolyte.

Transfer Hydrogenolysis and Hydrogenation of DNA-Conjugated Substrates in Aqueous Micellar Media

Key words palladium catalysis - micellar catalysis - DNA-encoded libraries - transfer hydrogenolysis - transfer hydrogenation

Photocatalysis in Aqueous Micellar Media Enables Divergent C–H Arylation andN-Dealkylation of Benzamides

Photocatalysis in aqueous micellar media has recently opened wide avenues to activate strong carbon–halide bonds. So far, however, it has mainly explored strongly reducing conditions, restricting the available chemical space to radical or anionic reactivity. Here, we demonstrate a controllable, photocatalytic strategy that channels the reaction of chlorinated benzamides via either a radical or a cationic pathway, enabling a chemodivergent C–H arylation or N-dealkylation. The catalytic system operates under mild conditions with methylene blue as a photocatalyst and blue LEDs as the light source. Factors determining the reactivity of substrates, their selectivity, and preliminary mechanistic studies are presented.