Carbonyl Products Research Articles

Synergistic enhancement of electrochemical alcohol oxidation by combining NiV-layered double hydroxide with an aminoxyl radical

Electrochemical alcohol oxidation (EAO) represents an effective method for the production of high-value carbonyl products. However, its industrial viability is hindered by suboptimal efficiency stemming from low reaction rates. Here, we present a synergistic electrocatalysis approach that integrates an active electrode and aminoxyl radical to enhance the performance of EAO. The optimal aminoxyl radical (4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl) and Ni0.67V0.33-layered double hydroxide (LDH) are screen as cooperative electrocatalysts by integrating theoretical predictions and experiments. The Ni0.67V0.33-LDH facilitates the adsorption and activation of N-(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)acetamide (ACTH) via interactions with ketonic oxygen, thereby improving selectivity and yield at high current densities. The electrolysis process is scaled up to produce 200 g of the steroid carbonyl product 8b (19-Aldoandrostenedione), achieving a yield of 91% and a productivity of 243 g h-1. These results represent a promising method for accelerating electron transfer to enhance alcohol oxidation, highlighting its potential for practical electrosynthesis applications.

Carbonylation and Other Transformations of Polyfluorobenzocyclobutenols in Super Acids

Acid-catalyzed carbonylation of a number of polyfluorinated benzocyclobuten-1-ols, as well as cyclic sulfoesters of benzocyclobuten-1,2-diols, in reaction with carbon monoxide has been carried out. The efficiency of using TfOH and FSO3H-SbF5 as acidic systems was evaluated. Both products of CO addition with the remaining four-membered ring — the corresponding carboxylic acids, and various products of carbonylation accompanied by its transformations (ring opening, opening followed by heterocyclization with the formation of isochromane derivatives, expansion to a five-membered one) were obtained. In some cases, the formation of polycyclic dimeric products was also observed.

Enantioselective Electrocatalysis for Cross‐Dehydrogenative Heteroarylation with Indoles, Pyrroles, and Furans

AbstractOxidative cross‐dehydrogenative C−H/C−H functionalizations represent an exemplary approach for synthesizing carbonyl compounds via α‐heteroarylation. Here we present the development of a direct anodic oxidative coupling process between 2‐acylimidazoles and divergent heterocyclic systems including indole, pyrrole, and furan, facilitated by ferrocene‐assisted asymmetric nickel electrocatalysis with high levels of enantioselectivity. Mechanistic investigations indicate that the reaction initially involves the formation of a chiral Ni‐bound α‐carbonyl radical, which is then captured by the heteroarene radical cation via intermolecular stereoselective radical/radical cation coupling. The mild, scalable, and robust reaction conditions allow for a broad substrate scope and excellent functional group tolerance, enabling access to a wide range of chiral hetero‐compounds. The consequential α‐heteroaromatic carbonyl products can potentially be transformed into a plethora of synthetically valuable frameworks, as exemplified by their application in the asymmetric total synthesis of (−)‐COX‐2 inhibitor, (+)‐acremoauxin A, and (+)‐pemedolac.

Enantioselective Electrocatalysis for Cross-Dehydrogenative Heteroarylation with Indoles, Pyrroles, and Furans.

Oxidative cross-dehydrogenative C-H/C-H functionalizations represent an exemplary approach for synthesizing carbonyl compounds via α-heteroarylation. Here we present the development of a direct anodic oxidative coupling process between 2-acylimidazoles and divergent heterocyclic systems including indole, pyrrole, and furan, facilitated by ferrocene-assisted asymmetric nickel electrocatalysis with high levels of enantioselectivity. Mechanistic investigations indicate that the reaction initially involves the formation of a chiral Ni-bound α-carbonyl radical, which is then captured by the heteroarene radical cation via intermolecular stereoselective radical/radical cation coupling. The mild, scalable, and robust reaction conditions allow for a broad substrate scope and excellent functional group tolerance, enabling access to a wide range of chiral hetero-compounds. The consequential α-heteroaromatic carbonyl products can potentially be transformed into a plethora of synthetically valuable frameworks, as exemplified by their application in the asymmetric total synthesis of (-)-COX-2 inhibitor, (+)-acremoauxin A, and (+)-pemedolac.

Organocatalyzed Carbonylation of Alkyl Halides Driven by Visible Light

AbstractHerein, we describe a new strategy for the carbonylation of alkyl halides with different nucleophiles to generate valuable carbonyl derivatives under visible light irradiation. This method is mild, robust, highly selective, and proceeds under metal‐free conditions to prepare a range of structurally diverse esters and amides in good to excellent yields. In addition, we highlight the application of this activation strategy for 13C isotopic incorporation. We propose that the reaction proceeds by a photoinduced reduction to afford carbon‐centered radicals from alkyl halides, which undergo subsequent single electron‐oxidation to form a carbocationic intermediate. Carbon monoxide is trapped by the carbocation to generate an acylium cation, which can be attacked by a series of nucleophiles to give a range of carbonyl products.

Organocatalyzed Carbonylation of Alkyl Halides Driven by Visible Light.

Herein, we describe a new strategy for the carbonylation of alkyl halides with different nucleophiles to generate valuable carbonyl derivatives under visible light irradiation. This method is mild, robust, highly selective, and proceeds under metal-free conditions to prepare a range of structurally diverse esters and amides in good to excellent yields. In addition, we highlight the application of this activation strategy for 13C isotopic incorporation. We propose that the reaction proceeds by a photoinduced reduction to afford carbon-centered radicals from alkyl halides, which undergo subsequent single electron-oxidation to form a carbocationic intermediate. Carbon monoxide is trapped by the carbocation to generate an acylium cation, which can be attacked by a series of nucleophiles to give a range of carbonyl products.

Synthesis of Lactic Acid via Palladium-Catalyzed Carbonylation of Vinyl Acetate

The methoxycarbonylation of vinyl acetate monomer (VAM) was studied with Pd-catalysts at 5.4 MPa CO partial pressure and 373 K. The effects of several acidic and basic ligands in the presence and absence of a promoter were investigated. Using pyridine as ligand in the [PdCl2(PPh3)2]-TsOH catalyst system resulted in 90.01% conversion of VAM and 76.12% selectivity for carbonylation products (methyl-2-acetoxypropionate and methyl lactate). The VAM methoxycarbonylation could be facilitated in a non-polar solvent media and produces methyl-2-acetoxypropionate and methyl lactate, which can be easily converted to lactic acid via hydrolysis.

Plasma-activated water pretreatment as a promising technique to reduce the formation of heterocyclic aromatic amines and advanced glycation end products in roasted fish patties

Plasma-activated water pretreatment as a promising technique to reduce the formation of heterocyclic aromatic amines and advanced glycation end products in roasted fish patties

Preparation of polymer bitumen binder in the presence of a stabilizer

AbstractThis research investigates the improvement of asphalt binder performance by adding polymers, with a specific emphasis on the viscoelastic qualities that impact fatigue resistance. The main objective is to examine the impact of polymer alteration on asphalt binders under different temperatures, degrees of strain, and frequencies by using the linear amplitude sweep test. An elaborate technique was used to assess the complex modulus (G*), phase angle (δ), and crossover frequency of binders that were changed using poly(styrene‐co‐butadiene‐co‐styrene) (SBS), poly(ethylene‐co‐vinyl acetate), and crumb rubber. The experiments were carried out within a temperature range of 20–40°C, strain levels varying from 1% to 10%, and frequencies ranging from 0.1 to 10 Hz. The findings indicate that the complex modulus (G*) of SBS‐modified binders reduced from 9000 to 2800 Pa when the strain rose from 2% to 8% at a temperature of 30°C. The rheological index of the SBS‐modified binder was measured to be 0.6, suggesting a higher level of fatigue resistance. The results highlight the practical benefits of using polymer‐modified binders to increase the durability of asphalt pavements, especially in areas with heavy traffic and severe weather conditions.Highlights This research aims to investigate the protective characteristics of polymers. Styrene‐co‐butadiene‐co‐styrene has a capacity to decrease the production of carbonyls. The crumb rubber‐modified asphalt was followed by the ethylene‐co‐vinyl acetate modified asphalt.

Arabinoxylan from pearl millet bran: Optimized extraction, structural characterization, and its bioactivities

Arabinoxylan (AX) from cereals and millets have garnered attention due to the myriad of their bioactivities. Pearl millet (Pennisetum glaucum) bran, an underexplored milling by-product was used to extract AX (PMAX) by optimized alkali-assisted extraction using Response Surface Methodology and Central Composite Design, achieving a yield of 15.96±0.39% (w/w) under optimal conditions (0.57M NaOH, 1:17g/mL solid-to-liquid ratio, 60°C, 4h). Structural analysis revealed that PMAX was primarily composed of arabinose, xylose, glucose, galactose, and mannose (molar ratio 45.1:36.1:10.4:7.1:1.8), with a highly substituted (1→4)-linked β-D-xylopyranose backbone and a molecular weight of 794.88kDa. PMAX displayed a significant reducing power of 0.617, metal chelating activity of 51.72%, and DPPH, and ABTS radical scavenging activities (64.43 and 75.4%, respectively at 5mg/mL). It also demonstrated anti-glycation effects by inhibiting fructosamine (52.5%), protein carbonyl (53.6%), and total advanced glycation end products (77.0%) formation, and reduced protein oxidation products such as dityrosine (84.7%), kynurenine (80.2%), and N'-formyl-kynurenine (50.0%) at 5mg/mL. PMAX induced the growth of Lactobacillus spp. in vitro and modulate gut microbiota in male Wistar rats by increasing Bacteroidetes and decreasing Firmicutes. These results provide a basis for further research on pearl millet arabinoxylan and its possible nutraceutical application.

Enhanced Organic Nitrate Formation from Peroxy Radicals in the Condensed Phase.

Organic alkoxy (RO) and peroxy (RO2) radicals are key intermediates in multiphase atmospheric oxidation chemistry, though most of the study of their chemistry has focused on the gas phase. To better understand how radical chemistry may vary across different phases, we examine the chemistry of a model system, the 1-pentoxy radical, in three phases: the aqueous phase, the condensed organic phase, and the gas phase. In each phase, we generate the 1-pentoxy radical from the photolysis of n-pentyl nitrite, run the chemistry under conditions in which RO2 radicals react with NO, and detect the products in real time using an ammonium chemical ionization mass spectrometer (NH4 + CIMS). The condensed-phase chemistry shows an increase in formation of organic nitrate (RONO2) from the downstream RO2+NO reaction, which is attributed to potential collisional and solvent-cage stabilization of the RO2-NO complex. We further observe an enhancement in the yield of carbonyl relative to hydroxy carbonyl products in the condensed phase, indicating changes to RO radical kinetics. The different branching ratios in the condensed phase impact the product volatility distribution as well as HO x -NO x chemistry, and may have implications for nitrate formation, aqueous aerosol formation, and radical cycling within atmospheric particles and droplets.

Continuous Flow Approach for Benzylic Photo-oxidations Using Compressed Air.

A continuous flow approach for the aerobic photo-oxidation of benzylic substrates to ketone and aldehyde products is presented. The resulting process exploits UV-A LEDs (375 nm) in combination with a Corning AFR reactor that ensures effective gas-liquid mixing and leads to short residence times of 1 min. A variety of benzylic substrates are converted to their corresponding carbonyl products, and scalability is demonstrated to produce multigram quantities of products within a few hours. Overall, this continuous flow approach offers several improvements over alternative oxidation methods due to the combined use of air as an oxidant and SAS (sodium anthraquinone-2 sulfonate) as a water-soluble photocatalyst. The use of greener and safer conditions together with process intensification principles renders this flow approach attractive for further industrial applications.

Water mediated redox-neutral cleavage of arylalkenes via photoredox catalysis

Cleavage of carbon-carbon bonds remains a challenging task in organic synthesis. Traditional methods for splitting Csp2=Csp2 bonds into two halves typically involve non-redox (metathesis) or oxidative (ozonolysis) mechanisms, limiting their synthetic potential. Disproportionative deconstruction of alkenes, which yields one reduced and one oxidized fragment, remains an unexplored area. In this study, we introduce a redox-neutral approach for deleting a Csp2 carbon unit from substituted arylalkenes, resulting in the formation of an arene (reduction) and a carbonyl product (oxidation). This transformation is believed to proceed through a mechanistic sequence involving visible-light-promoted anti-Markovnikov hydration, followed by photoredox cleavage of Csp3-Csp3 bond in the alcohol intermediate. A crucial consideration in this design is addressing the compatibility between the highly reactive oxy radical species in the latter step and the required hydrogen-atom-transfer (HAT) reagent for both steps. We found that ethyl thioglycolate serves as the optimal hydrogen-atom shuttle, offering remarkable chemoselectivity among multiple potential HAT events in this transformation. By using D2O, we successfully prepared dideuteromethylated (-CD2H) arenes with good heavy atom enrichment. This work presents a redox-neutral alternative for alkene deconstruction, with considerable potential in late-stage modification of complex molecules.

A broad-spectrum oxidation capability Ru-CeO2 catalyst for efficient synergistic selective oxidation of benzyl alcohol

A broad-spectrum oxidation capability Ru-CeO2 catalyst for efficient synergistic selective oxidation of benzyl alcohol

Neurotoxic and behavioral deficit in Drosophila melanogaster exposed to photocatalytic products of Paraquat

The Advanced Oxidative Processes have demonstrated potential for application in the degradation of organic pollutants, such as Paraquat (PQ) from water and wastewater, due to their low price, high efficiency, and non-toxic properties. In this study, we investigated whether the photodegradation of PQ with TiO2 nanotubes reduced its toxicity in Drosophila melanogaster. However, dietary ingestion of degradation products PQ for larvae resulted in a low axial ratio (pupal volume). In the adults, products of photodegradation of PQ exposure markedly diminished climbing ability in a time-dependent manner after 10 days of feeding. In addition, exposure of D. melanogaster to photodegradation of PQ reduced acetylcholinesterase and citrate synthase activities but improved oxidative stress, as evidenced by oxide nitric, protein carbonyl, and lactate production. These results suggest that the photodegradation of PQ with TiO2 nanotubes produced PQ fragments with higher toxicity than PQ, while the precise mechanism of its action needs further investigation.

Organic Synthesis Away from Equilibrium: Contrathermodynamic Transformations Enabled by Excited-State Electron Transfer.

ConspectusChemists have long been inspired by biological photosynthesis, wherein a series of excited-state electron transfer (ET) events facilitate the conversion of low energy starting materials such as H2O and CO2 into higher energy products in the form of carbohydrates and O2. While this model for utilizing light-driven charge transfer to drive catalytic reactions thermodynamically "uphill" has been extensively adapted for small molecule activation, molecular machines, photoswitches, and solar fuel chemistry, its application in organic synthesis has been less systematically developed. However, the potential benefits of these approaches are significant, both in enabling transformations that cannot be readily achieved using conventional thermal chemistry and in accessing distinct selectivity regimes that are uniquely enabled by excited-state mechanisms. In this Account, we present work from our group that highlights the ability of visible light photoredox catalysis to drive useful organic transformations away from their equilibrium positions, addressing a number of long-standing synthetic challenges.We first discuss how excited-state ET enabled the first general methods for the catalytic anti-Markovnikov hydroamination of unactivated alkenes with alkyl amines. In these reactions, an excited-state iridium(III) photocatalyst reversibly oxidizes secondary amine substrates to their corresponding aminium radical cations (ARCs). These electrophilic N-centered radicals can then react with olefins to furnish valuable tertiary amine products with complete anti-Markovnikov regioselectivity. Notably, some of these products are less thermodynamically stable than their corresponding amine and alkene starting materials. We next present a strategy for light-driven C-C bond cleavage within various aliphatic alcohols mediated by homolytic activation of alcohol O-H bonds by excited-state proton-coupled electron transfer (PCET). The resulting alkoxy radical intermediates then undergo C-C β-scission to ultimately provide isomeric linear carbonyl products that are often higher in energy than their cyclic alcohol precursors. Applications of this chemistry for the light-driven depolymerization of lignin biomass, commercial phenoxy resin, hydroxylated polyolefin derivatives, and thermoset polymers are presented as well. We then describe a method for the contrathermodynamic positional isomerization of highly substituted olefins by means of cooperative photoredox and chromium(II) catalysis. In this work, generation of an allylchromium(III) species that can undergo highly regioselective in situ protodemetalation enables access to a less substituted and thermodynamically less stable positional isomer. Product selectivity in this reaction is determined by the large differential in oxidation potentials between differently substituted olefin isomers. Lastly, we discuss a light-driven deracemization reaction developed in collaboration with the Miller group, wherein a racemic urea substrate undergoes spontaneous optical enrichment upon visible light irradiation in the presence of an iridium(III) chromophore, a chiral Brønsted base, and a chiral peptide thiol. Excellent levels of enantioselectivity are achieved via sequential and synergistic proton transfer (PT) and H atom transfer (HAT) steps. Taken together, these examples highlight the ability of excited-state ET events to enable access to nonequilibrium product distributions across a wide range of catalytic, redox-neutral transformations in which photons are the only stoichiometric reagents.

Three‐Component Reactions of Alkenes with C−C Bond Formation: Recent Developments

AbstractAlkenes are highly valuable materials in organic synthesis, and their three‐component reactions offer a promising method for C−C bond formation and carbon chain elongation. This approach not only reduces the number of reaction steps but also minimizes waste generation, enabling the preparation of polysubstituted alkanes from simple starting materials. In this review, we provide an overview of recent advancements in this field from 2013 to 2023. We have classified the developments into three main categories: (1) reactions triggered by C‐radicals or heteroatom‐radicals; (2) cascades involving three‐membered ring intermediates; and (3) transformations catalyzed by metals. We will discuss a wide range of reactions that involve diazoium salts, arylhydrazines, acids, aldehydes, 1,3‐dicarbonyls, diazo compounds, amines, malononitriles, diacyl peroxides, ethers, 1,3‐dithiane, arenes, CuSCF3, selectfluor, Et3N ⋅ 3HF, TBHP, CH2Cl2, CHCl3, CO2, CO, KCl, H2O, and other reagents. These reactions lead to alkylation, arylation, or carbonylation products. We believe that this review will be helpful for future research in this area.

Berberine attenuates brain aging via stabilizing redox homeostasis and inflammation in an accelerated senescence model of Wistar rats.

Aging is a multifaceted and progressive physiological change of the organism categorized by the accumulation of deteriorating processes, which ultimately compromise the biological functions. The objective of this study was to investigate the anti-aging potential of berberine (BBR) in D-galactose (D-Gal) induced aging in rat models. In this study, male Wistar rats were divided into four groups: The control group was given only vehicle, the BBR group was treated with berberine orally, the D-Gal group was treated with D-galactose subcutaneously and the BBR + D-Gal group was treated with D-galactose and berberine simultaneously. D-galactose exposure elevated the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl and advanced oxidation protein products (AOPP) in the brain. It decreased the anti-oxidants such as reduced glutathione (GSH) and ferric reducing antioxidant potential (FRAP) in the brain. D-galactose treatment also reduced the mitochondrial complexes (I, II, III and IV) activities and elevated the inflammatory markers such as interleukine-6 (IL-6), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of IL-6 and TNF-α in the brain were upregulated following D-galactose exposure. Berberine co-treatment in D-galactose induced aging rat model prevented the alteration of pro-oxidant and anti-oxidant in the brain. Berberine treatment restored the mitochondrial complex activities in the brain and also normalized the inflammatory markers. Based on these findings we conclude that berberine treatment has the potential to mitigate brain aging in rats via stabilizing the redox equilibrium and neuroinflammation.

Palladium Catalyzed Selective 1,4‐Dihydrosilylation of Alkynones

AbstractAn efficient and selective Pd‐catalyzed 1,4‐dihydrosilylation of alkynones has been firstly described to provide a convenient access to β‐aryl carbonyl compounds under mild conditions. Various β‐aryl carbonyl compounds have been synthesized with good yields and functional group tolerance. β‐aryl carbonyl products have been shown to be further application in the synthesis of secondary alcohol, silyl‐ether, trifluoromethylsilyl‐ether and vinyl acetate derivative.

Competing Mechanisms in Palladium-Catalyzed Alkoxycarbonylation of Styrene.

Palladium-catalyzed carbonylation is a versatile method for the synthesis of various aldehydes, esters, lactones, or lactams. Alkoxycarbonylation of alkenes with carbon monoxide and alcohol produces either saturated or unsaturated esters as a result of two distinct catalytic cycles. The existing literature presents an inconsistent account of the procedures favoring oxidative carbonylation products. In this study, we have monitored the intermediates featured in both catalytic cycles of the methoxycarbonylation of styrene PhCH=CH2 as a model substrate, including all short-lived intermediates, using mass spectrometry. Comparing the reaction kinetics of the intermediates in both cycles in the same reaction mixture shows that the reaction proceeding via alkoxy intermediate [PdII]-OR, which gives rise to the unsaturated product PhCH=CHCO2Me, is faster. However, with an advancing reaction time, the gradually changing reaction conditions begin to favor the catalytic cycle dominated by palladium hydride [PdII]-H and alkyl intermediates, affording the saturated products PhCH2CH2CO2Me and PhCH(CO2Me)CH3 preferentially. The role of the oxidant proved to be crucial: using p-benzoquinone results in a gradual decrease of the pH during the reaction, swaying the system from oxidative conditions toward the palladium hydride cycle. By contrast, copper(II) acetate as an oxidant guards the pH within the 5-7 range and facilitates the formation of the alkoxy palladium complex [PdII]-OR, which favors the oxidative reaction producing PhCH=CHCO2Me with high selectivity. Hence, it is the oxidant, rather than the catalyst, that controls the reaction outcome by a mechanistic switch. Unraveling these principles broadens the scope for developing alkoxycarbonylation reactions and their application in organic synthesis.