Primary Alcohols Research Articles

Photothermal catalytic transfer hydrogenolysis of protolignin

Photothermal catalysis is a promising strategy to combine the advantages of both thermal-catalysis and photocatalysis. Herein we achieve the protolignin conversion to aromatics via the photothermal catalytic transfer hydrogenolysis process intensified by the in-situ protection strategy. The Pd/TiO2 at 140 °C with UV irradiation can catalyze the reforming of primary alcohols to aldehydes and active H* species, which further participate in the acetalation protection of the 1,3-diol group of β-O-4 linkage and mediate the hydrogenolysis of Cβ–OAr bonds, respectively. The conversion of birch sawdust with ethanol as the hydrogen donor provides a 40 wt% yield of phenolic monomers, compared with an 11 wt% monomer yield obtained from the conversion of extracted 1,3-diol-protected lignin under the same conditions. The synergistic effect of photocatalysis and thermal-catalysis contributes to the prior cleavage of the Cβ–OAr bond before other C–O bonds. The feasibility of solar-light-driven photothermal catalytic system is demonstrated.

(Invited) Electrochemical TEMPO-Mediated Oxidation of Cellulose Nanocrystals: Gaining a Mechanistic Understanding of a New Non-Conventional Process

This research aims to address the limitations of traditional (2,2,6,6 tetramethylpiperidin-1-yl)oxyl (TEMPO)-mediated chemical oxidation by introducing electrochemical oxidation as a novel approach. Our interest lies in using electrochemical TEMPO-mediated oxidation for the carboxylation of cellulose nanocrystals (CNCs). CNCs are bio-based “rice-shaped” nanoparticles that have low density and high strength, making them useful in materials, medicine, electronics, and adhesives.1 The carboxylation of the native alcohol groups on the surface of CNCs is an important functionalization which imparts electrostatic charge to the nanoparticles – allowing them to form colloidally stable suspensions.2 These are crucial properties for CNC users because they allow for long-term stability and predictability of CNC performance.In this research, an electrochemical approach is used to replace chemical oxidizing agents in TEMPO-mediated CNC oxidation. In conventional TEMPO-mediated oxidation, strong secondary oxidants, usually toxic halogenated compounds, are required to drive the overall reaction: (i) TEMPO reacts with an oxidizer to form the corresponding nitrosonium ion (TEMPO+), (ii) TEMPO+ oxidizes a substrate to form an oxidized product and generate a TEMPO hydroxylamine (TEMPOH), (iii) the secondary oxidants react with TEMPOH to regenerate the TEMPO radical, and the cycle continues.3 CNCs were electrochemically carboxylated at pH 4, 6, 8, 10, and 12 using TEMPO and 4-acetamido TEMPO to elucidate the impact of pH and catalyst type on product selectivity and CNC properties (charge, crystallinity, degree of polymerization, and size). Chronoamperometry reveals that in the presence of CNCs, higher pH increases the turnover frequency of TEMPO to TEMPO+. However, bulk electrolysis demonstrates that lower pH increases reaction conversion of alcohols to carboxylic acids. This interesting mismatch between reaction rate and product formation was further investigated using model compounds, such as glucose, to deconvolute the mechanism and improve oxidation efficiency and selectivity for desired products. The presented research supports the opportunity to replace secondary chemical oxidants with electrochemical oxidation.(1) Vanderfleet, O. M.; Cranston, E. D. Production Routes to Tailor the Performance of Cellulose Nanocrystals. Nat. Rev. Mater. 2021, 6 (2), 124–144. https://doi.org/10.1038/s41578-020-00239-y.(2) Antoniw, J. M.; Hallman, M. T.; Kiriakou, M. V.; Morse, T.; Cranston, E. D. Colloidal Stability Window for Carboxylated Cellulose Nanocrystals: Considerations for Handling, Characterization, and Formulation. Langmuir ACS J. Surf. Colloids 2023, 39 (30), 10321–10334. https://doi.org/10.1021/acs.langmuir.3c00319.(3) De Nooy, A. E. J.; Besemer, A. C.; Van Bekkum, H. Highly Selective Tempo Mediated Oxidation of Primary Alcohol Groups in Polysaccharides. Recl. Trav. Chim. Pays-Bas 1994, 113 (3), 165–166. https://doi.org/10.1002/recl.19941130307. Figure 1

Discovery of Sporachelins by Genome Mining of a Micromonospora Strain.

Myxochelins are a group of catecholate siderophores encoded by mxc biosynthetic gene clusters (BGCs). They are mainly produced by myxobacteria and display a wide variety of bioactivities. Herein, we report a group of new myxochelins produced not by a myxobacterial strain but by an actinobacteria strain, Micromonospora sp. TMD166. They consisted of six new compounds, designated as sporachelins A (1), A1 (2), B (3), C (4), D (5), and E (6), and the known compound myxochelin A (7). The planar structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations were confirmed by Marfey's analysis and chemical synthesis. The six sporachelins are the first examples of acylated derivatives at the primary alcohol of myxochelin A. These molecules were found to inhibit human 5-lipoxygenase. In addition, 1-7 exhibited antifibrotic activity in the TGFβ1-induced human hepatic cell line LX-2 by suppressing fibrosis-related genes COL1A1, ACTA2, and TGFB1 expression. This is the first report of antifibrotic activity by myxochelins.

Iron-Catalyzed sp3 C-H Alkylation of Fluorene with Primary and Secondary Alcohols: A Borrowing Hydrogen Approach.

The utilization of earth-abundant, cheap, and nontoxic transition metals in important catalytic transformations is essential for sustainable development, and iron has gained significant attention as the most abundant transition metal. A mixture of FeCl2 (3 mol %), phenanthroline (6 mol %), and KOtBu (0.4 eqivalent) was used as an effective catalyst for the sp3 C-H alkylation of fluorene using alcohol as a nonhazardous alkylating partner, and eco-friendly water was formed as the only byproduct. The substrate scope includes a wide range of substituted fluorenes and substituted benzyl alcohols. The reaction is equally effective with challenging secondary alcohols and unactivated aliphatic alcohols. Selective mono-C9-alkylation of fluorenes with alcohols yielded the corresponding products in good isolated yields. Various postfunctionalizations of C-9 alkylated fluorene products were performed to establish the practical utility of this catalytic alkylation. Control experiments suggested a homogeneous reaction path involving borrowing hydrogen mechanism with the formation and subsequent reduction of 9-alkylidene fluorene intermediate.

Supported Nickel Nanoparticles as Catalyst in Direct sp3 C-H Alkylation of 9H-Fluorene Using Alcohols as Alkylating Agent.

Herein, we report an inexpensive first-row transition metal Ni heterogeneous catalytic system for the Csp3-mono alkylation of fluorene using alcohols as alkylating agents via borrowing hydrogen strategy. The catalytic protocol displayed versatility with high yields of the desired products using various types of primary alcohols, including aryl/hetero aryl methanols, and aliphatic alcohols as alkylating agents. The catalyst Ni NPs@N-C was synthesized via high-temperature pyrolysis strategy, using ZIF-8 as the sacrificial template. The Ni NPs@N-C catalyst was characterized by XPS, HR-TEM, HAADF-STEM, XRD and ICP-MS. The catalyst is stable even in the air at room temperature, displayed excellent activity and could be recycled 5 times without appreciable loss in its activity.

Local structure and mobility in melts of ionic liquids-selected primary and secondary alcohols

We present the results of a systematic study of the influence of isomerism of selected primary and secondary alcohols on their processes of solvation in dimethylimidazolium (dmim+) chloride ionic liquids. The properties of this system are investigated near the melting temperature by means of the molecular dynamics method. The study of single particle tracking (SPT) trajectories plays a significant role in the present analysis of the features of the microscopic movement of molecules of the dissolved substance in the solution. We demonstrate that the isomerism of alcohol molecules in case of isobutanol and isopentanol leads to the increase of their self-diffusion coefficients due to the growth of the IL’s local structure near the solute as we move from the alcohol to its isomer. The motion of butanol/isobutanol and pentanol/isopentanol alcohols molecules in this process is determined both by the mass, and the hydrophobic properties of the solute. Conversely, we demonstrate that the motion of systems with propanol/isopropanol are determined by the structure of the solute.

Efficient Formylation of Alcohols Using a Core-Shell Magnetic Nanocomposite via Vilsmeier-Haack Complex Formation

Introduction: The protection of the hydroxyl group as formamides is a crucial initial step in pharmaceutical synthesis. Methods: In this study, we investigated the O-formylation of alcohols using dimethylfor-mamide (DMF) in a mixture with a new magnetic nanocomposite Fe3O4@Chitosan/POCl2-x. Results: The results demonstrate that this core-shell heterogeneous nanocomposite facili-tates the formation of alkylformate, yielding products with high efficiency ranging from 79% to 96% within a remarkably short reaction time of 1 to 12 hours at room temperature, depending on the substrate structure. Significantly, the presence of this nanocomposite ex-hibits remarkable selectivity, favoring the formylation of less hindered benzylic and ali-phatic primary alcohols. However, bulkier alcohols and phenols exhibit lower reactivity under these conditions and thiols do not react. The simplicity of the work-up procedure, combined with the magnetic recyclability, makes it reusable and environmentally friendly. Conclusion: This study highlights the efficacy of this novel magnetic nanocomposite in facilitating formylation reactions, emphasizing its potential for application in pharmaceu-tical synthesis and bio compounds. This is due to its attributes of non-toxic nature, stabil-ity, and significant advantages over conventional methodologies.

Manganese‐Catalyzed Three‐Component Vinylation of Phosphines with Sulfones and Alcohols

AbstractHerein, we report a manganese‐catalyzed three‐component vinylation strategy for the synthesis of vinylphosphines from readily available alcohols, sulfones, and phosphines via acceptorless dehydrogenative strategy. This multi‐component, four‐stage, one‐pot protocol offers a stereoselective approach, overcoming the challenges associated with achieving these products through the hydrophosphination of terminal alkynes. The reaction utilizes sulfones and common alcohols to access both (E)‐β‐substituted vinylphosphines (using methanol) and α‐substituted vinylphosphines (using primary alcohols) in yields ranging from 52% to 99%, with E:Z stereoselectivity of 95:5 to 99:1. Importantly, the synthesized branched‐substituted vinylphosphines exhibited superior ligand performance in the copper‐catalyzed cross‐coupling of aryl bromides with pyrazole compared to the commercially available PPh3 and diphenyl(vinyl)phosphane.

Iridium‐Pyrazolato Complex Catalyzed Dehydrogenative Alkylation of Ketones and Arylacetonitriles with Primary Alcohols

AbstractHerein, we report the use of an air‐stable iridium pyrazolato complex as an effective catalyst for the α‐alkylation of ketones and arylacetonitriles with primary alcohols, employing borrowing hydrogen strategy. The alkylation reactions were efficiently conducted at 120 °C in toluene utilizing a very low catalyst loading (0.1 mol %). A broad range of ketones and arylacetonitriles, in combination with various aromatic and aliphatic primary alcohols, were successfully transformed into the corresponding α‐alkylated products. Additionally, quinoline derivatives were synthesized from 2‐aminobenzylalcohol and ketones using dehydrogenative coupling strategy. A mechanistic investigation unveiled that the key step involved alcohol activation via metal‐ligand cooperation.

ALKALI ALCOHOLYSIS OF 2-PHENYL-gem-DICHLOROCYCLOPROPANE UNDER MICROWAVE RADIATION CONDITIONS

By alkaline alcoholysis of 2-phenyl-gem-dichlorocyclopropane, α-phenylacrolein acetals were synthesized under microwave irradiation (MWI) conditions: [1-(diethoxymethyl)vinyl]benzene, [1-(di-propyloxymethyl)vinyl]benzene, [1-(di- iso-propyloxymethyl)vinyl]benzene, [1-(dibutoxymethyl)vinyl]benzene, [1-(di-iso-butoxymethyl)-vinyl]benzene, {1-[bis(1-methylbutoxy)methyl]vinyl}benzene, [1-(dially-loxymethyl)vinyl]benzene, 1,1-[(2-phenylprop-1-en-3,3-diyl)bis(oxymethylene)]dibenzene. It was found that microwave radiation reduces the synthesis time by 70%, while the yield is more than 80%, and the selectivity of acetal formation is more than 90%. Using the method of competitive kinetics, it was established that primary alcohols such as ethanol, propanol and butanol are similar in activity. The structures of the obtained compounds were studied using nuclear magnetic resonance (NMR) and chromatography-mass spectrometry methods. The formation of acetals is proven by the presence of signals from the quaternary carbon atom in the region δс 142.35-146.49 ppm, and a doublet signal from protons at δн 5.01–5.71 ppm. and a singlet signal of the proton of the methine group in the region at 4.89-5.50 ppm. Analysis of the mass spectra of acetals showed the presence of maximum intensity of oxonium ions, due to α-, β-break relative to the oxygen atom. For the obtained acetals, the presence in the mass spectra of [M-H]+ cations, formed as a result of the release of a hydrogen radical from a molecular radical ion, was recorded. The peaks of [M-R]+ and [M-H]+ ions were inferior in intensity to [M-RO]+ cations. Most likely, this is explained by the stability of the [M-RO]+ cations relative to [M-C6H5C2H2]+ and [M-H]+, as well as the ease of eliminating RO• from the alkoxy group. In addition, for acetals of this type, the formation of a radical cation with m/z = 132 was observed, resulting from the release of the R radical from the second alkoxy group. Also, the mass spectra of acetals were characterized by the presence of a cation m/z = 77 and an intensity of 29-80%. Borisova Yu.G., Musin A.I., Voinov A.V., Spirikhin L.V., Raskil’dina G.Z., Sultanova R.M., Zlotskii S.S. Alkali alcoholysis of 2-phenyl-gem-dichlorocyclopropane under microwave radiation conditions. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 11. P. 15-21. DOI: 10.6060/ivkkt.20246711.7046.

C‐C Coupling of Methylene Ketones with Alcohols Enabled by Fe‐Catalysis: Access to Substituted Pyrroles and Pharmaceuticals

Herein, we have reported a sustainable and chemo‐selective strategy for the synthesis of functionalized branched alcohols. Commercially available catalytic system does not need any special ligand and liberated water and hydrogen as side product. A series of alkyl primary alcohols (C4‐C10) including methanol were tolerated in good to high yield. Sequential transformations to substituted pyrroles, chromenes and synthesis of donepezil drug were obtained (>57 entries). Preliminary mechanistic investigations were performed to understand the catalytic pathways.

Efficient construction of a quinoline framework from alcohols, nitroarenes, and alkenes promoted by a trimetallic catalyst system

A Pd/Fe/In-trimetallic catalyst system promotes the three-component coupling reaction of primary alcohols, nitroarenes, and terminal alkenes to construct quinoline frameworks in a single operation. These consecutive coupling reactions proceed via an oxidative Povarov reaction of alkenes and aldimines derived from primary alcohols and nitroarenes by a redox hydrogen transfer system. This reaction may contribute to the efficient development of pharmaceuticals and medicinal products.

TEMPO‐Catalyzed Continuous‐Flow Aerobic Oxidations of Alcohols on Silica

Abstract2,2,6,6′‐Tetramethylpiperidine‐N‐oxyl (TEMPO) is a highly efficient oxidation catalyst, valued for its environmentally benign nature, particularly in comparison to transition‐metal catalysts. Despite their merits, TEMPO‐based catalysts are not notably cost‐effective. Immobilization of TEMPO onto supports offers a promising strategy to overcome this limitation. In this work, we present the synthesis and application of immobilized TEMPO catalysts 2–5, prepared via a straightforward condensation reaction, for the aerobic oxidation of alcohols. These catalysts demonstrate remarkable activity for alcohol oxidations under continuous‐flow conditions, employing nitric acid as the co‐catalyst. Notably, catalyst 2 immobilized by COOH silica gel exhibits outstanding performance for the oxidation of benzyl alcohol by oxygen gas, achieving a turnover frequency (TOF) of 15 h−1 and a turnover number (TON) exceeding 300. Catalyst 2 further demonstrates broad substrate scope, effectively oxidizing primary, secondary, and benzylic alcohols. Post‐reaction analysis of spent catalyst 2 reveals that deactivation primarily stems from nitrosation of the N−O bond. Interestingly, the amide moiety remains intact despite the harsh acidic reaction conditions.

Organophotocatalyst Enabled Deoxycyclopropanation of Alcohols.

Cyclopropane fragments, which widely exist in marketed drugs and natural products, can confer special pharmacological properties to small-molecule drugs. Therefore, developing methods to construct cyclopropanes is of great significance. Nevertheless, the introduction of cyclopropane primarily relies on already-formed cyclopropyl groups, which significantly restricts the diversity of cyclopropane skeletons. Late-stage direct cyclopropanation is still a challenging task. Herein, a photo-induced intermolecular deoxycyclopropanation reaction that employs alcohols as substrates, and 1 mol.% of 2,3,5,6-tetrakis(carbazol-9-yl)-1,4-dicyanobenzene (4CzTPN)as organophotocatalyst is reported. This method proceeds with high transformation efficiency (up to 98% yield) and exhibits broad functional group tolerance, such as primary, secondary, and tertiary alcohols as well as various activated β-halogenated alkenes. This process is mild, easy to operate, and has low equipment requirements. The power of this technology is demonstrated by the late-stage functionalization of five marketed drugs and five natural products.

Advancements in Primary Alcohol Oxidation Leading to Carboxylic Acids: A Detailed Review

This review article explores the direct oxidation of primary alcohols into carboxylic acids, highlighting its importance in organic synthesis for producing valuable chemicals in a sustainable and efficient manner. Carboxylic acids are widely employed in a wide range of applications, encompassing food preservatives, insecticides, dye intermediates, coatings, plasticizers, spices, flavors, scents, and a variety of industries such as polymers, solvents, and medications. This review article covers recent advancements in catalytic systems, including catalysts based on transition metals, organocatalysts, nanocatalysts, and electrochemical methods. It examines the impact of reaction conditions such as solvents, temperature, and substrate scope on these processes. The review also delves into mechanistic insights and recent developments in tandem and cascade reactions, aiming to provide a comprehensive understanding of current strategies and future research directions in this field.

Palladium-Catalyzed Ortho Alkoxylation of Oxazoline Derivatives: An Avenue to Reach Meta-Substituted Electron-Rich Arenes Exploiting Oxazoline as a Removeable Directing Group.

An efficient and highly regioselective palladium-catalyzed oxazoline-directed alkoxylation is reported. The reaction proceeds under air and mild temperatures (60 °C). A series of alcohols can be used as alkoxylating agents and concomitantly act as reaction solvents, whereas primary and secondary alcohols are tolerated. Furthermore, fluorinated alcohols can be applied as well, introducing pharmaceutically relevant fluorine-containing groups. 1,3-Dialkoxylated products can be further subjected to hydrolysis transforming the oxazoline-directing group to a carboxylic acid, which can be removed by decarboxylation if desired. This approach demonstrates the capability to reverse the conventional site selectivity of electrophilic aromatic substitution reactions, since it allows the synthesis of arenes with two electron-donating groups in a 1,3-relationship.

A reagent-free, sequence-dependent in situ peptide self-cyclization strategy under physiological condition

Cyclic peptides are an important class of bioactive molecules used as drugs as well as biomolecular probes. Peptide cyclization under the physiological environment, without added chemicals or reagents, would be a highly useful technique for in situ applications. A simple, highly efficient, and green procedure for side-chain to side-chain in situ peptide cyclization is established here at the physiological condition. The methodology further allows the release of small biologically active molecules through peptide self-cyclization. Bioactive molecules, as well as other organic leaving groups (having primary or secondary alcohol as a functional group), were conjugated to a short peptide RXE sequence (X = Pro/Ala/Gly). The peptides were designed to undergo cyclization under physiological conditions and release the covalently attached chemotherapeutic drug and nucleobases, in a controlled manner. In vitro studies were performed in detail, with optimized physiological parameters, to understand the kinetics as well as the mechanism of self-cyclization. The mechanism of action was investigated by HPLC and ESI-Mass spectrometry. The conformational change, due to cyclization of the peptides, was monitored by CD spectroscopy. The present concept of peptide self-cyclization leading to a bond cleavage could be a potential method of delivery of small, bioactive molecules such as chemotherapeutic drugs.

Determination of Chain Transfer Constants of Alcohols for High‐Pressure Polyethylene Polymerization

AbstractIn low‐density polyethylene (LDPE) production, low‐molecular‐weight species are used as chain transfer agents (CTAs). They reduce the degree of polymerization, which has an impact on the polymer properties, such as processability. To specifically adjust the product properties, a detailed understanding of the transfer kinetics to CTAs is indispensable. Thus, the transfer activity of various primary, secondary, and tertiary alcohols as well as diols was investigated experimentally between 120 °C and 250 °C at 2000 bar. The results were evaluated using the Mayo and chain length distribution (CLD) method, and the latter was found to give more reliable results. It was observed that the hydroxy group systematically increases transfer activity compared to alkanes. Additionally, a linear increase of transfer activity with the number of hydrogen atoms is found.

Molecular dynamics investigation of IEPOX chemical behavior at the interface and in the bulk phase of acidic aerosols

Isoprene epoxydiol (IEPOX) is an important reactive gas-phase intermediate produced by the photooxidation of isoprene under low NOx conditions, playing a key role in the formation of secondary organic aerosols (SOA). Previous studies have mostly focused on the liquid-phase reactions of IEPOX within aerosols; however, interfacial heterogeneous chemical reactions are equally important in SOA formation. This study systematically explores the reaction mechanisms of IEPOX at the acidic aerosol interface and in the bulk phase using classical molecular dynamics (MD) and ab initio molecular dynamics simulations (AIMD). The study found that the free energy of IEPOX at the aerosol interface significantly decreases, indicating that interfacial heterogeneous chemical reactions are indispensable for the formation of IEPOX-derived SOA. The research reveals the formation pathways of 2-methyltetrols (2-MTO) and 1,3,4-trihydroxy-3-methylbutan-2-yl sulfates (2-MTOOS), finding that the protonation of the epoxy O atom and the cleavage of the C–O bond are the rate-controlling steps, while the nucleophilic addition is a spontaneous process. Through multiple sets of simulations, it was observed that the formation frequency of 2-MTO at the acidic aerosol interface and in the bulk phase reached 53.8%, significantly higher than the 30.8% of 2-MTOOS, which is consistent with field observation data. Additionally, through metadynamics (MTD) simulations, it was suggested that IEPOX could undergoes acid-catalyzed ring-opening reactions at the interface, potentially followed by the transfer of H atoms from primary alcohols into the aerosol, leading to the possible formation of the intermediate product 3-methylbut-3-ene-1,2,4-triol (one of the proposed structures of C5-alkene triols). These findings provide new insights into the formation mechanism of IEPOX-derived SOA and offer a scientific basis for future studies on their physicochemical properties and atmospheric fate.

An improved synthesis of alkyl AMP esters

Enzymes belonging to the Acyl-CoA/NRPS/Luciferase (ANL) superfamily of enzymes, are significant targets in drug development. One member of this superfamily is Acetyl-CoA Synthetase (ACS). This enzyme is an emerging target for the treatment of various infectious diseases and cancer. Alkyl AMP esters have emerged as potent inhibitors of ACS. Previous methods for synthesizing these esters often involved water-based reactions or necessitate purification through reverse phase prep-HPLC or ion-exchange chromatography. To address these challenges, we developed a new approach utilizing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) to couple 5′-adenylic acid to the corresponding alcohol, utilizing triethylamine as the base. This method yielded primary, secondary, unsaturated, and cyclic alcohols in excellent yields. Importantly, we optimized the reaction conditions to achieve excellent yield and purity without the need for reverse phase prep-HPLC or ion exchange chromatography. Instead, purification was achieved through silica gel chromatography using Biotage ® Sfar spherical silica gel.