We were able to tentatively assign the structure of the reaction intermediates by performing column chromatography on incomplete reaction mixtures and analyzing the filtrates collected during reaction workups. Of these, the most notable intermediates are dicarboxyphthalimides 4-X-R and 5-X-R, which correspond to the asymmetric and symmetric possibilities, respectively, for monophthalimide formation between the tetraacids 2-X and an amine. It is again worth noting that during the reaction, however, it is difficult to rule out whether mixed acetic acid anhydride derivatives are the dominant species. Liquid chromatography mass spectrometry analysis of crude reaction mixtures corroborates the 1 H NMR and preparatory observations of 4-X-R and 5-X-R as the primary reaction byproducts, but also reveal one other identifiable product corresponding to a diamidophthalimide species 6-X-R. We believe this isomer is more likely because the analogous diamido derivative of 4-X-R should be more likely to proceed to cyclize into 3-X-R. From a purely statistical perspective, intermediates 4-X-R and 5-X-R should be formed in a 3 to 1 ratio because both the 1-and 2-carboxamide derivatives of 2-X can dehydrate into intermediate 4-X-R, while only the 2-carboxamide can cyclize into intermediate 5-X-R. To add context to our understanding, we performed density functional theory calculations (M062X/6-31G(d)) with implicit acetic acid solvent to evaluate the energy landscape of the reaction for the reaction between methylamine and either 2-H or 2-Cl. In both cases, the formation of the less symmetric 4-X-Me is thermodynamically favorable compared to the formation of 5-X-Me. Interestingly, the transformation of 4-H-Me into 3-H-Me is found to be an uphill process by 3.5 kcal/mol, while the analogous conversion of 4-Cl-Me into 3-Cl-Me costs only 0.3 kcal/mol. Although these calculations do not account for the added complexities of mixed anhydride formation or R group identity, they do correlate with our experimental findings that 3-X-R formation is higher yielding when X = halogen. Taken together, it is reasonable to posit that the statistical advantage of monophthalimide formation balances against substrate-specific energetic differences to influence overall conversion into MDI products.