Experiment 16:
SYNTHESIS OF
p-METHYLACETANILIDE
O
H
N
H
H
+
H 3C
O
O
C
C
O
N
C
CH
3
O
+
CH
3
H 3C
C
OH
Objectives:




To synthesize p-methylacetanilide from pmethylaniline and acetic anhydride.
To isolate the product through a
crystallization.
To evaluate purity through melting point
analysis.
To analyze the product using IR and NMR
spectra.
Before coming to lab…

Review these techniques:

Suction filtration

recrystallization
SYNTHESIS OF THE AMIDE
O
H
N
H
H
+
H 3C
O
O
C
C
O
N
C
CH 3
+
H 3C
CH 3
C 7H 9N
C 4H 6O 3
C 9H 11N O
M W :1 0 7 .1 5 g /m o l
M W :1 0 2 .0 8 g /m o l
M W :1 4 9 .1 9 g /m o l
o
m p : 4 1 -4 6 C
O
d :1 .0 8 g /m L
o
C
OH
C 2H 4O 2
M W :6 0 .0 5 g /m o l
o
m p : 1 4 8 -1 5 1 C
d :1 .0 4 g /m L
in g e stio n h a za rd
bp: 140 C
in g e stio n h a za rd
b p : 1 1 7 -1 1 8 C
in h a la tio n h a za rd
in g e stio n h a za rd
in h a la tio n h a za rd
fla m m a b le
in h a la tio n h a za rd
fla m m a b le
co rro siv e
o
co rro siv e
MECHANISM
O
O
C
H
O
H
N
O
+
H 3C
Nucleophilic
nitrogen attacks
electrophilic
carbonyl of acetic
anhydride…
O
H 3C
C
O
H
N
H
CH 3
The pi bond of
the carbonyl
reforms. A CO bond breaks,
expelling the
acetoxy group.
CH 3
CH 3
…to form
tetrahedral
intermediate.
CH 3
O
O
H
C
N
CH 3
+
H 3C
C
H
N
O
C
H
+
C
H 3C
O
OH
CH 3
CH 3
O
CH 3
Loss of a
proton to the
acetoxy
group
produces the
amide.
SYNTHESIS



Add solid amine and deionized water
to 50 mL Erlenmeyer flask. Swirl to
mix.
Add acetic anhydride dropwise while
swirling.
React at room temp for 5 minutes,
swirling occasionally.

Dissolve solid on hotplate.

Cool to room temp.

Cool to 0o in ice water bath.
PRODUCT ISOLATION








Set up a suction filtration apparatus, clamping
filter flask to ring stand.
Attach red tubing to vacuum line.
Weigh a small filter paper. Place it in the
Buchner funnel and wet it with cold deionized
water.
Apply vacuum.
Swirl flask and pour solid SLOWLY into center
of funnel
Leave under suction for several minutes.
Transfer small filter paper containing product
to a large preweighed filter paper.
Submit product to instructor to dry until next
lab period.
Table 16.1
Theoretical yield (g)
Actual yield (g)
Cannot be obtained until following
lab period since solid will not be dry.

Cannot be calculated until following
lab period when actual yield is
obtained.

% yield
Melting range
Can be calculated during
experiment.

(oC)
Product Appearance
Cannot be obtained until following
lab period when solid is sufficiently
dry.

physical state and color of your
product.

Table 16.2
Can be calculated during the
experiment.
 Review Experiment 13 for calculation.

Atom Economy (%)
Can be calculated during the
experiment.
 Review Experiment 13 for calculation.

Experimental Atom Economy (%)
Cannot be calculated until the next lab
period, as it is based on % yield!
 Review Experiment 13 for calculation.

“Eproduct”
Can be calculated after synthesis has
been started based on the amount of
each reagent used. Cost per bottle of
reagent is given on p. 142.

Cost per Synthesis ($)
Cost per Gram ($/g)
COST PER GRAM cannot be calculated
without the value of actual product mass!

PRODUCT ANALYSIS
(Melting Point)



The melting point of a pure solid is an important
characteristic of the compound.
A pure solid has a sharp characteristic melting
point, but a solid that contains impurities will
have a broader and lower melting point range.
By comparing the experimental melting point to
the literature value for pure p-methylacetanilide,
the purity of the product can be determined.
PRODUCT ANALYSIS
(IR Spectroscopy)
NH
2
1
2
6
5
3
4
CH 3
7
O
H
C
N
8
CH 3
9
1
6
2
5
3
4
CH 3
7
Table 16.3
Functional
Group
Base Values
p-methylaniline
p-methylacetanilide
Frequency
(cm-1)
Frequency
(cm-1)
Frequency
(cm-1)
Amines have two
absorptions!
Amides have one
absorption!
N-H stretch
3150-3500
sp2 CH stretch
3000-3100
sp3 CH stretch
2800-3000
C=O stretch
1650-1740
PRODUCT ANALYSIS
(NMR Spectroscopy)
3H, s
2.2 d
NH
2
1
H3,5
2H, d
6.9 d
H2,6
2H, d
6.6 d
6
2
5
3
4
2H, s
3.5 d
CH 3
7
O
H
3H, s
2 .1 d
C
N
8
CH 3
9
3H, s
2 .3 d
1
6
2
5
3
H2,6
2H, d
7.4 d
4
CH 3
7
1H, s
7.9 d
H3,5
2H, d
7.1 d
Table 16.4
p-methylaniline
p-methylacetanilide
NH
O
NH
2
N
H2, 6
1
H2, 6
2
5
3
H3,5
C2, 6
9
3
2
H7
5
3
C4
C7
4
3
CH
H9
7
C2, 6
C3, 5
6
C3, 5
H7
CH
8
H3,5
4
CH
C
1
C1
6
C1
H
C7
NH
3
7
C8
C9
C4
Enter chemical shift ONLY in blank based on spectra on p. 138-139!
SAFETY CONCERNS


Nasty fumes are given off when the
reaction mixture is heated.
Acetic anhydride and acetic acid can
cause burns.
WASTE MANAGEMENT


Slowly add 10% NaHCO3 to your combined
filtrate (containing mainly water, acetic
acid, and acetic anhydride) until vigorous
bubbling of CO2 has ceased. Rinse down
the drain in the hood.
Next lab period, after you have weighed
your amide product and determined its
melting range, you will use it as the
reactant for the next experiment!
CLEANING



All glassware should be cleaned with
soap, water, and brush if necessary.
Rinse all glassware with wash acetone
before returning to lab drawer.
DO NOT return any glassware to
drawer wet or dirty!