Preparation of the Grignard Reagent
All of the glassware needs to be very dry for
this reaction to work, so the instructor will
supply oven-dried kits to each lab group at the
start of the lab. Each kit should contain: a
25-mL round bottom flask, two large screw top
vials, a 50-mL Erlenmeyer, a Claisen adapter, a
drying tube, and a Pasteur pipet. Roughly
calibrate the pipet by making marks with a wax
pencil or Sharpie as shown on in Mohrig (inside
front cover).
Assemble a reaction apparatus suitable for the
slow addition of a reagent under anhydrous
conditions (Mohrig, Chap 7.5a). The basis for
this apparatus is shown in fig 7.5a. However, a
drying tube filled with CaCl2 needs
to be placed at the top of the reflux condenser
(similar to the setup shown in fig 7.2b). Also,
you will need to use a 25-mL round bottom flask
in place of the conical vial shown in fig 7.3.
(Also note that the syringe does not get
inserted until you are actually ready to begin
adding a reagent using it.)
Temporarily disassemble the reaction apparatus
so that you can add 15 mmol magnesium and a
magnetic stirbar to the round bottom flask.
Reassemble the apparatus.
Obtain approximately 40 mL anhydrous ethyl
ether using your dry Erlenmeyer. This is your
stock of ether for the first part of the
reaction. Keep the flask capped when not
actively removing ether from it.
Weigh a dry vial with cap. Add 15 mmol
1-bromoheptane to it and reweigh it to get the
actual mass used. Add 8 mL ether (from your
stock vial) and swirl to dissolve.
Add 2 mL ether (by syringe) to the reaction
flask and begin stirring.
Add 1.5 mL of the prepared 1-bromoheptane
solution. Stir with slight warming (cupping the
flask with your hand works well or you can use a
warm water bath (40-45 °C) but take care to not
get water into the flask!).
Watch carefully for signs that the Grignard
reaction has commenced. These include bubbles
coming off the surface of the metal, gray/brown
cloudiness to the solution, and signs of
corrosion on the surface of the metal. If the
reaction has not started on its own within 10
min of warming, then you will need to "jump
start" it.
To jump start the reaction, discontinue warming
and disassemble the rb flask from the rest of
the apparatus. Working quickly, carefully use a
dry spatula or glass rod to crush or break in
half some of the Mg pieces. Doing so exposes
unoxidized reactive surfaces on the metal which
then allow the reaction to begin.
Once the reaction has started begin adding the
rest of the 1-bromoheptane solution over a
period of about 15 minutes. Maintain a rate of
addition such that the solution refluxes on its
own without external heating. If the addition is
done too rapidly then the reaction may threaten
to become too vigorous, in which case you should
cool the flask briefly on a cold water bath
(just enough to slow down the reaction take care
not to stop it entirely). If the addition is too
slowly, the reaction will start to subside as it
runs out of starting material. If this happens
to the point of it appearing that the reaction
may stop altogether then it is important that
you add more 1-bromoheptane solution and/or
apply gentle warming to get it going again.
After all of the alkyl halide has been added,
add 2.0 mL ether to the vial it was in, rinsing
to dissolve any remaining 1-bromoheptane and
then add this rinse solution to the reaction
flask. The reaction will naturally start to die
out once all of the halide has been added. Once
it starts to do this, but before it stops
entirely, apply heat from a warm water bath so
as to keep it refluxing. Reflux on the warm
water bath for 10-15 min and then cool to room
temperature. During this period go on to get
ready for the next step.
Reaction of the Grignard Reagent with the
Aldehyde
Add 15 mmol octanal to approx 2 mL of anhydrous
ether in a dry vial. Using the same syringe used
for the alkyl halide addition to add this
solution to the Grignard reagent. The addition
can be done quickly but watch out for the
exothermicity and do not add it so quickly that
the solution begins to boil. Continue stirring
as the reaction cools to room temperature and
the adduct forms over the course of approx 20
min.
Work-up
(Note: for the remaining procedures the ether
does not need to be anhydrous.)
Cautiously neutralize the solution by adding 12
mL 6M HCl. This step serves to both protonate
the adduct alkoxide and to dissolve any
remaining Mg(s).
Add 10 mL ether and transfer the entire
contents to a separatory funnel.
Transfer the reaction mixture into a separatory
funnel and allow the layers to separate. Make
sure there are two distinct layers with no
solids present and, if necessary, add more ether
and/or HCl as needed to dissolve remaining
solids.
Drain the lower aqueous layer into a flask or
beaker and then transfer the organic layer
through the top of the sep funnel into a dry
125-mL Erlenmeyer flask.
Return the aqueous layer to the separatory
funnel and extract it with an additional 5 mL
ether.
Wash the combined ether layers with water (2 x
5 mL) and then dry the liquid over sodium
sulfate.
Decant the liquid into a dry pre-weighed round
bottom and remove the ether solvent on the
rotary evaporator (Mohrig pp 139-140).
Determine the yield of the crude and, if time
permits, recrystallize it from ethyl acetate.
Characterization. Obtain the mp (lit mp1
= 52-52.6 °C) as well as 1H NMR (in
CDCl3) and IR spectra of the final
product. Use the cast film method (Mohrig p 287)
and a disposable IR sample card (Mohrig p 289). A
handy recipe for the cast film method is to
prepare the solution for step 4 (p 287) by
dissolving 5 mg of your solid in 5 drops of DCM in
a small test tube One group will also be
asked to obtain a C-13 NMR.
Literature Reference
(1) Breusch, F.
L.; Sokullu, S. Chemische Berichte 1953,
86, 678-84.