Flash Photolysis of 2,2,6-Trimethyl-4H-1,3-dioxin-4-one in Aqueous Solution:  Hydration of Acetylketene and Ketonization of Acetoacetic Acid Enol

Abstract

Acetylketene was produced by flash photolysis of 2,2,6-trimethyl-4H-1,3-dioxin-4-one in aqueous solution, and rates of hydration of the ketene to acetoacetic acid enol and subsequent ketonization of the enol were measured in this solvent across the acidity range [H+] = 1−10-13 M. Acetylketene proved to be a remarkably reactive substance, undergoing uncatalyzed hydration with the rate constant k = 1.5 × 106 s-1, some 104 times more rapidly than ketene itself; the acetylketene hydration reaction was also catalyzed weakly by hydroxide ion but not by hydrogen ion. Ketonization of acetoacetic acid enol was much slower with rates in the millisecond to second range. The reaction showed a complex rate profile that could be interpreted in terms of rate-determining carbon protonaton of the carboxylate-ionized form of the enol in the acid region and rate-determining carbon protonation of the doubly ionized carboxylate−enolate form in the basic region. Analysis of the data provided the acidity constant pQ a = 4.05 for the carboxylic acid group of the enol and pQ a E = 13.18 for its enolic hydroxyl group. (These acidity constants are concentration quotients referring to an ionic strength of 0.10 M). Combination of the present results with information on the enolization of acetoacetic acid available from the literature gave K E = 5.6 × 10-3, pK E = 2.25, as an estimate of the keto−enol equilibrium constant.

Solvent isotope effect on the hydroxide-ioncatalyzed hydration of ketenes in aqueous solution

“…The present inverse isotope effects are quite different from the value, k HO /k DO = 1.87, reported for the only previous example of a solvent isotope effect on a ketene plus hydroxide ion reaction (2). The substrate in that case was acetylketene, 11, and it was argued then that the acetyl group assisted hydroxide ion attack, as evidenced by its strong rate acceleration, by allowing strong hydrogen bond formation between the hydroxyl group and the acetyl oxygen atom in the transition state of this reaction, 12, eq.…”

“…The data so obtained have been summarized, as supplementary material, in Table S1. 2 As Fig. 1 illustrates, the observed first-order rate constants determined in this way are accurately proportional to sodium hydroxide concentration.…”

“…[1], catalyzed by the hydronium ion, as well as on the uncatalyzed reaction, have proved to be useful in elucidating the mechanisms of these processes, and they have also served to help identify new examples (1). The same is not true of the hydroxide-ion-catalyzed reaction: we are aware of only one published determination of this isotope effect made prior to the present work, and that was done using a rather special substrate containing a second functional group that perturbed the isotope effect and gave it an atypical value (vide infra) (2).…”

Dual Macrolactonization/Pyran–Hemiketal Formation via Acylketenes: Applications to the Synthesis of (−)‐Callipeltoside A and a Lyngbyaloside B Model System

“…Several alternative intermediates or processes can be envisioned for the transformation of 7 to 8 : a) Hemiketal formation in 9 prior to lactonization would afford 12 , which could further cyclize to the macrolactone/pyran 8 . We presume that the acylketene 9 would lactonize considerably faster than the simple ketene 12 (for example, water reacts with acetylketene (AcCHCO) approximately 42 000 times faster than with ketene (H 2 CCO) itself) 11. Moreover, whereas no intermediates are involved in the transformation of 9 to 10 , hemiketal formation ( 9 to 12 ) likely requires catalysis by an external agent.…”

Room Temperature Acylketene Formation? 1,3-Dioxin-4-ones via Silver(I) Activation of Phenylthioacetoacetate in the Presence of Ketones

“…The parent acetylketene ( 1 , R 1 = Me, R 2 = H) has a half-life of <1 microsecond in water ii. In most instances, the fate of acylketenes 1 is to acylate nucleophilic oxygen or nitrogen functional groups to produce esters/acids or amides.…”