Disubstituted Benzenes: The Strongest Electron-Donor “Wins”

by James

in Aromatic Reactions, Organic Chemistry 2

Having gone through the mechanism of electrophilic aromatic substitution, explored activating and deactivating substituents, and seen the importance of directing groups, let’s now take the opportunity to use these concepts to answer some slightly thornier questions.

For instance: What happens when there are two substituents on benzene?

And say that one of them is an ortho-, para- director and one is a meta- director, and they “direct” electrophiles to different carbons on the ring?

Which directing group “wins?”.

In this post we’ll go through four common types of examples and establish two important principles to use when trying to solve these kinds of problems.

An Easy One: p-Nitroanisole

Let’s start with 1-methoxy-4-nitrobenzene, which also goes by the name, p-nitroanisole.  Say we try to perform an electrophilic aromatic substitution reaction. Where does the electrophile react? What’s the directing group, OCH3 or NO?

 [Note that I’ve used “chlorination” as an example of an electrophilic aromatic substitution reaction, but the principles we will learn in this post apply to all electrophilic aromatic substitution reactions].

The first thing to do is to analyze each substituent individually.

  • The –OCH3 is an ortho-,para- director, but since the para- position is already substituted (with NO2), only the ortho- positions are available.
  • The –NO2 is a meta- director, and the positions meta- to the NO2 happen to also be the positions ortho- to the OCH3.

As it turns out, both substituents direct to the same position (C–2).  This gives us the product 2-chloro-1-methoxy-4-nitrobenzene, which indeed is the major product. [Note]

Example 2: p-Methylanisole

That example was a little too easy. Let’s look at a slightly more ambiguous example: p-methylanisole. Here there are two o-, p- directors: –OCH3 and –CH3. 

The tricky part is that they each direct to different carbons. So which substituent “wins” here?

Here’s a good rule of thumb:

 Rule #1: When two or more substituents are present on an aromatic ring, the directing group will be the most activating substituent.
(that is, the more activating substituent “wins”)

Here is a useful (but not comprehensive) ranking of activating / deactivating groups:

 

Since OCH3 is a more activating substituent than CH(i.e. OCH3 accelerates the rate more, because it is a better electron-donor),  the substituent will end up ortho to the OCH3, not ortho to CH3.

A more technical way of describing our rule is: since the rate determining step in electrophilic aromatic substitution is formation of the (electron-poor) carbocation intermediate, the substituent which is most electron-donating will result in the lowest-energy transition state and therefore the lowest activation energy, and therefore will determine the major product.

Example 3:  m-dimethoxybenzene

Here’s another disubstituted example. m-dimethoxybenzene has two identical groups, both of which are ortho-, para- directors.

When we analyze the influence of the directing groups, we again see that their directing effects are additive.  Attack at three positions is “favored”: C-2 (in between the two methoxy groups), C-4, and C-6.

As it turns out, attack at C-4 / C-6 will result in the same product, so we really have only two reasonable products to consider.

Which of the two products will dominate?

Attack at C-2, C-4, and C-6 is equally favorable from an electronic standpoint (that is, they are all equally electron-rich). However, they are not equally favorable from a steric standpoint.

The C-2 carbon is flanked by two methoxy groups, while the C-4 and C-6 carbons are adjacent only to one. Attack at C-2 will be much slower owing to to this greater steric hindrance.

Here comes the second important rule of thumb:

Rule #2: When attack at two or more electronically equivalent sites is possible, the electrophile will favor the position flanked by the fewest number of substituents. 

You might recall that we observed this effect previously in electrophilic aromatic substitution reactions of mono-substituted benzene derivatives like methoxybenzene. Even though there are two available ortho- positions, the para- is the major product because it’s less sterically hindered!

One Last Example

Let’s finish with a last example that lets us tie these examples together.  1-t-butyl-3-nitrobenzene.

Here we again have a situation where two groups direct to different positions.

What’s a stronger activating group, t-butyl or nitro? (hint : the answer to a question like this is almost never “nitro”  : – ) ) .  This would suggest that substitution would occur at C-2, C-4, and/or C-6.

Which of these three positions is flanked by the fewest substitutents? Clearly, C-2 is out, being flanked by two groups. This leaves us with C-6 and C-4, which are each flanked by a single group.

However, nothing says “STERIC EFFECTS” quite like a t-butyl group. In this case, C-6 is adjacent to the hugely bulky t-butyl group while attack at C-4 is adjacent to the relatively small NO2 group. So in this case, we’d expect to obtain only one major product.

Summary

When faced with trying to predict the product of an electrophilic aromatic substitution reaction of a disubstituted benzene, there are two important rules of thumb:

  1. The most activating group will act as the directing group.
  2. Among positions that are similarly “electronically favored”,  the site with the fewest adjacent substituents is more likely to be the site of attack.

(Or, as a wag might describe it, it all boils down to  “electronics” and “sterics”).  

One can apply these two principles to a large variety of commonly encountered situations.

In the next series of posts, we’ll go through some key electrophilic aromatic substitution reactions in detail. Next up: halogenation.


  1. Note that this “addition” of directing group effects will be observed any time there is an “ortho” or “para” relationship between an ortho,para– director and a meta– director.
  2. Although an example with two meta- directors wasn’t included, the same principles apply. One has to look at a table that ranks substituents in detailed order of deactivating ability (esters are less deactivating than nitro groups, for example, and would “win” in a competition experiment). One of the complications here is that when there are too many deactivating groups on the benzene ring, certain electrophilic aromatic substitution reactions stop working altogether since the aromatic ring isn’t nucleophilic enough (Friedel-Crafts reactions are in that category)
  3. [Advanced]. Not covered here is the ortho- effect. When a meta-directing group is meta to an ortho-para directing group, the incoming group primarily goes ortho- to the meta- directing group rather than para-.  For example, with 1-chloro-3-nitrobenzene, one might expect that two products are formed in roughly equal amounts (perhaps even a bit more of 1,2-dichloro-4-nitrobenzene, since Cl is less sterically demanding than NO2 (A values: 0.43 for Cl, 1.1 for NO2).

In fact the dominant product is 1,4-dichloro-2-nitrobenzene, and almost no 1,2-dichloro-4-nitrobenzene is formed. The reason is not well understood but is likely due to be through intramolecular assistance from the meta-directing group. [See March’s Advanced Organic Chemistry 5th ed. p. 688 and references therein. ]

 

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{ 3 comments… read them below or add one }

Victor

Waving off the case with two EWG’s as the “the same principles apply” is a bit too much of a generalization. The problem with the meta-directors is with the wording we use: it’s more appropriate to call them o,p-deactivating groups rather than “directors” like the EDG’s. In that regard, o- and p- orientations of the two strong EWG’s in the ring deactivates the rest of the ring significantly, while m-orientation leaves one position untouched. So, with two EWG’s in o/p to each other, EAS is stupidly slow even with a strong electrophile. This is a very common exam “trick” question when students are asked what’s the product of, say, EAS halogenation of p-dinitrobenzene, which is no reasonably observable reaction.

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James

It’s not “waved off”, it’s addressed two sentences later. Still, it begs the question: how would one reasonably be expected to know in advance which reactions work when there are two EWGs in the ring, and which do not? In the absence of such information, which must be obtained empirically, “the same principles apply” is the best advice I can give.

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Victor

I my experience, many instructors try to avoid those examples altogether. Those who don’t, generally say that two strong EWG’s in o/p positions to each other slow reactions to a halt. AND they test it as a “no reaction” in their tests. However, if a student remembers that, say, nitro group is a m-director, they see no reason why 1,4-dinitrobenzene wouldn’t react with an electrophile in the available “meta-directed” spot. And that’s a problem ?

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