The Effect of Substituents on Reactivity

•  Substituents that donate electron density to the benzene ring increase

benzene s nucleophilicity and stabilize the carbocation intermediate.

•  Substituents that withdraw electron density to the benzene ring

decrease benzene s nucleophilicity and destabilize the carbocation intermediate.

© 2014 Pearson Education, Inc.

 Inductive Electron Withdrawal and Donation

•  A substituent more electronegative than a hydrogen withdraws σ electrons

inductively from the benzene ring more than a hydrogen will.

•  An alkyl group donates electrons by hyperconjugation.

© 2014 Pearson Education, Inc.

 Resonance Electron Donation

A lone pair on an atom directly attached to the ring

donates electrons by resonance.

© 2014 Pearson Education, Inc.

 Resonance Electron Withdrawal

An atom directly attached to the ring that is doubly or triply bonded to

an electronegative atom withdraws electrons by resonance.

© 2014 Pearson Education, Inc.

 Strongly Activating Substituents

All the strongly activating substituents donate electrons by resonance.

All the strongly activating substituents withdraw electrons inductively.

Because the substituents are activating, electron donation by resonance is more

significant than inductive electron withdrawal.

© 2014 Pearson Education, Inc.

 Moderately Activating Substituents

Moderately activating substituents donate electrons by resonance.

© 2014 Pearson Education, Inc.

 Moderately Activating Substituents

Moderately activating substituents are less effective than

strongly activating substituents because they
donate electrons in two competing directions.

© 2014 Pearson Education, Inc.

 Weakly Activating Substituents

Alkyl substituents donate electrons by hyperconjugation.

Aryl and CH═CHR donate and withdraw electrons by resonance:

electron donation is more important.

© 2014 Pearson Education, Inc.

 Weakly Deactivating Substituents

All the weakly activating substituents donate electrons by resonance.

All the weakly activating substituents withdraw electrons inductively.

Because the substituents are deactivating, electron withdrawal

is more important than electron donation.

© 2014 Pearson Education, Inc.

 Moderately Deactivating Substituents

All the moderately deactivating substituents withdraw electrons by

resonance and withdraw electrons inductively.

© 2014 Pearson Education, Inc.

 Strongly Deactivating Substituents

All the strongly deactivating substituents (except ammonium ions)

withdraw electrons inductively and by resonance.

Ammonium ions strongly withdraw electrons inductively.

© 2014 Pearson Education, Inc.

© 2014 Pearson Education, Inc.
 The Effect of Substituents on Orientation

When an electrophilic aromatic substitution reaction occurs on a

substituted benzene, where does the new substituent attach itself?

© 2014 Pearson Education, Inc.

 Ortho–Para Directors

•  All activating substituents are ortho–para directors.

•  Weakly deactivating substituents (halogens) are ortho–para directors.

© 2014 Pearson Education, Inc.

 Meta Directors

All moderately and strongly deactivating substituents are meta directors.

© 2014 Pearson Education, Inc.

 Which Carbocation Intermediate
is the Most Stable?

For substituents that donate electrons by resonance,

ortho or para substitution forms a relatively stable resonance contributor.
© 2014 Pearson Education, Inc.
 Which Carbocation Intermediate
is the Most Stable?

For substituents that donate electrons inductively,

ortho or para substitution forms a relatively stable resonance contributor.
© 2014 Pearson Education, Inc.
 Which Carbocation Intermediate
is the Most Stable?

For substituents that withdraw electrons,

ortho or para substitution forms a relatively unstable resonance contributor.
© 2014 Pearson Education, Inc.
 Substituents on the Benzene Ring
Affect the pKa

© 2014 Pearson Education, Inc.

 Substituents on the Benzene Ring
Affect the pKa of Phenol

electron donating groups decrease the acidity

(destabilize the conjugate base)

electron withdrawing groups increase the acidity

(stabilize the conjugate base)

© 2014 Pearson Education, Inc.

 Substituents on the Benzene Ring
Affect the pKa of Benzoic Acid

electron donating groups decrease the acidity

(destabilize the conjugate base)

electron withdrawing groups increase the acidity

(stabilize the conjugate base)

© 2014 Pearson Education, Inc.

 Substituents on the Benzene Ring
Affect the pKa of Protonated Aniline

electron donating groups decrease the acidity

(destabilize the conjugate base)

electron withdrawing groups increase the acidity

(stabilize the conjugate base)

© 2014 Pearson Education, Inc.

 The Ortho–Para Ratio

The size of a substituent affects the ortho–para ratio.

© 2014 Pearson Education, Inc.
 Halogenation with a
Strongly Activating Group Present
halogenation of a ring with a strongly activating substituent
does not require a catalyst

if a catalyst is used,
substitution occurs at all ortho and para positions

© 2014 Pearson Education, Inc.

 Friedel–Crafts Reactions Do Not
Occur with Meta Directors

Friedel–Crafts reactions are the slowest of the electrophilic aromatic substitution

reactions and do not occur if the ring is moderately or strongly deactivated.

© 2014 Pearson Education, Inc.

 Anilines Do Not Undergo
Friedel–Crafts Reactions

The lone pair on the amino group forms a complex with the Lewis acid
catalyst, which converts the substituent to a meta director.

© 2014 Pearson Education, Inc.

 Aniline Must Be Protected in
Order to Be Nitrated

•  Aniline cannot be nitrated directly because nitric acid will oxidize an NH2 group.

•  If the amino group is protected by acetylation, the ring can be nitrated.

•  An acetyl group is removed by acid-catalyzed hydrolysis.

© 2014 Pearson Education, Inc.

 Designing a Synthesis

two routes for the synthesis of 2-phenylethanol

The preferred route depends on the number of steps, the complexity of

each reaction, and the overall yield.
The first route is preferable.

© 2014 Pearson Education, Inc.

 The Order of the Reactions is Important

The order of the reactions is important.

© 2014 Pearson Education, Inc.

 The Order of the Reactions is Important

The acetyl group must be added first because a

Friedel–Crafts acylation will not occur with a meta director on the ring.

© 2014 Pearson Education, Inc.