From: Eugen Leitl (eugen$##$leitl.org)
Date: Wed Sep 25 2002 - 14:59:33 EDT
I've been asked offlist, what I meant by 'wet' solvent, so I just snipped
the whole article, since more people might be interested.
Grignard Reactions in "Wet" Ether
by David H. Smith, J. Chem. Ed. 76(10) 1427-8 (1999)
Procedure
Students can run Grignard reactions in regular laboratory grade ether and
in equipment that has not been specially dried. The reaction begins within
one minute and the product alcohol is ready for assay in one hour. This
technique, which requires only the simplest of glassware and a low-power
ultrasonic laboratory cleaner, is so robust that it deserves wider use.
Because no particular care is needed to dry either the solvent or the
equipment, large savings in time result for instructors and students.
Using this technique, the magnesium can be handled with the fingers during
weighing. The diethyl ether can come from a half-full can of "anhydrous
reagent ether" open for two months and in use in an undergraduate
laboratory (even the can containing the Pasteur pipet and bulb lost by a
student). The bromide and the ketone are from bottles suffering from
numerous years of student use. The glassware is right off the shelf. The
yield of product is typical of student reactions. This "non-dry" procedure
has worked as described on the second day of a rain storm, with open
laboratory windows, hoods pulling in the very humid air, and using
glassware directly out of student desks.
The ultrasonic initiation of Grignard reactions (1) does not appear to
have made the "mainstream" of use in current lab manuals. However, its
theory and applications have been discussed in this journal (2) and
elsewhere (3), and, indeed, the use of ultrasonic initiation of the
Grignard reaction has been reported in this Journal (4). The use of allyl
bromide and acetophenone, mediated by zinc in water and THF, has recently
been proposed (5) to circumvent the perceived problems with the need for
anhydrous solvents, ultradry glassware, and slow initiation for Grignard
reactions.
Experimental Procedure
CAUTION: All steps need to be conducted in a fume hood, as considerable
amounts of ether will evaporate. The instructor should put water in an
ultrasonic bath to a depth of about three inches. Several beakers filled
with water to the same depth are placed in the bath to support students'
test tubes. A beaker filled with cold tap water should be handy in case
rapid cooling of the reaction is needed. Then:
1. Add 0.010 mol (0.25 g) of clean magnesium turnings to a 6" test tube
(tube A). Add 0.100 mol (1.41 g) of pure 1-bromobutane and 3.1 mL of
anhydrous ether to a similar tube (tube B). Mix well. Note the level of
liquid in tube B and place a line on tube A at this height.
2. Use a Pasteur pipet to add enough of the bromideether solution to
tube A to partially cover the magnesium. Place this tube into a
water-filled beaker in the ultrasonic bath and begin sonicating. CAUTION:
Make sure the tube points away from other people! Watch the contents of
the tube. When the liquid turns gray or white, remove the tube. The ether
should begin to boil spontaneously. If it doesn't, put the tube back into
the ultrasonic bath.
3. When the reaction starts boiling spontaneously, remove the tube from
the ultrasonic bath. Add about 0.5 mL of pure ether. When the initial
boiling has slowed, add more 1-bromobutaneether solution at a rate to keep
the reaction going moderately well. If the reaction slows, add another 0.5
mL of pure ether to make up for evaporation loss. If it goes too
vigorously, place the tube in cool water.
4. After adding all of the bromide-ether solution, add enough ether to
keep the liquid level to the mark on the test tube. When the reaction
slows and almost all of the magnesium is gone, sonicate the mixture for a
few minutes more.
5. Remove the tube from the ultrasonic bath. Pipet the solution into a
dry 50-mL Erlenmeyer flask. Rinse the test tube once with 0.5 mL of ether
and add the washings to the 50-mL flask. Cool the flask and its contents
in an ice bath. Any Magnesium remaining in the tube can be air-dried and
weighed.
6. Any property scaled standard procedure for adding the ketone to a
Grignard reagent may be used at this point. CAUTION: It is important that
the ether solution of the ketone be added dropwise into the 50-mL
Erlenmeyer flask using cold reagents! The reaction with the ketone is very
vigorous and material explodes from the open end of a test tube with a
range of about two laboratory benches!
Results and Discussion
A standard laboratory ultrasonic parts cleaner of 125 W, 60 kHz has been
used. A single unit of 3-L size is adequate for a tab section of 20 or
more, with only slight crowding or waiting. Such a cleaner lists in
laboratory supply catalogs for about $470. The water bath will heat up to
about 35°C in about an hour of continuous sonicating. Students should go
to another hood after their reaction starts. A sizable amount of ether
evaporates during sonication and reaction.
My students follow the general procedure above for forming Grignard
reagents, and the scaled version of the ketone addition step from their
regular laboratory manual. They are assigned alkyl or aryl bromides and
ketones almost at random, but some care being taken by the instructor that
the product will give a pattern in the NMR that a beginner can interpret
(see list below). Students are responsible for adjusting the mass of
reagents to the formula weights of their compounds and for predicting the
IR and NMR of their product.
Compounds Used for Grignard Reaction
Bromides: 4-Bromotoluene, Bromobenzene, 2-Bromopropane,
3-Methyl-1-bromobutane, 1-Bromobutane, Bromoethane, 1-Bromopropane,
2-Methyl-1-bromopropane
Ketones: Cyclohexanone, 2-Butanone, 3-Pentanone, 4-Methyl-2-pentanone,
Cyclopentanone, 2-Pentanone, Benzophenone, Acetophenone
Of these reagents, only p-bromotoluene has been slow, but it started as
well as the others. Aldehydes work well, but their odor is unnecessarily
strong. Virtually all students have an active Grignard reaction going
within five minutes; most start within 45 seconds - In contrast, without
sonication, 1-bromobutane does not begin reacting with magnesium for at
least two minutes.
GC and IR assays of a typical reaction between 1-bromobutane and
acetophenone show that some of the 1-bromobutane (2%) and some of the
acetophenone (5%) remain. About 15% of the magnesium remains. Yields of
alcohol of 60-80% are observed. The product distribution (via GC is
identical to the nonsonicated reaction (die alcohol, some unreacted ketone
and bromide, and 1530% of an unidentified material that is not n-octane
dimer [GC] or an alkene [IR]).
What Are the Limits of This Procedure?
A reaction was performed using diethyl ether that had been shaken with
water, the mixture then being allowed to stand for one hour. The ether was
so wet that 1-bromobutane formed a cloudy mixture when it was added. The
reaction of this mixture with magnesium proceeded satisfactorily after
sonication for about 50 min. The yield of product alcohol was about 50%
(GC).
The reaction of 1-bromobutane and magnesium started successfully within
two minutes in undried either and undried equipment on the 10-g scale. The
yield of alcohol was about 60%.
Old magnesium turnings with a black surface and just a small amount of
brighter metal were also tried. The reaction started in the same time as
the reaction with better quality magnesium. Alkyt chlorides in
sodium-dried ether began reaction sooner with ultrasonication than
without. However, the initiation time is greater than 30 minutes,
impractical in the undergraduate laboratory. 1-Bromobutane in methyl
tert-butyl ether did not react using the ultrasonic method. However, this
less flammable solvent can be substituted for diethyl ether as the solvent
for the aldehyde or ketone (7). Methyl tert-butyl ether and
dichloromethane can be used in the extraction step, but some people find
the odor of methyl tert-butyl ether to be objectionable and
dichloromethane may be a weak carcinogen.
There is no question that thoroughly drying all components of a Grignard
reaction will give better results, with or without ultrasonication. The
use of the ultrasonicator will initiate Grignard reactions with organic
bromides very rapidly with very little failure under conditions that
prevail in undergraduate laboratories. The ultrasonicator also allows the
use of much less expensive grades of ether, with no apparent penalty in
product yield or quality.
Literature Cited
1. J. Am. Chem. Soc. 102, 7926-7927 (1980).
2. J. Chem. Educ. 63, 427 (1986).
3. Chem. Ber. 47-50 (1996).
4. J Chem. Educ. 63, 176 (1986).
5. J. Chem. Educ. 75, 85 (1998).
6. Wilcox, C. E. Jr. Experimental Organic Chemisoy; McMillan: New York, 1988.
7. Williamson, K. L. Macroscale and Microscale Organic Experiments, 2nd
ed; Heath: Lexington, MA, 1994.
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