Effect of Mixed-Solvent Environments on the Selectivity of Acid-Catalyzed Dehydration Reactions

The composition of
the liquid phase can alter the rates of individual
reaction steps and thus alter the selectivity of acid-catalyzed reactions,
but these solvent effects are difficult to anticipate for design purposes.
Herein, we report the kinetics and selectivity of Brønsted acid-catalyzed
1,2-propanediol dehydration in pure water and in aqueous mixtures
of the polar aprotic cosolvents γ-valerolactone, 1,4-dioxane,
tetrahydrofuran, N-methyl-2-pyrrolidone, tetramethylene
sulfoxide, and dimethyl sulfoxide at 433 K. We find that the major
product of 1,2-propanediol dehydration is propanal in most mixed-solvent
environments with selectivities between 1 and 68 mol %. In contrast,
1,2-propanediol dehydration in aqueous mixtures of dimethyl sulfoxide
affords acetone as the major product with up to 48% selectivity with
minimal propanal formation. We use classical molecular dynamics simulations
to probe these solvent effects by computing the difference between
the solvation free energies of 1,2-propanediol and propanal in aqueous
mixtures of polar aprotic cosolvents and in pure water. We find that
the difference in the solvation free energies is correlated with the
rates of propanal formation in all mixed-solvent environments, indicating
that the solvent-mediated stabilization of the product state relative
to the reactant state translates to increased selectivity toward the
same product. Similar agreement between simulated solvation free energies
and experimental reaction rates/selectivities is established for the
acid-catalyzed dehydration of cis- and trans-1,2-cyclohexanediol and 1,3-cyclohexanediol. Finally, analysis of
the solvation environment around 1,2-propanediol shows that dimethyl
sulfoxide uniquely competes against water to solvate reactive hydroxyl
groups, which causes a change in reaction mechanism in this solvent
system that leads to the formation of acetone rather than propanal.
These results represent a step toward the computationally efficient
screening of solvent systems for acid-catalyzed, liquid-phase processes.