Study Set Content:
The mechanism of the electrophilic bromination of benzene the reaction occurs in two steps and involves a resonance-stabilized carbocation
An electron pair from the benzene ring attacks the positively polarized bromine, forming a new C-Br bond and leaving a nonaromatic carbocation intermediate
A base removes H+ from the carbocation intermediate and the neutral substitution products forms as two electrons from the C-H bond moves to re-form the aromatic ring
Chlorine bromine, and iodine are introduced in the aromatic ring ring by EAS
Aromatic halogenation
- F is too reactive
Fluorination
F containing Medicines:
Sitagliptin (Januvia), Fluoxetine (Prozac)
Aromatic rings react with CI2 in the presence of FeCI3 catalyst; use in synthesis of anti allergy med.
Chlorination
Chlorination medicine
Loratad (Laritin)
- lodine is unreactive in aromatic ring so H202 or CuCI2 is added.
Iodination
Example of Iodination
Biosynthesis of Thyroxine (growth regulating hormone)
Aromatic rings are nitrated by reaction with a mixture of concentrated nitric and sulfuric acids.
Aromatic Nitration
Aromatic rings are sulfonated by reaction with so-called fuming sulfuric acid, a mixture of SO3 and H2S04.
Sulfonation
- The introduction of an alkyl group onto the benzene ring
Alkylation
Alkylation
aka
- Friedel-Crafts alkylation reaction
reaction is carried out by treating the aromatic compound with an alkyl chloride, RCI, in the presence of AlCI3(catalyst) to generate a carbocation electrophile, R
Alkylation
Loss of H+ then completes the reaction
Alkylation
Substituent Effects in Electrophilic Substitution
2 effects of the initial presence of the substituent in the ring:
- Substituents affect the reactivity of an aromatic ring.
- Substituents affect the orientation of a reaction.
The substituent can be classified as
meta-directing deactivators, ortho-& para directing deactivators, and ortho & para-directing activators.
All activating groups are
ortho- and para-directing
and all deactivating groups other than halogen are
Meta-directing
The halogens are unique in being deactivating but
ortho- and para-directing.
donate electrons to the ring thereby making the ring more electron-rich, stabilizing the carbocation intermediate, and lowering the activation energy for its formation.
Activating Group:
