Download The Grignard Reagent

Chemistry 2412L
Grignard Reaction Pre-lab lecture
The Grignard Reaction
• The Grignard reaction is a very important
reaction in organic synthesis used to make
carbon-carbon bonds.
• It involves the reaction of an appropriate organic
molecule with a organomagnesium halide,
called the Grignard reagent.
The Grignard Reagent
• Grignard reagents (RMgX) are formed from the reaction of an alkyl
halide and magnesium
• The solvent is typically diethyl ether (“ether”, Et2O) or
tetrahydrofuran (THF)
Mg
R
R
X
Mg
X
Et2O
• The reaction occurs on the metal surface, and is often difficult to
start. You can help the reaction start by gently heating the flask,
grinding the Mg against the inside of the flask with a glass stir rod.
• The reaction has started when the mixture becomes cloudy and
generates enough heat to boil the solvent without additional heat
being added.
The Grignard Reagent
• The Grignard reaction will not take place in the
presence of water. Water “kills” the Grignard
reagent by reacting with the reagent:
R
Mg
X
H2O
HO
Mg
X
+
R
H
• It is very important that the reaction apparatus,
reagents, and solvents must all be kept dry. You will
be using glassware from your organic lab kits for
this experiment. It is a good idea to dry your
glassware in the oven before starting the reaction.
Also make sure to keep the reagent bottles capped.
The Grignard Reaction
• Grignard reagents react with carbonyl compounds to
form alcohols. The type of alcohol produced
depends on the type of carbonyl reacted.
• In this experiment you will generate a tertiary
alcohol from the reaction of a Grignard reagent with
an ester. This process consists of two reactions:
1. Formation of Grignard Reagent
2. Reaction of Grignard Reagent to form the alcohol
1. Formation of Grignard Reagent
• Bromobenzene reacts with Mg metal in ether to
form phenylmagnesium bromide:
Br
MgBr
Mg
Et2O
2. Reaction of Grignard Reagent
• Methyl benzoate reacts with phenylmagnesium
bromide (step 1), followed by aqueous acid
work-up (step2), to form triphenylmethanol:
O
CH3
C
1. 2
MgBr
O
C
2. H3O
+
OH
Procedure Notes
• Pictures of the apparatus and reaction in progress
can be found at this site. It will be very helpful for
you to look at these pictures before you begin this
experiment.
• Week 1:
– Preparation of Grignard reagent (reaction 1) and first
step of reaction 2
– Once reaction 1 has started it should keep going on its
own. If the reaction slows you may need to add a little
heat to continue the reflux.
– Be careful not to overheat the reaction. Remember
ether boils at 35°C. Do not confuse the reaction starting
with the ether boiling. You will see a cloudiness and
change in color when the reaction has started.
– Use your time wisely. While one partner monitors
reaction 1 the other should prepare the ester for
reaction 2.
– Most of the Mg will dissolve during the reaction. Any
remaining Mg will dissolve in the work-up (week 2).
– At the end of this week’s procedure, stopper and label
the round-bottom flask and put in in the Rotovap hood.
Procedure Notes
• Week 2:
– Finish reaction and isolate product
– Make sure you keep all layers during the
extractions until you are certain you have
recovered your product
– Petroleum ether is not the same thing as
diethyl ether. Be careful you are using the
correct solvent. Pet ether is used to remove
a common by-product of this reaction:
biphenyl. Think about how biphenyl was
formed in this reaction.
– Analysis of product (yield, mp, IR)
Safety Notes
• Ether is highly flammable. There should
be no flames in the laboratory during
this experiment.
• Dispose of all waste as directed by your
instructor. Do not pour anything down
the drain.