discounted. It is known, for example, that metal bis(trifluoro-
methanesulfonyl)amides are, in general, much more active than the
3 4
Table 1 Comparison of acylation reactions using an InCl -[C mim]Cl
{X(InCl
benzoic anhydride (BA), benzoyl chloride (BC) or ethanoic anhydride
EA). With the exception of reactions performed using benzene and
3
) 5 0.67} ionic liquid, j 5 5, unless otherwise indicated, and
14
corresponding triflate salts. In 1,4-dioxane, again no conversion
to product was found, presumably due to deactivation of the
indium(III) chloride by complexation with 1,4-dioxane. As
expected, increasing the volume of the ionic liquid, such that
j 5 10, resulted in a higher rate of reaction. In addition, neither
basic nor neutral chloroindate ionic liquids were found to catalyse
the reaction. This is also the case with aluminium(III) chloride
(
naphthalene, a 1.1 molar excess of acylating agent was used. For
benzene and naphthalene, a 1.5 molar excess of acylating agent was
used
Substrate/acylating
agent
Selectivity
Time/h Temp./uC Yield/% (2- : 3- : 4-)
Benzene/BA
Benzene/BC
Toluene/BA
Toluene/BA
Toluene/BC
Toluene/EA
Isobutylbenzene/BA 48
Isobutylbenzene/BC 48
Chlorobenzene/BC
Chlorobenzene/BC
Fluorobenzene/BC
48
48
3
48
18
48
80
80
80
22
81
51
86
93
2
87
96
78
75
96
41
81
79
62
97
34
89
94
—
—
6
,7
sytstems. The shape of the conversion versus time curves shown
in Fig. 1 is indicative of the catalyst being deactivated. In similar
reactions, it has been shown that the addition of 4-methoxybenzo-
14 : 0 : 86
16 : 3 : 81
15 : 3 : 82
14 : 5 : 81
13 : 1 : 86
16 : 1 : 83
11 : 2 : 87
11 : 2 : 87
4 : 0 : 96
110
110
110
120
120
120
120
80
80
80
80
80
a
15
phenone reduces the reaction rate but benzoic acid had no effect.
The latter is due to the poor solubility of the acid in the ionic liquid.
Although the chloroindate(III) system requires more indium(III)
chloride to produce an effective catalytic system than, for example,
b
69
96
96
48
48
3
3
48
3
c
4 2
indium(III) chloride dissolved directly in [C mim][NTf ], the
d
e
workup and recycle of the reaction are significantly more efficient.
In [C mim][NTf ], the product can be removed by solvent
Naphthalene/BA
Naphthalene/BC
2 : 1
6 : 1
d
e
4
2
Anisole/BA
Anisole/BA
6 : 0 : 94
6 : 0 : 94
2 : 0 : 98
2 : 0 : 98
2 : 0 : 98
6 : 0 : 94
extraction using, for example, mesitylene; however, the extraction
efficiency is poor due to the strong affinity of the ketone product
with the ionic liquid. For the chloroindate(III) system, an aqueous
workup is possible. To recycle the chloroindate(III) system, the
minimum amount of solvent, which could be the anisole starting
material, was added to the reaction mixture in order to ensure that
the solution became homogeneous. Water was then added and
separated by decantation which removes the ionic liquid and this
phase is subsequently dehydrated to recover the ionic liquid. The
products were then separated by washing the anisole phase with
hot aqueous NaOH to remove the benzoic acid and the anisole
recovered by distillation. Using this procedure, the reaction system
was recycled 5 times with only a small loss in activity of the ionic
liquid system, as shown in Table 1, and no change in selectivity.
Furthermore, the indium content in the 4-methoxybenzophenone
was , 0.3 mg indium/gram of product for each recycle, analysed by
ICP analysis, i.e. , 0.00003% loss of ionic liquid. Since the small
amount of indium detected by ICP is insignificant, the decrease in
activity observed on recycle may be associated with mechanical
losses on work up.
f
Anisole/BA
Anisole/EA
Anisole/EA
80
80
80
100
48
18
c
a
Anisole/BC
a
b
j 5 12.5. j 5 15. InCl
3
-[P6,6,6,14]Cl {X(InCl
3
e
5 0.67}, j 5 10.
d
3 4 3
InCl -[C mim]Cl {X(InCl ) 5 0.60}, j 5 10. Selectivity for the
f
1- : 2- products. 5th recycle.
It should be noted that the recycle procedure described for the
benzoylation reaction mixture could not be applied to mixtures
containing ethanoic anhydride due to the poor phase separation
between the organic and aqueous phases. This is probably due to
the presence of ethanoic acid, which is highly soluble in both
phases. Due to the lower distillation temperature of methoxyace-
tophenone (85 uC at 0.1 mm Hg) compared with methoxybenzo-
phenone, however, direct distillation under vacuum was possible
without decomposition of the ionic liquid.
It should be noted that it is exceptionally difficult to obtain good
yields in genuinely catalytic Friedel–Crafts acylation reactions with
1
6
Friedel–Crafts acylation of a range of aromatic compounds has
also been successfully performed using benzoic anhydride, benzoyl
chloride and ethanoic anhydride in the chloroindate(III) ionic liquid,
Table 1. Chlorobenzene and fluorobenzene were not found to react
at 80 uC with benzoic anhydride; however, some reaction (ca. 5%)
was observed at 120 uC. Using benzoyl chloride, both chlorobenzene
and fluorobenzene gave excellent yields and selectivities for the
aromatic compounds less reactive than benzene. With indium(III)
chloride ionic liquids as catalysts, 75–96% yields were obtained
with these unreactive compounds.
We are indebted to QUILL (MJE), EU Marie Curie Early
Stage Training Site Fellowship, contract number HPMT-2000-
00147 (UH), the EPSRC and LINK under grant GR/N02085
(BJMcA, JMT) for financial support.
4
-isomer, albeit with an increased catalyst concentration in the case
a
d
ab
of chlorobenzene. Benzene, isobutylbenzene, toluene and naphtha-
lene all gave good yields with both benzoyl chloride and benzoic
anhydride; although higher temperatures were required for the more
sterically hindered isobutyl derivative. In all cases the anhydride
acylating agent was less reactive, as expected, compared with the acid
chloride. It is interesting to note that, in the case of naphthalene, the
more bulky anhydride increased the formation of the less favoured
Martyn J. Earle, Ullastiina Hakala, Christopher Hardacre,
e a ac
Johanna Karkkainen, Barry J. McAuley, David W. Rooney,
ab
ab
d
Kenneth R. Seddon, Jillian M. Thompson and Kristina W a¨ h a¨ l a¨
a
QUILL, The Queen’s University of Belfast, Stranmillis Road, Belfast,
Northern Ireland, UK BT9 5AG
School of Chemistry, The Queen’s University of Belfast, Stranmillis
Road, Belfast, Northern Ireland, UK BT9 5AG
School of Chemical Engineering, The Queen’s University of Belfast,
Stranmillis Road, Belfast, Northern Ireland, UK BT9 5AG.
E-mail: c.hardacre@qub.ac.uk; Fax: 44 28 90382 117;
Tel: 44 28 9097 4592
Laboratory of Organic Chemistry, Department of Chemistry, Faculty
of Science, University of Helsinki, PO Box 55, FIN-00014, Finland
b
c
2-substituted product. As shown above, anisole was easily acylated
with benzoic anhydride and benzoyl chloride although, as expected,
the rate of reaction for anisole using ethanoic anhydride was slower
in comparison. A similar reduction in rate was also observed for
toluene.
d
e
Department of Chemistry, University of Oulu, PO Box 3000,
FIN-90014, Finland
9
04 | Chem. Commun., 2005, 903–905
This journal is ß The Royal Society of Chemistry 2005