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::: Application Report
Efficient Grignard Reaction under Sealed
Vessel Conditions
The Grignard reaction is a powerful, frequently used organometallic
transformation to add important structural motifs to carbonyl
compounds resulting in secondary or tertiary alcohols.
Since usually the low boiling THF is used as a solvent, closed vessel
conditions and elevated temperatures can significantly enhance the
reaction. This is best done in a conventional synthesis reactor.
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1 Introduction
3 Reaction Conditions
The formation of organometallic Grignard reagents from
halides and elemental magnesium is a rather tricky and
often slow starting process. Prevention of moisture and air
is crucial. Therefore standard reaction conditions in open
vessels require special precautions to activate the
magnesium and to keep the moisture away from the
reagents.
110 mg (4.5 mmol) Mg turnings in 2 mL dry THF were
admixed with 0.42 mL (4 mmol) bromobenzene in an
argon-flushed reaction vial. After the exothermic reaction
has stopped, the vial is sealed with the silicone cap, placed
in the reactor and heated for 20 min at 90 °C to form the
Grignard reagent (see Figure 2, step 1). After cooling
300 mg (2 mmol) ethylbenzoate dissolved in 1 mL dry THF
are added and the mixture is heated for another 10 min at
90 °C.
After cooling the mixture is treated with 5 mL HCl (2 M) and
then evaporated. The residue is extracted with diethyl
ether and dried over MgSO4. Evaporation of the solvent
furnishes triphenylmethanol in 56% yield (292 mg).
Sealed vessel conditions allow for simple creation of inert
atmosphere and elevated reaction temperatures, thus
successful initiation and short reaction times are granted.
2 Equipment
The preparation of the Grignard reagent and the
subsequent Grignard reaction was performed as a one-pot
two-step sequence in a Monowave 50 synthesis reactor
utilizing 10 mL glass vials with silicone cap and PTFE
septum.
Fig. 2 One-pot, two-step reaction to form triphenylmethanol
4 Results
Heating beyond the boiling point of the employed solvent
allows reduction of the reaction time. Typically the
formation of the Grignard reagent as well as the Grignard
reaction itself require 30-60 minutes at reflux. Under sealed
vessel conditions both steps, especially the Grignard
reaction, can be significantly shortened. Due to the short
reaction process the isolated product can be obtained
within only one hour.
Fig. 1 Conventionally heated closed vessel synthesis reactor
Monowave 50
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::: Application Report
This is because of the high field density in modern
microwave reactors, which leads to rapid and tremendous
heating of the magnesium and causes degradation and
carbonization of the solvent on the surface of the
magnesium turnings.2
Comparison experiments with a closed vessel immersed in
a preheated oilbath showed that identical reaction times at
identical temperatures lead to identical yields (see
Table 1).
Table 1: Comparison of conditions and outcome under oilbath
conditions, microwave heating and conventional autoclave heating
(Monowave 50)
Oilbath
Microwave
Monowave 50
Temp.
90 °C
90 °C
90 °C
Reaction Time 1
20 min
20 min
20 min
Reaction Time 2
10 min
--
10 min
Yield
55 %
n.a.
56 %
5 Conclusion
Rapid heating under sealed vessel conditions allows a
quick, reproducible and failsafe procedure to generate
Grignard reagents. The subsequent Grignard reaction
furnishes the desired product in much shorter time
compared to classical reflux conditions.
6 References
The significant advantage of Monowave 50 compared to
oilbath heating lies in the easy and quick handling, the safe
and trouble-free operation at elevated temperatures, and
the permanent and comprehensive recording of data.
Experimental work from the Karl-Franzens University
Graz, Institute of Chemistry
[1] D. Obermayer, J. M. Kremsner, A. Stadler, Minutes, not
Hours! A Practical Guide to High-speed Organic Synthesis
in Modern Microwave Reactors, Anton Paar selfpublishing, 2016, p 58-59, ISBN 978-3-200-04434-0
Using microwaves as heating source for the formation of
the Grignard reagent (with the potential to activate the Mg
turnings) has proven unsuccessful. While microwaves can
be nicely used for the Grignard reaction, using the already
prepared magnesium bromide reagent,1 the direct
preparation of the Grignard reagent can be troublesome.
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[2] B. Gutmann et al., Angew. Chem. Int. Ed. 2011, 123,
7778
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