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 [Formula: see text] 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 [Formula: see text] changes in the (ZZ [Formula: see text])NCO- substituents, we measured and modeled the p [Formula: see text] with Z=Z [Formula: see text] =H and Z=Z [Formula: see text] =methyl. The dominant contribution to the observed p [Formula: see text] 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 [Formula: see text] 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.