Clustering Modulates Reaction Mechanisms: A Case Study on Ester C-O Bond Cleavage

There exist two pathways in the cleavage of ester bonds, R-(O═)C-O-C-R', which are central to polyester recycling and organic synthesis. Traditional views emphasize electronic effects, where the more positively charged carbon is considered the preferred site for nucleophilic attack, resulting in the breaking of C_acyl-O bond. However, halide based ionic liquids were found to selectively cleave the C_alkoxy-O bond of polyesters, a finding that cannot be rationalized by charge considerations alone. In this work, we propose that it is the presence of clusters in solutions that leverages the accessibility of reactants and thus determines the reaction pathways. The idea has been demonstrated in the study of a model binary system of methyl benzoate (MB) and 1-butyl-3-methylimidazolium bromide ([BMIm]Br) using excess infrared spectroscopy, molecular dynamics simulations, and density functional theory calculations. Excess infrared spectroscopy reveals seven distinct aggregate species in solution, including ionic liquid-ester clusters and MB self-aggregates, providing direct experimental evidence that the solution is microheterogeneous and that cluster formation dictates the local reaction environment. In the catalytically relevant cluster, [BMIm]Br(MB)₃, DFT optimized geometries show that the Br^-···C_alkoxy distance (3.56 Å) is significantly shorter than the Br^-···C_acyl distance (5.53 Å). Molecular dynamics simulations confirm the preferential solvation of C_alkoxy around Br^-. A potential energy surface scan with respect to the Br^-···C distance identifies a critical distance of approximately 3.5 Å where the alkoxy C-O bond begins to deviate from equilibrium, marking the incipient stage of partial bonding. At 2.34 Å, the C_alkoxy-O bond undergoes abrupt elongation, corresponding to an energy maximum, showing a pattern of the transition state in classic S_N2 reactions. These findings establish the proximity effect, through cluster mediated spatial preorganization, as the governing principle of C-O bond cleavage selectivity in ionic liquid-ester systems.