Experiment 9: Nucleophilic Substitution: Preparation of Phenacetin

A formal lab report is required for this experiment.

This report should by typed (1.5 spacing for text) and taped into your notebook and then turned
in the week of April 4th at the beginning of lab. Here are the sections that need to be included.
For sections that are new or different, specific instructions are included.
Be sure that you get a good portion of this report completed before and during lab. Show what
you have so far to your lab instructor and ask questions before you leave lab.
Title:
Names:
Date:
Introduction: (approximately 2 paragraphs)
In this experiment, you will convert acetaminophen to phenacetin. See what you can find in the
literature about their biological significance and describe your findings in a coherent paragraph.
The reaction that you are performing is known as a Williamson Ether Synthesis. We are using
potassium carbonate as a base catalyst. Search the chemical literature and report on other
catalysts that scientists have used for the Williamson Ether synthesis. Be sure to cite your
sources in the reference section. Remember that Wikipedia is not a viable source for this
course.
Purpose:

Physical Properties
Compound

Structure

Formula

MW

Mp

Density BP

(g/mol)

(C)

(g/mL)

Acetaminophen

(C)
N/A

Ethyl iodide
Potassium

N/A

carbonate
Methyl ethyl
ketone
Phenacetin
Potassium iodide
Potassium hydrogen
carbonate
Diethyl ether
Sodium hydroxide
Anhydrous sodium

N/A

N/A
N/A

N/A

sulfate
Diagrams: Cut these out from the back of the lab manual and tape them to your report.

Reaction:

Experimental Procedure: This section should be written in the style used by the Journal of
Organic Chemistry.

It will assume that readers of your report are familiar with organic

techniques. In the journal article format, they also include details of the product characterization.
In your case, you will have Percent recovery, appearance, melting point and IR data to include.
Look at the example below that was taken from the Journal of Natural Products as an example.
Azido-thiazole. To a solution of Ph3P (423 mg, 1.6 mmol) in THF (3 mL) at
0C was added DIAD (0.33 mL, 1.6 mmol). After 10 min, a solution of 15
(162 mg, 538 mol) in THF (2 mL) was added. After an additional 15 min,
thioacetic acid (115 L, 1.6 mmol) was added and the reaction mixture was
allowed to slowly warm to rt with stirring over 2 h. Diethyl ether and pH 7
aqueous phosphate buffer (ca. 10 mL each) were added, the organic phase
was separated, and the aqueous phase was extracted with diethyl ether (3 x
25 mL). The combined organic extracts were dried over MgSO4, filtered, and
concentrated by rotary evaporation.
The crude product was purified by recrystallization with methanol. The
azido-thiazole product was isolated as a yellow powder (103 mg, 86% yield)
with mp = 155-157C; IR (neat) 3360, 2974, 2932, 2120, 1723, 1681, 1514,
1368, 1275, 1161 cm-1.

Calculations:
moles of acetaminophen (grams acetaminophen x 1/MW)

moles of ethyl iodide (grams ethyl iodide x 1/MW)

moles of potassium carbonate (grams K2CO3 x 1/MW)

Limiting Reagent:

Theoretical Yield: (moles Limiting Reagent x MW of product)

Percent Yield:

Mechanism: (Supply the missing arrows.)

Data:

Mass of Phenacetin

Appearance of Phenacetin

Mp of Phenacetin

Post-Lab Question:
1. What could result if the reaction mixture was not constantly stirred during the reflux?

Conclusion: (approximately 2 paragraphs)

Discuss the technique of reflux. Include its purpose and a few details. There are organic
technique books in the library or you may find this information online. Be sure to cite your
sources.

State the appearance of the recrystallized phenacetin and its melting point. Were these results
close to literature values?

State your percent yield and comment on how this reaction might be improved in the future.

References: Cite the lab manual, physical property references, sources for the introduction and
conclusion. For journal article references or books, please use ACS format. Here is an example:
ACS Format:
Journal Articles:
Stermitz, Frank R.; Cashman, Kevin K.; Halligan, Kathleen M.; Morel, Cecile; Tegos,
George P.; Lewis, Kim. Polyacylated neohesperidosides From Geranium caespitosum:
bacterial multidrug resistance pump inhibitors.

Bioorganic & Medicinal Chemistry

Letters, 2003, 13(11), 1915-1918.

Books:
Bruice, P. Y. In Organic Chemistry; Folchetti, N., Mullaney, R., Kaveney, D., Eds.; Pearson
prentice Hall: Upper Saddle River, NJ, 2007, 5th Edition, pp 184-188.