Our research builds on this body of research and improves previous characterization of the RNCO + H 2 O reactions in four important ways. First, we thoroughly consider the H 2 O reaction across the isocyanate C --O bond which is often ignored and assumed to be high enough in energy to be unimportant. Even if that is generally the case, it would be helpful to test this assumption for many substituents and understand what conditions might result in exceptions. It is a possibility that imidic acid formation could be favored over carbamate depending on the energetic barriers of each process. Second, our work rigorously characterizes the energetic landscape of the parent HNCO + H 2 O reaction and uses these results to benchmark the levels of theory used to analyze the substituent trends. Previous studies used differing theoretical methods, making it difficult to compare results across the literature and determine consistent trends. Our reliable ab initio results will lay a firm and consistent foundation for any future work on isocyanate alcoholysis reactions. Third, we systematically study how substituents influence the electronic structure of important cooperative catalytic pathways (i.e. multiple water or RNCO molecules) that previous research has suggested as very important for these systems. Finally, our sophisticated ab initio predictions are analyzed with Natural Bond Order analyses to provide detailed understanding of the electronic structure manifest in each process in order to characterize relationships that could generalize to larger or more complex isocyanate reactions. subset of the aforementioned substituents. The influence of these substituents on their efficiency is systematically studied for the first time. Our work should motivate and ground future study of these systems and, our findings can be extended in conjunction with other advanced analyses (e.g. kinetic models, solvent effects, etc.).