Friedel-craft’s acylation of anisole
Introduction:
The purpose of this experiment is to perform Friedel-Crafts acylation of anisole, and
to determine whether this would yield the para-, ortho-, or meta-isomer of methoxy
acetophenone, or a mixture of the isomers. A Friedel-Craft reaction is an example of
a substitution of aromatic compounds in which a new carbon-carbon bond is formed
by the substitution of an alkyl or an acyl (COCH3) group.
In this experiment we will use Aluminum chloride as a catalyst and acetic anhydride
as the acetylating agent. The aluminum chloride can act as a Lewis acid by receiving
an electron pair from the acetic anhydride. This causes the acetic anhydride to split
into an acetate ion and a potential acetyl group with a carbocation (the acylium ion).
After this work up step, the acylium ion reacts with the aromatic ring of anisole in a
twostep substitution with the formation of methoxy acetophenone.
Theoretically there is the possibility that the acetyl group will be added to any carbon
on the benzene ring which could result in the formation of the meta, para and ortho,
isomers. It is expected that, one product can be predominantly forming due to the
activating nature of the substituent present in anisole(-OCH3). The alkoxy group can
activates the benzene ring and directs the electrophilic acyl group to the para position
due to its electron donor capability. However, the possible products can be identified
by the different absorption bands on the IR and 1H NMR spectra due to different
amount of adjacent hydrogen atoms to the substituted groups.
Reaction Diagram, Mechanism and Structures of Relevant Molecules:
Formation of intermediate acylium ion:
Methoxy group as para directing.
Methoxy group as ortho directing.
Reagent Table & Theoretical Yield Calculation:
Name
Formu
la
MW
(g/m
ol)
MP
(°C)
BP (°C)
Densi
ty
(g/ml
)
1.000
at
3.98°
C
1.325
at
25°C
1.082
Weight
(g)
Volu
me
(ml)
mmoles
Water
H2O
18.02
0
100
Dichloromethane
(Methylene
Chloride)
Acetic Anhydride
CH2Cl2
84.93
-97
39.840
13.25
10
156
C4H6O
102.1
-73
140
1.082
1
10.6
AlCl3
133.3
193
2.44
2.9
318
Sublim
es
1390
NaOH
MgSO
4
40
120.3
7
2.13
2.66
0.6
NaCl
HCl
58.44
36.46
801
-30
1413
>100
C7H8O
108.2
-38
155
2.165
1.18
at
25°C
0.996
Anisole
4'Methoxyacetophe
none
C9H10
O2
150.2
39
258
1.082
3
Aluminum
Chloride
Sodium Hydroxide
Magnesium
Sulfate,
Anhydrous
Sodium Chloride
Hydrochloric Acid
22
5
15
5
1.08
1.09
10
1.502
(Theoreti
cal yield)
1.39
10
(Theoreti
cal yield)
Operations Flowchart, Diagrams, & Apparatus Set-up
-
Step-by-step Experimental Procedure:
Reaction:
 Assemble an apparatus for addition under reflux using a 25-mL round-bottom
flask.
 Fit the condenser with a Y-adapter (provided) to trap HCl gas via an inverted longstem funnel.
 One end of the Y-adapter should be clasped, while the other end be attached to
the acid trap (an inverted long-step funnel fitted over a beaker filled with water).
The trap dissolves escaping HCl in water.
 Connect the Y adapter on the condenser with a straight tube and a thermometer
adapter.
 Place a stir bar in the 25 mL round bottom flask. Assemble the glassware and add
the reagents to the flask.
 Weigh 10.0 mmol anisole and combine it with 10 mL DCM (as a solvent) in a
round bottom flask.
 Collect AlCl3 (2.9 g, 22 mmol) which would be provided in glass vials.
 Transfer AlCl3 to the round bottom flask. If necessary, use an extra 5 mL solvent,
DCM, to rinse residual AlCl3 from the vial into the flask.
 And add a stir bar or boiling chips, to the reaction flask.
 Quickly attach the round bottom flask to the condenser and start the stirring
 Reassemble the apparatus under the hood, measure the Acetic anhydride (1 mL,
11 mmol) into a separatory addition funnel, stopper the funnel immediately.
 Add the acetic anhydride slowly (dropwise) via the addition funnel.
 After all the acetic anhydride has been added, turn on the heat to the water bath.
 Have a beaker of cold water ready to moderate the reaction. The ice-cold water
can be transferred to the water bath to subside the vigorous boiling if required.
Separation and purification:
 Slowly pour the reaction mixture over 10 g of ice in a 250 mL beaker.
 Add 10 mL distilled water to a graduated cylinder and place the cylinder in an ice
bath. Use ice-cold water to transfer any residue from the round bottom flask to the
beaker.
 Use a glass stir rod to break-up the ice and fully dissolve the contents of the beaker.
 Transfer the mixture to a separatory funnel.
 Drain the aqueous layer from the separatory funnel.
 Wash the organic layer (DCM) with 5 mL 3M NaOH followed by 5 mL saturated
aq. NaCl and remove the aqueous layer after each step.
 Dry the organic layer over MgSO4 and gravity filter off the contents into a preweighed round bottom flask.
 Use a rotavap to remove the organic solvent.
 Weigh the final product and record its mass.
 If the product remains a liquid at room temperature, we can’t acquire its melting
point (mp 38-39 ºC) measurement.
Analysis:
 For TLC analysis, develop a plate of the starting materials (acetic anhydride,
anisole), alongside the synthesized final product and co-spot lane.
 To spot the plate with the product, dissolve a portion of it in dichloromethane
(DCM).
 The developing solvent of 90% hexanes and 10% ethyl acetate and the standard
starting materials would be provided by TA.
Cheat sheet notes:
 Clamp the neck of the round-bottom flask and use blue keck clips to secure all
joints. Your TA and/or instructor must review the apparatus set-up before you turn
on the water to the condenser.
 Anhydrous aluminum AlCl3 can deactivated by water; protect it from
atmospheric moisture and be sure that your glassware is free of residual water
and acetone.
 Avoid contact with AlCl3, acetic anhydride and DCM and do not breath their
vapours. Keep acetic anhydride away from water.