Decreasing reactivity with increasing nucleophile basicity. The effect of solvation on .beta.nuc for phosphoryl transfer to amines.

Rate constants for the reactions of substituted quinuclidines with pnitrophenyl phosphate, 2,4-dinitrophenyl phosphate, 2,4-dinitrophenyl phosphate complexed with calcium, and phosphorylated pyridine decrease with increasing pKa of the amine. Plots of log k against pK, give slopes of @ , , = -0.05, -0.10, -0.1 1, and 4.10, respectively, for these.compounds; &, = -0.01 for phosphorylated 4-morpholinopyridine. These negative slopes are attributed to a requirement for desolvation of the amine before nucleophilic attack, which is more difficult with more basic amines; a value of Pd = -0.2 for the desolvation step is suggested. Nucleophilic reagents are likely to be hydrogen bonded to hydroxylic solvents, so that structure-reactivity correlations may reflect the behavior of the desolvation step as well as nucleophilic attack. The dependence of the reaction rate on the basicity of an attacking nucleophile is given by the slope, &,, of a plot of log k against the pKa of the protonated nucleophile, BH”. The observed value of Dnuc includes the dependence of desolvation as well as nucleophilic attack on the basicity of the nucleophile, so that the amount of nucleophilic attack in the transition state may be underestima.ted if desolvation is neglected. The desolvation step will have a small or negligible influence on the observed value of &, when there is a large amount of bond formation in a late transition state that resembles BH”, which is the reference compound for the Br~ns ted correlation and corresponds to the development of a full positive charge on the amine.2,3 However, for early transition states, in which the nucleophilic attack step has only a small dependence on basicity, the increase in the strength of hydrogen bonding to the solvent with increasing basicity can cause a significant decrease in the observed dependence of the rate on the basicity of the nucleophile if an initial desolvation step is required. Conversely, in the reverse reaction or in any reaction in which there is a large amount of bond breaking in the transition state, incomplete solvation of the leaving group may cause an increase in -@, and an overestimation of the amount of bond breaking. We report here several reactions of monosubstituted phosphates with substituted quinuclidines that decrease in rate with increasing basicity of the quinuclidine; i.e., &,, is negative. The reaction requires desolvation of the attacking amine, with the equilibrium constant Kd in eq 1, before nucleophilic attack of the free amine, with the rate constant k. A negative value of onw will be observed