ppt

1. Presentation By
Aadil Ali Wani
The Elimination-Addition Mechanism
of Nucleophilic Aromatic Substitution:
Benzyne

2. Cl NH2
Aryl Halides Undergo Substitution When
Treated With Very Strong Bases
KNH2, NH3
–33°C
(52%)

3. 2
NH3
–33°C
Regiochemistry
new substituent becomes attached to either
the carbon that bore the leaving group or
the carbon adjacent to it
CH3 CH3 CH3
Br NaNH2, NH
+
NH2

4. +
2
Regiochemistry
new substituent becomes attached to either
the carbon that bore the leaving group or
the carbon adjacent to it
CH3 CH3 CH3
NaNH2, NH3
–33°C NH
Br NH2

5. Regiochemistry CH3
NH2
NaNH2, NH3 –33°C
CH3 CH3 CH3
NH2
+ +
NH2
NH2

6. Same result using 14C label
* Cl
KNH2, NH3 –33°C
NH2
* + * NH2
(52%) (48%)

7. Cl •
••
• NH2•H H
Mechanism
Step 1
H
H
••
•
–
••
H

8. –
••• Cl•H Cl • • •H
• NH2•H H H
2
••
Mechanism
Step 1
H H
• ••
•
•• ••
–
••
H NH
H H
compound formed in this step is called benzyne

9. Benzyne
H
H
H
H
Benzyne has a strained triple bond.
It cannot be isolated in this reaction, but is
formed as a reactive intermediate.

10. • NH2•
Mechanism
Step 2
H
H –
••
H
H

11. ••
• NH2•
NH2H H
Mechanism
Step 2
H H
H – H –
••
••
H H
Angle strain is relieved. The two sp-hybridized
ring carbons in benzyne become sp2 hybridized
in the resulting anion.

12. ••
••
••
Mechanism
Step 3
H H NH2
H –
H NH2
H

13. NH2• HH NH2 H•
••
••••
Mechanism
Step 3
–
•• ••
H H H –
H NH2 H NH2
H H

14. reaction of
with NaOH
Hydrolysis of Chlorobenzene
14C labeling * Cl
indicates that
the high-
temperature NaOH, H2O 395°C
chlorobenzene OH
goes via
benzyne. * + * OH
(43%) (54%)

15. Diels-Alder Reactions of Benzyne

16. Other Routes to Benzyne
Benzyne can be prepared as a reactive
intermediate by methods other than treatment of
chlorobenzene with strong bases.
Another method involves loss of fluoride ion
from the Grignard reagent of 1-bromo-2-
fluorobenzene.

17. Mg, THF
• •F
••
F
••
• •
Other Routes to Benzyne
Br MgBr
•• heat ••
+ FMgBr

18. Benzyne as a Dienophile
Benzyne is a fairly reactive dienophile, and
gives Diels-Alder adducts when generated in
the presence of conjugated dienes.

19. +
F
Benzyne as a Dienophile
Br
Mg, THF
heat
(46%)