DFT Study To Explore the Importance of Ring Size and Effect of Solvents on the Keto-Enol Tautomerization Process of α- and β-Cyclodiones.

We have explored the effect of ring size on keto-enol tautomerization of α- and β-cyclodiones using the M062X-SMD(aq)/6-31+G(d,p)//M062X/6-31+G(d,p) level of theory. The calculated results show that the activation free energy barrier for the keto-enol tautomerization process of α-cyclopropanedione (1) is 54.9 kcal/mol, which is lower compared to that of the other cyclic diketo systems studied here. The four-membered α- and β-cyclobutanedione (2 and 6) do not favor keto-enol tautomerization unlike other studied cyclic systems because of the ring strain developed in the transition-state geometries and their corresponding products. Water-assisted keto-enol tautomerization with one molecule reveals that the free energy activation barriers reduce almost half compared to those for the uncatalyzed systems. The two-water-assisted process is favorable as the activation free energy barriers lowered by ∼10 kcal/mol compared to those of the one-water-assisted process. The ion-pair formation seems to govern the lowering of activation barriers of α- and β-cyclodiones with two water molecules during the keto-enol tautomerization process, which however also overcomes the favorable aromatization in the three-membered ring system. The free energy activation barriers calculated with the M062X-SMD(aq)/6-31+G(d,p) level predicted that the keto-enol tautomerization process for the α-cyclodiones follows the following trend: 2 > 3 > 4 > 5 > 1. Water-assisted tautomerization of α-cyclodiones also predicted 1-W and 1-2W as the most favored processes; however, 5-W and 5-2W were found to be disfavored in this case. The β-cyclodione systems also showed similar trends as obtained with α-diketone systems. The influence of bulk solvent on the keto-enol tautomerization process favors the formation of the enol form in a more polar solvent medium even under mixed solvent conditions in acetonitrile and hexane at M062X-SMD(acetonitrile)/6-31+G(d,p) and M062X-SMD(hexane)/6-31+G(d,p) levels of theory.