Thin Layer Chromatography‐Freeze Surface‐Enhanced Raman Spectroscopy: A Powerful Tool for Monitoring Synthetic Reactions

Abstract Thin layer chromatography (TLC) is widely used to confirm the formation of the target compound in chemical synthesis. The key issue in TLC is spot identification as it primarily relies on retention factors. Coupling of TLC with surface‐enhanced Raman spectroscopy (SERS), which gives direct molecular information, is an appropriate choice, to overcome this challenge. However, interference from the stationary phase and impurities on the nanoparticles added for SERS measurements significantly degrades TLC‐SERS efficiency. It was found that freezing effectively eliminates such interferences and dramatically improves the performance of TLC‐SERS. In this study, TLC‐freeze SERS is applied to the monitoring of four chemically important reactions. The proposed method can identify the product and side‐products of similar structures, detect compounds with high sensitivity, and provide information of quantities that allows the reliable determination of the reaction time based on kinetic analysis.