Abstract
<jats:p>Vibrational strong coupling (VSC) brings together a fascinating combination of cavity quantum electrodynamics and chemistry. The formation of hybrid light-matter states under VSC affects the outcomes of chemical reactions. However, the role of solvent VSC in controlling ground-state chemical reactions remains unexplored beyond cooperative strong coupling. In this work, we assess the role of solvent VSC in an industrially relevant imine-forming condensation reaction between aniline and p-anisaldehyde in a non-aqueous medium. We employ post-VSC NMR spectral analysis to determine the impact of VSC, rather than using the typical optical spectroscopic readouts, to be free of any unwanted effects the cavity and its mirrors can have on the optical readouts. We show that the VSC of the stretching vibrational mode of C2H5OH(D) suppresses imine formation by ca. 62%. By comparing imine formation under VSC of the -OH and -OD stretching modes, we establish the role of solvent VSC in altering chemical reactions. Surprisingly, the suppression of the reactivity nearly vanishes when the reactant vibrational modes and the -OD stretching mode of C2H5OD are simultaneously strongly coupled to two different cavity modes, revealing the complexities of reactive landscapes under VSC. Our approach of using post-VSC NMR spectroscopy as the observable makes the QED-Chemistry reaction analysis direct and readily available to chemists. Thus, VSC can be developed as a regular physical tool in synthetic chemistry labs and industries to tune reactivity by targeting vibrational modes.</jats:p>