Synthesis of fused tetrahydro-β-carbolinequinoxalinones in 1-n-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide ([bdmim][Tf2N]) and 1-n-butyl-2,3-dimethylimidazolium perfluorobutylsulfonate ([bdmim][PFBuSO3]) ionic liquids

Article abstract of DOI:10.1016/j.tetlet.2005.06.153

Starting from tryptophan methyl ester, a three-step synthesis of fused tetrahydro-β-carbolinequinoxalinones in two new ionic liquids, [bdmim][Tf₂N] and [bdmim][PFBuSO₃], was described. Both ionic liquids can be readily prepared from commercially available starting materials in high yields. Unlike the commonly used [PF₆]-based ionic liquids that evidently undergo slow hydrolysis of the PF₆ anion with the concomitant release of HF, ionic liquids of [bdmim][Tf₂N] and [bdmim][PFBuSO₃] are not only chemically stable but also apparently inert to hydrolysis and therefore organic reactions carried out in both ionic liquids proceed smoothly with good yields. The overall isolated yields for this three-step synthesis of tetrahydro-β-carbolinequinoxalinones were 34-55%. To the best of our knowledge, the preparation of fused tetrahydro-β- carbolinequinoxalinones was unprecedented.

Full text of DOI:10.1016/j.tetlet.2005.06.153

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6131–6136
Synthesis of fused tetrahydro-b-carbolinequinoxalinones in
1-n-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)-
imide ([bdmim][Tf2N]) and 1-n-butyl-2,3-dimethylimidazolium
perfluorobutylsulfonate ([bdmim][PFBuSO3]) ionic liquids
Ming-Chung Tseng, Yang-Min Liang and Yen-Ho Chu*
Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi 621, Taiwan
Received 8 March 2005; revised 27 June 2005; accepted 29 June 2005
Available online 14 July 2005
Abstract—Starting from tryptophan methyl ester, a three-step synthesis of fused tetrahydro-b-carbolinequinoxalinones in two new
ionic liquids, [bdmim][Tf2N] and [bdmim][PFBuSO3], was described. Both ionic liquids can be readily prepared from commercially
available starting materials in high yields. Unlike the commonly used [PF6]-based ionic liquids that evidently undergo slow hydro-
lysis of the PF6 anion with the concomitant release of HF, ionic liquids of [bdmim][Tf2N] and [bdmim][PFBuSO3] are not only
chemically stable but also apparently inert to hydrolysis and therefore organic reactions carried out in both ionic liquids proceed
smoothly with good yields. The overall isolated yields for this three-step synthesis of tetrahydro-b-carbolinequinoxalinones were
34–55%. To the best of our knowledge, the preparation of fused tetrahydro-b-carbolinequinoxalinones was unprecedented.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Ionic liquids are a class of highly polar solvents that are
entirely constituted of ions.1 They are liquid at low tem-
perature (melting point typically below 100 ꢁC),2 and are
often considered as recyclable and environmentally
friendly substitutes for conventional organic solvents,
mainly due to their attractive negligible vapor pressure,
chemical and thermal stability, non-flammability, and
high ionic conductivity. Because of these intriguing
properties, ionic liquids have recently been found to be
the solvents of choice for a large array of organic reac-
tions.1 When applicable, this non-volatile nature of ionic
liquids ensures an effective product isolation by distilla-
tion. In addition, the high solubility of ionic liquids to
many organic and inorganic compounds can in principle
lead to enhanced rates, better selectivity, and improved
yields in reactions.1,3,4
example, 1-n-butyl-3-methylimidazolium hexafluoro-
phosphate ([bmim][PF6]) ionic liquid has been widely
used by many researchers for a combination of reasons,
including its ease of preparation, lack of vapor pressure,
and, most significantly, hydrophobicity that presents an
obvious advantage as a potential replacement for vola-
tile organic solvents in developing green processes.
Though useful in organic synthesis and popular in ionic
liquid research, [bmim][PF6] however is not totally sta-
ble chemically; it is well documented for the instability
of PF6 anion towards slow hydrolysis upon contact with
moisture.5
Our idea of the present work to develop new and chem-
ically inert ionic liquids as solvents for organic synthesis
came from reports5 that the popular [PF6]-based ionic
liquids have the propensity to decompose to release
HF, HPO2F2, H2PO3F, and H3PO4, and also from our
own experience6 that the ÔC2-unmodifiedÕ [bmim]-based
ionic liquids are not compatible with the highly basic
reaction conditions. In addition, various experimental
observations of the chemical instability of hexafluoro-
phosphate containing ionic liquids has been noted or
discussed in the literature.7 Moreover, Earle et al. have
recently reported that certain ionic liquids are chemi-
cally reactive and can greatly influence the outcome of
A number of ionic liquids are known from the litera-
ture.1 Up to now, alkylimidazolium salts are still the
most studied and best characterized ionic liquids. For
Keywords: Ionic liquid; Organic synthesis; Tetrahydro-b-
carbolinequinoxalinone.
*
Corresponding author. Tel.: +886 5 2428148; fax: +886 5 2721965;
e-mail: cheyhc@ccu.edu.tw
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.153

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M.-C. Tseng et al. / Tetrahedron Letters 46 (2005) 6131–6136
the electrophilic aromatic substitution reactions.8 These
disadvantages limited the application of ionic liquids to
synthetic reactions. Therefore, there should be an urgent
need to develop ionic liquids with new formulation. For-
tunately, many valuable results from detailed to system-
atic studies of room temperature ionic liquids have been
made available in the literature.1 It is known, for exam-
ple, that the diversity of possible cations and anions,
along with the types of substituent groups on the cat-
ions, allows fine-tuning of melting points, hydrophobic-
ity, and solvent properties of ionic liquids. In our
program of ionic liquid research, we aim to develop
new ionic liquids as direct replacements for conventional
organic solvents in multistep organic synthesis and re-
port here our preliminary progress towards preparing
chemically stable ionic liquids for the synthesis of, for
example, fused tetrahydro-b-carbolinequinoxalinones.
[bdmim][Tf2N] is a liquid at ambient temperature. We
were interested in the bis(trifluoromethylsulfon-
yl)imide-based ionic liquids because of their reported
minimal water association with the liquid (<2%)12,14
and unusual low melting points.1b We rationalized that,
mainly due to its low viscosity, resistance to thermal and
electrochemical reactions, and immiscibility with water
and less polar organic solvents, the [bdmim][Tf2N] ionic
liquid should be a superb solvent for applications in or-
ganic synthesis. As the other choice, the [bdmim][PFBu-
SO3] ionic liquid is a solid at room temperature (mp 59–
61 ꢁC), but becomes a clear liquid with modest heating
or when small amounts of water (or organic solvents)
are added. This was totally expected because previous
reports have demonstrated that methylation at the C2
carbon of alkylimidazolium cation greatly increases
the melting point of ionic liquids.1,15
In this letter, two new hydrophobic and chemically sta-
ble ionic liquids, 1-n-butyl-2,3-dimethylimidazolium
bis(trifluoromethylsulfonyl)imide ([bdmim][Tf2N])9 and
1-n-butyl-2,3-dimethylimidazolium perfluorobutylsulfo-
nate ([bdmim][PFBuSO3]), are described. Both ionic liq-
uids can be conveniently prepared by direct
quaternization of 1,2-dimethylimidazole; different
anions can subsequently be introduced by anion
exchange.10 The [bdmim] cation was employed in the
new ionic liquids for good reasons that the proton at
the C2 carbon in [bmim] cations is chemically acidic
and can be readily exchanged with D2O at room temper-
ature and neutral pH,11 and under basic conditions this
[bmim] cation readily reacts with various electrophiles
such as aldehydes.6 The [bdmim] cation is chemically
inert under the above conditions, since its C2 carbon
has been substituted and blocked by a methyl group.
Fluoroanions of [Tf2N] and [PFBuSO3] were chosen in
our new ionic liquid formulation because the strong
delocalization of the negative charge in the fluoroanions
weakens its interaction with the cation, eventually
resulting in lower melting points of ionic liquids.12 In
addition, the organofluoro compounds are known to
possess unique properties such as resistance to extremes
of temperature and pressure, resistance to corrosive
acids and bases, and inertness to oxidizing agents.13
Furthermore, both sulfonate and sulfonimide functional
groups present in ionic liquids are thought to be hydro-
lytically more stable than, for example, the ester linkage
in organosulfate-based ionic liquids such as the hydro-
philic [bmim][octylsulfate] at elevated temperatures.
Both [bdmim][Tf2N] and [bdmim][PFBuSO3] ionic liq-
uids are miscible with polar organic solvents—metha-
nol, acetone, dichloromethane, ethyl acetate, and
acetonitrile—and insoluble in less polar species such as
diethyl ether, n-hexane, and toluene. Like ionic liquids
incorporating PF6, the two new ionic liquids are immis-
cible with water.
In this work, we demonstrated for the first time the syn-
thesis of fused tetrahydro-b-carbolinequinoxalinones in
both [bdmim][Tf2N] and [bdmim][PFBuSO3] ionic liq-
uids. For compounds of tetrahydro-b-carbolinequinox-
alinones, the structure of tetrahydro-b-carboline is a
central core for many biologically important indole
alkaloids16 and the moiety of quinoxalinone often exhib-
its a wide spectrum of biological activities such as anti-
HIV agents, antihypertensives, and ligands for a number
of protein receptors.17 Most recently, several new qui-
noxalinone-based antithrombotic agents were synthe-
sized and reported as highly specific subnanomolar
inhibitors for blood coagulation factor Xa.18 Scheme 1
outlines our total synthesis of fused tetrahydro-b-carbo-
linequinoxalinones in ionic liquids.19 Three reactions
were incorporated in the synthesis: the Pictet–Spengler
condensation16,6a used in step a, the nucleophilic aro-
matic substitution as step b, and the cyclization-upon-
reduction reaction for the last step. With respect to the
first step of synthesis, in our laboratory we have rou-
tinely employed the Pictet–Spengler reaction to con-
struct tetrahydro-b-carbolines.6a Under our optimized
condition in ionic liquid, it required only a short reac-
tion time to complete the reaction (Table 1). As shown
in Table 1, all aldehydes studied complete the Pictet–
Spengler reaction in less than 2 h. The isolated yields
for the Pictet–Spengler adducts were good to excellent
(75–96%). Under our experimental condition, the
desired products were isolated as a mixture of two dia-
stereoisomers with the cis/trans ratios close to unity,
that is, no apparent preference for a particular product
isomer was resulted.6a The tetrahydro-b-carbolines
obtained were directly used for the subsequent step of
nucleophilic aromatic substitution reaction to set up
for the core preparation of quinoxalinones. Quinoxali-
nones have been studied and prepared both in solution
and on solid support.20 Our quinoxalinone synthesis in
ionic liquids first involved the direct coupling of 2-nitro-
fluorobenzene with sterically hindered and less reactive
tetrahydro-b-carbolines. This problem of unusual low
reactivity of the secondary amine of tetrahydro-b-carb-
olines has been previously encountered by us and oth-
ers.6a After a few experimental trials, we were pleased
to find that these ipso-fluoro displacement reactions
proceeded smoothly to afford arylamines in both ionic
CH3
N
CH3
N
N(CF3SO2)2
C4F9SO3
H3C
N
nBu
H3C
N
nBu
[bdmim][Tf2N]
[bdmim][PFBuSO3]

M.-C. Tseng et al. / Tetrahedron Letters 46 (2005) 6131–6136
6133
CO2Me
NH2
CO2Me
NH
(a)
(b)
N
H
N
H
R
CO2Me
NO2
O
H
N
(c)
NH
N
N
H
N
H
R
R
Scheme 1. Synthesis of tetrahydro-b-carbolinequinoxalinones. Reagents and conditions: (step a) L-tryptophan methyl ester (0.39 mmol), 10% TFA,
ionic liquid (0.2 mL), aldehyde (4 equiv), 70 ꢁC; (step b) 1-fluoro-2-nitrobenzene (2 equiv), DMAP (2 equiv), ionic liquid (0.2 mL), 70 ꢁC; (step c)
SnCl2 (4 equiv), ionic liquid/ethanol (1:1, 0.2 mL), 70 ꢁC.
Table 1. Synthesis of fused tetrahydro-b-carbolinequinoxalinones in ionic liquids of [bdmim][Tf2N] and [bdmim][PFBuSO3]a
Entry
Products
Ionic liquid
Step a
Yieldb (%)
Step b
Yieldb (%)
Step c
Yieldb (%)
Reaction
time (h)
Reaction
time (h)
Reaction
time (h)
O
H
NH
N
1
2
[bdmim][Tf2N]
[bdmim][Tf2N]
1.5
0.6
82
80
3
8
87
74
4
64
66
N
H
OCH3
O
H
NH
N
3.5
N
H
O
H
NH
N
3
4
[bdmim][Tf2N]
0.7
0.9
75
81
4
5
90
69
4
71
61
N
H
Cl
O
H
NH
N
[bdmim][PFBuSO3]
3.5
N
H
F
O
H
NH
NH
N
5
6
[bdmim][PFBuSO3]
[bdmim][PFBuSO3]
1.5
91
96
8
5
69
93
3
3
61
62
N
H
O
H
N
1
N
H
CH3
a The reaction conditions: (step a) L-tryptophan methyl ester (0.39 mmol), 10% TFA, ionic liquid (0.2 mL), aldehyde (4 equiv), 70 ꢁC; (step b) 1-
fluoro-2-nitrobenzene (2 equiv), DMAP (2 equiv), ionic liquid (0.2 mL), 70 ꢁC; (step c) SnCI2 (4 equiv), ionic liquid/ethanol (1:1, 0.2 mL), 70 ꢁC.
b Isolated yield.
liquids at 70 ꢁC with respectable yields (69–93%) (Table
1). Conventional methods for arylamine synthesis typi-
cally involve the use of excessive bases and polar sol-
vents such as DMF or DMSO; they often took days
at ambient temperature21 or much longer hours at high
temperatures to complete the reactions.22 It is noted that
our approach of using ionic liquid as the reaction
medium was effective with sterically hindered and substi-
tuted tetrahydro-b-carbolines.23 Moreover, if this nucleo-
philic aromatic substitution reaction was conducted in

6134
M.-C. Tseng et al. / Tetrahedron Letters 46 (2005) 6131–6136
Figure 1. 1H NMR spectrum of the 1-fluoro-2-nitrobenzene conjugated [bmim][PF6] adduct in DMSO-d6.
the commonly used [bmim][PF6] ionic liquid under the
same experimental condition, the desired arylamine
products were obtained with low yields (20% and 19%
for entries 2 and 6 in step b reaction, respectively) and
found to be contaminated with the 1-fluoro-2-nitrobenz-
ene-conjugated [bmim][PF6] adduct (1). The chemical
nature of adduct 1 could be readily verified and unam-
biguously confirmed by proton NMR (Fig. 1). The dis-
appearance of the C-2 proton signal at d 9.07 ppm
clearly indicated the site of conjugation of [bmim][PF6]
with the electrophilic 1-fluoro-2-nitrobenzene. This
chemical reactivity of [bmim][PF6] ionic liquid to elec-
trophilic compounds under basic conditions has previ-
ously been reported.4,6b We performed the last,
cyclization-upon-reduction reaction (step 3 in Scheme
1) without the aid of additional bases. Our results indi-
cated that, under the standard reduction condition by
tin chloride and the subsequent intramolecular cycliza-
tion, the desired tetrahydro-b-carbolinequinoxalinones
were readily formed as sole products in moderate overall
isolated yields (34–55%). Furthermore, under the exper-
imental conditions developed in this study, only minute
amounts of ionic liquids were used to dissolve all
required starting materials and, in such high concentra-
tions, the total synthesis of tetrahydro-b-carbolinequin-
oxalinones could therefore be readily achieved in
short reaction time. Accordingly, two new ionic liquids
developed in this work apparently are chemically stable
to all reagents and conditions employed in this study
and therefore should emerge as useful replacements
for the popular PF6-based ionic liquids and other
volatile organic solvents commonly used in organic
synthesis.
uids open exciting perspectives of use as solvents for
synthetic applications of many heterocycles and non-
heterocycles of biological significance. Furthermore,
these ionic liquids may enable new applications that
are not possible with conventional solvents.
Acknowledgments
We gratefully acknowledge support of this work
through grants from the National Science Council
(NSC93-2113-M-194-019, NSC92-2751-B-001-014, and
NSC92-2218-E-194-015).
References and notes
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In this study, we report two new ionic liquids,
[bdmim][Tf2N] and [bdmim][PFBuSO3], that appear to
fulfill the requirement as inert solvents in organic syn-
thesis. We have demonstrated that both ionic liquids
were well suited for the three-step synthesis of fused tetra-
hydro-b-carbolinequinoxalinones. These new ionic liq-

M.-C. Tseng et al. / Tetrahedron Letters 46 (2005) 6131–6136
6135
H. Tetrahedron 2003, 59, 2253–2258; (e) Lourenco, N. M.
T.; Afonso, C. A. M. Tetrahedron 2003, 59, 789–794; (f)
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Reichert, W. M.; Griffin, S. T.; Rogers, R. D. Ind. Eng.
Chem. Res. 2000, 39, 3596–3604.
0.90–1.33 (m, 2H, CH2), 1.64–1.72 (m, 2H, CH2), 2.57 (s,
3H, CH3), 3.74 (s, 3H, NCH3), 4.09 (t, 2H, J = 7.24 Hz,
NCH2), 7.59 (d, 1H, J = 1.96 Hz, C@CH), 7.62 (d, 1H,
J = 2.00 Hz, C@CH). 13C NMR (100 MHz, DMSO-d6) d
9.3, 13.5, 19.0, 31.3, 34.8, 47.5, 118.1, 119.7 (q,
JCF = 320 Hz, CF3), 121.0, 122.5, 144.4; FAB-HRMS
m/z [M]+ calcd = 153.1386, obsd = 153.1390.
6. (a) Yen, Y.-H.; Chu, Y.-H. Tetrahedron Lett. 2004, 45,
8137–8140; (b) Hsu, J.-C.; Yen, Y.-H.; Chu, Y.-H.
Tetrahedron Lett. 2004, 45, 4673–4676.
11. Morrison, D. W.; Forbes, D. C.; Davis, J. H., Jr.
Tetrahedron Lett. 2001, 42, 6053–6055.
12. Bonhote, P.; Dias, A.-P.; Papageorgiou, N.; Kalyanasun-
daram, K.; Gratzel, M. Inorg. Chem. 1996, 35, 1168–1178.
13. Chambers, R. D. Fluorine in Organic Chemistry; Wiley-
Interscience: New York, 1973.
14. Koch, V. R.; Nanjundiah, C.; Battista; Appetecchi, G.;
Scrosati, B. J. Electrochem. Soc. 1995, 142, L116–L118.
15. Using the same experimental procedure for [bdmim][PF-
BuSO3] synthesis,10 we also prepared the [bmim][PF-
BuSO3] ionic liquid and found that it is, as expected, a
liquid at ambient temperature.
16. Cox, E. D.; Cook, J. M. Chem. Rev. 1995, 95, 1797–1842.
17. Chicharro, R.; de Castro, S.; Reino, J. L.; Aran, V. J. Eur.
J. Org. Chem. 2003, 2314–2326.
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K. Green Chem. 2003, 5, 236–239; (b) Davis, J. H.; Fox, P.
A. Chem. Commun. 2003, 1209–1212; (c) Wasserscheid, P.;
van Hall, R.; Bosmann, A. Green Chem. 2002, 4, 400–404;
(d) Cammarata, L.; Kazarian, S. G.; Salter, P. A.; Welton,
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S. I.; Mancheno, D.; Castro, S.; Behaj, V.; Cohen, J. I.;
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8. Earle, M. J.; Katdare, S. P.; Seddon, K. R. Org. Lett.
2004, 6, 707–710.
9. [bdmim][Tf2N] ionic liquid was previously prepared and
solely used to investigate its affinity with water by infrared
spectroscopy.7d
18. Willardsen, J. A.; Dudley, D. A.; Cody, W. L.; Chi, L.;
McClanahan, T. B.; Mertz, T. E.; Potoczak, R. E.;
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Edmunds, J. J. J. Med. Chem. 2004, 47, 4089–4099.
19. General procedure for the synthesis of tetrahydro-b-
carbolinequinoxalinones. L-Tryptophan methyl ester
hydrochloride (0.393 mmol) was dissolved in an ionic
liquid (0.2 mL; [bdmim][Tf2N] or [bdmim][PFBuSO3])
containing 10% (v/v) trifluoroacetic acid. The aldehyde
(1.57 mmol) was added in one portion to the stirred
mixture at 70 ꢁC and the reaction was allowed to proceed
until tryptophan methyl ester was completely consumed as
indicated by TLC (for reaction time, see Table 1). To this
crude reaction mixture was added ether, the products were
extracted with water, and the resulting aqueous solution
was lyophilized to afford solid tetrahydro-b-carboline
products with isolated yields ranging from 75% to 96%.
The obtained Pictet–Spengler adduct was then mixed with
N,N-dimethyl pyridine (2 equiv) in ionic liquid (0.2 mL;
[bdmim][Tf2N] or [bdmim][PFBuSO3]). To the reaction
solution, 1-fluoro-2-nitrobenzene (0.136 mmol) was added
to proceed the nucleophilic aromatic substitution reaction.
The reaction was carried out at 70 ꢁC (for reaction time,
see Table 1). After the completion of the substitution
reaction, the nitro aryl products were directly purified by
flash chromatography to give a yellow solid with good to
excellent yields (74–93%).
10. Preparation and characterization of [bdmim][PFBSO3]
and [bdmim][Tf2N] ionic liquids: To a round-bottomed
flask containing 1,2-dimethylimidazole (15.0 g, 156 mmol)
was added 1-bromobutane (18.5 mL, 172 mmol). The
mixture was stirred and refluxed at 80 ꢁC for 2 h. Using
iodine for compound visualization, TLC could be
employed to monitor the progress of the reaction. The
resulting viscous reaction solution was cooled to room
temperature and mixed with water (20 mL), and then
washed with ethyl acetate (3 · 20 mL). The residual ethyl
acetate present in aqueous solution was removed by
heating to 60 ꢁC under reduced pressure. The lyophiliza-
tion of the aqueous solution afforded the 1-n-butyl-2,3-
dimethylimidazolium bromide ([bdmim][Br]) with good
isolated yield (88%, 32.8 g).
Synthesis of [bdmim][PFBuSO3]: To a solution containing
[bdmim][Br] (8 g, 34 mmol) and water (20 mL) was added
potassium nonafluorobutanesulfonate (11.6 g, 34 mmol).
The mixture was allowed to proceed the ion exchange for
12 h at room temperature. Two phases were formed in the
mixture solution. The resulting solution was diluted with
dichloromethane (20 mL) and then washed with water
(3 · 20 mL). Removal of the solvent under reduced
pressure afforded the 1-n-butyl-3-methylimidazolium per-
fluoro-1-butanesulfonate ([bdmim][PFBuSO3]) with good
isolated yield (88%, 13.2 g); mp 59–61 ꢁC. 1H NMR
(400 MHz, DMSO-d6) d 0.89 (t, 3H, J = 7.40 Hz, CH3),
1.23–1.32 (m, 2H, CH2), 1.66–1.73 (m, 2H, CH2), 2.57 (s,
3H, CH3), 3.73 (s, 3H, NCH3), 4.09 (t, 2H, J = 7.24 Hz,
NCH2), 7.59 (d, 1H, J = 1.96 Hz, C@CH), 7.63 (d, 1H,
J = 2.00 Hz, C@CH). 13C NMR (100 MHz, DMSO-d6) d
9.3, 13.4, 19.1, 31.4, 34.8, 47.5, 105.0–120.0 (m, C4F9),
The yellow nitro aryl compounds were dissolved in the
solution of ionic liquid/ethanol (1:1, v/v; 0.2 mL) contain-
ing SnCl2 (4 equiv) to carry out the final cyclization-upon-
reduction reaction at 70 ꢁC (for reaction time, see Table 1).
The reaction was allowed to proceed until the nitro
compounds were completely consumed and cyclized as
monitored by TLC. Upon completion of the total three-
step synthesis, the solution mixture containing the desired
tetrahydro-b-carbolinequinoxalinones was concentrated
under reduced pressure and purified by silica gel flash
chromatography (ethyl acetate/hexane = 2:3). The final
tetrahydro-b-carbolinequinoxalinone products were affor-
ded as a colorless solid with overall isolated yields of 34–
55%.
121.1,
122.5,
144.5;
FAB-HRMS
m/z
[M]+
calcd = 153.1386, obsd = 153.1392.
Synthesis of [bdmim][Tf2N]: To a solution containing
[bdmim][Br] (8.0 g, 34 mmol) and water (20 mL) was added
bistrifluoromethanesulfonimide lithium salt (9.85 g,
34 mmol). The mixture was allowed to proceed the ion
exchange for 12 h in room temperature. Two phases were
formed in the mixture solution. The resulting solution was
diluted with dichloromethane (20 mL) and then washed
with water (3 · 20 mL). Removal of solvent under reduced
pressure afforded the 1-n-butyl-3-methylimidazolium
bistrifluoromethanesulfonimide ([bdmim][Tf2N]) with
excellent isolated yield (98%, 15.1 g). 1H NMR
(400 MHz, DMSO-d6) d 0.90 (t, 3H, J = 7.28 Hz, CH3),
20. For the synthesis of quinoxalin-2-ones in solution, see: (a)
Willardsen, J. A.; Dudley, D. A.; Cody, W. L.; Chi, L.;
McClanahan, T. B.; Mertz, T. E.; Potoczak, R. E.;
Narasimhan, L. S.; Holland, D. R.; Rapundalo, S. T.;
Edmunds, J. J. J. Med. Chem. 2004, 47, 4089–4099; (b)
Chen, B.-C.; Zhao, R.; Bednarz, M. S.; Wang, B.;

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979; For the solid-phase synthesis of quinoxalin-2-ones,
see: (a) Lee, J.; Murray, W. V.; Rivero, R. A. J. Org.
Chem. 1997, 62, 3874–3879; (b) Morales, G. A.; Gorbett,
J. W.; DeGrado, W. F. J. Org. Chem. 1998, 63, 1172–
1177; (c) Mazurov, A. Tetrahedron Lett. 2000, 41, 7–
10.
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22. (a) Cho, Y. H.; Park, J. C. Tetrahedron Lett. 1997, 38,
8331–8334; (b) Brown, G. R.; Foubister, A. J.; Ratcliffe, P.
D. Tetrahedron Lett. 1999, 40, 1219–1222.
23. Yadav, J. S.; Reddy, B. V. S.; Basak, A. K.; Narsaiah, A.
V. Tetrahedron Lett. 2003, 44, 2217–2220.