The solvent molecules are explicitly included in the simulation box, in contrast to the implicit solvation approach in the XP-PCM method. Molecular dynamics (MD) simulations or Monte Carlo simulations (an early example by Klärner et al. ) are performed to obtain reaction profiles at high pressures and activation volumes. Due to the large size of the system using a simulation box, the MD simulations were usually done with force fields, as illustrated in the works from the Weinberg group, or by a hybrid quantum mechanics/molecular mechanics (QM/MM) approach, as shown in the work by Plotnikov and Martinez 49 and a recent work by Loco et al. We now report a thorough consideration of the potential energy surface (PES) of the thermal dimerization 1,3-cyclohexadiene, including [4+2]-ene pathways that were not considered previously. In addition, we report, for the first time, XP-PCM calculations on the activation volumes for the various dimerization reactions of 1,3-cyclohexadiene, offering a new approach for computationally studying the competing mechanisms of this reaction.