Aldridge

Hannah Aldridge
Williamson Ether Synthesis of Phenacetin
03/10/2022
Organic Chemistry II Lab
Abstract
The experiment preformed was a Williamson ether synthesis. This forms ether from an
alkyl halide and an alcohol. Acetaminophen was converted to phenacetin using the reflux
technique then went through extraction and recrystallization for the pure final product. Percent
yield was calculated, and melting point was obtained through the Mel-Temp. IR and TLC were
also taken.
Reaction

1
 2
 3

Table of chemical and physical properties 4

Chemical Structure Molar Melting Boiling Density Hazards

Mass point Point
4- C8H9NO2 151.16 169 ° C 420° C 1.26
acetamidophenol g/cm^3
Bromoethane CH3CH2Br 108.97 -116- - 38° C 1.47
120° C g/cm^3

ethanol C2H5OH 46.07 -114° C 78° C 0.789

g/cm^3
Phenacetin C10H13NO2 179.22 133- 355.1 1.24
136° C °C g/cm^3
Sodium NaOH 40.00 318° C 1388° C 2.13
Hydroxide g/cm^3
Water H2O 18.00 0° C 100° C 1.00 N/A
g/cm^3

1
Millpore Sigma Catalog
2
Millpore Sigma Catalog
3
Millpore Sigma catalog
4
Millpore Sigma Catalog

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Calculations

Theoretical Yield:
( 1.05 g∗151.16
mol )
g
=1.2449 g
g
179.22
mol
0.7109 g
Percent Yield: ∗100=57.11 %
1.2449 g
Procedure
Approximately 1.05 g of acetaminophen were added to a 25 mL round bottom flask that
was fixed in a clamp attached to a ring stand over a hotplate. A stir bar was then added to the
round bottom flask and turned on. Approximately 8 mL of 1 M ethanolic NaOH was then added
to the flask. A reflux condenser was fixed in place on the ring stand and the water was positioned
properly. The hotplate was then turned on to 120° C and the solution was refluxed for 15
minutes.
After 15 minutes the flask was raised from the hotplate and allowed to cool. 0.75 mL of
bromoethane was added via the condenser and the flask was set back on the hotplate to reflux at
120° C for an additional 15 minutes. Once finished a TLC plate was then gathered and three
lanes were set up. In the first lane went a prepared acetaminophen solution, in the second lane
went a drop of the reaction mixture, the third lane was taken later of the recrystallized solid of
phenacetin. Once done with the solution, it was poured into a beaker containing 10 mL of ice and
10 mL of water. The solids were collected via vacuum filtration.
The crude solid was then recrystallized using ethanol and water, the solid was then
collected via vacuum filtration once more. This is the solid used in the third lane of the TLC
plate, rehydrated by a little bit of acetone. The mass, IR, and melting point were all taken.
Results
Phenacetin
Final mass 0.7109 g
Melting Point 124.9-128.0° C Lit.133-136° C
IR Peaks at 3300, 2900, 1650
TLC Rf Value Acetaminophen: 0.60, Phenacetin: 0.75

Discussion
The goal of this experiment was to further understand the Williamson Ether Synthesis
through a reaction with acetaminophen to prepare phenacetin and follow up the reaction with an
analysis that utilized TLC, IR and melting point. In comparison to the cited article “Microwave
Irradiation Reactions: Synthesis of Analgesic Drugs” where the percent yield of phenacetin was
80%, the percent yield of this experiment’s phenacetin was calculated at 57.11%. This is a low
percent yield, and it is possible some product was lost during the refluxing of the reaction. The

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theoretical yield was calculated using the limiting reagent, acetaminophen, for a value of 1.2449g
whereas the actual yield was only 0.7109g, this shows that a little bit was lost as previously
stated for precent yield. Another possibility is that too much ethanol was added during the
recrystallization process.
The melting point started at 124.9 and ended at 128.0. The melting point for phenacetin is
between 133-136 Celsius. It is possible that some of the substance was impure which led to
lower melting points but overall, it was still a decent melting point. On the TLC the Rf value for
pure acetaminophen was 0.60 and for the phenacetin was 0.75. This shows that because of the
lower Rf value, pure acetaminophen is more polar than phenacetin. The higher Rf value also
demonstrates that it is likely to be less polar in phenacetin. This shows correct data of pure
acetaminophen being more polar than that of phenacetin.
In the IR spectroscopy there were peaks at 3300 cm-1 and another near 1700 cm-1. The
first indicated that there was a detection of an amine stretch, while the second indicated there
was a carbonyl stretch. The IR spectroscopy graph is correct because both functional groups are
found in the structure of phenacetin.

Cite:

Kasey L. Yearty, Ryan K. Maynard, Christina N. Cortes, Richard W. Morrison. “A

Multioutcome Experiment for the Williamson Ether Synthesis.” J. Chem. Educ. 2020, 97, 2,
578–581 Publication Date: January 14, 2020 https://doi.org/10.1021/acs.jchemed.9b00503
Gholam A. Mirafzal, Jolene M. Summer. “Microwave Irradiation Reactions: Synthesis of
Analgesic Drugs.” J. Chem. Educ. 2000, 77, 3, 356 Publication Date: March 1, 2000
https://doi.org/10.1021/ed077p356
Sigma Aldrich Online Catalog. www.sigmaaldrich.com (accessed March 14, 2022)