The Grignard Reaction:

Preparation of Benzoic Acid

________________________________________________________________________

This experiment is based on one included in Pavia, Organic Laboratory Techniques: A
Microscale Approach, 4
th
ed.

NOTES: Review the technique of crystallization in Zubrick (Ch. 13) before
coming to lab today. The bottom line on crystallization: Dissolve the compound to be
recrystallized in the minimum amount of hot solvent it takes to entirely dissolve the
compound. Let this solution cool, undisturbed, on the benchtop. If no crystal growth is
apparent after several minutes, scratch the bottom of the flask with a glass stir rod. If
after several more minutes there is still no crystal growth, move the flask without
disturbing the solution onto an ice bath.

Review melting points (Zubrick, Ch. 12, and the handout available on the course
website).

READ the sections on organometallic and Grignard reagents in Wade, 6
th
edition: pp.
432-442.
________________________________________________________________________

Grignard reagents (RMgX) are commonly used reagents in the organic laboratory. They
are available commercially as solutions, or can be made in the lab and used immediately.
Treatment of an alkyl halide with magnesium metal in an ethereal solvent such as diethyl
ether or tetrahydrofuran (THF) generates the Grignard reagent:

Br
Mg
Et
2
O
MgBr


The carbon-magnesium bond is considered to be polar covalent, giving the carbon atom
significant anionic character and making the Grignard reagent both a strong base and a
good nucleophile. One of the most frequent uses of these reagents is nucleophilic
addition to carbonyl compounds such as ketones and aldehydes:

MgBr
H
O
H
O
MgBr
HO
H
3
O
+


The nucleophilic carbon of the Grignard reagent attacks the electrophilic carbonyl
carbon, forming the magnesium salt of an alkoxide. This alkoxide ion is protonated in
the aqueous workup to give the alcohol product.

Grignard reagents will also react similarly with carbon dioxide to provide a convenient
synthesis of carboxylic acids. The Grignard reagent attacks the electrophilic carbon,
forming a magnesium carboxylate. The carboxylate is protonated in aqueous workup to
give the carboxylic acid product.

Because Grignard reagents are so basic, they react quite readily (sometimes even
violently) with compounds containing acidic protons, such as water and alcohols:

MgBr
+ H
2
O CH
3
CH
3
+ HOMgBr



The magnesium salt formed in the above reaction is a white solid, so if you find a white
precipitate in your reaction today, you must start the reaction over with dry glassware.
Because of the sensitivity of these reagents to moisture, the solvents used in these
reactions must be anhydrous there can be no traces of water in them. You will be using
anhydrous diethyl ether, and special care must be taken when you transfer it to your
reaction containers. Transfer the solvent as rapidly as possible using a syringe. The ether
container should only be uncapped if you are removing liquid from it with a syringe. As
soon as your syringe leaves the bottle, cap it immediately.

Initiation of the reaction to form the Grignard reagent can be sluggish. Exposure to air
causes the outer layer of the magnesium metal to oxidize. Once a coating of magnesium
oxide forms on the metal surface, the metal itself cant react easily. The magnesium
oxide coating must therefore be removed. If you observe a white coating on the
magnesium today, consult your instructor.

Today, you will prepare the Grignard reagent, phenylmagnesium bromide, then react it
with CO
2
(s) (dry ice) to prepare benzoic acid.



Safety Precautions

Diethyl ether is extremely flammable. Therefore, there must be no open flames in this
lab. Aqueous hydrochloric acid can cause burns if it contacts your skin. Bromobenzene
is a mild irritant. The Grignard reagent itself, once formed, is strongly basic and should
be handled with care. Dry ice can cause burns with prolonged handling. Avoid skin and
eye contact with all chemicals and wear protective gloves and clothing.


Experimental Procedure

Preparation of the Grignard Reagent, Phenylmagnesium Bromide

Your glassware must be totally dry or the reaction will not initiate. You will receive two
new, clean test tubes for the reaction. (Please return them clean at the end of the lab
period.) Be sure your 10 mL graduated cylinder is not wet; if it is wet, you cannot rinse it
with acetone to clean and dry it. (See Questions at the end of the lab.)

Weigh out 6 mmole of magnesium metal. Cut the magnesium strips into small, square
pieces and place the pieces in one test tube. Place 6 mmole of bromobenzene and about 1
mL of anhydrous diethyl ether in the other test tube. The ether measurement can be
approximate; you dont need exactly 1 mL. (A full Pasteur pipet contains about 1.5 mL).
Use a Pasteur pipet to transfer only enough of the bromobenzene solution to just cover
the magnesium in the other test tube. Cover this test tube loosely with a small piece of
foil. Carefully observe the solution for the presence of small bubbles coming from the
metal surface, indicating that the reaction has begun.

Once the reaction is initiated as shown by bubbling and the brown color of the mixture,
add about 1 mL of anhydrous ether to your original bromobenzene solution, then
carefully transfer a few drops of bromobenzene solution to the Grignard reagent. As the
reaction proceeds, you will notice bubbling, the brown color of the newly formed
Grignard reagent, and the production of heat. Keep adding bromobenzene solution
slowly and carefully to the Grignard reagent at a rate which keeps the reaction going. It
should take about 10-15 minutes to add all of the bromobenzene solution.

Once all of the bromobenzene solution has been added to the Grignard reagent, check the
reaction for loss of solvent (the ether may evaporate because of the heat produced in the
reaction) and continued reaction. If the volume of the Grignard reagent solution drops
below 2 mL, add a small amount of anhydrous diethyl ether. Once the bubbling stops, the
Grignard reagent is ready and should be used as soon as possible.

If your reaction fails to initiate: Using a test tube clamp, hold the test tube containing the
magnesium and bromobenzene mixture over a hot plate and warm it gently without
contacting the hot plate. (Remember that ether has a very low boiling point, so only
gentle warming is necessary.) If this procedure fails to initiate the reaction, consult your
instructor.

Preparation of Benzoic Acid

Place about 4 g of dry ice in a dry beaker with about 5 mL anhydrous ether. Moisture
from the air will condense on the surface of the dry ice; this will interfere with the
reaction, so weigh out the dry ice as quickly as possible and begin the reaction
immediately. Using a Pasteur pipet, transfer the Grignard reagent solution onto the dry
ice. When all the Grignard reagent has been transferred, rinse the test tube with 2 mL
anhydrous ether and add this rinse to the dry ice/Grignard reagent mixture.
Cover the beaker with a watch glass and let it stand until all of the dry ice has sublimed.

When the dry ice has sublimed and/or reacted, slowly add 20 mL of chilled 3M
hydrochloric acid to the reaction flask, stirring if possible. If you observe any solids, add
more ether. Transfer the mixture to your separatory funnel. Do not transfer any
magnesium to the separatory funnel. Rinse the beaker with ether and add this rinse to
your separatory funnel. Stopper the funnel, shake it gently, then vent it carefully into the
fume hood. Allow the layers to separate and drain off the lower, aqueous layer. You
may discard this layer.

Wash the organic layer twice, each time with 5 mL of 5% sodium hydroxide solution.
After each wash, drain off the lower aqueous layer into a clean container (both these
washes should be combined in one container).

Place a stir bar in the combined aqueous layers and heat the solution to boiling for about
5 minutes to remove any ether. Allow the solution to cool, and add 10 mL of 3M
hydrochloric acid while you stir the solution. Place the mixture on an ice bath while you
set up an apparatus for vacuum filtration (a Hirsch funnel and sidearm flask). Isolate the
solid by vacuum filtration.

Recrystallize the benzoic acid from hot water. Isolate the crystals using vacuum
filtration. Determine the mass of your crystals. Obtain a melting point, a yield, and an IR
spectrum of your product.

Pre-lab Questions (answer these questions in your lab notebook and have them ready
with your prelab)

1. Show how primary, secondary, and tertiary alcohols can be formed using
Grignard reactions with aldehydes and ketones as starting materials.

2. Secondary and tertiary alcohols can be synthesized using various combinations of
Grignard reagent and carbonyl compound. Propose three different syntheses of this
compound using Grignard reactions:

CH
3
OH
CH
3


Discussion and Conclusions

Comment on the success of your reaction as evidenced by your yield, the IR spectrum,
and the melting point of your product.

1. Assuming your test tube was not entirely dry when you added bromobenzene to
magnesium to form the Grignard reagent, what would be the structure of the white solid
that would form?

2. Why can you not use acetone to clean test tubes that you plan to use in Grignard
reactions, either for preparing Grignard reagents or for running Grignard reactions?

3. a. Immediately after you quench the reaction with 3M HCl(aq), you should
have two layers. Identify both layers. Where is your product?

b. What is the purpose of the aqueous sodium hydroxide washes?

c. What is the purpose of treating the combined aqueous layers with aqueous
hydrochloric acid?