A biphasic oxidation of alcohols to aldehydes and ketones using a simplified packed-bed microreactor

Abstract

We demonstrate the preparation and characterization of a simplified packed-bed microreactor using an immobilized TEMPO catalyst shown to oxidize primary and secondary alcohols via the biphasic Anelli-Montanari protocol. Oxidations occurred in high yields with great stability over time. We observed that plugs of aqueous oxidant and organic alcohol entered the reactor as plugs but merged into an emulsion on the packed-bed. The emulsion coalesced into larger plugs upon exiting the reactor, leaving the organic product separate from the aqueous by-products. Furthermore, the microreactor oxidized a wide range of alcohols and remained active in excess of 100 trials without showing any loss of catalytic activity.

Keywords: TEMPO; alcohol oxidation; flow chemistry; heterogeneous catalysis; microreactors.

Scheme 1

Preparation of azide-modified AO resin 2.

Scheme 2

Preparation of AO-TEMPO 6.

Figure 1

The simplified microreactor setup. Empty tubing (A) is packed with functionalized AO resin and attached to caps (B). The packed bed is woven between metal bars (C) and connected to syringe pumps (D).

Figure 2

The organic (colored solution) and aqueous phases (colorless solution) forming plugs at the Y-junction (A). The phases mix upon reaching the packed bed, leading to a coalescence of drops at the outlet of the microchannel (B).

Scheme 3

The AO-TEMPO-catalyzed oxidation of benzyl alcohol.

Figure 3

The long-term activity of AO-TEMPO packed beds in the oxidation of 4-chlorobenzyl alcohol. A solution of 4-chlorobenzyl alcohol (0.2 M in CH₂Cl₂) set to 44 μL min⁻¹ (8.8 μmol min⁻¹, 1.0 equiv min⁻¹) and an aqueous solution consisting of NaOCl (0.25 M), adjusted to pH 9.1 with NaHCO₃, and KBr (0.5 M, 30 µL per mL NaOCl) set to 56 µL min⁻¹ (1.5 equiv NaOCl min⁻¹, 0.10 equiv KBr min⁻¹) were passed through the AO-TEMPO packed bed for 9 h. Fractions were collected and analyzed by GC using an internal standard.