Homogeneous Reaction Mixtures Research Articles

Efficient Synthesis of Hydrolytically Degradable Block Copolymer Nanoparticles via Reverse Sequence Polymerization-Induced Self-Assembly in Aqueous Media.

Hydrolytically degradable block copolymer nanoparticles are prepared via reverse sequence polymerization-induced self-assembly (PISA) in aqueous media. This efficient protocol involves the reversible addition-fragmentation chain transfer (RAFT) polymerization of N,N'-dimethylacrylamide (DMAC) using a monofunctional or bifunctional trithiocarbonate-capped poly(ϵ-caprolactone) (PCL) precursor. DMAC monomer is employed as a co-solvent to solubilize the hydrophobic PCL chains. At an intermediate DMAC conversion of 20-60 %, the reaction mixture is diluted with water to 10-25 % w/w solids. The growing amphiphilic block copolymer chains undergo nucleation to form sterically-stabilized PCL-core nanoparticles with PDMAC coronas. 1 H NMR studies confirm more than 99 % DMAC conversion while gel permeation chromatography (GPC) studies indicate well-controlled RAFT polymerizations (Mw /Mn ≤1.30). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) indicate spheres of 20-120 nm diameter. As expected, hydrolytic degradation occurs within days at 37 °C in either acidic or alkaline solution. Degradation is also observed in phosphate-buffered saline (PBS) (pH 7.4) at 37 °C. However, no degradation is detected over a three-month period when these nanoparticles are stored at 20 °C in deionized water (pH 6.7). Finally, PDMAC30 -PCL16 -PDMAC30 nanoparticles are briefly evaluated as a dispersant for an agrochemical formulation based on a broad-spectrum fungicide (azoxystrobin).

Resolving the incompatibility between SET-LRP and non-disproportionating solvents

Cu(0)-catalyzed single-electron transfer-living radical polymerization (SET-LRP) has shown great potential for applications in which well-defined chain end-functionalized polymers are demanded as final products or as intermediates. However, the use of polar reaction media favoring the disproportionation of Cu(I)X species into Cu(0) and Cu(II)X2 was considered a limiting factor specially in the synthesis of complex hydrophobic polymers with functional chain ends. “Self-generated” biphasic systems, in which the polymer phase-separates from the homogeneous reaction mixture above a certain molecular weight, together with fundamental studies on the role of solvent, including catalytic solvent effect, and methodological developments such us the “mixed-ligand” concept served as inspiration, although sometimes in an unknown way, to solve this problem. Today, SET-LRP of both acrylic and methacrylic vinyl monomers is already feasible in both polar and non-polar non-disproportionating solvents using their corresponding bi(multi)phasic “programmed” mixtures with water. Under these conditions, SET-LRP is an interfacial process in which disproportionation and activation events occur independently in the aqueous and organic compartments, and the “self-controlled” reversible deactivation takes place at the interface. Consequently, this design entirely defeats the limiting requirement to exclusively use disproportionating solvents. After a brief discussion of the historical evolution of the field of LRP, starting with the landmark work of Otsu from 1950th, this feature article will describe the elaboration of “programmed” bi(multi)phasic SET-LRP systems starting from initial inspiration to development in laboratory large-scale experiments.

Continuous Production of Carbon-Supported and Surfactant-Free Pt-M (M=Fe, Co, Ni, and Cu) Nanocrystals for Catalyzing Oxygen Reduction

Scalable production of carbon-supported Pt-M (M=Co, Ni, and Fe) alloy nanocrystals is of great importance for their practical application as catalysts towards the oxygen reduction reaction (ORR), a process key to the operation of proton-exchange membrane fuel cells. Here we report the use of a fluidic device for the in situ nucleation and growth of Pt-M nanocrystals on a commercial carbon support in a continuous and scalable fashion. The use of dimethylformamide not only enables well dispersion of the carbon powders for the creation of a homogeneous reaction mixture but also helps reduce metal precursors for the heterogeneous nucleation and growth of nanocrystals on the carbon surface. The size, shape, and composition of the nanocrystals can all be tuned by changing the metal precursors added into the reaction mixture, resulting in Pt-M nanocrystals uniformly distributed across the surface of the carbon support. Among the nanocrystals, the carbon-supported Pt-Co nanocrystals show the highest ORR specific and mass activities at 0.9 V, demonstrating 11.4- and 8.8-fold enhancements over the state-of-the-art commercial Pt/C catalyst.

Nickel-Catalyzed Cyanation of (Hetero)aryl Bromides Using DABAL-Me3 as a Soluble Reductant.

A nickel-catalyzed cyanation of (hetero)aryl halides using air-stable bis(trimethylaluminum)-1,4-diazabicyclo[2.2.2]octane (DABAL-Me3) as a soluble reductant has been developed. The reaction uses readily available and inexpensive Ni(dppf)Cl2 as a precatalyst, a substoichiometric amount of Zn(CN)2, and DABAL-Me3 as an alternative to commonly prescribed insoluble reductants. We found the addition of catalytic tetrabutylammonium bromide (TBABr) to be beneficial, due to facilitating dissolution of low levels of the cyanide salt (confirmed via a control study). Similarly, slow addition of a tetrabutylammonium cyanide (TBACN) solution is effective and results in a completely homogeneous reaction mixture.

C-NMR studies on the structure of linear p–substituted phenol polymer

Linear polymer of p – substituted phenol with Methylene Bridge has been prepared by using condensation polymerization. To this homogeneous reaction mixture of p – substituted phenol (Bisphenol-A; p – hydroxyacetophenone and p – chlorophenol ) along with NaOH solution and formaldehyde was added while stirring. 13C – NMR spectroscopy allowed identification of the linkage formed and qualification of the main functional groups in the p – substituted phenol with methylene bridge; which were greatly influenced by the preparation conditions. Methylene bridges in the linear polymers were found to be mainly associated with the para position linkage methylene unit. The linear p–substituted phenol condensed polymer had no free formaldehyde. p – Substituted dimethylol phenol was indulged into the condensed polymers by reacting with phenolic units to results in condensed methylene bridges. The linear polymer with p – substituted phenol having Methylene Bridge possessed relatively high degree of polymerization and very low percentage of unreacted methylene groups. The synthesized polymer samples were characterization by the 13C – NMR technique excellently.

Ultrahigh-Throughput Experimentation for Information-Rich Chemical Synthesis.

The incorporation of data science is revolutionizing organic chemistry. It is becoming increasingly possible to predict reaction outcomes with accuracy, computationally plan new retrosynthetic routes to complex molecules, and design molecules with sophisticated functions. Critical to these developments has been statistical analysis of reaction data, for instance with machine learning, yet there is very little reaction data available upon which to build models. Reaction data can be mined from the literature, but experimental data tends to be reported in a text format that is difficult for computers to read. Compounding the issue, literature data are heavily biased toward "productive" reactions, and few "negative" reaction data points are reported even though they are critical for training of statistical models. High-throughput experimentation (HTE) has evolved over the past few decades as a tool for experimental reaction development. The beauty of HTE is that reactions are run in a systematic format, so data points are internally consistent, the reaction data are reported whether the desired product is observed or not, and automation may reduce the occurrence of false positive or negative data points. Additionally, experimental workflows for HTE lead to datasets with reaction metadata that are captured in a machine-readable format. We believe that HTE will play an increasingly important role in the data revolution of chemical synthesis. This Account details the miniaturization of synthetic chemistry culminating in ultrahigh-throughput experimentation (ultraHTE), wherein reactions are run in ∼1 μL droplets inside of 1536-well microtiter plates to minimize the use of starting materials while maximizing the output of experimental information. The performance of ultraHTE in 1536-well microtiter plates has led to an explosion of available reaction data, which have been used to identify specific substrate-catalyst pairs for maximal efficiency in novel cross-coupling reactions. The first iteration of ultraHTE focused on the use of dimethyl sulfoxide (DMSO) as a high-boiling solvent that is compatible with the plastics most commonly used in consumable well plates, which generated homogeneous reaction mixtures that are perfect for use with nanoliter-dosing liquid handling robotics. In this way, DMSO enabled diverse reagents to be arrayed in ∼1 μL droplets. Reactions were run at room temperature with no agitation and could be scaled up from the ∼0.05 mg reaction scale to the 1 g scale. Engineering enhancements enabled the use of ultraHTE with diverse and semivolatile solvents, photoredox catalysis, heating, and acoustic agitation. A main driver in the development of ultraHTE was the recognition of the opportunity for a direct merger between miniaturized reactions and biochemical assays. Indeed, a strategy was developed to feed ultraHTE reaction mixtures directly to a mass-spectrometry-based affinity selection bioassay. Thus, micrograms of starting materials could be used in the synthesis and direct biochemical testing of drug-like molecules. Reactions were performed at a reactant concentration of ∼0.1 M in an inert atmosphere, enabling even challenging transition-metal-catalyzed reactions to be used. Software to enable the workflow was developed. We recently initiated the mapping of reaction space, dreaming of a future where transformations, reaction conditions, structure, properties and function are studied in a systems chemistry approach.

Nanofibers made from acetylparamylons by a soaking method

A novel method was developed for preparing nanofibers from acetylparamylons, which are acetylated derivatives of a β-1,3-glucan (paramylon) produced by Euglena cells. This method was primarily based on the self-assembling tendency of β-1,3-glucans. First, a solid consisting of aggregated nanofibers (~100 nm in diameter) was precipitated by pouring a homogeneous reaction mixture containing acetylparamylons into water. Second, the solid precipitate was soaked in a halogenated solvent. Scanning probe microscopic observations confirmed that soaking in chloroform liberated nanofibers (105.0 ± 8.9 nm in diameter and over ~7.0 μm in length) from the solid precipitates of acetylparamylon with an acetylation degree of ~1.4.

Development of a Graphite-Based Nanostructured Nickel Telluride (n-NiTe/GP) Electrode for Electrochemical Detection of Antiplatelet Agent Clopidogrel

The present work illuminates the synthesis and electrochemical characterization of nano-structured semi-metallic chalcogenide nickel telluride (n-NiTe) based graphite paste (GP) electrode as low- cost, selective, and sensitive sensing platform for the analysis of Clopidogrel (CLO), an important anticoagulant agent. By using the reducing agent, sodium borohydride, NiTe nanocrystallites were synthesized from homogeneous reaction mixtures of tartrate complex of Ni2+ and Te4+ at room temperature. The material was characterized by scanning electron microscopy and x-ray diffraction.In this work, the analytical parameters were optimized to carry out cyclic and differential pulse voltammetry. Under optimized condition (0.1M phthalate buffer, pH-5) the electrode exhibited pretty good sensitivity in two linear ranges: 0.5- $10~\mu \text{M}$ , and 20- $200~\mu \text{M}$ with a lower detection limit of 340 nM. Also, the n-NiTe/GP electrode was employed to determine CLOin pharmaceutical samples and the results showed recoveries more than 90.40%.

Influence of non-ideal behavior on esterification kinetics modeling

The well-known kinetics of Fischer esterification has already been reported for various systems. Despite this fact, the kinetic model of esterification of oleic acid and methanol under catalysis with sulfuric acid is still debated in the literature. The main reason is the two-phase character of the reaction mixture being neglected in kinetic studies. Contrary to this, the kinetics of autocatalytic esterification of cyclic alcohols with formic acid have not been published so far. Here, we present a kinetic study of both systems to assess the influence of the non-ideal (multi-phase) behavior on kinetic modeling. For the system of autocatalytic esterification of cyclic alcohols, we have found that a simple kinetic model without activity coefficients provides a good description of the experimental data. However, the same model is insufficient for the system of oleic acid and methanol. Therefore, we have developed a new approach based on kinetic modeling, including activity coefficients. Consequently, we have been able to describe for the first time the kinetics of oleic acid esterification in a homogeneous reaction mixture. Moreover, we provide a novel explanation for the commonly observed inhibition of this reaction by water as a result of phase equilibria in the reaction mixture.

Polymerization Assisted by Upconversion Nanoparticles under NIR Light.

Photopolymerization of nanocomposite materials using near infrared light is one of the unique technologies based on the luminescent properties of lanthanide-doped upconversion nanoparticles (UCNPs). We explored the UCNP-triggered radical polymerization both in oligomer bulk and on the nanoparticle surface in aqueous dispersion. Core/shell UCNPs NaYF4:Yb3+ and Tm3+/NaYF4 with emitting lines in the ultraviolet and blue regions were used to activate a photoinitiator. The study of the bulk photopolymerization in an initially homogeneous reaction mixture showed the UCNP redistribution due to gradient density occurring in the volume, which led to formation of UCNP superlattices and spheres “frozen” in a polymer matrix. We also developed a strategy of “grafting from” the surface, providing polymer shell growth directly on the nanoparticles. The photosensitization of the endogenous water-soluble photoinitiator riboflavin by the resonance energy transfer from UCNPs was demonstrated in the course of monomer glycidyl methacrylate polymerization followed by photocrosslinking with poly(ethylene glycol) diacrylate on the nanoparticle surface.

Batch and Continuous-Flow Iron(II)-Catalyzed Synthesis of Sulfilimines and Sulfoximines using N-Mesyloxycarbamates.

The synthesis of sulfilimines and sulfoximines with N-mesyloxycarbamates in presence of catalytic iron(II) chloride hydrate is described. The use of 1-butylimidazole as a base proved instrumental in enabling a homogeneous reaction mixture compatible with continuous flow processes. The amination is applicable to a wide range of substrates, and affords the desired product in good to excellent yields within 1 to 60 minutes.

Deep Insights into the Processes Occurring during Early Stages of the Formation and Room-Temperature Evolution of the Core (Amorphous SiO2)@Shell (Organocations) Nanoparticles

Following the assumption that the crucial processes governing the formation, properties, and evolution of the core (amorphous silica)@shell (organocations) nanoparticles (NPs) take place during short-time, room-temperature (rt) stirring/aging of the homogeneous reaction mixtures (HmRMs) formed by hydrolysis of tetraethyl orthosilicate (TEOS) in solutions of Org(OH)n, we investigated these processes by various experimental methods (pH, ionic conductivity, 29Si NMR, dynamic light scattering, and atomic force microscopy). The analysis of the data obtained by detailed and careful investigation of the “model” HmRMs having the starting chemical composition, xTEOS/0.25TPAOH/20H2O (TPAOH = tetrapropylammonium hydroxide; x = 0.05–1), offer some new elements for the understanding of the mechanisms of the formation and rt evolution of the core@shell silica NPs: (1) There is a resolute evidence of the formation of the stable, about 1.2 nm-sized core (amorphous SiO2)@shell (TPA+ ions) NPs below the critical aggregatio...

Chemical synthesis of nanoparticles of nickel telluride and cobalt telluride and its electrochemical applications for determination of uric acid and adenine

Nickel telluride (NiTe) and cobalt telluride (CoTe) nanocrystallites were synthesized from homogeneous reaction mixtures of tartrate complex of Ni2+/Co2+ and Te4+ at room temperature by reduction with sodium borohydride. The morphology and the structure of the synthesized particles were characterized by XRD, FESEM, TEM and EDX. The nanocrystallites have shown narrow size distribution with diameter 10.8nm and 3.8nm for NiTe and CoTe respectively. The electrochemical properties of the synthesized materials were carried out by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). NiTe modified graphite paste electrode (NiTe/GP) showed electrocatalytic oxidation towards uric acid (UA) and adenine (AD) and two well separated oxidation peaks were obtained in DPV measurement. The peak separation between UA and AD was 633mV. Under optimized experimental condition, the linear response ranges for the determination of UA and AD were 3–200μM and 3–50μM for NiTe/GP and the detection limits (S/N=3) were 95nM and 206nM respectively in the mixture. CoTe modified graphite paste electrode (CoTe/GP) displayed electrocatalytic oxidation towards uric acid (UA) only. Both the modified electrodes were used in human urine and blood sample analysis with better sensitivities than earlier reports.

A simple fast microwave-assisted synthesis of thermoelectric bismuth telluride nanoparticles from homogeneous reaction-mixture

A new simple chemical method for synthesis of nanocrystalline bismuth telluride (Bi2Te3) has been developed by microwave assisted reduction of homogeneous tartrate complexes of bismuth and tellurium metal ions with hydrazine. The reaction is performed at pH 10. The nano-crystallites have rhombohedral phase identified by XRD. The size distribution of nanoparticle is narrow and it ranges between 50 to 70 nm. FESEM shows that the fine powders are composed of small crystallites. The TEM micrographs show mostly deformed spherical particles and the lattice fringes are found to be 0.137 nm. Energy dispersive X-ray spectroscopy (EDX) analysis shows the atomic composition ratio between bismuth and tellurium is 2:3. Thermoelectric properties of the materials are studied after sintering by spark plasma sintering method (SPS). The grain size of the material after sintering is in the nanometer range. The material shows enhanced Seebeck coefficient and electrical conductivity value at 300 K. The figure of merit is found to be 1.18 at 300 K.

Catalytic photodegradation of pharmaceuticals - homogeneous and heterogeneous photocatalysis.

Photocatalytic degradation of pharmaceuticals (hydrocortisone, estradiol, and verapamil) and personal care product additives (parabens-methyl, ethyl, and propyl derivatives) was investigated in the homogeneous phase (with ferric ions as the catalyst) and on TiO2. Ferric ions in concentrations corresponding to concentrations in natural water bodies were shown to be a significant accelerator of the degradation in homogeneous reaction mixtures. In heterogeneous photocatalytic reactions on TiO2, lower reaction rates, but mineralisation to higher extents, were observed.

Single-Step Access to Long-Chain α,ω-Dicarboxylic Acids by Isomerizing Hydroxycarbonylation of Unsaturated Fatty Acids

Dicarboxylic acids are compounds of high value, but to date long-chain α,ω-dicarboxylic acids have been difficult to access in a direct way. Unsaturated fatty acids are ideal starting materials with their molecular structure of long methylene sequences and a carboxylate functionality, in addition to a double bond that offers itself for functionalization. Within this paper, we established a direct access to α,ω-dicarboxylic acids by combining isomerization and selective terminal carbonylation of the internal double bond with water as a nucleophile on unsaturated fatty acids. We identified the key elements of this reaction: a homogeneous reaction mixture ensuring sufficient contact between all reactants and a catalyst system allowing for activation of the Pd precursor under aqueous conditions. Experiments under pressure reactor conditions with [(dtbpx)Pd(OTf)2] as catalyst precursor revealed the importance of nucleophile and reactant concentrations and the addition of the diprotonated diphosphine ligand (dt...

Probing Cu(I) in homogeneous catalysis using high-energy-resolution fluorescence-detected X-ray absorption spectroscopy.

Metal-to-ligand charge transfer excitations in Cu(I) X-ray absorption spectra are introduced as spectroscopic handles for the characterization of species in homogeneous catalytic reaction mixtures. Analysis is supported by correlation of a spectral library to calculations and to complementary spectroscopic parameters.

Design of renewable poly(amidoamine)/hemicellulose hydrogels for heavy metal adsorption

ABSTRACTRenewable poly(amidoamine)/hemicellulose hydrogels were prepared from O‐acetylated galactoglucomannan (AcGGM)‐rich biomass and shown to display a significantly high adsorption capacity for Cu2+, Cd2+, Pb2+, Zn2+, Ni2+, Co2+, and . Two different acrylamido end‐capped poly(amidoamine) oligomers (PAA) were prepared and covalently immobilized onto an in situ formed polysaccharide network via water‐based free radical graft copolymerization and cross‐linking. The synthetic approach was shown to be viable when using a highly purified AcGGM or a crude spruce hydrolysate, an AcGGM and lignin containing biomass fraction as a reactant. Homogeneous reaction mixtures were obtained in both cases with polysaccharide contents up to 20% by weight. Oscillatory shear measurements indicated a predominantly solid‐like behavior of the hydrogels with an increase in shear storage modulus with increasing cross‐link density. The mechanical integrity of the PAA/hemicellulose hydrogels showed higher water swelling capacity and less fragility than the parent PAA hydrogels and they retained the heavy metal ion absorption ability of the PAA component, even in the presence of the least purified hemicellulose fraction. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41695.

High Tg copolyesters of lactide, isosorbide and isophthalic acid

Using SnCl2, ZnCl2, Zn-lactate or Zr-acetylacetonate as catalysts l-lactide was oligomerized in bulk with isosorbide as initiator. The ratio isosorbide/lactide was varied from 8/2 to 2/8. The resulting oligomers were in situ polycondensed with isophthaloyl chloride in various aromatic solvents. In chlorobenzene homogeneous reaction mixtures were obtained, whereas molten copolyesters precipitated from toluene and xylene. The obtained average molecular weights indicated high polydispersities. According to MALDI-TOF MS the low molar mass reaction products (<4kDa) almost exclusively consisted of cyclics with a composition depending on the feed ratio. The glass-transition temperatures (Tg) varied between the values of poly(l-lactide (64°C) and poly(isosorbide isophthalate) (180°C). Four polyesters prepared from 5-tert-butyl isophthalic acid displayed higher Tg values. Differential thermoanalysis evidenced that the thermostability decreases with higher fractions of lactide, but processing from the melt seems to be feasible up to temperatures of 260°C without risking degradation.

Surfactant micelles as microreactors for the synthesis of quinoxalines in water: scope and limitations of surfactant catalysis

The scope and limitations of surfactants as catalysts for the synthesis of quinoxalines using microreactors made of the surfactants in water has been assessed. The catalytic potential followed the order: non-ionic surfactants > anionic surfactants > Bronsted acid surfactants > cationic surfactants. The non-ionic surfactant, Tween 40, is the most effective catalyst affording excellent yields within a short reaction time at room temperature and is compatible with different variations of the 1,2-diketones and 1,2-diamines. The reaction medium (spent water) containing the catalyst, as well as the catalyst itself (recovered Tween 40) can be reused for five consecutive reactions. The better catalytic efficiency of the surfactant (Tween 40) compared to the various Lewis/Bronsted acids, as well as the surfactant combined Lewis acid, suggests that surfactants, which generate microreactor assemblies at the interface, are better suited as catalytic aids to promote organic reactions in water. The inferior results obtained in organic solvents, which provide a homogeneous reaction mixture compared to those obtained in water, indicate the specific role of water. This has been depicted as a synergistic dual activation through the hydrogen bond mediated formation of supramolecular assemblies involving a water dimer and the reactants. The catalytic assistance of the surfactant could be ascribed to the ability of the surfactant molecule to undergo hydrophobic and hydrogen bond forming interactions with water and the reactants in orienting the reactants at the water interface and encapsulating inside the microreactors to facilitate the cyclocondensation.