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Order of Operations!

One thing you may have noticed about electrophilic aromatic substitutions: the order of operations really matters!

For example, let’s say you start with benzene. In one sequence, you do nitration first, then do a bromination. The NO2 will direct the bromine to the meta position so you get 1,3-bromonitrobenzene.

If you do it the othe way around, you brominate first, and then since bromine is an o-p director, when you do the nitration it will end up ortho or para to the bromine.

So you’ll get a mixture of 1,2 and 1,4 bromonitrobenzene.

Cool, huh?

Remember this when it comes to synthesis!


A second point. Thee are certain reactions that will change the nature of a substitutient from o-p directing to m-directing (or vice versa). Pay attention to these reactions! They are crucial if you want to synthesize certain molecules.


For example it isn’t possible to make propylbenzene directly from benzene using a Friedel-Crafts alkylation, since the alkyl group will rearrange. The right way to tdo it is to do a Friedel-Crafts acylation, followed by a Clemmensen reduction [Zn(Hg), H+) or similar.

Also by doing this you “flip” the polarity of the directing group. You can use this to make “meta’ products or “ortho-para” product depending on which order you do the sequence.

Thanks for reading! James