Deciphering complexity in Pd-catalyzed cross-couplings.

Understanding complex reaction systems is critical in chemistry. While synthetic methods for selective formation of products are sought after, oftentimes it is the full reaction signature, i.e., complete profile of products/side-products, that informs mechanistic rationale and accelerates discovery chemistry. Here, we report a methodology using high-throughput experimentation and multivariate data analysis to examine the full signature of one of the most complicated chemical reactions catalyzed by palladium known in the chemical literature. A model Pd-catalyzed reaction was selected involving functionalization of 2-bromo-N-phenylbenzamide and multiple bond activation pathways. Principal component analysis, correspondence analysis and heatmaps with hierarchical clustering reveal the factors contributing to the variance in product distributions and show associations between solvents and reaction products. Using robust data from experiments performed with eight solvents, for four different reaction times at five different temperatures, we correlate side-products to a major dominant N-phenyl phenanthridinone product, and many other side products.

Sustainable methods for the carboxymethylation and methylation of ursolic acid with dimethyl carbonate under mild and acidic conditions.

Ursolic acid is a triterpene plant extract that exhibits significant potential as an anti-cancer, anti-tumour, and anti-inflammatory agent. Its direct use in the pharmaceutical industry is hampered by poor uptake of ursolic acid in the human body coupled with rapid metabolism causing a decrease in bioactivity. Modification of ursolic acid can overcome such issues, however, use of toxic reagents, unsustainable synthetic routes and poor reaction metrics have limited its potential. Herein, we demonstrate the first reported carboxymethylation and/or methylation of ursolic acid with dimethyl carbonate (DMC) as a green solvent and sustainable reagent under acidic conditions. The reaction of DMC with ursolic acid, in the presence of PTSA, ZnCl2, or H2SO4-SiO2 yielded the carboxymethylation product 3ß-[[methoxy]carbonyl]oxyurs-12-en-28-oic acid, the methylation product 3ß-methoxyurs-12-en-28-oic acid and the dehydration product urs-2,12-dien-28-oic acid. PTSA demonstrated high conversion and selectivity towards the previously unreported carboxymethylation of ursolic acid, while the application of formic acid in the system led to formylation of ursolic acid (3ß-formylurs-12-en-28-oic acid) in quantitative yields via esterification, with DMC acting solely as a solvent. Meanwhile, the methylation product of ursolic acid, 3ß-methoxyurs-12-en-28-oic acid, was successfully synthesised with FeCl3, demonstrating exceptional conversion and selectivity, >99% and 99%, respectively. Confirmed with the use of qualitative and quantitative green metrics, this result represents a significant improvement in conversion, selectivity, safety, and sustainability over previously reported methods of ursolic acid modification. It was demonstrated that these methods could be applied to other triterpenoids, including corosolic acid. The study also explored the potential pharmaceutical applications of ursolic acid, corosolic acid, and their derivatives, particularly in anti-inflammatory, anti-cancer, and anti-tumour treatments, using molecular ADMET and docking methods. The methods developed in this work have led to the synthesis of novel molecules, thus creating opportunities for the future investigation of biological activity and the modification of a wide range of triterpenoids applying acidic DMC systems to deliver novel active pharmaceutical intermediates.

Optimising Low Temperature Pyrolysis of Mesoporous Alginate-Derived Starbon® for Selective Heavy Metal Adsorption.

In response to the ever increasing need to develop more efficient and sustainable methods for removing heavy metal contaminants from aqueous systems, the following article reports on the design of highly mesoporous alginate-derived materials (Starbon®) and their application to the adsorption of heavy metals. Using the Starbon® process to expand, dry and pyrolyse an inherently porous polysaccharide precursor, it was possible to produce mesoporous materials (BJH mesopore volumes 0.81-0.94 cm3 g-1) with large surface areas (157-297 m2 g-1) across a range of low pyrolysis temperatures (200-300 °C). The mechanisms of thermal decomposition were explored in terms of chemical and structural changes using N2-sorption porosimetry, thermogravimetric analysis, titration, FT-IR spectroscopy and 13C NMR spectroscopy. It was found that, as a result of intermolecular dehydration and crosslinking, sufficient chemical stability is obtained by the intermediate temperature of 250 °C, with limited improvement seen at higher temperatures. In addition, the materials retained large metal adsorption capacities (0.70-1.72 mmol g-1) as well as strong selectivity for Cu2+ ions (over Co2+ and Ni2+), as compared to commercial petrochemical-derived cation exchange resin Amberlite™ Mac 3H. Thus, highlighting the potential of Starbon® materials as a sustainable answer to the widespread problem of heavy metal-contaminated wastewaters.

Application of hindered ether solvents for palladium catalyzed Suzuki-Miyaura, Sonogashira and cascade Sonogashira cross-coupling reactions.

Cross-coupling and cascade reactions typically rely on unsustainable and toxic volatile organic solvents. 2,2,5,5-Tetramethyloxolane (TMO) and 2,5-diethyl-2,5-dimethyloxolane (DEDMO) are both inherently non-peroxide forming ethers, and have been used in this work as effective, more sustainable, and potentially bio-based alternative solvents for Suzuki-Miyaura and Sonogashira reactions. Suzuki-Miyaura reactions demonstrated good yields for a range of substrates, 71-89% in TMO and 63-92% in DEDMO. In addition, a Sonogashira reaction exhibited the excellent yields of 85-99% performed in TMO, which was significantly higher than traditional volatile organic solvents, THF or toluene, and higher than those reported for another non-peroxide forming ether, namely eucalyptol. Cascade Sonogashira reactions utilizing a simple annulation methodology were particularly effective in TMO. Furthermore, a green metric assessment confirmed that the methodology employing TMO was more sustainable and greener than the traditional solvents THF and toluene, thereby demonstrating the promise of TMO as an alternative solvent for Pd-catalyzed cross-coupling reactions.

Work-hardening Photopolymer from Renewable Photoactive 3,3'-(2,5-Furandiyl)bisacrylic Acid.

The design of a photopolymer around a renewable furan-derived chromophore is presented herein. An optimised semi-continuous oxidation method using MnO2 affords 2,5-diformylfuran from 5-(hydroxymethyl)furfural in gram quantities, allowing the subsequent synthesis of 3,3'-(2,5-furandiyl)bisacrylic acid in good yield and excellent stereoselectivity. The photoactivity of the diester of this monomer is confirmed by reaction under UV irradiation, and the proposed [2+2] cycloaddition mechanism supported further by TD-DFT calculations. Oligoesters of the photoreactive furan diacid with various aliphatic diols are prepared via chemo- and enzyme-catalysed polycondensation. The latter enzyme-catalysed (Candida antarctica lipase B) method results in the highest Mn (3.6 kDa), suggesting milder conditions employed with this protocol minimised unwanted side reactions, including untimely [2+2] cycloadditions, whilst preserving the monomer's photoactivity and stereoisomerism. The photoreactive polyester is solvent cast into a film where subsequent initiator-free UV curing leads to an impressive increase in the material stiffness, with work-hardening characteristics observed during tensile strength testing.

Synthesis and application of tuneable carbon-silica composites from the microwave pyrolysis of waste paper for selective recovery of gold from acidic solutions.

Microwave pyrolysis bio-oil from waste paper and K60 silica gel has successfully been utilised to synthesise mesoporous carbon-silica composites with uniquely tuneable surface properties, where functionality and structural characteristics can be altered and even enhanced by curing at different temperatures. This temperature-dependence resulted in composites ranging from highly oxygenated polymerised bio-oil composites at 300 °C to aromatic carbonaceous materials covering the silica surface at 800 °C, making them attractive materials for gold recovery from mining wastewater. The composite materials exhibit exceptional ability and selectivity to recover gold from dilute solutions. Metal adsorption on the surface of these composites proceeded via both chemisorption and physisorption leading to the reduction of Au(iii) to Au(0), resulting in high recovery capacities for gold. Composite material prepared at 500 °C demonstrated the optimum combination of surface functionality and porosity, allowing for an adsorption capacity of 320 mg g-1 of gold and with 99.5% removal being achieved at concentrations mimicking those of real-life mine tailing wastes. All materials pioneered in this research display great potential as selective adsorbents for the recovery of gold from acidic media.

Dehydration of Alginic Acid Cryogel by TiCl4 vapor: Direct Access to Mesoporous TiO2 @C Nanocomposites and Their Performance in Lithium-Ion Batteries.

A new strategy for the synthesis of mesoporous TiO2 @C nanocomposites through the direct mineralization of seaweed-derived alginic acid cryogel by TiCl4 through a solid/vapor reaction pathway is presented. In this synthesis, alginic acid cryogel can have multiple roles; i) mesoporous template, ii) carbon source, and iii) oxygen source for the TiO2 precursor, TiCl4 . The resulting TiO2 @alginic acid composite was transformed either into pure mesoporous TiO2 by calcination or into mesoporous TiO2 @C nanocomposites by pyrolysis. By comparing with a nonporous TiO2 @C composite, the importance of the mesopores on the performance of electrodes for lithium-ion batteries based on mesoporous TiO2 @C composite was clearly evidenced. In addition, the carbon matrix in the mesoporous TiO2 @C nanocomposite also showed electrochemical activity versus lithium ions, providing twice the capacity of pure mesoporous TiO2 or alginic acid-derived mesoporous carbon (A600). Given the simplicity and environmental friendliness of the process, the mesoporous TiO2 @C nanocomposite could satisfy the main prerequisites of green and sustainable chemistry while showing improved electrochemical performance as a negative electrode for lithium-ion batteries.

Laminaria digitata and Palmaria palmata Seaweeds as Natural Source of Catalysts for the Cycloaddition of CO2 to Epoxides.

Seaweed powder has been found to act as an effective catalyst for the fixation of CO2 into epoxides to generate cyclic carbonates under solvent free conditions. Model background reactions were performed using metal halides and amino acids typically found in common seaweeds which showed potassium iodide (KI) to be the most active. The efficacy of the seaweed catalysts kelp (Laminaria digitata) and dulse (Palmaria palmata) was probed based on particle size, showing that kelp possessed greater catalytic ability, achieving a maximum conversion and selectivity of 63.7% to styrene carbonate using a kelp loading of 80% by weight with respect to epoxide, 40 bar of CO2, 120 °C for 3 h. Maximizing selectivity was difficult due to the generation of diol side product from residual H2O found in kelp, along with a chlorinated by-product thought to form due to a high quantity of chloride salts in the seaweeds. Data showed there was loss of organic matter upon use of the kelp catalyst, likely due to the breakdown of organic compounds and their subsequent removal during product extraction. This was highlighted as the likely cause of loss of catalytic activity upon reuse of the Kelp catalyst.

Geminal Diol of Dihydrolevoglucosenone as a Switchable Hydrotrope: A Continuum of Green Nanostructured Solvents.

The addition of water to dihydrolevoglucosenone (Cyrene) creates a solvent mixture with highly unusual properties and the ability to specifically and efficiently solubilize a wide range of organic compounds, notably, aspirin, ibuprofen, salicylic acid, ferulic acid, caffeine, and mandelic acid. The observed solubility enhancement (up to 100-fold) can be explained only by the existence of microenvironments mainly centered on Cyrene's geminal diol. Surprisingly, the latter acts as a reversible hydrotrope and regulates the polarity of the created complex mixture. The possibility to tune the polarity of the solvent mixture through the addition of water, and the subsequent generation of variable amounts of Cyrene's geminal diol, creates a continuum of green solvents with controllable solubilization properties. The effective presence of microheterogenieties in the Cyrene/water mixture was adequately proven by (1) Fourier transform infrared/density functional theory showing Cyrene dimerization, (2) electrospray mass-spectrometry demonstrating the existence of dimers of Cyrene's geminal diol, and (3) the variable presence of single or multiple tetramethylsilane peaks in the 1H NMR spectra of a range of Cyrene/water mixtures. The Cyrene-water solvent mixture is importantly not mutagenic, barely ecotoxic, bioderived, and endowed with tunable hydrophilic/hydrophobic properties.

Starbon/High-Amylose Corn Starch-Supported N-Heterocyclic Carbene-Iron(III) Catalyst for Conversion of Fructose into 5-Hydroxymethylfurfural.

Iron-N-heterocyclic carbene complexes (Fe-NHCs) have come to prominence because of their applicability in diverse catalytic reactions, ranging from C-C cross-coupling and C-X bond formation to substitution, reduction, polymerization, and dehydration reactions. The detailed synthesis, characterization, and application of novel heterogeneous Fe-NHC catalysts immobilized on mesoporous expanded high-amylose corn starch (HACS) and Starbon 350 (S350) for facile fructose conversion into 5-hydroxymethylfurfural (HMF) is reported. Both catalyst types showed good performance for the dehydration of fructose to HMF when the reaction was tested at 100 °C with varying time (10 min, 20 min, 0.5 h, 1 h, 3 h and 6 h). For Fe-NHC/S350, the highest HMF yield was 81.7 % (t=0.5 h), with a TOF of 169 h-1 , fructose conversion of 95 %, and HMF selectivity of 85.7 %, whereas for Fe-NHC/expanded HACS, the highest yield was 86 % (t=0.5 h), with a TOF of 206 h-1 , fructose conversion of 87 %, and HMF selectivity of 99 %. Iron loadings of 0.26 and 0.30 mmol g-1 were achieved for Fe-NHC/expanded starch and Fe-NHC/S350, respectively.

Fast microwave-assisted acidolysis: a new biorefinery approach for the zero-waste utilisation of lignocellulosic biomass to produce high quality lignin and fermentable saccharides.

Generally, biorefineries convert lignocellulosic biomass into a range of biofuels and further value added chemicals. However, conventional biorefinery processes focus mainly on the cellulose and hemicellulose fractions and therefore produce only low quality lignin, which is commonly burnt to provide process heat. To make full use of the biomass, more attention needs to be focused on novel separation techniques, where high quality lignin can be isolated that is suitable for further valorisation into aromatic chemicals and fuel components. In this paper, three types of lignocellulosic biomass (softwood, hardwood and herbaceous biomass) were processed by microwave-assisted acidolysis to produce high quality lignin. The lignin from the softwood was isolated largely intact in the solid residue after acidolysis. For example, a 10 min microwave-assisted acidolysis treatment produced lignin with a purity of 93% and in a yield of 82%, which is superior to other conventional separation methods reported. Furthermore, py-GC/MS analysis proved that the isolated lignin retained the original structure of native lignin in the feedstock without severe chemical modification. This is a large advantage, and the purified lignin is suitable for further chemical processing. To assess the suitability of this methodology as part of a biorefinery system, the aqueous phase, produced after acidolysis of the softwood, was characterised and assessed for its suitability for fermentation. The broth contained some mono- and di-saccharides but mainly contained organic acids, oligosaccharides and furans. While this is unsuitable for S. cerevisiae and other common ethanol producing yeasts, two oleaginous yeasts with known inhibitor tolerances were selected: Cryptococcus curvatus and Metschnikowia pulcherrima. Both yeasts could grow on the broth, and demonstrated suitable catabolism of the oligosaccharides and inhibitors over 7 days. In addition, both yeasts were shown to be able to produce an oil with a similar composition to that of palm oil. This preliminary work demonstrates new protocols of microwave-assisted acidolysis and therefore offers an effective approach to produce high purity lignin and fermentable chemicals, which is a key step towards developing a zero-waste lignocellulosic biorefinery.

Subtle Microwave-Induced Overheating Effects in an Industrial Demethylation Reaction and Their Direct Use in the Development of an Innovative Microwave Reactor.

A systematic study of the conventional and microwave (MW) kinetics of an industrially relevant demethylation reaction is presented. In using industrially relevant reaction conditions the dominant influence of the solvent on the MW energy dissipation is avoided. Below the boiling point, the effect of MWs on the activation energy Ea and k0 is found nonexistent. Interestingly, under reflux conditions, the microwave-heated (MWH) reaction displays very pronounced zero-order kinetics, displaying a much higher reaction rate than observed for the conventionally thermal-heated (CTH) reaction. This is related to a different gas product (methyl bromide, MeBr) removal mechanism, changing from classic nucleation into gaseous bubbles to a facilitated removal through escaping gases/vapors. Additionally, the use of MWs compensates better for the strong heat losses in this reaction, associated with the boiling of HBr/water and the loss of MeBr, than under CTH. Through modeling, MWH was shown to occur inhomogeneously around gas/liquid interfaces, resulting in localized overheating in the very near vicinity of the bubbles, overall increasing the average heating rate in the bubble vicinity vis-à-vis the bulk of the liquid. Based on these observations and findings, a novel continuous reactor concept is proposed in which the escaping MeBr and the generated HBr/water vapors are the main driving forces for circulation. This reactor concept is generic in that it offers a viable and low cost option for the use of very strong acids and the managed removal/quenching of gaseous byproducts.

Processed Lignin as a Byproduct of the Generation of 5-(Chloromethyl)furfural from Biomass: A Promising New Mesoporous Material.

The lignin by-product of the conversion of lignocellulosic biomass to 5-(chloromethyl)furfural (CMF) has been characterised by thermogravimetric analysis, N2 physisorption porosimetry, attenuated internal reflectance IR spectroscopy, elemental analysis and solid-state NMR spectroscopy. The lignin (LCMF) has a moderate level of mesoporosity before thermal treatment and a surface area of 63 m(2) g(-1) , which increases dramatically on pyrolysis at temperatures above 400 °C. An assessment of the functionality and textural properties of the material was achieved by analysing LCMF treated thermally over a range of pyrolysis temperatures. Samples were sulfonated to test their potential as heterogeneous acid catalysts in the esterification of levulinic acid. It was shown that unpyrolysed catalysts gave the highest ester yields of up to 93 %. To the best of our knowledge, this is the first example of mesoporous lignin with an appreciable surface area that is produced directly from a bio-refinery process and with further textural modification of the material demonstrated.

Microwave assisted step-by-step process for the production of fucoidan, alginate sodium, sugars and biochar from Ascophyllum nodosum through a biorefinery concept.

The biorefinery is an important concept for the development of alternative routes to a range of interesting and important materials from renewable resources. It ensures that the resources are used fully and that all parts of them are valorized. This paper develops this concept, using brown macroalgae Ascophyllum nodosum as an example, by assistance of microwave technology. A step-by-step process was designed to obtain fucoidan, alginates, sugars and biochar (alga residue) consecutively. The yields of fucoidan, alginates, sugars and biochar were 14.09%, 18.24%, 10.87% and 21.44%, respectively. To make an evaluation of the biorefinery process, seaweed sample was also treated for fucoidan extraction only, alginate extraction only and hydrothermal treatment for sugars and biochar only. The chemical composition and properties of each product were also analyzed. The results indicated that A. nodosum could be potentially used as feedstock for a biorefinery process to produce valuable chemicals and fuels.

Synthesis of Unsaturated Polyester Resins from Various Bio-Derived Platform Molecules.

Utilisation of bio-derived platform molecules in polymer synthesis has advantages which are, broadly, twofold; to digress from crude oil dependence of the polymer industry and secondly to reduce the environmental impact of the polymer synthesis through the inherent functionality of the bio-derived platform molecules. Bulk polymerisation of bio-derived unsaturated di-acids has been employed to produce unsaturated polyester (UPEs) which have been analysed by GPC, TGA, DSC and NMR spectroscopy, advancing on the analysis previously reported. UPEs from the diesters of itaconic, succinic, and fumaric acids were successfully synthesised with various diols and polyols to afford resins of MN 480-477,000 and Tg of -30.1 to -16.6 °C with solubilities differing based on starting monomers. This range of properties allows for many applications and importantly due to the surviving Michael acceptor moieties, solubility and cross-linking can be specifically tailored, post polymerisation, to the desired function. An improved synthesis of itaconate and succinate co-polymers, via the initial formation of an itaconate bis-diol, is also demonstrated for the first time, resulting in significantly improved itaconate incorporation.

Microwave assisted extraction of sulfated polysaccharides (fucoidan) from Ascophyllum nodosum and its antioxidant activity.

Sulfated polysaccharides (fucoidan) from brown seaweed Ascophyllum nodosum were extracted by microwave assisted extraction (MAE) technology. Different conditions of temperature (90-150°C), extraction time (5-30 min) were evaluated and optimal fucoidan yield was 16.08%, obtained from 120°C for 15 min's extraction. Compositional analysis, GPC, HPAEC and IR analysis were employed for characterization of extracted sulfated polysaccharides. Fucose was the main monosaccharide of fucoidan extracted at 90°C while glucuronic acid was the main monosaccharide of fucoidan extracted at 150°C. Both the molecular weight and sulfate content of extracted fucoidan increased with decreasing extraction temperature. All fucoidans exhibited antioxidant activities as measured by DPPH scavenging and reducing power, among which fucoidan extracted at 90°C was highest. This study shows that MAE is an efficient technology to extract sulfated polysaccharides from seaweed and Ascophyllum nodosum could potentially be a resource for natural antioxidants.

Simultaneous recovery of organic and inorganic content of paper deinking residue through low-temperature microwave-assisted pyrolysis.

Significant amounts of paper deinking residue (DIR) has been and is still being generated from paper deinking processes, representing both an economic and environmental burden for recycled paper mills. Our research on low-temperature (<200 °C) microwave-assisted (MW-assisted) pyrolysis of DIR allows for simultaneously efficient fast separation and recovery of the organic and inorganic content of DIR at relatively low temperature and within 15 min. Our study is the first highly detailed account of the use low-temperature MW-assisted pyrolysis to effect this change. The obtained liquid and solid products were characterized by a variety of analytical techniques (e.g., attenuated total reflection infrared, gas chromatography-mass spectrometry, liquid-state nuclear magnetic resonance (NMR), X-ray diffraction, solid-state cross-polarization/magic-angle spinning (13)C NMR, and Bloch-decay (13)C NMR). The results reveal that the process efficiently separates the inorganic minerals as microwave residue (mainly calcite and kaolinite) from organic matter, and hence the microwave residue could be reused to produce new paper/cardboard products. The organic fraction bio-oil generated is energy-densified and rich in carbohydrates and is a potential source for valuable aromatic compounds.

Direct microwave-assisted hydrothermal depolymerization of cellulose.

A systematic investigation of the interaction of microwave irradiation with microcrystalline cellulose has been carried out, covering a broad temperature range (150 → 270 °C). A variety of analytical techniques (e.g., HPLC, (13)C NMR, FTIR, CHN analysis, hydrogen-deuterium exchange) allowed for the analysis of the obtained liquid and solid products. Based on these results a mechanism of cellulose interaction with microwaves is proposed. Thereby the degree of freedom of the cellulose enclosed CH2OH groups was found to be crucial. This mechanism allows for the explanation of the different experimental observations such as high efficiency of microwave treatment; the dependence of the selectivity/yield of glucose on the applied microwave density; the observed high glucose to HMF ratio; and the influence of the degree of cellulose crystallinity on the results of the hydrolysis process. The highest selectivity toward glucose was found to be ~75% while the highest glucose yield obtained was 21%.

The combined role of catalysis and solvent effects on the Biginelli reaction: improving efficiency and sustainability.

The traditional Biginelli reaction is a three-component condensation between urea, benzaldehyde and an acetoacetate ester to give a dihydropyrimidinone. An investigation into catalytic and solvent effects has returned the conclusion that the diketo-enol tautomerisation equilibrium of the dicarbonyl reactant dictates the yield of the reaction. Whereas the solvent is responsible for the tautomerisation equilibrium position, the catalyst only serves to eliminate kinetic control from the reaction. Generally, to preserve reaction efficiency and improve sustainability, bio-derivable p-cymene was found to be a useful solvent. The metal-enolate intermediate that results from the application of a Lewis acidic catalyst often cited as promoting the reaction appears to hinder the reaction. In this instance, a Brønsted acidic solvent can be used to return greater reactivity to the dicarbonyl reagent.