Substituent effects on carbocation stability: The pK_R for p-quinone methide

A value of k_H = 1.5 × 10^-3 M^-1 s^-1 has been determined for the generation of simple p-quinone methide by the acid-catalyzed cleavage of 4-hydroxybenzyl alcohol in water at 25 °C and / = 1.0 (NaClO₄). This was combined with k_s = 5.8 × 106 s^-1 for the reverse addition of solvent water to the 4-hydroxybenzyl carbocation [J. Am. Chem. Soc. 2002, 124, 6349-6356] to give pK_R = -9.6 as the Lewis acidity constant of O-protonated p-quinone methide. Values of pK_R = 2.3 for the Lewis acidity constant of neutral p-quinone methide and pK_add = -7.6 for the overall addition of solvent water to p-quinone methide to form 4-hydroxybenzyl alcohol are also reported. The thermodynamic driving force for transfer of the elements of water from formaldehyde hydrate to p-quinone methide to form formaldehyde and p-(hydroxymethyl)-phenol (4-hydroxybenzyl alcohol) is determined as 6 kcal/mol. This relatively small driving force represents the balance between the much stronger chemical bonds to oxygen at the reactant formaldehyde hydrate than at the product p-(hydroxymethyl) phenol and the large stabilization of product arising from the aromatization that accompanies solvent addition to p-quinone methide. The Marcus intrinsic barrier for nucleophilic addition of solvent water to the "extended" carbonyl group at p-quinone methide is estimated to be 4.5 kcal/mol larger than that for the addition of water to the simple carbonyl group of formaldehyde. O-Alkylation of p-quinone methide to give the 4-methoxybenzyl carbocation and of formaldehyde to give a simple oxocarbenium ion results in very little change in the relative Marcus intrinsic barriers for the addition of solvent water to these electrophiles.