Preparation of a Phenylalcohol by a
Grignard Reaction
CH344
Bruce A. Hathaway
1
The Reaction
OH
O
Br
MgBr
Mg
ether
C
O
CH2CH3
2-butanone
R2
R1 C
R2
2. HCl, HOH
O
H3C
1.R1 C
H3C
C
O
CH2CH2CH3
2-pentanone
CH3CH2 C
CH2CH3
3-pentanone
2
Safety Issues
• Bromobenzene causes eye and skin irritation, and
inhalation, ingestion, or skin absorption may be
harmful. Avoid contact with the liquid and do not
breathe its vapors.
• Ethyl ether is extremely flammable and may be
harmful if inhaled. Do not breathe its vapors and
keep it away from flames and hot surfaces.
• Magnesium can cause dangerous fires if ignited;
keep it away from flames and hot surfaces.
3
The Apparatus
• Put some cotton in the
drying tube, followed by
CaCl2, then by more cotton.
• Put the iodine, Mg, and a stir
bar in the round-bottomed
flask before you assemble
the apparatus.
• Assemble the apparatus,
then remove the thermowell
by removing the stirrer; then
replace the stirrer.
• Start the water flowing
slowly through the
condenser.
Ground-Glass
Stopper
Drying tube
Neoprene Adapter
Thermometer Adapter
Addition
Funnel
West
Condenser
Water Out
Claisen
Adapter
Water In
Thermowell
To transformer
Magnetic Stirrer
4
Reaction of Bromobenzene
• Add a crystal of iodine to the round-bottomed
flask.
• Weigh out about 0.7 - 0.8 grams of magnesium
turnings into a weigh boat.
• Transfer them to a mortar, and grind them for
about a minute, to expose the shiny magnesium.
• Weigh 0.6 - 0.7g (record exactly what you use) of
clean, dry magnesium turnings and transfer then
to the round-bottomed flask.
• Add a stir bar to the round-bottomed flask.
5
Reaction of Bromobenzene
• Weigh 4.0g of dry bromobenzene into a 25 mL
dry Erlenmeyer flask and dissolve it in 5 mL of
anhydrous ethyl ether.
• Transfer this solution to the addition funnel and
stopper it, placing a tiny strip of filter paper
between the stopper and the neck of the funnel.
• Add the bromobenzene solution all at once to the
reaction flask.
• Replace the bromobenzene solution in the
addition funnel by 8 mL of anhydrous diethyl
ether.
6
Reaction of Bromobenzene
• Begin stirring the solution, and observe the
reaction mixture closely for evidence of a
reaction, such as cloudiness and the evolution of
bubbles from the magnesium surface.
• If the reaction does not begin within 5 minutes or
so, consult your instructor.
• When the reaction mixture begins to boil quite
vigorously without external heating, add the
ether drop by drop at a rate just sufficient to keep
the reaction mixture boiling.
7
Reaction of Bromobenzene
• When all the ether has been added, let the reaction
continue until the boiling has nearly stopped, then use a
heating mantle or thermowell to heat the reaction mixture
under gentle reflux for another 15-20 minutes.
• The reflux ring of condensing ether should be in the lower
third of the condenser.
• If a significant amount of ether evaporates, reducing its
volume in the reaction flask, replace it with fresh
anhydrous ether.
• Do not stop at this point, because the phenylmagnesium
bromide solution will not keep for long.
• Remove the thermowell, but keep the reaction stirring
while you do the next part.
8
Reaction of Phenylmagnesium Bromide
• Dissolve 1.4-1.5g of 2-butanone, or 1.7-1.8g of 2-pentanone
or 3-pentanone, in 20 ml of anhydrous diethyl ether in a dry
Erlenmeyer flask and place it in the addition funnel.
• When the reaction mixture has cooled so that the ether is
no longer boiling, add this solution drop by drop to the
reaction mixture with shaking or magnetic stirring.
• The addition rate should be sufficient to keep the ethyl
ether boiling gently without external heating.
• When the addition is complete, use a heating mantle or
thermowell to heat the reaction mixture under gentle
reflux for another 30 minutes.
• Remove the thermowell to allow the reaction to cool.
9
Reaction of Phenylmagnesium Bromide
• After the reaction mixture has cooled to room temperature,
add 5 mL of water drop by drop through the addition funnel
while shaking or stirring, and then add 25 mL of 5% (1.4 M)
hydrochloric acid. (We are using 1M HCl).
• Wait for the reaction to subside and continue stirring or
shaking until most or all of the white solid has dissolved
(some magnesium may remain undissolved).
• If any undissolved white solid remains, detach the reaction
flask from the apparatus and use a spatula to break up the
solid, then shake the capped flask, adding enough diethyl
ether or 5% HCl as needed to dissolve all of the solid.
• There must be at least 20 mL of ether in the reaction mixture
at this time; if necessary, add diethyl ether to replace any
ether that evaporated.
10
Separation of the Product
• If there is undissolved magnesium present,
remove it by gravity filtration through your Hirsch
funnel without filter paper, washing the
magnesium with a small amount of diethyl ether.
• Transfer the reaction mixture to a separatory
funnel, and shake gently to mix the layers
thoroughly.
• Allow the layers to separate, then drain out and
discard the lower aqueous layer.
11
Separation of the Product
• Carefully wash the ether layer with 15 mL of 5%
aqueous sodium bicarbonate.
• Then wash the ether layer with 15 mL of saturated
aqueous sodium chloride.
• Dry the ether solution over anhydrous magnesium
sulfate, and filter it into a dry round-bottomed flask.
• Evaporate the ether using a rotovap. Put the roundbottomed flask in your drawer until next lab period.
• Hopefully, everyone will get at least this far!
• We will stop here for the day.
12
Thin Layer Chromatography
• Draw a pencil line 1 cm from the bottom of a
silica-gel TLC plate.
• Make 2 tic marks on the line.
• Dissolve a tiny amount of your product in
several drops of acetone, and spot it on one of
the tic marks.
• Finally, spot the TLC standard of biphenyl on
the remaining tic mark.
13
Thin Layer Chromatography
• Make sure you write down what compound is
spotted on each tic-mark in your notebook.
• Check the TLC plate under a UV lamp to
determine if you spotted enough material.
• Put a folded piece of filter paper in a 400 mL
beaker, and add 10 mL of 1:19 ethyl
acetate:hexane solvent.
• Swirl the beaker to wet the filter paper, and
then place the TLC plate in the beaker.
14
Thin Layer Chromatography
• Cover the beaker with a watch glass, and allow the
solvent to rise within 1-2 cm of the top of the plate.
• Remove the plate, draw a pencil line at the solvent
front, wave the plate in the air to evaporate the
solvent off of it, and check the plate under a UV lamp.
• Be sure to circle all of the spots.
• Pour the solvent into the “Non-Halogenated WaterInsoluble Organic Waste" bottle.
• Keep the TLC plate: you will be turning it in with your
report.
15
Finishing Up
• When you are finished with the hexanes filtrate,
pour it into the “Non-Halogenated WaterInsoluble Organic Waste" bottle in the hood.
• You will take an IR spectrum of your product.
• I will collect your product during the next lab
period.
• Label a product vial as follows:
–
–
–
–
Product name
Weight
Melting point range
Your name(s)
16