Real-time reaction monitoring of silylation and acylation of carbohydrates with a conductometry set-up.

The chemical synthesis of carbohydrates requires multiple protecting group manipulations, yet reaction monitoring is still largely relying on offline methods such as TLC, HPLC, or LC-MS. The absence of simple real-time reaction monitoring tools limits reproducibility, scalability, and integration into automated glycan synthesis platforms. Reported herein is the first application of electrical conductometry for monitoring of reactions involving protecting group manipulation with carbohydrates in situ. In particular, silylation and acylation reactions were used as representative cases to demonstrate how well conductivity profiles correlate with reaction progress. It was showcased that plateaus in conductivity profile coincides with complete substrate consumption, whereas variations in electrophiles and bases produced characteristic conductivity signatures. This work establishes conductometry as a low-cost, non-invasive, and accessible process analytical technology for carbohydrate chemistry. Beyond its immediate use in academic laboratories, the method holds promise for integration into automated and continuous-flow systems, ultimately advancing real-time monitoring, intervention, control, reproducibility in glycan synthesis.