Ketones, halogenation electronic effects

A trihalo compound may be formed from the halogenation of a methyl ketone. The electron-withdrawing effect of the trihalomethyl group makes the carbonyl group very sensitive to nucleophilic addition. Consequently, in the presence of a mild base the trihalomethyl compound easily decomposes with the formation of chloroform, bromoform or iodoform, depending on the halogen. The other product of the haloform reaction is a carboxylic acid (Scheme 3.86). 

We recall that chlorine and bromine are deactivating groups in electrophilic aromatic substitution because they withdraw electron density by an inductive effect but are ineffective in the donation of electron density by resonance. The same features are important in controlling the rate of the second step of ketone halogenation. The bromine atom withdraws electron density from the carbonyl carbon atom, making the carbonyl oxygen atom less basic. Therefore, the enol forms more slowly in the second step. 

The previous discussion of the halogenation of ketones is incomplete in one important respect concerning base-induced halogenation. That is, once an a-halo ketone is formed, the other hydrogens on the same carbon are rendered more acidic by the electron-attracting effect of the halogen and are replaced much more rapidly than the first hydrogen ... 

However, it is difficult to stop the reaction at mono-halogenation because the product formed is generally more acidic than the starting ketone because of the electron-withdrawing effect of the halogen. Due to this, another enolate ion is quickly formed leading to further halogenation. 

Substituent effects on rate constants of base-promoted ionisation of ketones have led to the conclusion that an electron-withdrawing substituent increases the rate of ionisation, in agreement with the anionic character of the transition state. This is based chiefly on studies on halogenation and isotope exchange of aromatic ketones. Data on p-values observed by plotting ionisation rate constants versus Hammett -parameters (Table 3) for substituted... 

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. 

Simple sulfonyl carbanions which do not contain additional carbanion-stabilising groups, e.g. carbonyl groups or heteroatoms, can be readily alkylated in high yield by modern techniques with the use of alkyllithiums and lithium amide bases. A number of allylic halides have been successfully used. In allylic halides, the halogen directly attached to the double-bonded carbon is relatively inert towards nucleophilic attack (Scheme 41). In this way, sulfones (96) can be transformed via desulfonation into vinyl halides (97) or into ketones (98) by hydrolysis (Scheme 41). In contrast to ordinary alkyl sulfones, triflones (99) can be alkylated under mildly basic conditions (potassium carbonate in boiling acetonitrile) (Scheme 42). The ease of carbanion formation from triflones (99) arises from the additional electron-withdrawing (-1) effect of the trifluoromethyl moiety. 

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