Friedel-Crafts reaction in acidic or basic chloroaluminate-
(III) ionic liquids),10 we have found no case where the type
of reaction that occurs is completely changed by the choice
of the ionic liquid.4-8
outside of the patent literature25 in ionic liquids, but one is
described here.
These three classes of reactions were attempted in a
number of ionic liquids. The ionic liquids chosen were those
that were stable to the reagents, were not water sensitive,
and could be recycled and reused. Also, reactions were
chosen to produce the minimum amount of waste products,
with water as the only byproduct. In the course of this
investigation, it was found that the outcomes of these
classical reactions were highly dependent on the ionic liquid
employed.
We have investigated here a number of ionic liquids as
media for chemical reactions, in particular, classical chemical
reactions such as aromatic nitration, halogenation, and
oxidation. Conventionally, the nitration of an aromatic
compound involves the use of a nitrating agent made from
mixtures of nitric and sulfuric acid.11 At the end of the
reaction, a large amount of sulfuric acid waste is formed,
which is then neutralized prior to disposal. These reactions
have also been investigated using lanthanide(III) triflate
catalysts,12 in perfluorocarbon solvents,13 and by ourselves.14
Nitrations in ionic liquids such as [Et3NH][NO3] using
ultrasound15 and reactions involving nitrating agents such
as [NO2][BF4], [NH4][NO3]/trifluoroethanoic acid or alkyl
nitrates16 are known, but in these cases, the ionic liquids were
either consumed or the reaction required toxic and/or
explosive nitrating agents.
Halogenation of aromatic compounds usually involves the
reaction of the arene with a halogen, using a metal halide
catalyst.11 This process produces hydrogen chloride as a
stoichiometric waste product.11 Halogenations have also been
attempted in chloroaluminate ionic liquids on both alkenes17
and arenes,18 but again the arene halogenation procedure
produces hydrogen chloride waste. Oxidative halogenation,
using nitric acid and a metal halide, has also been described
in the patent literature.19,20
The nitration of various aromatic compounds was at-
tempted using 67% nitric acid as the nitrating agent, leaving
water as the only byproduct of reaction. The nitration of
benzene proceeds smoothly to give nitrobenzene in quantita-
tive yield in the hydrophobic ionic liquid 1-decyl-3-meth-
ylimidazolium trifluoromethane sulfonate, [C10mim][OTf],26
and in the hydrophilic ionic liquid 1-butyl-3-methylimida-
zolium trifluoromethane sulfonate, [bmim][OTf]. The nitra-
tion of chlorobenzene was much slower than with benzene
and gave the three isomers of nitrochlorobenzene in excellent
yield, in a 69:2:29 ratio of 2-:3-:4-isomers. To determine if
the ionic liquids enhanced the reaction rate or selectivity in
the nitration of toluene, a control experiment was performed.
This involved heating toluene and 67% nitric acid at 110
°C for a day, which gave a 73% conversion to the three
isomeric nitrotoluenes. The nitration of toluene with 67%
HNO3 in [bmim][OTf] gave the three isomers of nitrotoluene
in quantitative yield. Quantitative dinitration could be
achieved by prolonged heating with 100% HNO3. A reaction
was performed with 10 mol % [bmim][OTf]. This gave
similar results to the use of stoichiometric quantities of
[bmim][OTf], which means that [bmim][OTf] acts as a
nitration catalyst. It is interesting to note that neither 2,4,6-
trinitrotoluene (TNT) nor the nitrated imidazolium cation
were detected by NMR spectroscopy using this method of
nitration. Reactions in [C10mim][OTf] and 1-ethyl-3-meth-
ylimidazolium hydrogensulfate [emim][HSO4]27 gave similar
reaction rates but lower ortho:para isomer ratios than [bmim]-
[OTf]. The nitration of biphenyl gave a maximum yield of
94% after 18 h; for longer reaction times, dinitrobiphenyls
are formed. The reaction of anisole with 67% nitric acid in
[bmim][OTf] is rapid and exothermic at room temperature,
so cooling of the reaction vessel is essential. A 2:1 ratio of
para-:ortho-nitroanisole was obtained in 99% yield. The
The oxidation of compounds such as toluene or xylene is
an important reaction and is carried out on a large scale.21
The products of the oxidation reactions, e.g., benzoic or
terephthalic acid, are widely used in the polymer industry.
The aerial oxidations of alkyl arenes such as toluene are well-
known. These can be achieved by the action of homogeneous
cobalt(II) catalysts,22 by the vapor-phase reaction with
dioxygen over a V2O5 catalyst,23 or by the action of
concentrated nitric acid (under carefully controlled condi-
tions).24 To date, an effective reaction has not been reported
(10) Boon, J. A.; Levisky, J. A.; Pflug, J. L.; Wilkes, J. S. J. Org. Chem.
1986, 51, 480-483.
(11) Taylor, R. Electrophilic Aromatic Substitution; Wiley: Chichester,
1990.
(12) Braddock, C. Green Chem. 2001, 3, G26-G32.
(13) Crampton, M. R.; Cropper, E. L.; Gibbons, L. M.; Millar, R. W.
Green Chem. 2002, 4, 275.
(14) Earle, M. J.; Katdare, S. P.; Seddon, K. R. World Patent WO
0230865, 2002.
(15) Rajagopal, R.; Srinivasan, K. V. Ultrasonics Sonochem. 2003, 10,
41-43.
(16) Laali, K. K.; Gettwert, V. J. J. Org. Chem. 2001, 66, 35-40.
(17) Patell, Y.; Winterton N.; Seddon, K. R. World Patent WO 0037400,
2000.
(18) Boon, J. A.; Lander, S. W., Jr.; Levisky, J. A.; Pflug, J. L.;
Skrznecki-Cooke, L. M.; Wilkes, J. S. Proceedings of the Joint International
Symposium on Molten Salts, 6th ed.; 1987, 979-990.
(19) Notaro, V. A.; Selwitz, C. M. US Patent US 3636170, 1972.
(20) Earle, M. J.; Katdare, S. P.; Seddon, K. R. World Patent WO
0230852, 2002.
(21) Partenheimer, W. Catal. Today 1995, 23, 69-158.
(22) Chavan, S. A.; Halligudi, S. B.; Srinivas, D.; Ratnasamy, P. J. Mol.
Catal. A 2000, 161, 49-61.
(23) Dias, C. R.; Portela, M. F.; Gala´n-Fereres, M.; Ban˜ares, M. A.;
Lo´pez Granados, M.; Pen˜a, M. A.; Fierro, J. L. G. Catal. Lett. 1997, 43,
117-121.
(24) Koelsch, C. F. Organic Syntheses; Wiley: New York, 1955; Collect.
Vol. III, pp 791-795.
(25) Earle, M. J.; Katdare, S. P.; Seddon, K. R. World Patent WO
0230862, 2002.
(26) Typical Experimental Procedure. Benzene (0.78 g, 10 mmol) and
67% nitric acid (2.8 g, 30 mmol) were heated under reflux in [C10mim]-
[OTf] (2.5 g) for 18 h to give a monophasic solution (99% conversion by
GC analysis). The residual nitric acid and nitrobenzene were separated from
the ionic liquid by Kugelrohr distillation from the reaction vessel at 100
°C, 1 mmHg. The nitrobenzene was separated from the dilute nitric acid
by phase separation. NMR analysis was in accordance with authentic
nitrobenzene (Aldrich). NMR analysis of the ionic liquid showed that it
did not undergo nitration in the imidazole ring and was unchanged.
(27) Ethyl-3-methylimidazolium hydrogensulfate was synthesized from
the reaction of 1-methylimidazole with diethyl sulfate to give 1-ethyl-3-
methylimidazolium ethyl sulfate, followed by hydrolysis for 5 days at 100
°C with water. The excess water was distilled off and the ionic liquid dried
at 120 °C (1 mmHg) for 48 h.
708
Org. Lett., Vol. 6, No. 5, 2004