Nucleophilic Aromatic Substitution…contd

CH3 CH3 CH3

NaOH +
H2O, 350 °C
OH
Cl OH

Mixture of regioisomers observed !!!

How do we explain?

Elimination-Addition mechanism
Elimination-Addition Mechanism
CH3 CH3 CH3

NaOH +
H2O, 350 °C
OH
Cl OH
Direct substitution Cine substitution Benzyne
Nucleophilic Aromatic Substitution…contd
Question

Draw the product(s) for the following reaction

CH3 CH3 CH3 CH3

NH2
NaNH2 + +
liq. NH3
Cl NH2
NH2
Generation of Benzyne
Kinetics for the Reaction
Formation of benzyne is the rate determining step

X
SNAr

X = F, Cl, Br or I (halogen)

Rate: F < Cl < Br < I

Proof for the Mechanism
• Trapping of the benzyne intermediate

Diels-Alder Adduct

• No reaction observed when ortho positions substituted

CH 3

Cl
CH 3
Excerise
• Which compound will react faster with NaOCH3?
Cl F OCH3 Cl

H 3CO O2N O2N NO 2

• Which of the following compounds give a single benzyne

intermediate on reaciton with sodium amide?

CH 3 CH 3 CH 3
Br

Br
Br
Excerise

• Synthesize the following compounds from benzene

NO 2 OMe
NO 2
OH

NH 2 Br