A kinetic study is reported for the hydrolysis of 2,2-diphenyl-2-methoxy-1,3,2-dioxaphospholane 1. This phosphorane exists in aqueous solution in a pseudo acid–base equilibrium with an observable phosphonium ion, the ring-opened (2′-hydroxyethoxy)diphenylmethoxyphosphonium ion 5. The equilibrium constant Ka ([1][H+]/[5]) is 9 × 10−9, values determined by kinetic and spectroscopic methods being in good agreement. This phosphonium ion is, however, not involved in the overall hydrolysis reaction, which proceeds via the thermodynamically less stable cyclic five-membered phosphonium ion derived by loss of the exocyclic methoxy group from the phosphorane, the 2,2-diphenyl-1,3,2-dioxaphospholan-2-ylium ion 6. This route for the overall hydrolysis is established by analysis of the products, and by the observation that the rate constant for the disappearance of 5 in acid solutions is 40 000 times greater than that for an analog that differs only in not being able to cyclize, the (2′-methoxyethoxy)diphenylmethoxyphosphonium ion 7. At all pH, the phosphorane 1 and the ring-opened phosphonium ion 5 exist in equilibrium, and the rate-limiting step in the overall hydrolysis is the cleavage of the exocyclic methoxy group to give the cyclic phosphonium ion 6, which is rapidly converted to products by reaction with water. The actual equilibration reaction involving 1 and 5 cannot be observed at any pH, even with stopped-flow spectroscopy. The non-catalyzed ring closure of the phosphonium ion 5 reforming the phosphorane 1 occurs with a rate constant of 200–500 s−1, corresponding to an effective molarity of (2–5) × 107 M for the intramolecular hydroxy group in this reaction. The rate-limiting exocyclic cleavage is assisted by H+, with a very large rate constant 2 × 109 M−1 s−1. Catalysis by general acids is also observed. The Brønsted plot has a slope α of 1.0 for the weaker acids, with a break for acids with pKa < 3. This "Eigen"-type behavior is proposed to arise from a transition state with little phosphonium ion character, in which the proton is almost completely transferred for the weaker acids. Key words: phosphorane, phosphate, phosphonium, hydrolysis.
Direct n.m.r. evidence for substrate-induced conformational changes in a β-lactamase