Understanding the Exceptional Properties of Nitroacetamides in Water: A Computational Model Including the Solvent.

Proton transfer in water involving C⁻H bonds is a challenge and nitro compounds have been studied for many years as good examples. The effect of substituents on acidity of protons geminal to the nitro group is exploited here with new p K a measurements and electronic structure models, the latter including explicit water environment. Substituents with the amide moiety display an exceptional combination of acidity and solubility in water. In order to find a rationale for the unexpected p K a changes in the (ZZ ' )NCO- substituents, we measured and modeled the p K a with Z=Z ' =H and Z=Z ' =methyl. The dominant contribution to the observed p K a can be understood with advanced computational experiments, where the geminal proton is smoothly moved to the solvent bath. These models, mostly based on density-functional theory (DFT), include the explicit solvent (water) and statistical thermal fluctuations. As a first approximation, the change of p K a can be correlated with the average energy difference between the two tautomeric forms (aci and nitro, respectively). The contribution of the solvent molecules interacting with the solute to the proton transfer mechanism is made evident.