11/30/2012
Magnesium – The Song
For alkyl halides' majesty
Magnesium is meant,
Assisted by completely dry
E-ther-e-al sol-vent.
Magnesium, Magnesium,
A Grignard has M-g,
It's understood, its bonds are good
From C to shining C.
A carbonyl is polarized,
Its carbon end is plus.
A nucleophile will thus attack
The carbon nucleus.
Magnesium, Magnesium,
A Grignard has M-g,
Each one is fond of making bonds
From C to shining C.
Plus 4 more
verses!
Reactions of Grignard Reagents
Synthesis of an Unknown Alcohol
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Grignard reagents - Structure
Grignard reagents are defined as
compounds containing an organic group
bonded to magnesium monohalide by a
carbon-magnesium bond.


R
MgBr
R MgBr
The C-Mg bond is polarized so that the
carbon atom is nucleophilic - the opposite to
the polarization for carbon atoms bonded to
electronegative atoms.
Grignard reagents - Preparation
Organomagnesium halides were first
prepared by Victor Grignard. He found that
these reagents could be prepared from
reaction of magnesium metal with alkyl
halides provided that the solvent used was
an ether solvent.
R-Br
Mg
R'-O-R'
R MgBr
R'-O-R' is diethyl ether, tetrahydrofuran, or other ether
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Grignard reagents - Utility
Grignard reagents are important in
organic chemistry, because they provide
a reagent containing a nucleophilic
carbon. Reaction of Grignard reagents
with compounds containing a carbonyl
group (with an electrophilic carbon)
provides a very general synthesis of
alcohols with a more complex carbon
skelton than the starting materials.
Grignard reagents - Utility
R MgBr
H2C O
ether
+
H3O
workup
RCH2 OH
1o
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Grignard reagents - Utility
R MgBr
R MgBr
ether
H3O+
workup
R'CH O
ether
H3O
workup
H2C O
RCH2 OH
1o
+
R'CH OH
R
2
o
Grignard reagents - Utility
R MgBr
R MgBr
H2C O
+
ether
H3O
workup
R'CH O
ether
H3O+
workup
RCH2 OH
1o
R'CH OH
R
R'C O
R MgBr
R"
ether
+
H3O
workup
2o
R
R'C OH
R'' 3o
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Grignard reagents - Utility
R'C O
R MgBr
R"
RC O
R"
R' MgBr
R
R'C OH
R'' 3o
RC O
R'
R" MgBr
Grignard reagents - Difficulties
The major difficulty in conducting Grignard
reactions in a student lab is getting the
reaction of the alkyl halide with magnesium
started.
Magnesium metal reacts with atmospheric
oxygen to form an unreactive magnesium
oxide coating on the surface of the metal.
Any moisture present makes initiation even
more difficult.
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Grignard reagents - Ultrasound
We are going to use a method to help
abrade the oxide coating while the
magnesium is shielded from air and alkyl
halide is present to react immediately with
the fresh magnesium metal surface.
The method we will use is ultrasound
sonication. We will use simple ultrasonic
baths of the type that are used to clean very
dirty glassware and jewelry.
Grignard reagents - Ultrasound
Ultrasound refers to sound waves with
frequencies above human hearing; i.e.
> 18,000 Hz.
Ultrasonic irradiation of a liquid results in
acoustic cavitation - the formation, growth
and implosive collapse of bubbles in a
liquid. The cavitational collapse causes
intense localized high pressure and
localized heating of the bubbles.
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Grignard reagents - Ultrasound
The effect of sonication on magnesium
turnings is the abrasion of the oxide surface
and localized heating of the metal. These
effects produce clean, warm magnesium
metal that will react with the alkyl halide.
Although ultrasonic baths produce
relatively low intensity ultrasound, they are
sufficient to make a big difference in our
ability to initiate the Grignard reaction.
Grignard Reaction - Objective
You will prepare a 3o alcohol by reaction of
one of three possible primary alkyl halides
with one of four possible ketones (12
possible products).
You will use IR spectra to identify your
alcohol product. This will allow you to
determine which starting materials you
were given to conduct the reaction.
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Grignard Reaction - Procedures
This experiment is a 2-week experiment.
Today, you will prepare the Grignard
reagent and allow the ketone to react with
it. After aqueous work-up of the reaction,
you will store your product solution in a
sample vial containing drying agent until
next week.
Next week, you will distill the solvent, and
then distill your product and use infrared
spectroscopy to identify your product.
Grignard Reaction - Procedures
Starting Materials - Two vial racks in the
lab room contain THF solutions of the
starting materials. The vial numbers
correspond to Bin numbers. Therefore, the
student with Bin #1 will use the vial labeled
1H (H=halide) and the vial labeled 1K
(K=ketone).
Empty reagent vials (with caps) should be
returned to the vial racks before the end of
the lab!
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Drying Apparatus
Use one of the heat guns to heat your flask,
Claisen head, air condenser, and stir bar
BEFORE you begin the procedure described
in the handout. Get them warm enough that
they are hot to the touch. We want to make
sure all moisture has been driven from the
interior walls of the glassware.
DO NOT heat your plastic disposable pipette
with the heat gun!
Grignard Reaction - Apparatus
Set the 25-mL round-bottomed flask on a
cork ring. Then add the stir bar, a
measured amount of magnesium metal, and
a small amount of THF solvent.
You will then assemble the apparatus
shown on the next slide by attaching a
Claisen head and air condenser. Securely
clamp this apparatus to your rack when you
add the alkyl halide.
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Grignard Reaction - Apparatus
open to atmosphere
air condenser
.
.
additions
can be made
through septum
with syringe
Claisen head
use a Keck clamp to
secure this joint
You will add your
reagents with a plastic
disposable pipette
through the open top of
the air condenser as
described in the lab
manual. One pipette can
be used for both
reagents.
Grignard Reaction
 BE SURE you use the halide solution to
prepare the Grignard reagent. The
reaction will NOT work if you add ketone
to the magnesium.
 The disposable plastic pipette in your bin
has a mark that shows the 1-mL fill level
for your first addition of halide to the
reaction flask.
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Grignard Reaction
1-mL
mark
You may leave
your disposable
pipette standing
in your open vial
of alkyl halide or
ketone between
additions. Do
not lay the
pipette on the
counter-top.
Grignard Reaction - Safety
READ everything in this procedure up to
the point labeled “Second Week” BEFORE
you start the procedure. Make sure you
note and use the revisions given in this
presentation.
THF (tetrahydrofuran) is flammable, but
less so than diethyl ether. NO heat guns are
to be used after THF as been added to any
flasks.
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Grignard Reaction - Safety
You want the reaction to warm while you are
adding the alkyl halide, but not boil so
vigorously that solvent vapors escape
through the air condenser.
The liquid in the original mixture of
magnesium, THF and a small amount of
alkyl halide solution will be clear. After the
reaction initiates, the stirred mixture will
become cloudy because of suspended
magnesium oxides.
Grignard Reaction - Safety
IF you cannot feel the reaction warming as
you add alkyl halide, STOP the addition and
return to the ultrasonic bath for additional
sonication. Have an ice bath ready to
moderate the reaction ONLY if solvent
vapor starts to rise to the top of the
condenser.
If the reaction still has not begun at this
time, talk to your TA about adding a small
crystal of iodine to your reaction flask.
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Grignard Reaction - Safety
The reaction of the Grignard reagent with
the ketone will also be exothermic. Add
the ketone solution slowly to avoid
overheating.
Storage Procedures
Your product solution from the extraction
procedure will be stored until next week,
when you will remove solvent and distill the
product.
Transfer the product solution to a sample
vial. Add magnesium sulfate to dry the
solution. Cap the vial tightly, label it with
your name and section number, and have
your TA store it in the appropriate section
drawer until next week.
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Cleanup Procedures
Your 25-mL round-bottomed flask needs to
be meticulously cleaned before you return
your bin at the end of the lab period. Use
soapy water AND the test tube brush in
your drawer to clean the flask. Rinse the
flask with acetone and then use a gentle
stream of pressurized air to evaporate the
acetone.
Rinse other glassware with acetone.
Cleanup Procedures (Cont.)
Dispose of the disposable pipette in the
labeled beaker in the Chem 238 hood. DO
NOT return this pipette with your
glassware bin.
Empty reagent vials (with caps) should be
returned to the vial racks before the end of
the lab! TAs should place these racks in
the section drawer with the sample vials (in
racks) containing today’s products.
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11/30/2012
Aggie Honor Code
An Aggie does not lie, cheat or steal,
or tolerate those who do.
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