EFFECT OF LEWIS ACIDS ON DIELS–ALDER REACTION
Sc(Otf)3 did not dissolve completely). Reactions were carried out
at 258C. Alternatively the reactions were carried out in a high
pressure IR cell with sapphire windows at 58C for 2 h with spectra
recorded at 2 min intervals.[37] FT-IR spectroscopic data were
analysed using TimeBase version 2.0 (Perkin-Elmer). Numerical
analyses were carried out with Scientist 2.0 (Micromath).
After reaction, the products were analysed by 13C NMR
spectroscopy and GC. NMR spectra were recorded on Bruker DRX
400 MHz spectrometer. GC analyses were carried out on a Varian
Chrompack CP-3380 equipped with capillary (25 m ꢂ 0.25 mm,
using He as carrier gas). Sonicated reactions were performed
as described for silent reactions except vials were sonicated in
an ultrasonic bath operating at 40 kHz. Reactions were carried
at 258C and were monitored periodically by 1H and 13C NMR
spectroscopy. Microwave reactions were performed as described
for the silent reactions in a microwave reactor under the fixed
temperature of 608C and power of 300 W for 10 min. All
the samples were closed in special vials equipped with a
stirrer and analysed immediately after reaction by 1H NMR
spectroscopy.
CONCLUSIONS
Herein, the influence of physical activation modes (high pressure,
ultrasound and microwave heating) individually or in combi-
nation with chemical activation modes (Lewis acid catalysts), on
the Diels–Alder reaction in ionic liquids have been investigated. It
has previously been reported that the strength of ion pairing
between the ionic liquid cation and anion is important in
controlling Diels–Alder reactions.[8] That is, the weaker the ion
pairing interaction the stronger the interaction between the ionic
liquid anion and substrate, leading to increased selectivities. Our
correlations fit very well with data reported by Chiappe and
coworkers who demonstrated by ESI-MS the relative ion pairing
strengths of a series of ionic liquid cations and anions, and
notably that [Tf2N]ꢀ interacts relatively weakly with ionic liquid
cations.[31] Weak anion–cation interactions allow the substrate to
interact more intimately with the ionic liquid cation in agreement
with the work of Welton and coworkers.[9]
From this study, we were able to show that the relatively high
concentrations of Lewis acid catalysts can improve the selectivity
and the yield of Diels–Alder reactions conducted in the ionic
liquids. High concentrations of InCl3 gave good results,
presumably due to its high solubility and stability in the ionic
liquid, in agreement with a previous study on alkylation
reactions.[22] These results demonstrate that the interaction of
the substrate(s) with the Lewis acid catalyst dissolved in ionic
liquid is the dominant factor.
Acknowledgement
We thank Novartis for financial support.
High pressure accelerates the catalysed reaction, although only
minor improvements in the selectivity were observed. Microwave
irradiation accelerates the reaction considerably, although the
selectivities are lower then those obtained at room temperature,
but still significantly higher than in reactions using conventional
heating. These results imply that microwave dielectric heating in
ionic liquids does not only include the ‘thermal effect’ but also
‘nonthermal microwave effects’. Ultrasound irradiation leads to an
increase in the reaction yields and the selectivities. In the best
case, reactions in ionic liquids containing Lewis acids under
sonication give selectivities of up to 21:1 under optimized
conditions.
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1
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Diels–Alder reactions
In a typical reaction, cyclopentadiene (0.16 mL, 1.9 mmol) and
dienophile (1.6 mmol) were added to the ionic liquid or organic
solvent (2 mL) at 08C. For catalysed reactions, the ionic liquid was
doped with the appropriate Lewis acid catalyst in a glovebox and
stirred at 808C for 2 h until dissolved (>10% mol ratio of ZnI2, and
J. Phys. Org. Chem. 2008, 21 264–270
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