21.10 Friedel-Crafts on aniline
Suppose you wanted to make o- or p-methylaniline from aniline using a Friedel-Crafts alkylation. You might think you could react methyl chloride (CH3Cl) with aluminum trichloride (AlCl3) with aniline. You would find that this reaction does not work.
The reason it does not work is that AlCl3 is a good Lewis acid and wants electrons. The amino NH2- group of aniline has a negative, lone pair of electrons on it that can attack the AlCl3 Lewis acid. This makes a positively charged quaternary ammonium salt that is a deactivating, meta-directing group. The reaction would, therefore, not proceed at all.
Like many times before in human history, when we hit a roadblock, we have figured out a way around it. In order to do a Friedel-Crafts alkylation on aniline to make o- or p-methylaniline, we need to turn the amino NH2 group into something that is still electron donating and o,p-directing, but does not have such a reactive negative lone pair of electrons on it. The way we do that is we can turn the amino group into an amido group. To do this, we add an acid chloride like acetyl chloride to the aniline making N-phenylacetamide. The amido group has a lone pair of electrons on the nitrogen atom, but they are not as concentrated on the nitrogen atom as they were in aniline. The lone pair is spread out towards the oxygen atom of the amide through resonance. In fact, the electrons are now spread out enough that they will not react with the AlCl3 Lewis acid. There is a lone pair of electrons on the nitrogen atom, so the amido group is still an o,p-director.
This amido compound can now undergo a Friedel-Crafts reaction.
This amido compound can now undergo a Friedel-Crafts reaction.
In this roundabout way, the Friedel-Crafts reaction of an amino benzene can occur. The amino group is transformed into an amido group, the Friedel-Crafts reaction occurs, then the amido group is hydrolyzed to an amino group once again.
12.
a) Why is the following Friedel-Crafts reaction NOT a good way to make isopropyl aniline from aniline?
b) What is a better synthesis of isopropyl aniline?
12.
a) The lone pair of electrons on the amino group would react with the Lewis Acid, AlCl3 instead of the AlCl3 helping pull off the chloride of isopropyl chloride.
