Oxidation Of Primary Alcohols Research Articles

An efficient electrocatalytic system composed of nickel oxide and nitroxyl radical for the oxidation of bio-platform molecules to dicarboxylic acids

Selective oxidation of biomass and its derivatives to dicarboxylic acids represents a promising route for biomass valorization. However, the co-presence of multiple functional groups in biomass molecules makes the selective oxidation of particular functional a challenging task. Here, we demonstrate an efficient electrocatalytic system consisting of nickel oxide (NiO) and a nitroxyl radical, i.e., 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 4-acetamido-TEMPO (ACT), for the selective oxidation of key bio-platform molecules including glucose, xylose and 5-hydroxymethylfurfural (HMF) into corresponding dicarboxylic acids, i.e., glucaric acid, xylaric acid, and 2,5-furandicarboxylic acid (FDCA). NiO is clarified as the active catalyst for the oxidation of aldehyde in bio-platform molecules to carboxylic acid, while TEMPO or ACT is responsible for the oxidation of primary alcohol to aldehyde. The combination of NiO and TEMPO or ACT significantly accelerated the tandem oxidation of aldehyde and hydroxyl groups in glucose, xylose and HMF, thus achieving excellent yields (83%–99%) of dicarboxylic acids. Moreover, the combination catalyst enables the selective oxidation of glucose and xylose with high concentrations (e.g., 20 wt%), which offers a promising strategy for biomass valorization.

Candida parapsilosis carbonyl reductase as a tool for preliminary screening of inhibitors for alcohol dehydrogenase induced skin sensitization

Human alcohol dehydrogenases, specifically ADH1 oxidize primary alcohols to aldehydes in the skin. These aldehydes act as haptens, leading to sensitization. Inhibition of these ADH enzymes may help in combating skin allergies. In the present study, the recombinantly purified stereospecific enzyme from Candida parapsilosis ATCC 7330, Candida parapsilosis Carbonyl Reductase (CpCR) has 23.31 % sequence similarity with human alcohol dehydrogenase ADH1B1. These two enzymes have perfectly overlapping cofactor and zinc binding domains. CpCR was found to oxidize primary alcohols to their corresponding aldehydes. Oxidation of primary alcohols by CpCR was further optimized with cinnamyl alcohol as the model substrate that initially showed a conversion of 56 % ± 0.25, and upon optimization increased to 98.2 % ± 0.23. An increase of 20–50 % in the conversion rate has been observed for various primary alcohols under the optimized reaction conditions. A simple and efficient model was designed for the screening of compounds that inhibit CpCR with the possibility of mitigating the action of skin allergens by inhibiting ADH1. p-Nitrophenylglyoxal (PNG) was found to be a good inhibitor for CpCR which showed inhibitory activity at very low concentration (IC50,100 mM ± 1.27) as compared to the standard inhibitor 4-methyl pyrazole (4MP) (IC50, 400 mM ± 2.05).

Chemoselective derivatisation and ultrahigh resolution mass spectrometry for the determination of hydroxyl functional groups within complex bio-oils.

Bio-oils are a renewable alternative resource for the production of fine chemicals and fuels. Bio-oils are characterised by a high content of oxygenated compounds with a diverse array of different chemical functionalities. Here, we performed a chemical reaction to transform the hydroxyl group of the various components in a bio-oil prior to characterisation with ultrahigh resolution mass spectrometry (UHRMS). The derivatisations were first evaluated using twenty lignin-representative standards with different structural features. Our results indicate a highly chemoselective transformation of the hydroxyl group despite the presence of other functional groups. Mono- and di-acetate products were observed in acetone-acetic anhydride (acetone-Ac2O) mixtures for non-sterically hindered phenols, catechols and benzene diols. Dimethyl sulfoxide-Ac2O (DMSO-Ac2O) reactions favoured the oxidation of primary and secondary alcohols and the formation of methylthiomethyl (MTM) products of phenols. The derivatisations were then performed in a complex bio-oil sample to gain insights into the hydroxyl group profile of the bio-oil. Our results indicate that the bio-oil before derivatisation is composed of 4500 elemental compositions containing 1-12 oxygen atoms. After the derivatisation in DMSO-Ac2O mixtures, the total number of compositions increased approximately five-fold. The reaction was indicative of the variety of hydroxyl group profiles within the sample in particular the presence of phenols that were ortho and para substituted, non-hindered phenols (about 34%), aromatic alcohols (including benzylic and other non-phenolic alcohols) (25%), and aliphatic alcohols (6.3%) could be inferred. Phenolic compositions are known as coke precursors in catalytic pyrolysis and upgrading processes. Thus, the combination of chemoselective derivatisations in conjunction with UHRMS can be a valuable resource to outline the hydroxyl group profile in elemental chemical compositions in complex mixtures.

Acetamido-TEMPO mediated electrochemical oxidation of alcohols to aldehydes and ketones.

A protocol for the oxidation of alcohols to aldehydes and ketones employing an electrochemical aminoxyl-mediated reaction is presented. The approach employs a catalytic amount of the radical and the use of a base is not required. It is performed using readily available electrodes in a commercially available electrochemistry apparatus and does not require a reference electrode. The methodology is applicable to a range of structurally and electronically diverse substrates, including the oxidation of primary alcohols to aldehydes rather than the more commonly formed carboxylic acids.

Copper-catalyzed aerobic oxidation of primary alcohols to carboxylic acids.

Here, the first copper-catalyzed aerobic oxidation of primary alcohols to carboxylic acids with TEMPO and KHSO4 as the co-catalysts has been developed. The reaction exhibits excellent substrate scope and functional group compatibility under mild conditions. Even the very sensitive chiral alcohols, chiral amino alcohols, and alcohol-containing steroid skeletons may be oxidized to afford the corresponding carboxylic acids or lactones without racemization.

Basic Ionic Liquid [Bmim]OH as Efficient Greener Medium for the Oxidation α-Hydroxy Ketone Compounds and Alcohols to Carbonyl Compounds with Potassium Permanganate

In this work, a convenient and greener procedure for synthesizing 1,2-diarylethane-1,2-dione derivatives as well as the oxidation of primary and secondary alcohols was explored using an oxidizing agent (KMnO4) in a basic ionic liquid of 1-butyl-3-methylimidazolium hydroxide ([Bmim]OH) as greener medium. The selective oxidation of α-hydroxy ketone compounds together with primary and secondary alcohols in the presence of KMnO4 in [Bmim]OH afforded corresponding carbonyl compounds of 1,2-diarylethane-1,2-dione derivatives and aldehydes or ketones in high yields (85-97% and 83-97%, respectively). The reactions are mild, fast, and efficient. Moreover, KMnO4 in [Bmim]OH medium was easily recovered and reused for at least four additional reactions without significant loss of efficiency with a consistent yield of about 80%.

Auto Machine Learning Assisted Preparation of Carboxylic Acid by TEMPO‐Catalyzed Primary Alcohol Oxidation

Comprehensive SummaryThough alcohol oxidations were considered as well‐established reactions, selecting productive conditions or predicting reaction yields for unseen alcohols remained as major challenges. Herein, an auto machine learning (ML) model for TEMPO‐catalyzed oxidation of primary alcohols to the corresponding carboxylic acids is disclosed. A dataset of 3444 data, consisting of 282 primary alcohols and 45 conditions, were generated using high‐throughput experimentation (HTE). With the HTE data and 105 descriptors, a multi‐label prediction was performed with AutoGluon (an open‐source auto machine learning framework) and KNIME (an open‐source data analytics platform). For the independent test of 240 reactions (a full matrix of 20 unseen alcohols and 12 conditions), AutoGluon with multi‐label prediction for yield prediction (AGMP) gave excellent performance. For external test of 1308 reactions (consisting of 84 alcohols and 45 conditions), AGMP still afforded good results with R2 as 0.767 and MAE as 4.9%. The model also revealed that the newly generated descriptor (Y/N, classification of the reaction reactivity) was the most relevant descriptor for yield prediction, offering a new perspective to integrate HTE and ML in organic synthesis.

Convergent paired electrosynthesis of different types of bis-β-diketone derivatives based on the knoevenagel condensation reaction under green conditions

A green convergent paired electrochemical protocol has been developed for the synthesis of some bis-β-diketones via Knoevenagel condensation reaction. In this method, the electrochemical oxidation of primary alcohols to the corresponding aldehydes have taken at anode and the reduction of β-diketones to active methylene compounds has happened in cathode. In next step, the cathodically activated methylene reacts with anodically generated aldehyde. Different types of bis-β-diketones have been synthesized using C1–C5 primary alcohols and different β-diketones. In this work, we proposed a unique convergent paired mechanism for the synthesis of bis-β-diketones based on possible anodic and cathodic reactions. The effective parameters such as, solution pH, current density, electrode material, alcohol concentration and type of cell have also been optimized. This method provides a new strategy for the synthesis of a wide range of products in the mild conditions and in an undivided cell without using the any catalyst and toxic solvent.

Copper Pyrithione (CuPT)-Catalyzed Oxidation of Secondary and Primary Benzyl Alcohols with Molecular oxygen or Air Under Mild Conditions

Copper Pyrithione (CuPT)-Catalyzed Oxidation of Secondary and Primary Benzyl Alcohols with Molecular oxygen or Air Under Mild Conditions

Porous Heteroatom‐Doped Carbons: Efficient Catalysts for Selective Oxidation of Alcohols by Activated Persulfate

AbstractAldehydes are essential chemicals for industrial feedstock. However, the traditional processes to produce these chemicals face many limitations, such as waste generation, low selectivity, or high cost. Herein, we report the synthesis and characterization of a group of porous heteroatom (P, B or N)‐doped carbons and their use as catalysts for the oxidation of primary alcohols by activating peroxydisulfate. Among the heteroatom‐doped carbons, porous N‐doped carbons pyrolyzed at 700 or 800 °C show the highest activity. Experimental studies were performed suggesting a considerable contribution of a non‐radical oxidation process. Furthermore, N‐doped carbons can act as a catalyst in the oxidation of a large substrate scope of substituted alcohols.

Efficient synthesis 1,4-cyclohexanedicarboxaldehyde by an engineered alcohol oxidase

In this study, we selected and engineered a flavin adenine dinucleotide (FAD)-dependent alcohol oxidase (AOX) to produce 1,4-cyclohexanedicarboxaldehyde (CHDA), an initial raw material for spiral compounds, from 1,4-cyclohexanedimethanol (CHDM). First, the structure of alcohol oxidase from Arthrobacter cholorphenolicus (AcCO) was analyzed, and the mechanism of AcCO-catalyzed primary alcohol oxidation was elucidated, demonstrating that the energy barrier of the hydride (H−) transfer (13.4 kcal·mol−1 and 20.4 kcal·mol−1) decreases the catalytic efficiency of the primary alcohol oxidation reaction. Therefore, we designed a protein engineering strategy to adjust the catalytically active conformation to shorten the distance of hydride (H−) transfer and further decreased the core energy barrier. Following this strategy, variant W4 (S101A/H351V/N378S/Q329N) was obtained with 112.5-fold increased catalytic efficiency to produce CHDA compared to that of the wild-type strain. The 3 L scale preparation of CHDA reached a titer up to 29.6 g·L−1 with a 42.2% yield by an Escherichia coli whole-cell catalyst, which demonstrates the potential of this system for industrial application.Graphical

Oxidation of Organic Compounds Using Water as the Oxidant with H2 Liberation Catalyzed by Molecular Metal Complexes.

ConspectusOxidation reactions of organic compounds play a central role in both industrial chemical and material synthesis as well as in fine chemical and pharmaceutical synthesis. While traditional laboratory-scale oxidative syntheses have relied on the use of strong oxidizers, modern large-scale oxidation processes preferentially utilize air or pure O2 as an oxidant, with other oxidants such as hydrogen peroxide, nitric acid, and aqueous chlorine solution also being used in some processes. The use of molecular oxygen or air as an oxidant has been very attractive in recent decades because of the abundance of air and the lack of wasteful byproduct generation. Nevertheless, the use of high-pressure air or, in particular, pure oxygen can lead to serious safety concerns with improper handling and also necessitates the use of sophisticated high-pressure reactors for the processes.Several research groups, including ours, have investigated in recent times the possibility of carrying out catalytic oxidation reactions using water as the formal oxidant, with no added conventional oxidants. Along with the abundant availability of water, these processes also generate dihydrogen gas as the reaction coproduct, which is a highly valuable fuel. Several well-defined molecular metal complexes have been reported in recent years to catalyze these unusual oxidative reactions with water. A ruthenium bipyridine-based PNN pincer complex was reported by us to catalyze the oxidation of primary alcohols to carboxylate salts with alkaline water along with H2 liberation, followed by reports by other groups using other complexes as catalysts. At the same time, ruthenium-, iridium-, and rhodium-based complexes have been reported to catalyze aldehyde oxidation to carboxylic acids using water. Our group has combined the catalytic aqueous alcohol and aldehyde oxidation activity of a ruthenium complex to achieve the oxidation of biomass-derived renewable aldehydes such as furfural and 5-hydroxymethylfurfural (HMF) to furoic acid and furandicarboxylic acid (FDCA), respectively, using alkaline water as the oxidant, liberating H2. Ruthenium complexes with an acridine-based PNP ligand have also been employed by our group for the catalytic oxidation of amines to the corresponding lactams, or to carboxylic acids via a deaminative route, using water. Similarly, we also reported molecular complexes for the catalytic Markovnikov oxidation of alkenes to ketones using water, similar to Wacker-type oxidation, which, however, does not require any terminal oxidant and produces H2 as the coproduct. At the same time, the oxidation of enol ethers to the corresponding esters with water has also been reported. This account will highlight these recent advances where water was used as an oxidant to carry out selective oxidation reactions of organic compounds, catalyzed by well-defined molecular complexes, with H2 liberation. The oxidation of alcohols, aldehydes, amines, alkenes, and enol ethers will be discussed to provide an outlook toward other functional groups’ oxidation. We hope that this will aid researchers in devising other oxidative dehydrogenative catalytic systems using water, complementing traditional oxidative processes involving strong oxidants and molecular oxygen.

One-Pot O2-Oxidation and the Horner-Wadsworth-Emmons Reaction of Primary Alcohols for the Synthesis of (Z)-α,β-Unsaturated Esters.

We developed one-pot oxidation/olefination procedures of primary alcohols giving Z-α,β-unsaturated esters 3. TEMPO-(CuCl or CuBr2)-(2,2'-bipyridine) (1:1:1) catalyzed O2 oxidation of primary alcohols in the presence of Z-selective Horner-Wadsworth-Emmons reagent 1b and K3PO4 or NaH gave 3 with Z/E = 84:16 to 96:4 in high yields. A stepwise reaction was also developed. After TEMPO-CuBr2-(2,2'-bipyridine)-K3PO4 (1:1:1:1) catalyzed O2 oxidation of alcohols in MeCN, the resulting mixture was treated with a THF solution of 1b and t-BuOK at -78 °C to 0 °C, giving 3 with higher selectivity (Z/E = 91:9 to 99:1).

Front Cover Picture: Aryl‐Alcohol‐Oxidase‐Mediated Synthesis of Piperonal and Other Valuable Aldehydes (Adv. Synth. Catal. 14/2022)

The front cover image illustrates the oxidation of primary aromatic and aliphatic allylic alcohols to valuable aldehydes catalyzed by a recombinant aryl-alcohol oxidase of Pleurotus eryngii P34. This versatile enzyme demonstrates high stability against the by-product of the reaction, H2O2, and in the presence of organic solvents. After reaction optimization, a space-time-yield of 9.5 g piperonal/l/h was achieved on a preparative scale. The produced aldehydes are of great interest as fragrances or building blocks in the synthesis of pharmaceuticals. Further details can be found in the Research Article by Urlacher and co-workers (N. Jankowski, K. Koschorreck, V. B. Urlacher, Adv. Synth. Catal. 2022, 364, XXXX–XXXX; DOI: 10.1002/adsc.202200381)

Selective oxidation of primary benzylic alcohols to aldehydes using NaNO3 under ball milling

A facile method for oxidation of primary benzylic alcohols to the corresponding aldehydes is reported using NaNO3/P2O5 under high-speed ball-milling conditions. This approach is clean, efficient, and exhibits broad functional group compatibility.

Copper(II) complexes supported by 8-hydroxyquinoline-imine ligands: Synthesis, characterization and catalysis in aerobic alcohols oxidation

Treatment of Cu(OAc)2·4H2O with 8-hydroxylquinoline-imine ligands [2-(ArN = HC)-8-OH]C9H5N (Ar = 2,6-iPr2C6H3, L1H; Ar = 4-ClC6H4, L2H; Ar = 4-BrC6H4, L3H and Ar = 4-OMeC6H4, L4H) in refluxing EtOH gave the dual-ligand coordinated copper complexes [L2Cu] 1a-1d in good yields, respectively. All the four Cu complexes were characterized by IR, EPR, elemental analysis and HR-MS. Furthermore, the molecular structures of complexes 1a and 1d were further confirmed by X-ray crystallographic analysis. These complexes displayed high catalytic activity and good selectivity for aerobic oxidation of primary and secondary alcohols in the presence of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl) as the co-catalyst. The yields of desired aldehydes are decent (up to 84%) and the corresponding yields of ketones are in the range of 78–91%.

Electrochemical Oxidation of Primary Alcohol in Single-Pass Continuous Flow

Electrochemical Oxidation of Primary Alcohol in Single-Pass Continuous Flow

Simple and low–cost transition metal-free borophosphate glass catalyst for aromatic alcohol oxidation by sodium hypochlorite

The oxidation of primary and secondary alcohols to their respective aldehydes/ketones is one of the most important reactions in fine chemistry due to the industrial application of these products. Based on this, a large number of new catalysts and oxidants have been tested using this reaction as a catalytic model, mainly looking for a process that ensures high aldehyde selectivity. In this paper, we have used moisture stable borophosphate glass doped with 10 mol% Al2O3 as a heterogeneous catalyst in the oxidation of sodium hypochlorite, an effective, greener, and low-cost oxidant, using acetonitrile as solvent under mild conditions. The glass catalyst mass and the particle size were evaluated, as were the reaction temperature and oxidant amount, to determine the ideal reaction conditions where the conversions achieved 87.0 mol% for 1-phenylethanol to acetophenone and 79.4 mol% for benzyl alcohol to benzaldehyde, with benzaldehyde selectivity above 95%. Although sodium hypochlorite is a strong oxidant, benzaldehyde was the main product of the oxidation of benzyl alcohol due to the formation of a biphasic organic-aqueous system that protects the aldehyde from oxidation and allows the reaction to occur without the use of a phase transfer catalyst (PTC). HPLC analysis of both phases showed that alcohols, aldehyde, and ketone were mostly present in the organic phase (concentrations above 98.7%). During the reaction, a small amount of alcohol is transferred to the aqueous phase, where the oxidation took place. Once formed, the products are transferred back to the organic phase. ICP-OES analysis indicates that borophosphate glass acts in the reaction by partially releasing phosphate-based groups, reducing the pH of hypochlorite to 9. In this sense, borophosphate glasses prove to be a simple and inexpensive alternative for the development of new catalysts.

Gold Nanoparticles Supported on Poly(2,6‐dimethyl‐1,4‐phenylene oxide) as Robust, Selective and Cost‐Effective Catalyst for Aerobic Oxidation and Direct Oxidative Esterification of Alcohols

AbstractA new catalytic system based on gold nanoparticles (AuNPs) incarcerated in poly(2,6‐dimethyl‐1,4‐phenylene oxide) (PPO) matrix has been synthesized and successfully tested in aerobic oxidation of alkyl alcohols. PPO is a cheap and commercially available polymer, showing nanoporous morphology, high glass transition temperature (Tg =220 °C), semi‐crystallinity, excellent thermal stability, and interesting chemo‐physical properties. The synthesis of the AuNPs‐PPO catalyst is simple, cost‐effective and allows a fine control of the gold concentration, as well as an optimal dispersion of 7–8 nm sized AuNPs in the polymer matrix. AuNPs‐PPO is an efficient, robust and selective catalyst active in the aerobic oxidation and oxidative esterification of alcohols in water under mild reaction conditions (35 °C, atmospheric pressure of oxygen). The testing of AuNPs‐PPO in aerobic oxidation of 1‐phenylethanol to acetophenone, as a benchmark reaction, highlighted that this gold catalyst exhibits activity values among the highest so far reported for polymer‐supported AuNPs under mild reaction conditions. The oxidation of primary alcohols, such as benzyl and cinnamyl alcohols, could be addressed to the corresponding aldehyde or carboxylate derivatives. Alkyl cinnamates were obtained with efficiency in the one‐pot aerobic oxidation of cinnamyl alcohol in the presence of alkyl alcohols, such as n‐butanol or n‐hexanol. The role of the polymer matrix and the reaction conditions on both activity and selectivity of the AuNPs‐PPO catalyst were also investigated and discussed.

Copper complexes bearing tridentate salicylaldimine Schiff-base ligands: Synthesis, characterizations and catalytic performance in the oxidation reaction of alcohols

Treatment of Cu(OAc)2·H2O with salicylaldimine Schiff-base (C9H6N)N = CH(3,5-tBu2C6H2OH) (L1H), (Et2N)(CH2)2N = CH(3,5-tBu2C6H2OH) (L2H), (2-C5H4N)CH2N = CH(3,5-tBu2C6H2OH) (L3H) in refluxing ethanol afforded three mononuclear copper complexes [(L1)Cu(OAc)] (1), (L2)Cu(OAc) (2) and (L3)Cu(OAc) (3), respectively. The three new complexes were fully characterized using elemental analysis, IR and HR-MS, and X-ray diffraction analysis. They all exhibited efficient catalytic activity in the oxidation of primary and secondary alcohols into the corresponding carbonyl derivatives with hydrogen peroxide (H2O2) as the oxidation agent. The catalytic system is operationally simple, clean and generates water as the only by-product.