Hydrolysis of cyclic phosphoramides. Evidence for syn lone pair catalysis

Abstract

Hydrolysis between 1.5 < pH < 4 of five and six membered cyclic phosphoramides has been followed by UV and ³¹PNMR spectroscopy. The observed rates fit the equation: k_obs = k_H2O [H⁺]/([H⁺] + Ka) + k′_H2O, where k_H2O and k′_H2O are the pseudo first-order rate constants of water attack on the protonated phosphoramide and its unprotonated form, respectively, and Ka is the phosphoramide acidity equilibrium constant. Although, faster hydrolysis rates on the five membered ring are expected due to the energy released in going from a strained cyclic to a “strained free” trigonal-bipyramidal-pentacoordinated intermediate, with one of the cyclic nitrogens occupying the apical position, these compounds react slightly faster (k_H2O values) but slower regarding the k′_H2O values than the six membered analogs. The balance in reactivity is attributed to the additional stability obtained in the six membered cyclic compounds by a syn orientation of the two lone pairs of the cyclic nitrogen to the water attack. This stabilization does not exist in the five membered phospholidines since the water attack is perpendicular to the electron pairs of the cyclic nitrogen. In agreement with the incoming water orientation, the product ratios from the hydrolysis show that in the five membered rings the main product is the one produced by endocyclic cleavage; meanwhile, in the six membered cyclic phospholines the kinetic product is the one produced by exocyclic cleavage. The syn orientation of two electron pairs on nitrogen stabilizes the transition state of water approach to the phosphoramides by ca. 3 kcal mol⁻¹ when compared to the orthogonal attack.