Design and application of a modular and scalable electrochemical flow microreactor

Electrochemistry constitutes a mild, green and versatile activation method of organic molecules. Despite these innate advantages, its widespread use in organic chemistry has been hampered due to technical limitations, such as mass and heat transfer limitations which restraints the scalability of electrochemical methods. Herein, we describe an undivided-cell electrochemical flow reactor with a flexible reactor volume. This enables its use in two different modes, which are highly relevant for flow chemistry applications, including a serial (volume ranging from 88 μL/channel up to 704 μL) or a parallel mode (numbering-up). The electrochemical flow reactor was subsequently assessed in two synthetic transformations, which confirms its versatility and scale-up potential. Electronic supplementary material The online version of this article (10.1007/s41981-018-0024-3) contains supplementary material, which is available to authorized users.


General information
All reagents and solvents were used as received without further purification, unless stated otherwise. Reagents and solvents were bought from Sigma Aldrich and TCI and if applicable, kept under argon atmosphere. Technical solvents were bought from VWR International and Biosolve, and are used as received. All capillary tubing and microfluidic fittings were purchased from IDEX Health & Science. Disposable syringes were from BD Discardit II® or NORM-JECT®, purchased from VWR Scientific. Syringe pumps were purchased from Chemix Inc. model Fusion 200 Touch. Product isolation was performed manually, using silica (60, F254, Merck™) or automatically by a Biotage® Isolera Four, with Biotage® SNAP KP-Sil 10 or 25 g flash chromatography cartridges. The temperature of the system was detected with a Voltcraft K204 thermomether, equipped with a 0.25 mm thick thermocouple. TLC analysis was performed using Silica on aluminum foils TLC plates (F254, Supelco Sigma-Aldrich™) with visualization under ultraviolet light (254 nm and 365 nm) or appropriate TLC staining. 1 H (400MHz) and 13 C (100MHz) spectra were recorded on ambient temperature using a Bruker-Avance 400 or Mercury 400. 1 H NMR spectra are reported in parts per million (ppm) downfield relative to CDCl3 (7.26 ppm) and all 13 C NMR spectra are reported in ppm relative to CDCl3 (77.2 ppm) unless stated otherwise. NMR spectra uses the following abbreviations to describe the multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, h = hextet, hept = heptet, m = multiplet, dd = double doublet, td = triple doublet. NMR data was processed using the MestReNova 9.0.1 software package. Known products were characterized by comparing to the corresponding 1 H NMR and 13 C NMR from literature. GC analyses were performed on a GC-MS combination (Shimadzu GC-2010 Plus coupled to a Mass Spectrometer; Shimadzu GCMS-QP 2010 Ultra) with an auto sampler unit (AOC-20i, Shimadzu). Melting points were determined with a Buchi B-540 capillary melting point apparatus in open capillaries and are uncorrected. The names of all products were generated using the PerkinElmer ChemBioDraw Ultra v.12.0.2 software package.
For all electrochemical reactions, the newly designed flow cell was used, together with a Velleman LABPS3005D power supply that is connected to the flow cell. The cell consists of a working electrode and a counter electrode, both made of stainless steel, with a PTFE (Polytetrafluoroethylene) gasket containing micro-channels in between. Depending on whether a 0.25 mm or 0.5 mm thick gasket is used, the active reactor volume is either 700μL or 1300μL. This results in an undivided electrochemical cell. In the cell, direct contact between the electrode surface and the reaction mixture is established. The reaction mixture is pumped through the system via syringe pump, and is collected in a glass vial. Both electrodes can be set to be the anode or the cathode at any time.
All the technical data of the electrochemical setup are reported in the second file of the Supporting Information.

Preparative scale
The sulfide was dissolved in the corresponding amount of stock solution (

Sulfide oxidation
Assuming a complete anodic oxidation for the sulfoxide (2 eper mole of substrate) and sulfone (4 e -