Propiophenone halogenation

Disubstitution products are obtained when dihalobenzenes (Cl, Br, I) react with aliphatic ketone enolate anions. Conversely, the reactions of o-iodohalobenzenes (X = I, Br, Cl) with the enolate anions of aromatic ketones, such as acetophenone, propiophenone and 2-naphthyl methyl ketone in DMSO yield mainly monosubstitution with the retention of one halogen (Scheme 10.7). The extent of dehalogenation is explained in terms of the energetics of the intramolecular ET from the ArCO-7t-system to the C—X bond in the monosubstituted radical anions proposed as intermediates [19]. 

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. 

Halogenation in base is much less useful, because it is often difficult to stop the reaction after addition of just one halogen atom to the a carbon. For example, treatment of propiophenone with Br2 and aqueous OH yields a dibromo ketone. 

In a few instances, not only methyl ketones but other alkyl ketones are degraded to shorter carboxylic acids resulting from halogenation of the methylene group adjacent to the carbonyl and subsequent hydrolysis [103, 160,1172]. The reaction between propiophenone and sodium hypobromite at 22-25 °C gives a 96% yield of benzoic acid [303]. Under similar conditions, 5-butyl-2-butyrylpyridine is converted into 5-butyl-a-picolinic acid in 79% yield [160]. Methyl 3-(a-pyridyl)propyl ketone yields not only the... 

Pyridine bromide is a useful reagent for halogenation of alkenes and ketones, but both pyridine and bromine are noxious reagents, and the solid pyridinium perbromide complex is dangerous to handle. Poly(vinylpyridine perbromide) (21) quantitatively produces a-bromo ketones from cyclohexanone and propiophenone and is easy to handle. Bromination of (Z)-stilbene and ( )- and (Z)-1-phenylpropene gave 98-100% anti addition, as in equation (2), while bromine in solution yielded dibromophenylpropanes with 25-92% anti addition, depending upon the solvent. 

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