Synthesis of 1,3-Dialkyl-1,2,3-triazolium ionic liquids and their applications to the baylis-hillman reaction

Article abstract of DOI:10.1021/jo100618d

Novel 1,3-dialkyl-1,2,3-triazolium ionic liquids were synthesized via click reactions using 1-trimethylsilylacetylene and alkyl azides and were efficient reaction media for the Baylis-Hillman reaction. The problems associated with deprotonation of the C-2

Full text of DOI:10.1021/jo100618d

pubs.acs.org/joc
Synthesis of 1,3-Dialkyl-1,2,3-triazolium Ionic Liquids and Their
Applications to the Baylis-Hillman Reaction
Yunkyung Jeong and Jae-Sang Ryu*
Center for Cell Signaling & Drug Discovery Research, College of Pharmacy and Division of Life &
Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu,
Seoul 120-750, Korea
ryuj@ewha.ac.kr
Received April 1, 2010
Novel 1,3-dialkyl-1,2,3-triazolium ionic liquids were synthesized via click reactions using 1-trimethyl-
silylacetylene and alkyl azides and were efficient reaction media for the Baylis-Hillman reaction. The
problems associated with deprotonation of the C-2 hydrogen of [bmim][PF6] could be suppressed in
the reaction of [bmTr][PF6] or [bmTr][NTf2]. 1,3-Dialkyl-1,2,3-triazolium ionic liquids are chemically
inert under basic conditions and more suitable media for the reactions involving bases than the
common 1,3-dialkylimidazolium ionic liquids.
SCHEME 1. Baylis-Hillman Reaction
Introduction
The Baylis-Hillman reaction is one of the most important
C-C bond-forming processes in modern organic synthesis.1
This versatile reaction basically involves a reaction between
an aldehyde and an activated alkene in the presence of a
tertiary amine base to afford a densely functionalized pro-
duct (Scheme 1). Since the Baylis-Hillman reaction was first
reported by Baylis and Hillman in 1972,2 it has attracted
organic chemists’ interest due to its inherent advantages,
including a high atom economy, organocatalysis, mild reac-
tion conditions, and wide functional group compatibility.
However, this reaction sometimes has a long reaction time
and moderate yields.1 In particular, the reactions with acrylic
esters were quite sluggish, and the hydrolysis of acrylic esters
in aqueous media could be a potential side reaction.3 To
circumvent these problems, several reaction conditions have
been developed using supercritical CO2,4 ultrasound,5 mi-
crowave irradiation,6 and ionic liquids.7 Most notably, the
use of ionic liquids as an alternate solvent has been exten-
sively studied for the past decade.7
Ionic liquids (ILs) are defined as organic salts, mostly
consisting of organic cations and inorganic anions, which
melt below 100 °C. Since ethylammonium nitrate was first
reported in 1914,8 a number of cation types of ionic liquids
have been developed, including imidazolium, pyridinium,
ammonium, and phosphonium. Among them, imidazolium
cations like 1-butyl-3-methylimidazolium ([bmim]) are the
most commonly used as ionic liquids (1, Figure 1). However,
(1) For reviews, see: (a) Basavaiah, D.; Rao, K. V.; Reddy, R. J. Chem.
Soc. Rev. 2007, 36, 1581–1588. (b) Basavaiah, D.; Rao, A. J.; Satyanarayana,
T. Chem. Rev. 2003, 103, 811–891.
(2) (a) Baylis, A. B.; Hillman, M. E. D. Ger. Offen. 2 155 113, 1972. (b)
Hillman, M. E. D.; Baylis, A. B. US Patent 3 743 669, 1973. (c) Morita, K.; Suzuki,
Z.; Hirose, H. Bull. Chem. Soc. Jpn. 1968, 41, 2815. (d) Rauhut, M.; Currier, H.
US Patent 3 074 999, 1963.
(3) (a) Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001, 66, 5413–5418. (b)
Krishna, P. R.; Manjuvani, A.; Kannan, V.; Sharma, G. V. M. Tetrahedron
Lett. 2004, 45, 1183–1185.
(4) (a) Rose, P. M.; Clifford, A. A.; Rayner, C. M. Chem. Commun. 2002,
968–969. (b) Chandrasekhar, S.; Narsihmulu, C.; Saritha, B.; Sultana, S. S.
Tetrahedron Lett. 2004, 45, 5865–5867.
(5) Ge, S.-Q.; Hua, Y.-Y.; Xia, M. Ultrason. Sonochem. 2009, 16, 743–
746.
(6) Kundu, M. K.; Mukherjee, S. B.; Balu, N.; Padmakumar, R.; Bhat,
S. V. Synlett 1994, 444.
(7) Chowdhury, S.; Mohan, R. S.; Scott, J. L. Tetrahedron 2007, 63, 2363–
2389. and references therein.
(8) Sugden, S.; Wilkins, H. J. Chem. Soc. 1929, 1291–1298. and references
therein.
DOI: 10.1021/jo100618d
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Published on Web 05/26/2010
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Jeong and Ryu
JOCArticle
FIGURE 1. 1-Butyl-3-methylimidazolium ([bmim]) and 1-butyl-2,3-
dimethylimidazolium ([bdmim]) ionic liquids.
SCHEME 2. Side Reaction of 1-Butyl-3-methylimidazolium
([bmim]) Ionic Liquid with Benzaldehyde
FIGURE 2. Design of 1,3-dialkyl-1,2,3-triazolium ionic liquids.
SCHEME 3. Synthesis of 1-Benzyl-3-methyl-1,2,3-triazolium
Ionic Liquids [BnmTr][X]a
the C-2 proton of the 1,3-dialkylimidazolium cation is acidic
and removed even under mild basic conditions.9 The gener-
ated carbene, which could act as a ligand for metal catalysts,
showed advantageous effects in the Heck reaction and in the
Suzuki coupling.7 However, the carbene significantly inhib-
ited the desired chemical transformations in the Horner-
Wadsworth-Emmons reaction, Knoevenagel condensation,
Claisen-Schmidt condensation, and the Baylis-Hillman
reaction.7 In the case of the Baylis-Hillman reaction,
deprotonation at the imidazolium C-2 position produced
a nucleophile, which directly reacted with the aldehyde,
leading to the adduct 3 (Scheme 2).9 The undesired side
reaction was partly suppressed by introducing a substituent
at the C-2 position of imidazolium salts,10 e.g., 1-butyl-2,3-
dimethylimidazolium ([bdmim]) (2, Figure 1). However, the
C-2 methyl group also undergoes slow proton exchange in
the presence of triethylamine.11 Therefore, there is a need
for chemically inert ionic liquids suitable for reactions
involving strong bases.12
aReagents and conditions: (a) CuSO4, sodium ascorbate, t-BuOH/
H2O (1/1), rt, 1 d; (b) TBAF, THF, rt, 6 h; (c) CH3I, 80 °C, 17 h; (d) 9a:
LiNTf2, H2O, 40 °C, 1 d; 9b: KOTf, H2O, 40 °C, 1 d; 9c: LiPF6, H2O,
40 °C, 1 d; 9d: AgBF4, H2O, 40 °C, 1 d.
similar ionic liquid properties and structural features to con-
ventional [bmim] cations, while the problematic acidic C-2
proton of 1,3-dialkylimidazolium cation has been replaced by
the nitrogen of the 1,3-dialkyl-1,2,3-triazolium cation to ob-
tain the stability under basic conditions. Since the properties of
ionic liquids can be controlled to a large degree by varying the
nature of either the cation or the anion, it is particularly
interesting to test whether the introduction of a third nitrogen
impacts the chemical or physical properties or charge distribu-
tion of the ring relative to the 1,3-imidazole.
In this context, we herein report the development of a
chemically inert 1,2,3-triazolium-based ionic liquid and its
application to the Baylis-Hillman reaction. The stereotype
of our novel 1,2,3-triazolium ionic liquid is shown in Figure
2. The 1 and 3 positions of 1,2,3-triazolium13 have been
functionalized with n-butyl, methyl, or benzyl to maintain
(9) (a) Santos, L. S.; Da Silveira Neto, B. A.; Consorti, C. S.; Pavam,
C. H.; Almeida, W. P.; Coelho, F.; Dupont, J.; Eberlin, M. N. J. Phys. Org.
Chem. 2006, 19, 731–736. (b) Aggarwal, V. K.; Emme, I.; Mereu, A. Chem.
Commun. 2002, 1612–1613.
(10) Hsu, J.-C.; Yen, Y.-H.; Chu, Y.-H. Tetrahedron Lett. 2004, 45, 4673–
4676.
(11) Handy, S. T.; Okello, M. J. Org. Chem. 2005, 70, 1915–1918.
Results and Discussion
Synthesis of 1,2,3-Triazolium Ionic Liquid. The 1-benzyl-3-
methyl-1,2,3-triazolium salts ([BnmTr][X]) were easily accessed
by Cu-catalyzed Huisgen 1,3-dipolar cycloaddition using ben-
zyl azide (4) and 1-trimethylsilylacetylene (5) (Scheme 3), which
proved useful for the synthesis of unsymmetrically substituted
ꢀ
(12) Jurcık, V.; Wilhelm, R. Green Chem. 2005, 7, 844–848.
´
(13) For 1,3,4-trialkyl-1,2,3-triazolium and pyrrolidine-tethered 1,3,4-
trialkyl-1,2,3-triazolium, see: (a) Hanelt, S.; Liebscher, J. Synlett 2008,
1058–1060. (b) Yacob, Z.; Shah, J.; Leistner, J.; Liebscher, J. Synlett 2008,
2342–2344.
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SCHEME 4. Synthesis of 1-Butyl-3-methyl-1,2,3-triazolium
Ionic Liquids ([bmTr][X])a
SCHEME 5. Synthesis of 1,3-Dibutyl-1,2,3-triazolium Ionic
Liquids ([dbTr][X])a
aReagents and conditions: (a) NaH, n-butyl iodide (5 equiv), CH3CN,
80 °C, 19 h; (b) n-butyl iodide (1 equiv), neat, 80 °C, 15 h; (c) (17a) LiNTf2,
H2O, 40 °C, 15 h; (17b) KOTf, H2O, 40 °C, 11 h; (17c) LiPF6, H2O, 40 °C,
22 h; (17d) AgBF4, H2O, 40 °C, 20 h.
aReagents and conditions: (a) NaN3, DMF, 80 °C, 20 h; (b) 5, CuI,
DMF, 80 °C, 40 h; (c) TBAF, THF, rt, 6 h.; (d) CH3I, 80 °C, 1 d; (e) 14a:
LiNTf2, H2O, 40 °C, 1 d; 14b: KOTf, H2O, 40 °C, 1 d; 14c: LiPF6, H2O,
40 °C, 1 d; 14d: AgBF4, H2O, 40 °C, 1 d.
TABLE 1. Thermal Decomposition Temperatures of 1,2,3-Triazolium
Salts
1,3-dialkyl-1,2,3-triazolium because direct alkylation of the 1H-
1,2,3-triazole generally produces mixtures of regioisomers or
symmetrically dialkylated products. The “click” reaction of
benzyl azide (4) and 1-trimethylsilylacetylene (5) provided
complete conversion to triazole 6, the TMS of which was
removed by TBAF. 1-Benzyl-1,2,3-triazole (7) was quaternized
at N-3 by reaction with equivalent amounts of methyl iodide
under neat reaction conditions at 80 °C to afford 1,2,3-triazo-
lium iodide salt 8 in nearly quantitative yield and high purity.
Not surprisingly, this iodide salt has a rather high melting
point (127.5-129.5 °C). Metathesis of 8 with LiNTf2, KOTf,
LiPF6, or AgBF4 in water afforded new quaternary salts 9a-d
in moderate to excellent yields. Compounds 9a and 9b are
liquids at room temperature. Compounds 9c and 9d are solids
that melt below 100 °C. Our 1,2,3-triazolium salts 9c and 9d
have slightly lower melting points (9c: 90.5 °C, 9d: 74.3 °C)
compared to the corresponding imidazolium salts (e.g., 1-benzyl-
3-methylimidazolium hexafluorophosphate ([Bnmim][PF6]):
130.6 °C,14 1-benzyl-3-methylimidazolium tetrafluoroborate
([Bnmim][BF4]): 77 °C15).
entry
ionic liquidsa
Tdb (°C)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
[BnmTr][I] (8)
178
278
160
287
284
196
333
170
355
340
350
195
341
345
[BnmTr][NTf2] (9a)
[BnmTr][OTf] (9b)
[BnmTr][PF6] (9c)
[BnmTr][BF4] (9d)
[bmTr][I] (13)
[bmTr][NTf2] (14a)
[bmTr][OTf] (14b)
[bmTr][PF6] (14c)
[bmTr][BF4] (14d)
[dbTr][NTf2] (17a)
[dbTr][OTf] (17b)
[dbTr][PF6] (17c)
[dbTr][BF4] (17d)
a[BnmTr] = 1-benzyl-3-methyl-1,2,3-triazolium, [bmTr] = 1-butyl-3-
methyl-1,2,3-triazolium, [dbTr] = 1,3-dibutyl-1,2,3-triazolium. Thermal
decomposition temperature.
b
TABLE 2. Miscibilitya of Various Ionic Liquids in Organic Solvents
with Dielectric Constant εb
ionic liquidsc
hexane
Et2O
EtOAc
CH2Cl2
H2O
Next, we prepared 1-butyl-3-methyl-1,2,3-triazolium salts,
which are structurally similar to the most commonly used
[bmim] ionic liquids. The 1-butyl-3-methyl-1,2,3-triazolium
salts ([bmTr][X]) (14a-d) were prepared in three steps
(Scheme 4). The n-butyl azide was generated in situ from
n-butyl chloride (10) and NaN3, whereupon it was captured
by 1-trimethylsilylacetylene via a Cu-catalyzed “click” reac-
tion. Unlike the click reaction using benzyl azide (4), the click
reaction with n-butyl azide led to the formation of the 4-TMS-
substituted 1,2,3-triazole product 11 and 4,5-unsubstituted
1,2,3-triazole analogue 12. The subsequent deprotection of
TMS converted 11 to 12, which was readily quaternized with
methyl iodide under neat conditions at 80 °C in 97% yield.
The regiochemistry of N-methylation was unambiguously
[BnmTr][NTf2] (9a)
[BnmTr][OTf] (9b)
[bmTr][I] (13)d
[bmTr][NTf2] (14a)
[bmTr][OTf] (14b)
[bmTr][PF6] (14c)d
[bmTr][BF4] (14d)
[dbTr][I] (16)
[dbTr][NTf2] (17a)
[dbTr][OTf] (17b)
[dbTr][PF6] (17c)
[dbTr][BF4] (17d)
am = miscible, nm = nonmiscible, pm = partially miscible. bDielectric
constant ε at 20 °C; hexane = 1.89; Et2O = 4.34; EtOAc = 6 (25 °C);
CH2Cl2 = 9.08; H2O = 78.54. c[BnmTr] = 1-benzyl-3-methyl-1,2,3-triazo-
lium, [bmTr] = 1-butyl-3-methyl-1,2,3-triazolium, [dbTr] = 1,3-dibutyl-
1,2,3-triazolium. dMiscibility was checked when ionic liquids melted.
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
nm
m
m
m
nm
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
m
nm
pm
pm
nm
pm
nm
m
m
nm
pm
nm
m
nm
nm
nm
(14) Peng, J. J.; Li, J. Y.; Bai, Y.; Gao, W. H.; Qiu, H. Y.; Wu, H.; Deng,
Y.; Lai, G. Q. J. Mol. Catal. A: Chem. 2007, 278, 97–101. [Bnmim][PF6] is
commercially available, and the melting point obtained from the Aldrich
database is 136 °C.
(15) SakiZdeh, K.; Olson, L. P.; Cowdery-Corvan, P. J.; Ishida, T.;
Whitcomb, D. R. US Patent 7 163 786, 2007. [Bnmim][BF4] is commercially
available, and the melting point obtained from Aldrich database is 77 °C.
determined by 1D-NOE experiments (see the Supporting
Information). Finally, the desired [bmTr] salts (14a-d) were
obtained by a metathesis reaction of iodide salt 13 with LiNTf2,
KOTf, LiPF6, or AgBF4. All of the synthesized [bmTr] salts 13
and 14a-d were liquids at room temperature when they were
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JOCArticle
TABLE 4. Baylis-Hillman Reactions with Methyl Acrylate and Various
Aldehydes in [bmTr][NTf2] (14a)a
FIGURE 3. Miscibility of [bmTr][PF6] in common organic solvents.
Picture was taken when IL melted: (A) hexane (top layer) and
[bmTr][PF6] (bottom layer); (B) Et2O (top layer) and [bmTr][PF6]
(bottom layer); (C) EtOAc and [bmTr][PF6] (miscible); (D) CH2Cl2
and [bmTr][PF6] (miscible); (E) H2O (top layer) and [bmTr][PF6]
(bottom layer).
TABLE 3. Baylis-Hillman Reactions of p-Chlorobenzaldehyde and
Methyl Acrylate in Various 1,2,3-Triazolium Ionic Liquidsa
entry
ionic liquid
R1
R2
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
[BnmTr][NTf2] (9a)
[BnmTr][OTf] (9b)
[bmTr][I] (13)
[bmTr][NTf2] (14a)
[bmTr][OTf] (14b)
[bmTr][PF6] (14c)
[bmTr][BF4] (14d)
[dbTr][I] (16)
[dbTr][NTf2] (17a)
[dbTr][OTf] (17b)
[dbTr][PF6] (17c)
[dbTr][BF4] (17d)
[bmim][PF6]
benzyl
benzyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
methyl
methyl
methyl
methyl
methyl
methyl
methyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
61
77
46
83
63
96
80
74
91
77
80
83
67
68
[bmim][NTf2]
aReaction conditions: p-chlorobenzaldehyde (144 mg, 1.00 mmol),
methyl acrylate (173 mg, 2.01 mmol), DABCO (230 mg, 2.01 mmol),
ionic liquid (0.1 mL), room temperature, 24 h.
aReaction conditions: aldehyde (1.00 mmol), methyl acrylate (173 mg,
2.01 mmol), DABCO (230 mg, 2.01 mmol), [bmTr][NTf2] (0.1 mL), room
temperature.
prepared. Interestingly, 13 and 14c were solidified very slowly
and melted at 42 and 47 °C, respectively. Once they melted,
they remained liquid for several hours at room temperature.
This phenomenon was also reported for the imidazolium-based
[mPhmim][PF6] ionic liquid having mp close to room tempera-
ture. It was also used as a solvent for the Baylis-Hillman
reaction.12
The 1,3-dibutyl-1,2,3-triazolium salts ([dbTr][X]) (17a-d)
were prepared via direct alkylation. 1H-1,2,3-Triazole (15)
was treated with 1 equiv of NaH before the addition of excess
n-butyl iodide in the CH3CN (Scheme 5). We obtained the
desired dialkylated product 16 as a sole product in 75% yield
in one step from commercially available 1H-1,2,3-triazole
(15). Alternatively, 16 could be synthesized from 1-butyl-
1,2,3-triazole (12) using 1 equiv of n-butyl iodide under neat
conditions in 95% yield. Metathesis of 16 in the presence of
LiNTf2, KOTf, LiPF6, or AgBF4 provided the desired [dbTr]
salts 17a-d as ionic liquids.
The three types of 1,2,3-triazolium salts, including [BnmTr],
[bmTr], and [dbTr] have been synthesized: 9a, 9b, 14a, 14b,
14d, 16, and 17a-d are liquids at room temperature; 9c, 9d, 13,
and 14c, solid salts at room temperature, melt below 100 °C.
Therefore, all 1,2,3-triazolium salts except 8 may be classified
as ionic liquids. Water content of some prepared triazolium
salts are given in the Experimental Section, and their thermal
decomposition temperatures were determined by thermogra-
vimetric analysis and described in Table 1. The thermal
stabilities of the 1,2,3-triazoliun compounds might be a con-
cern because they contain three nitrogens. However, they show
good thermal stabilities up to 355 °C (Table 1, entry 9). The
thermal stabilities of the prepared 1,2,3-triazolium salts depend
on the anion species. Iodide and TfO- dramatically reduce the
thermal stability with the onset of decomposition occurring
approximately 100 °C below the corresponding ionic liquids
with PF6-, Tf2N-, BF4- anions. Relative anion stabilities have
been suggested as PF6-, Tf2N-, BF4- . TfO-, I-.
4186 J. Org. Chem. Vol. 75, No. 12, 2010

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JOCArticle
TABLE 5. Baylis-Hillman Reactions with Methyl Acrylate and Various
Aldehydes in [bmTr][PF6] (14c)a
TABLE 6. Baylis-Hillman Reactions with Acrylonitrile and Various
Aldehydes in [bmTr][NTf2] (14a) a
aReaction conditions: aldehyde (1.00 mmol), methyl acrylate (173 mg,
2.01 mmol), DABCO (230 mg, 2.01 mmol), [bmTr][PF6] (0.1 mL), room
temperature.
aReaction conditions: aldehyde (1.00 mmol), acrylonitrile (107 mg,
2.01 mmol), DABCO (230 mg, 2.01 mmol), [bmTr][NTf2] (0.1 mL), room
temperature.
In general, the product and byproduct can be separated
from ionic liquid media by simple extraction with organic
solvents, which enables ionic liquids to be recycled. The
solubility of ionic liquid in organic solvents is an important
factor for recycling. Thus, we tested the solubilities of 1,2,3-
triazolium ionic liquids in several common organic solvents
(Table 2). The solubilities increase with the dielectric con-
stant of the solvents. The ionic salts do not dissolve in hexane
or Et2O, but their solubilities increase in CH2Cl2 or ethyl-
acetate. The solubility in H2O depends on the anion of the
ionic liquid. The NTf2 salts and the PF6 salts are not miscible
with H2O, but the BF4 salts are. The miscibility of the
representative 1,2,3-triazolium ionic liquid [bmTr][PF6] is
shown in Figure 3. With the novel ionic liquids in hand, we
then shifted our focus to the feasibility of the Baylis-Hillman
reaction in a variety of 1,2,3-triazolium ionic liquids.
first examined the Baylis-Hillman reaction of p-chloroben-
zaldehyde (1 mmol), methyl acrylate (2 mmol), and DABCO
(2 mmol) in the presence of 1,2,3-triazolium ionic liquids
(0.1 mL). All reactions were performed at ambient tempera-
ture for 24 h, and the product 18a was purified by column
chromatography. [bmTr][I] (13) and [bmTr][PF6] (14c) were
loaded as a liquid after slight warming. All 1,2,3-triazolium
ionic liquids were good reaction media for the Baylis-
Hillman reaction (Table 3). The results clearly demonstrate
that the Baylis-Hillman reaction can be greatly accelerated
in [bmTr][NTf2] (14a), [bmTr][PF6] (14c), and [dbTr][NTf2]
(17a) (entries 4, 6, and 9). In particular, we were interested in
the comparison of [bmim][PF6], [bmim][NTf2], and our
1,2,3-triazolium ionic liquids. Thus, the Baylis-Hillman
reaction in [bmim][PF6] or [bmim][NTf2] was conducted
under the same reaction conditions (entries 13 and 14). As
expected, almost all 1,2,3-triazolium ionic liquids except
[BnmTr][NTf2] (9a), [bmTr][I] (13), and [bmTr][OTf] (14b)
Baylis-Hillman Reaction in 1,2,3-Triazolium Ionic Liquid.
To compare the reaction rates in these novel ionic liquids, we
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JOCArticle
TABLE 7. Baylis-Hillman Reactions with Acrylonitrile and Various
TABLE 8. Reuse of the Ionic Liquid [bmTr][PF6]a
Aldehydes in [bmTr][PF6] (14c)a
isolated yield (%)
cycle
method Ab
method Bc
1
2
3
4
95
89
98
100
99
99
100
100
aReaction conditions: p-chlorobenzaldehyde (431 mg, 3.01 mmol),
acrylonitrile (321 mg, 6.02 mmol), DABCO (690 mg, 6.03 mmol),
[bmTr][PF6] (0.3 mL), room temperature, 2 h. bIL was recovered by
Et2O extraction. cIL was recovered by column chromatography without
extraction (see the Experimental Section).
the electron-withdrawing resonance effect of the nitro group in
p-nitrobenzaldehyde and the nitrogen on the pyridine ring in
4-pyridinecarboxaldehyde is important in accelerating the Baylis-
Hillman reaction. On the other hand, the aliphatic aldehyde
(Table 4 and 5, entry 8) and aromatic aldehydes bearing
electron-donating groups (Table 4 and 5, entries 6 and 9) react
comparatively slowly and produce the corresponding adducts
in moderate yields. The current substrate scope in [bmTr]-
[NTf2] (14a) and [bmTr][PF6] (14c) is similar to that in [bmim]-
[PF6], but [bmTr][NTf2] (14a) and [bmTr][PF6] (14c) afford
reliably higher yields than [bmim][PF6].16
To demonstrate the extended applicability of [bmTr][NTf2]
(14a) and [bmTr][PF6] (14c) for the Baylis-Hillman reactions,
acrylonitrile was also tested as another Michael acceptor with
various aldehydes (Table 6 and Table 7). Compared to methyl
acrylate reactions, higher yields were achieved for all the
reactions in a shorter reaction time. Regardless of substituents,
almost all substrates were quantitatively converted to the
desired Baylis-Hillman products. On the other hand, furfural
only provided a moderate yield of the desired product 19d,
which was decomposed rapidly during the reaction (Table 7,
entry 4). 19d is rather unstable with [bmTr][PF6] (14c) reaction
conditions.17 However, this decomposition was not observed in
the [bmTr][NTf2] (14a) reaction, and 96% of isolated yield was
obtained (Table 6, entry 4).
aReaction conditions: aldehyde (1.00 mmol), acrylonitrile (107 mg,
2.01 mmol), DABCO (230 mg, 2.01 mmol), [bmTr][PF6] (0.1 mL), room
temperature.
Due to chemical stability and negligible volatility, ionic
liquids are amenable to multiple recycling cycles, which
considerably decrease the production of environmentally
harmful waste and the cost of a process, two criteria for
“green solvents”. Thus, we tested the recycling of our novel
[bmTr][PF6] (14c) for the reaction of p-chlorobenzaldehyde
and acrylonitrile. Upon the completion of the first reaction,
the product was extracted from [bmTr][PF6] (14c) with Et2O
and purified by column chromatography (method A). After
drying the ionic liquid under reduced pressure, a second
batch of aldehyde, acrylonitrile, and DABCO was added.
During recycling, 1H NMR analysis of the ionic liquid
showed a trace of DABCO. Alternately, [bmTr][PF6] (14c)
provided better yields than [bmim][PF6] (74-96% vs 67%).
In particular, the 1,2,3-triazolium ionic liquids with the same
PF6 anion (entries 6 and 11) afforded better yields than
[bmim][PF6] (96% and 80% vs 67%). Presumably, the
problems associated with deprotonation of C-2 hydrogen
of [bmim] cation could be suppressed in the reaction of
[bmTr] or [dbTr].
Based on the screening above, we selected [bmTr][NTf2]
(14a) and [bmTr][PF6] (14c) to explore the substrate scope of
the Baylis-Hillman reaction. We then investigated the Baylis-
Hillman reaction with a variety of aldehydes, such as aliphatic,
aromatic, and R,β-unsaturated aldehydes in [bmTr][NTf2] (14a)
(Table 4) and [bmTr][PF6] (14c) (Table 5). [bmTr][NTf2] (14a)
is a free-flowing liquid at room temperature and even at -78 °C.
All reactions occurred smoothly under standard conditions,
giving the corresponding products 18b-k. The reaction rates
were most rapid for substrates bearing 4-pyridyl or p-nitrophenyl
groups (Table 4 and 5, entries 1 and 4). These results imply that
(16) Rosa, J. N.; Afonso, C. A. M.; Santos, A. G. Tetrahedron 2001, 57,
4189–4193.
(17) The rapid decomposition of the product 19d was also reported in the
literature; see: Aggarwal, V. K.; Emme, I.; Fulford, S. Y. J. Org. Chem. 2003,
68, 692–700.
4188 J. Org. Chem. Vol. 75, No. 12, 2010

Jeong and Ryu
JOCArticle
was recovered without extraction by column chromatogra-
phy (method B). In both methods, [bmTr][PF6] (14c) could
be recycled up to four times without significant loss in yield
(Table 8).
reaction mixture was cooled to rt and extracted with CH2Cl2. The
combined extracts were washed with deionized water, dried over
anhydrous MgSO4, filtered, and concentrated. The residue was
further dried in vacuo (0.3 mmHg) to afford analytically pure 9a
1
(496 mg, 100%) as a brown liquid. Water content (0.07%). H
NMR (400 MHz, CDCl3): δ 8.38 (d, 1H, J = 1.6 Hz), 8.30 (d, 1H,
J = 1.6 Hz), 7.43 (brs, 5H), 5.69 (s, 2H), 4.33 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 132.1, 130.7, 130.6, 130.5, 130.0, 129.6, 119.9
(q, JCF = 319.1 Hz), 58.1, 40.7. LRMS (FAB) m/z (rel int): (pos)
91 ([C7H7]þ, 24), 174 ([C10H12N3]þ, 100). HRMS: m/z calcd for
C10H12N3 174.1031, found 174.1027. Anal. Calcd for C12H12F6-
N4O4S2: C, 31.72; H, 2.66; N, 12.33; S, 14.11. Found: C, 31.76; H,
2.70; N, 12.34; S, 14.37.
Conclusions
We have developed 1,3-dialkyl-1,2,3-triazolium ionic liquids
as stable and recyclable solvents. The applicability of the ionic
liquids as new reaction media is shown for the Baylis-Hillman
reaction. 1,3-Dialkyl-1,2,3-triazolium ionic liquids showed
comparable properties to imidazolium ionic liquids in terms
of thermal stability and miscibility. However, the 1,2,3-triazo-
lium ionic liquids are chemically inert under basic condition,
which makes them more suitable media for base-mediated
reactions. They could be used as base-stable surrogates for
imidazolium ionic liquids. Further applications of the 1,2,3-
triazolium-based ionic liquids to other important reactions are
underway in our laboratory.
1-Benzyl-3-methyl-1,2,3-triazolium Trifluoromethylsulfonate
(9b). In a screw cap vial, a mixture of 8 (1.00 g, 3.33 mmol)
and KOTf (0.67 g, 3.33 mmol) in deionized water (4.8 mL) was
stirred at 40 °C for 24 h. Upon completion of the reaction, the
reaction mixture was cooled to rt and extracted with CH2Cl2.
The combined organic extracts were washed with deionized
water, dried over anhydrous MgSO4, filtered, and concentrated.
The residue was further dried in vacuo (0.3 mmHg) to afford
analytically pure 9b (0.62 g, 57%) as a brown liquid. 1H NMR
(400 MHz, CDCl3): δ 8.88 (d, 1H, J = 1.6 Hz), 8.85 (d, 1H, J =
1.6 Hz), 7.51-7.49 (m, 2H), 7.41-7.39 (m, 3H), 5.81 (s, 2H),
4.39 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 132.4, 131.4, 131.0,
130.2, 129.7, 129.6, 120.7 (q, JCF = 318.3 Hz), 57.7, 40.8. LRMS
(FAB) m/z (rel int): (pos) 91 ([C7H7]þ, 30), 174 ([C10H12N3]þ,
100). HRMS: m/z calcd for C10H12N3 174.1031, found 174.1035.
1-Benzyl-3-methyl-1,2,3-triazolium Hexafluorophosphate (9c).
In a screw cap vial, a heterogeneous mixture of 8 (600 mg,
1.99 mmol) and LiPF6 (309 mg, 1.99 mmol) in deionized water
(2.0 mL) was stirred at 40 °C for 24 h. Upon completion of the
reaction, the reaction mixture was cooled to rt, and extracted with
CH2Cl2. The combined organic extracts were washed with de-
ionized water, dried over anhydrous MgSO4, filtered, and concen-
trated. The residue was further dried in vacuo (0.3 mmHg) to
afford analytically pure 9c (606 mg, 95%) as a yellow solid. Mp:
90.5-92.5 °C. Water content (0.02%). 1H NMR (400 MHz,
CDCl3): δ 8.38 (s, 1H), 8.27 (s, 1H), 7.45 (m, 5H), 5.70 (s, 2H),
4.36 (s, 3H). 1H NMR (400 MHz, DMSO-d6): δ 8.96 (d, 1H, J =
1.6 Hz), 8.84 (d, 1H, J = 1.6 Hz), 7.47-7.43 (m, 5H), 5.88 (s, 2H),
4.30 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 133.0, 132.1,
130.8, 129.2, 129.1, 128.8, 56.0, 39.5. LRMS (FAB) m/z (rel int):
(pos) 91 ([C7H7]þ, 26), 174 ([C10H12N3]þ, 100). HRMS: m/z calcd
for C10H12N3 174.1031, found 174.1036. Anal. Calcd for
C10H12F6N3P: C, 37.63; H, 3.79; N, 13.16. Found: C, 37.80; H,
3.88; N, 13.31.
1-Benzyl-3-methyl-1,2,3-triazolium Tetrafluoroborate (9d). In
a screw cap vial, a heterogeneous mixture of 4 (806 mg, 2.68 mmol)
and AgBF4 (521 mg, 2.68 mmol) in deionized water (2.7 mL) was
suspended at 40 °C for 24 h. Upon completion of the reaction,
the reaction mixture was cooled to rt and extracted with CH2Cl2.
The combined organic extracts were washed with deionized
water, dried over anhydrous MgSO4, filtered, and concentrated.
The residue was further dried in vacuo (0.3 mmHg) to afford
analytically pure 9d (603 mg, 62%) as a white solid. Mp:
74.3-76.3 °C. Water content (<0.01%). 1H NMR (400 MHz,
CDCl3): δ 8.55 (d, 1H, J = 1.6 Hz), 8.48 (d, 1H, J = 1.6 Hz),
7.48-7.45 (m, 2H), 7.45-7.42 (m, 3H), 5.72 (s, 2H), 4.36 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 132.3, 131.7, 130.9, 130.1,
129.6, 129.5, 57.5, 40.4. LRMS (FAB) m/z (rel int): (pos) 91
([C7H7]þ, 39), 174 ([C10H12N3]þ, 100). HRMS: m/z calcd for
C10H12N3 174.1031, found 174.1026. Anal. Calcd for
C10H12BF4N3: C, 46.01; H, 4.63; N, 16.10. Found: C, 46.15;
H, 4.57; N, 16.33.
Experimental Section
Synthesis of Ionic liquids. 1-Benzyl-4-trimethylsilyl-1,2,3-triazole
(6). Benzyl azide (266 mg, 2.00 mmol), trimethylsilylacetylene
(196 mg, 2.00 mmol), CuSO4 (16 mg, 0.10 mmol), and sodium
ascorbate (40 mg, 0.20 mmol) were suspended in a mixed solution
of tert-butyl alcohol/water (4 mL, 1/1) at rt. After the mixture was
stirred for 24 h, a brown crystalline solid precipitated from the
reaction. Filtration and washing with water afforded 6 (460 mg,
100%) as a brown solid. TLC: Rf 0.14 (3:1 hexane/EtOAc). Mp:
54-56 °C. 1H NMR (400 MHz, CDCl3): δ 7.43 (s, 1H), 7.39-7.35
(m, 3H), 7.27 (dd, 2H, J = 5.6, 1.6 Hz), 5.55 (s, 2H), 0.30 (s, 9H).
13C NMR (100 MHz, CDCl3): δ 148.3, 136.1, 130.2, 129.8, 129.7,
129.2, 54.6, 0.0. LRMS (FAB) m/z (rel int): 91 ([C7H7]þ, 63), 232
([M þ H]þ, 100). HRMS: m/z calcd for C12H18N3Si 232.1270,
found 232.1270.
1-Benzyl-1,2,3-triazole (7). To a solution of triazole 6 (2.26 g,
9.78 mmol) in anhydrous THF (9.8 mL) was dropwise added
TBAF (1 M in THF, 11.7 mL, 11.7 mmol). The reaction was
monitored for the disappearance of starting materials by TLC.
After 6 h at rt, the reaction mixture was concentrated in vacuo.
Column chromatography on silica gel (3:1 hexane/EtOAc)
afforded a desired triazole 7 (1.49 g, 96%) as a white solid.
1
TLC: Rf 0.12 (3:1 hexane/EtOAc). Mp: 61-63 °C. H NMR
(400 MHz, CDCl3): δ 7.71 (s, 1H), 7.47 (s, 1H), 7.38-7.36 (m,
3H), 7.28-7.25 (m, 2H), 5.57 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 134.9, 134.5, 129.3, 129.0, 128.2, 123.5, 54.2. LRMS
(FAB) m/z (rel int): 91 ([C7H7]þ, 63), 160 ([M þ H]þ, 80).
HRMS: m/z calcd for C9H10N3 160.0875, found 160.0872.
1-Benzyl-3-methyl-1,2,3-triazolium Iodide (8). In a screw cap
vial, a mixture of 7 (1.97 g, 12.4 mmol) and iodomethane (1.76 g,
12.4 mmol) was stirred at 80 °C for 17 h. Upon completion of the
reaction, the reaction mixture was concentrated in vacuo to afford
analytically pure 8 (3.62 g, 97%) as a pale yellow solid. Mp:
1
127.5-129.5 °C. Water content (0.03%). H NMR (400 MHz,
CDCl3): δ 9.39 (brs, 1H), 9.31 (brs, 1H), 7.61-7.58 (m, 2H),
7.44-7.42 (m, 3H), 5.97 (s, 2H), 4.51 (s, 3H). 1H NMR (400 MHz,
DMSO-d6): δ 8.98 (d, 1H, J = 1.2 Hz), 8.86 (d, 1H, J = 1.2 Hz),
7.49-7.42 (m, 5H), 5.89 (s, 2H), 4.30 (s, 3H). 13C NMR (100 MHz,
DMSO-d6): δ 133.0, 132.1, 130.8, 129.2, 129.0, 128.8, 56.0, 40.0.
LRMS (FAB) m/z (rel int): 91 ([C7H7]þ, 24), 174 ([C10H12N3]þ,
100). HRMS: m/z calcd for C10H12N3 174.1031, found 174.1027.
1-Benzyl-3-methyl-1,2,3-triazolium Bis(trifluoromethylsulfonyl)-
amide (9a). In a screw cap vial, a mixture of 8 (330 mg, 1.10 mmol)
and LiNTf2 (315 mg, 1.10 mmol) in deionized water (1.6 mL) was
stirred at 40 °C for 24 h. Upon completion of the reaction, the
1-Butyl-4-trimethylsilyl-1,2,3-triazole (11) and 1-Butyl-1,2,3-
triazole (12). In a screw cap vial, a mixture of 1-chlorobutane
(266 mg, 2.87 mmol) and sodium azide (476 mg, 7.32 mmol) in
J. Org. Chem. Vol. 75, No. 12, 2010 4189

Jeong and Ryu
JOCArticle
DMF (3.7 mL) was stirred at 80 °C for 20 h. After the mixture
was cooled to rt, trimethylsilylacetylene (359 mg, 3.66 mmol)
and CuI (70 mg, 366 μmol) were added, and the solution was
stirred at 80 °C for an additional 40 h. Upon completion of the
reaction, the reaction mixture was cooled to rt and concentrated
in vacuo. Column chromatography on silica gel (5:1 hexane/
EtOAc) afforded desired compounds 11 (114 mg, 16%) and 12
(229 mg, 64%) as light-yellow liquids.
for 24 h. Upon completion of the reaction, the reaction mixture was
cooled to rt, and extracted with IPA/CHCl3 (1/4). The combined
organic extracts were washed with deionized water, dried over
anhydrous MgSO4, filtered, and concentrated. The residue was
further dried in vacuo (0.3 mmHg) to afford analytically pure 14b
(213 mg, 84%) as a brown liquid. 1H NMR (400 MHz, CDCl3): δ
8.90 (d, 1H, J = 1.6 Hz), 8.90 (d, 1H, J = 1.6 Hz), 4.66 (t, 2H, J =
7.4 Hz), 4.44 (s, 3H), 2.03 (m, 2H), 1.42 (sextet, 2H, J = 7.4 Hz),
1.00 (t, 3H, J = 7.4 Hz). 13C NMR (100 MHz, CDCl3): δ 132.0,
131.1, 120.6 (q, JCF = 318.2 Hz), 54.0, 40.6, 31.3, 19.4, 13.3.
LRMS (FAB) m/z (rel int): (pos) 140 ([C7H14N3]þ, 100). HRMS:
m/z calcd for C7H14N3 140.1188, found 140.1186. Anal. Calcd for
C8H14F3N3O3S: C, 33.22; H, 4.88; N, 14.53. Found: C, 33.45; H,
5.05; N, 14.14.
11. TLC: Rf 0.42 (3:1 hexane/EtOAc). 1H NMR (400 MHz,
CDCl3): δ 7.48 (s, 1H), 4.38 (t, 2H, J = 7.4 Hz), 1.89 (m, 2H),
1.37 (sextet, 2H, J = 7.4 Hz), 0.96 (t, 3H, J = 7.4 Hz), 0.33 (s,
9H). 13C NMR (100 MHz, CDCl3): δ 146.7, 128.9, 49.7, 32.7,
20.0, 13.7, -0.9. LRMS (FAB) m/z (rel int): (pos) 198
([M þ H]þ, 100). HRMS: m/z calcd for C9H20N3Si 198.1427,
found 198.1425.
1-Butyl-3-methyl-1,2,3-triazolium Hexafluorophosphate (14c). In
a screw cap vial, a heterogeneous mixture of 13 (198 mg, 742 μmol)
and LiPF6 (115 mg, 742 μmol) in deionized water (1.5 mL) was
stirred at 40 °C for 11 h. Upon completion of the reaction, the
reaction mixture was cooled to rt and extracted with IPA/CHCl3
(1/4). The combined organic extracts were washed with deionized
water, dried over anhydrous MgSO4, filtered, and concentrated.
The residue was further dried in vacuo (0.3 mmHg) to afford
analytically pure 14c (176 mg, 83%) as a brown liquid. It was
decolorized according to the literature.18 Compound 14c was
solidified very slowly. Mp: 47 °C. Water content (<0.01%). I-
content (178 ppm). Cl- content (32 ppm). 1H NMR (400 MHz,
CDCl3): δ 8.47 (d, 1H, J = 1.2 Hz), 8.44 (d, 1H, J = 1.2 Hz), 4.58
(t, 2H, J =7.4 Hz), 4.36 (s, 3H), 2.00 (m, 2H), 1.41 (sextet, 2H, J =
7.4 Hz), 0.98 (t, 3H, J = 7.4 Hz). 13C NMR (100 MHz, CDCl3): δ
131.8, 130.7, 54.1, 40.4, 31.3, 19.5, 13.4. LRMS (FAB) m/z (rel int):
(pos) 140 ([C7H14N3]þ, 100). HRMS: m/z calcd for C7H14N3
140.1188, found 140.1186. Anal. Calcd for C7H14F6N3P: C,
29.48; H, 4.95; N, 14.74. Found: C, 29.61; H, 4.95; N, 14.82.
1-Butyl-3-methyl-1,2,3-triazolium Tetrafluoroborate (14d). In
a screw cap vial, a heterogeneous mixture of 13 (99.6 mg,
373 μmol) and AgBF4 (73.3 mg, 373 μmol) in deionized water
(0.8 mL) was suspended at 40 °C for 17 h. Upon completion of
the reaction, the reaction mixture was cooled to rt and extracted
with IPA/CHCl3 (1/4). The combined organic extracts were
washed with deionized water, dried over anhydrous MgSO4,
filtered, and concentrated. The residue was further dried in
vacuo (0.3 mmHg) to afford analytically pure 14d (62.6 mg,
12. TLC: Rf 0.16 (3:1 hexane/EtOAc). 1H NMR (400 MHz,
CDCl3): δ 7.70 (s, 1H), 7.53 (s, 1H), 4.40 (t, 2H, J = 7.4 Hz), 1.90
(m, 2H), 1.36 (sextet, 2H, J = 7.4 Hz), 0.96 (t, 3H, J = 7.4 Hz).
13C NMR (100 MHz, CDCl3): δ 134.0, 123.3, 50.1, 32.5, 19.9,
13.7. LRMS (FAB) m/z (rel int): (pos) 126 ([M þ H]þ, 86).
HRMS m/z calcd for C6H12N3 126.1031, found 126.1032.
1-Butyl-1,2,3-triazole (12). To a solution of triazole 11 (2.15 g,
10.9 mmol) in anhydrous THF (10.9 mL) was dropwise added
TBAF (1 M in THF, 16.3 mL, 16.3 mmol). The reaction was
monitored for the disappearance of starting materials by TLC.
After 6 h at rt, the reaction mixture was concentrated in vacuo.
Column chromatography on silica gel (3:1 hexane/EtOAc)
afforded a desired triazole 12 (1.32 g, 97%) as a light-yellow
liquid. TLC: Rf 0.16 (3:1 hexane/EtOAc). 1H NMR (400 MHz,
CDCl3): δ 7.70 (s, 1H), 7.53 (s, 1H), 4.40 (t, 2H, J = 7.4 Hz), 1.90
(m, 2H), 1.36 (sextet, 2H, J = 7.4 Hz), 0.96 (t, 3H, J = 7.4 Hz).
13C NMR (100 MHz, CDCl3): δ 134.0, 123.3, 50.1, 32.5, 19.9,
13.7. LRMS (FAB) m/z (rel int): (pos) 126 ([M þ H]þ, 86).
HRMS: m/z calcd for C6H12N3 126.1031, found 126.1032.
1-Butyl-3-methyl-1,2,3-triazolium Iodide (13). In a screw
cap vial, a mixture of 12 (3.52 g, 28.1 mmol) and iodomethane
(3.99 g, 28.1 mmol) was stirred at 80 °C for 24 h. Upon
completion of the reaction, the reaction mixture was concen-
trated in vacuo to afford analytically pure 13 (7.26 g, 97%) as a
brown liquid. 13 was solidified very slowly. Mp: 42 °C. Water
1
content (0.16%). H NMR (400 MHz, CDCl3): δ 9.50 (d, 1H,
J = 1.6 Hz), 9.31 (d, 1H, J = 1.6 Hz), 4.74 (t, 2H, J = 7.4 Hz),
4.53 (s, 3H), 2.05 (m, 2H), 1.44 (sextet, 2H, J = 7.4 Hz), 1.00 (t,
3H, J = 7.4 Hz). 13C NMR (100 MHz, CDCl3): δ 132.3, 131.4,
54.2, 41.3, 31.5, 19.4, 13.4. LRMS (FAB) m/z (rel int): (pos) 140
([C7H14N3]þ, 100). HRMS: m/z calcd for C7H14N3 140.1188,
found 140.1186. Anal. Calcd for C7H14IN3: C, 31.48; H, 5.28; N,
15.73. Found: C, 31.51; H, 5.24; N, 15.65.
1-Butyl-3-methyl-1,2,3-triazolium Bis(trifluoromethylsulfonyl)-
amide (14a). In a screw cap vial, a mixture of 13 (43.1 mg, 161 μmol)
and LiNTf2 (46.3 mg, 161 μmol) in deionized water (0.8 mL) was
stirred at 40 °C for 24 h. Upon completion of the reaction, the
reaction mixture was cooled to rt and extracted with CH2Cl2. The
combined organic extracts were washed with deionized water, dried
over anhydrous MgSO4, filtered, and concentrated. The residue
was further dried in vacuo (0.3 mmHg) to afford analytically pure
14a (60.9 mg, 90%) as a brown liquid. 1H NMR (400 MHz,
CDCl3): δ 8.50 (d, 1H, J = 1.6 Hz), 8.44 (d, 1H, J = 1.6 Hz),
4.59 (t, 2H, J = 7.4 Hz), 4.38 (s, 3H), 2.02 (m, 2H), 1.42 (sextet, 2H,
J = 7.4 Hz), 1.00 (t, 3H, J = 7.4 Hz). 13C NMR (100 MHz,
CDCl3): δ 131.5, 130.5, 119.9 (q, JCF = 319.1 Hz), 54.2, 40.4, 31.2,
19.4, 13.2. LRMS (FAB) m/z (rel int): (pos) 140 ([C7H14N3]þ, 100).
HRMS: m/z calcd for C7H14N3 140.1188, found 140.1188. Anal.
Calcd for C9H14F6N4O4S2: C, 25.72; H, 3.36; N, 13.33; S, 15.26.
Found: C, 25.98; H, 3.27; N, 13.26; S, 15.36.
1
74%) as a light-yellow liquid. H NMR (400 MHz, CDCl3): δ
8.58 (s, 1H), 8.54 (s, 1H), 4.58 (t, 2H, J = 7.4 Hz), 4.36 (s, 3H),
1.99 (m, 2H), 1.41 (sextet, 2H, J = 7.4 Hz), 0.98 (t, 3H, J = 7.4
Hz). 13C NMR (100 MHz, CDCl3): δ 132.0, 130.9, 53.9, 40.2,
31.3, 19.5, 13.4. LRMS (FAB) m/z (rel int): (pos) 140
([C7H14N3]þ, 100). HRMS: m/z calcd for C7H14N3 140.1188,
found 140.1182. Anal. Calcd for C7H14BF4N3: C, 37.04; H, 6.22;
N, 18.51. Found: C, 37.49; H, 6.29; N, 18.01.
1,3-Dibutyl-1,2,3-triazolium Iodide (16). In a oven-dried flask,
NaH (157 mg, 6.21 mmol) was suspended in anhydrous MeCN
(5 mL) at 0 °C under nitrogen atmosphere. 1H-1,2,3-Triazole
(358 mg, 5.18 mmol) was then added via syringe. After the
mixture was stirred for 20 min, 1-iodobutane (4.81 g, 25.9 mmol)
was added. The reaction mixture was stirred at 80 °C for 19 h.
Upon completion of the reaction, the reaction mixture was
cooled to rt. Column chromatography on silica gel (1:1 hexane/
EtOAc f 4:1 CH2Cl2/MeOH) afforded a desired compound 16
(1.21 g, 75%) as a brown liquid. Water content (0.05%). 1H NMR
(400 MHz, CDCl3): δ 9.48 (s, 2H), 4.79 (t, 4H, J = 7.4 Hz), 2.05
(m, 4H), 1.42 (sextet, 4H, J = 7.4 Hz), 1.00 (t, 6H, J = 7.4 Hz). 13
C
NMR (100 MHz, CDCl3): δ 131.6, 54.3, 31.6, 19.5, 13.5. LRMS
(FAB) m/z (rel int): (pos) 182 ([C10H20N3]þ, 100). HRMS: m/z
calcd for C10H20N3 182.1657, found 182.1651. Anal. Calcd for
1-Butyl-3-methyl-1,2,3-triazolium Trifluoromethylsulfonate (14b).
In a screw cap vial, a mixture of 13 (234 mg, 874 μmol) and KOTf
(168 mg, 874 μmol) in deionized water (1.3 mL) was stirred at 40 °C
(18) Earle, M. J.; Gordon, C. M.; Plechkova, N. J.; Seddon, K. R.;
Welton, T. Anal. Chem. 2007, 79, 758–764.
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C10H20IN3: C, 38.85; H, 6.52; N, 13.59. Found: C, 39.32; H, 6.71;
N, 12.94.
(m, 4H), 1.40 (sextet, 2H, J = 7.4 Hz), 0.98 (t, 3H, J = 7.4 Hz). 13
C
NMR (100 MHz, CDCl3): δ 131.1, 54.0, 31.4, 19.5, 13.4. LRMS
(FAB) m/z (rel int): (pos) 182 ([C10H20N3]þ, 100). HRMS: m/z
calcd for C10H20N3 182.1657, found 182.1657. Anal. Calcd for
C10H20BF4N3: C, 44.63; H, 7.49; N, 15.62. Found: C, 44.66; H,
7.41; N, 15.51.
General Procedure for the Baylis-Hillman Reaction of Alde-
hyde and Methyl Acrylate in Ionic Liquid. In a oven-dried flask,
aldehyde (1.00 mmol) and DABCO (230 mg, 2.01 mmol) were
dissolved in Ar-degassed [bmTr][PF6] (14c) (0.1 mL). Methyl
acrylate (173 mg, 2.01 mmol) was then added. The homoge-
neous mixture was stirred at ambient temperature, and the
reaction progress was monitored by TLC. Upon completion
of the reaction, the mixture was concentrated by rotary eva-
poration. Purification by silica flash chromatography afforded
the desired compound (see the Supporting Information for
characterization data).
General Procedure for the Baylis-Hillman Reaction of Alde-
hyde and Acrylonitrile in Ionic Liquid. In a oven-dried flask,
aldehyde (1.00 mmol) and DABCO (230 mg, 2.01 mmol) were
dissolved in Ar-degassed [bmTr][PF6] (14c) (0.1 mL). Acrylo-
nitrile (107 mg, 2.01 mmol) was then added. The homogeneous
mixture was stirred at ambient temperature, and the reaction
progress was monitored by TLC. Upon completion of the
reaction, the mixture was concentrated by rotary evaporation.
Purification by silica flash chromatography afforded the desired
compound (see the Supporting Information for characterization
data).
Reuse of [bmTr][PF6] Ionic Liquid. In a oven-dried 1 mL round-
bottom flask, 4-chlorobenzaldehyde (0.431 g, 3.01 mmol), acrylo-
nitrile (321 mg, 6.02 mmol), and DABCO (690 mg, 6.03 mmol)
were dissolved in [bmTr][PF6] (14c) (409 mg, 0.3 mL). The
homogeneous mixture was stirred at ambient temperature, and
the reaction progress was monitored by TLC.
It could be synthesized from n-butyl triazole 12. In a screw
cap vial, a mixture of 12 (36.5 mg, 292 μmol) and 1-iodobutane
(53.7 mg, 292 μmol) was stirred at 80 °C for 14.5 h. Upon
completion of the reaction, the reaction mixture was concen-
trated in vacuo to afford analytically pure 16 (86.0 mg, 95%) as a
brown liquid.
1,3-Dibutyl-1,2,3-triazolium Bis(trifluoromethylsulfonyl)amide
(17a). In a screw cap vial, a mixture of 16 (37.0 mg, 0.12 mmol)
and LiNTf2 (34.4 mg, 0.12 mmol) in deionized water (0.6 mL) was
stirred at 40 °C for 15 h. Upon completion of the reaction, the
reaction mixture was cooled to rt and extracted with IPA/CHCl3
(1/4). The combined organic extracts were washed with deionized
water, dried over anhydrous MgSO4, filtered, and concentrated.
The residue was further dried in vacuo (0.3 mmHg) to afford
analytically pure 17a (55.1 mg, 100%) as a brown liquid. 1H NMR
(400 MHz, CDCl3): δ 8.52 (s, 2H), 4.61 (t, 4H, J = 7.4 Hz), 2.03
(m, 4H), 1.42 (sextet, 4H, J = 7.4 Hz), 1.00 (t, 6H, J = 7.4 Hz). 13
C
NMR (100 MHz, CDCl3):δ130.9, 119.9 (q, JCF = 319.1 Hz), 54.3,
31.3, 19.5, 13.3. LRMS (FAB) m/z (rel int): (pos) 182 ([C10H20N3]þ,
100). HRMS: m/z calcd for C10H20N3 182.1657, found 182.1661.
Anal. Calcd for C12H20F6N4O4S2: C, 31.17; H, 4.36; N, 12.12;
S, 13.87. Found: C, 31.55; H, 4.35; N, 12.07; S, 13.80.
1,3-Dibutyl-1,2,3-triazolium Trifluoromethylsulfonate (17b).
In a screw cap vial, a mixture of 16 (328 mg, 1.06 mmol) and
KOTf (204 mg, 1.06 mmol) in deionized water (1.5 mL) was
stirred at 40 °C for 11 h. Upon completion of the reaction, the
reaction mixture was cooled to rt and extracted with IPA/CHCl3
(1/4). The combined organic extracts were washed with deionized
water, dried over anhydrous MgSO4, filtered, and concentrated.
The residue was further dried in vacuo (0.3 mmHg) to afford
analytically pure 17b (331 mg, 94%) as a brown liquid. 1H NMR
(400 MHz, CDCl3): δ 8.99 (s, 2H), 4.68 (t, 4H, J = 7.4 Hz), 2.02
(m,4H), 1.41(sextet,4H, J=7.4Hz), 0.99(t, 6H, J =7.4Hz). 13
C
Method A. Upon completion of the reaction, Et2O (5 mL) was
added to the reaction mixture. The ionic liquid-Et2O mixture
was stirred for a couple of minutes and stopped. Then, the ionic
liquid-Et2O mixture clearly showed two separate layers,
although <0.5 mL of ionic liquid was used. The upper Et2O
layer was carefully removed by decantation. This procedure was
repeated five times. The combined Et2O fractions were evapo-
rated. Purification by silica flash chromatography (3:1 hexane/
EtOAc) afforded the desired compound 19a (553 mg, 95%). The
ionic liquid was dissolved in CH2Cl2 and transferred to the 1 mL
round-bottom flask for the second reaction. After evaporation
of CH2Cl2, the recovered ionic liquid (414 mg) was dried in
vacuo and reused for the next cycle.
NMR (100 MHz, CDCl3): δ 131.0, 120.6 (q, JCF = 318.2 Hz),
53.9, 31.3, 19.3, 13.2. LRMS (FAB) m/z (rel int): (pos) 182
([C10H20N3]þ, 100). HRMS: m/z calcd for C10H20N3 182.1657,
found 182.1661. Anal. Calcd for C11H20F3N3O3S: C, 39.87; H,
6.08; N, 12.68. Found: C, 39.89; H, 6.28; N, 13.08.
1,3-Dibutyl-1,2,3-triazolium Hexafluorophosphate (17c). In a
screw cap vial, a heterogeneous mixture of 16 (362 mg, 1.17 mmol)
and LiPF6 (182 mg, 1.17 mmol) in deionized water (1.7 mL) was
stirred at 40 °C for 22 h. Upon completion of the reaction, the
reaction mixture was cooled to rt and extracted with IPA/CHCl3
(1/4). The combined extracts were washed with deionized water,
dried over anhydrous MgSO4, filtered, and concentrated. The
residue was further dried in vacuo (0.3 mmHg) to afford analy-
tically pure 17c (359 mg, 94%) as a brown liquid. 1H NMR
(400 MHz, CDCl3): δ 8.56 (s, 2H), 4.61 (t, 4H, J = 7.4 Hz), 2.01
Method B. Upon completion of the reaction, Purification by
silica flash chromatography (3:1 hexane/EtOAc f MeOH)
afforded the desired compound 19a (577 mg, 99%) and ionic
liquid (563 mg). The recovered ionic liquid was reused for the
next cycle.
(m,4H), 1.41(sextet,4H, J=7.4Hz), 0.99(t, 6H, J =7.4Hz). 13
C
NMR (100 MHz, CDCl3): δ 130.9, 54.2, 31.4, 19.5, 13.4. LRMS
(FAB) m/z (rel int): (pos) 182 ([C10H20N3]þ, 100). HRMS m/z
calcd for C10H20N3 182.1657, found 182.1661. Anal. Calcd for
C10H20F6N3P: C, 36.70; H, 6.16; N, 12.84. Found: C, 36.68; H,
6.19; N, 12.90.
1,3-Dibutyl-1,2,3-triazolium Tetrafluoroborate (17d). In a screw
cap vial, a heterogeneous mixture of 16 (279 mg, 903 μmol) and
AgBF4 (178 mg, 903 μmol) in deionized water (1.3 mL) was
suspended at 40 °C. After being stirred for 20 h, the reaction
mixture was cooled to rt and extracted with IPA/CHCl3 (1/4). The
combined organic extracts were washed with deionized water,
dried over anhydrous MgSO4, filtered, and concentrated. The
residue was further dried in vacuo (0.3 mmHg) to afford analyti-
cally pure 17d (217 mg, 89%) as a yellow liquid. 1H NMR
(400 MHz, CDCl3): δ 8.62 (s, 2H), 4.62 (t, 4H, J = 7.4 Hz), 2.00
Acknowledgment. This research was supported by Basic
Science Research Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of
Education, Science and Technology (No. 2009-0066777).
We thank Hwayoung Yun and Dr. Seung-Mann Paek for
mass spectroscopy.
Supporting Information Available: Spectroscopic data for
all Baylis-Hillman products, 1D-NOE spectra of 13 and 9d,
TGA spectra, and H and 13C NMR spectra for 6-8, 9a-d,
1
11-13, 14a-d, 16, 17a-d, 18a-k, 19a-j. This material is
available free of charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 12, 2010 4191