Synthesis of new dicationic azolium salts and their application as NHC precursors in Suzuki-Miyaura coupling

Article abstract of DOI:10.1055/s-0029-1218837

Novel dicationic azolium salts were developed as N-heterocyclic carbene (NHC) precursors wherein two 1,2,3-triazolium, one 1,2,3-triazolium and one imidazolium, or two imidazolium units, are tethered to each other through alkylene bridges. These dicationic systems were applied as precursors for ligands in palladium-catalyzed Suzuki-Miyaura couplings using different leaving groups. Interestingly, the combination of an imidazolium and a 1,2,3-triazolium unit performed better than either a single azolium salt or than dications where two imidazolium or two 1,2,3-triazolium units are found. Aryl chlorides, iodides and triflates turned out to be the best substrates for this new catalytic system. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1218837

PAPER
2609
Synthesis of New Dicationic Azolium Salts and Their Application as NHC
Precursors in Suzuki–Miyaura Coupling
Synthesis and
a
A
pplication
d
of Dication
a
ic
A
zolium
f
Salts Sadiq Khan, Jürgen Liebscher*
Institute of Chemistry, Humboldt-University Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany
Fax +49(30)20937552; E-mail: liebscher@chemie.hu-berlin.de
Received 5 February 2010; revised 22 April 2010
Dedicated to Prof. Dr. Helmut Vorbrüggen on the occasion of his 80th birthday
pling included.23–30 Here, they could also be applied to the
– often reluctant – chloroarenes.23,25,31 As a precondition
for good coupling activity, bulky aryl substituents have to
be present at both nitrogen atoms of the imidazolin-2-
Abstract: Novel dicationic azolium salts were developed as N-het-
erocyclic carbene (NHC) precursors wherein two 1,2,3-triazolium,
one 1,2,3-triazolium and one imidazolium, or two imidazolium
units, are tethered to each other through alkylene bridges. These di-
cationic systems were applied as precursors for ligands in palladi- ylidene. The preparation of the NHC ligands in situ from
um-catalyzed Suzuki–Miyaura couplings using different leaving
the corresponding imidazolium salts by bases, in the pres-
groups. Interestingly, the combination of an imidazolium and a
ence of a suitable palladium species, provides a straight-
1,2,3-triazolium unit performed better than either a single azolium
forward method for obtaining the catalysts.23,25
salt or than dications where two imidazolium or two 1,2,3-triazoli-
um units are found. Aryl chlorides, iodides and triflates turned out
to be the best substrates for this new catalytic system.
As a special type of imidazol-2-ylidene ligands for palla-
dium complexes, compounds were used wherein more
than one imidazole moiety were covalently connected to
each other.28,32,33 Amongst them, crown carbene complex-
es were found.34 In such cases, the corresponding imida-
zolium salts were used and treated with an excess of base,
thus implying that each imidazolium unit was transformed
into the corresponding carbene. Other NHC ligands, such
as pyrazolylidenes, pyridinylidenes, thiazolylidenes, or
1,2,4-triazolylidenes, are rare.22,35
Key words: cycloaddition, cross-coupling, catalysis, alkylation,
heterocycles
Imidazolium salts are probably the most important class
of ionic liquids (ILs). They are easy to synthesize and
their properties can be tuned by adjusting the substituents
attached to the imidazolium ring as well as by changing
the anions within an extremely wide range.1–3 They have
been used as inert solvents in a variety of chemical reac-
tions, palladium-catalyzed reactions included,4–10 and of-
ten provide advantages over the use of traditional organic
solvents. Their application in catalysis can improve the
catalyst stability, the overall catalytic performance, and
can allow convenient biphasic catalysis. As a special sub-
class of IL geminal or triple imidazolium11 salts have at-
tracted interest as di- and tricationic ionic liquids,
respectively.12,13 Although ILs are often considered as in-
nocent solvents, there are also a number of cases wherein
imidazolium-based ILs directly participate in the reac-
tions, for example, under strongly basic conditions and/or
in the presence of transition metals. Here, they are depro-
tonated at the 2-position to form N-heterocyclic carbenes
(NHCs) or undergo oxidative addition to the metal, lead-
ing to complexes.14–17 Palladium salts or palladium com-
plexes can form NHC complexes even under non-basic
conditions.17–21 On the other hand, such strongly nucleo-
philic, imidazole-based NHCs were purposely synthe-
sized and have turned out to be efficient ligands for heavy
metals (Pd, Ru, etc.).22 Their palladium complexes have
advantageously been used in a number of palladium-cata-
lyzed cross-coupling reactions, the Suzuki–Miyaura cou-
We recently developed 1,2,3-triazolium salts as a new
class of ionic liquid.36 They can be synthesized in a
straightforward, two-step procedure by copper(I)-cata-
lyzed [3+2] cycloaddition of organic azides to alkynes in
a click process developed by Meldal and Sharpless,37,38
followed by N-alkylation. This methodology has also
been used for the synthesis of so-called39 IL-tagged orga-
nocatalysts by tethering organocatalytic moieties to tria-
zolium salts.40,41 1,2,3-Triazolium salts are much less
acidic than imidazolium salts and, thus, can be inert under
basic conditions where imidazolium-based ILs are depro-
tonated. Nevertheless, 1,2,3-triazolium salts were recently
shown to undergo complex formation with palladium ac-
etate by deprotonation at a ring carbon atom.42 This result
prompted us to investigate whether mixtures of 1,2,3-tria-
zolium salts and palladium species can act as catalysts in
Suzuki–Miyaura reactions.
We chose the known 1,4-dibutyl-3-methyl-1,2,3-triazoli-
um iodide (4a)43 and, for comparison, commercial 1-bu-
tyl-3-methylimidazolium tetrafluoroborate (bmimBF4) as
precursors for the NHC. In addition, we synthesized a new
1,2,3-triazolium salt 4b (Scheme 1), wherein the acidic 5-
position is flanked by two voluminous mesityl groups.
Such steric shielding was shown to be essential for good
performance of imidazolium-based NHCs (see above). In
order to investigate possible synergistic effects, we further
synthesized NHC precursors wherein two azolium units,
i.e., two 1,2,3-triazolium rings (7), one 1,2,3-triazolium
SYNTHESIS 2010, No. 15, pp 2609–2615
x
x.
x
x
.
2
0
1
0
Advanced online publication: 25.06.2010
DOI: 10.1055/s-0029-1218837; Art ID: T02910SS
© Georg Thieme Verlag Stuttgart · New York

2610
S. S. Khan, J. Liebscher
PAPER
and one imidazolium moiety (11) and two imidazolium
structures (14), are tethered to each other. The syntheses
of the dicationic 1,2,3-triazolium compounds 7 and 11
were again based on our versatile two-step methodology
based on copper-catalyzed [3+2] cycloaddition of azides
and terminal alkynes to 1,4-disubstituted 1,2,3-triazoles
and final N-alkylation (Scheme 2 and Scheme 3).
N
R1
N
N
1
N
method A
(64–89%)
N
N
R1
N
+
N
n
N
10a R1 = Bn, n = 3
N
10b R1 = n-Bu, n = 1
10c R1 = n-Bu, n = 9
n
9
N
method B
(82–94%)
R1
N
method A:
N
R1
CuSO4 (cat.)
1
N
sodium ascorbate, MeOH
N
N
+
r.t., 2–3 d
(89–94%)
X
X
R2
Me
Me
N
R2
N
N
R1
N
3a R1 = R2 = n-Bu
2
N
n
3b R1 = R2 = mesityl
method B:
MeI, MeCN,
reflux, 12 h
11a R1 = Bn, n = 3, X = I
11b R1 = n-Bu, n = 1, X = I
11c R1 = n-Bu, n = 9, X = I
R1
N
method C
(85–92%)
N
N
Me
12a: R1 = Bn, n = 3, X = BF4
(97–99%)
I
12b: R1 = n-Bu, n = 1, X = BF4
R2
4a R1 = R2 = n-Bu
Scheme 3 Synthesis of mixed imidazolium triazolium salts 11a–
4b R1 = R2 = mesityl
12b
Scheme 1 Synthesis of 1,2,3-triazolium salts 4a and 4b
X
Me
N
N
N
N
N
N
N
N
N
N
method B
(89%)
N
5
N
N
N
N
method A
N
N
N
X
+
N
N
(R2 = n-Bu)
(88%)
R2
n-Bu
Me
n-Bu
13
2
6
14 X = I
15 X = BF4
method C
(85%)
2
method B
(96%)
Scheme 4 Synthesis of diimidazolium salts 14 and 15
X
X
Me
Me
N
N
new azolium salts 4b, 5b, 7, 8, and 14 are solids, whereas
11, 12, and 15 appeared as oils. All structures were eluci-
dated by NMR spectroscopy and by MS analysis.
N
N
N
N
n-Bu
n-Bu
With these NHC precursors in hand, we investigated their
performance in the Suzuki–Miyaura reaction of arylbo-
ronic acids 16 with haloarenes, aryltriflates, and aryltosy-
lates 17 (Scheme 5) by adopting a procedure reported for
the application of imidazolium NHC precursors25 involv-
ing Pd2(dba)3 as palladium source in the presence of cesi-
um carbonate as base. First, we screened the NHC
precursors in the reaction of phenylboronic acid with 4-
chlorotoluene (Table 1, entry 1). As a reference, the reac-
tion was first performed without the addition of an NHC
precursor (31% yield). The addition of either bmimBF4 or
the trialkyl-1,2,3-triazolium iodide 4a did not show a sig-
nificant effect. This phenomenon corresponds with the
known fact that bulky aryl substituents have to be present
at both N-atoms of the imidazole ring. The sterically
shielded 1,4-dimesityl-1,2,3-triazolium salt (4b) gave a
somewhat higher yield (48%) but this was far from satis-
factory and worse than those obtained in known cases
where the corresponding imidazolium salts were used.23,25
Whereas the application of the twin 1,2,3-triazolium NHC
precursors 7 and 8 did not improve the yield, an increase
method C:
AgBF4, MeOH, r.t.
(92%)
7 X = I
8 X = BF4
Scheme 2 Synthesis of di(1,2,3-triazolium) salts 7 and 8
For the synthesis of the ditriazolium product 7, 1,3-diazi-
dopropane (5) and two equivalents of 1-hexyne were used
as starting materials and both 1,2,3-triazole rings of the
cycloaddition product 6 were finally methylated. When
imidazolylalkynes 9 were applied in this sequence, the
1,2,3-triazoles 10 that were formed in the first step under-
went methylation of both the triazole and the imidazole
ring in the final step, thus giving the dicationic azolium
products 11. The corresponding 1,3-diimidazoliumpro-
pane 14 was obtained by double methylation of the known
1,3-di(imidazol-1-yl)propane (13; Scheme 4).
All syntheses provided high yields of products. In order to
investigate the effect of the anion in the NHC precursors,
the iodides 7, 11, and 14 were transformed into the corre-
sponding tetrafluoroborates 8, 12, and 15 by salt metathe-
sis with silver tetrafluoroborate in quantitative yields. The
Synthesis 2010, No. 15, 2609–2615 © Thieme Stuttgart · New York

PAPER
Synthesis and Application of Dicationic Azolium Salts
2611
Table 1 Effect of the Addition of NHC Precursors on Yields of 18 in Suzuki–Miyaura Reaction of Phenylboronic Acid (Scheme 5)
Yield (%) of products 18
Entry R1
R2
Y
None bmimBF4 4a
4b
7
8
11a
75
11b
81
11c
12a
59
12b
14
65
61
15
48
21
1
2
3
4
H
H
H
H
Me
Me
Me
Me
Cl
Br
I
31
31
74
83
32
10
65
69
36
26
48
30
38
15
83
68
a
a
–
–
35
11
51
70
90
90
a
a
a
a
OTf
–
–
–
07
96
99
100
–
21
a Only starting material was recovered.
R2
idazolalkylenes 11 as NHC precursors (entry 3; increase
in yield from 74% without an additive to 90% with addi-
tion of 11b). However, the effect was not as marked as in
the case of chlorotoluene (Table 1, entry 1; improvement
from 31% to 81% with 11b). Triflate turned out to be the
best leaving group in this Suzuki–Miyaura reaction
(Table 1, entry 4). Quantitative yields were obtained with
the mixed NHC precursors 11 and 12. Again for unknown
reasons, the addition of the 1,2,3-triazolium salt 4 or the
dicationic azolium salts 7 or 14 blocked the Suzuki–
Miyaura coupling of 4-tolyltriflate.
B(OH)2
Y
NHC precursor (3 mol%)
Pd2(dba)3 (1.5 mol%)
Cs2CO3
+
dioxane, 80 °C, 1.5 –2 h
R1
16
R2
17
R1
18
Scheme 5 Suzuki–Miyaura cross-coupling reaction
We further tested our preferred NHC precursor 11b with
other substrates 17 (Table 2). As shown with 4-meth-
ylphenyltosylate (Table 2, entry 1), tosylate seems to be a
disfavored leaving group in the Suzuki–Miyaura reaction
(Scheme 5) since it failed to react in the presence of our
otherwise optimal NHC precursor 11b. Fluoride is also
not suitable as a leaving group (5% yield; Table 2, entry
2). In reactant 17 (R2 = Cl, Y = OTf), bearing two differ-
ent potential leaving groups, the triflate was substituted
(Table 2, entry 3; 55% yield), while the triflate group sur-
vived the coupling and bromide functioned as leaving
group in 4-bromophenoxytriflate (Table 2, entry 4; yield
86%).
was achieved with the twin imidazolium NHC precursors
14 (65%) and 15 (48%) (Table 1, entry 1).
Remarkably, a significant improvement was observed
when the mixed NHC precursors 11a (75%), 11b (81%),
or 11c (83%) were used in the Suzuki–Miyaura reaction
of 4-chlorotoluene with phenylboronic acid (Table 1, en-
try 1). Since their performance was much better than those
of the symmetric di(1,2,3-triazolium) 7, 8 and diimidazo-
lium 14, 15 compounds, there must exist a considerable
synergistic effect caused by the presence of the two differ-
ent heterocycles in the mixed system 11. At this stage it
was difficult to find a reason for this phenomenon. We as-
sumed that the imidazole moiety of the mixed systems 11
is deprotonated by cesium carbonate, forming an imida-
zole-2-ylidene, which acts as a ligand for the palladium.
The 1,2,3-triazolium moiety is much less acidic and thus
less likely to be transformed into an NHC ligand. This is
in line with the poor performance of the di-1,2,3-triazoli-
umpropanes 7 and 8. But other reasons, such as formation
of IL-stabilized nanoparticles in situ could also be respon-
sible for the observed phenomena. In this context, it is
worth mentioning that palladium nanoparticles prepared
in situ can efficiently catalyze Suzuki–Miyaura reac-
tions.44
Table 2 Effect of Substituents and Leaving Groups on Yields of
Products 18 of the Suzuki–Miyaura Reactions According to
Scheme 5 Using 11b as NHC Precursor
Entry
R1
R2
Y
Yield (%)
a
1
2
3
4
5
6
7
H
Me
Me
Cl
OTs
F
–
H
5
55
H
OTf
Br
H
OTf
Me
Me
Me
86
OMe
OMe
Ac
Cl
100
100
24
Investigations into the use of leaving groups other than
chloride revealed that bromide performed worse in all cas-
es (Scheme 5, and Table 1, entry 2) and thus is not a good
choice for our methodology. In the coupling of 4-bromo-
toluene, some cases were even observed wherein the ad-
dition of 1,2,3-triazolium NHC precursors prohibited the
reaction (Table 1, entry 2; compounds 4b and 7). Some
improvements could be achieved in the case of Suzuki–
Miyaura coupling of 4-iodotoluene by using the triazolim-
OTf
OTf
a Only starting material was recovered.
Although this leaving group tendency corresponds to re-
ported cases using phosphanes as ligands,45 it was diffi-
cult to explain why 11b performed so badly in the reaction
Synthesis 2010, No. 15, 2609–2615 © Thieme Stuttgart · New York

2612
S. S. Khan, J. Liebscher
PAPER
1,4-Dimesityl-1H-1,2,3-triazole (3b)
Yield: 94%; colorless crystals; mp 155 °C.
possible that this effect is due to the more electron-defi- 1H NMR (CDCl3, 300 MHz): d = 7.50 (s, 1 H, CHtriaz), 7.06 (s, 2 H,
of 4-bromotoluene (Table 1, entry 2) while 4-bromophe-
nyltriflate gave high yields (Table 2, entry 4, 86%). It is
ArH-Ctriaz), 7.01 (s, 2 H, ArH-Ntriaz), 2.44 (s, 3 H, p-CH3Ar-Ntriaz),
2.41 (s, 3 H, p-CH3Ar-Ctriaz), 2.22 (s, 3 H, o-CH3ArH-Ntriaz), 2.08 (s,
3 H, o-CH3Ar-Ctriaz).
cient nature of 4-bromophenyltriflate leading to a more
rapid oxidative addition to the palladium than the 4-bro-
motoluene. Electron-donating substituents in the arene
13C NMR (CDCl3, 75 MHz): d = 145.4 (Ctriaz), 140.8 (CAr), 138.3
ring of the arene boronic acid 16 seem to be favorable,
(CAr), 137.8 (CAr), 135.1 (CAr), 133.6 (CAr), 131.8 (CAr), 129.1
since 4-methoxyphenylboronic acid gave quantitative
(CHAr), 128.4 (CHAr), 127.6 (CHAr), 124.5 (CHtriaz), 21.2 (p-CH3Ar-
yields with 4-chlorotoluene as well as with 4-methylphe-
Ctriaz), 20.9 (o-CH3Ar-Ctriaz), 20.7 (p-CH3Ar-Ntriaz), 17.3 (o-CH3Ar-
nyltriflate (Table 2, entries 5 and 6). On the other hand, 4-
acetylphenylboronic acid gave only 24% coupling prod-
uct, indicating that electron-withdrawing substituents in
the boronic acid are disfavored (Table 2, entry 7).
Ntriaz).
HRMS (ESI): m/z [M + H]+ calcd for C20H23N3: 306.1970; found:
306.1956.
Anal. Calcd for C20H23N3: C, 78.65; H, 7.59; N, 13.76. Found: C,
78.44; H, 7.90; N, 13.57.
In summary, a number of new 1,2,3-triazolium salts were
synthesized wherein an additional 1,2,3-triazolium or im-
idazolium moiety was tethered to the triazole ring via
alkylene bridges. The novel compounds were synthesized
by copper-catalyzed [3+2] cycloaddition of alkynes with
azides and final N-alkylation. An investigation into the
suitability of several 1,2,3-triazolium salts to act as pre-
cursors for NHC ligands in palladium-catalyzed Suzuki–
Miyaura reactions revealed that the combination of a
1,2,3-triazolium and imidazolium moiety tethered to each
other by alkylene bridges (compounds 11 and 12) repre-
sents a new and effective catalyst system in particular for
coupling of chloro arenes or aryl triflates. The application
of 1,2,3-triazolium salts lacking an additional imidazoli-
um salt either do not, or only marginally improve the per-
formance of the Suzuki–Miyaura reactions even if two
bulky mesityl groups flank the potentially acidic 5-posi-
tion of the triazolium ring. We are presently designing
other 1,2,3-triazolium-based dicationic NHC precursors
to highlight the function of the triazolium moiety and to
extend the scope of this methodology.
1,3-Di(4-butyl-1H-1,2,3-triazol-1-yl)propane (6)
Recrystallized from EtOAc.
Yield: 88%; white solid; mp 145 °C.
1H NMR (CDCl3, 300 MHz): d = 7.31 (s, 2 H, CHtriaz), 4.27 (t,
J = 6.14 Hz, 4 H, CH2N), 2.61–2.65 (m, 4 H, CH2Ctriaz), 2.42–2.46
(m, 2 H, NCH2CH2), 1.56–1.60 (m, 4 H, CH3CH2CH2), 1.25–1.37
(m, 4 H, CH3CH2), 0.86 (t, J = 7.29 Hz, 6 H, CH3CH2).
13C NMR (CDCl3, 75 MHz): d = 121.7 (CHtriaz), 46.5 (NCH2), 31.4
(CH3CH2CH2), 30.6 (CH2C), 25.2 (CH3CH2), 22.2 (NCH2CH2),
13.7 (CH3CH2).
HRMS (ESI): m/z [M + H]+ calcd for C15H26N6: 291.2297; found:
291.2282.
4-[3-(1H-Imidazol-1-yl)propyl]-1-benzyl-1H-1,2,3-triazole
(10a)
Yield: 89%; light-yellow oil.
1H NMR (CDCl3, 300 MHz): d = 7.30–7.40 (m, 9 H, CHAr + CHtriaz
+ CHimidaz), 5.49 (s, 2 H, Ph-CH2), 4.06 (m, 2 H, CH2NCH), 2.61
(m, 2 H, CH2CN), 2.22 (m, 2 H, CH2CH2CH2).
13C NMR (CDCl3, 75 MHz): d = 146.5 (Ctriaz), 135.3 (NCHN), 134.7
(CAr), 129.1 (CHAr), 128.8 (CHAr), 128.3 (CHAr), 128.2 (CHtriaz),
128.0 (CH2NCHCH), 121.6 (CH2NCHCH), 54.7 (PhCH2), 42.0
(CH2NCHN), 30.1 (CH2CN), 22.4 (CH2CH2CH2).
Chemicals were purchased from Aldrich and Acros. Silica gel 60
(0.04–0.063 mm, Acros) was used for preparative column chroma-
tography. Melting points were determined with a Boetius hotstage
HRMS (ESI): m/z [M + H]+ calcd for C15H17N5: 268.1562; found:
268.1551.
1
apparatus and are uncorrected. H and 13C NMR spectra were re-
corded at 300 and 75.5 MHz, respectively, on a Bruker AC-300 with
TMS as an internal standard. Elemental analyses were ascertained
with a Euro EA analyser. High-resolution mass spectra (ESI) were
measured with a Thermo Finnigan LTQ-FT-ICR-MS with MeOH
as a solvent. The structures of the Suzuki coupling products 18 were
confirmed by comparison of the NMR spectra with reported da-
ta.45,46
4-[(1H-Imidazol-1-yl)methyl]-1-butyl-1H-1,2,3-triazole (10b)
Yield: 64%; yellow oil.
HRMS (ESI): m/z [M + H]+ calcd for C10H15N5: 206.1406; found:
206.1417.
4-[9-(1H-Imidazol-1-yl)nonyl]-1-butyl-1H-1,2,3-triazole (10c)
Yield: 97%; light-yellow oil.
Synthesis of 1,2,3-Triazoles 4, 6, and 10; General Procedure
(Method A)
1H NMR (CDCl3, 300 MHz): d = 7.50 (s, 1 H, NCHN), 7.28 (s, 1 H,
CH2NCHCHN), 7.24 (s, 1 H, CH2NCHCHN), 6.99 (s, 1 H, CHtriaz),
4.30 (t, J = 7.23 Hz, 2 H, CH2NN), 3.93 (t, J = 7.09 Hz, 2 H,
CH2NCHN), 2.56–2.63 (m, 2 H, CH2Ctriaz), 1.81–1.91 (m, 2 H,
CH3CH2CH2), 1.74–1.78 (m, 2 H, CH2CH2Ctriaz), 1.60–1.70 (m,
2 H, CH3CH2), 1.28–1.38 (m, 12 H, 6 × CH2), 0.94 (t, J = 7.35 Hz,
3 H, CH3CH2).
13C NMR (CDCl3, 75 MHz): d = 148.2 (Ctriaz), 133.3 (NCHN),
129.4 (CHtriaz), 127.5 (CH2NCHCHN), 120.3 (CH2NCHCHN), 49.8
(CH2NN), 47.2 (CH2NCHN), 32.3 (CH2CH2CH2Ctriaz), 31.0
(CH3CH2CH2), 29.4 (alkyl-CH2), 29.2 (alkyl-CH2), 29.1 (alkyl-
CH2), 29.1 (alkyl-CH2), 28.9 (CH2CH2CH2NCHN), 26.4
(CH2CH2Ctriaz), 25.6 (CH2Ctriaz), 19.7 (CH3CH2), 13.4 (CH3CH2).
To a solution of azide 1 or 5 (20 mmol) in MeOH (100 mL), sodium
ascorbate (800 mg, 20 mol%), CuSO4 (480 mg, 15 mol%) and the
alkyne 2 or 9 (20 mmol) were added (for triazole 6 the amounts of
alkyne 2, copper sulfate and sodium ascorbate were doubled). The
solution was stirred at r.t. for 2–3 d (reaction monitored by TLC).
After completion of the reaction, H2O (500 mL) was added and the
mixture was extracted with EtOAc (3 × 500 mL). The combined or-
ganic layers were washed with brine (500 mL) and then dried over
Na2SO4. Evaporation of the solvent in vacuo gave the product,
which was pure according to TLC and NMR analyses and thus was
used in subsequent alkylation without prior purification.
Synthesis 2010, No. 15, 2609–2615 © Thieme Stuttgart · New York

PAPER
Synthesis and Application of Dicationic Azolium Salts
2613
HRMS (ESI): m/z [M + H]+ calcd for C18H31N5: 318.2658; found:
318.2607.
3-Butyl-1-methyl-5-[(3-Methyl-1H-imidazol-3-ium-1-yl)meth-
yl]-3H-1,2,3-triazol-1-ium Diiodide (11b)
Yield: 82%; brownish yellow oil.
Synthesis of 1,2,3-Triazolium and Imidazolium Salts 4, 7, 11,
and 14; General Procedure (Method B)
1H NMR (CD3OD, 300 MHz): d = 9.11 (s, 1 H, NCHN), 8.29 (s,
1 H, CH2NCHCH), 7.70 (s, 1 H, CH2NCHCH), 7.62 (s, 1 H, CHtri-
az), 4.46 (m, 2 H, CH2NN), 4.03 (m, 2 H, CH2NCHN), 3.96–4.00
(m, 6 H, CH3NCHN + CH3NN), 1.89–1.94 (m, 2 H, CH3CH2CH2),
1.32–1.37 (m, 2 H, CH3CH2), 0.97 (t, J = 7.36 Hz, 3 H, CH3CH2).
13C NMR (CD3OD, 75 MHz): d = 141.5 (Ctriaz), 138.1 (NCHN),
132.3 (CH2NCHCH), 125.2 (CH2NCHCH), 123.7 (CHtriaz), 50.0
(CH2NN), 43.9 (CH2NCHN), 38.7 (CH3NCHN), 35.5 (CH3NN),
31.8 (CH3CH2CH2), 19.2 (CH3CH2), 12.4 (CH3CH2).
A solution of the 1,2,3-triazole 3a, 3b, 6, 10a, 10b, 10c, or imida-
zole 13 (20 mmol) and MeI (5 equiv for 3a and 3b and 10 equiv for
the other 1,2,3-triazoles and imidazoles) in anhydrous MeCN (30
mL) was heated at reflux for 12 h. All volatile compounds were re-
moved under vacuum with a rotary evaporator to give iodides 4a,
4b, 7, 11a, 11b, 11c, and 14 as solids or clear sticky oils, which were
then washed with Et2O (3 × 50 mL) to afford the pure product after
removing traces of solvents under vacuum.
HRMS (ESI): m/z [M]2+ calcd for C12H21N52+: 117.5893; found:
117.5892.
3,5-Dimesityl-1-methyl-3H-1,2,3-triazol-1-ium Iodide (4b)
Yield: 97%; white solid; mp 185 °C.
1H NMR (CDCl3, 300 MHz): d = 9.30 (s, 1 H, CHtriaz), 6.99–7.01
(m, 4 H, CHAr), 4.21 (s, 3 H, CH3N), 2.31–2.33 (m, 6 H, o-
CH3ArNtriaz), 2.12 (m, 12 H, o,p-CH3ArCtriaz + p-CH3ArNtriaz).
3-Butyl-1-methyl-5-[9-(3-methyl-1H-imidazol-3-ium-1-yl)non-
yl]-3H-1,2,3-triazol-1-ium Iodide (11c)
Yield: 98%; yellow oil.
1H NMR (CD3OD, 300 MHz): d = 9.08 (s, 1 H, NCHN), 8.70 (s,
1 H, CH2NCHCHN), 7.71 (s, 1 H, CH2NCHCHN), 7.61 (s, 1 H,
CHtriaz), 4.63 (t, J = 7.26 Hz, 2 H, CH2NN), 4.28 (t, J = 7.23 Hz,
2 H, CH2NCHN), 4.27 (s, 3 H, CH3NN), 3.98 (s, 3 H, CH3NCH),
13C NMR (CDCl3, 75 MHz): d = 142.5 (Ctriaz), 137.8 (CAr), 134.0
(CAr), 132.4 (CAr), 131.0 (CAr), 129.8 (CHAr), 129.3 (CHAr), 116.9
(CHtriaz), 39.4 (CH3N), 21.2 (p-CH3ArCtriaz + p-CH3ArNtriaz), 20.6
(o-CH3ArCtriaz), 17.8 (o-CH3ArNtriaz).
2.93 (t, J = 7.82 Hz, 2 H, CH2Ctriaz), 2.00–2.05 (m,
2 H,
Anal. Calcd for C21H26IN3: C, 56.38; H, 5.86; I, 28.37; N, 9.39.
Found: C, 56.33; H, 5.79; I, 28.79; N, 9.41.
CH3CH2CH2), 1.94 (m, 2 H, CH2CH2Ctriaz), 1.82 (m, 2 H, CH3CH2),
1.38–1.48 (m, 12 H, 6 × alkyl-CH2), 1.01 (t, J = 7.37 Hz, 3 H,
CH3CH2).
+
HRMS (ESI): m/z [M]+ calcd for C21H26N3 : 320.2127; found:
320.2099.
13C NMR (CD3OD, 75 MHz): d = 144.8 (Ctriaz), 136.4 (NCHN),
128.0 (CHtriaz), 123.5 (CH2NCHCHN), 122.3 (CH2NCHCHN), 53.3
(CH2NN), 49.5 (CH2NCHN), 37.0 (CH3NCH), 35.5 (CH3NN), 30.9
(CH2CH2CH2Ctriaz), 29.7 (CH3CH2CH2), 28.7 (alkyl-CH2), 28.6
(alkyl-CH2), 28.6 (alkyl-CH2), 28.5 (alkyl-CH2), 26.4
(CH2CH2CH2NCHN), 25.7 (CH2CH2Ctriaz), 23.0 (CH2Ctriaz), 19.0
(CH3CH2), 12.4 (CH3CH2).
1,1¢-(Propane-1,3-diyl)bis(4-butyl-2-methyl-1H-1,2,3-triazol-2-
ium) Diiodide (7)
Yield: 96%; yellow solid; mp 131 °C.
1H NMR (CDCl3, 300 MHz): d = 7.31 (s, 2 H, 2 × CHtriaz), 4.27 (t,
J = 6.23 Hz, 4 H, 2 × CH2N), 4.21 (s, 6 H, 2 × CH3N), 2.74–2.79
(m, 6 H, NCH2CH2 and 2 × CH2Ctriaz), 1.62–1.72 (m, 4 H, 2 ×
CH3CH2CH2), 1.31–1.43 (m, 4 H, 2 × CH3CH2), 0.86 (t,
J = 7.29 Hz, 6 H, 2 × CH3CH2).
HRMS (ESI): m/z [M]2+ calcd for C20H37N52+: 173.6519; found:
173.6518.
13C NMR (CDCl3, 75 MHz): d = 144.9 (Ctriaz), 129.4 (2 × CHtriaz),
49.7 (2 × NCH2), 39.0 (2 × CH3N), 28.4 (2 × CH3CH2CH2), 28.3 (2
× CH2Ctriaz), 23.6 (2 × CH3CH2), 22.0 (NCH2CH2), 13.4 (2 ×
CH3CH2).
1,1¢-(Propane-1,3-diyl)bis(3-methyl-1H-imidazol-3-ium) Diio-
dide (14)
Yield: 89%; yellow solid; mp 137 °C.
1H NMR (CD3CN, 300 MHz): d = 9.12 (s, 2 H, 2 × NCHN), 7.65
(m, 2 H, 2 × CH2NCHCH), 7.43 (m, 2 H, 2 × CH2NCHCH), 4.36 (t,
J = 7.18 Hz, 4 H, 2 × CH2N), 3.88 (s, 6 H, 2 × CH3N), 2.46–2.55
(m, 2 H, CH2CH2CH2).
13C NMR (CD3CN, 75 MHz): d = 137.3 (2 × NCHN), 124.4 (2 ×
CH2NCHCH), 123.1 (2 × CH2NCHCH), 46.8 (2 × CH2N), 37.0 (2
× CH3N), 30.8 (CH2CH2CH2).
Anal. Calcd for C17H32I2N6: C, 35.55; H, 5.62; I, 44.20; N, 14.63.
Found: C, 35.37; H, 5.61; I, 44.66; N, 14.41.
HRMS (ESI): m/z [M]2+ calcd for C17H32N62+: 160.1344; found:
160.1300.
3-Benzyl-1-methyl-5-[3-(3-methyl-1H-imidazol-3-ium-1-
yl)propyl]-3H-1,2,3-triazol-1-ium Diiodide (11a)
Yield: 94%; brownish yellow oil.
1H NMR (CDCl3, 300 MHz): d = 9.45 (s, 1 H, NCHN), 8.97 (s, 1 H,
CH2NCHCH), 7.87 (s, 1 H, CH2NCHCH), 7.30–7.45 (m, 6 H, CHAr
+ CHtriaz), 5.66 (s, 2 H, PhCH2), 4.52 (t, J = 7.34 Hz, 2 H,
CH2NCHN), 4.27 (s, 3 H, CH3NN), 3.88 (s, 3 H, CH3NCHN), 3.12
(t, J = 7.51 Hz, 2 H, CH2CN), 2.44 (m, 2 H, CH2CH2CH2).
13C NMR (CDCl3, 75 MHz): d = 143.2 (Ctriaz), 136.4 (NCHN), 130.9
(CAr), 129.9 (CHAr), 129.4 (CHAr), 129.2 (CHAr), 128.7 (CHtriaz),
128.1 (CH2NCHCH), 123.2 (CH2NCHCH), 57.4 (PhCH2), 48.2
(CH2NCHN), 39.1 (CH3NCHN), 36.6 (CH3NN), 27.7 (CH2CN),
20.7 (CH2CH2CH2).
Anal. Calcd for C11H18I2N4: C, 28.72; H, 3.94; I, 55.16; N, 12.18.
Found: C, 28.71; H, 3.89; I, 55.32; N, 11.90.
HRMS (ESI): m/z [M]2+ calcd for C11H18N42+: 103.076; found:
103.0758.
Synthesis of 1,2,3-Triazolium Salts and Imidazolium Salts 8, 12,
and 15; General Procedure (Method C)
A solution of AgBF4 (10 mmol) in anhydrous MeOH (30 mL) was
added portion-wise to a stirred solution of triazolium salts 7, 11a,
11b or imidazolium salt 14 (10 mmol) in MeOH (30 mL) until no
more precipitate of AgI was formed. The supernatant was decanted,
evaporated and washed with Et2O (2 × 10 mL) to afford pure prod-
ucts 8, 12a, 12b, and 15 after removing traces of solvents under
vacuum.
HRMS (ESI): m/z [M]2+ calcd for C17H23N52+: 148.5971; found:
148.5971.
Synthesis 2010, No. 15, 2609–2615 © Thieme Stuttgart · New York

2614
S. S. Khan, J. Liebscher
PAPER
Suzuki Cross-Coupling Reaction; General Procedure25
1,1¢-(Propane-1,3-diyl)bis(4-butyl-2-methyl-1H-1,2,3-triazol-2-
ium) Ditetrafluoroborate (8)
Yield: 92%; colourless solid; mp 72 °C.
Under an argon atmosphere, 1,4-dioxane (3 mL), aryl chloride, io-
dide, bromide, triflate or tosylate 17 (1.0 mmol), and arylboronic
acid 16 (1.5 mmol) were added in turn to a Schlenk tube charged
with Pd2(dba)3 (14 mg, 0.015 mmol), the NHC precursor (0.03
mmol), Cs2CO3 (652 mg, 2.00 mmol) and a magnetic stirring bar.
The Schlenk tube was placed in an 80 °C oil bath and the reaction
mixture was stirred for 1.5–2.0 h. The mixture was then allowed to
cool to r.t. and the mixture was purified either by flash chromatog-
raphy, or filtered through a pad of Celite, concentrated and then pu-
rified by flash chromatography. The structure of the coupling
product 18 was confirmed by comparison of the NMR data to those
reported in the literature.25
1H NMR (CD3OD, 300 MHz): d = 8.43 (s, 2 H, 2 × CHtriaz), 4.69 (t,
J = 6.88 Hz, 4 H, 2 × CH2N), 4.21 (s, 6 H, 2 × CH3N), 2.85 (t,
J = 7.30 Hz, 4 H, 2 × CH2Ctriaz), 2.66–2.75 (pent, J = 6.92 Hz, 2 H,
NCH2CH2), 1.70–1.80 (m, 4 H, 2 × CH3CH2CH2), 1.49 (sext,
J = 7.31 Hz, 4 H, 2 × CH3CH2), 0.99 (t, J = 7.33 Hz, 6 H, 2 ×
CH3CH2).
13C NMR (CD3OD, 75 MHz): d = 146.5 (Ctriaz), 129.3 (2 × CHtriaz),
50.9 (2 × NCH2), 37.8 (2 × CH3N), 29.5 (2 × CH3CH2CH2), 29.4 (2
× CH2Ctriaz), 23.7 (2 × CH3CH2), 23.0 (NCH2CH2), 13.8 (2 ×
CH3CH2).
HRMS (ESI): m/z [M]2+ calcd for C17H32N62+: 160.1344; found:
160.1300.
Acknowledgment
Financial support by the Deutsche Forschungsgemeinschaft (DFG,
priority programme ‘Organocatalysis’ SPP1179) is gratefully ack-
nowledged. We thank Saltigo GmbH, Bayer Services GmbH & Co.
OHG, BASF AG and Sasol GmbH.
3-Benzyl-1-methyl-5-[3-(3-methyl-1H-imidazol-3-ium-1-
yl)propyl]-3H-1,2,3-triazol-1-ium Ditetrafluoroborate (12a)
Yield: 92%; yellow oil.
1H NMR (CD3OD, 300 MHz): d = 8.80 (s, 1 H, NCHN), 8.53 (s,
1 H, CH2NCHCH), 7.62 (s, 1 H, CH2NCHCH), 7.41–7.53 (m, 6 H,
CHAr + CHtriaz), 5.76 (s, 2 H, PhCH2), 4.34 (t, J = 7.24 Hz, 2 H,
CH2NCHN), 4.20 (s, 3 H, CH3NN), 3.90 (s, 3 H, CH3NCHN), 2.94
(m, 2 H, CH2CN), 2.28–2.38 (m, 2 H, CH2CH2CH2).
13C NMR (CD3OD, 75 MHz): d = 143.5 (Ctriaz), 136.7 (NCHN),
130.2 (CAr), 129.2 (CHAr), 128.9 (CHAr), 128.8 (CHAr), 127.8 (CHtriaz),
123.6 (CH2NCHCH), 122.1 (CH2NCHCH), 56.7 (PhCH2), 48.0
(CH2NCHN), 36.6 (CH3NCHN), 35.1 (CH3NN), 26.6 (CH2CN),
19.5 (CH2CH2CH2).
References
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1H NMR (CD3OD, 300 MHz): d = 8.81 (s, 1 H, NCHN), 8.35 (s,
1 H, CH2NCHCH), 7.59 (s, 1 H, CH2NCHCH), 7.52 (s, 1 H, CHtriaz),
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117.5892.
1,1¢-(Propane-1,3-diyl)bis(3-methyl-1H-imidazol-3-ium) Ditet-
rafluoroborate (15)
Yield: 85%; colourless oil.
1H NMR (CD3OD, 300 MHz): d = 8.75 (s, 2 H, 2 × NCHN), 7.58
(m, 2 H, 2 × CH2NCHCH), 7.51 (m, 2 H, 2 × CH2NCHCH), 4.29
(m, 4 H, 2 × CH2N), 3.90 (s, 6 H, 2 × CH3N), 2.44–2.53 (m, 2 H,
CH2CH2CH2).
13C NMR (CD3OD, 75 MHz): d = 137.9 (2 × NCHN), 124.9 (2 ×
CH2NCHCH), 123.3 (2 × CH2NCHCH), 47.2 (2 × CH2N), 36.3 (2
× CH3N), 31.1 (CH2CH2CH2).
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103.0758.
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Synthesis and Application of Dicationic Azolium Salts
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