Investigation of carbon-2 substituted imidazoles and their corresponding ionic liquids

Article abstract of DOI:10.1016/j.tetlet.2011.08.010

The functionality at the C-2 position of the imidazole ring plays a key role in defining the chemical properties of the imidazoles and their corresponding ionic liquids. Imidazoles 1-6 with different C-2 functionality were synthesized and their corresponding ionic liquids were systematically investigated. Based on their physical properties the six imidazoles can be divided into three groups. (1) The imidazoles 2 and 3 are capable of self-polymerization to form poly(ionic liquid)s, and they are characterized with a strong leaving group at the C-2 position. (2) The imidazoles 4 and 5 can form ionic liquids, but they are very sensitive to moisture. (3) The imidazoles 1 and 6 can form stable ionic liquids, and their stabilities were influenced by the electronic effects of the substituents at the C-2 position.

Full text of DOI:10.1016/j.tetlet.2011.08.010

Tetrahedron Letters 52 (2011) 5308–5310
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Investigation of carbon-2 substituted imidazoles and their corresponding
ionic liquids
Chen Liao a, Xiang Zhu b,c, Xiao-Guang Sun a, , Sheng Dai a,b
⇑
a Chemical Sciences Division, Oak Ridge National Laboratory, One Bethel Valley Road, Oak Ridge, TN 37831, United States
b Department of Chemistry, University of Tennessee, Knoxville, TN 37996, United States
c Department of Chemistry, East China University of Science and Technology, Shanghai 200237, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The functionality at the C-2 position of the imidazole ring plays a key role in defining the chemical prop-
erties of the imidazoles and their corresponding ionic liquids. Imidazoles 1ꢀ6 with different C-2 function-
ality were synthesized and their corresponding ionic liquids were systematically investigated. Based on
their physical properties the six imidazoles can be divided into three groups. (1) The imidazoles 2 and 3
are capable of self-polymerization to form poly(ionic liquid)s, and they are characterized with a strong
leaving group at the C-2 position. (2) The imidazoles 4 and 5 can form ionic liquids, but they are very sen-
sitive to moisture. (3) The imidazoles 1 and 6 can form stable ionic liquids, and their stabilities were influ-
enced by the electronic effects of the substituents at the C-2 position.
Received 18 June 2011
Revised 29 July 2011
Accepted 1 August 2011
Available online 9 August 2011
Keywords:
Imidazole
Ionic liquid
Organic synthesis
Substituent
Published by Elsevier Ltd.
Since the first discovery by Walden in 1914, ambient tempera-
ture ionic liquids (ILs) have attracted considerable interest due to
their favorable properties such as non-flammability, high chemical
and thermal stability, negligible vapor pressure, and high ionic
conductivity.1 As a result, ionic liquids have been used in a wide
range of applications such as organic synthesis,2 nanostructure
materials,3 separation,4 electrolytes for lithium-ion battery,5 and
electrochemical capacitors.6 The discovery of air-stable ionic liquid
based on 1-ethyl-3-methylimidazolium cation with BFꢀ4 has in-
spired researchers to focus more on these imidazolium ionic liq-
uids.7 Compared with the ionic liquids based on phosphonium,
tetraalkylammonium, and pyridinium structures, imidazolium io-
nic liquids usually have the advantages of low viscosity and high
ionic conductivity because of their highly delocalized charges.6
The functionalization of imidazolium ionic liquids is mainly fo-
cused on the appendages at the N-1 and N-3 positions (Scheme
1).8 For example, task-specific ionic liquids were synthesized by
incorporating functional groups such as urea, thiourea, metal
complexes, phosphine and silicate at the N-1 and N-3 positions,
in order to tune their physical properties such as polarity, hydro-
phobicity/hydrophilicity, and miscibility with solvents.9 However,
so far few studies have focused on C-2 functionalized imidazolium
ionic liquids. In fact, most of the imidazolium ionic liquids have
one proton at the C-2 position and the acidity of this particular
proton reduces the electrochemical window of the ionic liquids
Scheme 1. The structures of imidazoles 1–6.
and thus limits their application in electric energy storage
applications.6,10 With a simple methyl substitution at the C-2
position, the chemical and electrochemical stability of the 1-bu-
tyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl) imide
([bdmim]- TFSI) is greatly improved than its C2-H analog,
[bmim]TFSI.10 In this study, a series of C-2 substituted imidazoles
(1ꢀ6, Scheme 2) were synthesized and used to prepare ionic
liquids for the first time. Because of the different functional groups
at the C-2 position, they show remarkable difference in their
stability and reactivity, which will be discussed in detail later.
The six C-2-modified 1-methylimidazoles 1–6 shown in Scheme
1 were synthesized via three different reactions. (1) A simple
reaction between 1-methylimidazole and a cyanating reagent.
⇑
Corresponding author. Tel.: +1 865 241 8822; fax: +1 865 576 5235.
E-mail address: sunx@ornl.gov (X.-G. Sun).
0040-4039/$ - see front matter Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2011.08.010

C. Liao et al. / Tetrahedron Letters 52 (2011) 5308–5310
5309
Scheme 3. Imidazolium iodides 7 and 8.
Scheme 2. Self-polymerization of 2 and 3.
reactive 1-iodopropane in anhydrous benzene under inert atmo-
sphere. Compared with its original imidazole 4, the reactivity of
imidazolium iodide 7 (Scheme 3) toward moisture increased dra-
matically. In fact, upon exposure to air, all the TMS leaving groups
in 7 were immediately replaced by protons. The imidazolium
iodide 8 (Scheme 3) showed lower but still significant reactivity to-
ward water, and slowly decomposed to the 1-propyl-2,3-dimethy-
limidazolium iodide. The 1H NMR spectrum of the 8 still shows loss
of TMS group (ꢁ33%, Supplementary Information).
Imidazole 1 was prepared by the reaction of 1-methylimidazole
with 1-cyano-4-dimethylaminopyridinium bromide salt11 in a
one-step synthesis. (2) A reaction involving the formation of 2-
hydroxymethyl-1-methylimidazole.12 This category includes the
compounds 2, 3, and 6. Compound 2 was obtained quantitatively
by the reaction of 2-hydroxymethyl-1-methylimidazole with
thionyl chloride. Compound 3 was obtained by the nucleophilic
reaction of 2 with sodium cyanide in DMSO solution at room
temperature. For the synthesis of compound 6, 2-(hydroxy-
methyl)-1-methylimidazole was deprotonated with excess NaOH
before addition of 1-bromobutane. Catalytical amount of tetrabu-
tylammonium bromide was used in the reaction as the phase
transfer catalyst.13 (3) A reaction involving lithiation by n-butyl-
lithium at ꢀ78 °C followed by addition of trimethylsilyl chloride.
Synthesis of the compounds 4 and 514 falls into this category.
The details of the synthesis and structure characterization of 1–6
were presented in the Supporting Information.
In group 3 the reaction of both 1 and 6 with 1-bromopropane
went smoothly in toluene with high yields. The resulting imidazo-
lium bromide was stable toward water and can undergo metathe-
sis with LiTFSI. The TFSI anion was chosen because its negative
charge is highly delocalized and the corresponding ionic liquids
have low melting points, as well as high chemical and electro-
chemical stability. The resulting stable ionic liquids are 9 and 10,
(Scheme 4), respectively. Their analog with a methyl substitution
at the C-2 position (([bdmim][TFSI], IL 11, Scheme 4) was also syn-
thesized as a reference compound.
The stability of the imidazoles (hence imidazolium ionic liquid)
largely depends on the C-2 functionality. The deprotonation of the
C2-H imidazolium cations and decarboxylation in 1,3-dimethylim-
idazolium-2-carboxylates lead to the formation of N-heterocyclic
carbene (NHC).15 Another common side reaction that occurs with
C2-H imidazolium cations is the Baylis–Hillman reaction.16 The
C-2 substitutes of the imidazoles in our work (Scheme 1) avoid
the use of carboxylate groups and can prevent the carbene forma-
tion. The reactivities of these C-2 substituted imidazoles (1–6) and
the stabilities of their corresponding ionic liquids are investigated.
Based on their behaviors, these imidazoles can be divided into
three groups: (1) the imidazoles 2 and 3 are capable of self-poly-
merization to generate poly(ionic liquid)s; (2) the imidazoles 4
and 5 can form ionic liquids, but are very moisture-sensitive and
(3) the imidazoles 1 and 6 can lead to stable ionic liquids with
properties tunable by the electronic effect of the substituents at
the C-2 position.
The thermal stability of IL 9ꢀ11 was studied by TGA under
nitrogen atmosphere between RT and 700 °C at a heating rate of
10 °C/min. The bromide impurities in these ILs were negligible be-
cause during the synthesis, the ionic liquids were repeatedly
washed with copious amount of water until the chloride test with
0.1 M AgNO3 is negative. As shown in Figure 1, all the ionic liquids
are thermally stable above 300 °C. Interestingly, TGA trace of 10
shows a small plateau between 500 and 750 °C, which was due
to the carbon formation via the crossing linking of the CN func-
tional group, as studied by our group previously.20
These C-2 substituted ionic liquids 9ꢀ11 showed enhanced
chemical stability. Common methodologies to test the chemical
O
CN
TFSI
N
N
N
N
TFSI
In group 1, upon heating both 2 and 3 underwent self-polymer-
ization quickly (Scheme 2) because of the good leaving ability of
the chloro and cyano groups, respectively. A similar self-reaction
was utilized to synthesized the cyclic 1-butyl-2,3-trimethyleneim-
idazolium bis(trifluoro methanesulfonyl)imide ([b-3C-im][TSFI]).17
In the case of 2 and 3, the alkyl chain linkage is too short to self-
alkylate to form a cyclic product. The self-polymerization of similar
imidazoles with chloroalkyl substituents at the N-1 position has
been reported,18 and the advantage of such polymerization is that
no inhibitor is required. The resulting poly(ionic ꢀliquids) can un-
CðCNÞꢀ3 ) in order to tune their physical properties such as polarity,
hydrophobicity, and miscibility with solvent. These poly(ionic liq-
uids) can be used as surface coating agent for a variety of applica-
tions and also can be used as electrolytes for fuel cell, solar cell and
lithium ion battery applications.19
9
10
N
N
TFSI
11
Scheme 4. Structures of ionic liquids 9ꢀ11.
100
dergo metathesis with different anions (TFSI
,
NðCNÞꢀ2 , and
80
9
60
10
11
40
20
0
In group 2 both 4 and 5 underwent hydrolysis quickly upon
exposure to air and moisture because of their instability as 2-tri-
methylsilyl N-heterocyclic compounds. The C–Si bond cleaves
0
200
400
600
800
under mild conditions because of the assisting role of the sp2
N
Temperature /oC
atom.14 In order to avoid long reaction time and exposure to
moisture, the alkylation of 4 and 5 were carried out with the highly
Figure 1. TGA traces of IL 9ꢀ11.

5310
C. Liao et al. / Tetrahedron Letters 52 (2011) 5308–5310
Scheme 5. Deuterium exchange reaction of 9.
stability include the deuterium exchange reaction and the methyl-
ation with methyl iodide after deprotonation with a strong base
such as sodium hydride.17b Both reactions reflect the acidity of
the protons at the possible reactive sites such as C-2, C-4, C-5,
and ꢀCH3 on C-2.21 We carried out deuterium exchange reactions
in both neutral and strongly basic condition. The reaction was con-
ducted in a NMR tube containing a mixture of 1 M ionic liquid in
0.5 mL CD3OD. Since the C2-subsituted ionic liquids are less sus-
ceptible to exchange, it is not surprising that neither of the stable
ionic liquids underwent any detectable deuterium exchange under
neutral condition. To further test their stability, KOH powder
(0.5 mmol) was added to the above solutions and the disappear-
ance of the 1H signal was followed as a function of reaction time.
We observed an uneven deuteration on the three types of protons
in IL 9 and 11. The deuterium exchange occurred on the protons at
C-4, and C-5, as well as in ꢀCH3 (or ꢀCH2OCH2CH2CH2CH3) at C-2,
as shown in Scheme 5 using IL 9 as an example. Under the strong
basic condition, both IL 9 and 11 underwent fast deuteration on the
Acknowledgments
This research was supported by the U.S. Department of Energy’s
Office of Basic Energy Science, Division of Materials Sciences and
Engineering, under contract with UT-Battelle, LLC. C.L. acknowl-
edges Professor Robert C. Corcoran at University of Wyoming for
helpful discussions.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.08.010.
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In conclusion we have synthesized three different types of
imidazoles and their ionic liquids. Depending on their C-2 substit-
uents, the imidazoles can be used as monomers for polymerization,
precursors for moisture-sensitive and air stable ionic liquids.