Self-Optimization of Continuous Flow Electrochemical Synthesis Using Fourier Transform Infrared Spectroscopy and Gas Chromatography.

A continuous-flow electrochemical synthesis platform has been developed to enable self-optimization of reaction conditions of organic electrochemical reactions using attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) and gas chromatography (GC) as online real-time monitoring techniques. We have overcome the challenges in using ATR FT-IR as the downstream analytical methods imposed when a large amount of hydrogen gas is produced from the counter electrode by designing two types of gas-liquid separators (GLS) for analysis of the product mixture flowing from the electrochemical reactor. In particular, we report an integrated GLS with an ATR FT-IR probe at the reactor outlet to give a facile and low-cost solution to determining the concentrations of products in gas-liquid two-phase flow. This approach provides a reliable method for quantifying low-volatile analytes, which can be problematic to be monitored by GC. Two electrochemical reactions the methoxylation of 1-formylpyrrolidine and the oxidation of 3-bromobenzyl alcohol were investigated to demonstrate that the optimal conditions can be located within the pre-defined multi-dimensional reaction parameter spaces without intervention of the operator by using the stable noisy optimization by branch and FIT (SNOBFIT) algorithm.