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 f or alkaline hydrolysis of MEP in vacuum and solution. Hydroxyl ion att ack opposite a ring oxygen of MEP with the methyl group oriented towar d the incoming OH- leads to the lowest energy pathway for endo- and ex o-cyclic cleavage. Hydroxyl attack of MEP is concerted with pseudorota tion to yield a TBP intermediate with the hydroxyl group equatorial. T he factors driving pseudorotation are identified as well as the reason s why pseudorotation is preferred to S(N)2(P) ring opening. In contras t to the common belief that ring strain in cyclic phosphates is reliev ed upon forming the TBP intermediate with the hydroxyl group equatoria l, the geometry of the latter shows evidence for ring strain. This cau ses the P-O(apical) bond in the ring to be weaker than that outside th e ring, which, in turn, results in a smaller barrier for ring opening relative to cleavage of the exo-cyclic P-O(apical) bond. Thus, hydroxy l ion attack of MEP in solution results in exclusive ring opening as o bserved experimentally. The calculations predict that both endo- and e xo-cyclic cleavage would occur with retention of configuration.