1. What happens when there is a substituent already present?
Where does the second substitution go?
Is the attack by the second electrophile directed, or is its approach strictly random?
WWU -- Chemistry

2. In order to answer this kind of question, let us examine two typical examples:
WWU -- Chemistry

3. The Nitration of Anisole
WWU -- Chemistry

4. The Nitration of Anisole
The first thing that we notice is that the reaction is a great deal faster than the nitration of benzene -- a sulfuric catalyst is not required here. The methoxy group has activated the ring toward electrophilic substitution.
Second, the substitution is directed substantially toward the para position with respect to the methoxy group.
Some degree of substitution also seems directed toward the ortho postion.
Subsitution in the meta position is negligible.
WWU -- Chemistry

5. one to yield the ortho product one to yield the meta product
In order to decide this question, let us consider three alternative mechanisms:
one to yield the ortho product
one to yield the meta product
one to yield the para product
When we see the alternatives, perhaps we can decide if one of them is better than the others!
In the following, assume that the preliminary step to generate the electrophile (nitronium ion is our example, here) has already happened
Also, assume that the last step (loss of proton from the arenium ion to yield the final product) will happen even though it’s not shown.
WWU -- Chemistry

6. ..
WWU -- Chemistry

7. The resonance stabilization of the arenium ion for ortho substitution and for para substitution is greater than for meta substitution.
We say, therefore, that the methoxy substituent is an ortho-para director.
The ortho-para directing ability of the methoxy group stems from its ability to delocalize its unshared electron pairs in order to stabilize the arenium ion -- this is an example of a resonance effect.
The activating property of the methoxy group also stems from its electron-releasing resonance effect.
The electrophile “sees” a ring with enhanced electron-density.
YUM!!!
WWU -- Chemistry

8. But why is the para product major, while the ortho product is minor?
WWU -- Chemistry

9. The Nitration of Nitrobenzene
WWU -- Chemistry

10. The Nitration of Nitrobenzene
The first thing that we notice is that the reaction is a great deal slower than the nitration of benzene -- the sulfuric catalyst is necessary here, and fuming nitric acid is also required. The nitro group has deactivated the ring toward electrophilic substitution.
Second, the substitution is directed substantially toward the meta position with respect to the nitro group.
Subsitution in the ortho and para positions is negligible.
WWU -- Chemistry

11. one to yield the ortho product one to yield the meta product
In order to decide this question, let us again consider three alternative mechanisms:
one to yield the ortho product
one to yield the meta product
one to yield the para product
When we see the alternatives, perhaps, once again, we can decide if one of them is better than the others!
As before, in the following, assume that the preliminary step to generate the electrophile (nitronium ion is our example, here) has already happened
Also, assume that the last step (loss of proton from the arenium ion to yield the final product) will happen even though it’s not shown.
WWU -- Chemistry

12. 4/6/2017
ortho
BAD!
meta
para
BAD!
WWU -- Chemistry

13. The resonance stabilization of the arenium ion for ortho substitution and for para substitution is worse than for meta substitution.
We say, therefore, that the nitro substituent is a meta director.
The meta directing ability of the nitro group stems from the positive charge borne by the atom directly attached to the benzene ring. This charge destabilizes resonance forms that place positive charge on the adjacent ring carbon -- this is also an example of a resonance effect.
The deactivating property of the nitro group also stems from its electron-withdrawing resonance effect.
The electrophile “sees” a ring with diminished electron-density.
YUCK!!!
WWU -- Chemistry

14. Substituent Effects on Electrophilic Aromatic Substitution
WWU -- Chemistry

15. In the following, note that:
-I represents an electron-withdrawing inductive effect
+I represents an electron-releasing inductive effect
-R represents an electron-withdrawing resonance effect
+R represents an electron-releasing resonance effect.
WWU -- Chemistry

16. meta-Directing Substituents
WWU -- Chemistry

17. Why is -N(CH3)3+ a -I group? Why isn’t it also a -R group?
WWU -- Chemistry

18. ortho-para-Directing Groups (Activating)
WWU -- Chemistry

19. ortho-para-Directing Groups (Deactivating)
WWU -- Chemistry

20. Where does the third substitution go, when there are already two substituent groups on benzene?
WWU -- Chemistry

21. When there are two or more substituent groups attached to benzene, they will compete.
If their directing effects complement one another, it is easy to predict the position of substitution.
If their directing effects do not complement one another, then it is much more difficult to predict where the next substitution will go. It becomes necessary to compare the strengths of the directing effects.
WWU -- Chemistry

22. GROUPS ACTING IN CONCERT
4/6/2017
GROUPS ACTING IN CONCERT
steric
crowding
o,p director
m-director
very
little
formed
HNO3
H2SO4
When groups direct to the
same positions it is easy to
predict the product.
major
product
WWU -- Chemistry

23. GROUPS COMPETING X o,p-directing groups win over m-directing groups
4/6/2017
GROUPS COMPETING
o,p-directing groups win
over m-directing groups
too
crowded X
HNO3 +
H2SO4
WWU -- Chemistry

24. RESONANCE EFFECT versus HYPERCONJUGATION
4/6/2017
RESONANCE EFFECT versus HYPERCONJUGATION +R
HNO3
H2SO4
major
product
+R (by hyperconjugation)
resonance effects are more
important than hyperconjugation
WWU -- Chemistry

25. 4/6/2017
SOME GENERAL RULES
1) Activating (o,p) groups (+R, +I) win over deactivating (m)
groups (-R,-I).
2) Resonance groups (+R) win over inductive (+I) groups
or over groups that are +R by hyperconjugation.
3) 1,2,3-Trisubstituted products rarely form due to excessive
steric crowding.
4) With bulky directing groups, there will usually be more
p-substitution than o-substitution.
5) The incoming group replaces a hydrogen, it will not
usually displace a substituent already in place.
WWU -- Chemistry

26. Predict where the aromatic substitution will take place (to form the major product)
minor
WWU -- Chemistry

27. More...
WWU -- Chemistry