A Constant-Current Electrochemical Microreactor-Mass Spectrometry Platform: In Situ Intermediate Capture and Reaction Prediction for C−N Coupling

Abstract Industrial-scale organic electrosynthesis predominantly employs galvanostatic (constant-current) electrolysis, yet electrochemistry−mass spectrometry (EC−MS) methods for mechanistic studies have been developed almost exclusively under potentiostatic (constant-potential) conditions. Here, we report a robust constant-current electrochemical microreactor-mass spectrometry (CCEM-MS) platform that bridges this methodological gap, enabling real-time mechanistic investigation under galvanostatic conditions directly relevant to industrial practice. We demonstrate its utility across three mechanistically distinct C−N bond-forming electrosynthetic reactions, unambiguously detecting and structurally assigning key reactive intermediates: (i) pyridine radical cations and aryl pyridinium ions from the anodic coupling of electron-rich arenes with pyridine; (ii) carbon-centered neutral radicals and carbocations from non-Kolbe electrolysis; and (iii) nitrogen-centered radical cations from cross-coupling reactions that furnish triarylamine derivatives. These experimentally validated mechanistic insights directly informed the predictive design and experimental realization of two new electrosynthetic methodologies: (a) anodic generation of previously unreported heterocyclic pyridinium ions and (b) oxidative assembly of acridine-based triarylamines.