[sumedh]

1.why in case of aromatic electrophilic substitution of disubstituted compounds eg. 4-cyanonitrobenzene substitution ocrs with respect to meta of cyano & not wrt nitro?

2.why actvating group dominates over deactivating one in case f electrophilic aromatic substitution?

Plz let me know urgently

[orgopete]

For #2, the title of the reaction type is electrophilic aromatic substitution. The reagents are electrophiles (electron deficient) and the aromatic rings are the nucleophiles. The best place for an electron deficient reagent to react with an aromatic ring will be the most electron rich position. Coulombs Law, opposites attract and like repel. Therefore, not only do electrophilic reactions occur ortho and para to activating groups, but overall the reaction occur faster.

[sumedh]

okay but in que 1 one group is highly deactivating & other is only deactivating then which will dominate why?

[Schrödinger]

The electrophile attacks the place of relatively greater electron density.
You should be able to apply this for both the questions.

Draw resonance structures to find out such positions.

[orgopete]

I avoided answering Q1 because I was dubious of that result. It isn't as though a nitration is going to be all that selective anyway. If you nitrate toluene, you will get three mononitro products. If you nitrate methyl benzoate, the ratio of isomers formed is meta:ortho:para = 78:20:2. I believe the mechanism is rather more complex than presented in textbooks, so I answered Q2.

If I wanted to prepare 2,4-dinitrobenzonitrile in the lab (or commercially), I would not nitrate p-nitrobenzonitrile. It would be a better reaction to do a nitration and then a function group transformation.

I always advocated to students that in an instance in which you have competing electron donating or withdrawing substituents, you should expect to have a mixture. That would be my expectation for Q1. Q2 asked for why donating substituents control substitution. I felt I could more rationally answer it.

[sumedh]

Thanks for the detailed explanation

[orgoclear]

@orgopete,

I think he meant to ask that if we perform electrophilic aromatic substitution on a disubstituted benzene. why is the effect of the o,p directing groups more than the effect of m-directing group,

Suppose we have m-nitrotoluene and we want to nitrate it (say) then why the major product is the one ortho to CH3 and para to NO2 and para to CH3 and ortho to NO2 even though NO2 is the strongest (one of the) m-directing group

[orgopete]

I thought that is what my first reply stated, but perhaps too cryptically.

My preferred way to determine reactivity and regiochemistry is to draw the resonance structures of the starting materials. If you drew them from toluene, the greatest resonance contributors would have a positive charge at the tertiary carbon and negative charges at the ortho and para carbons. In contrast, the greatest resonance contributors for nitrobenzene would place positive charges on the ortho and para carbons and negative charges on the two acinitro oxygen atoms.

If the aromatic ring were to react as a nucleophile, the carbons with the greatest negative charge (or not positive) would be the expected sites of reaction. Also, it seems intuitive that a faster reaction would occur at a carbon with a negative charge rather than the uncharged atom as inferred from the nitro resonance structure.

If we understood this, then one should rationally predict that activating groups (those that have negative charges in their resonance structures), should direct the site of electrophilic substitution. One might also guess that if an activating and deactivating groups negated each other or if activating groups or deactivating groups competed with each other, then mixtures may result. If activating and deactivating groups reenforced each other, then the predictions should hold. Because no conflict exists in this latter case, it does not require determining which group would be the most directing.

[sumedh]

can u plz explain the same for case of 4-cyanonitrobenzene? In this case  substitution occurs mainly at meta with respect to cyano.(observed).For this case if we draw resonance structures then we find that for meta product wrt cyano ,carbon attached to nitro bears + ve charge ,which is highly unstable. Still this product is major Why?Plz expalin in detail & if possible send me attachment on [Edit: email address deleted].
Thank u.

[sjb]

What is the nature of the resonance forms when you attack meta to the nitro?

[orgopete]

Well, I had hoped someone else might have saved me.

Let me present the two cases. In the first, I have drawn the resonance structures for nitrobenzene and benzonitrile. The arrow shows where one might expect electrophilic attack to occur from. It is the most electron rich by virtue of it not being electron poor. Compared to benzene, one might anticipate these compounds to be less reactive than benzene.

If I had to predict at which position substitution would occur, I would have guessed meta to the nitro as nitro is a more potent electron withdrawing group. I would expect the two oxygen atoms could draw electron density to them more strongly than a single nitrogen. I believe you can find this is generally true from the Hammett sigma values as well.

Now, I have also drawn the more traditional analysis of the intermediate resonance structures. In this analysis, we must decide that a positive charge adjacent to the positive charge of a nitro group is the most destabilizing. That would make the nitration meta to the CN an unfavorable position.

A similar analysis for nitration at the alternate position puts the charge adjacent to the CN group. Here, a formal charge is not present, simply an sp carbon. Since an sp carbon is the most electron withdrawing, it too would no be favored. However, if one were to predict, one would predict this is where substitution should occur.

As I stated earlier, if the substitutents conflict in direction, I would anticipate a mixture to form. If as in this case, the major product (50.1 v 49.4) is in fact the unexpected ortho to the nitro, I cannot provide a satisfactory explanation.

Again, I prefer the upper analysis as it does not require drawing as many resonance structures, it does not require one to recognize one of the resonance structures as destabilizing or a greater preference, and it does not suggest that they actually form. I believe the rate determining step is the actual attack. If attack did occur (as it does) at positions that give the lesser contributing resonance structures, they still go to product. I also find it easier to predict whether a compound will react faster or slower than benzene from the charge present in the resonance contributors.

[sjb]

Is there not perhaps a steric argument for preferring 2,4-dinitrobenzonitrile, rather than 3,4-nitrobenzonitrile? I acknowledge that both are probably relatively disfavoured due to the deactivating effects on the ring. Also, a slightly wacky thought but could there be a sort of directing effect co-ordinating a generic E⁺ ortho to the nitro (with the partial negative charge on an oxygen of the nitro group)?

[sumedh]

So finally which one is the major product? I am not getting the meaning of the last reply

[orgopete]

This problem is described in a difficult way. If you were to ask an organic chemist what the product of nitration of p-nitrobenzonitrile was, I believe most would say 2,4-dinitrobenzonitrile. Even though both substitutents are meta directors, a nitro group is more electron withdrawing. As you may note from the resonance structure of the arenium ion, formation of the 3,4-dinitrobenzonitrile would have a positive charge adjacent to the nitrogen positive charge. That should more strongly disfavor its formation. That would be the prediction.

However, it has been asserted that 3,4-dinitrobenzonitrile is in fact the major product. Explain. Even with a single group, mixtures result. From that result and because two groups are competing in their orienting directions, I am expecting a mixture to result. I for one thought that okay, if 3,4- is the major product, I really don't know why, but I furthermore thought even if it were, there is still going to be a lot of the 2,4- product.

[sjb]

So finally which one is the major product? I am not getting the meaning of the last reply

Basically, what I am trying to get over (and obviously not succeeding ) is that there are many factors that affect reactivity, you have alluded to electronics, but there are also steric (spatial) considerations that may affect regioselectivity. Generally you fit mechanisms to products, not the other way around.