Order of Operations!

by James

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!

1-order

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.

2-reversal

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

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