Hydrogen bond donor/acceptor mixed-solvent systems for solutes that exhibit strong specific interactions are not readily characterized with methods that depend on solvatochromic parameters. In this work, the reaction of two monomers, 4,4′-oxidianiline (ODA) and pyromellitic dianhydride (PMDA), to form the common engineering plastic precursor, poly(amic acid) (PAA), are studied for the tetrahydrofuran (THF) mixed-solvent systems (THF-methanol, THF-ethanol, THF-water) with spectroscopy. Solute-centric (SC) Kamlet-Taft solvatochromic (K-T) parameters for the solvent environment around the monomer are determined using a proposed model that incorporates spectroscopically determined local composition (XL) around the ODA monomer and the preferential solvation model. For the example reaction to occur under homogeneous conditions, mixed-solvent conditions need have HBA-rich local compositions (0.30 <L XHBAL < 0.83), high solute-centric basicity (βSC > 0.60), high solute-centric polarity, (πSC∗ > 0.63), and low solute-centric acidity (αSC < 0.63). The method developed allows characterization of mixed-solvent effects and can be readily extended to other systems that have strong specific interactions.