Relative Thermodynamic Stabilities of Isomeric Dimethyl Acetals Derived from 2-Acetyltetrahydrofuran. An Experimental and Computational Study

In the presence of an acid catalyst, the dimethyl acetal of 2-acetyltetrahydrofuran (1) is converted into a mixture of three isomeric acetals composed of the reactant and two diastereomers of 2-methoxy-2-(1-methoxyethyl)tetrahydrofuran (2). The relative thermodynamic stabilities of these acetals have now been determined by chemical equilibration. The least stable isomer is 1, in the liquid phase 4–6 kJ mol^–1 less stable than the two diastereomers. The geometry-optimized structures and relative energies of the title compounds were also studied by theoretical calculations (ab initio and DFT). Comparison of the theoretically determined relative stabilities of the diastereomers with the corresponding experimental data suggests the more volatile (and more stable) diastereomer to exist as a racemic mixture of the (R,S) and (S,R) configurations.