NEW INSIGHTS INTO THE BASE-CATALYZED-HYDROLYSIS OF METHYL ETHYLENE PHOSPHATE

Quantum mechanical calculations and continuum dielectric methods have been employed to map out the detailed activation free-energy profile for alkaline hydrolysis of MEP in vacuum and solution. Hydroxyl ion attack opposite a ring oxygen of MEP with the methyl group oriented toward the incoming OH- leads to the lowest energy pathway for endo- and exo-cyclic cleavage. Hydroxyl attack of MEP is concerted with pseudorotation to yield a TBP intermediate with the hydroxyl group equatorial. The factors driving pseudorotation are identified as well as the reasons why pseudorotation is preferred to S(N)2(P) ring opening. In contrast to the common belief that ring strain in cyclic phosphates is relieved upon forming the TBP intermediate with the hydroxyl group equatorial, the geometry of the latter shows evidence for ring strain. This causes the P-O(apical) bond in the ring to be weaker than that outside the ring, which, in turn, results in a smaller barrier for ring opening relative to cleavage of the exo-cyclic P-O(apical) bond. Thus, hydroxyl ion attack of MEP in solution results in exclusive ring opening as observed experimentally. The calculations predict that both endo- and exo-cyclic cleavage would occur with retention of configuration.