Computational Studies of the Gas Phase Reactions of Ethers with Anions: Kinetic Barriers,Isotope Effects,Consecutive Eliminations and Site Selectivity

Bimolecular elimination reactions (E2) are fundamentally important processes in organic chemistry. Our current work focuses on a computational investigation of several interesting and unexpected experimental results previously obtained in our laboratory. In particular, we have examined the detailed mechanisms for generating CH₂CHO⁻ from the reaction of HO⁻ + CH₃CH₂OCH₂CH₂OCH₃, the unusually large isotope effect (k_H/k_D = 5.5) for the reaction of NH₂⁻ + CH₃CH₂OCH₂CH₃, and the possible kinetic barriers in the reaction of H⁻ + CH₃CH₂OCH₂CH₃. Moreover, we have explored the high site selectivity in the reaction of NH₂⁻ + CH₃CH₂OC(CH₃)₃. In the HO⁻ + CH₃CH₂OCH₂CH₂OCH₃ reaction, three ion-neutral encounter complexes were located and fully optimized. The corresponding transition states were confirmed during the first E2 hydrogen-transfer process and they all possess E1_cb-like antiperiplanar conformations. The formation of loosely bonded CH₃O⁻ and H₂O moieties was found to be essential for the second E2-type hydrogen transfer, and an intriguing E1_cb-like gauche transition state (CH₃OH–C _α –C_β–OCHCH₂ dihedral = 40.9°) was located, which results in the formation of ionic CH₂CHO⁻ and neutral CH₃OH, H₂O, and C₂H₄ products. The lowest kinetic barrier for the reaction of NH₂⁻ + CH₃CH₂OCH₂CH3 is −5.3 kcal mol⁻¹ (–22.2 kJ mol⁻¹), which is 1.5 kcal mol⁻¹ (6.3 kJ mol⁻¹) higher in energy than the lowest barrier for the reaction HO⁻ + CH₃CH₂OCH₂CH3. The higher kinetic barrier of the NH₂⁻ + CH₃CH₂OCH₂CH₃ reaction is consistent with the observation of a larger isotope effect. The lowest kinetic barrier for the reaction of H⁻ + CH₃CH₂OCH₂CH₃ is +5.4 kcal mol⁻¹ (22.6 kJ mol⁻¹), indicating that, although H⁻ is a strong base, this reaction cannot occur at room temperature, which agrees well with the experimental results. The high selectivity in the formation of CH₃CH₂O⁻ from the reaction of NH₂⁻ + CH₃CH₂OC(CH₃)₃ is explained by an electrostatic potential analysis of the ether molecule. Thus, this computational study provides important insight into the detailed mechanisms of elimination reactions.