One-pot Process Research Articles

One-Pot Synthesis of Difluorobicyclo[1.1.1]pentanes from α-Allyldiazoacetates.

Rapid access to 2,2-difluorobicylco[1.1.1]pentanes is enabled from an α-allyldiazoacetate precursor in a one-pot process through cyclopropanation to afford a 3-aryl bicyclo[1.1.0]butane, followed by reaction with difluorocarbene in the same reaction flask. The modular synthesis of these diazo compounds affords novel 2,2-difluorobicyclo[1.1.1]pentanes that were inaccessible through previously reported methods. The reactions of chiral 2-arylbicyclo[1.1.0]butanes in the same manner generate altogether different products with high asymmetric induction, methylene-difluorocyclobutanes. Larger ring systems including bicyclo[3.1.0]hexanes are also rapidly furnished due to the modular nature of the diazo starting material.

2-Benzyl-7-(4-chlorophenyl)-3-morpholino-6-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

The new polyheterocyclic compound, 2-benzyl-7-(4-chlorophenyl)-3-morpholino-6-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one, was synthesized by a sequential combination of 4-chlorobenzaldehyde, (1-phenyl-1H-1,2,3-triazol-4-yl)methanamine, 2-isocyano-1-morpholino-3-phenylpropan-1-one, and maleic anhydride under a microwave-assisted one-pot process [Ugi-Zhu/aza Diels-Alder cycloaddition/N-acylation/decarboxylation/dehydration] with a 28% overall yield. The synthesized compound was fully characterized by 1D (1H, 13C) and 2D (COSY, HSQC, and HMBC) NMR, FT-IR, and HRMS.

Chemoselective Lipase-Catalyzed Synthesis of Amido Derivatives from 5-Hydroxymethylfurfurylamine.

The acylations of furfurylamine and 5-hydroxymethylfurfurylamine (HMFA) have been studied finding immobilized Candida antarctica lipase B (CALB) as an ideal biocatalyst. CALB was used immobilized on two different supports (Novozyme 435 and EziG-CALB), with the polymer-coated controlled porosity glass carrier material from EnginZyme being an excellent carrier to yield an active and stable enzymatic preparation for the acylation of the primary amine group. The amount of the acyl donor in the reaction was a key factor to achieve the mono- and chemoselective N-protection of HMFA with large excess of ethyl acetate leading to the formation of the N,O-diacetylated product. Thus, a series of 16 nonactivated esters were used to selectively modify the amine group of HMFA, obtaining 9 hydroxy amides under mild reaction conditions and with quantitative yields through chromatography-free transformations. The influence of substrate concentration was studied, resulting in complete conversions in all cases after 22 h (100-1000 mM). Excellent results were observed at 100 and 200 mM of HMFA, while higher concentrations led to longer reaction times and, to some extent, the formation of the diacetylated product (up to 7% after 22 h at 1 M). After this optimization, a metric analysis was performed to confirm the high sustainability of the presented process (E-factor of 1.1 excluding solvents) upon intensification of the biotransformation to 1 g at 200 mM HMFA concentration. The possibility of obtaining orthogonally protected HMFA-derived amido esters has been achieved through a clean and sequential one-pot process using EziG-CALB, which involved the use of ethyl methoxy acetate as the nonactivated ester for N-acylation and the activated vinyl acetate for O-protection.

Cascading One-Pot Synthesis of Biodegradable Uronic Acid-Based Surfactants from Oligoalginates, Semi-Refined Alginates, and Crude Brown Seaweeds.

The present article describes a one-pot and cascade mode process using biocompatible/biodegradable reagents, for simply obtaining surfactant compositions comprising mixtures of d-mannuronic acid and l-guluronic acid directly from oligoalginates or semi-refined alginates (mixtures of alginate, cellulose, hemicellulose, laminaran, and fucan). Simple treatments of partial purification of the reaction crudes (elimination of the salts and/or the residual fatty alcohols) or isolation of the surfactant compositions result in sugar-based compounds having performance levels appropriate to applications in detergency. In addition, the challenging extension of this cascading one-pot synthesis technology to crude milled brown seaweeds was successfully carried out to provide promising surface-active compositions made up of alkyl uronate and alkyl glycoside monosaccharides.

On the Sustainability of Palladium in Organic Synthesis: A Perspective

What’s the long- and short-term prognosis for palladium in organic synthesis, the key platinum group metal (pgm) for transition metal-based catalysis used today by the fine chemicals industries? Are these processes green and sustainable? Are they environmentally respectful of the metals, especially the pgms, so essential to modern day society? Are non-pgm ‘earth abundant’ metals an attractive alternative? Where does the up-and-coming area of chemoenzymatic catalysis, which combines chemo- and biocatalysis in one-pot processes in water, fit into the future of drug syntheses? And what about agricultural targets also being made that include palladium catalysis? These and related timely topics are discussed in this Perspective.

Biomass-based single- and double-network hydrogels derived from cellulose microfiber and chitosan for potential application as plant growing substrate

A series of hydrogels were synthesized from renewable and low-cost micro-sized cellulose fiber. The single-network hydrogel was composed of cellulose fiber and a small amount of another polysaccharide, chitosan, which ‘glued’ individual cellulose fiber pieces together through Schiff-base bonding. The double-network hydrogel was constructed by adding a secondary network, the covalently crosslinked polyacrylamide, into the single-network hydrogel, which was synthesized by conducting Schiff-base reaction and free radical polymerization at the same time in a facile one-pot process. In both single- and double-network hydrogels, cellulose fiber constituted the dominant component. Both types of hydrogels exhibited good swelling properties. The double-network hydrogel showed much improved stability against soaking in water and higher salt tolerance. Germination experiment with choy sum seeds sowed on hydrogel surface showed that the seeds were able to germinate and further develop roots, shoots, and true leaves, demonstrating the potential of the biomass-derived hydrogels for soilless plant growing applications.

Synthesis of Single Crystal 2D Cu2FeSnS4 Nanosheets with High-Energy Facets (111) as a Pt-Free Counter Electrode for Dye-Sensitized Solar Cells.

Two-dimensional Cu2FeSnS4 (CFTS) nanosheets with exposed high-energy facets (111) have been synthesized by a facile, scalable, and cost-effective one-pot heating process. The CFTS phase formation is confirmed by both X-ray diffraction and Raman spectroscopy. The formation mechanism of exposed high-energy facet CFTS growth is proposed and its electrochemical and photoelectrochemical properties are investigated in detail to reveal the origin of the anisotropic effect of the high-energy facets. Dye-sensitized solar cells (DSSC) achieve a favorable power conversion efficiency of 5.92% when employing CFTS thin film as a counter electrode, suggesting its potential as a cost-effective substitute for Pt in DSSCs.

Fabrication of pH-responsive co-delivery system for nano selenium and doxorubicin with PEGylated chitosan: Effect of PEGylation

Drug delivery system has shown multi advantages in cancer treatment, but the complex fabrication process limits their clinical application. This work developed a chitosan-based co-delivery system for doxorubicin and nano selenium. The one-pot co-precipitation process was utilized to form the PEGylated nanoparticles. It was found that the PEGylation might affect the co-precipitation process and result in different nanoparticle sizes and drug release behavior. The PEGylated nanoparticles (Se@DOX/CS-PEG) present a larger diameter (about 230 nm) and higher drug loading capacity (31%). A faster drug release was also observed for PEGylated Se@DOX/CS-PEG nanoparticles and drug release could be completed in 2 h at pH 5.0 while the drug release at pH 7.4 could be limited (<5%, 10 h). In vitro cell experiments confirmed the anti-cancer efficiency and intracellular delivery ability of the co-delivery system. In conclusion, this work presents a novel way to fabricate co-delivery system and may provide more insights into the development of smart drug delivery systems.

Organocatalytic Deoxyhalogenation of Alcohols with Inorganic Halides

Direct substitution of alcohols has been a popular topic in organic chemistry. Deoxyhalogenation of alcohols represents one of the most important transformations for accessing organic halides. However, a practical catalytic protocol with readily available, inexpensive, and stable inorganic halides is still unknown. Herein, we report an organocatalytic deoxyhalogenation of alcohols with inorganic halides, which avoids the employment of stoichiometric activators and organic halogenating reagents. Various alcohols are transformed to the corresponding organic bromides and iodides in good yield. Through the one-pot sequential process, C–N, C–O, C–F, C–Cl, and C–S bond formation can also be achieved with good yield.

Enzymatic One-Pot Hydrolysis of Extracted Sugar Beet Press Pulp after Solid-State Fermentation with an Engineered Aspergillus niger Strain

Extracted sugar beet press pulp (SBPP) is a promising agricultural residue for saccharification and further bioconversion. Combining solid-state fermentation of SBPP with engineered Aspergillus niger for enzyme production followed by hydrolysis of additionally added SBPP in the same bioreactor was studied to produce a sugar solution (hydrolysate) in a one-pot process. The initial aerobic solid-state fermentations were carried out in duplicate on non-milled, wet SBPP (moisture content of 72% (w/v)) with an A. niger strain engineered for constitutive pectinase production for 96 h, and this resulted in polygalacturonase activities of up to 256 U mL−1 in the wet media. Afterwards, water was added to the bioreactor, and the remaining solids were suspended by stirring to dissolve the hydrolytic enzymes. Metabolic activities of A. niger were inactivated by a N2-atmosphere and by increasing the temperature to 50 °C. High solid loads of milled SBPP were added to the stirred-tank reactor with a delay of 24 h to enable sugar yield calculations based on the compositional analysis of the SBPP used. The resulting final sugar concentrations of the hydrolysate after 166 h were 17 g L−1 d-glucose, 18.8 g L−1 l-arabinose, and 12.5 g L−1 d-galacturonic acid, corresponding to sugar yields of 98% d-glucose, 86% l-arabinose, and 50% d-galacturonic acid, respectively. Including the other sugars released during enzymatic hydrolysis in the one-pot process (d-xylose, d-mannose, d-galactose), a total sugar concentration of 54.8 g L−1 was achieved in the hydrolysate. The one-pot process combining hydrolytic enzyme production in solid-state fermentation with high solid loads during enzymatic hydrolysis of the milled SBPP reduces hydrolytic process costs by replacing chemical pre-treatments, enabling the in situ production of SBPP-adapted hydrolytic enzymes, as well as avoiding intermediate enzyme extraction and preparation steps.

In-doped Sn3O4 flower-like nanosheets for efficient visible-light photocatalytic hydrogen production

Improving photocatalytic activity is crucial for promoting photocatalytic hydrogen production. Element doping is a feasible strategy to accelerate carrier separation and migration rate. Herein, a simple one-pot hydrothermal process was used to create In doped Sn3O4 composite photocatalyst. It was demonstrated that the addition of In considerably raises the concentration of oxygen vacancy, which provides more unsaturated active sites, thus regulating the photocatalyst's electronic structure and surface properties, and promoting the carrier migration efficiency. Meanwhile, the light absorption range of samples after doping is redshifted, and the light absorption capacity is enhanced, which effectively improves the photocatalytic activity. Due to this, the optimal sample's average hydrogen production under visible light reached 22.83 μmol g−1 h−1, 4.5 folds more than that of Sn3O4, and shown good stability. This research presents a novel approach for the development of metal oxide photocatalyst with excellent activity and durability.

Diversity-Oriented Synthesis of Benzo[f][1,4]oxazepine-, 2H-Chromene-, and 1,2-Dihydroquinoline-Fused Polycyclic Nitrogen Heterocycles under Microwave-Assisted Conditions.

An efficient, diversity-oriented synthesis of oxazepino[5,4-b]quinazolin-9-ones, 6H-chromeno[4,3-b]quinolines, and dibenzo[b,h][1,6]naphthyridines was established involving a substrate-based approach under microwave-assisted and conventional heating conditions in high yields (up to 88%). The CuBr2-catalyzed, chemoselective cascade annulation of O-propargylated 2-hydroxybenzaldehydes and 2-aminobenzamides delivered oxazepino[5,4-b]quinazolin-9-ones involving a 6-exo-trig cyclization-air oxidation-1,3-proton shift-7-exo-dig cyclization sequence. This one-pot process showed excellent atom economy (-H2O) and constructed two new heterocyclic rings (six- and seven-membered) and three new C-N bonds in a single synthetic operation. On the other side of diversification, the reaction between O/N-propargylated 2-hydroxy/aminobenzaldehydes and 2-aminobenzyl alcohols delivered 6H-chromeno[4,3-b]quinolines and dibenzo[b,h][1,6]naphthyridines involving sequential imine formation-[4 + 2] hetero-Diels-Alder reaction-aromatization steps. The influence of microwave assistance was superior to conventional heating, where the reactions were clean, rapid, and completed in 15 min, and the conventional heating required a longer reaction time at a relatively elevated temperature.

Synthesis of magnetic nanoparticles coated zirconia using one-pot solvothermal processes as adsorbent for Pb(II) and Cd(II) removal

Indonesia, notably in Central Kalimantan, has the potential for raw zirconia mineral, but it has not been successfully developed as a material that has ecologically friendly, high economic and technical value. The magnetic nanoparticles coated zirconia mineral was synthesized by using one-pot solvothermal processes, and then was used as adsorbent for water and wastewater treatment in adsorption process. Zirconia minerals are turned into composites with magnetic nanoparticles with the addition of hexane diamine to create the composite with amino groups (MH@ZrO2). It was then utilized as adsorbent to adsorb lead and cadmium metal in an artificial solution, and lower the metal content of lead/ (Pb(II)) and cadmium (Cd(II)) in it. The first stage was to determine the equilibrium of contact time (30, 60, 120, 240, and 360 min) of the adsorbent in binding Pb(II) and Cd(II) ions. The variations of pH 3, 5, 7, and 9 in the solution during adsorption were also examined to establish appropriate conditions for the adsorption process. The observations of magnetic nanoparticles composites based on a Scanning Electron Microscopy (SEM) analysis showed that magnetic nanoparticles with the diameter of 30–50 nm were generated on the face of zirconia minerals. X-Ray Diffraction (X-RD) analysis revealed that zirconia minerals treatment lowered the Crystallinity Index by 11.19% and the silica content by 98%. A Fourier Transform Infra-Red (FT-IR) spectrometer showed an adsorption peak of 590 cm−1 for the Fe-O bond on Fe3O4. Meanwhile, the optimum condition for Pb(II) and Cd(II) adsorption with pHe around 7 ± 0.2 for 360 min resulted in an adsorption density of 117.67 mg/g and 24.19 mg/g, respectively. The MH@ZrO2 led to development for high potential adsorbent due to stable material and easy separation, and capable for absorbing Pb(II) and Cd(II) ions from an aqueous solution.

Direct Tertiary Butyl Alcohol Formation via Catalytic Liquid Phase Isobutane Oxidation with Molecular Oxygen

A safe one-pot catalytic process for directly producing tertiary butyl alcohol (TBA) from liquid-phase isobutane oxidation with oxygen is demonstrated. This is achieved by operating outside the vapor phase flammability envelope and catalytically decomposing tertiary butyl hydroperoxide (TBHP), the main product of homogeneous isobutane oxidation, at 125 °C and 35 bar. Among a dozen heterogeneous metal-based catalysts tested, amorphous MnO2 (AMO) was found to be roughly an order of magnitude more active than supported Pd, Co, Au, and Nb-based catalysts for TBHP decomposition to TBA. As a result, high TBA/TBHP (up to 20.4) selectivity was achieved during isobutane oxidation in the presence of the AMO catalyst. The yield of gas phase C1 products was <1% and only a minor amount of acetone was produced as a β-scission byproduct. The use of n-hydroxy phthalimide (NHPI) as an initiator was found to enhance the TBA yield. This process provides a possible low energy pathway for making isobutylene from isobutane, avoiding the energy-intensive dehydrogenation and isobutane/isobutylene separation steps.

Integrated lactic acid production from lignocellulosic agricultural wastes under thermal conditions

The production of lactic acid (LA) from agricultural wastes attracts great attention because of the sustainability and abundance of lignocellulosic feedstocks, as well as the increasing demand for biodegradable polylactic acid. In this study, we isolated a thermophilic strain Geobacillus stearothermophilus 2H-3 for use in robust production of L-(+)LA under the optimal conditions of 60 °C, pH 6.5, which were consistent with the whole-cell-based consolidated bio-saccharification (CBS) process. Sugar-rich CBS hydrolysates derived from various agricultural wastes, including corn stover, corncob residue, and wheat straw, were used as the carbon sources for 2H-3 fermentation by directly inoculating 2H-3 cells into the CBS system, without intermediate sterilization, nutrient supplementation, or adjustment of fermentation conditions. Thus, we successfully combined two whole-cell-based steps into a one-pot successive fermentation process to efficiently produce LA with high optical purity (99.5%), titer (51.36 g/L), and yield (0.74 g/gbiomass). This study provides a promising strategy for LA production from lignocellulose through CBS and 2H-3 fermentation integration.

Ruthenium-Catalyzed Synthesis of Aryl and Alkenyl Halides from Fluorosulfonates.

Aryl and alkenyl halides are widely used as key intermediates in organic synthesis, particularly for the formation of organometallic reagents or as radical precursors. They are also found in pharmaceutical and agrochemical ingredients. In this work, the synthesis of aryl and alkenyl halides from the corresponding fluorosulfonates using commercially available ruthenium catalysts is reported. Notably, this is the first conversion of phenols to aryl halides that is efficient with chloride, bromide, and iodide. Fluorosulfonates are readily prepared using sulfuryl fluoride (SO2 F2 ) and less expensive substitutes for triflates. Although aryl fluorosulfonates and their reactions are well known, this is the first report of an efficient coupling of alkenyl fluorosulfonates. To finish, it was demonstrated, by means of representative examples, that the reaction is possible in a one-pot process, starting directly from phenol or aldehyde.

One-pot glycerol conversion to acrylic acid catalyzed by Cu modified HY zeolite synthesized from natural resources and pro-analytical precursor

The conversion of glycerol to acrylic acid was carried out by the one-pot process method. The catalyst used in this conversion is Cu-modified HY zeolite synthesized using pro-analytical precursors and alternative precursors from natural resources i.e., Indonesian natural zeolite and kaolin. The crystal structure and physicochemical properties of catalysts were determined by various characterization techniques such as XRD, FTIR, SEM-EDX, TEM, SAA, and TPD-NH3. Based on XRD analysis, it shows that HY and CuHY, both from synthetic and alternative precursors, are confirmed to have typical peaks of Y zeolite. EDX mapping images show a uniform distribution of Cu on the HY surface. In addition, the TEM analysis also shows uniform particle size distribution. The results of catalytic glycerol conversion show that Cu-modified HY catalysts give a higher acrylic acid yield than HY. The results also show that the highest yield of acrylic acid was obtained in 27.5% and 25.8% at a dehydration time of 3 h using pro-analytical and natural resources CuHY catalyst, respectively. The Cu-modified HY catalysts having weak acid sites show the best catalytic activity in the conversion of glycerol to acrylic acid.

One-pot synthesis of fuel precursor from acetoin fermentation broth using ionic liquid-based salting-out extraction system

BackgroundThe development of biofuels, especially liquid hydrocarbon fuels, has been widely concerned due to the depletion of fossil resources. In order to obtain fuel precursors, the reaction of C–C bond formation is usually carried out with biomass derived ketones/aldehydes as reactants. Acetoin and 2,3-butanediol are two platform chemicals, which are co-existed in fermentation broth and traditionally separated by distillation, and then acetoin could be use as C4 building block to prepare hydrocarbon fuels. In order to mitigate the process complexity, direct aldol condensation reaction of acetoin in fermentation broth was studied in this work.ResultsA one-pot process of product separation and acetoin derivative synthesis was proposed based on salting-out extraction (SOE). Aldol condensation reaction of acetoin and 5-methyl furfural in different SOE systems was compared, and the results showed that the synthesis of C10 fuel precursors and separation of C10 products and 2,3-butanediol from fermentation broth were achieved in one-pot with ethanolammonium butyrate (EOAB) and K2HPO4 as SOE reagents and catalysts. The SOE and reaction conditions such as the concentrations of EOAB and K2HPO4, reaction temperature and time were optimized. When the system was composed of 6 wt% EOAB-44 wt% K2HPO4 and the mixture was stirred for 6 h at 200 rpm, 40 ℃, the yield of C10 products was 80.7%, and 95.5% 2,3-butanediol was distributed to the top EOAB-rich phase. The exploration of reaction mechanism showed that an imine intermediate was rapidly formed and the subsequent C10 product formation was the key step for aldol condensation reaction.ConclusionsWith EOAB and K2HPO4 as SOE reagents and catalysts, one-pot synthesis of fuel precursor from acetoin fermentation broth was achieved without prior purification. A yield of 80.7% for C10 products was obtained which was accumulated at the interface of two aqueous-phase, and 95.5% 2,3-BD was distributed to the top EOAB-rich phase. This work provides a new integration process of product separation and derivative synthesis from fermentation broth based on ionic liquid SOE.Graphical

High-performance electrocatalytic reduction of CO2 to CO by ultrathin PdCu alloy nanosheets

Electrochemical reduction of carbon dioxide (CO2RR) into fuels and chemicals is a significant step to balance the carbon cycle. For CO2 reduction to CO, the binding energy of intermediates *COOH and *CO is crucial for the electrocatalytic activity and selectivity. Herein, we prepare a series of ultrathin and tunable PdCu alloy nanosheets by a one-pot wet chemistry process and demonstrate that the bimetallic nanosheets can improve the electronic configurations and break the inherent scaling relationship of intermediate binding energy, which leads to a high performance of CO2RR. Specifically, Pd1Cu1 exhibits the best CO2RR performance among the series, with a faraday efficiency (FE) of 97% CO at − 0.80 V vs reversible hydrogen electrode (RHE) in 0.1 M KHCO3 and 96% at − 0.88 V in 1 M KOH with a current density of 521 mA cm−2. This is ascribed to moderate *COOH binding and weak binding of *CO on Pd1Cu1, as manifested in both experimental and theoretical studies. Results from this work highlight the unique potentials of bimetallic alloy nanosheets as high-performance catalysts for electrochemical reduction of CO2.

Cyclic Carbonates through the Photo-Induced Carboxylative Cyclization of Allylic Alcohol with CO2: A Comprehensive Kinetic Study of the Reaction Mechanism by In Situ ATR-IR Spectroscopy

A one-pot multicomponent green process is investigated for the synthesis of perfluoroalkylated cyclic carbonate which merges the photo-promoted Atom Transfer Radical Addition (ATRA) of a perfluoroalkyl iodide (Rf-I) onto allyl alcohols with the Lewis-base-promoted carboxylative cyclization. The evolution of the complex mixture during the reaction was monitored by in situ ATR-IR and Raman spectroscopies that provided insights into the reaction mechanism. The effect on the kinetics and the carbonate yields of key parameters such as the stoichiometry of reagents, the nature of the Lewis base and the solvent, the temperature and the pressure were evaluated. It was found that high yields were obtained using strong Lewis bases that played both the role of activating the allyl alcohol for the generation of the allyl carbonate in the presence of CO2 and promoting the ATRA reaction through the activation of C4F9I by halogen bonding. This protocol was also extended to various unsaturated alcohols.