Palladium Catalyzes The Hydroxylation Reaction Of Electrochemical Oxidation Of Aromatic Hydrocarbons

Benzoxazinone derivatives,as important nitrogen-containing heterocyclic compounds,have anti-cardiovascular disease and anti-cancer activities,and are widely used in the field of drug.Phenol hydroxyl group is an important functional group existed in bioactive molecules,natural products and drugs,most of them have anti-tumor and anti-cancer properties.Benzoxazinones containing phenolic hydroxyl groups have the potential to be important intermediates for drugs or medicines,so the synthesis of such compounds by direct hydroxylation has important theoretical and applied research significance.First,a synthetic route of 2-arylbenzoxazinone and its derivatives was designed:salicylic acid compounds were used as starting materials to synthesize salicylamide compounds through esterification and aminolysis in two steps,and then esterify with arylformyl chloride to synthesize 2-carbamoylaryl aryl carboxylate compounds.Finally,2-arylbenzoxazinone compounds were obtained in 81-94%yield through dehydration cyclization reaction.Then,using 2-arylbenzoxazinone compounds as substrates,a palladium-catalyzed electrochemical oxidation hydroxylation reaction scheme was developed.The reaction conditions were screened including the catalysts,electrolytes,currents,solvents and temperatures.The best reaction conditions were:using 10 mol%Pd?OAc?₂ as the catalyst,1.0 equiv.of Oxone as the hydroxylation agent,1.0 equiv.of n-Bu₄NPF₆ as electrolyte in CH₃CN under constant-current electrolysis conditions at 6 m A at 50°C.27 hydroxylation products were synthesized using the optimal reaction conditions.The structure of the compounds were characterized by melting point,high resolution mass spectrometry,elemental analysis,¹H-NMR,¹³C-NMR,ultraviolet spectroscopy,infrared spectroscopy and X-single crystal diffraction.Finally,a gram-scale experiment was performed on 2-?2-hydroxy?phenylbenzoxazinone and the drug deferasirox was further synthesized in high yield,which proved the practicability of the hydroxylation reaction.Based on the research of control experiment,cyclic voltammetry curve and kinetic isotope experiment,a reasonable reaction mechanism was proposed.