One-pot Two-step Process Research Articles

One-pot sequential aldol condensation and hydrodeoxygenation of furfural and acetone to 1-octanol over multifunctional acid-based catalytic system

Furfural and acetone are two of the most promising chemicals derived from lignocellulosic biomass. Coupling these two compounds expands the broad range of value-added chemicals that can be derived from biomass. In this study, 1-octanol, a promising medium chain-length alcohol, was produced from furfural and acetone through a series of reactions: aldol condensation (R1), hydrogenation (R2), and hydrogenolysis (R3). Each step was individually investigated to understand its mechanism and requirements, enabling seamless integration into one-pot, two-step (R1, R2 + R3) and one-pot, three-step (R1 + R2 + R3) processes. To facilitate these reactions, bifunctional alumina–zirconia-based catalysts were synthesized. Additionally, to enhance the yield of 1-octanol, solid acidic additives, particularly sulfonic acid-functionalized silica (KCC-1-APSO3H), were incorporated into the reaction. The highest yield of 1-octanol (69.1 %) was achieved with the three-step process (R1, R2, R3), followed by the one-pot two-step process (R1, R2 + R3, 64.8 %), and the one-pot, three-step process (R1 + R2 + R3, 48.7 %) using the combined Ni/Al2O3-ZrO2 and KCC-1-APSO3H catalyst. Among all the processes investigated, the one-pot, two-step process emerged as the best approach balancing the efficiency of the process integration and 1-octanol yield. The present study offers valuable insights into the development of catalytic methods for producing linear alcohols from biomass.

Radical Cascade Cyclization of N-(o-Cyanobiaryl)acrylamides with Sulfonium Salts via Synergetic Photoredox and Copper Catalysis.

As the magic methyl effect is well acknowledged in pharmaceutical molecules, the development of simple and efficient methods for the installment of methyl groups on complex molecules is highly coveted. Hence, we provide a general strategy for radical cascade cyclization of N-(o-cyanobiaryl)acrylamides by utilizing sulfonium salts as the sources of methyl radical and merging photoredox and copper catalysis. This novel protocol can access a wide variety of methylation or remote thioether-substituted benzo-fused N-heterocycle derivatives, which can be easily transformed into diverse highly valuable sulfone and sulfoximine compounds via late-stage diversification. Moreover, to further demonstrate the synthetic utility of this conversion, the methyl(phenyl)sulfide, which serves as both raw material and byproduct, can be recovered and reused in this transformation. The scale-up experiment for the one-pot two-step process directly offers the target product in good yield under the standard conditions.

N-heterocyclic carbene promoted one-pot synthesis of 1,2-diols and ɑ-Hydroxyketones from simple aldehydes

The α-hydroxyketones and 1,2-diols are versatile building blocks for the preparation of many natural and synthetic bioactive compounds. In this study, N-heterocyclic carbon (NHC) promoted coupling of several aldehydes with formaldehyde enabled the synthesis of 1,2-diols in moderate to high yields. The highly selective conversion of several aldehydes and formaldehyde into 1,2-diols and α-hydroxyketones was achieved in a one-pot two-step process via [BHMIm][OAc] as a key intermediate. In the first step, formaldehyde was quantitatively converted to [BHMIm][OAc] through the carbene addition. In the second step, 1,2-diol was produced through the intermediate-promoted aldol reaction. The results showed that benzaldehyde was capable to react with [BHMIm][OAc] efficiently, with a 54.1% yield of 1,2-diol after the 3-hour reaction at 85 °C. Among the tested benzaldehyde derivatives, the 4-nitrobenzaldehyde showed the highest yield of 1,2-diol (73.3%) under the optimized reaction conditions. Incorporation of an electron rich group on benzaldehyde promoted carbene regeneration. With 4-methoxybenzaldehyde as the substrate, the yield of α-hydroxyketone reached a maximum of 30.6%. Additionally, dihydroxyacetone derivatives were detected in the system. In situ NMR technique confirmed that it was generated from the further reaction of the carbene/1,2-diol complex with another aldehyde. Based on the results of NMR spectroscopy and mass spectrometry, a possible reaction pathway was also proposed.

Enantiocomplementary C–H bond hydroxylation through a dual-enzyme catalyzed one-pot two-step process

A one-pot, two-step C–H bond hydroxylation process that integrates HRP-catalyzed oxidation and carbonyl reductase-catalyzed reduction for the enantiocomplementary synthesis of benzyl alcohols.

Exploiting poly(ε-caprolactone) grafted from hydrohydroxymethylated sunflower oil as biodegradable coating material of water-soluble fertilizers

In the present study, hyperbranched poly(ε-caprolactones) were prepared and used as coating materials to prepare slow release diammonium phosphate (DAP) fertilizer. Firstly, the sunflower oil was hydrohydroxymethylated by one-pot two-step process using Rh(acac)(CO)2 as catalyst, and triethylamine as ligand. Next, the bio-based hyperbranched poly(ɛ-caprolactone) (PCL) were prepared in open air by in-situ ring-opening polymerization of ε-caprolactone using hydrohydroxymethylated sunflower oil as macro-initiator and tetra(phenylethynyl)tin (Sn(C ≡ CPh)4) as catalyst. The structures of the prepared polymers (SFO-O-g-PCL) were confirmed by nuclear magnetic resonance (1H NMR) and the infrared spectroscopy (FTIR). Furthermore, molecular weight values around 20.000 g.mol−1 of PCL grafted in SFO-O-g-PCL were obtained, the thermal stability and morphology of the coated film were also evaluated using thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) respectively. The hydrophobic character of the films prepared from SFO-O-g-PCL was confirmed by measuring the contact angle of water droplets. In the second part, the DAP granular fertilizers were uniformly coated by the prepared material (SFO-O-g-PCL) using a laboratory rotary drum. Then the slow release performance in water of the coated and uncoated DAP fertilizer granules was evaluated by tracking the cumulative concentration of P2O5 released. Thus, it was found that only 10 % of P2O5 was released after 2 h of essay from the coated DAP compared to a total release of P2O5 from uncoated DAP (conventional fertilizer) during the same period. This finding opens a wide perspective to combine the advantages of hydrophobic polyesters and bio-based oils to produce biodegradable coating agents.

Strain-Release Driven Epoxidation and Aziridination of Bicyclo[1.1.0]butanes via Palladium Catalyzed σ-Bond Nucleopalladation.

The development of preparative methods for the synthesis of four-membered carbocycles is gaining increasing importance due to the widespread utility of cyclic compounds in medicinal chemistry. Herein, we report the development of a new methodology for the production of spirocyclic epoxides and aziridines containing a cyclobutane motif. In a two-step one-pot process, a bicyclo[1.1.0]butyl sulfoxide is lithiated and added to a ketone, aldehyde or imine, and the resulting intermediate is cross-coupled with an aryl triflate through C-C σ-bond alkoxy- or aminopalladation with concomitant epoxide or aziridine formation. After careful optimization, a remarkably efficient reaction was conceived that tolerated a broad variety of both aromatic and aliphatic substrates. Lastly, through several high yielding ring-opening reactions, we demonstrated the excellent applicability of the products as modular building blocks for the introduction of three-dimensional structures into target molecules.

Herbal molecule-mediated dual network hydrogels with adhesive and antibacterial properties for strain and pressure sensing.

Multifunctional integration is the focus of hydrogel-based flexible sensors, and formation of a dual network (DN) could shed light on the fabrication of hydrogels with multifunctionality and enhanced properties. In this study, a DN hydrogel was fabricated by the self-assembly of herbal molecule glycyrrhizic acid (GA) as the first hydrogel network and subsequent photocrosslinking of methacrylated sodium alginate (SA-MA) to form the second network. Profiting from the good compatibility between the two hydrogel networks, the obtained DN hydrogels with a homogeneous porous microstructure were endowed with remarkably enlarged stretching (114.5%) and compression (74.4%) strains. In addition, they were demonstrated to display excellent bacteriostatic activity (>99.9%) against Escherichia coli and Staphylococcus aureus owing to the synergetic antibacterial effect of GA and SA-MA. The DN hydrogels as strain sensors possessed high sensitivity (GF = 1.39), linear sensing (R 2 > 0.99), rapid response (180 ms), and good stability (1300 times) for human motion detection. Besides, the DN hydrogels could also be used to conduct pressure sensing such as application of heavy weights and even human pulses. All results suggest that the developed DN hydrogels have great potential in serving as epidermal and implantable flexible sensors for human health monitoring.

Sequential 1,3-Dipole Cycloaddition of Nitrile Imines with Alkenyl Isoxazoles and Aromatization: A One-Pot Access to 1,3,4-Triarylpyrazoles

AbstractA novel one-pot two-step process for the preparation of 1,3,4-triarylpyrazoles is disclosed. This process involves a 1,3-dipolar cycloaddition reaction of alkenyl isoxazoles with nitrile imines generated in situ, followed by SnCl2-promoted aromatization/elimination reaction to give a range of 1,3,4-triarylpyrazoles in a fully regioselective manner. This protocol features mild reaction conditions, easily available raw materials, and excellent regioselectivity.

One-pot self-assembly fabrication of chitosan coated hollow sphere for pH/ glutathione dual responsive drug delivery

Chitosan-coated poly (methacrylic acid) (PMAA) hollow spheres with 64 ± 3% drug loading capacity and low drug leakage (7 ± 2%, 54 h) were prepared through a novel one-pot two-step self-assembly process. Site-specific doxorubicin (DOX) loading and chitosan coating were achieved by electrostatic interaction to fulfill efficient drug loading and well-controlled drug release behavior. In vitro drug release profile revealed the pH and glutathione (GSH) dual responsive fast triggered drug release behavior, reaching 62 ± 3% during the first 10 h. And completely drug release could be achieved in 54 h. The high drug content and sensitive tumor microenvironment responsibility lead to similar anti-cancer efficiency with free doxorubicin in in vitro MTT assay. This self-assembly guided one-pot two-step fabrication process was proved to be an effective and convenient way to prepare the well-defined multi-layer structure and might be further employed in fabricating high-performance drug delivery systems.

Microwave-Assisted Copper(II)-Catalyzed Cascade Cyclization of 2-Propargylamino/Oxy-Arylaldehydes and O-Phenylenediamines: Access to Densely Functionalized Benzo[f]Imidazo[1,2-d][1,4]Oxazepines and Benzo[f]Imidazo[1,2-d][1,4]Diazepines.

A highly efficient microwave-assisted copper(II)-catalyzed cyclization cascade was established starting from readily accessible O/N-propargylated 2-hydroxy or 2-aminobenzaldehydes and o-phenylenediamines to synthesize densely functionalized imidazo[1,2-d][1,4]oxazepines and imidazo[1,2-d][1,4]diazepines in high yields (up to 93%). This one-pot two-step process was found to be highly atom economical (-H2O, -H2) and operationally simple and enabled the generation of two new heterocycle rings (seven- and five-membered) and three new C-N bonds in a single synthetic operation. These reactions well tolerated a variety of substituents including electron-donating and electron-withdrawing groups and furnished the desired fused heterocycles in high yields under microwave irradiation in a very short reaction time. The mechanism of the established protocol involves sequential imine formation-intramolecular cyclization-air oxidation followed by 7-exo-dig cyclization steps. A comparative study between the microwave-assisted approach and conventional heating was also performed to demonstrate the advantages of the microwave-assisted protocol in terms of high yield and shorter reaction time.

An Efficient One-Pot and Regioselective Synthesis of Novel Heterocyclic Systems of 5,6-Dihydrobenzo[b]Pyrimido[5,4-f][1,4]Oxazepine

An efficient and convenient one-pot two-step process for the regioselective synthesis of the novel tricyclic system 2-chloro-4-methyl-5,6-dihydrobenzo[b]pyrimido[5,4-f][1,4] oxazepine has been described via heterocyclization of 5-(chloromethyl)-2,4-dichloro-6-methylpyrimidine and 2-aminophenol under mild condition followed by reaction with the various secondary amine in moderate to good yields and short time (4a-f).

Design of a green chemoenzymatic cascade for scalable synthesis of bio-based styrene alternatives

We present the strategic development of a synthetic onepot two-step process for the manufacture of acetyl-protected hydroxystyrenes from phenolic acid substrates using environmentally benign (bio)catalysts in an eco-friendly solvent.

One-pot two-step process directly converting biomass-derived carbohydrate to lactide.

This study proposed a strategy for the production of lactide from biomass-derived carbohydrate with excellent yield, involving sugar to racemic lactic acid conversion over Sn-containing Beta zeolite and racemic lactic acid to lactide conversion over H-Beta zeolite. Structural characteristics of the resulting lactide and extensive applicability for various substrates are also presented.

C(sp2)-C(sp2) Suzuki cross-coupling of arylammonium salts catalyzed by a stable Pd–NHC complex

We have developed the Suzuki-Miyaura cross-coupling of aryl ammonium salts via C–N bond activation catalyzed by an easily prepared and bench-stable palladium-N-heterocyclic carbene complex. The reaction proceeded well under mild conditions with phenylboronic acid, pinacol ester or anhydride and provided yields of products up to 97% with good functional group compatibility. The direct arylation of arylamine can be performed by a two-step one-pot process and the protocol can be performed on the gram scale.

C70 Fullerene Catalyzed Photoinduced Aerobic Oxidation of Benzylamines to Imines and Aldehydes.

C70 fullerene catalyzed photoinduced oxidation of benzylic amines at ambient conditions has been explored here. The developed strategy's main feature includes the additive/oxidant-free conversion of benzylic amine to corresponding imine and aldehydes. The reaction manifests broad substrate scope with excellent function group leniency and is applicable up to the gram scale. Further, symmetrical secondary amines can also be synthesized from benzylic amine in a one-pot two-step process. Various experiments and density functional theory studies revealed that the current reaction involves the generation of reactive oxygen species, single electron transfer reaction, and benzyl radical formation as key steps under photocatalytic conditions.

Selective Reductive Dimerization of CO2 into Glycolaldehyde

The selective dimerization of CO2 into glycolaldehyde is achieved in a one-pot two-step process via formaldehyde as a key intermediate. The first step concerns the iron-catalyzed selective reductio...

Copper and N-Heterocyclic Carbene-Catalyzed Oxidative Amidation of Aldehydes with Amines

AbstractA one-pot two-step oxidative process has been developed for the tert-butyl hydroperoxide mediated transformation of aldehydes and amines into amides catalyzed by copper(I) iodide and an N-heterocyclic carbene. The process is additive-free and does not require the amine to be transformed into its hydrochloride salts. The method is simple and practicable, has a broad substrate scope, and uses economical, feasible, and abundant reagents.

Assembly of functionalized π-extended indolizine polycycles through dearomative [3+2] cycloaddition/oxidative decarbonylation.

Reported herein is an unexpected construction of functionalized π-extended indolizine polycycles through a one-pot two-step cascade process comprising the base-promoted dearomative [3+2] cycloaddition of quinilinium salts and 3-alkenyl oxindoles, followed by a DDQ-mediated oxidative decarbonylation. Moreover, we could achieve the substrate-controlled diverse synthesis of structurally strained cyclopropane spirooxindole by using pyridinium salts as starting materials.

A facile synthesis of 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic β-enaminones

A new and efficient method for the synthesis of 6-chloro-substituted 2-methylene-2,3-dihydro-1,4-oxazepines has been demonstrated. Upon treatment with N -chlorosuccinimide in acetonitrile, N -propargylic β-enaminones underwent chlorination to afford α-chlorinated N -propargylic β-enaminones, which was then subjected to electrophilic cyclization with zinc chloride in refluxing chloroform to yield 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines. It was shown for the first time that on N -propargylic β-enaminone systems, α-chlorination exclusively preponderates over the formation of chloronium ion. The method was found to be general for a diversity of N -propargylic β-enaminones and tolerated the presence of a wide range of aryl, heteroaryl and alkyl groups with electron-donating and electron-withdrawing substituents. The method was also applicable as the one-pot two-step process without isolating the intermediate α-chlorinated N -propargylic β-enaminones. This operationally easy method may provide a rapid entry to a library of highly functionalized 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines with potential medicinal applications for human health. • A new and practical method for synthesis of 6-chloro-substituted 1,4-oxazepines. • One-pot conversion of N-propragyl β-enaminones to 6-chloro-substituted 1,4-thiazepines. • High efficiency, large substrate scope and broad functional group tolerance. • Synthesis of chlorine-bearing 1,4-thiazepines as potential scaffolds and pharmacophores.

Redox-driven deracemization of secondary alcohols by sequential ether/O2-mediated oxidation and Ru-catalyzed asymmetric reduction

The deracemization of benzylic alcohols has been achieved using a redox-driven one-pot two-step process. The racemic alcohols were oxidized by bis(methoxypropyl) ether and oxygen to give the ketone intermediates, followed by an asymmetric transfer hydrogenation with a chiral ruthenium catalyst. This compatible oxidation/reduction process gave the enantiomerically enriched alcohols with up to 95% ee values.