Chapter 17 Aromatic Substitution Reactions 1
17.1 Mechanism for Electricphilic Aromatic Substitution Arenium ion resonance stabilization 2
Example 1. Example 2. 3
Example 2. Mechanism of the nitration of benzene 4
Addition reaction vs. Electrophilic aromatic substitution 5
< Stability < E H E < ΔGa < ΔGs Bezene is very stable so it is very diificult to break the resonance stabilization 6
Is the addition reaction possible for a benzene? Very difficult because of the stability of the product E resonance stabilization 7
17.2 Effect of Substituent 17 times faster than the substitution tut of benzenee e Why? Resonance stabilization 8
Ortho attack Meta attack Para attack Meta and para attack is favored 9 CH 3 is an ortho/para directing group
Nitration of anisole (methoxy benzene) 10,000 times faster than the substitution of benzene Why? Resonance stabilization ti 10
The effect of methoxy group 1.Inductive effect, then as the oxygen is electronegative Methoxy is deactivating group not true 2. Resonance effect explanation p 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 11
Nitration of nitrobenzene 1. 10 17 times slower than the substitution of benzene 2. meta director 12
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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 14
F Cl, Br, I 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! 15
@ 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) 16
See P 680 17
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! 18
17.4 Nitration 19
Preparation of NO 2 + 20
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! 21
Amide group: much less basis, still activator and o/p director Example, 22
17.5 Halogenation Mechanism Same as the nitration Resonance stabiliztion, Activating group faciliate the reaction Cl +AlCl 3 + HCl 23
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17.6 Sulfonation Fuming sulfuric acid 25
Mechanism 26
17.7 Friedel-Craft Alkylation 27
Mechanism of the Friedel-Craft Alkylation 28
Drawbacks 1. The alkyl groups that is added to the ring is an activated group: a large amount of products w/ two or more alkyl l groups 2. Aromatic compound w/ strongly deactivating groups cannot be alkylated. 3. Rearrangement Because CH 3 CH 2 CH 2 CH 2 Cl + AlCl 3 CH 3 CH 2 CH 2 CH 2 AlCl 4 CH 3 CH 2 CHCH 3 29
Other ways to generate carbocations Strong acid, TsOH, can eliminate water, then CH 3 -ph-ch 2+ can be generated Other examples Lewis acid is used 30
Synthetic detergents 31
BHT and BHA are anti oxidant added to food prepared by Friedel-Crafts alkylation reactions 32
17.8 Friedel-Craft Acylation Generation of acyl cation 33
Drawback: like the alkylation, this reaction does not work with strongly deactivated substrates (m directors) Examples 34
Examples 35
17.9 Electrophilic Substitution of Polycyclic Aromatic Compounds Why the 1 position is preferred? 36
Containing stable benzene ring Containing stable benzene ring 37
17.10 Nucleophilic Aromatic Substitution; Diazonium ion 38
Examples 39
17.11 Nucleophilic Aromatic Substitution; Addition-Elimination 40
Mechanism Not S N 2 but Addition-Elimination 41
The order of leaving group ability Examples 42
17.12 Nucleophilic Aromati Substitution; Elimination-Addition When there is no electron withdrawing group at o/p position, then elimination-addition i occurs with very strong base (amide anion) or with weak base at high temperature 43
Mechanism 44
Benzyne The existence of benzyne 45
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 SnCl 2 ) O H 3 CH 2 COC NH 2 Cl Application 46
Reduction of carbonyl group (aldehyde or ketone) to a methylene group 1. Clemmenson reduction 2. Wolff-Kishner reduction 3. Catalytic hydrogenation 47
H 2 /Pt reduction vs Wolff-Kishner and Clemmenson 2 reduction -H 2 /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 48
17.14 Synthesis of Aromatic Compound 49
Preparation of m-chlorobenzene and p-chlorobenzene Preparation of o-bromophenol HO HO + Br 2 Br HO + Mixuture Br 50
Preparation of m-bromochlorobenzene Problem: both chloro and bromo groups are o/p directors Solution: use NO 2, a m director Preparation of m-bromotoluene Problem: methyl group is an o/p director Solution: use NO 2, the m director 51
Preparation of m-butylbenzenesulfonic acid Benzene sulfonic acid cannot be alkylated because the Friedel- Craft alkyl- or acylation does not work with deactivating group 52
Preparation of bezene 53