{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:45:05Z","timestamp":1768873505574,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["LH2022H094"],"award-info":[{"award-number":["LH2022H094"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aromatic ketones are important pharmaceutical intermediates, especially the pyridin-2-yl-methanone motifs. Thus, synthetic methods for these compounds have gained extensive attention in the last few years. Transition metals catalyze the oxidation of Csp3-H for the synthesis of aromatic ketones, which is arresting. Here, we describe an efficient copper-catalyzed synthesis of pyridin-2-yl-methanones from pyridin-2-yl-methanes through a direct Csp3-H oxidation approach with water under mild conditions. Pyridin-2-yl-methanes with aromatic rings, such as substituted benzene, thiophene, thiazole, pyridine, and triazine, undergo the reaction well to obtain the corresponding products in moderate to good yields. Several controlled experiments are operated for the mechanism exploration, indicating that water participates in the oxidation process, and it is the single oxygen source in this transformation. The current work provides new insights for water-involving oxidation reactions.<\/jats:p>","DOI":"10.3390\/molecules28227587","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T09:46:13Z","timestamp":1699955173000},"page":"7587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oxygen-Free Csp3-H Oxidation of Pyridin-2-yl-methanes to Pyridin-2-yl-methanones with Water by Copper Catalysis"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-1815","authenticated-orcid":false,"given":"Ming","family":"Zeng","sequence":"first","affiliation":[{"name":"School of Pharmacy and Life Science, Jiujiang University, Jiujiang 332005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Le","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Life Science, Jiujiang University, Jiujiang 332005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Jiao","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Life Science, Jiujiang University, Jiujiang 332005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao-Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Dai","sequence":"additional","affiliation":[{"name":"Analytical and Testing Center, Jiujiang University, Jiujiang 332005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deng-Zhao","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Life Science, Jiujiang University, Jiujiang 332005, China"},{"name":"Jiujiang Key Laboratory for the Development and Utilization of Traditional Chinese Medicine Resources in Northwest Jiangxi, Jiujiang 332005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Jing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1021\/ja01191a046","article-title":"Beckmann Rearrangement of the Oximes of Phenyl 2-Pyridyl Ketone (2-Benzoylpyridine)","volume":"70","author":"Huntress","year":"1948","journal-title":"J. Am. Chem. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7436","DOI":"10.1021\/ja061942s","article-title":"Synthesis of Aromatic Ketones by a Transition Metal-Catalyzed Tandem Sequence","volume":"128","author":"Zhao","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1021\/jo0352169","article-title":"Convenient Processes for the Synthesis of Aromatic Ketones from Aryl Bromides and Carboxylic Anhydrides Using a Cobalt Catalysis","volume":"69","author":"Kazmierski","year":"2004","journal-title":"J. Org. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13323","DOI":"10.1039\/D1NJ02508B","article-title":"Facile one-pot synthesis of ketones from primary alcohols under mild conditions","volume":"45","author":"Bui","year":"2021","journal-title":"New. J. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.1039\/D2CS00093H","article-title":"Manganese-catalyzed hydrogenation, dehydrogenation, and hydroelementation reactions","volume":"51","author":"Das","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1021\/cr500610p","article-title":"Transition-Metal-Catalyzed Direct Addition of Unactivated C\u2013H Bonds to Polar Unsaturated Bonds","volume":"115","author":"Yang","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4114","DOI":"10.1002\/anie.200900013","article-title":"Palladium-Catalyzed Carbonylation Reactions of Aryl Halides and Related Compounds","volume":"48","author":"Neumann","year":"2009","journal-title":"Angew. Chem., Int. Ed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4289","DOI":"10.6023\/cjoc202104049","article-title":"Progress in the Synthesis of Aroyl Compounds","volume":"41","author":"Liu","year":"2021","journal-title":"Chin. J. Org. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1039\/c2gc36896j","article-title":"Direct aerobic oxidation of 2-benzylpyridines in a gas\u2013liquid continuous-flow regime using propylene carbonate as a solvent","volume":"15","author":"Pieber","year":"2013","journal-title":"Green Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1002\/ajoc.201800576","article-title":"DMSO-Promoted Metal-Free Aerobic Oxidation of Heterobenzylic Methylene to Prepare N-Heterocyclic Ketones","volume":"7","author":"Zhang","year":"2018","journal-title":"Asian J. Org. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1021\/ol300853z","article-title":"Direct and Selective Benzylic Oxidation of Alkylarenes via C\u2013H Abstraction Using Alkali Metal Bromides","volume":"14","author":"Moriyama","year":"2012","journal-title":"Org. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1021\/jo01092a039","article-title":"Preparation of Substituted Cyclopropanes Containing Aldehyde and Ketone Groups","volume":"24","author":"Warner","year":"1959","journal-title":"J. Org. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1039\/D1OB00081K","article-title":"Recent advances in the copper-catalyzed aerobic Csp3\u2013H oxidation strategy","volume":"19","author":"Kim","year":"2021","journal-title":"Org. Biomol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1039\/C5SC03530A","article-title":"Mechanism of the CuII-catalyzed benzylic oxygenation of (aryl)(heteroaryl)methanes with oxygen","volume":"7","author":"Sterckx","year":"2016","journal-title":"Chem. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/adsc.200600553","article-title":"Iron-Catalyzed Benzylic Oxidation with Aqueous tert-Butyl Hydroperoxide","volume":"349","author":"Nakanishi","year":"2007","journal-title":"Adv. Syn. Catal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1002\/cssc.201300378","article-title":"Manganese-Catalyzed Selective Oxidation of Aliphatic C\u2014H groups and Secondary Alcohols to Ketones with Hydrogen Peroxide","volume":"6","author":"Dong","year":"2013","journal-title":"ChemSusChem"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1007\/s12274-017-1676-2","article-title":"Ag\/C nanoparticles catalysed aerobic oxidation of diaryl and aryl(hetero) methylenes into ketones","volume":"10","author":"Guo","year":"2017","journal-title":"Nano Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16776","DOI":"10.1039\/D0NJ03907A","article-title":"Visible-light-driven photochemical activity of ternary Ag\/AgBr\/TiO2 nanotubes for oxidation C(sp3)\u2013H and C(sp2)\u2013H bonds","volume":"44","author":"Dehghani","year":"2020","journal-title":"New. J. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1016\/j.tetlet.2015.03.115","article-title":"Fe(TAML)Li\/tert-butyl hydroperoxide as a new combination for benzylic C\u2013H oxidation","volume":"56","author":"Napoly","year":"2015","journal-title":"Tetrahedron Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/ejoc.201301035","article-title":"Synthesis of \u03b1-Keto-1,2,3-triazoles Through Copper Iodide Catalyzed Oxygenation","volume":"2014","author":"Nawratil","year":"2014","journal-title":"Eur. J. Org. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/cctc.201200590","article-title":"PNNP-Ligated RuII Complexes as Efficient Catalysts for Mild Benzylic C H Oxidation","volume":"5","author":"Hsu","year":"2013","journal-title":"ChemCatChem"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113428","DOI":"10.1016\/j.mcat.2023.113428","article-title":"A new metal\u2013organic complex with coordination unsaturated Co(II) as high-efficiency heterogeneous catalyst for selective oxidation of alkylbenzenes","volume":"548","author":"Li","year":"2023","journal-title":"Molecular Catal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1039\/C7CC09602J","article-title":"An efficient approach for enhancing the catalytic activity of Ni-MOF-74 via a relay catalyst system for the selective oxidation of benzylic C\u2013H bonds under mild conditions","volume":"54","author":"Guo","year":"2018","journal-title":"Chem. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1002\/anie.201108540","article-title":"Synthesis of Aryl(di)azinyl Ketones through Copper- and Iron-catalyzed Oxidation of the Methylene Group of Aryl(di)azinylmethanes","volume":"51","author":"Maes","year":"2012","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1246\/cl.161074","article-title":"Copper-catalyzed Selective Oxygenation of Methyl and Benzyl Substituents in Pyridine with O2","volume":"46","author":"Abe","year":"2017","journal-title":"Chem. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.3762\/bjoc.12.16","article-title":"Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen","volume":"12","author":"Sterckx","year":"2016","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1039\/C5CC07597A","article-title":"From DNA to catalysis: A thymine-acetate ligated non-heme iron(iii) catalyst for oxidative activation of aliphatic C\u2013H bonds","volume":"52","author":"Repo","year":"2016","journal-title":"Chem. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/anie.201409580","article-title":"Chloroacetate-Promoted Selective Oxidation of Heterobenzylic Methylenes under Copper Catalysis","volume":"54","author":"Liu","year":"2015","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1039\/C6SC03831J","article-title":"Co\/NHPI-mediated aerobic oxygenation of benzylic C\u2013H bonds in pharmaceutically relevant molecules","volume":"8","author":"Hruszkewycz","year":"2017","journal-title":"Chem. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1002\/cctc.201701587","article-title":"Aerobic Oxygenation of Alkylarenes over Ultrafine Transition-Metal-Containing Manganese-Based Oxides","volume":"10","author":"Nakai","year":"2018","journal-title":"ChemCatChem"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1002\/adsc.201700588","article-title":"Copper-Catalyzed Aerobic Oxygenation of Benzylpyridine N-Oxides and Subsequent Post-Functionalization","volume":"359","author":"Sterckx","year":"2017","journal-title":"Adv. Syn. Catal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.catcom.2019.04.022","article-title":"Amphiphilic ligands for Cu-catalyzed aerobic oxidation to synthesize 9-fluorenones in water","volume":"127","author":"Li","year":"2019","journal-title":"Catal. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"117529","DOI":"10.1016\/j.apcata.2020.117529","article-title":"Cu (II) Schiff base complex grafted guar gum: Catalyst for benzophenone derivatives synthesis","volume":"601","author":"Krishna","year":"2020","journal-title":"Appl. Catal. A Gen."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5335","DOI":"10.1021\/jo00018a024","article-title":"Oxidation of diethyl (pyridylmethyl)malonates with manganese(III) acetate, cerium(IV) ammonium nitrate, and iron(III) perchlorate in the presence of alkenes and alkynes","volume":"56","author":"Citterio","year":"1991","journal-title":"J. Org. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1021\/acs.orglett.1c04154","article-title":"Selective Oxidation of Alkylarenes to the Aromatic Ketones or Benzaldehydes with Water","volume":"24","author":"Zhang","year":"2022","journal-title":"Org. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"20065","DOI":"10.1039\/D2NJ04417J","article-title":"Direct \u03b1-methylenation of triazines to terminal olefins with DMA","volume":"46","author":"Zeng","year":"2022","journal-title":"New. J. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1039\/D2OB00582D","article-title":"The copper-catalyzed oxidation of arylmethyl triazines with H2O toward the oxidant-free synthesis of aroyl triazines","volume":"20","author":"Zeng","year":"2022","journal-title":"Org. Biomol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5044","DOI":"10.1021\/ja9006657","article-title":"Mechanistic Study of Copper-Catalyzed Aerobic Oxidative Coupling of Arylboronic Esters and Methanol: Insights into an Organometallic Oxidase Reaction","volume":"131","author":"King","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1021\/ol203442a","article-title":"Cu-Catalyzed Oxidative C(sp2)\u2013H Cycloetherification of o-Arylphenols for the Preparation of Dibenzofurans","volume":"14","author":"Zhao","year":"2012","journal-title":"Org. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00706-005-0425-5","article-title":"Room Temperature Catalytic Aromatization of Hantzsch 1,4-Dihydropyridines by Sodium Nitrite in the Presence of Acidic Silica Gel","volume":"137","author":"Hashemi","year":"2006","journal-title":"Monatshefte f\u00fcr Chemie."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1021\/jo01017a048","article-title":"The Hantzsch Reaction. I. Oxidative Dealkylation of Certain Dihydropyridines","volume":"30","author":"Loev","year":"1965","journal-title":"J. Org. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3850","DOI":"10.1021\/ja00325a024","article-title":"Ferricyanide oxidation of dihydropyridines and analogs","volume":"106","author":"Powell","year":"1984","journal-title":"J. Am. Chem. Soc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1039\/c2gc35950b","article-title":"Laccase-catalyzed oxidation of Hantzsch 1,4-dihydropyridines to pyridines and a new one pot synthesis of pyridines","volume":"14","author":"Conrad","year":"2012","journal-title":"Green Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1039\/b208328k","article-title":"Silica modified sulfuric acid\/NaNO2 as a novel heterogeneous system for the oxidation of 1,4-dihydropyridines under mild conditions","volume":"4","author":"Zolfigol","year":"2002","journal-title":"Green Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"71662","DOI":"10.1039\/C6RA08720E","article-title":"New page to access pyridine derivatives: Synthesis from N-propargylamines","volume":"6","author":"Vessally","year":"2016","journal-title":"RSC Adv."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8225","DOI":"10.1039\/C6NJ01620K","article-title":"Ruthenium-catalyzed synthesis of tri-substituted 1,3,5-triazines from alcohols and biguanides","volume":"40","author":"Zeng","year":"2016","journal-title":"New. J. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6140","DOI":"10.1039\/C8OB01397G","article-title":"Ruthenium-catalyzed synthesis of arylethyl 1,3,5-triazines from arylallyl alcohols and biguanides","volume":"16","author":"Zeng","year":"2018","journal-title":"Org. Biomol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11905","DOI":"10.1039\/C8NJ02035C","article-title":"Ruthenium-catalyzed synthesis of 1,3,5-triazin-2(1H)-ones and dihydro[1,3,5]triazino[1,2-a]benzimidazoles from alcohols and guanides","volume":"42","author":"Zeng","year":"2018","journal-title":"New. J. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1021\/j100674a021","article-title":"Kinetics of copper(II)- and copper(I)-catalyzed deuterium exchange in sulfuric and perchloric acid solutions","volume":"75","author":"Peters","year":"1971","journal-title":"J. Phys. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1021\/om500003d","article-title":"Isolation and characterization of a trinuclear cobalt complex containing trigonal-prismatic cobalt in secondary alcohol aerobic oxidation","volume":"33","author":"Karthikeyan","year":"2014","journal-title":"Organometallics"},{"key":"ref_51","unstructured":"Mikami, S., Nakamura, S., Ashizawa, T., Sasaki, S., Taniguchi, T., Nomura, I., and Kawasaki, M. (2013). Preparation of 2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide Derivatives as PDE2A Inhibitors. (WO2013161913 A1)."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1021\/acs.orglett.7b00691","article-title":"Bifunctional Oxo-Tethered Ruthenium Complex Catalyzed Asymmetric Transfer Hydrogenation of Aryl N-Heteroaryl Ketones","volume":"19","author":"Wang","year":"2017","journal-title":"Org. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1039\/D1OB00288K","article-title":"Continuous flow as an enabling technology: A fast and versatile entry to functionalized glyoxal derivatives","volume":"19","author":"Lima","year":"2021","journal-title":"Org. Biomol. Chem."},{"key":"ref_54","first-page":"587","article-title":"Synthesis, Characterization and Fluorescence of a New \u03b2-Diketone Ligand and Its Europium(III) Complexes","volume":"27","author":"Dou","year":"2009","journal-title":"Zhongguo Xitu Xuebao"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19415","DOI":"10.1021\/jacs.9b10364","article-title":"Asymmetric Hydroboration of Heteroaryl Ketones by Aluminum Catalysis","volume":"141","author":"Lebedev","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1021\/jo00243a029","article-title":"Synthesis of (trimethylsilyl)thiazoles and reactions with carbonyl compounds. Selectivity aspects and synthetic utility","volume":"53","author":"Dondoni","year":"1988","journal-title":"J. Org. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/22\/7587\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:22:46Z","timestamp":1760131366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/22\/7587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,14]]},"references-count":56,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["molecules28227587"],"URL":"https:\/\/doi.org\/10.3390\/molecules28227587","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,14]]}}}