Multi-Gram Scale Synthesis of 1,2,3-Triazolium Ionic Liquids and Assay of Their Resistance towards Bases

Article abstract of DOI:10.1002/ejoc.201800925

An easily upscalable synthesis method for 1,2,3-triazolium ionic liquids is presented. Several ionic liquids were synthesized and characterized. The influence of the side chain structure on the base-stability was investigated. One example, functionalized with linear alkyl side chains, was found to exhibit excellent stability against hot concentrated NaOH solutions and Grignard reagents.

Full text of DOI:10.1002/ejoc.201800925

A Journal of
Accepted Article
Title: Multi-gram scale synthesis of 1,2,3-triazolium ionic liquids and
assay of their resistance towards bases
Authors: Stijn Raiguel, Joice Thomas, Koen Binnemans, and Wim
Dehaen
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800925
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10.1002/ejoc.201800925
European Journal of Organic Chemistry
FULL PAPER
Multi-gram scale synthesis of 1,2,3-triazolium ionic liquids and
assay of their resistance towards bases
Stijn Raiguel,[a] Joice Thomas,[a] Koen Binnemans[a] and Wim Dehaen*[a]
Abstract: An easily upscalable synthesis method for 1,2,3-triazolium
ionic liquids is presented. Several ionic liquids were synthesized and
characterized. The influence of the side chain structure on the base-
stability was investigated. One example, functionalized with linear
alkyl side chains, was found to exhibit excellent stability against hot
concentrated NaOH solutions and Grignard reagents.
as reaction media and extractants.[5] For similar reasons, long-
chain phosphonium ionic liquids are also compatible with strong
bases without the formation of phosphine oxides.[13] However,
they suffer from increased viscosities and lower loading
capacities in solvent extraction, due to the large volume of the
cation.[13–17] In addition, conflicting reports do exist, as some
authors report observing the α-deprotonation of long-chain
phosphonium ionic liquids, resulting in the formation of a nonionic
phosphorane.[3,18]
The lesser-known 1,2,3-triazolium ionic liquids do not
behave like imidazolium ionic liquids when combined with bases,
as a result of the nitrogen atom present at their 2-position.[19,20]
Deprotonation or addition at this position are no longer significant
pathways of degradation. However, Hofmann elimination could
potentially occur, a pathway which is not observed in the alkaline
decomposition of imidazolium ionic liquids.[8,21] To investigate the
dependence of the stability towards bases on the nature of the
side chain, we have synthesized peralkylated 1,2,3-triazolium
ionic liquids with linear and branched alkyl chains located on the
N1- and N3-positions. As reported by Lethesh and coworkers,
branching at the β-position is effective at sterically inhibiting
Hofmann elimination, should this process occur.[5]
Introduction
Ionic liquids are generally solvents with wide electrochemical
windows, making them resistant to oxidation and reduction.[1,2]
However, the cations of most ionic liquids are susceptible to
attack by strong Brønsted bases, precluding their use in
combination with strong alkalis and rendering them poor solvents
for reactions involving organometallic reagents. Quaternary
ammonium ionic liquids degrade via a β-elimination reaction
known as the Hofmann elimination, affording an alkene and the
corresponding amine.[3–5] Phosphonium ionic liquids, while
structurally analogous to quaternary ammonium ionic liquids,
decompose through an entirely different mechanism, involving the
attack of hydroxide ions at the phosphorus center, eventually
Earlier literature on 1,2,3-triazolium salts has mainly
focused on trisubstituted triazolium salts.[20,22–26] Liquid 1,2,3-
triazolium salts have been used as solvents for the Baylis-
Hilmann, Michael, aldol and Vilsmeyer-Haack reactions, as chiral
reaction media, as electrolytes in dye-sensitized photovoltaics
and as extractants for metal ions.[21,23,27–30] Previous studies have
also reported on liquid crystalline phases and the effect of side
chain branching in 1,2,3-triazolium ionic liquids.[31,32] Outside the
field of ionic liquids, these salts have been used as
organocatalysts, as precursors to mesionic carbene ligands and
as structural units in anion-selective probes.[23] While 1,2,3-
triazolium ionic liquids are relatively novel, the 1,2,3-triazole
platform has been popularized in other fields.[33–38] This is largely
a result of the copper- and ruthenium-catalyzed azide-alkyne click
reactions, which provide very convenient pathways towards 1,4-
and 1,5-disubstituted 1,2,3-triazoles, respectively.[39,40] While very
effective for certain applications, the reaction has several notable
drawbacks. Primarily, both azides and alkynes are uncommon
reagents with limited commercial availability. In addition, only
terminal alkynes tend to be sufficiently reactive to afford high
yields of the desired product in the copper-catalyzed variant of the
method.[39] The ruthenium-catalyzed click reaction is compatible
with internal alkynes, but the high cost of the catalyst, sensitivity
to steric hindrance and variable regiochemistry render this variant
less attractive.[40,41] The toxicity of the metal catalysts is a further
disadvantage, which is especially pertinent in medicinal chemistry.
In this paper, we present a new method for the synthesis of
1,2,3-triazolium ionic liquids with high resistance towards bases.
This pathway is inspired by a method described by Thomas and
Dehaen in 2016, which affords trisubstituted 1,2,3-triazoles from
primary amines and ketones via an enamine intermediate.[42,43]
The procedure is metal-free and requires the synthesis of only
forming
a
phosphine oxide and an alkane.[4,6] 1,3-
Dialkylimidazolium ionic liquids are by far the most base-sensitive
of all commonly used classes of ionic liquids.[3] Inductive effects
of the nitrogen atoms flanking the C2-position strongly polarize
this methine moiety, rendering it sufficiently acidic for quantitative
deprotonation by bases as weak as Cs2CO3.[7] The resulting
product is a reactive but neutral N-heterocyclic carbene, so that
the ionic character of the solvent is lost.[3]
Several researchers have attempted to improve the base-
stability of ionic liquids, often compromising upon their physical
properties, such as melting point or viscosity. Alkylation of the C2-
position of imidazolium ionic liquids limits deprotonation at this site,
thereby improving their usability in alkaline conditions.[3,8–10]
However, this position remains susceptible to nucleophilic attack
and proton exchange even after substitution.[3,8,11,12] Hugar et al.
reported that the only way to entirely eliminate the reactivity of this
position is to functionalize this position with a 2,6-dimethylphenyl
group, which results in high melting points.[8] A similar strategy of
steric shielding can be employed for ammonium and
phosphonium ionic liquids. Ionic liquids based on the bis(2-
ethylhexyl)dimethylammonium cation have shown excellent
stability in 50 wt% NaOH. However, the resulting ionic liquids are
all very viscous and water-soluble, making them rather unsuited
[a]
S. Raiguel, J. Thomas, K. Binnemans and W. Dehaen
Department of Chemistry
KU Leuven
Celestijnenlaan 200F P.O. Box 2404, B-3001 Leuven, Belgium
E-mail: wim.dehaen@kuleuven.be
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800925
European Journal of Organic Chemistry
FULL PAPER
one common organic azide, regardless of the compound of
interest. This compound can thus be synthesized in bulk, while all
of a larger excess of the amine. Presumably, the poor solubility of
the azidobenzoate salts of these amines reduces their availability
other reagents can be obtained commercially at relatively low cost. to react with the ketone, which is the rate-determining step in the
In our adjusted method, 4-nitrophenyl azide is replaced by 4-
azidobenzoic acid. The carboxylic acid group serves the same
activating function as the nitro group does in the original method,
but its acidity allows for convenient removal of the spent azide by
extraction with an alkaline aqueous solution. The method further
makes use of the basicity of the amine and the volatility of most
simple ketones to facilitate the purification of the final product.
Highly pure, peralkylated 1,2,3-triazoles can thus be obtained in
larger quantities without the need of using column
chromatography for purification, making this method ideal for the
synthesis of triazole-derived ionic liquids. Up to 30 g of starting
azide could be used without compromising upon the yield of the
procedure (see synthesis of 4-ethyl-1,3-bis(2-ethylhexyl)-5-
methyl-1,2,3-triazolium nitrate).
mechanism of the triazolation described by Dehaen and
coworkers.[42] This strategy was effective for isobutylamine and
other lower amines (Figure 1). For heavier, poorly-soluble amines,
dimethylformamide provided an excellent reaction medium.
Benzylamine yielded two regioisomers, 4-methyl-5-ethyl-
and 4-ethyl-5-methyl-substituted 1-benzyltriazole, as base-
induced cleavage of the 1,3-dibenzyltriazolium-4-ethyl-5-methyl
cation afforded a product mixture displaying identical resonances
in its 1H NMR spectrum. The formation of these two regioisomers
was observed in both acetonitrile and solvent-free conditions. The
formation of only one product was described by Thomas et al.
when similar substrates were used.[42] Based on their
observations, the 4-methyl-5-ethyl derivative is expected to be
formed selectively. The ratio of both products changed from 45:55
to 92:8 in favor of the expected regioisomer in solvent-free
conditions.[42] Treating the 92:8 mixture with aminobenzoic acid in
acetonitrile at 80 °C did not cause a change in the isomer ratio,
implying that the observed 1,3-‘shift’ occurs during the formation
of the product, and is not an acid-catalyzed rearrangement of the
final product.
Scheme 1. General reaction scheme for the synthesis of 1,2,3-triazolium ionic
liquids.
Results and Discussion
The reaction conditions used in the method described by Thomas
et al. were adapted and optimized for the new reagent
combination. Parameters retained from the original procedure
were the stoichiometric excess of amine (1.4 eq.) and the use of
4.0 Å molecular sieves to promote the formation of the
intermediate enamine. 4-Azidobenzoic acid is in general less
soluble than the nitro-substituted analog, requiring a change in
solvent conditions. Initially, test reactions were performed in
Figure 1. Scope with respect to 1,2,3-triazoles that are useful as ionic liquid
precursors. The given percentages indicate the obtained yields. Reaction
conditions: 1.4 eq. amine, solvent-free for 1, 4, 5, 7, 9, 10; 3.0 eq. amine, solvent
free for 2, 3, 8; 1.4 eq. amine, DMF for 6; 0.5 eq. amine, DMF for 11.
acetonitrile
with
3-pentanone,
2-ethylhexylamine
and
isobutylamine as model substrates. The obtained yields were
modest: 44% and 23% for the 2-ethylhexyl and isobutyl products,
respectively. All reaction mixtures were turbid due to the poor
solubility of 4-azidobenzoic acid or its ammonium salts in
acetonitrile. Increasing the excess of 3-pentanone and performing
the reaction under solvent-free conditions led to a reduction of the
turbidity of most reaction mixtures, with some even becoming fully
homogeneous. This increase in solubility of the azide led to
correspondingly higher yields. Furthermore, the elimination of the
nitrile solvent increases the ‘green’ character of this synthetic
procedure.[44] High molecular weight amines were observed to
afford better yields under identical conditions than amines with
low molecular weights. However, due to the lower cost of low
molecular weight amines, this can be counteracted by the addition
As shown in Figure 1, various useful precursors to
peralkylated 1,2,3-triazolium ionic liquids can be obtained in good
to fair yields. Unfortunately, the high acidity of the reaction
medium renders this procedure ineffective if derivatives obtained
from highly reactive ketones (e.g. acetone or cyclohexanone) are
targeted. Acid-sensitive functional groups (e.g. alcohols or
acetals) are also poorly tolerated. Regardless, this is of little
concern when applying this method to the synthesis of ionic liquid
precursors, as mostly aliphatic, linear side chains are required in
order to obtain desirable physical properties (low melting point
and low viscosity).
1,2,3-Triazoles were found to be readily quaternized by alkyl
methanesulfonates. Iodoalkanes react as well, albeit much more
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10.1002/ejoc.201800925
European Journal of Organic Chemistry
FULL PAPER
Table 1. Physicochemical properties of the synthesized ionic liquids.
[EhEhT][Tf2N]
[iBuiBuT][Tf2N]
[EhiPrT][Tf2N]
[HHT][Tf2N]
[EhEhT][NO3]
Dynamic viscosity, dry, 30 °C (mPa·s)
Density, dry, 20 °C (g·cm-3)
276
4600
1.35
210
67
4581
1.02
1.20
1.26
1.24
Residual water after drying (ppm)
Water content at saturation (wt%)
4850
1700
3600
1480
1.55 wt%
1.52
207
5.89
293
2.30
135
0.51
54
30.3
30
Dynamic viscosity, water saturated, 30 °C
(mPa·s)
Decomposition temperature[a] (°C)
305
74
308
290
614
333
45
220
Solubility in water (ppm)
1218
7.2 wt%
All products are liquid at room temperature. aGiven as onset point. Temperature scan rate 3 °C · min-1. Procedure shown in supporting information, page S2.
slowly. The resultant methanesulfonate (mesylate) ionic liquids
are water-soluble, even with hydrophobic cations, and can thus
be easily purified and subsequently converted to
bis(trifluoromethylsulfonyl)imide (bistriflimide) ionic liquids. We
used this method to prepare five ionic liquids with varying degrees
of branching (Figure 2). These ionic liquids were then
characterized and their resistance against strong bases was
evaluated by recording the 1H NMR of base-contacted ionic
liquids. The results of these assays are shown in Tables 1 and 2.
could be attributed to its compact cation undergoing strong
electrostatic interactions. One ionic liquid with a nitrate anion was
prepared, which features a lower degree of charge delocalization.
As a result, this ionic liquid is more viscous and more hydrophilic
than its bis(trifluoromethylsulfonyl)imide analog. These typical
physical properties contrast with the chemical properties of the
ionic liquids, which are quite unlike those observed for quaternary
ammonium ionic liquids. Most notably, [HHT][Tf2N] displays
excellent resistance to both concentrated NaOH at elevated
temperatures and Grignard reagents, although it is decomposed
by n-butyllithium. The branched ionic liquids [EhEhT][Tf2N] and
[EhiPrT][Tf2N] are more easily attacked by bases. Decomposition
of [EhiPrT][Tf2N] by NaOH selectively gives 5-ethyl-1-(2-
ethylhexyl)-4-methyltriazole as decomposition product, which is in
agreement with a Hofmann elimination occurring at the sensitive
isopropyl side chain. However, the stability of the n-hexyl side
chain and the sensitivity of the 2-ethylhexyl side chains in
[HHT][Tf2N] and [EhEhT][Tf2N] cannot be explained by a simple
E2 decomposition mechanism. This differs from what is observed
for quaternary ammonium ionic liquids.[3–5] Furthermore, only the
side chain adjacent to the methyl group appears susceptible to
elimination in [EhEhT][Tf2N], selectively yielding the precursor
triazole and 2-ethylhexanol as decomposition products.
Ethylmagnesium bromide affects [EhEhT][Tf2N] and [HHT][Tf2N]
in more or less the same manner as concentrated NaOH does. A
different behavior is observed for [EhiPrT][Tf2N], which appears to
form two decomposition products when treated with a Grignard
base, with the parent triazole being the minority product. This also
disagrees with a Hofmann-type mechanism.
Figure 2. Structures of the synthesized 1,2,3-triazolium ionic liquids
The physical properties largely follow the same trends as
observed for other classes of ionic liquids. Due to the increase in
energy barrier for side chain rotation, branching increases the
viscosity of ionic liquids.[45] The highest hydrophobicity (lowest
water solubility) was observed for the ionic liquids with the most
hydrophobic side chains. The high viscosity of [iBuiBuT][Tf2N]
Deuterium isotope exchange studies were conducted on
[EhEhT][Tf2N] and [HHT][Tf2N] to gain more insight into the
possible pathway of degradation. After 3 h at 80 °C in 40 wt%
NaOD in D2O, the degree isotope exchange was 49% and 51%,
Table 2. Stability assay of the synthesized ionic liquids.
[EhEhT][Tf2N]
[iBuiBuT][Tf2N]
[EhiPrT][Tf2N]
[HHT][Tf2N]
[EhEhT][NO3]
mol% remaining after contact with:
50 wt% NaOH, 60°C, 24h
EtMgBr, RT, 90 min
97
93
0
n.d.a
91
63
100
98
0
95
100b
90-100
90-100
n-BuLi, RT, 90 min
n.d.
n.d.
aNot determined, pathway of degradation is dissimilar to that of other ionic liquids. bAnionic decomposition occurs.
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10.1002/ejoc.201800925
European Journal of Organic Chemistry
FULL PAPER
respectively, occurring selectively on the C4-methyl groups. This
suggests a possible involvement of the C4-methyl group in the
decomposition mechanism, possibly due to an intramolecular
rearrangement involving an attack on the adjacent side chain,
explaining the occurrence of only one decomposition product.
Determining the stability of the [iBuiBuT][Tf2N] was less trivial, as
the precursor triazole does not appear to be a decomposition
product of this ionic liquid. Alkaline attack occurs most readily by
NaOH and appears to take place on the core ring structure itself,
resembling the decomposition pathway of imidazoles.[8] For this
reason, it was not possible to determine the exact degree of
decomposition of this ionic liquid in concentrated NaOH. The
structural integrity of this cation was better conserved in the
presence of the organometallic bases ethylmagnesium bromide
and n-butyllithium. While some other minor, poorly defined signals
did not observe any decomposition or reduction of [HHT][Tf2N]
under Grignard reaction conditions and therefore propose this
ionic liquid as a more robust medium for Grignard reactions.
Conclusions
In conclusion, several new 1,2,3-triazolium ionic liquids were
synthesized using a new method that is easily upscalable. Up to
30 g of starting azide was used without a significant reduction in
yield. The described products cannot be obtained via CuAAC-
based methods as the copper-catalyzed triazole synthesis is
incompatible with internal alkynes. Advantages of this method
over RuAAC-based methods are the absence of the costly
catalyst, the lower cost and risks associated with the starting
materials and the fixed regiochemistry. The influence of the side
chain structure on the stability of 1,2,3-triazolium ionic liquids in
basic media was studied. Linear side chains afford the highest
stability against concentrated NaOH and Grignard reagents.
When decomposition does occur, it appears to proceed via a
previously unreported mechanism, in which linear side chains
display lower rates of decomposition than branched side chains.
However, both the degree of decomposition and the mechanism
through which it occurs are strongly dependent on the nature of
the cation and the anion of the ionic liquid being studied. These
ionic liquids show promise as media for several organic reactions
in which strongly basic reagents are required.
1
appear in the H NMR spectra after treating [iBuiBuT][Tf2N] with
organometallic bases, no major pathways of decomposition could
be discerned. These bases may be sterically hindered from
attacking in a similar fashion to the more compact hydroxide anion,
kinetically protecting the ionic liquid under harsh conditions.
The nitrate analog of [EhEhT][Tf2N], [EhEhT][NO3],
demonstrates similar stability with respect to concentrated NaOH
as the bistriflimide ionic liquid. However, signals corresponding to
1
an alkene and two isomeric triazoles are detected by H NMR,
indicating that β-elimination is the main pathway of decomposition
for the more hydrophilic nitrate ionic liquid. This possibly results
from the high water content of this ionic liquid, allowing hydroxide
anions to diffuse into the ionic liquid phase more effectively and
attacking the cation directly, rather than deprotonating the cation
at the interface. The most striking difference in behavior of the
nitrate ionic liquid is observed when contacting it with
ethylmagnesium bromide in tetrahydrofuran. Whilst the degree of
cationic decomposition was very limited, a symmetric product
Experimental Section
General synthesis of 1,2,3-triazolium ionic liquids: The ketone (12 eq.),
amine (1.4 eq.) and azide (1.0 eq.) reagents are combined and stirred at
80 °C for 16-20h with 4 Å molecular sieves. After the reaction, excess
starting materials are evaporated and the reaction mixture is suspended in
toluene and filtered. The filtrate is washed three times with 10 wt%
NaH2PO4 and three times with 1 M NH3 mixed with 20 vol% brine. The
organic phase is dried over MgSO4 and concentrated under vacuum to
afford the 1,2,3-triazole. Alkyl mesylate (1.1 eq.) is added to the 1,2,3-
triazole. The resulting mixture is stirred at 80-100 °C for 2-3 d. The reaction
mixture is dissolved in water and washed 3 times with heptane. A lithium
bis(trifluoromethylsulfonyl)imide solution is added, upon which the ionic
liquid forms a second phase. A 50/50 volume ratio mixture of heptane and
ethyl acetate is added to dissolve the ionic liquid phase, which is then
1
yielding an ABX3 spectrum on H NMR was observed to have
formed. We hypothesize this is a product of the reduction of the
nitrate anion by the Grignard reagent, similar to the product which
are observed when nitro compounds are treated by Grignard
reagents.[46] COSY and HSQC spectra for this compound are
provided in the supporting information.
The feasibility of Grignard reactions in [HHT][Tf2N] was
investigated. Iodobutane was metalated with magnesium in
[HHT][Tf2N] and subsequently treated with benzaldehyde. While
an acid-soluble precipitate did develop upon quenching with water,
acidifying and extracting with heptane did not however afford any
product other than the starting benzaldehyde. Law et al. reported
that iodide Grignard reagents could be generated in N-
butylpyridinium tetrafluoroborate, but readily convert to aggregate
organomagnesium species, which do not undergo typical
Grignard reactions either.[47] Adding a Lewis basic cosolvent
regenerates the free Grignard reagent and allows one to perform
Grignard reactions in ionic liquid media.[47–49] As proof of concept,
we report without optimization that the expected Grignard addition
product was observed when a solution of n-dodecylmagnesium
bromide in diethyl ether was added to a solution of n-pentanal in
[HHT][Tf2N], similar to what is reported by Law et al., who used
pyridine as cosolvent for their pyridinium ionic liquid. It should be
noted that Grignard reagents can add to pyridinium salts.[50] We
washed
with
lithium
bis(trifluoromethylsulfonyl)imide
solution.
Concentration under reduced pressure yields the ionic liquid.
5-Ethyl-1-(2-ethylhexyl)-4-methyl-1,2,3-triazole (1): brown oil, yield 68%.
1H NMR (300 MHz, CDCl3, δ/ppm): 0.89 (2t, 6H), 1.14-1.40 (m+t, 11H),
1.91 (m, 1H), 2.29 (s, 3H), 2.63 (q, 2H, 3J=8.0 Hz), 4.07 (d, 2H). 13C NMR
(100 MHz, CDCl3, δ/ppm): 139.97, 134.43, 51.61, 40.07, 30.47, 28.54,
23.75, 22.93, 16.09, 14.01, 12.29, 10.52, 10.48. FT-IR (ν cm-1): 2959, 2931,
2873, 2860, 1575, 1458, 1348, 1343, 1241, 1136, 1061, 1023, 966, 905,
810, 760, 727, 615.
4-Ethyl-5-methyl-1-(2-methylpropyl)-1,2,3-triazole (2): brown oil, yield
61%. 1H NMR (300 MHz, CDCl3, δ/ppm): 0.94 (d, 6H, 3J=6.5 Hz), 1.17 (t,
3
3
3H, 3J=8.0 Hz), 2.29 (s, 3H), 2.63 (q, 2H, J=7.5 Hz), 3.99 (d, 2H, J=7.5
Hz). 13C NMR (100 MHz, CDCl3, δ/ppm): 10.45, 13.31, 16.03, 19.98, 29.52,
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10.1002/ejoc.201800925
European Journal of Organic Chemistry
FULL PAPER
54.99, 134.42, 139.88. FT-IR (ν cm-1): 2969, 2959, 2929, 2887, 2875, 1573,
1539, 1465, 1444, 1240, 1216, 1181, 1026, 809.
1,8-Bis(5-ethyl-4-methyl-1,2,3-triazolyl)octane (11): yellow oil, yield
29%. 1H NMR (300 MHz, CDCl3, δ/ppm): 1.18 (t, 6H, 3J=7.5 Hz), 1.33
(broad m, 8H), 1.85 (broad 5-et, 4H), 2.27 (s, 6H), 2.64 (q, 4H, 3J=7.5 Hz),
4.18 (t, 4H, 3J=7.0 Hz). 13C NMR (100 MHz, CDCl3, δ/ppm): 10.40, 23.36,
15.97, 26.47, 28.85, 30.27, 47.82, 134.09, 140.00. FT-IR (ν cm-1): 2971,
2929, 2857, 1576, 1458, 1386, 1344, 1193, 1024.
1-Butyl-5-ethyl-4-methyl-1,2,3-triazole (3): yellow oil, yield 60%. 1H
NMR (300 MHz, CDCl3, δ/ppm): 0.95 (t, 3H), 1.18 (t, 3H), 1.38 (6-et, 2H,),
1.58 (5-et, 2H), 2.27 (s, 3H), 2.65 (q, 2H), 4.20 (t, 2H). 13C NMR (100 MHz,
CDCl3, δ/ppm): 10.41, 13.37, 13.60, 15.99, 19.89, 32.40, 47.65, 134.13,
139.93. FT-IR (ν cm-1): 2956, 2929, 2859, 1576, 1457, 1385, 1344, 1252,
1240, 1160, 1024, 966, 729.
4-Ethyl-1,3-bis(2-ethylhexyl)-5-methyl-1,2,3-triazolium
bis(trifluoromethylsulfonyl)imide [EhEhT][Tf2N]: brown oil, yield 67%.
1H NMR (300 MHz, CDCl3, δ/ppm): 0.86-0.96 (m, 12H, 1.18-1.42 (m, 19H),
3
3
5-Ethyl-4-methyl-1-hexyl-1,2,3-triazole (4): brown oil, yield 63%. 1H
NMR (300 MHz, CDCl3, δ/ppm): 0.88 (t, 3H), 1.18 (t, 3H), 1.32 (broad m,
6H), 1.86 (5-et, 2H), 2.27 (s, 3H), 2.65 (q, 2H), 4.19 (t, 2H). 13C NMR (100
MHz, CDCl3, δ/ppm): 10.42, 13.37, 13.96, 22.47, 26.34, 30.37, 31.30,
47.94, 134.08, 139.96. FT-IR (ν cm-1): 2955, 2929, 2871, 2859, 1577, 1458,
1240, 1196, 1024, 1039.
1.96 (m, 2H), 2.46 (s, 3H), 2.85 (q, 2H, J=7.5 Hz), 4.30 (2d, 4H, J=7.0
Hz). 13C NMR (100 MHz, CDCl3, δ/ppm): 8.61, 10.10, 12.67, 13.89, 16.57,
22.78, 23.38, 28.20, 30.10, 39.08, 39.38, 54.45, 119.73 (q, 1J=320 Hz),
137.22, 142.03 . FT-IR (ν cm-1): 2962, 2934, 2875, 2864, 1597, 1462, 1383,
1350, 1225, 1181, 1136, 1055, 616 570, 512. CHN calculated for
C23H42F6N4O4S2: C 44.79%, H 6.86%, N 9.08%; found: C 45.23%, H
6.84%, N 8.82%.
5-Ethyl-4-methyl-1-(2,2-dimethylpropyl)-1,2,3-triazole (5): orange oil,
1
4-Ethyl-5-methyl-1,3-bis(2-methylpropyl)-1,2,3-triazolium
yield 46%. H NMR (300 MHz, CDCl3, δ/ppm): 1.00 (s, 9H), 1.16 (t, 3H,
bis(trifluoromethylsulfonyl)imide [iBuiBuT][Tf2N]: brown oil, yield 35%.
1H NMR (300 MHz, CDCl3, δ/ppm): 0.99+1.00 (2d, 12H, 3J=6.5 Hz), 1.27
(t, 3H, 3J=7.5 Hz), 2.29 (m, 2H), 2.46 (s, 3H), 2.85 (q, 2H, 3J=7.5 Hz),
3
3J=7.5 Hz), 2.29 (s, 3H), 2.66 (q, 2H, J=7.5 Hz), 3.99 (s, 2H). 13C NMR
(100 MHz, CDCl3, δ/ppm): 10.40, 13.09, 16.39, 27.96, 33.34, 58.31,
135.00, 139.44. FT-IR (ν cm-1): 2958, 2913, 2872, 1604, 1480, 1470, 1448,
1365, 1252, 1242, 1074, 1062, 1039, 911, 813, 769, 698, 612.
3
4.25/4.22 (2d, 4H, J=7.5 Hz). 13C NMR (100 MHz, CDCl3, δ/ppm): 8.55,
12.22, 16.50, 19.56, 28.55, 28.82, 57.80, 57.92, 39.38, 54.45, 119.73
(q,1J=-320 Hz), 137.22, 142.03. FT-IR (ν cm-1): 2969, 2939, 2880, 2850,
1597, 1470, 1347, 1180, 1134, 1055, 613, 570, 511. CHN calculated for
C15H26F6N4O4S2: C 35.71%, H 5.19%, N 11.11%; found: C 35.84%, H
4.85%, N 9.21%.
1-Cyclohexyl-5-ethyl-4-methyl-1,2,3-triazole (6): yellow oil, yield 52%.
1H NMR (300 MHz, CDCl3, δ/ppm): 1.16 (t, 3H, 3J=7.5 Hz), 1.26-2.16 (m,
3
10H), 2.64 (q, 2H, J=7.5 Hz), 4.03 (m, 1H). 13C NMR (100 MHz, CDCl3,
δ/ppm): 10.29, 13.76, 15.95, 25.16, 25.69, 33.40, 57.72, 133.45, 139.36.
FT-IR (ν cm-1): 2931, 2857, 1576, 1450, 1386, 1239, 1218, 893, 825, 764.
4-Ethyl-1-(2-ethylhexyl)-5-methyl-3-methylethyl-1,2,3-triazolium
bis(trifluoromethylsulfonyl)imide [EhiPrT][Tf2N]: brown oil, yield 88%.
1H NMR (300 MHz, CDCl3, δ/ppm): 0.91 (m, 6H), 1.30 (m, 11H), 1.62 (d,
6H, 3J=6.5 Hz), 1.97 (m, 1H), 2.49 (s, 3H), 2.85 (q, 2H, 3J=6.5 Hz, 3J=8.0
Hz), 4.30 (d, 2H), 4.88 (7-et, 1H). 13C NMR (100 MHz, CDCl3, δ/ppm): 8.34,
10.17, 12.25, 13.88, 16.47, 21.65, 22.76, 23.49, 28.11, 30.13, 39.31, 54.54,
54.99, 119.78 (q, 1J=-320 Hz), 136.25, 141.87. FT-IR (ν cm-1): 2962, 2920,
2876, 2850, 1599, 1462, 1349, 1179, 1134, 1055, 614, 570, 511. CHN
calculated for C18H32F6N4O4S2: C 39.55%, H 5.90%, N 10.25%; found: C
40.03%, H 6.05%, N 9.21%.
1-Benzyl-5-ethyl-4-methyl-1,2,3-triazole (7a) and 1-benzyl-4-ethyl-5-
methyl-1,2,3-triazole (7b) (10:1): yellow oil, yield 46%. 1H NMR (300 MHz,
CDCl3, δ/ppm): 0.94, 1.16 (t, 0.3H, 3J=7.5 Hz), 2.06 (s, 0.3H), 2.27 (s, 3H),
2.52 (q, 2H, J=7.5 Hz), 2.84 (q, 0.2H, J=7.5 Hz), 5.45 (s, 2H), 7.1-7.55
(m, 5H). 13C NMR (100 MHz, CDCl3, δ/ppm): 8.29, 10.40, 12.77, 13.18,
15.99, 30.75, 51.80, 127.02, 128.12, 128.41, 128.85, 129.66, 134.54,
135.50, 135.98, 137.05, 138.23, 140.69. FT-IR (ν cm-1): 3063, 3032, 2972,
2933, 2875, 1576, 1497, 1455, 1240, 1204, 1156, 1074, 1025, 733.
3
3
5-Ethyl-4-methyl-1-(2-methoxyethyl)-1,2,3-triazole (8): yellow oil, yield
61%. 1H NMR (300 MHz, CDCl3, δ/ppm): 1.17 (t, 3H, 3J=7.5 Hz), 2.28 (s,
3H), 2.69 (q, 2H, 3J=8.0 Hz), 3.30 (s, 3H), 3.79 (t, 2H, 3J=5.5 Hz), 4.38 (t,
2H, 3J=7.5 Hz). 13C NMR (100 MHz, CDCl3, δ/ppm): 10.40, 13.19, 15.87,
47.81, 59.00, 71.37, 135.40, 139.82. FT-IR (ν cm-1): 2973, 2931, 2877,
2833, 2817, 1576, 1454, 1387, 1196, 1117.
4-Ethyl-5-methyl-1,3-dihexyl-1,2,3-triazolium
bis(trifluoromethylsulfonyl)imide [HHT][Tf2N]: brown oil, yield 64%. 1H
NMR (300 MHz, CDCl3, δ/ppm): 0.90 (t, 6H, 3J=7.0 Hz), 1.22-1.34 (m, 15H),
1.95 (6-et, 4H, 3J=7.0 Hz), 2.46 (s, 3H), 2.85 (q, 2H, 3J=8.0 Hz), 4.38 (2t,
4H). 13C NMR (100 MHz, CDCl3, δ/ppm): 8.42, 12.23, 14.00, 14.14, 16.46,
22.31, 25.92, 25.96, 28.30, 28.83, 33.93, 30.96, 51.12, 51.25, 119.81 (q,
1J=-320 Hz), 136.72, 141.72. FTIR (ν/cm-1): 2958, 2933, 2862, 1599, 1461,
1349, 1135, 1179, 1054, 615, 570, 512. CHN calculated for
C19H34F6N4O4S2: C 40.71%, H 6.11%, N 9.99%; found: C 41.48%, H
6.26%, N 10.71%.
4-Ethyl-1-(2-ethylhexyl)-5-propyl-1,2,3-triazole (9): orange oil, yield
1
49%. H NMR (300 MHz, CDCl3, δ/ppm): 0.84-1.01, 1.16-1.40 (m, 11H),
1.57 (6-et, 2H, 3J=7.5 Hz), 1.94 (m, 1H), 2.54-2.70 (2q, 4H,), 4.07 (d, 2H,
3J=7.5 Hz,). 13C NMR (100 MHz, CDCl3, δ/ppm): 10.58, 13.68, 14.00,
14.14, 18.62, 22.57, 22.93, 23.89, 24.60, 28.60, 30.56, 40.08, 51.57,
132.50, 145.97. FT-IR (ν cm-1): 2960, 2930, 2873, 2861, 1571, 1459, 1378,
1191, 1088, 966, 772, 728.
4-Ethyl-5-methyl-1,3-dihexyl-1,2,3-triazolium nitrate [EhEhT][NO3]:
brown oil, total isolated yield 57% with respect to azide. 1H NMR(300 MHz,
CDCl3, δ/ppm): 0.91 (2t, 12H), 1.31 (m, 19H), 1.98 (m, 2H), 2.54 (s, 3H),
2.91 (q, 2H), 4.38 (d, 4H). 13C NMR(100 MHz, CDCl3, δ/ppm): 142.05,
137.42, 54.44, 39.40, 39.12, 30.15, 28.26, 23.44, 22.82, 16.66, 13.94,
12.38, 10.22, 8.80. FTIR(ν/cm-1): 2959, 2931, 2873, 2861, 1596, 1460,
1328, 1181, 1109, 1096, 1038, 971, 586, 829, 771, 728.[2,3] CHN
calculated for C21H42N4O3·H2O: %C 60.54, %H 10.65, %N 13.45,
found %C 60.87, %H 10.41, %N 12.93.
5-Ethyl-1-(2-(1-cyclohexenyl)ethyl)-4-methyl-1,2,3-triazole
(10):
orange oil, yield 46%. 1H NMR (300 MHz, CDCl3, δ/ppm): 1.18 (3t, 3H,
3J=7.5 Hz), 1.58 (m, 4H), 1.96 (m, 4H), 2.27 (s, 3H), 2.47 (m, 2H), 2.64 (q,
3
2H), 4.25 (m, 2H, J=7.5 Hz), 5.43 (m, 1H). 13C NMR (100 MHz, CDCl3,
δ/ppm): 10.42, 13.38, 15.99, 22.15, 22.78, 25.19, 28.35, 38.82, 46.87,
124.22, 133.52 , 134.12, 139.86. FT-IR (ν cm-1): 2970, 2926, 2875, 2857,
2835, 1576, 1668, 1447, 1437, 1386, 1343, 1240, 1198, 1112, 1025, 966,
919, 801.
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10.1002/ejoc.201800925
European Journal of Organic Chemistry
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The authors wish to thank FWO Flanders for funding (PhD
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Keywords: ionic liquids • green chemistry • Grignard reaction •
triazolium salts
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A new, upscalable method for the
synthesis of 1,2,3-triazolium ionic
liquids is described for scales up to
40+ grams. The influence of various
substituents on the stability of these
structures towards bases is
Triazolium ionic liquids
Stijn Raiguel, Joice Thomas, Koen
Binnemans, Wim Dehaen*
Page No. – Page No.
Multi-gram scalesynthesis of 1,2,3-
triazolium ionic liquids and assay of
their resistance towards bases
investigated. One example was
found to exhibit noteworthy stability
towards NaOH and Grignard
reagents.
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