BenZene Ractions Dr Md Ashraful Alam Assistant Professor Department of Pharmaceutical Sciences

Benzene does not undergo electrophilic addition It undergoes electrophilic aromatic substitution maintaining the aromatic core Electrophilic aromatic substitution replaces a proton on benzene with a.nother electrophile 2

3 electrophilic aromatic substitution

Electrophilic Aromatic Substitution

Ortho-Para and Meta Directing Substituents When substituted benzenes undergo further substituents, the substituent group present in the benzene derivative will influence electrophilic substitution in 2 ways which are: i) Reactivity ii)Orientation

EFFECTS OF SUBSTITUENTS ON THE REACTIVITY OF ELECTROPHILIC AROMATIC SUBSTITUTION Substituent group present in the benzene ring can influence the rate of reaction of further substitutions. Electron-donating groups make the ring more reactive (called activating groups) thus influence the reaction become faster. Electron-withdrawing groups make the ring less reactive (called deactivating groups) thus influence the reaction become slower.

A substituents group already in the ring influences the position of further electrophilic substitution whether at ortho, meta or para position. Ortho-para directors: the groups that tend to direct electrophilic substitution to the C2 and C4 positions. Meta directors: the groups that tend to direct electrophilic substitution to the C3 position. EFFECTS OF SUBSTITUENTS ON THE ORIENTATION OF ELECTROPHILIC AROMATIC SUBSTITUTION

Effetcs of substituent groups on the benzene ring Activating groups (electron donating) Deactivating groups (electron-withdrawing) -NH 2 -R -OH -OR -NHCOCH 3 -F -Cl -Br -I ortho-para directors meta directors

Disubstituted Benzenes : Orientation Orientation Effects of Substituents in Electrophilic Aromatic Substitution : Meta directorsOrtho, para directors -NO2 -SO3H -COOH, -COOR -CHO, -COR -CN -OH, -OR -NH2, -NHR, -NR2 -C6H5 -CH3, -R (alkyl) -F, -Cl, -Br, -I

10 Substituent Effects in Aromatic Rings Substituents can cause a compound to be (much) more or (much) less reactive than benzene Substituents affect the orientation of the reaction – the positional relationship is controlled –ortho- and para-directing activators, ortho- and para- directing deactivators, and meta-directing deactivators

11 Activators/ Deactivators

Specific Electrophilic Aromatic : Substitution Reactions

EAS Reactions of Benzene

Benzene’s  electrons participate as a Lewis base in reactions with Lewis acids –Lewis acid: electron pair acceptor –Lewis base: electron pair donor The product is formed by loss of a proton, which is replaced by a halogen 14 Bromination / Chlorination

Bromination Mechanism

Nitration

Nitration Mechanism

Nitration of Toluene

Sulfonation is Reversible

Desulfonation

Friedel-Crafts Acylation

1 st, Formaton of Electrophile

Acylation Mechanism

Intermediate is Resonance-Stabilized

An Acylation

Friedel-Crafts Alkylation many more limitations

Mechanism

Carbocation Generated From Alkene

Unexpected Product?

Carbocations Rearrange…

1 o RX Typically Undergoes Shift

Side Chain Reactions 1) Reduction of Aromatic Ketones

Straight-chain Alkylation can be Accomplished in 2 steps: Acylation, then Reduction

2) Oxidation of Alkyl Substituents

3) Benzylic Bromination with NBS N-Bromosuccinimide

4) Alkali Fusion of Sulfonic Acids

5) Reduction of Nitro Groups

Directing Effects

ortho/para-Directing Activating Groups

Nitration of Anisole

Nitration Affords ortho and para Products

Activating ortho/para directors

meta-Directing Deactivating Groups

Electron-Withdrawing Nitro Group Directs meta

meta Directors

Comparison

More Limitations with Friedel Crafts Reactions

Substituent Summary

Halogens are the Anomoly Deactivators and o,p-Directors

Reactions of Rings With Two or More Substituents

The (More) Activated Ring Reacts

Mixtures with Conflicting Directing Effects

Provide the Reagents

Must Acylate First

Sulfonic Acid Blocks para Position

Give the Reagents

Provide the Reagents

65 Reactions of Benzene