Ketones, halogenation enolisation

Bromination of the methyl group can be restricted to monosubstitution when the reaction is carried out in acidic media. The mechanism involves protonation of the carbonyl-oxygen, followed by proton loss to give the enol. After monobromination, protonation of the bromoketone is less favourable owing to the presence of the electron-withdrawing halogen atom. Further enolisation does not occur therefore and halogenation ceases (contrast the behaviour of methyl ketones on bromination under alkaline conditions, p. 667) the product is an aryl bromomethyl ketone or phenacyl bromide. 

Comparison of the overall rate constants (when ionisation occurs along two competitive paths) or of the rate constants (when there is only one enolisation site) with that of a parent unsubstituted methyl ketone, e.g. acetone or acetophenone, shows that an alkyl group usually decreases ketone reactivity under conditions of base catalysis. This is in agreement with a small electron-repelling inductive effect which makes the carbanion ion less stable (e.g. the halogenation rate constant decreases by a factor of 6.5 on going from acetophenone to propiophenone when the reaction is catalysed by acetate ion [acetic acid-water 75 25 at 25°CI (Evans and Gordon, 1938). However, the factor is very small and could be explained by steric effects as well. 

We solved the problem by using a three-membered ring (epoxide) for (2) and an a-halo carbonyl compound for (3) two apparently different devices which in fact rely on the same principle. The atoms marked + in (2) and (3) are easily made nucleophilic —by enolisation (i) for example—and the common principle is to use a preliminary nucleophilic attack on a heteroatom to reverse the natural polarity of the atom from nucleophilic to electrophilic. Halogenation (i, E = Br) of a ketone provides a reagent for (3) and epoxidation... 

Chelate systems can also occur in certain cases. Rasmussen and Brattain [6] have observed this in a-acetyl-7-butyrolactone, which has the j3-keto ester structure. The non-enolised form gives rise to bands at 1773 cm (five-membered ring lactone) and 1718 cm (ketone), but there is also a band at 1656 cm , which the authors attribute to a chelated carbonyl group similar to those observed in open-chain products. Halogen substitution in the a-position also raises the carbonyl frequencies. In the extreme case, perflouro-butyrolactone absorbs at 1873 cm due to the influence of the fluorine atoms [29], 2-bromobutyrolactone [12] absorbs at 1797 cm . Anomalous frequencies also occur when electronegative substituents are present on the carbon atom of 7-lactones. Brugel et al. [60] have cited a number of such cases, of which 7-acetoxy-7-valerolactone which absorbs at 1797 cm is a typical example... 

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