Microfluidic Synthesis of tert-Butyl Peresters via KI-Catalyzed Oxidative Coupling of Methyl Arenes and tert-Butyl Hydroperoxide

Abstract

A green and efficient organic–aqueous two-phase reaction route for the synthesis of tert-butyl peresters by KI-catalyzed C–H oxidation of methyl arenes in a microfluidic chip reactor has been developed. Moreover, a series of tert-butyl perester products were obtained in moderate to good yields under metal-free conditions. A scale-up continuous flow system was constructed to verify the application of this method.

The Chemistry of Peresters

“…One of the most convenient ways of accessing tertiary peresters is through the oxidation of C‐H bonds in the presence of a tertiary hydroperoxide, most commonly TBHP. Oxidation of reactive carbon bonds (whether by preactivation with a heteroatom of as a H) with excess tert ‐butyl hydroperoxide (TBHP) in the presence of n‐ Bu 4 NI (TBAI) offers a convenient synthesis of tert ‐butyl peresters where starting materials have included aldehydes alcohols, benzylic chlorides, dicarbonyl compounds or hydroxycarbonyls and even benzylic methyl groups; these processes have also been conducted in the presence of a copper catalyst . Benzylic nitriles are converted to tert ‐butyl peresters by room temperature reaction with Cu(II) and TBHP, presumably via a series of steps involving α‐peroxynitriles and acyl cyanides .…”

“…TBHP within a heated coil (40 °C) transit times are on the order of 60 sec vs. 24 h for batch chemistry. Reactions were performed on up to 10 mmol of substrate . Three classes of microreactors (orifice with titanium plates, split and recombine in which reaction channels are divided and then recombined, and capillary tube with mixing provided by ultrasonication) were recently compared for production of tert ‐butyl peroxyesters , .…”