Reactions of Aromatic Molecules
Disubstituted Benzenes: The Strongest Electron-Donor “Wins”
Last updated: October 6th, 2022 |
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.
Table of Contents
- Electrophilic Aromatic Substitution With Two Directing Groups: Which Group “Wins” ?
- An Easy One: p-Nitroanisole
- When Two Or More Substituents Are Present, The Directing Group Will Be The Most Activating Substituent.
- If Attack At Two Or More Positions Is Possible, Pick The Least Sterically Hindered One
- Nothing Says “Steric Effects” Quite Like A t-Butyl Group
- Summary: Electrophilic Aromatic Substitution on Disubstituted Benzenes
- Quiz Yourself!
- (Advanced) References and Further Reading
1. Electrophilic Aromatic Substitution With Two Directing Groups: Which Group “Wins” ?
Here’s a thorny question: What happens when we perform an electrophilic aromatic substitution reaction 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?”.
2. 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 NO2 ?
[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 1]
3. When Two Or More Substituents Are Present, The Directing Group Will Be The Most Activating Substituent.
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 CH3 (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.
4. If Attack At Two Or More Positions Is Possible, Pick The Least Sterically Hindered One
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!
5. Nothing Says “Steric Effects” Like A t-Butyl Group
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.
6. Summary: Electrophilic Aromatic Substitution on Disubstituted Benzenes
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:
- The most activating group will act as the directing group.
- 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.
Note 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.
Note 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)
Note 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. ]
(Advanced) References and Further Reading
- —The nature of the alternating effect in carbon chains. Part V. A discussion of aromatic substitution with special reference to the respective roles of polar and non-polar dissociation; and a further study of the relative directive efficiencies of oxygen and nitrogen
Christopher Kelk Ingold and Edith Hilda Ingold
J. Chem. Soc. 1926, 1310-1328
An early paper examining the directing effects of 2 substituents on a benzene ring, in this case -OMe and -NHAc.
- —The nature of the alternating effect in carbon chains. Part VI. A study of the relative directive efficiencies of oxygen and fluorine in aromatic substitution
Eric Leighton Holmes and Christopher Kelk Ingold
J. Chem. Soc. 1926, 1328-1333
This paper discusses the product distribution obtained upon nitration of o-fluoroanisole. The nitration occurs either ortho to the -OMe (66%) or para to -OMe (31%).
- —The nature of the alternating effect in carbon chains. Part XXIII. Anomalous orientation by halogens, and its bearing on the problem of the ortho–para ratio, in aromatic substitution
Christopher Kelk Ingold and Charles Cyril Norrey Vass
J. Chem. Soc. 1928, 417-425
This paper discusses directing effects in 1,2-dihalobenzenes.
- Volume effects of alkyl groups in aromatic compounds. Part V. The monosulphonation of p-cymene
R. J. W. Le Fèvre
J. Chem. Soc. 1934, 1501-1502
In p-cymene, the major product obtained upon electrophilic sulfonation is the 2-product (ortho to the methyl group), likely due to sterics.
- Effects of Alkyl Groups in Electrophilic Additions and Substitutions
COHN, H., HUGHES, E., JONES, M. and PEELING, M. G.
Nature 1952, 169, 291
This paper has data comparing the nitration of t-butylbenzene and toluene. T-butylbenzene is much more p-directing than toluene (79.5% para for t-butylbenzene vs. 40% para for toluene), which is likely due to sterics (ortho approach is blocked by the bulkier t-butyl group).
- Distribution of Isomers in the Mononitration of Ethyl- and Isopropylbenzene. Further Evidence for a Steric Effect in Isomer Distribution
Herbert C. Brown and W. Hallam Bonner
Journal of the American Chemical Society 1954, 76 (2), 605-606
Table II in this paper illustrates that the ortho product obtained from nitration of monoalkylbenzenes decreases as the alkyl group gets larger (e.g. t-butylbenzene yields very little ortho product upon nitration compared to toluene).
- Some aspects of the nitration of the mononitrotoluenes
J. G. Tillett
J. Chem. Soc. 1962, 5142-5148
In this paper the rates for nitration of all three nitrotoluenes are measured and compared. The major product for nitration of m-nitrotoluene is 3,4-dinitrotoluene, consistent with the strongest donor (ortho-para directing methyl) “winning” over the (meta-directing) nitro group. Note that nitration of 2,4- or 2,6-nitrotoluene leads to the common explosive 2,4,6-trinitrotoluene (TNT)!
26 thoughts on “Disubstituted Benzenes: The Strongest Electron-Donor “Wins””
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.
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.
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 ?
Thank you for posting this! I have been having the toughest time trying to understand all of the different benzene substitution rules using my textbook and lecture notes, but reading this post has resulted in a TENFOLD increase in my understanding in just under fifteen minutes! Thank you, thank you, thank you!
Awesome to hear, thank you Kaitlin!
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Thank you for the kind comment.
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Glad you found it useful and thanks for stopping by!
It has proven to be the bestest of all.. I have shared this site to all my friends nd they all are so grateful.. so a word of thanks from our group (of 40-45 students who checks your site for any reference.. not bragging.. nor I’m trying to show that i have done something great by sharing your site..) peace 😊
How do both substituents in the p-Nitroanisole direct to the same c-2 position if one is at the meta position and the other at ortho-, para-? I think I just need more specific clarification because it looks like two different spots to me?
“Ortho-director” and “meta-director” describe *relative*, not absolute relationships.
C-2 is ortho *relative* to -OCH3 , and C-2 is meta *relative* to the NO2.
Does that make sense?
Yes! I believe I get it now thank you :) thank you
What about adding to a disubstituted benzene and all groups are deactivating? Is it the strongest or weakest deactivator who “wins” directing effects
It would be whichever group is less deactivating. Do you have a specific example?
Such as what would the major product be for mono-chlorination of 4-nitrobenzonitrile?
I believe it would be ortho to the nitrile group because nitrile is less deactivating than NO2 according to this paper. https://pubs.acs.org/doi/pdf/10.1021/ja00775a028
Maybe in the example of p-Bromobenzenesulfonic acid?
The bromine group is less deactivating then sulfonyl, so you’ll end up performing substitution ortho to the sulfonic acid.
If there is a -OEt gr in carbon 3 in anisole then what is the major and minor product?
I want to ask if there are two substituent…one is a weak activator and the other is a strong deactivator…does the weak activator still wins? So does it mean that any activating group will win whenever there are also deactivating groups?
Yes, exactly. If there is CH3 and NO2, for example, then CH3 will determine the position of the new substituent.
You won’t get good selectivity. The ethyl group is not very sterically hindered relative to methyl. You’ll get a mix of substitution products ortho to the OMe and ortho to the OEt.
I want to ask what if I have benzene like “2-nitrobenzoic acid”, what position is the next substituent that will be attached? why?
Probably the position meta to COOH and para to NO2 since COOH is not as deactivating as NO2.
I got perfectly what I wanted in two minutes. Thanks.