Williamson Introduction:
The ether synthesis is a base catalyzed, nucleophilic substitution
reaction between a metal alkoxide/phenoxide ion and an alkyl halide/tosylate. The
alkoxide nucleophile is generated from a primary/secondary alcohol and a strong base. In
this experiment the nucleophile will be generated from cresol using potassium hydroxide.
The electrophile is chloroacetic acid. The purpose of this experiment is to produce a
methylphenoxy acetic acid product. Reflux will be used to accelerate the reaction,
followed by liquid/liquid extraction, which separates compounds based on their
solubility. Acid/base extraction will be used to extract the compounds based on their
relative acidities. Once the layers have been separated, suction filtration will be used to
recrystallize the product, followed by product characterization via IR spectroscopy.
Balanced Equation:
Reaction Mechanism:
Safety Information:
Safety glasses and lab gloves must be worn at all times. Use caution at all times
when working with flames and hot glassware. NEVER heat a closed vessel. Cresol is
extremely toxic. Chloroacetic acid is both toxic and highly acidic. Ingesting chloroaceric
acid can cause serious internal burns and/or irritation. It can also cause severe irritation
and/or burns if inhaled or if they come into contact with the skin/eyes. Concentrated
hydrochloric acid and potassium hydroxide is highly caustic and emits harmful vapors.
Ethyl acetate is a highly flammable solvent and should not be brought into contact with
anything that could cause it to ignite. Exposure to diethyl ether can cause headaches,
dizziness, and nausea. Make sure the snorkels are turned on and working properly before
dispensing any liquids Incidents of exposure to harmful chemicals should be reported to
the TA immediately. Properly dispose of all waste in the appropriate bottles under the
fume hood.
MSDS
Cresol: Toxic if swallowed or in contact with skin. Fatal if inhaled. Toxic to
aquatic life. Do not breathe dust, fume, gas, mist, vapors, or spray. Wear
protective gloves and clothing. Wear respiratory protection.
(4-methylphenoxy)acetic acid: May be harmful if inhaled, absorbed through skin,
and swallowed. May cause eye irritation.
Water: May be harmful if inhaled, absorbed through skin, or swallowed. May
cause eye irritation.
Potassium Hydroxide: Toxic if swallowed. Causes severe skin burns and eye
damage. Harmful to aquatic life. May be harmful if inhaled. Material is extremely
destructive to the tissue of the mucous membranes and upper respiratory tract.
Causes severe eye burns.
Chloroacetic Acid: Toxic if swallowed or in contact with skin. Causes severe skin
burns and eye damage. Very toxic to aquatic life. Wear protective gloves,
protective clothing, eye protection, and face protection.
Hydrochloric Acid: Cause severe skin burns and eye damage. May cause damage
to organs. Do not breathe dust, fume, gas, mist, vapors, and spray. Wash skin
thoroughly after handling. Do not eat, drink, smoke or when using this product.
Wear protective gloves, protective clothing, eye protective, and face protection.
Ethyl Acetate: Highly flammable liquid and vapor. Causes serious eye irritation.
May be harmful if inhaled. May cause drowsiness or dizziness. Keep away from
heat, sparks, open flames, and hot surfaces. Avoid breathing dust, fumes, gas,
mist, vapors, and spray.
Potassium Carbonate: Harmful if swallowed. May cause skin, eye, and respiratory
irritation. Avoid breathing dust, fumes, gas, mist, vapors, or spray. Do not eat,
drink, or smoke when using this product. Use only outdoors or in a wellventilated area. Wear protective glove, eye protection, and/or face protection.
Table of Reagents:
Compound Name
Cresol
Structure
MW
(g/mol)
108.14
MP
(C)
35.5
BP
(C)
----
Density
(g/ml)
----
(4-methylphenoxy)
acetic acid
166.17
140142
----
----
Water
18.0
----
100
1.00
Potassium Hydroxide
56.11
361
----
----
Chloroacetic Acid
94.50
60-63
----
----
Hydrochloric Acid
36.46
----
>100
1.2
Ethyl Acetate
88.11
----
76.577.5
0.902
Potassium Carbonate
138.21
----
decom
poses
2.29
Experimental Procedures:
Dissolve 2.0g of potassium hydroxide pellets in a 100mL beaker using 4mL of
deionized water.
Pour the solution into a 50mL round bottom flaks and add 1.5g of p-cresol.
Dissolve the cresol into the solution and construct a reflux apparatus.
Begin gently boiling the solution.
Add 3,L of 50% chloroacetic acid in a dropwise fashion over 10minutes via the
top of the condenser. Once this addition is complete reflux the mixture for an
additional 10minutes.
Allow the mixture to cool to room temperature. Any solid that is formed must be
dissolved back into the mixture using deionized water.
Pour the mixture into a separatory funnel and acidify it using hydrochloric acid.
Monitor the pH using pH paper.
As the solution is acidified, a precipitate will form.
Extract the mixture with two 10mL portions of ethyl acetate and combine the
extracts in a 100mL beaker.
Drain the aqueous layer and save it til the end of the lab period.
Pour the ethyl acetate extract back into the separatory funnel and wash it with
10mL of water.
Drain off the aqueous layer and extract the organic layer using two 10mL portions
of 5% potassium carbonate. Collect and combine the potassium carbonate
solution in a 100mL beaker
Acidify the basic solution using hydrochloric acid.
Collect the yellow precipitate via suction filtration.
Wash the product with two 10mL portions of cold water. Transfer the product to a
250mL beaker and recrystallize it using a minimal amount of boiling water.
Place the purified product in an ice-water bath to aid in precipitation.
Collect the purified product via suction filtration and continue to pull air through
the filtration apparatus for 5 additional minutes.
Transfer the crystals to a watch glass and place them in a drying oven for about 10
minutes.
Determine the final mass, melting point, and IR of the product.