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

Abstract

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.

Diketo–Ketoenol Tautomers in Curcuminoids: Synthesis, Separation of Tautomers, and Kinetic and Structural Studies

“…Second, the tautomer exchange slowed down in the presence of water. This clearly contradicts the previously suggested transition-state structures for the tautomerization that involved several water molecules. − Third, the equilibration rate is very sensitive to the amount of water and trace impurities. It would be very difficult to guarantee the same content of water and trace impurities throughout this study.…”

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

“…Unlike cyclic 1,3-dicarbonyls, the acyclic 1,3-dicarbonyls possess intramolecular hydrogen bonding and are in rapid equilibrium with their keto-form. In polar solvents, the stability of the enol form is further decreased and, therefore, the keto-enol equilibrium lies more towards the keto-form [42][43][44][45]. Presumably for this reason, the acyclic 1,3dicarbonyls did not react in the desired way under our experimental conditions.…”

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

“…Unlike cyclic 1,3-dicarbonyls, the acyclic 1,3-dicarbonyls possess intramolecular hydrogen bonding and are in rapid equilibrium with their keto-form. In polar solvents, the stability of the enol form is further decreased and, therefore, the keto-enol equilibrium lies more towards the keto-form [ 53 – 56 ]. Presumably for this reason, the acyclic 1,3-dicarbonyls did not react in the desired way under our experimental conditions.…”