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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
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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%
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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%
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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
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• 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
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• 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
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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
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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
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Example• Nitration of anisole
• See benzene worksheet questions 20-24
• o,p-Intermediates have more resonance structures (4) than m-intermediate (3)
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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)
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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)
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Summary
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EAS on Disubstituted Benzenes• Example 1:
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EAS on Disubstituted Benzenes• Example 2:
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EAS on Disubstituted Benzenes• Example 3:
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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
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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:
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Synthesis Example 2• Target molecule:
• Look at possible precursors
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Synthesis Example 2, cont.• Then, look at possible precursors to that target
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Synthesis Example 2, cont.• Finally, create synthesis scheme:
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Synthesis Example 3From McMurry, Organic Chemistry, 8th ed., 2012
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Synthesis Example 3, cont.
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Synthesis Example 3, cont.
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Synthesis Example 3, cont.
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Synthesis Problems
a)
b)
c)
Cl
C(O)CH3
CO2H
Cl
CH3
NO2
Cl
C
O
HO