Carbonyl compounds can be halogenated in the α position by halogens (such as bromine, Br2) in acidic or basic solutions. We shall look at the acid-catalysed reaction first because it is simpler. Ketones can usually be cleanly brominated using acetic acid as solvent.

The first step is acid-catalysed enolization and the electrophilic bromine molecule then attacks the nucleophilic carbon of the enol. The arrows show why this particular carbon is the one attacked.

Notice that the acid catalyst is regenerated at the end of the reaction. The reaction need not be carried out in an acidic solvent, or even with a protic acid at all. Lewis acids make excellent catalysts for the bromination of ketones. This example with an unsymmetrical ketone gives 100% yield of the bromoketone with catalytic AlCl₃ in ether as solvent.

Bromination occurs nowhere else in the molecule—not on the benzene ring (which, as you will see in the next chapter, it easily might under these conditions), nor on any other atom of the aliphatic side chain. This is because only one position can form an enol and the enol is more reactive towards bromine than the aromatic ring.

These mechanisms should remind you of alkene bromination — except that here the attack on the bromine is assisted by an electron pair on oxygen. Enols are more nucleophilic than simple alkenes—the HOMO is raised by the interaction with the oxygen’s lone pairs and looks not unlike the HOMO of the enolate anion . The product, instead of being a bromonium ion (which would undergo further reactions), loses a proton (or the Lewis acid) to give a ketone.

Bromination of acid derivatives is usually carried out not on the acid itself but by converting it to an acyl bromide or chloride, which is not isolated but gives the α-bromoacyl halide via the enol. This used to be done in one step with red phosphorus and bromine, but a two-step process is usually preferred now, and the bromoester is usually made directly without isolating any of the intermediates. We can summarize the overall process like this.

The formation of the acyl chloride with SOCl2 and the conversion of the α-bromoacyl chloride into the bromoester with MeOH are simple nucleophilic substitutions at the carbonyl group. The intermediate stage, the bromination of the very easily enolized acyl chloride, is a typical enol bromination.

مواضيع ذات صلة

The Robinson annelation

Intramolecular aldol reactions

How to control aldol reactions of aldehydes

How to control aldol reactions of esters

Specifi c enol equivalents from 1,3-dicarbonyl compounds

Conjugated Wittig reagents as specific enol equivalents

Silyl enol ethers in aldol reactions

Lithium enolates in aldol reactions

The Mannich reaction

Base-promoted halogenation

Racemization

Thermodynamically stable enols: 1,3-dicarbonyl compounds