Lecture 4

Friedel-Crafts acylation
O

Cl CH3

AlCl3 CH3

O
..
..

+ - +
CH3 – C – Cl – AlCl3 → CH3 – C ≡ O

O O

+ CH3 CH3
H

-
AlCl4
No rearrangement
O

Cl

AlCl3

O H H
Wolff
Kishner
R R' NH2-NH2
R R'
NaOH
HCl/Zn

H H

alkane
R R'
 O

O H H

Cl
Wolff
AlCl3 Kishner

Cl

AlCl3

O O

Cl Wolff
Kishner
AlCl3

Substituent effects
X

E+
How is X going to affect things?

NO2

HNO3
H2SO4

CH3

HNO3
25x faster
H2SO4

NO2

HNO3
Million times slower
H2SO4
Substituents can be divided into:
-Activating (-NH2, -OH, -OR, alkyl, acyl, etc.)
-Deactivating groups (Cl, Br, I, NO2, ketones, etc.)

Activating groups have electron density that can be pushed onto the ring.

Deactivating groups take electron density from the ring.

.. .. .. .. ..
O H O H +O H +O H +O H
..

..

.. - -

..
↔ ↔ ↔

..
-
Inductive effect Resonance effect
(electronegative)

Resonance effect is more important than inductive effect.

Hydroxyl group → activating (will react w/electrophiles a
lot faster)

.. .. .. .. .. .. .. ..
- O N .. - - ..
O
..

..

O
- .. N O - O N O
.. - .. O N O
.. -
..

..

..

..

..
.. ..

+ +
↔ ↔ ↔

Take e- density away

→ Ring is more electron poor
→ Ring is delocalised for reactions w/electrophiles

CH3
Alkyl groups only inductively donate into the ring
- slight increase in electron density
-mildly activated
..
NH2

→ activate the ring

..
X
→ lone pair activates the ring
-exceptions are Cl, Br, I

O C=X
C=N Double bonds
C=O deactivate
C≡N
CH3 +
N=O

O-

NH2 OH OCH3 CH3 Ph H F Cl Br I CHO SO3H CN NO2 +NR3

COCH3
NH CH3
activating CO2Me deactivating

But not every position is activated to the same extent in inductive effect
- favours greater negative charge
OH
-meta position is left as the least worst position
-meta position has not been deactivated as much as
ortho or para positions

X=Y
Deactivating groups are “meta” directors
Exceptions:

.. .. ..
Br Cl I
..

..

..
..

..

..
Deactivating groups.
But are ortho, para directors

..
O CH3 OCH3 OCH3
..

SO3H
SO3
+
H2SO4

SO3H

+
2 (for each ortho) : 1
SO3H

NH2 O NH2 O NH2

Cl CH3 CH3 +

O CH3

.. O .. O .. O
O O O
..

..

..

CH3 CH3 CH3

Br
Br2
FeBr3

Br

C≡N C≡N

HNO3 Meta position

H2SO4
NO2
 NO2 NO2
Br2
FeBr3

Br

CH3 Cl
Cl2 CH3 CH3
O AlCl3
O + O

Cl
Makes it count as an alkyl group