Electrophilic Substitution

Introduction:

a) Benzene does not undergo electrophilic addition

b) It undergoes electrophilic aromatic substitution maintaining the aromatic core

c) Electrophilic aromatic substitution replaces a proton on benzene with another electrophile

1) Halogenation of Benzene:

1.1) Benzene's pie electrons participate as a Lewis base in reactions with Lewis acids

a. Lewis Acid : Electron Pair Acceptor

b. Lewis Base : Electron Pair Donor

1.2) The product is formed by loss of a proton, which is replaced by a halogen

a) Chlorine and iodine (but not fluorine, which is too reactive) can produce aromatic substitution with the addition of other reagents to promote the reaction

b) Chlorination requires FeCl3

c) Iodine must be oxidized to form a more powerful I+ species (with Cu2+ from CuCl2)

2) Aromatic Nitration:

a) The combination of nitric acid and sulfuric acid produces NO2+ (nitronium ion)

b) The reaction with benzene produces nitrobenzene

c) The Nitro group can be reduced to an Amino group if needed

3) Aromatic Sulfonation:

a) Substitution of H by SO3 (sulfonation)

b) Reaction with a mixture of sulfuric acid and SO3 (''Fuming H2SO4)

c) Reactive species is sulfur trioxide or its conjugate acid

4) Alkylation of Aromatic Rings: The Friedel - Crafts Reaction:

a) Alkylation among most useful electrophilic aromatic substitution reactions

b) Aromatic substitution of R+ for H+

c) Aluminum chloride promotes the formation of the carbocation

5) Limitations of the Friedel-Crafts Alkylation:

a) Only alkyl halides can be used (F, Cl, I, Br)

b) Aryl halides and vinylic halides do not react (their carbocations are too hard to form)

c) Will not work with rings containing an amino group substituent or a strongly electron-withdrawing group

6) Other Problems with Alkylation:

a) Multiple alkylations can occur because the first alkylation is activating

b) Carbocation Rearrangements Occur During Alkylation

- Similar to those occuring during electrophilic additions to alkene

- Can involve H or alkyl shifts

7) Acylation of Aromatic Rings:

Overcome on fridel craft alkylation :

a) Reaction of an acid chloride (RCOCl) and an aromatic ring in the presence of AlCl3 introduces acyl group, - COR

b) Followed by wolf kishner or claimenson reduction to give alkyl chain.

- Benzene with acetyl chloride yields acetophenone

- Avoids many of the problems of alkylation

- Only substitutes once, because acyl group is deactivating

- No rearrangement because of resonance stabilized cation

Mechanism:

8) Directing Groups / Activating Groups & Deactivating Groups:

9) Ortho/Para-Directing Activators: Alkyl Groups:

a) Alkyl groups activate by induction: direct further substitution to positions ortho and para to themselves

b) Alkyl group has most effect on the ortho and para positions

10) Ortho/Para-Directing Activators: OH and NH2:

1.Alkoxyl, and amino groups have a strong, electron-donating resonance effect

2.Most pronounced at the ortho and para positions

11) Ortho/Para-Directing Deactivators: Halogens:

a) Electron-withdrawing inductive effect outweighs weaker electron-donating resonance effect

b) Resonance effect is only at the ortho and para positions, stabilizing carbocation intermediate

12) Meta-Directing Groups Deactivators:

a) Inductive and resonance effects reinforce each other

b) Ortho and para intermediates destabilized by deactivation of carbocation intermediate

c) Resonance cannot produce stabilization

NO2 :

12) Vilsmeier - Haack reaction:

The Vilsmeier - Haack reaction (also called the Vilsmeier reaction) is the chemical reaction of a substituted amide with phosphorus oxychloride and an electron-rich arene to produce an aryl aldehyde or ketone.

The reaction is named after Anton Vilsmeier andAlbrecht Haack.

The reaction of a substituted amide with phosphorus oxychloride gives a substituted chloroiminium ion, also called the Vilsmeier reagent.

The initial product is an iminium ion, which is hydrolyzed to the corresponding aromatic ketone oraldehyde during workup.