Katie Masters
Desk #17A
November 13, 2003
TA: Karen Heichel
Experiment: The Synthesis of Sulfanilamide, An Antibacterial Drug
Chem 36 Section 1
PreLab
Summary
Sulfanilamide, or p-aminobenzenesulfonamide, was first synthesized in 1908. It was discovered that sulfanilamide has
antibacterial properties, and the mode of action has been determined. Bacteria must synthesize folic acid in order to
grow. Sulfanilamide inhibits the formation of folic acid, and therefore, stops the growth of bacteria. Since humans do not
synthesize folic acid (must be acquired in food), only bacteria are affected by the use of sulfanilamide. Thus, there is no
negative side effect to taking sulfanilamide since it does not disrupt any critical biological action in the body.
This experiment focuses on the three-step synthesis of sulfanilamide, starting with acetanilide. The synthetic scheme is
shown in the “Diagrams of Special Apparatus/Reaction” section of this PreLab. In this three-step route, acetanilide is
subjected to chlorosulfonation, which is then followed by sulfonamide formation, and finally, reduction of the acetyl amide
to yield sulfanilamide. The final product, sulfanilamide, will be crystallized and weighed to determine the percent yield of
the pure product. The melting point and IR spectrum will be acquired to verify the purity and identity of sulfanilamide.
Reference: Handout downloaded from the Chem 36 website, www.courses.chem.psu.edu/chem36.
Goals
 To synthesize sulfanilamide via a three-step process starting with acetanilide.
 To purify sulfanilamide via recrystallization.
 To achieve a 90% recovery (as reported in the experimental procedure) for the recrystallization of the crude
product.
 To verify sulfanilamide’s purity and identity via melting point and IR analysis.
Diagrams of Special Apparatus/Reaction Scheme
Hydrogen Chloride Trap Apparatus:
Reaction Scheme of the Synthesis of Sulfanilamide:
H
N
O
C
H
N
O
C
CH3
CH3
NH3
+
HSO3Cl
SO2Cl
Acetanilide
H
N
O
C
chlorosulfonic
acid
CH3
p-acetaminobenzenesulfonyl
chloride
NH2
1. HCl (aq)
SO2NH2
p-acetaminobenzenesulfonamide
2. NaHCO3
SO2NH2
sulfanilamide
Experiment Chemical Data Table
Chemical Name
Structure*
Physical
State
BP or
MP
Liquid
Density
Quantity
MW
FW
Mmol
Flammability
Toxicity
Price
Waste
Comment
Acetanilide
Solid
113113°C
(MP)
N.A.
0.25 g
135.17
1.85
No
Yes
$17
for
100 g
NHO
Irritant
Chlorosulfonic acid
Liquid
1.753
g/mL
0.625
mL
116.52
9.40
No
Yes
$61
for 1
L
D
Corrosive;
reacts
violently
with water
pAcetaminosulfonyl
chloride
Solid
151152°C
at 755
mm
Hg
(BP)
145148°C
(MP)
N.A.
223.67
No
No
$18
for
100 g
HO
Corrosive
pAcetaminobenzene
sulfonamide**
Solid
Sulfanilamide
Solid
165167°C
(MP)
N.A.
172.21
No
No
$46
for
50 g
NHO
Irritant
*Note: Structures are not shown in this table (due to limitations in computer application program), but are required in all
Chemical Data Tables.
**Not found in Aldrich or online at ChemFinder.com
Note: Although NH3 and NaHCO3 are reagents used in this synthetic route, they are not included in the Chemical Data
Table. These compounds are listed on the Common Chemical Data Table and need not be listed here.
Chromatographic Behavior Comparison of Starting Material & Product
Acetanilide vs. Sulfanilamide
Sulfanilamide will have a lower Rf due to the more polar NH2 group and sulfonamide group (SO2NH2) - two polar groups.
Acetanilide only has one polar amide group, thus will have a higher Rf value.
Spectral Features Comparison of Starting Material & Product
1H NMR, Main Differences: Acetanilide will have 5 signals in its NMR spectrum while sulfanilamide will have 4 signals.
The aromatic protons for sulfanilamide will be shifted more downfield (in the range of 7 to 8 ppm) due to the presence of
more de-shielding groups. These aromatic protons will appear as two doublets.
Acetanilide’s aromatic protons will appear as a triplet and two doublets.
IR, Main Differences: Acetanilide will have an amide carbonyl stretch at ~1680 cm-1. Sulfanilamide will have, mostly likely,
two N-H stretches for the primary amine group at ~3300-3500 cm-1 and S=O stretch at ~1340cm-1.
MS, Main Differences: Acetanilide will show a M+ peak at 135; sulfanilamide will show a M+ peak at 172. Acetanilide
may show a –CH3 (-15) fragment where sulfanilamide will not.
Explanation of Isolation (Work-Up) and Purification
Sulfanilamide:
Once the reaction is complete, a yellow solution will remain that will be shaken with granulated decolorizing charcoal,
which will be filtered by removal of the solution with a pipette. The charcoal will serve to remove the colored impurities
from the solution.
The resulting colorless solution will be mixed with an aqueous solution of sodium bicarbonate in order to neutralize the
hydrochloride.
The pH will be tested with indicator paper to ensure that the solution is neutral.
The suspension will be cooled in ice to precipitate out the sulfanilamide product.
The solid will be collected via vacuum filtration (isolation of product).
The crude product will be recrystallized from water to purify sulfanilamide.
PreLab Exercise
Draw out the mechanism for the reaction of p-acetaminobenzene sulfonamide to form sulfanilamide.
H+
H
SO2NHR
O
SO2NHR
O
N
H
N
H
H
O
H
H+
H
H O
H
SO2NHR
O
H
H O
N
H
O
N
H H
SO2NHR
O
H3C
SO2NHR
OH
+
H2N