Metal‐Free Photocatalytic Aerobic Oxidation of Thiols to Disulfides in Batch and Continuous‐Flow

Abstract

Disulfides represent significant molecular and structural features in various biologically active compounds and fine chemicals. Therefore, the development of mild, efficient and sustainable methods to access disulfides is of great importance. Here, we describe the development of a mild metal‐free photocatalytic aerobic oxidation of thiols to disulfides using Eosin Y and visible‐light irradiation. A continuous flow procedure was developed to accelerate the photocatalytic process, enabling the preparation of disulfides with high purity in a timeframe of minutes. The mildness and applicability of our method was exemplified by the flow synthesis of the cyclic peptide hormone, oxytocin, requiring only a 200 s reaction time and an efficient one‐pot batch protocol for the preparation of the therapeutic thiuram disulfide, disulfiram.magnified image

Liquid phase oxidation chemistry in continuous-flow microreactors

“…The liquid phase contained substrate (0.5 M) and photosensitizer 2-tert-butylanthraquinone (10 mol %) in toluene. A yield of 48% was obtained for the photooxidation of 196 With Eosin Y (1 mol %) as metalfree photosensitizer and a 24W compact fluorescent light bulb they were able to obtain quantitative yield of disulfides for a variety of (hetero)aromatic and aliphatic thiols in an open flask procedure. It was observed that the mixing rate greatly influenced the rate of oxidation.…”

Metal-Free, Visible Light-Promoted Aerobic Aldehydes Oxidation

“…However, such direct photooxidation could only be observed using UV light due to the inability of aldehyde to absorb visible light. Visible-light photochemistry and, in particular, visiblelight photochemistry in flow offer unique opportunities to perform photochemical process [19][20][21][22]. Among these processes, photochemically generated singlet oxygen, 1 O 2 , can provide a clean and sustainable route to photo-oxidized compounds with high atom efficiency.…”

Accelerated gas-liquid visible light photoredox catalysis with continuous-flow photochemical microreactors

“…The reactor assembly is next demonstrated in the photocatalytic trifluoromethylation of heterocycles [14][15] and thiols 16 using cheap CF 3 I gas, and in the photocatalytic aerobic oxidation of thiols to prepare disulfides using oxygen gas ( Figure 2) [17][18] . The protocols provide a safe, reproducible and scalable alternative for the traditional batch scale methods.…”