Efficient synthesis of β-chlorovinylketones from acetylene in chloroaluminate ionic liquids

Article abstract of DOI:10.1021/ol201182t

A method for the Friedel-Crafts-type insertion reaction of acetylene with acid chlorides in chloroaluminate ionic liquids is presented. The use of ionic liquids not only serves to avoid the use of carbon tetrachloride or 1,2-dichloroethane but also suppresses side reactions, notably the polymerization of acetylene, which occurs in these chlorinated solvents. Consequently, the products can be isolated using a simpler purification procedure, giving a range of aromatic and aliphatic β-chlorovinyl ketones in high yield and purity.

Full text of DOI:10.1021/ol201182t

ORGANIC
LETTERS
2011
Vol. 13, No. 15
4048–4051
Efficient Synthesis of β-
Chlorovinylketones from Acetylene in
Chloroaluminate Ionic Liquids
Dennis J. M. Snelders and Paul J. Dyson*
ꢀ
Institut des Sciences et Ingenierie Chimiques, Ecole Polytechnique Federale de Lausanne
(EPFL), CH-1015 Lausanne, Switzerland
ꢀ ꢀ
paul.dyson@epfl.ch
Received June 10, 2011
ABSTRACT
A method for the FriedelꢀCrafts-type insertion reaction of acetylene with acid chlorides in chloroaluminate ionic liquids is presented. The use of
ionic liquids not only serves to avoid the use of carbon tetrachloride or 1,2-dichloroethane but also suppresses side reactions, notably the
polymerization of acetylene, which occurs in these chlorinated solvents. Consequently, the products can be isolated using a simpler purification
procedure, giving a range of aromatic and aliphatic β-chlorovinyl ketones in high yield and purity.
β-Chloro-R,β-unsaturated ketones are used as synthetic
intermediates in a wide variety of aromatic, aliphatic, and
heterocyclic compounds, many of which are important to
the chemical and pharmaceutical industries.1,2 A range of
compounds of this type are accessible via a Friedelꢀ
Crafts-type addition reaction of alkynes with acid chlor-
ides in the presence of a stoichiometric amount of AlCl3.1,3
Unsubstituted β-chlorovinyl ketones, a special subclass of
highly versatile intermediates, are prepared by the reaction
of acid chlorides with acetylene gas. Acetylene, which is
mainly produced from natural gas, may provide a compe-
titive alternative to the use of oil as feedstock for certain
chemical industrial processes.4 The synthesis of β-chloro-
vinyl ketones from acetylene works for a wide range of
substrates, with yields of typically 50ꢀ70%, but usually
requiresthe useof chlorinatedsolventsthatare highlytoxic
and/or damaging to the environment, such as carbon
tetrachloride and 1,2-dichloroethane.1,5ꢀ10 Transition-me-
tal-catalyzed methods for the addition of acid chlorides to
terminal alkynes are known, but these methods require the
use of expensive Rh- or Ir-based catalysts, and the use of
acetylene as substrate has not been reported.2,11ꢀ13 It is
therefore of considerable interest to search for alternative
methods for the synthesis of β-chlorovinyl ketones that
combine the use of cheap and environmentally less hazar-
dous substances with high product yields. Several examples
(7) Benson, W. R.; Pohland, A. E. J. Org. Chem. 1964, 29, 385–391.
(8) Rizzo, C. J.; Dunlap, N. K.; Smith, A. B. J. Org. Chem. 1987, 52,
5280–5283.
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(10) Luo, F.; Negishi, E. J. Org. Chem. 1985, 50, 4762–4766.
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Org. Lett. 2005, 7, 2241–2244.
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2008, 10, 5469–5472.
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2009, 131, 6668–6669.
(14) Yeung, K.-S.; Qiu, Z.; Farkas, M. E.; Xue, Q.; Regueiro-Ren,
A.; Yang, Z.; Bender, J. A.; Good, A. C.; Kadow, J. F. Tetrahedron Lett.
2008, 49, 6250–6253.
(1) Pohland, A. E.; Benson, W. R. Chem. Rev. 1964, 66, 161–197.
(2) Goossen, L. J.; Rodriguez, N.; Goossen, K. Angew. Chem., Int.
Ed. 2009, 48, 9592–9594.
(3) Martens, H.; Janssens, F.; Hoornaert, G. Tetrahedron 1975, 31,
177–183.
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2009, 146, 266–269.
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Wernicke, H.; Ebersberg, G.; Muller, R.; Bassler, J.; Behringer, H.;
Mayer, D. Acetylene; Wiley-VCH: Weinheim, 2008.
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r
10.1021/ol201182t
Published on Web 07/08/2011
2011 American Chemical Society

of FriedelꢀCrafts acylation14ꢀ17 and alkylation18ꢀ20 reac-
tions in chloroaluminate ionic liquids have been reported.
In contrast, as far as we are aware, the FriedelꢀCrafts-type
addition of acetylene to acid chlorides has not been studied
in ionic liquids. Herein, the potential of chloroaluminate
ionic liquids as solvents for this reaction is explored.
sulfonyl)imide) or [bmim][TCM] (TCM = tricyano-
methanide). However, in these solvents no conversion of
benzoyl chloride was observed. Changing the cation while
keeping Tf2N as anion, i.e., employing [3C4C13P][Tf2N]
(3C4C13P = tri(butyl)(tridecyl)phosphonium), did not lead
to any improvement. A possible explanation for these
observations could be deactivation of AlCl3 by coordination
of the anions of the ionic liquids. For example, the formation
of species of the type AlCl3ꢀn(Tf2N)n has been described
previously.23
Scheme 1. Synthesis of 3-Chloro-1-phenyl-2-propenone from
Acetylene and Benzoyl Chloride
The combination of [bmim]Cl with AlCl3 results in an
ionic liquid, the physical and chemical properties of which
depend on the mole fraction, N, of AlCl3. For N = 0.50, the
aluminum-containing species tends to have the form
AlCl4ꢀ. For higher mole fractions, species of the type
ꢀ
Al2Cl7 predominate and the ionic liquid is considered
Lewis acidic.18 These tunable properties have been
exploited in synthesis and catalysis.24ꢀ26 In the present
case, the use of an ionic liquid composed of [bmim]Cl and
AlCl3 with N = 0.67 resulted in a highly active system, in
which the ionic liquid acts as both solvent and Lewis acid
catalyst (Table 1, entries 7ꢀ10). When an amount of ionic
liquid was used that corresponds to a molar ratio of the
excess of AlCl3 in the ionic liquid to benzoyl chloride of 1.3,
a conversion of 93% was observed under the same reaction
conditions as employed for DCE (entry 8). In contrast to
DCE, the use of the ionic liquid did not require cooling of
the mixture during addition of benzoyl chloride. An in-
crease of the reaction temperature to 60 °C during addition
of acetylene resulted in quantitative conversion of the
substrate (entries 9 and 10). Importantly, in contrast
to DCE, no tar formation was observed when the reac-
tion was carried out in [bmim]ClꢀAlCl3, rendering the
extractionꢀpurification procedure more facile. Following
aqueousꢀorganic extraction, the productwasobtainedas a
clear, yellow-orange liquid in 70ꢀ74% yield. The effect of
using different cations in the ionic liquid (i.e., N-butyl-3-
methylpyridinium, bmpy) was also investigated (Figure 1),
affording an equally effective system (Table 1, entry 11).
The isolated yield of the reaction carried out in either
[bmim]ClꢀAlCl3 or [bmpy]ClꢀAlCl3 under the conditions
The addition of acetylene to benzoyl chloride, yielding
3-chloro-1-phenyl-2-propenone (1, Scheme 1), was chosen
as a model reaction. Initially the influence of the reaction
conditionswereinvestigatedfor1,2-dichloroethane (DCE)
as solvent (Table 1, entries 1ꢀ3). Typically, the acid
chloride was added to a suspension of AlCl3 in DCE and
stirred at 0 °C for 15 min, and then acetylene gas was
passed through the reaction mixture at 50 °C for 2 h. When
a small excess of AlCl3, with respect to benzoyl chloride
(1.3 equiv) was used, complete conversion of the starting
material was observed by GC. These conditions corre-
spond to those reported in the literature.1
As a major drawback of this procedure, a large amount
of a black tarlike material is formed as a byproduct.
Following initial aqueous/organic extraction, additional
purification by column chromatography or distillation6 is
therefore necessary to obtain the product in pure form.
When acetylene was added to a suspension of AlCl3 in
DCE in the absence of benzoyl chloride, a large amount of
tar was formed, indicating that the tar originates from a
reaction of acetylene withAlCl3, most likely corresponding
to the Al-catalyzed polymerization of acetylene.21,22
The tar formation could be avoided by using a smaller
amount of AlCl3 (1.0 equiv, Table 1, entry 3), but this led
to incomplete conversion of the benzoyl chloride
substrate, which did not increase as the reaction time was
extended.
In order to explore the potential of ionic liquids as solvents
for this reaction, several ionic liquids, containing different
anions and cations, were evaluated. The ionic liquids
[bmim][BF4] (bmim
= 1-butyl-3-methylimidazolium),
[bmim][PF6] and [bmim][OAc] were not suitable since they
were found to react with AlCl3. In contrast, no obvious
reaction was observed upon mixing of AlCl3 with the ionic
liquids [bmim][Tf2N] (Tf2N = bis(trifluoromethyl-
(19) Zhao, Z.-K.; Qiao, W.-H.; Li, Z.-S.; Wang, G.-R.; Cheng, L.-B.
J. Mol. Catal. A-Chem. 2004, 222, 207–212.
(20) Chen, M.; Luo, Y.; Li, G.; He, M.; Xie, J.; Li, H.; Yuan, X.
Korean J. Chem. Eng. 2009, 29, 1563–1567.
(21) Shelburne, J. A.; Baker, G. L. Macromolecules 1987, 20, 1212–
1216.
(22) Soga, K.; Miyoshi, K.; Inoue, N.; Kobayashi, Y. Synth. Met.
1988, 24, 239–244.
Figure 1. Cations and anions of ILs evaluated in the Friedelꢀ
Crafts-type reaction of benzoyl chloride with acetylene.
Org. Lett., Vol. 13, No. 15, 2011
4049

Table 1. Effect of the Solvent and Reaction Temperature on the Synthesis of 3-Chloro-1-phenyl-2-propenone (1)a
entry
solvent
T1b (°C) T2c (°C) conv (GC, %) isolated yield (%) purity (GC, %)d E/Z ratio (GC)d tar formation
1
DCE
DCE
DCE
0
50
50
50
50
50
50
50
50
50
60
60
98
80
79
0
60e
nd
nd
98
nd
nd
98/2
nd
yes
yes
no
no
no
no
no
no
no
no
no
2
25
0
3f
4
nd
[bmim][Tf2N]
0
5
[3C4C13P][Tf2N]
[bmim][TCM]
0
0
6
0
0
7f
8
[bmim]ClꢀAlCl3
[bmim]ClꢀAlCl3
[bmim]ClꢀAlCl3
[bmim]ClꢀAlCl3
[bmpy]ClꢀAlCl3
0
87
93
95
99
>99
nd
nd
nd
nd
98
98
nd
0
nd
nd
9
25
25
25
nd
nd
10
11
71g
74g
98/2
98/2
a Conditions: 1.3 equiv of AlCl3 with respect to benzoyl chloride; reaction time = 2 h. b Temperature for the addition of PhCOCl to AlCl3.
c Temperature for the addition of C2H2. d Purity and E/Z ratio of the isolated material after storage at 4 °C for 16 h. e After aqueousꢀorganic extraction,
followed by purification by column chromatography. f 1.0 equiv of AlCl3 with respect to benzoyl chloride was used. g After aqueousꢀorganic extraction.
Table 2. Effect of the Amount and Composition of the IL and the Reaction Time on the Synthesis of 3-Chloro-1-phenyl-2-propenone
(1)a
entry
molar ratio AlCl3/PhCOClb
mole fraction of AlCl3 in IL
t1 (h)c
t2 (h)d
conv (GC, %)
isolated yielde (%)
1
2
3
4
5
6
7
0.68
1.3
1.3
1.3
1.8
1.8
2.0
0.67
0.67
0.67
0.67
0.67
0.70
0.67
0.25
0.25
0.25
3
2
2
4
4
2
2
2
60
>99
>99
>99
>99
>99
>99
nd
74
73
73
90
93
93
0.25
0.25
0.25
a Solvent = [bmpy]Cl-AlCl3. b Molar ratio of the excess of AlCl3 in the IL with respect to benzoyl chloride. c Reaction time for the addition of
PhCOCl to AlCl3; reaction temperature = rt. d Reaction time for the addition of C2H2; reaction temperature = 60 °C. e After aqueousꢀorganic
extraction; product purity was in general 97ꢀ98% based on GC analysis.
employed was typically between 70 and 74% (three inde-
pendent experiments). Analysis of the aqueous layerusedin
the extraction procedure revealed the presence of benzoic
acid, although both the starting material and the product
were stable under the employed purification conditions.
Consequently, a further set of optimization reactions
was carried out using [bmpy]ClꢀAlCl3 as solvent. Ex-
tending the reaction times did not lead to any improve-
ment (Table 2, entries 2ꢀ4). Instead, an increase of the
molar ratio of the excess of AlCl3 in the ionic liquid with
respect to benzoyl chloride, from 1.3 to 1.8, led to an
increase of the isolated yield from 74 to 93%. This
increase may be achieved by employing either a larger
amount of IL of the same composition (Table 2, entry 5)
or by using a higher molar fraction of AlCl3 in the IL
(Table 2, entry 6). It has been reported that in similar
FriedelꢀCrafts reactions in ionic liquids the reaction
mechanism proceeds via an intermediate with the form
[RꢀCtOþ] and that an over stoichiometric excess of
AlCl3 may be required for the reaction to go to
completion.16ꢀ18 At an insufficient excess of AlCl3,
hydrolysis of the unreacted intermediate, giving benzoic
acid, may occur during aqueous workup, reducing the
yields. This may explain our observed increase in yield
despite the complete conversion by GC in both cases.
Increasing the ratio to 2.0 did not lead to a further
increase of the yield (Table 2, entry 7). The yield of the
product is significantly higher than literature yields for
the same reaction using organic solvents, which range
from 31% to 70%.1,7
In order to explore the scope of the chloroaluminate
IL system, a range of acid chlorides were tested as sub-
strates (Table 3), using the optimized conditions, with
[bmpy]ClꢀAlCl3 as solvent and Lewis acid catalyst. For
the aliphatic substrates, a reaction temperature of 0 °C was
used, in accordance with literature procedures,1 and good
yields of the corresponding β-chlorovinyl ketones were
obtained in all cases. Tar formation was not observed in
any of the reactions. The isolated products were analyzed
by 1H and 13C NMR spectroscopy and GC (see the
Supporting Information). In general, the GC spectra con-
tained peaks corresponding to the two stereoisomers of the
(23) Eiden, P.; Liu, Q.; Abedin, S. Z. E.; Endres, F.; Krossing, I.
Chem.;Eur. J. 2009, 15, 3426–3434.
(24) Dupont, J.; de Souza, R. F.; Suarez, P. A. Z. Chem. Rev. 2002,
102, 3667–3692.
(25) Dyson, P. J.; Geldbach, T. J. Metal Catalysed Reactions in Ionic
Liquids; Springer: Dordrecht, 2005.
(26) Welton, T. Chem. Rev. 1999, 99, 2071–2084.
4050
Org. Lett., Vol. 13, No. 15, 2011

a
Table 3. Substrate Scope for the Reaction of Acid Chlorides with Acetylene in [bmpy]ClꢀAlCl3
a Conditions: addition of RCOCl to [bmpy]Cl-AlCl3: rt, 15 min for entries 1ꢀ4 and 0 °C, 15 min for entries 5ꢀ8; addition of C2H2: 60 °C, 2 h for
entries 1ꢀ3 and 3 h for entry 4, and 0 °C, 2 h for entries 5ꢀ8; molar ratio (excess AlCl3 in IL)/RCOCl = 1.8. Molar fraction of AlCl3 in IL = 0.70.
b Isolated yield. c GC yield, determined using decane as internal standard; a small quantity was isolated for characterization of the product by 1H NMR
spectroscopy. d After storage of the isolated product at 4 °C for 3 days.
products, with purities in the range of 94ꢀ99%. β-Chlor-
ovinyl ketones, especially the aliphatic derivatives, are
unstable, and phenol or hydroquinone are added as
stabilizers.1 Indeed, when the isolated products were
stored for prolonged periods, a considerable darkening
of the material was observed. The aromatic derivatives,
however, could be stored at 4 °C for at least several days
without any noticeable decomposition (established by
NMR and GC analysis).
In summary, chloroaluminate ionic liquids are effi-
cient solvents for the FriedelꢀCrafts-type addition of
acetylene to benzoyl chloride, acting both as solvent
and Lewis acid catalyst. The procedure is compatible
with several aromatic and aliphatic acid chlor-
ides, which all gave the corresponding β-chlorovinyl
ketones in high yield and purity. Importantly, the
chloroaluminate ionic liquid solvent suppresses the
polymerization of acetylene which leads to improved
atom economies and simpler extractionꢀpurification
procedures and provides an alternative to chlorinated
organic solvents.
Acknowledgment. We acknowledge Lothar Ott and
Martina Dressel at Lonza, Visp, Switzerland, for funding
and valuable discussions.
Supporting Information Available. Experimental pro-
cedures and copies of NMR and GC spectra. This mate-
rial is available free of charge via the Internet at http://
pubs.acs.org.
Org. Lett., Vol. 13, No. 15, 2011
4051