Determination of the pK a of Cyclobutanone: Brønsted Correlation of the General Base-Catalyzed Enolization in Aqueous Solution and the Effect of Ring Strain

• Published in: Journal of organic chemistry Vol. 76; no. 2; pp. 380 - 390
• Main Authors: Cope, Steven M, Tailor, Dishant, Nagorski, Richard W
• Format: Journal Article
• Language: English
• Published: American Chemical Society 21-01-2011
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo101369w

The induction of strain in carbocycles, thereby increasing the amount of s-character in the C−H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constants for the enolization of cyclobutanone. The second-order rate constants for the general base-catalyzed enolization of cyclobutanone have been determined for a series of 3-substituted quinuclidine buffers in D2O at 25 °C, I = 1.0 M (KCl). The rate constants for enolization were determined by following the extent of deuterium incorporation (up to ∼30% of the first α-proton) into the α-position, as a function of time. The observed pseudo-first-order rate constants correlated to the [basic form] of the buffer and yielded the second-order rate constants for the general base-catalyzed enolization of cyclobutanone for four tertiary amine buffers. A Brønsted β-value of 0.59 was determined from the second-order rate constants determined. Comparison of the results for cyclobutanone to those previously reported for acetone and a 1-phenylacetone derivative, under similar conditions, indicated that the ring strain of the carbocycle appeared to have only a small effect on the general base-catalyzed rate constants for enolization. The similarity of the rate constants for the general base-catalyzed enolization of cyclobutanone to those determined for acetone allowed for an estimation of the limits of the rate constant for protonation of the enolate intermediate of cyclobutanone by the conjugate acid of 3-quinuclidinone (k BH = 5 × 108 − 2 × 109 M−1 s−1). Combining the rate constants for deprotonation of cyclobutanone (k B) and protonation of the enolate of cyclobutanone (k BH) by 3-quinuclidinone and its conjugate acid, the pK a of the α-protons of cyclobutanone has been estimated to be pK a = 19.7−20.2.