A new generation of aprotic yet Bronsted acidic imidazolium salts: Low toxicity, high recyclability and greatly improved activity

Article abstract of DOI:10.1039/c3gc40975a

Catalysts which have low antimicrobial toxicity and are aprotic, yet which can act as Bronsted acidic catalysts in the presence of protic additives have been developed. The catalysts are recyclable, considerably more active (i.e. can be used at 10-50 times lower loadings) and of broader scope than their antecedent generation.

Full text of DOI:10.1039/c3gc40975a

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A new generation of aprotic yet Brønsted acidic
imidazolium salts: low toxicity, high recyclability and
Cite this: DOI: 10.1039/c3gc40975a
greatly improved activity†
Lauren Myles,a Rohitkumar G. Gore,b Nicholas Gathergood*b and
Stephen J. Connon*a
Received 28th May 2013,
Accepted 24th July 2013
Catalysts which have low antimicrobial toxicity and are aprotic, yet which can act as Brønsted acidic cata-
lysts in the presence of protic additives have been developed. The catalysts are recyclable, considerably
more active (i.e. can be used at 10–50 times lower loadings) and of broader scope than their antecedent
generation.
DOI: 10.1039/c3gc40975a
www.rsc.org/greenchem
Since Forbes and Davis reported the design of a class of phos- acidity of which could be controlled in an ‘on–off’ fashion. In
phonium- and imidazolium ion-based ionic liquids (e.g. 1, short, these catalysts would be acidic only when required.
Fig. 1A) equipped with a pendant acidic sulfonic acid moiety,
Our inspiration for this work came from the serendipitous
interest in Brønsted acidic ionic liquids (BAILs) has gathered discovery that N-alkyl pyridinium ions could catalyse the aceta-
considerable pace.1,2 These materials afford the practitioner lisation of benzaldehyde in the absence of any discernible
the flexibility of a system which combines strong acidity with acidic species in solution.6,7 It was later demonstrated that
the traditional advantages3 associated with the use of non- this phenomenon also occurred in the case of N-alkyl imid-
volatile ionic liquids.
azolium ions, which allowed the design of a suite of demonstrably
Subsequently two other strategies for the design of acidic low antimicrobial toxicity salts (of which 4, Fig. 1A, proved the
imidazolium-ion based ionic liquids (ILs) were reported: the most active) capable of promoting the acetalisation of alde-
protonated imidazole conjugate acids3o,4 (i.e. 2) and traditional hydes (inter alia) at low catalyst loadings (e.g. 5–10 mol%,
imidazolium-ion based ILs which incorporate acidic counter- Fig. 1B).8a Along the same lines, we recently demonstrated that
anions (i.e. 3).5 While these systems have found application in a triazolium ion-based species could act in a similar fashion at
wide-range of acid-catalysed reactions, the potential uncertain- loadings of 1–2 mol%.8b It was proposed that the low reso-
ties from an environmental standpoint (to the best of our nance stabilisation energy of the imidazolium ion would allow
knowledge the toxicity and biodegradation profiles of these
materials have yet to be established) and potential storage
difficulties associated with the fact that these materials are
strongly Brønsted acidic, remain.
We therefore became interested in the design of aprotic
salts which could serve as acidic catalysts only when used in
conjunction with an additive. These materials hold promise as
catalysts which can be designed to be readily storable and of
minimal toxicity/environmental impact, the catalytically useful
aSchool of Chemistry, Centre for Synthesis and Chemical Biology, Trinity Biomedical
Sciences Institute, University of Dublin, Trinity College, Dublin 2, Ireland.
E-mail: connons@tcd.ie; Fax: +353 16712826
bSchool of Chemical Sciences and National Institute for Cellular Biotechnology,
Dublin City University, Glasnevin, Dublin 9, Ireland.
E-mail: Nick.Gathergood@dcu.ie; Fax: +353 17005503
†Electronic supplementary information (ESI) available: Synthesis of all catalysts
not detailed in the Experimental section, general procedures, characterisation
data and NMR spectra for all catalysts and products. See DOI:
10.1039/c3gc40975a
Fig. 1 Catalytically competent imidazolium ion-based acidic ionic liquids and
the proposed mode of action of catalyst 4.
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the addition of methanol to 4, leading to the presence of low
concentrations of 7/7a in methanolic solution (Fig. 1C). These
species could then serve as the Brønsted acidic agent respon-
sible for the observed catalysis. While it should be noted that
7/7a have not been directly observed experimentally, this
hypothesis can account all of the data obtained thus far.6–8
While 4 was shown to be catalytically active and completely
non-toxic to 20 sample microorganisms (8 bacteria and 12
fungi),8 we were nevertheless aware that the utility and poten-
tial environmental impact of these systems could be signifi-
cantly improved if: (a) catalytic activity could be increased
significantly (so that less of the material would be required for
use in synthetic applications) and (b) the tetrafluoroborate
counteranion9–13 (which is a sine qua non for high activity in
catalysts such as 4) could be replaced with a less hydrolytically
unstable14 substitute.
Table 1 Aprotic C-2 substituted imidazolium ions: catalyst evaluation
If the mechanistic hypothesis outlined in Fig. 1C accurately
captures the mode of action of 4, then it should be possible to
bias the equilibrium between 4 and 7/7a towards the latter
through the installation of electron withdrawing substituents
on the imidazolium ion, which would further reduce delocali-
sation and favour nucleophilic attack by the protic additive on
the heterocycle. Since Gathergood and Scammells15 had pre-
viously shown that the incorporation of hydrolytically suscep-
tible moieties into the N-alkyl substituents of imidazolium
salts improved biodegradability, we were also interested in
determining the (hitherto unknown) influence that equipping
the imidazolium ring with ester and amide substituents would
have on both the toxicity and the biodegradability of the candi-
date catalyst structures.
Entry
Catalyst
Loading (mol%)
Yielda (%)
1
2
3
4
5
6
7
8
4
8
9
10
11
12
13
13
5
1
1
1
1
1
1
0.1
85
80
83
86
86
85
91
72
a Determined by 1H NMR spectroscopy using an internal standard.
the influence of the anion on catalyst performance is consider-
ably less significant in this library that was the case with cata-
lysts devoid of ring-substitution (such as 4);8a we would
interpret this as strongly indicating that the more electrophilic
imidazolium ion units are making a greater contribution to
catalysis in this library. As before, we did observe more
efficient catalysis when the imidazolium ion incorporates a
tetrafluoroborate counterion (i.e. catalyst 13), which allows the
synthesis of the acetal 6 in 91% yield at 1 mol% catalyst
loading (entry 7). At loadings lower than 1 mol% product
yields diminish considerably (entry 8).
While it was clear that 8–13 represented a considerable step
forward in terms of catalytic activity, we were aware that the
designs were not optimal. One particular cause for concern
was the location of the electron-withdrawing substituent: while
installing this at C-2 allows the maximum amount of both
inductive and mesomeric forms of electron withdrawal to be
exerted by the amide/ester moiety at the proposed site of
nucleophilic attack by methanol, it also introduces a degree of
counterproductive steric crowding (i.e. 13a), which would be
expected to limit catalyst performance.
Herein we describe the contribution that these substituents
make to catalytic efficacy; their effect on toxicity and bio-
degradability is discussed in the next paper in this issue.
We began with the synthesis of a library of imidazolium
salts 8–13 incorporating an electron withdrawing group at C-2.
These materials were synthesised from the corresponding
available imidazole carboxylic acids and then sequentially
alkylated (full details in the ESI†). We also included structures
with and without pendant ester/amide functionality in the
N-alkyl substituent. These materials were evaluated as promoters
of the room temperature acetalisation of benzaldehyde in
methanol (Table 1).
The data associated with the prototype catalyst 4 is included
for comparison (entry 1). We were pleased to find that the C-2
amide-substituted imidazolium ion 8 promoted (at 1 mol%
loading) the formation of 6 from 5 in similar yield to that
obtained using 4 at 5 mol% levels (entry 2). Exchange of the
counterion from octylsulfate to bromide and tetrafluoroborate
(i.e. catalysts 9 and 10) led to a further (marginal) improve-
ment in catalytic activity (entries 3 and 4). The C-2 substituted
esters 11–13 also proved capable of promoting the reaction
with considerably improved efficacy relative to 4 (entries 5–7).
It appears that hydrogen-bonding to the C-2 substituent does
not play a significant role in catalysis – as can be deduced
from the similar performance of amides 8 and 9 to that of
esters 10–12 (entries 2–3 and 4–6). It is also noteworthy that
It therefore seemed prudent to design a library of catalysts
characterised by the location of the electron withdrawing
group at a further remove from C-2. The C-4 substituted ana-
logues 14–19 were therefore duly prepared from the corres-
ponding available imidazole carboxylic acids and evaluated
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Table 2 Aprotic C-4 substituted imidazolium ions: catalyst evaluation
Table 3 Aprotic disubstituted imidazolium ions: catalyst evaluation
Entry
Catalyst
Loading (mol%)
Yielda (%)
1
2
3
4
5
6
7
8
14
15
16
17
18
19
14
15
16
17
19
1
1
1
1
1
1
0.1
0.1
0.1
0.1
0.1
>98
>98
>98
>98
95
>98
81
88
78
86
85
Entry
Catalyst
Loading (mol%)
Yielda (%)
1
2
3
4
5
6
7
8
20
21
22
23
24
25
26
27
20
21
22
23
24
25
27
1
1
1
1
1
1
1
1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
>98
>98
>98
>98
>98
>98
98
>98
89
94
86
92
82
91
9
11
12
a Determined by 1H NMR spectroscopy using an internal standard.
9
10
11
12
13
14
15
under identical conditions (Table 2). This strategy was success-
ful – when utilised at 1 mol% loading, catalysts 14–17 and 19
promoted the reaction in essentially quantitative yield (entries
1–4 and 6). Imidazolium ion 18 (which incorporates an iodide
counteranion) is also an excellent catalyst (the product is
formed in 95% yield) yet is perceptibly less active than the
other members of the library (entry 5). Since the ranking of
14–17 and 19 on the basis of activity could not be determined
at 1 mol% loading, these materials were then re-evaluated at
0.1 mol% levels under otherwise identical conditions. Product
yields remained high (entries 7–12), however none of the cata-
lysts was capable of promoting the reaction to >90% yield
inside 24 h. The nature of the anion-, activating substituent
(i.e. ester vs. amide) and N-alkyl moiety appears to have little
impact on efficacy in these systems.
Given the dramatic effect of the introduction of one elec-
tron withdrawing group (especially when not located at C-2) on
catalyst activity, the final step in our optimisation study
involved the design of catalysts characterised by the presence
of two such groups at C-4 and C-5 (Table 3). As expected, cata-
lysts 20–27 all proved highly active at 1 mol% levels (entries
1–8), with only the iodide 26 failing to promote the reaction
to completion (entry 7). At 0.1 mol% loading, product yields
were attenuated, however using catalysts incorporating the
92
a Determined by 1H NMR spectroscopy using an internal standard.
tetrafluoroborate counteranion (i.e. entries 10, 12, 14 and 15)
yields remained over 90%.
In addition to the catalyst activity exhibited by the optimum
structure identified by this study (i.e. 21), the performance of
the simple structures 26 and 27 was also particularly gratify-
ing: these materials are readily prepared from the inexpensive
4,5-imidazole carboxylic acid in a relatively atom-economic
fashion (see Scheme 1) and are capable of acting as syntheti-
cally useful catalysts at loadings 5–50 times lower than those
previously necessary using the optimal first generation
material 4. Their activity is such that one is no longer depen-
dant on the nature of the anion to ensure high product
yields – the iodide 26 can promote the formation of 6 in >90%
yield at just 1 mol% loading. We also note with interest that
Fatemi and Izadiyan13 have very recently suggested that IL-
symmetry is linked to cytotoxicity to rat luekemia cell lines;
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Table 4 Catalytic acetalisation/ketalisation: evaluation of substrate scope
Entry Product
1
Loading (mol%) Time (h) Yielda (%)
0.1
0.1
0.1
24
24
24
95
96
98
2
3
Scheme 1 Synthesis of 26 and 27 from the inexpensive diacid 28.
with less symmetrical salts in general proving more cytotoxic
than more symmetrical counterparts.
4
5
1
1
24
24
90
92
The general catalyst order of activity (i.e. C-2 substituted
< C-4 substituted < C-4/C-5 disubstituted) and the diminished
influence of the anion relative to the case with 4 is in line with
what one would expect from the mechanistic hypothesis out-
lined in Fig. 1C, which provides further evidence supporting
this most unusual proposed mode of action.
With an active and easily prepared catalyst in hand, our
attention next turned to the question of substrate scope
(Table 4). Catalyst 21 could catalyse the smooth acetalisation
of activated- (i.e. 31–33, entries 1–3), hindered- (i.e. 34, entry 4)
deactivated- (i.e. 35, entry 5), heterocyclic- (i.e. 36, entry 6) and
α,β-unsaturated aldehydes (i.e. 37, entry 7) with higher (excel-
lent) isolated product yields at 10–50 times lower catalyst
loading (in shorter reaction times) than those required for the
synthesis of these acetals using catalyst 4. We also found that
21 could promote the ketalisation of p-nitrobenzaldehyde to
form 38 in good yield – a reaction which was completely
beyond the scope of catalyst 4.
6
7
1
1
24
24
92
90
8
10
48
63b
a Isolated yield after chromatography. b Reaction at 35 °C.
The synthetically useful dithiolane (a product usually
formed under elevated temperatures) and dioxane derivatives
39 and 40 could also be formed from 5 in good–excellent
yields at room temperature catalysed by 21 at low loading
(Scheme 2).
According to the principle of microscopic reversibility, 21
should also serve as a useful catalyst for the hydrolysis of
acetals/ketals. This proved to be the case: in an aqueous
medium 21 (1 mol%) could mediate the conversion of acetal 6
back to benzaldehyde (5) under mild, ambient temperature
conditions (Scheme 3).
Scheme 2 Dithiolane/dioxane formation: stoichiometric nucleophiles.
While at this juncture the superior activity and potential
utility of 21 (relative to 4) was beyond doubt, we were also
interested in evaluating the recyclability of 21. We carried out
the protection of 5 as its dithiolane derivative 39 (Table 5).
After 24 h, hexane was added to precipitate the catalyst and the
solution containing the product was decanted and dried
Scheme 3 Acetal hydrolysis under mild conditions promoted by 21.
in vacuo to give 39 in excellent yield. The solid catalyst was activity being observed. The study was terminated at this point
dried in vacuo to remove the condensation water16 and reused as the catalyst appeared to be beginning to show physical
in 5 subsequent iterative cycles without any loss of catalytic signs of decomposition. While 21 could not be recycled as
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catalyst loadings of 0.1–1 mol% and could catalyse both the
reverse hydrolytic process and a ketalisation reaction which
were beyond the scope of the first generation series.17,18 After
the reaction the catalyst can be recovered by simply adding
hexane and decanting the product. The recycled catalyst can
be reused in 5 iterative recycles (at 1 mol% loading) without
any discernible loss of catalytic activity. Biodegradation, anti-
bacterial and antifungal toxicity studies are reported in the fol-
lowing paper. We are grateful to the Environmental Protection
Agency for their financial support of this work.
Table 5 Catalyst recycling
Entry
Cycle
Yielda (%)
1
2
3
4
5
1
2
3
4
5
94
94
94
95
94
a Determined by 1H NMR spectroscopy using an internal standard.
Experimental
General
many times as 4 (which was recycled in our previous study 14
times),8 21 was employed at considerably lower loading in this
study (1 mol% vs. 10 mol%), and as such can be considered
more recyclable than 4 due to its significantly superior TON
over the accumulated cycles.
Proton nuclear magnetic resonance spectra were recorded on
400 MHz and 600 MHz spectrometers in CDCl3 referenced
relative to residual CHCl3 (δ = 7.26 ppm), DMSO-d6 referenced
relative to residual DMSO (H) (δ = 2.51 ppm). Chemical shifts
are reported in ppm and coupling constants in Hertz. Carbon
NMR spectra were recorded on the same instruments
(100 MHz and 150 MHz) with total proton decoupling. All
melting points are uncorrected. Infrared spectra were obtained
using neat samples on a Perkin Elmer Spectrum 100 FT-IR
spectrometer equipped with a universal ATR sampling acces-
sory. Flash chromatography was carried out using silica gel,
particle size 0.04–0.063 mm. TLC analysis was performed on
precoated 60F254 slides, and visualised by UV irradiation,
KMnO4 or anisaldehyde staining. All aldehydes were sourced
commercially and either distilled under vacuum (if liquid) or
dissolved in CH2Cl2 and washed with NaOH (if solid) prior to
use. Methanol and THF were distilled from sodium and stored
under argon best results were obtained using freshly distilled
methanol. All reactions were carried out in oven-dried glass-
ware with magnetic stirrers under an atmosphere of argon,
unless specified. Careful drying of all catalysts is essential for
best results a convenient procedure for this follows: the cata-
lysts were dissolved in dry toluene under argon. The solvent
was removed in vacuo and the procedure was repeated twice,
taking care the compound was not exposed to air. The catalysts
were then dried under high vacuum for 2 h and used in the
reaction.
Conclusions
In summary, we have designed a 3rd generation of aprotic salts
capable of behaving as Brønsted acids in an ‘on–off’ fashion,
controlled by the use of protic additives. These catalysts offer
greatly improved catalytic efficacy (with the attendant reduced
environmental impact) without compromising the low toxicity
profile associated with the first generation series. Analysis of a
previous study provided a measure of mechanistic insight,
which suggested that the installation of electron withdrawing
groups on the imidazolium ring would facilitate the formation
of greater equilibrium concentrations of the putative acidic
adduct with methanol, leading to faster catalysis. An initial
library was prepared, the members of which possessed either
an ester or an amide group at C-2. These catalysts proved con-
siderably more active than either the optimum 1st generation
benchmark material 48a or the 2nd generation triazolium ion-
based systems.8b Removal of the activating group to C-4 led to
further improvements in efficacy, while the installation of a
second electron withdrawing moiety at C-5 resulted in a suite
of catalysts capable of promoting the acetalisation of benz-
aldehyde by methanol at catalyst loadings 50 times lower than
that required to produce the product using 4.
2-(Isobutoxycarbonyl)-1,3-dimethyl-1H-imidazol-3-ium
tetrafluoroborate (13)
The optimum catalyst systems are prepared in a straight- A round-bottomed flask was charged with isobutyl 1-methyl-
forward manner from an inexpensive starting material and are 1H-imidazole-2-carboxylate (0.200 g, 1.1 mmol) and dry diethyl
characterised by a marked reduction in the relative contri- ether (10 mL) under nitrogen. To this solution was added tri-
bution of the anion to catalysis, which gives the practitioner methyloxonium tetrafluoroborate (0.162 g, 1.1 mmol) quickly.
the flexibility to choose the anion based on environ- The reaction mixture was stirred vigorously for 24 h. The
mental/toxicological/solubility/chemoselectivity considerations product precipitated as a white solid, was filtered, and then
if required. In addition it removes the obligation to use the washed with diethyl ether (2 × 10 mL). The product was dried
hydrolytically suspect tetrafluoroborate anion associated with in vacuo for 24 h to give 13 as a white solid (0.302 g, 97%).
the first generation catalyst series. The optimum catalyst in Mp 64–65 °C; δH (400 MHz, CDCl3); 1.05 (d, J = 6.8 Hz, 6H),
this study could promote ambient temperature acetalisation 2.14 (sept, J = 6.8, 6.4 Hz, 1H), 4.16 (s, 6H), 4.29 (d, J = 6.4 Hz,
and thioacetalisation reactions of a range of aldehydes at 2H), 7.65 (s, 2H); δC (100 MHz, CDCl3); 19.1, 27.5, 39.3, 74.2,
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126.7, 132.2, 153.9; m/z (ES) 197.1295 ([M
−
BF4−]+. (2 mL). Trimethyloxonium tetrafluoroborate (240 mg,
1.62 mmol) was added and the reaction mixture was stirred at
room temperature for 3 days. Upon completion of the reaction,
the solvent was removed in vacuo giving the pale yellow solid
27 (344 mg, 91%). δH (400 MHz, DMSO-d6); 3.95 (br.s, 12H),
C10H17N2O2+ requires 197.1285).
3-Benzyl-1,5-bis(ethoxycarbonyl)-1H-imidazol-3-ium
tetrafluoroborate (15)
To a 50 mL round bottomed flask fitted with a magnetic stir- 9.42 (s, 1H); δC (100 MHz, DMSO-d6); 38.1, 53.8, 126.7, 141.2,
+
ring bar, 14 (150 mg, 0.38 mmol) was added. To this NaBF4 157.3; m/z (ES) 213.0873 ([M − BF4−]+. C9H13N2O4 requires
(75 mg, 0.68 mmol) and acetone (10 mL) were added and the 213.0875).
mixture was placed under an argon atmosphere. The resulting
General procedure – acetalisation of aldehydes
suspension was stirred at room temperature for 4 days, after
which time a white precipitate was formed. This precipitate
was filtered using a Buchner funnel under vacuum and
washed with dry acetone (2 × 5 mL). The combined filtrate and
washings were then concentrated in vacuo giving the pure
product 15 as a pale yellow solid (146 mg, 96%). δH (400 MHz,
DMSO-d6); 1.32 (t, J = 6.8 Hz, 6H), 3.56 (q, J = 6.8 Hz, 4H), 4.69
(s, 1H), 5.95 (s, 1H), 7.26–7.48 (m, 5H), 7.86 (s, 1H), 8.95 (s,
1H); δC (100 MHz, DMSO-d6); 15.1, 15.2, 49.5, 58.1, 62.1, 62.5,
126.7, 128.9, 129.7, 130.1, 134.4, 137.5, 146.2, 161.2, 169.0; m/z
(ES) 317.1423 ([M − BF4−]+. C17H21N2O4+ requires 317.1422).
A 20 mL reaction vessel was fitted with a magnetic stirring bar,
charged with catalyst (0.08 mmol), fitted with a septum and
flushed with argon. Benzaldehyde (170 µL, 1.67 mmol) was
added followed by dry methanol (3.4 mL) via syringe. The solu-
tion was then stirred under argon at room temperature. When
conversion was judged to be either complete or >95% conver-
sion (by 1H NMR spectroscopic analysis) the reaction was
quenched with PhNHNH2 and solvent was removed in vacuo.
The crude product was either purified by flash-chromato-
graphy or the yield was calculated using an internal standard.
3-Benzyl-1-(2-ethoxy-2-oxoethyl)-4,5-bis(methoxycarbonyl)-1H-
imidazol-3-ium tetrafluoroborate (21)
Notes and references
To a 50 mL round bottomed flask fitted with a magnetic stir-
ring bar, 20 (250 mg, 0.57 mmol) was added. To this NaBF4
(74.8 mg, 0.68 mmol) and acetone (10 mL) were added and the
mixture was placed under an argon atmosphere. The resulting
suspension was stirred at room temperature for 4 days. After
which time a white precipitate was formed. This precipitate
was filtered and washed with dry acetone (2 × 5 mL). The com-
bined filtrate and washings were then concentrated in vacuo to
give the pure catalyst 21 as a pale yellow oil (249 mg, 98%). δH
(400 MHz, DMSO-d6); 1.23–1.26 (m, 3H), 3.78 (s, 3H), 3.81 (s,
3H), 4.22 (q, J = 7.1 Hz, 2H), 5.39 (s, 2H), 5.62 (s, 2H), 7.26 (s,
1H), 7.43 (d, J = 7.2 Hz, 2H), 7.64 (t, J = 7.2 Hz, 2H), 9.89 (s,
1H); δC (100 MHz, DMSO-d6); 14.2, 47.9, 50.4, 51.5, 53.9, 62.1,
123.7, 128.9, 129.6, 133.2, 138.7, 157.8, 159.7, 164.2, 166.9,
1 A. C. Cole, J. L. Jensen, I. Ntai, K. L. T. Tran, K. J. Weaver,
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5962.
2 For representative recent examples using this strategy see:
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Ind. Eng. Chem. Res., 2005, 44, 4147; (c) J. Guia, H. Bana,
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and Z.-Y. Xu, Green Chem., 2009, 11, 1239; (g) L. Yang,
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2007, 40, 1146; (i) A. A. H. Padua, M. F. Costa Gomes and
J. N. A. Canongia Lopes, Acc. Chem. Res., 2007, 40, 1087;
168.2; m/z (ES) 361.1392 ([M − BF4−]+. C18H21N2O6 requires
+
361.1394).
4,5-Bis(methoxycarbonyl)-1,3-dimethyl-1H-imidazol-3-ium
iodide (26)
A 25 mL round-bottomed flask, fitted with a magnetic stirring
bar, was charged with 22a (250 mg, 1.26 mmol) in acetonitrile
(2 mL). Methyl iodide (79 µL, 1.26 mmol) was added and the
resulting solution was stirred at room temperature for 3 days.
Upon completion of the reaction, the solvent was removed
in vacuo giving the pale yellow oil 26 (368 mg, 86%). δH
(400 MHz, DMSO-d6); 3.91–4.02 (m, 12H), 9.40 (s, 1H); δC
(100 MHz, DMSO-d6); 36.2, 53.8, 126.6, 141.2, 157.3; m/z (ES)
213.0877 ([M − I−]+. C9H13N2O4+ requires 213.0875).
4,5-Bis(methoxycarbonyl)-1,3-dimethyl-1H-imidazol-3-ium
tetrafluoroborate (27)
A 25 mL round-bottomed flask, fitted with a magnetic stirring
bar, was charged with 22a (250 mg, 1.62 mmol) in acetonitrile
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