WEEK 3:
GRIGNARD REACTION
PURPOSE:
This experiment will introduce the student to the synthesis
of a sensitive organometallic intermediate (the Grignard
reagent) which is very useful in the synthesis of a large number
of different functional groups.
IMPORTANT REACTIONS:
Part 1:
Br
MgBr
anhydrous ether
+ Mg
Bromobenzene
(M. Mass 157.02, bp 156oC)
phenylmagnesium bromide
Part 2:
+ MgBr
-
H3O+
+
C
O
Benzophenone
(M. Mass 182.22, mp 48oC)
C
OH
Triphenylmethanol
(M. Mass 260.34, mp 164.2oC)
BACKGROUND INFORMATION:
The Grignard reaction was discovered and developed by a
French Nobel laureate in the early 1900’s. It is an example of
an organometallic compound which has a carbon magnesium bond.
Grignard reagents have been extremely useful in the synthesis of
a large number of classes of organic functional groups for the
past century. Although Grignard reagents are unstable and
decompose in air and moisture, they can be prepared and used
immediately with moderate difficulty in the undergraduate
organic chemistry laboratory. Care will need to be exercised
and the equipment must be thoroughly dried before use to insure
success. No water may enter the reaction mixture until the
final product has been synthesized.
Group IA metals (Li, Na, and K) form very basic
organometallic compounds which are very hazardous to handle.
They can be spontaneously flammable in air and react explosively
with water to release hydrogen gas. In these cases, the C-M
bond is very polar and the carbon group is highly basic,
especially in sodium and potassium compounds.
With the Group IIA metal magnesium, the C-Mg bond is not as
polar and the compound is not as difficult to handle. Yet they
are reactive enough to be very useful in synthesis. The exact
nature of the bonding in Grignard reagents has been extensively
studied in the past century and is beyond the scope of this
discussion. For the purposes of this experiment, one can
consider the bonding to be R-MgBr, where R is an alkyl or aryl
group.
Organometallic compounds with transition metals (such as,
iron, mercury, lead, tin, cadmium, and many others) have an even
more covalent carbon metal bond. Many of these compounds are
stable and often very toxic. Organic mercury compounds are
often mentioned as environmental hazards in the New Jersey area.
One reason for the extreme toxicity of some organometallic
compounds is the volatility that the organic group imparts on
the molecule which makes it easier for entry into the body.
Returning to the chemistry of the organomagnesium
(Grignard) compounds, they are generally prepared by the
reaction of an alkyl or aryl halide with magnesium metal
turnings. The magnesium turnings are crushed in a mortar and
pestle just before use to expose a fresh surface on the metal.
Of the halides used, iodides are best, fluorides are the least
reactive and bromides are usually preferred for their good
reactivity and lower cost. Grignard reagents are usually
prepared in anhydrous ether as the volatile ether solvent helps
keep air away from the reaction. It cannot be stressed enough
that the ether must be very dry and kept that way if the
reaction is to be successful. Small traces of water will
destroy the reagent or keep the reaction from starting.
Once formed, the Grignard reagent must be used
immediately. One can react this reagent with a large number of
different functional groups to give a wide variety of possible
products. The Grignard reagent can react with:
1. any active hydrogen (such as water, alcohols, carboxylic
acids, etc.) to produce and alkane or arene (usually not
desirable).
2. formaldehyde to form a primary alcohol.
3. an aldehyde (other than formaldehyde) to form a secondary
alcohol.
4. a ketone to form a tertiary alcohol (which will be done in
this experiment).
5. an ester to form a tertiary alcohol.
6. carbon dioxide (as solid dry ice) to form a carboxylic
acid.
7. many other classes of compounds to form other useful
products.
Due to the great reactivity of Grignard reagents, the alkyl or
aryl halide starting material cannot have any reactive function
group as part of its molecule. This generally limits the halide
to be alkyl, alkenyl, alkynyl, or aryl. An ether group is also
compatible and unreactive with the Grignard reagent.
In today’s experiment, bromobenzene will react with
magnesium turnings to form phenyl magnesium bromide (the
Grignard reagent). This intermediate will then be immediately
treated with benzophenone to prepare triphenylmethanol (a solid
tertiary alcohol).
EXPERIMENTAL PROCEDURE:
In order to minimize the exposure of the Grignard reagent
to water, the equipment and reagents used in this experiment
must be absolutely dry. All glassware (two reaction tubes, two
sample vials and a stirring rod) must be pre-dried in an oven at
110oC for at least 30 minutes prior to use. The anhydrous diethyl
ether solvent and the bromobenzene will be stored over molecular
sieves to absorb any moisture they are exposed to and the
magnesium metal will be pre-dried in an oven.
PART 1: Generation of Grignard Reagent
Remove the first reaction tube from the oven and cap
it with a rubber septum. Add magnesium powder (50mg, 2 mmol) to
the tube, minimizing the time that the tube is un-capped.
Carefully add anhydrous diethyl ether (0.5 mL) to the tube using
a dry syringe, injecting the needle through the rubber septum.
If a glass syringe is not available a dried disposable glass
pipette can be used instead.
Remove a sample vial from the oven and cap it with a rubber
septum. To this vial add bromobenzene (330 mg, 2.1 mmol) and
diethyl ether (0.7 mL) via the syringe as you did for the first
tube. After addition of the ether solvent, do not remove the
needle from the septum. As soon as the ether has been added to
the vial, swirl the mixture and immediately remove the entire
bromobenzene-ether mixture by carefully sucking it up into the
syringe. Once this has been done, inject approx. one third of
the bromobenzene-ether mixture into the first reaction tube
containing the magnesium metal in ether. Mix the contents and
add a pressure release needle to the septa. If the reaction does
not appear to start at this point, first remove the syringe (if
used) containing the remaining bromobenzene-ether mixture.
Carefully remove the septa and the pressure release needle and
quickly grind the magnesium metal using the oven dried glass
stirrer rod. Replace the septa and pressure release needle as
soon as possible to minimize air-water exposure. Once the
reaction starts, the clear solution will become cloudy and the
ether may begin to boil. At this point, reattach the syringe
containing the remaining bromobenzene-ether mixture and add the
rest of the solution dropwise at such a rate that the reaction
does no go out of control. Once the entire contents of the
syringe has been added, continue to agitate the reaction vessel
until the reaction is complete, which will be visible when very
little, if any, magnesium metal remains. The synthesized
phenylmagnesium bromide is not isolated, but will be used in
situ for part 2.
PART 2: Synthesis of Triphenylmethanol
Remove the second oven dried vial and cap it with a
rubber septa. Add benzophenone (0.364 g, 2.0 mmol) and diethyl
ether (1.0 mL) in the same manner and using the same precautions
as you did in part 1. Shake the vial to dissolve the
benzophenone and remove the resulting solution by sucking it up
into the dry syringe.
Carefully remove the syringe containing the benzophenoneether solution and inject it dropwise into the reaction tube
containing the phenylmagnesium bromide. A red colour should be
observed at this point. After all the benzophenone solution has
been added, rinse the vial with a few drops of ether and inject
these washings into the reaction tube. The reaction is complete
when the red colour disappears.
On completion, cool the reaction tube in ice, and very
carefully add 3 M hydrochloric acid (2 mL) dropwise with
stirring. If there is any un-reacted magnesium metal in your
reaction tube be especially careful as acids react with metals
to release hydrogen gas. This could lead to your reaction
solution bubbling out of your tube. On addition of the acid, a
two-phase system should result, add more ether solvent if the
white triphenylmethanol product begins to crystallize out.
Carefully remove the lower aqueous layer using a Pasteur
pipette. To the remaining ether layer add an equal volume of
saturated aqueous sodium chloride solution, shake the tube,
allow the layers to settle and remove the lower aqueous layer as
before. Dry the ether layer over calcium chloride pellets for 510 minutes, then carefully transfer the ether layer via pipette
into a pre-weighed beaker. Wash the drying agent with a small
amount of ether and combine the washings with the solution in
the beaker. Remove the ether solvent by carefully blowing a
stream of air over the solution in the beaker. When it appears
to be dry, add ice-cold petroleum-ether (1 mL) to the white
residue and grind (triturate) the product with a glass rod.
Filter the product using a Hirsch funnel and air dry the solid.
Re-weigh the beaker to record the mass of triphenylmethanol
produced. Calculate the percent yield and determine the melting
point.
IMPORTANT INFORMATION ABOUT THE REPORT:
The report for this experiment will follow the usual
format. Be sure the percent yield calculation is carefully
done. Also, record the melting point range of the final product
and compare that melting point to the reported melting point of
triphenylmethanol. Using these data, discuss the relative
success on the experiment.
END OF EXPERIMENT.
© 2007 STEPHEN ANDERSON AND ROBERT SHINE