1. Aromatic Substitution Reactions
Chapter 17
Aromatic Substitution Reactions
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2. 17.1 Mechanism for Electricphilic Aromatic Substitution
Organic Chemistry II
Fall 1999
17.1 Mechanism for Electricphilic Aromatic Substitution
Arenium ion
resonance stabilization
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Chapter 18

3. Example 1.
Example 2.
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4. Example 2. Mechanism of the nitration of benzene
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5. Addition reaction vs. Electrophilic aromatic substitution
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6. Stability
Ga < Gs Bezene is very stable so it is very diificult to break the resonance stabilization
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7. Is the addition reaction possible for a benzene ?
Very difficult because of the stability of the product
resonance stabilization
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8. 17.2 Effect of Substituent Why ? Resonance stabilization
17 times faster than the substitution of benzene
Why ?
Resonance stabilization
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9. Ortho attack Meta attack Para attack Meta and para attack is favored
CH3 is an ortho/para directing group
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10. Nitration of anisole (methoxy benzene)
10,000 times faster than the substitution of benzene
Why ? Resonance stabilization
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11. The effect of methoxy group
Inductive effect,
then as the oxygen is electronegative Methoxy is deactivating group not true
2. Resonance effect explanation is possible
This is what scientists are doing, you also should have this attitude, then find reasons. Otherwise no result at all.
Therefore, any group that has an unshared pair of electrons is the ortho/para director
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12. Nitration of nitrobenzene
times slower than the substitution of benzene
2. meta director
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13. OrgChem-Chap17

14. Activating group (elecron donating group): ortho/para director
Until now,
Activating group (elecron donating group): ortho/para director
Deactivationg group (elecron withdrawing group): meta dircectot
Exception: Halogens,
ortho/para derector + deactivating group
1. 17 times slower than the substitution of benzene
2. ortho/para director
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15. F is highly electronegative, therefore inductive withdrawing effect is stronger than the resonance effect
Cl, Br, and I are not very electronegative, while the resonance effect is not strong enough as the methoxy
Because the overlapping netween 2p AO of carbon and 3p(Cl), 4p(Br), 5p(I) AOs are not good. (2p AO for oxygen)
Still halogens are ortho/para director because there is the resonance effect although it is much weaker.
Nose ring theory !
Accurate experiment results are most important !
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16. Two ortho positions and one para position, therefore statistically the ratio or ortho to para products should be 2 to 1,
Which is generally true! (nitration of toluene)
Steric effect !
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17. See P 680
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18. 17.3 Effect of Multiple Substituent
Methyl group controls the regiochemistry, because methyl group is a strong activating group
Rule: Groups that are closer to the top of Table 17.1 controls the regiochemistry!
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19. 17.4 Nitration
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20. Preparation of NO2+
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21. A problem occurs with amino substitution
N with unpaired electrons looks like a activating group and o/p director. But under acidic condition it can be protonated, then deactivating group and m director. Although the amine (strong activating group) conc. is very low, 18% is para product!
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22. Amide group: much less basis, still activator and o/p director
Example,
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23. 17.5 Halogenation Mechanism Same as the nitration
Resonance stabiliztion,
Activating group faciliate the reaction
+ AlCl3 + HCl
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24. OrgChem-Chap17

25. 17.6 Sulfonation
Fuming sulfuric acid
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26. Mechanism
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27. 17.7 Friedel-Craft Alkylation
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28. Mechanism of the Friedel-Craft Alkylation
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29. Drawbacks
The alkyl groups that is added to the ring is an activated group: a large amount of products w/ two or more alkyl groups
Aromatic compound w/ strongly deactivating groups cannot be alkylated.
Rearrangement
Because
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30. Other ways to generate carbocations
Strong acid, TsOH, can eliminate water,
then CH3-ph-CH2+ can be generated
Other examples
Lewis acid is used
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31. Synthetic detergents
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32. BHT and BHA are anti oxidant added to food prepared by Friedel-Crafts alkylation reactions
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33. 17.8 Friedel-Craft Acylation
Generation of acyl cation
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34. Drawback: like the alkylation, this reaction does not work with strongly deactivated substrates (m directors)
Examples
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35. Examples
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36. 17.9 Electrophilic Substitution of Polycyclic Aromatic Compounds
Why the 1 position is preferred?
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37. Containing stable benzene ring
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38. 17.10 Nucleophilic Aromatic Substitution; Diazonium ion
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39. Examples
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40. 17.11 Nucleophilic Aromatic Substitution; Addition-Elimination
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41. Not SN2 but Addition-Elimination
Mechanism
Not SN2 but Addition-Elimination
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42. The order of leaving group ability
Examples
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43. 17.12 Nucleophilic Aromati Substitution; Elimination-Addition
When there is no electron withdrawing group at o/p position, then elimination-addition occurs with very strong base (amide anion) or with weak base at high temperature
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44. Mechanism
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45. Benzyne
The existence of benzyne
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46. 17.13 Some Additional Useful Reactions
Reduction of nitro group to amine using hydrogen and a catalyst or by using acid and a metal (Fe, Sn, or SnCl2)
Application
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47. Reduction of carbonyl group (aldehyde or ketone) to a methylene group
1. Clemmenson reduction
2. Wolff-Kishner reduction
3. Catalytic hydrogenation
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48. H2/Pt reduction vs Wolff-Kishner and Clemmenson reduction
H2/Pt works for the carbonyl attached to the aromatic ring
Wolff-Kishner and Clemmenson reduction do not have this restriction
Oxidation of alkyl groups bonded to the aromatic ring
If the carbon bonded to the ring is not tertiary
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49. 17.14 Synthesis of Aromatic Compound
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50. Preparation of m-chlorobenzene and p-chlorobenzene
Preparation of o-bromophenol
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51. Preparation of m-bromochlorobenzene
Problem: both chloro and bromo groups are o/p directors
Solution: use NO2, a m director
Preparation of m-bromotoluene
Problem: methyl group is an o/p director
Solution: use NO2, the m director
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52. Preparation of m-butylbenzenesulfonic acid
Benzene sulfonic acid cannot be alkylated because the Friedel-Craft alkyl- or acylation does not work with deactivating group
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53. Preparation of
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bezene