Activation of bismuth(III) derivatives in ionic liquids: Novel and recyclable catalytic systems for Friedel-Crafts acylation of aromatic compounds

Article abstract of DOI:10.1021/ol034529n

(Matrix presented) The activity of four bismuth(III) derivatives when employed as Friedel-Crafts catalysts for the acylation of aromatics was found to increase dramatically when dissolved in ionic liquids. Solutions of bismuth oxide or triflate in [emim][NTf₂] and [bmim][NTf₂] are the most efficient catalytic systems, with catalyst loading as low as 1% leading to clean, high-yielding acylation of a variety of benzene derivatives. These improved Friedel-Crafts catalytic systems can also be efficiently recycled as opposed to traditional systems.

Full text of DOI:10.1021/ol034529n

ORGANIC
LETTERS
2003
Vol. 5, No. 13
2219-2222
Activation of Bismuth(III) Derivatives in
Ionic Liquids: Novel and Recyclable
Catalytic Systems for Friedel−Crafts
Acylation of Aromatic Compounds
Said Gmouh, Hongli Yang, and Michel Vaultier*
Laboratoire SESO, UMR 6510, Institut de Chimie de Rennes, UniVersite´ de Rennes1,
Bat10A, Campus de beaulieu, 35042 Rennes Cedex, France
michel.Vaultier@uniV-rennes1.fr
Received March 26, 2003 (Revised Manuscript Received May 22, 2003)
ABSTRACT
The activity of four bismuth(III) derivatives when employed as Friedel−Crafts catalysts for the acylation of aromatics was found to increase
dramatically when dissolved in ionic liquids. Solutions of bismuth oxide or triflate in [emim][NTf2] and [bmim][NTf2] are the most efficient
catalytic systems, with catalyst loading as low as 1% leading to clean, high-yielding acylation of a variety of benzene derivatives. These
improved Friedel−Crafts catalytic systems can also be efficiently recycled as opposed to traditional systems.
-
The Friedel-Crafts (F&C) acylation reaction produces
aromatic ketones, which are important intermediates in a very
wide variety of fields, including pharmaceutical dyes,
fragrances, and agrochemicals. Many of the industrial
processes still use HF or AlCl3 as catalysts.1 However, the
reaction requires more than a stoichiometric amount of these
catalysts, which cannot be recovered and reused after the
usual aqueous workup and therefore generates large amounts
of wastes in industrial processes. Considering the ecological
and economical problems associated with waste management
in most countries, safe and environmentally acceptable
processes for F&C reactions would be of high intrinsic
economic value and interest.2
In recent years, ionic liquids (ILs) have emerged as one
of the most important alternatives to volatile organic solvents
(VOS).2 One of the earliest examples of catalytic reactions
performed in room-temperature ionic liquids were the F&C
reactions.3 The first example of acylation reaction in ionic
liquids was performed by Wilkes et al.4 The rate of the
reaction was found to be dependent on the chloride/aluminum
chloride ratio and hence on the concentration of the [Al2Cl7 ]
ion. Recently, Seddon et al.5 have reported the F&C acylation
of both activated and deactivated aromatic compounds in
an ionic liquid system derived from [emim][Cl]-FeCl3 having
a mole ratio of FeCl3 to [emim][Cl] of 53.5%. More recently,
Xiao et al.6 have shown that the acylation of anisole with
benzoyl chloride can be readily performed, using metal
triflates that do not require special handling as catalysts in
[bmim][BF4] as the solvent.
Bismuth derivatives are also known to catalyze many
organic tansformations,7 including oxidation of acyloins to
diketones catalyzed by bismuth oxide,8 oxidation of sulfides9
catalyzed by Bi(NO3)3‚5H2O, or deprotection of O,O- and
S,S-acetals.10 Recently, Dubac and co-workers reported the
(4) Boon, J. A.; Levisky, J. A.; Pflug, J. L.; Wilkes, J. S. J. Org. Chem.
1986, 51, 480-483.
(5) Davey, N. P.; Earle, J. M.; Newman, C. P.; Seddon, R. K., World
Patent WO 99 19288, 1999.
(6) Ross, J.; Xiao, J. Green Chem. 2002, 4, 129-133.
(7) (a) Roux, C. L.; Dubac, J. Synlett 2002, 181-200. (b) Leonard, N.
M.; Wieland, L. C.; Mohan, R. S. Tetrahedron 2002, 58, 8373-8397.
(8) Rigby, W. J. Chem. Soc. 1951, 793-795.
(9) (a) Mashraqui, S.; Mudaliar, C.; Karnik, M. Synth. Commun. 1998,
939-943. (b) Komatsu, N.; Uda, M.; Suzuki, H. Chem. Lett. 1997, 1229-
1230.
(1) Olah, G. A. Friedel-Crafts and Related Reactions; Wiley-Inter-
science: New York, 1963.
(2) Lancaster, M. Green Chemistry: An Introductory Text; The Royal
Society of Chemistry: 2002.
(3) Earle, M. In Ionic liquids in Synthesis; Wasserscheid, P., Welton,
T., Eds.; Wiley-VCH: Weinheim, Germany, 2003; pp 196-204.
(10) (a) Komatsu, N.; Taniguchi, A.; Uda, M.; Suzuki, H. Chem.
Commun. 1996, 1847-1848. (b) Sabitha, G.; Babu, R.; Reddy, E.; Yadav,
J. Chem. Lett. 2000, 1074-1075.
10.1021/ol034529n CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/03/2003

use of bismuth trifluoromethane sulfonate as a catalyst for
Diels-Alder11 and aza-Diels-Alder12 reactions and in the
acylation of alcohols13 or of toluene, benzene, and chlo-
robenzene.14
In this paper, we disclose our preliminary results on the
Friedel-Crafts acylation of aromatic compounds with ben-
zoyl chloride using novel and recyclable catalytic systems
based on bismuth(III) derivatives immobilized in room-
temperature ionic liquids15 that are air- and moisture-
insensitive (Scheme 1). Four commercially available bismuth
room temperature. Bi(OTf)3 and BiOCl gave slightly better
results (43 and 30% conversions, respectively), but Bi2O3
showed the highest activity, leading to 53% conversion. No
reaction could be observed at room temperature in the
absence of the ionic liquid (<5% conversion). These results
clearly show the determining role of [emim][NTf2] in these
reactions as compared to organic solvents.
We then addressed the question of what would be the
smallest amount of bismuth catalyst that could be employed
in this reaction. Therefore, a study of the benzoylation of
anisole in the presence of 1 mol % catalyst was undertaken.
Results are reported in Figure 1. It is shown that with 1 mol
Scheme 1. Acylation of Aromatic Compounds Catalyzed by
Bi(III) Derivatives Dissolved in Ionic Liquids
derivatives were chosen for the study of the Friedel-Crafts
acylation of aromatics in the presence of ionic liquids,
namely, Bi(OTf)3, Bi2O3, BiCl3, and BiOCl. The benzoylation
of anisole and toluene was used as a test reaction to compare
the catalytic activity of these bismuth derivatives immobilized
in ionic liquids under standardized conditions.
In a typical reaction, a mixture of benzoyl chloride (1 mol)
and anisole (2 mol) was added to a preheated mixture of
catalyst (0.1 mol) and [emim][NTf2] (0.1 mol) at 80 °C.
Under these conditions, all catalysts used provided 100%
conversion of benzoyl chloride to the corresponding ben-
zophenones (ortho/meta/para ) 4/0/96 for the four catalysts)
after 0.5 h of reaction time. However, following the reactions
since the very beginning revealed that, under these condi-
tions, the acylation was over in less than 5 min with Bi-
(OTf)3 and Bi2O3 as catalysts. It is interesting to note that
the reaction mixtures are homogeneous at 80 °C. These
results were very promising and have to be compared to those
reported in the literature when ionic liquids were not used,
i.e., Bi(OTf)3 in neat anisole gave a 92% isolated yield of
benzophenones (ortho/meta/para ) 8/0/92) after 3 h at 110
°C. Interestingly, when the reaction was carried out at 20
°C in the presence of [emim][NTf2], BiCl3 appeared to be
the less active, producing only 10% conversion after 12 h at
Figure 1. Acylation of anisole with benzoyl chloride catalyzed
by 1 mol % Bi(III) derivatives in the absence of IL or immobilized
in [emim][NTf2]: (O) Bi(OTf)3 and [emim][NTf2]; (+) Bi(OTf)3;
(b) Bi2O3 and [emim][NTf2]; (×) BiOCl and [emim][NTf2]; (9)
BiCl3 and [emim][NTf2]; (/) Bi2O3; (() BiCl3; (2) BiOCl. Reaction
conditions: a mixture of 10 mM benzoyl chloride and 20 mM
anisole and 0.1 mM catalyst in the presence or absence of 0.1 mM
[emim][NTf2] was stirred at an oil bath temperature of 80 °C. The
selectivity ortho/meta/para was 4/0/96 in all cases.
% Bi(OTf)3 dissolved in [emim][NTf2], the reaction went
to completion in 4 h, which is quite remarkable. In the
presence of Bi(OTf)3 without IL or Bi2O3 in [emim][NTf2],
conversion was only in the range of 65-70%. BiCl3, in the
presence or absence of the ionic liquid, was less active.
To confirm the better activity of these bismuth derivatives
in ionic liquids, we have studied the acylation of toluene,
which is less reactive than anisole and therefore more
discriminating. Indeed, literature reveals that BiCl3, Bi2O3,
and BiOCl are ineffective catalysts for the acylation of neat
toluene.14a
The reactivity study was carried out at a temperature of
150 °C (oil bath) using 1 mol % catalyst and 2 equiv of
toluene in the presence of [emim][NTf2] used as the test ionic
liquid. Aliquots were withdrawn every hour over 5 h and
extracted with ether, and conversion levels were determined
by GC. Results are reported in Figure 2.
(11) (a) Garrigues, B.; Gonzaga, F.; H. R.; Dubac, J. J. Org. Chem. 1997,
62, 4880-4882. (b) Robert, H.; Garrigues B.; Dubac, J. Tetrahedron Lett.
1998, 39, 1161-1164.
(12) (a) Laurent-Robert, H.; Garrigues, B.; Dubac, J. Synlett 2000, 8,
1160-1162. (b) Motorina, I.; Grierson, D. Tetrahedron Lett. 1999, 40,
7215-7218.
(13) (a) Orita, A. C.; Tanahashi, A. K.; Otera, J. Angew. Chem., Int. Ed.
2000, 39, 2877-2879. (b) Carrigan, M. D.; Freiberg, D. A.; Smith, R. C.;
Zerth, H. M.; Mohan, R. S. Synthesis 2001, 14, 2091-2094.
(14) (a) Desmurs, J. R.; Labrouille`re, M.; Roux, C. L. H.; Gaspard, A.
L.; Dubac, J. Tetrahedron Lett. 1997, 38, 8871-8874. (b) Repichet, S.;
Roux, C. L.; Dubac, J.; Desmurs, J. R. Eur. J. Org. Chem. 1998, 2743,
3-2746. (c) Le Roux, C.; Dubac, J. Synlett 2002, 181-200. (d) Desmurs,
J.-R.; Labrouille`re, M.; Dubac, J.; Laporterie, A.; Gaspard, H.; Metz, F.
Ind. Chem. Libr. 1996, 8, 15-28. (e) Labrouillere, M.; Dubac, J.; Gaspard,
H.; Desmurs, J.; Laporterie, A.; Le roux, C. World Patent WO 9711930,
2001. (f) Laporte, C.; Dubac, J.; Marquie, J.; Desmurs, J.; Laporterie, A.
World Patent WO 9840039, 2002.
As for anisole, the best results were obtained with bismuth
triflate dissolved in [emim][NTf2]: 100% conversion was
observed after 3 h. Bismuth triflate in neat toluene and
bismuth oxide in the presence of the ionic liquid demonstrate
a similar catalytic activity (about 60% conversion after 4 h
of reaction). In general, a considerable activation of Bi(III)
(15) Gmouh, S.; Vaultier, M. Pli Cachete´, LPC N° 2026, 2002.
2220
Org. Lett., Vol. 5, No. 13, 2003

to 150 °C. In that case, after 10 h of reaction, the isolated
yield was only 77%, due to some decomposition, instead of
89% as obtained when the two reagents were introduced to
a reaction mixture preheated at 150 °C. Reducing the amount
of catalyst from 10 to 5 mol % did not alter the conversion
time (about 6 h) or yields, which were quantitative (Table 2
Table 2. Friedel-Crafts Benzoylation of Toluene in Different
Ionic Liquidsa
Figure 2. Acylation of toluene with benzoyl chloride catalyzed
by 1 mol % Bi(III) derivatives in the absence of IL or immobilized
in [emim][NTf2]: (O) Bi(OTf)3 and [emim][NTf2]; (+) Bi(OTf)3;
(b) Bi2O3 and [emim][NTf2]; (×) BiOCl and [emim][NTf2]; (9)
BiCl3 and [emim][NTf2]; (/) Bi2O3; (() BiCl3; (2) BiOCl. Reaction
conditions: 10 mM benzoyl chloride was added to a mixture of 20
mM toluene, 0.1 mM catalyst, and 0.1 mM [emim][NTf2] preheated
at 150 °C (oil bath temperature) in a Schlenk tube under argon.
conversion
entry
ionic liquids
[emim][NTf2]
[emim][PF6]
[bmim][NTf2]
(%)b
1
2
3
4
5
6
7
8
9
75
68
98
60
<5
52
35
15
<5
68
45
[bmim][PF6]
[bmim][BF4]
[troma][NTf2]c
[troma][PF6]c
[troma][OTf]c
[troma][BF4]c
catalysts in the presence of [emim][NTf2] was observed
(Figure 2), suggesting the selection of bismuth oxide or
triflate in the presence of an ionic liquid for synthetic
purposes.
The influence of the temperature on the benzoylation of
toluene carried out in the presence of 10 mol % Bi2O3 and
10 mol % [emim][NTf2] was then studied. No detectable
conversion could be observed after 48 h (Table 1, entry1) at
10
11
[P(C6H13)3C14H29][NTf2]d
[P(C6H13)3C14H29][ PF6]d
a Reaction conditions: 1 mM benzoyl chloride was added to a mixture
of 2 mM toluene, 5 mol % Bi2O3, and 0.1 mM ionic liquids preheated at
150 °C with stirring. The reaction mixture was stirred at this temperature
for 4 h. b Determined by GC. Selectivity: ortho/meta/para ) 19/2/79.
c Troma ) trioctylmethylammonium. d We wish to thank the CYTEC
company for a generous gift of the corresponding chloride.
entries 7 and 8). However, further lowering to 1 mol %
slowed the reaction noticeably and only 70% conversion after
15 h was observed (entry 9). In all cases, 19/2/79 mixtures
of ortho/meta/para benzophenones were isolated.
Table 1. Effect of Temperature and Amount of Bi2O3 on
Friedel-Crafts Acylation of Toluene in [Emim][NTf2]a
conversion
(%)
yield
(%)b
entry
mol % Bi2O3
T (°C)
t (h)
To examine the influence of the nature of the ionic liquid,
we have carried out the acylation of toluene with benzoyl
chloride in the presence of 5 mol % Bi2O3 in various air-
and moisture-stable RTILs16 at 150 °C for 6 h. We discovered
that the catalytic activity of Bi2O3 was strongly affected by
the nature of the cation and anion of the ionic liquid. Good
results were obtained with imidazolium cations such as
[emim][X] or [bmim][X] (Table 2 entries 1-4). However,
when tetraalkylammonium or phosphonium cations were
used, reactions were much slower and therefore product
yields were significantly lower as compared to those obtained
with imidazolium salts (Table 3 entries 6-11). With
hydrophobic anions such as [NTf2] or [PF6], the desired
ketones were obtained with good yields. By contrast, ILs
with hydrophilic anions such as tetrafluoborate or triflate led
to poor conversion levels, if any (Table 3, entries 5, 8, and
9). The use of [bmim][NTf2] instead of [emim][NTf2] led,
respectively, to 98 and 75% conversions (average values for
three assays) after 4 h of reaction (Table 2, entries 3 and 1),
thus illustrating the influence of the length of the alkyl group
on the cation on the activity of these systems.17
1
2
3
4
5
6
7
8
9
10
10
10
10
10
10
10
5
25
80
48
24
19
11
7.5
10
6
0
25
110
125
140
150
150
150
150
100
100
100
100
100
100
70
78
86
85
77c
89
85
64
6
15
1
a Reaction conditions: 1 mM benzoyl chloride was added to a mixture
of 2 mM toluene, 0.1 mM Bi2O3, and 0.1 mM [emim][NTf2] under stirring
at the indicated temperature. b Isolated yields of pure mixtures of ben-
zophenones after bulb to bulb purification; para/ortho/meta isomer ratios
were 79/19/2 in all cases. c Benzoyl chloride and toluene were mixed at
room temperature with the catalysts and then heated.
room temperature. After 24 h heating at 80 °C, a 25%
conversion was obtained, which has to be compared with
the 100% conversion of anisole in less than 5 min under the
same conditions. However, heating at 150 °C (oil bath
temperature) led to 100% conversion in 6 h. The addition
of benzoyl chloride must be carried out at the reaction
temperature (150 °C) in order to increase reaction yields and
reduce reaction time (entry 7). This is illustrated by the
experiment described in entry 6 where benzoyl chloride and
toluene were introduced at room temperature and then heated
(16) Preparation of ionic liquids: (a) Park, S.; Kazlauskas, R. J. Org.
Chem. 2001, 66, 8395-8401. (b) Bonhote, P.; Dias, A.; Parpageorigiou,
N.; Kalyanasundarama, K.; Gratzel, M. Inorg. Chem. 1996, 35, 1168-
1178.
Org. Lett., Vol. 5, No. 13, 2003
2221

a mixture of toluene and benzoyl chloride at 150 °C. We
obtained the same reactivity for the first three cycles. Then,
a longer reaction time was needed for the reaction to go to
completion. The sixth cycle took 15 h to produce a 75%
isolated yield. We noticed the precipitation of a solid on
cooling to room temperature, which was isolated as small
Table 3. Friedel-Crafts Benzoylation of Aromatic Compounds
in the Presence of [Emim][NTf2] and Bi2O3 Catalyst15 at an Oil
Bath Temperature of 150 °Ca
conversion
(%)b
yield
(%)c
entry
aromatic derivative
benzene
1,3-dimethybenzene
chlorobenzene
naphthalene
1-methylnaphthalene
2,6-dimethylnaphthalene
benzene
t (h)
1
white needles by filtration. H NMR analysis showed the
1
2
3
4
5
24
2.5
24
2.5
2.5
2.5
24
24
24
24
15
100
<5%
100
100
100
100
70
presence of the ethylmethyl imidazolium unit. 13C and 19F
NMR confirmed the absence of NTf2 anion. We have shown
this compound to be the ethylmethylimidazolium tetrachlo-
robismutate [emim][BiCl4] by elementary analysis and high-
resolution mass spectrometry. This anion could arise from
the reaction of bismuth oxide with HCl giving first BiCl3,
91
84
87
75
88
62
91
6
7d
8e
9d
10e
-
which is then transformed into BiCl4 by Cl- capture. The
benzene
chlorobenzene
chlorobenzene
100
58
[emim][BiCl4] salt is formed by metathesis. The melting
point of this salt is 112 °C, and the salt is therefore liquid at
the temperature used to carry out the F&C acylation of tolu-
ene. Using this ionic liquid with Bi2O3 as catalyst, reaction
does occur (45% yield after 6 h at 150 °C) but could not
compete with [emim][NTf2]. Recycling of the Bi(OTf)3 sys-
tem was attempted in the case of the benzoylation of toluene
using the bulb to bulb purification procedure. Excellent
results were obtained as shown by the following results: the
first recycling gave a 92% isolated yield after 3 h of reaction,
second 90% (3 h), third 88% (3 h), and fourth 90% (3 h)
with an ortho/meta/para ratio of 20/2/78 in all cases.
In conclusion, the use of bismuth oxide and bismuth triflate
as catalysts in properly chosen ionic liquids for Friedel-
Crafts acylation of aromatic compounds can be considered
as an interesting new alternative to existing homogeneous
catalysts. Furthermore, they are air-stable, easy to handle
reagents. Catalyst loads as low as 1 mol % can be used
leading to high yields with activated aromatic compounds
at an oil bath temperature of 150 °C. The catalytic system
Bi2O3-[emim][NTf2] can be reused up to six times, although
with some loss of activity. Bi(OTf)3/[emim] [NTf2] showed
a higher catalytic activity integrally maintained after four
recyclings. The simple procedures as well as easy recovery
and reuse of this novel catalytic system are expected to
contribute to the development of more benign acylation of
aromatics with acid chlorides.
a Reactions were conducted on a 2 mM scale operating under the same
conditions as above. b Conversion determined by GC-MS. c Isolated yields
of pure products obtained by bulb to bulb distillation or by column
chromatography. d Bi(OTf)3 used as a catalyst in the presence of
[emim][NTf2]. e Bi(OTf)3 used without IL.
Although less efficient than the [bmim][NTf2] systems,
the catalytic activity of Bi2O3 or Bi(OTf)3 in the presence
of [emim][NTf2] was investigated to further study the F&C
acylation of a variety of aromatic compounds. This allows a
much easier workup of the reaction mixtures since [emim]-
[NTf2] and the organic phases led to a two-phase system at
room temperature. Acylation of activated aromatics went to
completion within 2 h, whereas an aromatic containing
deactivating groups required longer reaction times, typically
24 h. Under such conditions, GC analysis of the crude
reaction mixtures showed a complete conversion in all cases.
Results are summarized in Table 3.
The benzoylation of activated aromatics yielded the
ketones in good to excellent yields (Table 3, entries 1-5).
However, the benzoylation of benzene and chlobenzene led
to only 20% conversion after 15 h in the presence of Bi2O3.
The same reactions conducted in the presence of Bi(OTf)3
and [emim][NTf2] led to 100% conversion within 24 h (Table
3, entries 7 and 9). In the absence of the ionic liquid,
benzoylation of benzene and chlorobenzene gave only 70
and 58% conversions, respectively.
Attempts were made to recycle these catalytic systems.
The benzoylation of 0.1 mol of toluene with benzoyl chloride
under the conditions described in Table 1 with Bi2O3 as
catalyst was run for six consecutive cycles, furnishing the
methyl-substituted benzophenones, after extraction with
toluene and bulb to bulb purification, with 89 (6 h), 87 (6
h), 90 (6 h), 86 (9 h), 85 (12 h), and 75% (15 h) isolated
yields and an ortho/meta/para ratio of 19/2/79. After the
extraction step, the ionic liquid layer was decanted, collected,
and dried under high vacuum for 1 h. A simple alternative
to this workup procedure is to purify the crude reaction
mixture by bulb to bulb distillation under high vacuum. The
next reaction was then initiated by reloading the reactor with
Acknowledgment. We thank Dr. S. Ratton (Rhodia) for
helpful discussions and Rhodia for partial financial support
of this work.
Note Added after Print Publication. Hongli Yang’s name
was misspelled in the version published on the Web June 3,
2003 (ASAP) and in the June 26, 2003 issue (Vol. 5, No.
13, pp 2219-2222); the correct electronic version of the
paper was published on July 17, 2003, and an Addition and
Correction appears in the August 21, 2003 issue (Vol. 5,
No. 17).
Supporting Information Available: Typical experimen-
tal procedure for the F&C reaction and characterization data
for all ketones listed in Table 4 and [emim][BiCl4]. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(17) Holbrey, D. J.; Visser, E. A.; Rogers, R. D. In Ionic liquids in
Synthesis; Wasserscheid, P.; Welton, T., Eds.; Wiley-VCH: Weinheim,
Germany, 2003; pp 68-81 and references therein.
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