Rate and equilibrium constants for formation and hydrolysis of 9-formylfluorene oxime: diffusion-controlled trapping of a protonated aldehyde by hydroxylamine

Equilibrium constants K add = 440 and K ox = 3.0 × 10 8 for formation of a carbinolamine adduct and oxime, respectively from 9-formylfluorene and hydroxylamine, and pK a = –1.62 for protonation of the oxime, have been evaluated at 25°C in aqueous solution, based on measurements in hydroxylamine buffers, acetic acid buffers, and dilute HCl. Rate constants for hydrolysis of the oxime have been measured in the acidity range pH 4–12 M HClO 4 . At the highest acidities, a reaction pathway via protonated carbinolamine has been identified: evidence is presented that the reverse of this reaction involves rate-determining attack of hydroxylamine upon protonated 9-formylfluorene. By assuming that the attack of hydroxylamine is diffusion-controlled, with rate constant 3 × 10 9 M –1 s –1 , a pK a for O-protonation of the aldehyde (–4.5) is derived. Taking account of the equilibrium constant for enolization of 9-formylfluorene (K E = 16.6), a pK a for for C-protonation of the enol tautomer ((–5.7) may also be obtained. Comparison of this pK a with that of the enol of acetophenone shows that the enol of 9-formylfluorene is less basic by a factor of 10 10 . By combining pK a s for protonation of the aldehyde and oxime with measured or estimated equilibrium constants for addition of water, hydroxide ion, and hydroxylamine to 9-formylfluorene, it is also possible to obtain values of pK R = –5.3, 4.1, and 12.25 for the protonated 9-formylfluorene, protonated oxime, and 9-formylfluorene, respectively. The usefulness of pK R in providing a general measure of equilibrium constants for electrophile-nucleophile combination reactions is discussed.