Ortho-, Para- and Meta- Directors in Electrophilic Aromatic Substitution

by James

in Aromatic Reactions, Uncategorized

Two Important Reaction Patterns: Ortho- , Para- and Meta- Directors

It’s one thing to learn about electrophilic aromatic substitution reactions of benzene itself. But once you move beyond benzene, that’s when things start getting really interesting.

Here’s a fascinating observation.

Start with a monosubstituted benzene. Then perform some kind of electrophilic aromatic substitution  (nitration, halogenation, sulfonylation – turns out it doesn’t matter).

Two important reaction patterns are observed. 

It’s important to note that these two patterns are wholly a function of the substituent and not the reaction itself.

In one pattern, ortho- and para– products dominate, and the meta- product is an extremely minor byproduct.

Substituents which lead to this result are called, “ortho-, para- directors”. Examples of ortho-, para– directors are hydroxyl groups, ethers, amines, alkyl groups, thiols, and halogens.

Here’s a concrete example: the nitration of methoxybenzene (also known as anisole).

ortho- and para- products dominate, while meta– products comprise less than 3%.

In the second pattern, the meta– product dominates, and the ortho- and meta– products are minor.

We call the substituents which lead to this result “meta- directors”. Examples of meta– directors include nitriles, carbonyl compounds (such as aldehydes, ketones, and esters), sulfones, electron-deficient alkyl groups, nitro groups, and alkylammoniums.

Specific example: nitration of trifluoromethylbenzene gives the meta product in about 90% yield. (Compare that to the case of anisole, above, where nitration resulted in a <5% yield of the meta product. )

So why does this happen?

What factors could be in play here? How do ortho-, para- and meta– directors differ, and how could this difference affect the product distribution?

Great question.

One aspect we’ve covered previously is the concept of “activating” and “deactivating” groups.

We said that

  • Activating groups increase the rate of electrophilic aromatic substitution, relative to hydrogen.
  • Deactivating groups decrease the rate of electrophilic aromatic substitution, relative to hydrogen.

If you look through the list of ortho- , para- directors, you might recognize that many of them are also activating groups.

Likewise, the list of meta- directors (nitro, CF3, cyano) is like a who’s who of deactivating groups.

If you’re a real nerd, you could even make a 2 × 2 matrix, like this:

What do we notice?

  • First: no activating groups are meta directors.
  • Second: what’s up with the halogens?

Yes indeed. What is up with the halogens, and how is it that they can be deactivating (i.e. slow down the reaction rate) and yet lead to ortho-, para- products?

There’s no quick and thorough answer to these questions, and it’s worth its own separate blog post for that reason.

However, the first place to start is that it has to do with the stability of the carbocation intermediate in electrophilic aromatic substitution reactions. [See this previous post on the mechanism of electrophilic aromatic substitution].  More specifically, how does each substituent affect the stability of that intermediate?

It might be worth going back and revisiting some of the factors that affect the stability of carbocations.

And also, if you prefer to look at it from the opposite side of the coin, here are some of the factors which make carbocations more unstable.

In our next post, we’ll explain the reasons for both ortho-, para- and meta- direction, and try to show why halogens fit in the former category but not the latter.

 

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