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Ch e m 3 1 2 5
Experiment 1
The Grignard Reagent: preparation and reaction
Overall Synthesis:
O
MgBr
Br
OMe
O
OH
HO
Part A
H
?
Part B
Part C
Week 1: Part A
Preparation of the Grignard reagent: phenylmagnesium bromide.
MgBr
Br
Mg0
Et2O
phenylmagnesium bromide
aka "phenyl Grignard"
bromobenzene
Apparatus Setup
Drying Tubes
H2O out
Addition
funnel
H2O in
Claisen Adapter
(100-mL round bottom)
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Procedure:
Special Note: The Claisen adapter, condenser and RB flask must be dried in an oven,
preferably overnight. Before retrieving these items from the oven, have the magnesium,
addition funnel and drying tubes ready.
Add a stirbar and ~ 1.2 g of magnesium turnings to a 100-mL RB flask and assemble the
apparatus as shown in the figure above. Add 8 mL of anhydrous ether to the RB to make a
suspension of magnesium in ether. To the addition funnel (stopcock closed!!) add 10 mL of
anhydrous ether and 4.70 mL of bromobenzene and swirl to homogenize. Ensure that water is
running through the condenser and heat the flask with a heating mantle at a setting of 2-3.
Add a portion of the bromobenzene/ether solution (~ 20-30 drops) from the addition funnel onto
the magnesium turnings. A chalky appearance or color change (brown) is indication that the
reaction has started. If the reaction has not started after 10 min, add an additional portion of the
bromobenzene/ether solution.
If the reaction still hasn’t begun after an additional 10 minutes, add 2 or 3 drops of 1,2dibromoethane to the mixture. This compound reacts very readily with magnesium to form
ethylene gas and MgBr2; this removes the unreactive oxide layer on the magnesium, leaving it
free to react with the bromobenzene.
Once the reaction has started, add an extra 8-mL portion of anhydrous diethyl ether to the
reaction mixture through the condenser. This serves to dilute the reaction mixture and to
minimize the coupling reaction. The rest of the bromobenzene/ether solution should now be
added dropwise to the reaction mixture at a rate that is just fast enough to maintain a gentle
reflux. If it is added too fast, the reaction may get out of control, and the yield will also be
reduced, owing to increased coupling. If the reaction becomes too vigorous turn off the heating
mantle and reduce the rate of addition. This total addition should take about 15 min. If the
spontaneous boiling of the mixture becomes too slow, increase the rate of addition slightly
and/or turn up the heating mantle
At the end of the reaction the solution will normally have a tan to brown color, and most of the
magnesium will have disappeared, although residual bits of metal usually remain.
Notes:
No characterization is required for Part A. Once prepared, the Grignard reagent
must be immediately reacted with the ester, the first stopping point being the first
asterisk below:
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Part B
The reaction of phenylmagnesium bromide with methyl benzoate to give triphenylmethanol.
Procedure:
Dissolve 2.50 mL of methyl benzoate in 8 mL of anhydrous diethyl ether and place this solution
in the addition funnel (stopcock closed). Heat the RB flask gently (mantle setting ~1-2), and then
begin slow, dropwise addition of the solution of methyl benzoate to the phenylmagnesium
bromide solution. This reaction is exothermic; control the rate of reaction by adjustment of the
addition rate and/or removing the heating mantle, if necessary.
Frequently, a white solid forms during the reaction and is a sign that the reaction is proceeding
normally. After the addition is complete and the exothermic reaction has subsided, heat the
reaction mixture at gentle reflux for 20 min. Near the end of this time, add H2SO4 (25 mL, 6M)
and ~ 20 g of ice to a 250-mL Erlenmeyer flask.
After allowing the RB flask to cool to room temperature, pour the reaction mixture into the
H2SO4/ice mix with swirling. Stopper the Erlenmeyer and store in the location given by your
instructor.
Week 2
Add enough methyl tert-butyl ether (MTBE) to dissolve all the solids and transfer the entire
mixture to a 125-mL separatory funnel. Shake the funnel vigorously but carefully, venting often
to relieve pressure.
Remove the aqueous layer and wash the remaining organic first with H2SO4 (25 mL, 3M) and
then with deionized water (20 mL). Collect the organic layer and dry over anhydrous magnesium
sulfate.
Gravity filter into a 100-mL RB flask and distill away most of the solvent. Remove the heating
mantle and recrystallize from a mixture of ethanol and water (80/20) or heptane (reread Mohrig
book about mixed solvent recrystallizations if you are rusty on recrystallizations).
Isolate the product by vacuum filtration, using a cold solution of ethanol and water (~50/50).
Allow the solids to dry for at least a day and record the isolated mass.
Notes:
Triphenylmethanol (MW = 260.3 g/mol; MP = 164.2˚C)
Required characterization: melting point, proton NMR (in CDCl3), and IR.
Lab report should include analysis of the spectra produced by drawing the
structure on the NMR or IR and labeling which peaks go with which
functional groups or protons.
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Week 3
Part C
Formation of an unknown derivative by reaction with HCOOH
O
OH
HO
H
?
Procedure:
In a 50 mL RB flask heat a mixture of 1.00 g of triphenylmethanol in 5 mL of formic acid to
reflux for 30 min. Allow the flask to cool to room temperature, isolate the product by vacuum
filtration and wash with a little methanol.
Recrystallize the solid from ethanol. After isolating the solids by vacuum filtration, allow them
to dry for at least a day before weighing.
Determine the percent yield of the product based on the molecular weight of the structure you
assign.
Required characterization: melting point, proton NMR (in CDCl3), and IR
spectrum.
Lab report should include analysis of the spectra produced by drawing the
structure on the NMR or IR and labeling which peaks go with which
functional groups or protons.