Substituent Effects

Chapter 12 : Reactions of Arenes. Electrophilic Aromatic Substitution

 

Substituent Effects

So far we have only seen electrophilic aromatic substitution of benzene but substituted benzenes can also undergo further substitution to give polysubstituted systems.

preparation of disubstituted aromatics
Two issues arise based on this general scheme...
ortho-, meta- and para- disubstituted benzene regioisomers

Experimental evidence from nitration experiments is tabulated below:

 Starting Material
Relative rate*
ortho
meta
para
Comments
toluene
25
63%
3%
34%
activated
ortho / para director
trifluoromethylbenzene
2.5 x 10-5
6%
91%
3%
deactivated
meta director

* relative rate is expressed with respect to benzene

The rate data shows that toluene is more reactive or activated with respect to benzene and the product distribution shows that the methyl group directs the new substituent to the ortho- and para- positions
In contrast, trifluoromethylbenzene is less reactive or deactivated with respect to benzene and directs the new substituent to the meta position.

The origin of these effects and application to substituents in general is discussed on the following page.

 

Here is a table that shows the effect of substituents on a benzene ring have on both the rate and orientation of electrophilic aromatic substitution reactions.
 

Table of Substituent Effects These effects are a combination of RESONANCE and INDUCTIVE effects (see below)
The effects are also important in other reactions and properties (e.g. acidity of the substituted benzoic acids).

Here are some general pointers for recognizing the substituent effects:

  • The H atom is the standard and is regarded as having no effect.
  • Activating groups increase the rate
  • Deactivating groups decrease the rate
  • EDG = electron donating group
  • EDG can be recognized by lone pairs on the atom adjacent to the p system, eg: -OMe
  • except -R, -Ar or -vinyl (hyperconjugation, p electrons)
  • EWG = electron withdrawing group
  • EWG can be recognized either by the atom adjacent to the p system having several bonds to more electronegative atoms, or

  • having a formal +ve or d +ve charge, eg: -CO2R, -NO2
  • EDG / activating groups direct ortho / para
  • EWG / deactivating groups direct meta
  • except halogens (-X) which are deactivating BUT direct ortho / para
  • EDG add electron density to the p system making it more nucleophilic
  • EWG remove electron density from the p system making it less nucleophilic

Thought provoking questions.....

Why are esters (-OCOR) and amides (-NHCOR) less activating than ethers (-OR) and amines (-NH) ? the lone pairs on O in esters and amides are also involved in resonance with the C=O group and therefore can not be donated to the arene as readily

Why do esters and amides appear in the table twice, once as an EDG and once as an EWG ? if the arene is connected via the heteroatom, the lone pairs can activate but if it is connected via the C=O group then it will deactivate

Why are amines (-NH2) better activators than alcohols (-OH) ? N is less electronegative than O so it is a better electron donor

There are two main electronic effects that substituents can exert:

RESONANCE effects are those that occur through the p system and can be represented by resonance structures. These can be either electron donating (e.g. -OMe) where p electrons are pushed toward the arene or electron withdrawing (e.g. -C=O) where p electrons are drawn away from the arene.

INDUCTIVE effects are those that occur through the s system due to electronegativity type effects.  These too can be either electron donating (e.g. -Me) where s electrons are pushed toward the arene or electron withdrawing (e.g. -CF3, +NR3) where s electrons are drawn away from the arene.

A simplified approach to understanding substituent effects is given here, based on the "isolated molecule approach".  The text uses the more rigorous approach of drawing the resonance structures for the intermediate formed by attack at each of the o-, m-  and p- positions.
 

Electron donating groups (EDG) with lone pairs (e.g. -OMe, -NH2) on the atoms adjacent to the p system activate the aromatic ring by increasing the electron density on the ring through a resonance donating effect.  The resonance only allows electron density to be positioned at the ortho- and para- positions. Hence these sites are more nucleophilic, and the system tends to react with electrophiles at these ortho- and para- sites.  schematic diagram to show sites of attack with an electron donating group present
resonance donation of an electron donating group

 
 
Electron withdrawing groups (EWG) with p bonds to electronegative atoms (e.g. -C=O, -NO2) adjacent to the p system deactivate the aromatic ring by decreasing the electron density on the ring through a resonance withdrawing effect.  The resonance only decreases the electron density at the ortho- and para- positions. Hence these sites are less nucleophilic, and so the system tends to react with electrophiles at the meta sites. schematic diagram to show sites of attack with an electron withdrawing group present
resonance withdrawal of an electron donating group

Halogen substituents are a little unusual in that they are deactivating but still direct ortho- / para-. The reason is that they are both inductive electron withdrawing (electronegativity) and resonance donating (lone pair donation).  The inductive effect lowers the reactivity but the resonance effect controls the regiochemistry due to the stability of the intermediates.

Besides the electronic effects, substitutents can also influence product distributions due to steric effects.  From the following data, notice how the yield of the para-nitro product increases as the size of the alkyl group -R increases and "blocks" the ortho- positions.

steric effects in electrophilic aromatic substitution
-R
%
%
%
-CH3
58
4
37
-CH2CH3
49
6
49
-CH(CH3)2
30
8
62
-C(CH3)3
16
11
73

 

The regioselectivity for further substitution of disubstituted benzenes can usually be predicted by looking at the cumulative effects of the substituents.

As a suggested method, look at each of the substituents, label their directing effects, then indicate the sites where they would promote reactivity  with small arrows. Some issues that can arise are shown by the following worked examples:
 

predicting regioselectivity of polysubs. benzenes