Perfluorinated Cyclic and Acyclic Keto−Enol Systems:  A Remarkable Contrast

Abstract

Recent reports from this laboratory have revealed that highly fluorinated 4- and 5-membered-ring enols are comparable in stability to, or more stable thermodynamically than, the corresponding ketones, even in non-Lewis-basic media. Work on perfluorinated keto−enol systems has now been extended to 2H-perfluorocyclohexanone plus its enol and to a series of acyclic analogues. In carbon tetrachloride, K E/K = 0.33 (22 °C) for the six-ring system, but only enol is detectable in Lewis-basic solvents. This shift is attributable to strong hydrogen-bond formation between the enol and Lewis base. A perfluoroenol has been shown to form significantly stronger hydrogen bonds than the potent hexafluoroisopropyl alcohol. Acyclic systems (e.g., 3H-perfluoro-2-butanone and its enol) contrast sharply with the cyclic, as no enol is detectable at equilibrium even in powerfully Lewis-basic media. Ab initio quantum mechanical calculations indicate that it is principally the enols, not the ketones, that are responsible for the difference between the two types of keto−enol systems, i.e. acyclic perfluoroenols are strongly destabilized relative to cyclic counterparts.

A Theoretical Study of Substituted Stepwise Fluorinated Cyclopropanone Keto-Enol System

“…The stability of enol is a result of the destabilization of ketone. This result agrees with previous work on trifluorocyclopropanone (perfluorination) [16]. The calculated charge distribution in 2H-perfluorocyclopropanone 5, obtained from the electron density (Table 4), may give a plausible explanation for its destabilization.…”

“…Cyclopropanone and its substituted precursors have never been studied as keto-enol tautomeric systems, except perfluorinated cyclopropanone [16]. This perfluorination was studied by ab initio calculations and has shown that the enol form should be present in substantial concentrations.…”

The Tautomeric Persistence of Electronically and Sterically Biased 2‐Quinolinones

“…[53] Ethyl 2-fluoroacetoacetate and ethyl 2-fluorobenzoylacetate are enolized to the extent of 4 % and Ͻ 3 %, respectively, [52] less than half as much as the corresponding parent compounds. [53][54] Spectacular substituent effects on the oxo/enol equilibria of polyfluoroketones were reported by Lemal et al [55] Whereas the enol forms of both cyclopentanone and 3H-heptafluoro-2-butanone were present only in undetectably small concentrations, 2H-nonafluorocyclohexanone, 2,2-H 2 -hexafluorocyclopentanone, 2H-heptafluoropentanone and 2H-pentafluorocyclobutanone were enolized to the extent of 25, 13, 99 and Ͼ99.5 %. [55] The structures of uracil and of the cancer drug 5-fluorouracil have also been extensively investigated.…”

“…[53][54] Spectacular substituent effects on the oxo/enol equilibria of polyfluoroketones were reported by Lemal et al [55] Whereas the enol forms of both cyclopentanone and 3H-heptafluoro-2-butanone were present only in undetectably small concentrations, 2H-nonafluorocyclohexanone, 2,2-H 2 -hexafluorocyclopentanone, 2H-heptafluoropentanone and 2H-pentafluorocyclobutanone were enolized to the extent of 25, 13, 99 and Ͼ99.5 %. [55] The structures of uracil and of the cancer drug 5-fluorouracil have also been extensively investigated. According to an early ab initio calculation at the 3-21G level, the tautomeric population of the parent heterocycle and its fluorinated congener turned out to be almost identical.…”

Functional Compounds Containing Oxygen, Sulphur or Nitrogen and their Derivatives

“…Remarkably, the pair 8.25A and 8.25B in Figure 8.25 cannot be equilibrated by acid or base; the enol 8.25A, for example, can be distilled from concentrated sulphuric acid. Enols of cyclic systems are also unusually stable [123] and the equilibrium constant depends on the solvent (Figure 8.26). Clearly, the tautomerism is inhibited by a kinetic barrier and this could be the relative instability of the anion 8.25C, where electron-pair repulsion involving non-bonding pairs on fluorine could be significant.…”