Kinetic Analysis of Electrochemical Lactonization of Ketones Using Water As the Oxygen Atom Source

Abstract

Lactones serve as key synthetic intermediates for the large-scale production of several important chemicals, such as polymers, pharmaceuticals, and scents. Current thermochemical methods for the formation of some lactones rely on molecular oxidants, which yield stoichiometric side products that result in a poor atom economy and impose safety hazards when in contact with organic substrates and solvents. Electrochemical synthesis can alleviate these concerns by exploiting an applied potential to enable the possibility of a clean and safe route for lactonization. In this study, we investigated the mechanism of electrochemical lactone formation from cyclic ketones. When using a platinum anode and cathode in acetonitrile with 10 M H2O and 400 mM cyclohexanone, we found that non-Baeyer-Villiger products, δ-hexanolactone and ɣ-caprolactone, are formed with a total Faradaic efficiency of ~20%. Isotope labeling experiments support that water is the oxygen atom source for this reaction. In addition, electrochemical kinetic data suggest a 1st order dependence on water at low water concentrations (<2 M H2O) and a 0th order dependence on the substrate, cyclohexanone. A Tafel slope of 139 mV/decade was measured at 400 mM cyclohexanone and 10 M H2O, implying an initial electron transfer as the rate determining step. Literature proposed mechanisms for similar transformations suggest an outer sphere pathway. However, based on the collected electrochemical kinetic data, we propose the possibility that Pt reacts with water in an initial electron transfer that forms Pt-OH, which can subsequently react with the ketone substrate. A subsequent electron transfer forms a ring opened carboxylic acid cation that can reclose to form either of the observed five- or six-member ring lactone products.

Accounting for species’ thermodynamic activities changes mechanistic interpretations of electrochemical kinetic data

“…In order to clearly illustrate the importance of the activity correction in a nonideal electrolyte mixture, we studied the water dependence in a blended electrolyte of one of the simplest, most well-studied electrocatalytic reactions: the hydrogen evolution reaction (HER). HER represents the cathodic half-reaction in oxidative electro-organic transformations such as oxygen-atom transfer chemistries 9,10 and is a foundational chemistry to understand in any solvent system under consideration for practical deployment. We elected to characterize HER on a Au rotating disk electrode (RDE) cathode using an electrolyte consisting of acetonitrile, water, 0.778 M TBABF4, and 0.022 M tetrabutylammonium hydroxide (TBAOH).…”

“…For example, some O-atom transfer (OAT) reactions require contacting waterthe O-atom sourcewith organic substrates, which are often relatively water-insoluble hydrocarbons. 9,10 An organic solvent is often used to bring these species into contact with one another in a single phase as an alternative to approaches involving two-phase [11][12][13] or segmented flow 14 setups. Acetonitrile is an example of such a solvent, often chosen due to its relative oxidative stability in the absence of a co-solvent.…”

“…51 In addition, research efforts utilizing water as an O-atom source have also historically been conducted in blended electrolytes. While some of these works included explicit measurements of the dependence of reaction rate on water concentration, 9,10,52 no extensive treatment has been given in any of these works to the nonidealities of the electrolyte mixture.…”

Biosynthesis of Lactones From Diols Mediated by an Artificial Flavin

“…1), due to their excellent physical and biological properties (Schulz et al 2015; Kim et al 2021). Over the past few years, various chemical methods for the production of lactones have been extensively studied, such as esteri cation of hydroxycarboxylic acid (Kauloorkar et al 2016), lactonization of hydroxy ester under acidic or basic conditions (Marco et al 2007), lactonization of cyclic ketones by Baeyer-Villiger reaction (Maalouf et al 2020) and iodolactonization of enoic acid (Nolsøe et al 2014). However, most of them suffer from disadvantages such as high temperature and pressure, strong acids or bases, rare metal catalysts and stoichiometric amounts of oxidizing agents (Sartori et al 2021).…”

Biosynthesis of lactones from diols mediated by an artificial flavin

“…1), due to their excellent physical and biological properties (Delgove et al 2018;Schulz and Hotling 2015;Kim et al 2021). Over the past few years, various chemical methods for the production of lactones have been extensively studied, such as esterification of hydroxycarboxylic acid (Kauloorkar and Kumar 2016), lactonization of hydroxy ester under acidic or basic conditions (Marco et al 2007), lactonization of cyclic ketones by Baeyer-Villiger reaction (Maalouf et al 2020) and iodolactonization of enoic acid (Nolsøe and Hansen 2014). However, most of them suffer from disadvantages, such as high temperature and pressure, strong acids or bases, rare metal catalysts and stoichiometric amounts of oxidizing agents (Sartori et al 2021).…”