Batch and Flow Synthesis of Disulfides by Visible‐Light‐Induced TiO₂ Photocatalysis

Abstract

A mild and practical method for the preparation of disulfides through visible-light-induced photocatalytic aerobic oxidation of thiols has been developed. The method involves the use of TiO2 as a heterogeneous photocatalyst. The catalyst's high stability and recyclability makes this method highly practical. The reaction can be substantially accelerated in a continuous-flow packed-bed reactor, which enables a safe and reliable scale-up of the reaction conditions. The batch and flow protocol described herein can be applied to a diverse set of thiol substrates for the preparation of homo- and hetero-dimerized disulfides. Furthermore, biocompatible reaction conditions (i.e., room temperature, visible light, neutral buffer solution, and no additional base) have been developed, which permits the rapid and chemoselective modification of densely functionalized peptide substrates without recourse to complex purification steps.

Electrochemically Oxidative Coupling of S‐H/S‐H for S‐S Bond Formation: A Facile Approach to Diacid‐disulfides

“…1 a is oxidized at the anode to generate the sulfur radical 4 , which undergoes dimerization to give 2,2′‐disulfanediyldibenzoic acid 2 a ( pathway 1 ). This pathway is similar to that reported by Lei . Another pathway for the oxidation of thiols to disulfides through an intermidate sulfenium ion is also possible in the presence of NaI ( pathway 2 ).…”

Flow Photochemistry: Shine Some Light on Those Tubes!

“…Another interesting example of gas-liquid reaction under segmented Stern-Volmer analysis: while fluorescence-quenching tests are used to determine whether a substrate or reagent is able to quench a photoredox catalysts (i.e., able to be oxidized or reduced), Stern-Volmer measurements provide quantitative information about the quenching. [28,31,33]; (B) tube-in-tube reactor for gas-liquid reactions [38]; (C) falling-film (micro)reactor [41]; (D) packed-bed reactor [47,48]; and (E) segmented flow for solid-liquid reactions [53]. flow conditions is the synthesis of the antimalarial drug artemisinin via photogenerated singlet oxygen oxidation directly from extracts of the plant Artemisia annua, containing both the precursor of this drug [dihydroartemisinic acid (DHAA)] and the chlorophyll photocatalyst, demonstrated by Gilmore [33].…”

“…Whereas packed-beds or similar have been employed in wastewater treatment [45,46], few synthetic photochemical applications have appeared. Interesting examples are the synthesis of artemisinin from DHAA with supercritical CO 2 and O 2 feeds using a packed-bed of a porphyrin catalyst, reported by George, Poliakoff, and Rossen [47], and the TiO 2 -catalyzed synthesis of disulfides under aerobic conditions, reported by Noë l [48]. The TiO 2 was here activated for visiblelight absorption via ligation with TMEDA.…”

A sensitivity analysis of a numbered-up photomicroreactor system

“…We have developed a number of photocatalytic approaches which allow for the mild synthesis of these compounds. 27,28 For this work, we used the photocatalytic oxidation of thiophenol to diphenyl disulfide as a benchmark reaction for the sensitivity analysis (Scheme 1). 27 The reaction utilizes Eosin Y as an inexpensive and metal-free photocatalyst, oxygen gas as the oxidant, N,N,N′,N′-tetramethylethane-1,2-diamine (TMEDA) as the base and ethanol as a cheap and green solvent.…”