EAS on Substituted Benzenes

• How do we know where E+ will substitute?• In general, consider:

1. Orientation• Z is either an ortho,para-director or a meta-director

2. Rate• Z is either activating (the rate of reaction is faster than benzene) or

deactivating (the rate of reaction is slower than benzene)

Z

E+

Z Z Z

E

E

E

Example 1• Nitration of nitrobenzene

• Is –NO2 (the existing substituent) an ortho,para-director or a meta-director?

• Is –NO2 an activator or a deactivator?

NO2

HNO3

NO2NO2 NO2

NO2

NO2

NO2

H2SO4

100 oC

93%

7%

Example 2• Bromination of anisole

• Is –OCH3 an ortho,para-director or a meta-director?

• Is –OCH3 an activator or a deactivator?

• Why more para product than ortho?

OCH3

Br2

OCH3 OCH3

Br

Br

H2O

4%

96%

Activating vs. Deactivating Substituents

• What structural features do activating substituents have in common?

• What structural features do deactivating substituents have in common?

• Electron-donating groups vs. electron-withdrawing groups

Activating/Deactivating Substituent

Strongly activating -NR2, -OR (R = H or alkyl)

Moderately activating -NHC(O)R, -OC(O)R

Weakly activating -R, -Ph

Weakly deactivating -X

Moderately deactivating -C≡N, -SO3H, -C(O)Z (Z = H, R, N, O)

Strongly deactivating -NO2, -NR3+

Remember, no F-C reactions with these substituents

• Activators• Electron-donating groups• Have lone pair on atom next to

benzene, or can donate electrons through induction (-R, -Ph)

• More electron density on ring makes benzene a better nucleophile

• Deactivators• Electron-withdrawing groups• Have + or d+ on atom next to

benzene• Less electron density on ring

makes benzene less nucleophilic

Activating vs. Deactivating Substituents

• Induction• Electrons moving

toward or away from ring through bonds

• Based on partial charges; electronegativity

• Resonance• Substituent on ring

can participate in resonance structures

Electron Donating and Withdrawing

Directing Effects

• Which of these substituents are ortho,para-directors?• Which of these substituents are meta-directors?• Why?

Activating/Deactivating Substituent

Strongly activating -NR2, -OR (R = H or alkyl)

Moderately activating -NHC(O)R, -OC(O)R

Weakly activating -R, -Ph

Weakly deactivating -X

Moderately deactivating -C≡N, -SO3H, -C(O)Z (Z = H, R, N, O)

Strongly deactivating -NO2, -NR3+

↑ o,p

↓ m

Directing Effects• Relationship between structure and orientation effects?• o,p-Directors

• Electron-donating groups

• m-Directors• Electron-withdrawing groups

• Why?• Look at how the intermediates (o,p and m) are stabilized through

resonance or induction

Example• Nitration of anisole

• See benzene worksheet questions 20-24

• o,p-Intermediates have more resonance structures (4) than m-intermediate (3)

Example• Nitration of

nitrobenzene

• See benzene worksheet questions 25-28

• m-Intermediate has more stable resonance structures (3) than o,p-intermediates (3 structure, but 1 is unlikely to form)

Summary• Electron-donating groups: activators and o,p-directors• Electron-withdrawing groups: deactivators and m-directors• Exception: halogens

• Deactivators (EWG due to electronegativity and inductive effect)• o,p-Directors (EDG through resonance)

Summary

EAS on Disubstituted Benzenes• Example 1:

EAS on Disubstituted Benzenes• Example 2:

EAS on Disubstituted Benzenes• Example 3:

Predict the major product(s)

a)

b)

c)

d)

e)

f)

Br2

FeBr3

Br2

FeBr3

O

C

O

CH3CH2COCl

AlCl3

NO2

CH3Cl

AlCl3

OH

Br2

FeBr3

NO2

HNO3

H2SO4

Synthesis Example 1• How would you prepare m-bromonitrobenzene from

benzene?• Process:

1. Identify steps that need to occur• Bromination • Nitration

2. Figure out the order in which the steps need to occur• Which reaction comes first?• Look at directing effects of the two substituents to decide

• Synthetic scheme:

Synthesis Example 2• Target molecule:

• Look at possible precursors

Synthesis Example 2, cont.• Then, look at possible precursors to that target

Synthesis Example 2, cont.• Finally, create synthesis scheme:

Synthesis Example 3From McMurry, Organic Chemistry, 8th ed., 2012

Synthesis Example 3, cont.

Synthesis Example 3, cont.

Synthesis Example 3, cont.

Synthesis Problems

a)

b)

c)

Cl

C(O)CH3

CO2H

Cl

CH3

NO2

Cl

C

O

HO