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Grignard Reaction (Part 1) Week 9

Introduction The Grignard reaction, named for the French chemist François Auguste Victor Grignard, is
a chemical reaction in which alkyl-, alkenyl-, or aryl-magnesium halides (Grignard
reagents), which act as nucleophiles, attack electrophilic carbon atoms that are present within
polar bonds (a carbonyl group, for example) to yield a carbon-carbon bond. The hybridization
of the carbon being attacked changes from sp2 to sp3. The Grignard reaction is an important
tool in the formation of carbon-carbon bonds.

Chemical In the first step of your experiment, you will prepare a Grignard reagent by reacting
Reaction bromobenzene with magnesium metal in ether as solvent. The Grignard reagent,
phenylmagnesium bromide, will then react with benzophenone and after the acidic work up a
tertiary alcohol, triphenylmethanol, will be isolated.

benzophenone
Br MgBr
O
Mg C6H5CC6H5 H2O, H+
C OMgBr C OH + Mg(OH)Br
Et2O

bromobenzene phenylmagnesium
bromide
triphenylmethanol

Mechanism
a nucleophile
that is a strong base

O O HB OH
+ Z R R(H) R R(H)
R R(H) B
Z Z

irreversible reaction:
Z is too basic to be expelled

One of the characteristic reactions of aldehydes and ketones is the nucleophilic addition
reaction. When a nucleophile adds to the carbonyl group of an aldehyde or a ketone, a
tetrahedral compound is formed. If the nucleophile is a strong base, the tetrahedral compound
does not have a group that can be expelled (see nucleophilic addition-elimination reaction)
therefore the tetrahedral compound is the final product of the reaction.
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Notes All glassware and the magnesium used in a Grignard synthesis should be scrupulously dry.
Even apparently dry glassware can contain moist air and a surprisingly large amount of water
adhered to the walls of the glass equipment. This can greatly lower your yield or even prevent
the reaction from starting. Your instructor will help you flame dry parts of your equipment
required for your reaction so please PAY ATTENTION to the prelab lecture. Alternatively,
the glass apparatus for experiment will be pre-dried in an oven and then quickly assembled.

Due to the occurrence of side reactions in this procedure the reactants for the Grignard
procedure will not be used in strictly stoichiometric amounts.

Magnesium: 0.160 g (6.6 mmole) (Balance room/location)

Bromobenzene: 0.7 mL (6.6 mmole) (Provided by TA)

Benzophenone: 1.10 g (6.00 mmole) (Balance room/location)

Safety Diethyl ether is extremely volatile and its vapours are flammable and explosive. No flames
Concerns can be present when any ether is being used in the room. The hotplate is used as a stirrer
ONLY. Also, remove the stirrer from your fumehood before you start extraction!

Procedure Place 0.160 g of magnesium turning into a 10 ml round-bottom flask fitted with a drying tube
containing CaCl2, place it in a 50 mL beaker and have your instructor flame dry them (if
Step 1
instructed - the plastic cap and o-rings would need to be removed in this instance). Once this
operation is completed, allow the walls of the flask to cool down, add the stirbar, then quickly
assemble the set-up that is illustrated at the end of this procedure. Do not waste anytime
doing this as the longer you take the more moisture will condense in your flask.

Obtain a vial of bromobenzene from your TA and carefully fill it to the top with anhydrous
diethyl ether provided in the central hood.

Step 2 Add all the alkyl halide to the magnesium in the round-bottom flask (without using a pipette,
simply and carefully pour the solution from the vial into the flask), stir the reaction mixture
for several minutes while carefully observing the mixture for signs of reaction. If after a few
minutes no reaction seems to be occurring, carefully remove the round-bottom flask and using
a stirring rod, start scratching the magnesium turnings, until a cloudy/milky solution appears
(consult your instructor for help in initiating the reaction if you still do not observe any
change). When the reaction has started the ether solvent will begin to reflux vigorously, as this
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reaction is exothermic, so make sure that you have cold water running through your reflux
condenser.

When the ether no longer refluxes on its own, use a warm water bath (~45°C tap water is good
Step 3
enough!) to heat the reaction mixture under gentle reflux for an additional 15 minutes to
complete the formation of the phenylmagnesium bromide. Note: the phenylmagnesium
bromide solution in diethyl ether is a dark brown smelly mixture! DO NOT USE THE
HEATER!

Step 4 While your phenylmagnesium bromide solution is gently refluxing, weigh 1.10 g of
benzophenone into a clean, dry 3 mL conical vial (previously rinsed with one mL of anhydrous
diethyl ether). Directly to the vial, add about 2 mL of anhydrous diethyl ether to the
benzophenone and make sure to dissolve it completely (use the gradations on the vial to
approximate the volume).

After your phenylmagnesium bromide reaction is complete, it is time to add your freshly
Step 5
prepared benzophenone solution. Using the provided clean syringe and needle, begin a
dropwise addition of the benzophenone solution through the septum on your Claisen head.
After all of the ketone has been added, gently reflux the mixture for 15 minutes using a warm
water bath. At this point the reaction might be thick and stirring it might be a problem. This
is not of concern as the reaction has occurred already.

After addition of the ketone, cool the reaction mixture to room temperature, open your Claisen
Step 6
side arm, and using a pipette, carefully add 1 mL of water dropwise; a gelatinous mixture of
magnesium salts should start forming, and stirring might still be a challenge. Slowly add
enough 6M HCl to completely dissolve the magnesium salts (no more than 3 mL is needed).
At this point you can remove the cap and Teflon liner and use your spatula to break up any
remaining solid. You should now observe two phases (organic and aqueous) in the flask, but
little or no solid. If there is a large white phase between the two layers, add a little more dilute
acid as well as diethyl ether, however if it’s a small amount, move to the next step.

Transfer this reaction mixture to a centrifuge tube and separate the layers, putting aside the
Step 7 aqueous phase while you continue to work with the organic phase. If your organic layer is too
small, add a few mL of diethyl ether, as it is easier to work with good size layers for better
separations. Remember to remove your stirrer from the fumehood. Wash the organic phase
with 3 mL of 10 % sodium bicarbonate solution followed by 3 mL of a saturated sodium
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chloride solution. Place the ether solution in a small Erlenmeyer and add anhydrous sodium
sulfate, to dry it for few minutes. Decant the ether solution from the drying agent into a small
50 mL beaker and remove the ether using the air outlet in your hood. When the ether is largely
gone cover the top of your beaker with aluminum foil and store it in your locker until your
next lab.

Set up

Drying tube

Reflux
Water out condenser

Water in

Claisen head

Round bottom
flask
Stir bar