Keto–enol tautomerism and hydration of 9-acylfluorenes

Abstract

Keto-enol tautomeric constants and ionisation constants have been measured for the keto and enol tautomers of 9-formyl-, 9-acetyl- and 9-benzoyl-fluorene in aqueous solution at 25 °C. Values of pK_E(K_E=[enol]/[ketone] and pK_E=–log K_E) are –1.22, 2.28 and 1.91, respectively, and the corresponding pK_as for enolate anion formation are 6.19, 9.94 and 9.44 for the keto tautomers and 7.41, 7.66 and 7.53 for the enols. The measurements demonstrate the effectiveness of the fluorenyl group in increasing enol stability and ketone acidity. For 9-formylfluorene, for which the enol is the stable tautomer, K_E is increased by a factor of more than 10⁷ and the acidity of the keto tautomer by more than 10⁹ relative to acetaldehyde (pK_E= 6.17, pK_a= 16.73). For 9-acetyl- and 9-benzoyl-fluorenes tautomeric constants were determined kinetically by combining rate constants for ketonisation measured spectrophotometrically following quenching of their enolate anions in carboxylic acid buffers with rate constants for enolisation measured by halogen trapping under the same conditions. For 9-formylfluorene rate constants for enolisation were measured by generating its unstable aldehyde tautomer from an ethanethiol hemithioacetal by reaction with iodine. Combining these rate constants with rate constants for ketonisation from trapping the aldehyde with bisulfite ion gave the tautomeric constant. In aqueous solution the aldehyde tautomer of 9-formylfluorene is appreciably hydrated and an equilibrium constant K_h=[hydrate]/[aldehyde]= 5.6 was derived from measurements of the (slower) equilibration of enol and hydrate following enolisation in acetic acid buffers. In aqueous solution therefore the enol (71%) and hydrate (24%) are the principal species. log k-pH profiles for enolisation, ketonisation and hydration reactions are reported. Intrinsic reactivities of the three enolate anions towards protonation by H₃O⁺ and carboxylic acids are compared within an extended Bronsted plot of log k versusΔpK with measurements by Kresge for the corresponding enolate anions derived from fluorene-9-carboxylic acid and its methyl, methylthio and methylthione esters. Surprisingly, not only are the thin and thione esters less acidic than the oxygen ester, but intrinsically less reactive.