A Car–Parrinello Molecular Dynamics Simulation Study of the Retro Diels–Alder Reaction for Partially Saturated 2-Pyrones in Water

Abstract

2-Pyrones have been identified as potential platform molecules derived from biomass to produce high-value chemicals. Theoretical studies utilizing density functional theory (DFT) simulations have shown the partially saturated form of these molecules undergoing a retro Diels−Alder (rDA) reaction in both vapor and solvent conditions. Developing an understanding of the effect of solvent media is crucial to improve the processing of these biomass-derived compounds. In this context, DFT simulations had shown limited access due to either implicit solvent or static explicit solvent environment applied in the model, which did not account for the contribution from the dynamics. Herein, Car−Parrinello molecular dynamics (CPMD) simulations, in conjunction with metadynamics, were performed to understand the effect of dynamics of the solvent on the rDA reaction of partially saturated 2-pyrones. For this, compounds containing both electron-donating and -withdrawing groups as substituent were studied. It was observed that, in the vapor phase, the results from CPMD simulations were in agreement with our previous DFT results. However, in water, a relative lowering in calculated activation barriers (by ∼10 kJ/mol) was observed, due to the dynamic behavior of solvent, differentially interacting with the reactant and the activated complex, along the minimum energy path. For hydroxyl substituted 2-pyrones, computed activation free energy of 63 ± 7 kJ/mol was in agreement with the apparent activation energy measured experimentally (42 ± 18 kJ/mol). CPMD-metadynamics simulations were further applied to study the reaction energetics of complex 2-pyrone molecule undergoing a similar rDA reaction.

Mechanistic Approaches toward Rational Design of a Heterogeneous Catalyst for Ring-Opening and Deoxygenation of Biomass-Derived Cyclic Compounds

“…Polar solvents were observed to preferentially to reduce the activation barrier as compared to the nonpolar solvents due to the relative stabilization of the polarized transition state . Further, in order to account for the effect of solvent dynamics on the reaction kinetics of rDA reaction of partially substituted 2-pyrones, Car–Parrinello Molecular Dynamics (CPMD) simulations were employed . A relative lowering in the activation barrier was observed due to the dynamic behavior of the solvent, which was differentially interacting with the reactant and the activated complex .…”

“…Further, in order to account for the effect of solvent dynamics on the reaction kinetics of rDA reaction of partially substituted 2-pyrones, Car–Parrinello Molecular Dynamics (CPMD) simulations were employed . A relative lowering in the activation barrier was observed due to the dynamic behavior of the solvent, which was differentially interacting with the reactant and the activated complex . These mechanistic insights are suggested to provide a unique opportunity to engineer the biocatalytic part so as to synthesize the 2-pyrone molecule as a precursor with different substituents, and to target the synthesis of the valuable chemical as shown in Figure . , …”

“…54 A relative lowering in the activation barrier was observed due to the dynamic behavior of the solvent, which was differentially interacting with the reactant and the activated complex. 54 These mechanistic insights are suggested to provide a unique opportunity to engineer the biocatalytic part so as to synthesize the 2-pyrone molecule as a precursor with different substituents, and to target the synthesis of the valuable chemical as shown in Figure 2. 28,51 Similar to TAL, 6-amyl-α-pyrone (6PP) 47,55 is another 2pyrone molecule which is derived directly from the solid state fermentation of biomass and was demonstrated as a potential platform molecule (Figure 2(d)).…”

Closer Look at Inverse Electron Demand Diels–Alder and Nucleophilic Addition Reactions on s-Tetrazines Using Enhanced Sampling Methods

“…For the unusual regio-and stereo-selectivity of DA reactions, selected works related to the inverse DA reaction are mentioned in the following. Shrivastav et al studied the reaction energetics and kinetics of 2-pyrone complex undergoing the retro DA reaction [23]. They also calculated the free energy surface (FES) of the DA reaction using Car-Parrinello molecular dynamics with MetaD to obtain the Gibbs activation energy.…”

On the Role of Hydrogen Bond Strength and Charge Transfer of a Diels-Alder Reaction On-Water: Semiempirical and Free Energy Calculations.

“…A lowering of the free energy barrier has been reported for a solvated retro-Diels-Alder reaction using 50 water molecules (in-water) in comparison to the vapor phase reaction. The authors used Car-Parrinello molecular dynamics 15 and concluded that water solvent is pivotal to this 1a; R=O, Hydrogen-bond-"on" 1b; R=S, Hydrogen-bond-"off"…”