wwu -- chemistry what happens when there is a substituent already present? where does the second...

WWU -- ChemistryWWU -- Chemistry

•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?

X

A

??

??

??

... or does it matter?


In order to answer this kind of question, let us examine two typical examples:


The Nitration of AnisoleO

CH3 HNO3

OCH3

OCH3

OCH3

NO2

++

NO2

O2N

minor

trace

major

anisole


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.


•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.


H NO2

H

O CH3

+

H NO2

H

O CH3

+

H NO2

H

O CH3+

H NO2

H

O CH3

+

H

H

NO2

O CH3

+

H

H

NO2

O CH3

+

H

H

NO2

O CH3

+H

H

NO2

O CH3+

H

H NO2

O CH3

+H

H NO2

O CH3

+H

H NO2

O CH3

+

ortho

meta

para :

:

EXTRA!

EXTRA!

..

..


•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!!!


But why is the para product major, while the ortho product is minor?

OCH3

sterichindrance

approachis OK


The Nitration of NitrobenzeneNO2

HNO3 (fuming)

NO2

NO2 NO2

NO2

++

NO2

O2N

trace

major

ca. 0%

nitrobenzene

H2SO4


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.


•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.


ortho

meta

para

BAD!

BAD!

H

NO2

NO O

H

NO2

NO O

H

NO2

NO O

NO O

NO O

NO O

H

NO2

H

NO2

H

NO2

NO O

NO O

NO O

H NO2 H NO2 H NO2


•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!!!


Substituent Effects on Electrophilic Aromatic Substitution


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.


meta-Directing SubstituentsNO2 N(CH3)3

C OH

O

C OR

O

C Cl

O

C NR2

O

C R

O

C H

O

C N S OH

O

O

-I

all are -I, -R, except

-N(CH3)3+


•Why is -N(CH3)3+ a -I group?

•Why isn’t it also a -R group?


ortho-para-Directing Groups (Activating)

OH O OR

S O C R

O

CH3

SH SR CR3

NH2 NR2 NH C R

O

All are -I, +R, except as indicated.

+I, +R

+I, +R

+I, +R


ortho-para-Directing Groups (Deactivating)

F Br

Cl I

All are -I, +R.


Where does the third substitution go, when there are already two substituent groups on benzene?


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.


GROUPS ACTING IN CONCERTGROUPS ACTING IN CONCERT

O CH3

NO2

m-director

o,p director

HNO3

H2SO4 O CH3

NO2

NO2 majorproduct

verylittleformed

O CH3

NO2O2N

stericcrowding

When groups direct to thesame positions it is easy topredict the product.


GROUPS COMPETINGGROUPS COMPETING

o,p-directing groups winover m-directing groups

HNO3

H2SO4

O CH3

NO2

NO2

O CH3

NO2

O2N

O CH3

NO2

toocrowded

X+


HNO3

H2SO4

RESONANCE EFFECT RESONANCE EFFECT versusversus HYPERCONJUGATIONHYPERCONJUGATION

O CH3

CH3

NO2

O CH3

CH3

+R

+R (by hyperconjugation)

resonance effects are moreimportant than hyperconjugation

majorproduct


SOME GENERAL RULESSOME 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.


Predict where the aromatic substitution will take place (to form the major product)

CH3

CH3

CH3

CH3

CH3

CH3

minor


More...

OCH3

CH3

OCH3

NO2

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