How to prepare pentabromobenzene from aniline?

1 Answer
Oct 23, 2016

I can't think of an easy synthesis for this; Ernest Z. suggested more or less what I would have done, but noted that sterics would play into making the yield quite poor.

EDG = electron-donating group
EWG = electron-withdrawing group
wrt = with respect to
EAS = electrophilic aromatic substitution

  1. The amine group is an EDG, so it activates the aromatic ring wrt EAS, allowing the ring to behave as a nucleophile (remember, EAS is where benzene reacts with an electrophile, but isn't an electrophile itself). That means no FeBr3 catalyst is required, and the three Br atoms add easily.
  2. The next Br needs to go on meta to the NH2, so we have to transform it into a meta-director. One way to do it is to perform a Friedel-Crafts Acylation to generate a protecting group.
    This becomes an EWG, which deactivates the ring wrt EAS. It would be a meta-director so that helps. Despite that, having the four EWGs on the ring makes it difficult for another Br to get on.
  3. We attempt to get a Br onto carbon-3 or 5 whichever wants to occur. Either one could occur. This time we do need an FeBr3 catalyst.
  4. This is the first step to removing the NH2. We wanted to try limiting steric clutter to maximize the chances of a fifth Br atom making it on. So, we add some acid and hydrolyze the amide bond back into NH2 and a carboxylic acid side product.
  5. The first step here is the conversion of ..NH2 into +NN:, a diazonium cation. The second step removes it completely, using hypophosphorous acid to replace it with an H.
  6. The last step would be a hopeful Br EAS onto one of the remaining carbons. It doesn't matter which one since it's a symmetric molecule.