Reaction of elemental chalcogens with imidazolium acetates to yield imidazole-2-chalcogenones: Direct evidence for ionic liquids as proto-carbenes

Article abstract of DOI:10.1039/c0cc05223j

Mechanistic analysis of the reaction between elemental sulfur or selenium and 1,3-dialkylimidazolium acetate ionic liquids, in the absence of an external base or solvent, affords evidence for the equilibrium presence of carbene species in these ionic liqu

Full text of DOI:10.1039/c0cc05223j

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COMMUNICATION
Reaction of elemental chalcogens with imidazolium acetates to yield
imidazole-2-chalcogenones: direct evidence for ionic liquids as
proto-carbenesw
ab
Hector Rodrıguez, Gabriela Gurau,ac John D. Holbreya and Robin D. Rogers*ac
´
´
Received 26th November 2010, Accepted 20th January 2011
DOI: 10.1039/c0cc05223j
Mechanistic analysis of the reaction between elemental sulfur or
selenium and 1,3-dialkylimidazolium acetate ionic liquids, in the
absence of an external base or solvent, affords evidence for the
equilibrium presence of carbene species in these ionic liquids. It
demonstrates the potential to control, through anion selection,
the concentration of carbene in stable ionic liquids.
Scheme 1 Possible acid–base equilibrium between the constitutive
ions of a 1,3-dialkylimidazolium IL.
suggesting that the equilibrium proposed in Scheme 1 can be
effectively tuned by appropriate choice of ions.6
Ionic liquids (ILs) have come under increasing scrutiny over the
last decade for, among many reasons, the ability to tailor and
introduce unique property sets into liquid systems, including, for
example, the ability to react and solubilize numerous (traditionally
hard to dissolve) substances.1 The solvating powers of ILs are
often considered to be a property of one or another of their
constitutive ions; not necessarily the combination of a particular
cation–anion pair. For example, the enhanced solubility and
possibly reactivity of chitin vs. cellulose in 1-ethyl-3-methylimid-
azolium acetate ([C2mim][OAc]) compared to 1-ethyl-3-methyl-
imidazolium chloride ([C2mim]Cl) has been credited to the
increased basicity of the acetate compared to the chloride anion.2
However, introduction of increasingly basic anions can also lead
to increasingly stronger interactions with the acidic protons in the
imidazolium ring of the IL cation.3
We have an interest in understanding how solubility and
reactivity in/of ILs can be controlled through the specific
combination of particular cations and anions.7 One aspect of
these ongoing investigations is the potential for nominally stable
ionic liquids, such as [C2mim][OAc], to be activated via direct
‘in situ’ NHC formation to uniquely combine favorable IL
properties (thermal/chemical stability, etc.) with NHC reactivity.
NHCs are versatile compounds with use as ligands in
organometallic chemistry, as catalysts, and as nucleophilic
reagents.8 Among the many materials that can be accessed
through carbene chemistry, imidazole-2-chalcogenones in general,
and thiones in particular, are of interest. Tao et al. have reviewed
the major applications of imidazole-2-thiones,9 which, besides
their pharmaceutical and clinical uses,10 include examples of
industrial application as antioxidants for rubber, as vulcanization
accelerators, and their utilization in light-sensitive photographic
and photothermographic materials. In addition, 1,3-disubstituted
imidazole-2-thiones are versatile catalysts for initiating cross-
linking of epoxy and isocyanate resins.11 Imidazole-2-selones
have been identified as potential anti-hyperthyroid drugs,12 and
also as catalysts for carbonylation reactions of amines.13
Similarly, (benz)imidazole-2-tellones have been shown to have
antimicrobial activity against Gram-positive bacteria.14
If the putative 1,3-dialkylimidazolium hydroxide ILs are con-
sidered (and they have been erroneously reported as pure materi-
als on a number of occasions4), in the absence of other proton
sources, the hydroxide anion will readily abstract a proton from
the C(2) ring position of the cation. Thus, imidazolium hydroxide
‘ionic liquids’ are unstable with respect to spontaneous
base-induced decomposition (Scheme 1) unless stabilized by the
presence of a proton donor such as a protic solvent, e.g., water,
methanol, etc., which will protonate the N-heterocyclic carbene
(NHC) formed and drive the equilibrium back to the left hand
side. In contrast, [C2mim][OAc] is a relatively stable IL,5
The most common approach to imidazole-2-thione preparation
consists of the reaction of an imidazolium salt with a base and
elemental sulfur, either sequentially (through the initial
formation of the carbene intermediate), or in a single step
(via transient carbene generation).15 The bases used include,
for instance, potassium tert-butoxide (in sequential reactions),
or potassium carbonate and sodium methoxide (in single step
reactions), yielding salt by-products which must be separated
from the imidazole-2-thione produced. In addition, the reaction
is conducted in the presence of an organic, typically flammable,
solvent, such as pentane, tetrahydrofuran, or methanol.
a QUILL, School of Chemistry and Chemical Engineering,
The Queen’s University of Belfast, Belfast, Northern Ireland, UK
b Department of Chemical Engineering, University of Santiago de
Compostela, E-15782, Santiago de Compostela, Spain
c Department of Chemistry and Center for Green Manufacturing,
The University of Alabama, Tuscaloosa, AL 35487, USA.
E-mail: RDRogers@as.ua.edu; Fax: +1 205-348-0823;
Tel: +1 205-348-4323
w Electronic supplementary information (ESI) available: Experimental
details. See DOI: 10.1039/c0cc05223j
c
3222 Chem. Commun., 2011, 47, 3222–3224
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More recently, it has been found that microwave irradiation
allows the use of softer bases such as potassium thioacetate or
potassium thiocyanate,9 and also a solvent-free process has
been reported.16 Although the latter avoids the problem of
using an organic solvent, typically a solid base is still required,
generating undesired inorganic by-products. The preparation
of imidazole-2-tellones by the reaction of NHCs with
elemental tellurium in solution has also been described,17 with
similar issues associated.
and no reaction was observed with sulfur in comparative
experiments. However, reaction was observed with another
acetate IL: 1-butyl-3-methylimidazolium acetate.
These results imply that the first mechanism is invalid, and
that the imidazolium acetate IL is acting as both the base and
carbene source, with in situ production of the carbene which
reacts with sulfur to give the thione without displacing
reagents. As such, the mechanism parallels that of the typical
chalcogenone synthesis from an imidazolium salt and the
elemental chalcogen in the presence of an external base.
This mechanism is also supported both by the direct
reaction of benzaldehyde with [C2mim][OAc] to form a carbene–
benzaldehyde adduct and the formation of Pd-bis(carbene)
complexes obtained by the addition of Pd2+ salts to this IL.
The initial data for these reactions are presented in the ESIw,
however more detailed studies will be forthcoming.
The solubilization of chalcogenides in a range of ILs
À
producing radical anionic species such as [S3]ꢀ has been
recently described by Boros et al.,1d and prompted us to
investigate whether imidazolium ILs with selected suitably
basic anions could be used to solubilize and then react directly
with elemental sulfur in the absence of any external bases to
produce imidazole-2-thiones through activated ‘in situ’ NHC
formation.
While the proposed mechanism might initially appear to be self-
evident (the acetate anion is known to be basic), if the mechanism
of formation of the carbene was just proton abstraction by the
acetate anion, then loss by volatilization of the acetic acid formed
would provide a continuous source of carbene. Consequently, this
would also lead to intrinsic instability and decomposition of the IL
in a manner comparable to that of the hydroxide case.
These first investigations were made with imidazolium
acetate ILs (Scheme 2). Upon stirring stoichiometric amounts
of S8(s) and [C2mim][OAc](l) at 25 1C for 24 h, reactive
dissolution occurred, with the formation of the corresponding
1-ethyl-3-methylimidazole-2-thione in a yield near 50 mol%.
Similarly, 1-ethyl-3-methylimidazole-2-selone was obtained in
90 mol% yield by directly stirring approximately stoichiometric
amounts of selenium powder and [C2mim][OAc] at 75 1C. We
did not find convincing evidence for the reaction with selenium
at 25 1C; however, the reactivity at 75 1C would be consistent
with a shift in the equilibrium in Scheme 1 sufficiently to the
right with increasing temperature to generate enough carbene
concentration for the reaction to proceed.
Complex anions, formed from acid + anion pairs, have been
known for some time in IL systems, and those with carboxylic
acid/carboxylate conjugate systems are particularly stable.18 If
complex anion formation is invoked (Scheme 3), the formed acid
would tie up the acetate acceptor, preventing further C(2) proton
abstraction and requiring the removal of the acid to continue the
reaction. The liberated acid is stabilized as a complex anion, but
can still be stripped under relatively mild conditions, shown here
where, by bubbling N2 into the mixture of [C2mim][OAc], acetic
acid, sulfur, and thione, the yields of the latter increased to
57 mol% after 24 h, and 67 mol% after 72 h.
No optimization of the reaction conditions was attempted
to improve the product yields, since our focus was rather on
understanding the nature of the reaction observed. Thus, the
products observed and isolated here demonstrate that, in
addition to the dissolution of chalcogens in ILs as previously
described,1d reactive processes leading to the efficient direct
synthesis of imidazole-2-chalcogenones without addition of
external bases or solvents, and without generation of salt
waste, can be achieved. However, the IL must be chosen such
that the specific combination of a cation and anion results in a
strong enough interaction to activate the C(2) proton on the
heterocyclic ring,6 as illustrated in Scheme 1, without leading
to spontaneous decomposition of the IL as observed for the
OHÀ salts.
In a further experiment, [C2mim][OAc] was mixed with an
excess of acetic acid (a 1 : 2 molar ratio), and then with
elemental sulfur. No evidence for formation of the thione was
observed, even after two days. This appears consistent with the
postulated mechanism shown in Scheme 3, in which the proton
formed through generation of the NHC intermediate is bound
in an acetate–acetic acid complex anion. Thus, the presence of
excess acetic acid buffers the IL, reducing the net concentration
of free acetate anions present and inhibiting their interaction
with the C(2) protons of the imidazolium rings.
For the direct reaction of [C2mim][OAc] with the
chalcogens, one of two possible mechanisms can be invoked:
either the chalcogen reacts directly with the imidazolium
cation, or the carbene is generated in situ and reacts with the
chalcogen. Other 1-alkyl-3-methylimidazolium based ILs containing
a range of anions (namely: ClÀ, [HSO4]À, [SCN]À, [CH3SO4]À,
[CH3C6H4SO3]À, [CF3SO3]À, and [CF3COO]À) were tested,
The reaction can also be inhibited by other hydrogen bond
donors such as water. In another experiment, [C2mim][OAc]
and water were mixed in a 50 : 50 wt/wt ratio, and sulfur in
excess was added. After two days no trace of thione was
observed, likely as a result of the disruptive action of water
on the interaction between the cation and the anion of the IL
(water being a better proton donor than [C2mim]+).
Scheme 2 Direct reaction of chalcogens (E = 1/8 S8, or Se(powder)
)
Scheme 3 Proposed mechanism for stabilization of the volatile acetic
with neat IL [C2mim][OAc] (see ESIw).
acid generated from proton abstraction.
c
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Chem. Commun., 2011, 47, 3222–3224 3223

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the Ministry of Science and Innovation of Spain (‘‘Ramon y
´
Cajal’’ program).
Notes and references
Scheme 4 One pot synthesis of symmetrical 1,3-dialkylimidazolium
acetate (1, R1 = R2) and statistical mixture of 1-alkyl-3-methyl-, 1,3-
dialkyl-, 1,3-dimethylimidazolium acetates (1 + 2 + 3, R1 = methyl,
R1 a R2).
1 (a) R. P. Swatloski, S. K. Spear, J. D. Holbrey and R. D. Rogers,
J. Am. Chem. Soc., 2002, 124, 4974–4975; (b) D. A. Fort,
R. C. Remsing, R. P. Swatloski, P. Moyna, G. Moyna and
R. D. Rogers, Green Chem., 2007, 9, 63–69; (c) H. Mizuuchi,
V. Jaitely, S. Murdan and A. T. Florence, Eur. J. Pharm. Sci.,
2008, 33, 326–331; (d) E. Boros, M. J. Earle, M. A. Gılea,
A. Metlen, A.-V. Mudring, F. Rieger, A. J. Robertson,
K. R. Seddon, A. A. Tomaszowska, L. Trusov and J. S. Vyle,
Chem. Commun., 2010, 46, 716–718.
To further explore the utility of this thione synthesis, we
investigated the one-pot reaction of both symmetrical
1,3-dialkylimidazolium acetate and 2 : 1 : 1 statistical mixtures
of 1-alkyl-3-methyl-, 1,3-dialkyl-, and 1,3-dimethylimidazolium
acetates, prepared in situ through cyclization of the corres-
ponding amines with glyoxal, formaldehyde, and acetic acid,19
with sulfur. The mixtures of ILs over the ‘pure’ IL alone have
potential environmental benefits and cost advantages over
current technologies. Unlike the single cation hydrophilic
ILs, the IL mixtures can be prepared in a one-pot, single step
process, using aqueous, readily available, cheap raw materials,
and therefore reducing or even eliminating the use of the
organic solvents (Scheme 4). By adding sulfur to a statistical
imidazolium acetate mixture, partial conversion to the corres-
ponding mixture of thiones was achieved. Interestingly, the
same ratios of the starting cations ratios were obtained in the
resulting thiones mixture product. In the case of symmetric
imidazole-2-thiones, only one product would be obtained,
which can be easily prepared, as seen, via a simple one-pot
strategy from cheap, commodity chemicals.
2 Y. Fukaya, A. Sugimoto and H. Ohno, Biomacromolecules, 2006,
7, 3295–3297.
3 T. Cremer, C. Kolbeck, K. R. J. Lovelock, N. Paape, R. Wolfel,
¨
P. S. Schulz, P. Wasserscheid, H. Weber, J. Thar, B. Kirchner,
F. Maier and H.-P. Steinruck, Chem.–Eur. J., 2010, 16, 9018–9033.
¨
4 For instance: (a) L. Yang, L.-W. Xu, W. Zhou, L. Li and
C.-G. Xia, Tetrahedron Lett., 2006, 47, 7723–7726; (b) L. Huang,
M. Zhai, J. Peng, L. Xu, J. Li and G. Wei, Carbohydr. Polym.,
2008, 71, 690–693.
5 N. Sun, M. Rahman, Y. Qin, M. L. Maxim, H. Rodrı
R. D. Rogers, Green Chem., 2009, 11, 646–655.
6 O. Holloczki, D. Gerhard, K. Massone, L. Szarvas, B. Ne
T. Veszpremi and L. Nyulaszi, New J. Chem., 2010, 34, 3004–3009.
´
guez and
´
´
meth,
´
´
7 (a) W. L. Hough-Troutman, M. Smiglak, S. Griffin,
W. M. Reichert, I. Mirska, J. Jodynis-Liebert, T. Adamska,
J. Nawrot, M. Stasiewicz, R. D. Rogers and J. Pernak, New J.
Chem., 2009, 33, 26–33; (b) M. Smiglak, A. Metlen and
R. D. Rogers, Acc. Chem. Res., 2007, 40, 1182–1192;
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´
S. K. Spear, D. T. Daly, J. Pernak, J. E. Grisel, R. D. Carliss,
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8 V. Nair, S. Bindu and V. Sreekumar, Angew. Chem., Int. Ed., 2004,
43, 5130–5135.
Finally, it can be noted that ILs such as 1-alkyl-3-methyl-
imidazolium acetates are among the most widely used in the
promising field of biomass treatment and processing with ILs.
It is important to understand the chemistry of the IL itself in
order to help explain such reports as side reactions at the C(2)
position with reducing end sugars,20 or other unexplained
decomposition pathways or reactivity.
9 X.-L. Tao, M. Lei and Y.-G. Wang, Synth. Commun., 2007, 37,
399–408; and references therein.
10 For instance: (a) R. C. Haynes, Jr. and F. Murad, in Goodman and
Gilman’s The Pharmaceutical Basis of Therapeutics, ed.
A. G. Gilman, L. S. Goodman, T. W. Rall and F. Murad,
Macmillan, New York, 1985; (b) L. I. Kruse, C. Kaiser,
W. E. DeWolf, J. A. Finkelstein, J. S. Frazee, E. L. Hilbert,
S. T. Ross, K. E. Flaim and J. L. Sawyer, J. Med. Chem., 1990,
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11 A. J. Arduengo, III and P. H. Corcoran, PCT Pat., 9 118 937,
1991.
12 G. Roy and G. Mugesh, J. Am. Chem. Soc., 2005, 127,
15207–15217.
Overall, our work has shown that pure 1,3-dialkylimidazolium
ILs can be induced to undergo reactive transformations via NHC
carbenes as both reactant and solvent even in the absence of
additional external sources of base. Here, this has been illustrated
by reaction of [C2mim][OAc] (or the corresponding statistical
mixture) with sulfur or selenium to directly form the corres-
ponding imidazole-2-chalcogenones. However, the acidity of the
C(2) proton of the IL imidazolium cation and the basicity of the
IL anion are in themselves not sufficient criteria to understand
13 P. Li, X. Wang, X. Yuan, S. Wang and S. Lu, Cuihua Xuebao,
2007, 28, 495–497.
14 (a) H. Kucukbay, R. Durmaz, E. Orhan and S. Gunal, Farmaco,
2003, 58, 431–437; (b) B. Cetinkaya, E. Cetinkaya and
H. Kucukbay, Arzneim.–Forsch., Beih., 1996, 46, 1154–1158.
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Org. Synth., 1986, 64, 92–95; (b) A. J. Arduengo, III, US Pat.,
5 104 993, 1992.
this chemistry, as suggested by Hollo
´
czki et al.6 The anion must
also be capable of stabilization of the parent acid through the
formation of complex anions, thus preventing the unchecked
reaction and decomposition of the IL.
16 A. J. Arduengo, US Pat., 0 171 883, 2008.
17 (a) N. Kuhn, G. Henkel and T. Kratz, Chem. Ber., 1993, 126,
2047–2049; (b) A. J. Arduengo, III, F. Davidson, H. V. R. Dias,
J. R. Goerlich, D. Khasnis, W. J. Marshall and T. K. Prakasha,
J. Am. Chem. Soc., 1997, 119, 12742–12749.
18 (a) K. M. Johansson, E. I. Izgorodina, M. Forsyth,
D. R. MacFarlane and K. R. Seddon, Phys. Chem. Chem. Phys.,
2008, 10, 2972–2978; (b) K. Bica and R. D. Rogers, Chem.
Commun., 2010, 46, 1215–1217.
19 (a) A. J. Arduengo, III, US Pat., 5 077 414, 1991; (b) R. X. Ren
and V. R. Koch, US Pat., 7 253 289, 2007.
20 G. Ebner, S. Schiehser, A. Potthast and T. Rosenau, Tetrahedron
Lett., 2008, 49, 7322–7324.
Considered in totality, the chemistry reported here can be
regarded as an example of a ‘carbene-in-a-bottle’, where,
through anion selection, the standing carbene concentration
present in equilibrium in ILs (something we could call the
effective pKa of the C(2) hydrogen in the imidazolium IL) can
be modified to provide both reactive carbene moieties and
solvent for a variety of applications.
We want to thank Petroliam Nasional Berhad (PETRONAS)
for financial support for this project. H.R. is also grateful to
c
3224 Chem. Commun., 2011, 47, 3222–3224
This journal is The Royal Society of Chemistry 2011