Bromination

Recently I was asked to review a proposed synthetic route and was reminded of the electrophilic aromatic bromination reaction that can be effected using hydrobromic acid in DMSO.  Wishing to re-acquaint myself with the reaction, I looked up the reference by G Majetich et al (JOC, 1997, 62, 4321) and summarise a couple of key features below.  The reaction requires an activated aromatic ring, and some selectivity can be achieved, although di- (and tri-) bromination can also occur.  The reaction can be done with either aqueous HBr in DMSO, or acetic can be added as co-solvent.

Some of the reactions were quite fast (ie of the order of minutes), so it begs the question if the mono-bromination might be better controlled by applying recent flow chemistry techniques?

I also noted with interest the reference to the 1968 paper by Landini et al which discloses the simultaneous N-alkylation and bromination when using ethyl bromide in DMSO.  An interesting feature and certainly a reaction to keep in mind when developing alkylation reactions – could you have trace DMSO from a previous step that results in new impurity formation?

The proposed mechanism was reported to be as below.  The paper makes the point that this reaction avoids the need to use bromine, but omits the need to contain (ie scrub) the dimethylsulphide by-product.  Owing to this very smelly by-product and the need to have an oxidising scrubber system, the alternative use of hydrogen peroxide/hydrogen bromide may still be preferred by many.