Reusable ammonium salt-tagged NHC-Cu(i) complexes: Preparation and catalytic application in the three component click reaction

Article abstract of DOI:10.1039/c1gc15871f

A series of ammonium salt-tagged SIPr-Cu(i) complexes have been conveniently synthesized and characterized by NMR and HRMS. They are highly active toward the three component click reaction of benzyl bromide, NaN ₃ and alkyne with water as solve

Full text of DOI:10.1039/c1gc15871f

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PAPER
Reusable ammonium salt-tagged NHC–Cu(I) complexes: preparation and
catalytic application in the three component click reaction†
Wenlong Wang,a,c Junliang Wu,a Chungu Xiaa and Fuwei Li*a,b
Received 19th July 2011, Accepted 8th September 2011
DOI: 10.1039/c1gc15871f
A series of ammonium salt-tagged SIPr–Cu(I) complexes have been conveniently synthesized and
characterized by NMR and HRMS. They are highly active toward the three component click
reaction of benzyl bromide, NaN3 and alkyne with water as solvent at rt. Current water soluble
NHC–Cu(I) catalyst could be efficiently used at least four times with an 84% isolated yield of the
desired triazole in the last run.
there is no account of the synthesis of ammonium salt-tagged
NHC-metal catalysts and their catalytic application using water
Introduction
Since the first isolation of “free” N-heterocyclic carbene (NHC)
as a green media.
by Arduengo in 1990,1 NHC-transition metal complexes have
Click chemistry is a chemical concept introduced by Sharpless
attracted considerable attention owing to their high stability and
and coworkers in 2001,11 and the Cu(I)-catalyzed azide-alkyne
outstanding application in homogeneous catalysis.2 However,
cycloaddition (CuAAC) has undoubtedly become the most
most of them are complicated to synthesize through multiple
popular click-reaction, and has found a wide application in
steps and only can be used for one time in the homogeneous
chemistry, biology and material science because of its mild
reaction. They could not be separated easily from the reaction
conditions and high efficiency.12 Recently, the CuAAC has
system and reused, which thus caused not only the waste of
been proved to be accelerated by Cu(I) species supported by
expensive transition metal complexes but also a contamination
nitrogen,13 sulfur,14 phosphine15 and NHC16 ligands, since these
problem in the product. In order to overcome these limitations,
ligands could stabilize the Cu(I) center and thus enhance its
a number of reusable NHC-transition metal catalysts have been
catalytic activity. However, recycling of the CuAAC catalyst is
developed by different supporting strategies such as immobi-
scarcely investigated due to the generally homogeneous nature of
lization of the complexes on the silica gel,3 polymer,4 SBA-16,5
these copper catalysts. On the other hand, most of the reported
MCM-416 and nanoparticle supports7 or via self-coordinative
CuAAC studies are two-component (organic azide and alkyne)
reaction systems; the organic azides need to be synthesized in
polymerization to be a recyclable catalyst.8
Introducing a water soluble moiety such as ammonium salt
advance, and the potential hazards of organic azides especially in
or sulfonate group onto the ligand to make the resultant metal
isolation or purification processing can be problematic. It is thus
complex more soluble in water is also an ideal solution for
desirable to develop an efficient one-pot methodology that uses
immobilization and recycling of the expensive (or hard to
halides and sodium azide for direct cycloaddition with alkyne.
prepare) metal catalyst by using aqueous solvent system; this
As part of our continuing studies on the preparation and
methodology has been applied in many kinds of ligands where
catalytic application of transition metal-NHC complexes17 and
phosphines are by far the ones that have been most widely
the three-component CuAAC,13a we herein describe the synthesis
studied,9 however it is rather surprising that these types of
of a new class of water soluble Cu(I)–NHC complexes and their
NHC ligands or metal complexes have rarely been developed for
recyclable application in the three component CuAAC with
catalytic reactions in water,9,10 and, to the best of our knowledge,
water as solvent at rt.
aState Key Laboratory for Oxo Synthesis and Selective Oxidation,
Results and discussion
Lanzhou Institute of Chemical Physics, Lanzhou, 730000, China.
E-mail: fuweili@licp.cas.cn; Fax: (+86)-931-4968129
bSuzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of
Sciences, Suzhou, 215123, China
Typical SIPr (SIPr
=
N,N¢-bis(2,6-diissopropylphenyl)-
imidazolidin-2-ylidene) has been applied in many catalytic
reactions as an effective ligand with various transition metals.2
However, Nolan and co-workers found that neutral [(SIPr)CuCl]
showed latent reactivity toward the standard two component
click reaction of benzyl azide and phenylacetylene only giving
cChinese Academy of Sciences and Graduate School of Chinese Academy
of Sciences, Beiijng 100049, China
† Electronic supplementary information (ESI) available: 1H NMR, 13
C
NMR spectra and HRMS analyses for unknown compounds. See DOI:
10.1039/c1gc15871f
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26% conversion of substrate after one week of reaction time
with water as solvent,16d introduction of an ammonium electron
withdrawing group (EWG) to the ligand of the complex can alter
its physical-chemical properties such as solubility in aqueous
media, and will possibly increase the catalyst’s activity.18
The synthetic route of Cu(I)–NHC catalysts (5 and 6)
investigated in this work are shown in Scheme 1, commercially
available 2,6-diisopropylaniline (1) was easily converted to 3
via morphine functionalized [SIPr]·HCl (2) according to the
reported procedure,19 and subsequent N-alkylation of 3 with
triethylamine or tributlyamine gave the desired ammonium
salt-tagged NHC-precursor 4a or 4b as white solid in high
yields (>90%), respectively. The formation of 4a and 4b was
confirmed by the characteristic downfield signal in the 1H NMR
spectra at 9.82 and 9.89 ppm for the NCHN proton and a base
peak in the HRMS(ESI) at m/z = 206.5226 and 262.5847 for
the ammonium-tagged H[SIPr]3+ fragment. Deuteration of the
NCHN proton of 4a and 4b was also observed when using D2O
as NMR solvent.20
a yield of 77% with CuI as the copper source, however, reaction
of carbene precursor 4a with CuBr in the presence of KOt-Bu
was found to be particularly inefficient, due to the significant
formation of unidentified products. In this case, 80% yield of 5b
could be achieved using CuBr.SMe2 as metal source under the
same reaction conditions with that of 5a and 5c. Similarly, 6a,
6b, and 6c could be obtained in 71%–82% yield by reaction of 4b
with the corresponding copper source with KOt-Bu as a base. All
the Cu–NHC coordination was established by the 13C NMR shift
at about 201 ppm, assignable to the 2C-imidazolidin-2-ylidene
1
carbon, and absence of the H resonance of NCHN proton.
It is worth to mention that methanol as solvent and heating
are crucial for the efficient synthesis of current ammonium salt-
tagged NHC–Cu(I) complexes.
We initially carried out the standard three component click
reaction of benzyl bromide and NaN3 with phenylacetylene in
water to investigate the catalyst activity of 5 and 6 (Table 1).
Unlike the latent activity of neutral [(SIPr)CuCl] in the two
component click reaction of benzyl azide and phenylacetylene at
room temperature,16d the current ionically tagged [(SIPr)CuCl]
(5a) showed efficient activity toward the model click reaction
affording a 98% isolated yield of triazole (7a) within 3 h (entry
1). Unfortunately, replacing the chloride on the copper center by
a bromide only gave trace catalytic activity (entry 2), this trend
demonstrated by 5b is opposite to the neutral [(SIMes)CuBr]
(SIMes = N,N¢-bis(2,6-dimethylphenyl)imidazolidin-2-ylidene),
which showed higher activity than that of [(SIMes)CuCl] in the
two component click reaction.16e Changing chloride to iodide
also resulting in a lower yield of 71% in 3 h and the reactivity
could be enhanced to 92% with prolonged reaction time (entry
3). Generally, complexes 6 displayed lower reactivity compared
to their corresponding analogues of 5 (entries 4–6), which is
possibly due to the catalyst solubility difference in water between
5 and 6 resulted from the longer hydrophobic alkyl chain of the
ammonium salt on 6. Interestingly, Similar trend in reactivity
of 5 and 6 with respect to their counterion was found for this
reaction (Cl > I ꢀ Br). Interestingly, the model click reaction
Table 1 Catalyst screening in the click synthesis of [1,2,3]-triazole (7a)a
Scheme 1 Synthesis of ammonium salt-tagged SIPr–Cu(I) (5 and 6).
Reagent and conditions: (i) triethylamine or tributlyamine, MeOH,
reflux; (ii) CuCl or CuBr∑SMe2 or CuI, KOtBu, MeOH, reflux.
Entry
1
Catalyst (mol%)
Time (h)
Yieldb (%)
Following the reported methodology,16a the initial synthesis
of ionically tagged [(SIPr)CuCl] by the reaction of CuCl with
in situ-generated free NHC from its imidazolium salt and 1.0
equivalent of a strong base (KOt-Bu) in THF or toluene at rt
only resulted in a low yield of the desired NHC–Cu(I) complex
during the prolonged reaction time (48 h), which is possibly
caused by the different physical-chemical properties between
standard [SIPr]·HCl carbene precursor and the current ionically
tagged one, and we did find most of the imidazolium salts was not
dissolved during the reaction and a quite number of unreacted
starting salt was recovered. Changing solvent to MeOH and
performing the reaction in reflux eventually led to a 74% yield
of [(NHC)CuCl] (5a). As seen in Scheme 1, these optimized
reaction conditions could be extended to the synthesis of 5c in
Complex 5a (5%)
6
3
6
6
3
6
3
6
98
98
trace
92
71
94
76
trace
66
95
2
3
Complex 5b (5%)
Complex 5c (5%)
4
Complex 6a (5%)
5
6
7
8
9
Complex 6b (5%)
Complex 6c (5%)
Complex 5a (2%)
Complex 5a (1%)
Complex 5a (0.5%)
6
24
36
48
91
88
a Reaction conditions: benzyl bromide (1.0 mmol), sodium azide (1.2
mmol), phenylacetylene (1.2 mmol), catalyst, water (2.0 mL), rt.
b Isolated yield.
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Scheme 2 Ammonium salt-tagged [(SIPr)CuCl]-catalyzed three component synthesis of triazoles. Reaction conditions: benzyl bromide (1.0 mmol),
NaN3 (1.2 mmol), alkyne (1.2 mmol), 5a (5.0 mol%), H2O (2.0 mL), rt.
could also proceed smoothly catalyzed by current ammonium-
tagged SIPr–u(I) with low catalyst loading (up to 0.5 mol%) and
prolonged reaction time. 2.0 mol% of catalyst 5a gave 95% yield
of 7a in 24 h (Entry 7) and 91% yield of the desired product
was obtained in the presence of further reduced catalyst loading
(Entry 8, 1.0 mol%). To our delight, catalyst loading could be
minimized to 0.5 mol%, affording excellent yield of 7a within
48 h (Entry 9).
was performed in the model click reaction of benzyl bromide,
sodium azide and phenylacetylene with 2 mol% of 5a for
24 h (Fig. 1). After the completion of reaction, ether was
added to the reaction tube, the upper organic phase containing
product was easily separated by simple liquid–liquid extraction
to produce triazole 7a, and the residual aqueous catalyst phase
was remained and reused for the next run because of the obvi-
ous solubility difference of the ammonium salt functionalized
[(SIPr)CuX] in ether and water. It is shown in Fig. 1 that current
water soluble catalyst could be used at least four times with the
fourth run giving an 84% isolated yield of 7a.
With the optimized catalyst 5a in hand, we then investigated
the scope of this three component catalytic system with pure
water as solvent, as shown in Scheme 2. To ensure short
reaction duration and minimize any decomposition of starting
substrates, 5 mol% of 5a was used. All reactions proceeded
smoothly giving high isolated yield of the desired triazoles
1
(7) with good NMR purity (based on H NMR spectra, see
ESI†) after simple filtration at room temperature. For the
organic bromides, benzyl bromides with electron-withdrawing
or electron-donating groups all afforded good yields. Electron-
rich or electron-poor alkynes all worked efficiently toward this
click transformation and the hydroxyl-functionalized alkyne was
also a good reaction partner resulting in 82%–93% yield of
the corresponding triazole (7e and 7k). Current catalyst system
could effectively tolerate the N-containing aryl acetylene (7f and
7l). The double click of diyne also proceeded efficiently affording
the desired meta-bis-triazole (7u) with 84% yield.
To validate the recyclability of current ammonium-tagged
SIPr–Cu(I) under lower catalyst loading, the reuse investigation
Fig. 1 The recyclability test of complex 5a.
3442 | Green Chem., 2011, 13, 3440–3445
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1
(m, 16 H), 4.48 (s, 4 H), 4.58 (s, 4 H), 7.43 (s, 4 H); H NMR
(DMSO-d6): 0.97 (t, 18 H), 1.21 (d, 16 H, J = 6.8 Hz), 1.28–1.37
(m, 20 H), 1.76 (s, 12 H), 3.15 (t, 16 H), 4.58 (s, 4 H), 4.65 (s,
4 H), 7.59 (s, 4 H), 9.89 (s, 1 H); 13C NMR (DMSO-d6): 13.6,
13.4, 23.3, 24.8, 28.2, 45.4, 53.8, 56.0, 57.9, 60.9, 125.4, 129.4,
131.0, 131.4, 146.8, 160.2. HRMS m/z (ESI) calcd for C53H95N4
[cation]3+ 262.5847, found 262.5853.
Conclusions
In summary, we have developed a series of reusable ammonium
salt-tagged [(SIPr)CuX] complexes, which showed highly effi-
cient reactivity toward the three component click-reaction of
a wide arrange of benzyl bromides and alkynes using water as
solvent at rt. The optimized catalyst 5a could be conveniently
recycled up to three times without a significant loss of its activity
with catalyst loading as low as 2.0 mol% in the fresh run.
The observed higher catalytic activities of this ammonium salt-
tagged [(SIPr)CuCl] compared to its standard neutral analogue
demonstrates the potential of ionic functionalization of NHC–
Cu(I) complex in promoting CuAAC catalysis and achieving
catalyst recycle. Current experiments in our laboratory are
directed at the synthesis of new recyclable transition metal-NHC
complexes and their catalytic applications.
General procedure for the preparation of ammonium salt-tagged
NHC–Cu(I) complexes (5 and 6)
An oven-dried Schlenk flask was charged with 4a (726 mg,
1.0 mmol), CuCl (109 mg, 1.1 mmol) and KOt-Bu (135 mg,
1.0 mmol). The flask was evacuated and backfilled with argon
three times before the addition of dried methanol (30 mL),
then the mixture was refluxed for 12h. After the completion
of reaction, the resultant reaction mixture was filtered through
a plug of Celite, and the filtrate was concentrated to about 10
mL under reduced pressure. Upon the addition of pentane to
the crude reaction mixture, complex 5a was slowly precipitated
and isolated as a yellow solid (584 mg, 74%).
Experimental
All the chemical and solvents were used as received
without purification except MeOH, which was dried by
distillation over magnesium powder and freshly distilled
prior to use. 1,3-Bis(2,6-diisopropyl-4-(chloromethyl)phenyl)-
4,5-dihydro-1-H-imidazol-3-ium-chloride (3) was synthesized
according to the reported procedure.19 NMR spectra were
recorded using a Bruker AvanceTM spectrometer operating at
400 MHz for 1H and 100 MHz for 13C. Chemical shifts are given
in ppm relative to TMS or to residual solvent proton resonances.
High resolution mass spectra (HRMS) were obtained on a
Bruker micrOTOF-Q spectrometer. All the reported yields in
the catalytic studies are isolated yields and averaged by at least
two runs.
Complex 5b, 5c, 6a, 6b and 6c were synthesized in high
yields by similar procedure to the preparation of 5a from
corresponding copper resource and carbene precursor (see
Scheme 1 and ESI†).
(1,3-Bis(2,6-diisopropyl-4-((triethylammonio)methyl)phenyl)
imidazolidin-2-yl)copper(I) chloride (5a). 1H NMR (D2O):
1.20–1.30 (m, 42 H), 3.10–3.16 (m, 16 H), 4.14 (s, 4 H), 4.36
(s, 4 H), 7.33 (s, 4 H). 13C NMR (D2O): 7.1, 22.7, 24.7, 28.3,
52.6, 53.5, 60.3, 128.6, 136.4, 148.7, 201.1. HRMS m/z (ESI)
calcd for C41H70ClCuN4 [cation]2+ 358.2287, found 358.2295.
(1,3-Bis(2,6-diisopropyl-4-((triethylammonio)methyl)phenyl)
General procedure for the synthesis of ammonium salt-tagged
SIPr-carbene precursor (4a and 4b)
imidazolidin-2-yl)copper(I) bromide dichloride (5b). White
solid, 77% yield; H NMR (D2O): 1.16–1.20 (m, 24 H), 1.25
1
(t, 18 H, J = 7 Hz), 3.03–3.13 (m, 16 H), 4.10 (s, 4 H), 4.33 (s,
4 H), 7.30 (s, 4 H). 13C NMR (D2O): 7.0, 22.7, 24.6, 28.3, 52.6,
53.4, 60.3, 128.5, 136.4, 148.7, 201.3. HRMS m/z (ESI) calcd
for C41H70BrCuN4 [cation]2+ 380.2034, found 380.2035.
10 mL triethylamine or tributylamine was added slowly to a
MeOH solution (80 mL) of freshly synthesized intermediate 3
(2 g, 3.82 mmol) at room temperature, the reaction mixture was
subsequently refluxed for 24 h. The solvent and excess tertiary
amines were evaporated under the reduced pressure, and 100 mL
of anhydrous ether was added to precipitate the product, and the
resultant white powder was collected and washed with 10 mL
of ether three times to give the corresponding ammonium salt-
tagged carbene precursor 4a (2.61 g, 94%) or 4b (3.14 g, 92%).
(1,3-Bis(2,6-diisopropyl-4-((triethylammonio)methyl)phenyl)
imidazolidin-2-yl)copper(I) iodide dichloride (5c). White solid
1
80% yield; H NMR (D2O): 1.10–1.15 (m, 24 H), 1.27 (t, 18
H, J = 7 Hz), 3.00–3.07 (m, 16 H), 3.98 (s, 4 H), 4.30 (s, 4
H), 7.21 (s, 4 H). 13C NMR (D2O): 7.0, 23.2, 24.6, 28.2, 52.3,
53.1, 59.8, 128.0, 137.2, 148.6, 201.4. HRMS m/z (ESI) calcd
for C41H70ICuN4 [cation]2+ 404.1965, found 404.1950.
1,3-Bis(2,6-diisopropyl-4-((triethylammonio)methyl)phenyl)-
1
4,5-dihydro-1H-imidazol-3-ium chloride (4a). White solid; H
NMR (D2O): 1.23 (t, 12 H), 1.35–1.40 (m, 30 H), 3.07–3.14 (m,
4 H, J = 6.8 Hz), 3.16–3.25 (m, 12 H), 4.46 (s, 4 H), 4.59 (s, 4
H), 7.46 (s, 4 H); 1H NMR (DMSO-d6): 1.21 (d, 12 H, J = 6.8
Hz), 1.31–1.38 (m, 30 H, J = 6.8 Hz), 3.13 (t, 4 H, J = 6.4 Hz),
3.16–3.22 (m, 12 H, J = 7.2 Hz), 4.59 (d, 8 H, J = 10.4 Hz), 7.57
(s, 4H), 9.82 (s,1 H); 13C NMR (D2O): 7.0, 22.4, 24.2, 28.7, 52.6,
53.6, 59.8, 128.8, 130.5, 131.1, 147.7. HRMS m/z (ESI) calcd
for C41H71N4 [cation]3+ 206.5221, found 206.5226.
(1,3-Bis(2,6-diisopropyl-4-((tributylammonio)methyl) phenyl)
imidazolidin-2-yl)copper(I) chloride (6a). Yellow solid, 71%
1
yield; H NMR (D2O): 0.85 (d, 18 H, J = 7.2 Hz), 1.20–1.26
(m, 32 H), 1.68 (s, 12 H), 1.98 (s, 4 H), 3.11 (s, 16 H), 4.12 (s, 4
H), 4.38 (s, 4 H), 7.29 (s, 4 H). 13C NMR (DMSO-d6): 13.5, 19.3,
23.4, 24.9, 28.1, 53.7, 57.9, 61.5, 129.1, 131.1, 136.2, 147.1, 201.0.
HRMS m/z (ESI) calcd for C53H94ClCuN4 [cation]2+ 442.3226,
found 442.3224.
1,3-Bis(2,6-diisopropyl-4-((tributylammonio)methyl)phenyl)-
4,5-dihydro-1H-imidazol-3-ium chloride (4b). White solid; H
NMR (D2O): 0.95 (t, 18 H, J = 7.2 Hz), 1.21 (d, 16 H, J =
6.8 Hz), 1.36 (d, 20 H, J = 6.8 Hz), 1.79 (s, 12 H), 3.08–3.14
(1,3-Bis(2,6-diisopropyl-4-((tributylammonio)methyl)phenyl)
1
imidazolidin-2-yl)copper(I) bromide dichloride (6b). White
1
solid, 82% yield; H NMR (D2O): 0.82–0.88 (m, 18 H), 1.19–
1.28 (m, 32 H), 1.69 (s, 12 H), 2.05 (s, 4 H), 3.03 (d, 16 H, J =
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4.8 Hz), 4.13 (s, 4 H), 4.39 (d, 4 H, J = 5.2 Hz), 7.30 (s, 4 H).
13C NMR (DMSO-d6): 13.5, 19.4, 23.3, 25.0, 28.2, 53.7, 58.0,
61.2, 129.2, 131.1, 136.2, 147.1, 201.1. HRMS m/z (ESI) calcd
for C53H94BrCuN4 [cation]2+ 464.2973, found 464.2977.
128.4, 129.0, 129.2, 129.8 130.5, 132.5, 133.8. HRMS m/z (ESI)
calcd for C15H12BrN3Na [M+Na]+ 336.0107, found 336.0096.
1-(4-Bromobenzyl)-4-(p-tolyl)-1H-1,2,3-triazole (7h). White
solid; 1H NMR (CDCl3): 2.36 (s, 2 H), 5.51 (s, 2 H), 7.16–7.22
(m, 4 H), 7.51 (d, 2 H, J = 8.4 Hz), 7.63 (brs, 1 H), 7.68 (d, 2 H,
J = 8.0 Hz). 13C NMR (CDCl3): 21.4, 53.7, 119.2, 123.1, 125.8,
127.7, 129.7, 129.8, 132.5, 133.9, 138.3. HRMS m/z (ESI) calcd
for C16H15BrN3 [M+H]+ 328.0444, found 328.0430.
(1,3-Bis(2,6-diisopropyl-4-((tributylammonio)methyl)phenyl)
imidazolidin-2-yl)copper(I) iodide dichloride (6c). White solid,
1
78% yield; H NMR (D2O): 0.83 (t, 18 H, J = 7.2 Hz), 1.18–
1.24 (m, 32 H), 1.67 (s, 12 H), 1.93 (s, 4 H), 3.01 (s, 16 H),
4.12 (s, 4 H), 4.38 (s, 4 H), 7.29 (s, 4 H). 13C NMR (DMSO-d6):
13.5, 19.4, 23.4, 24.9, 28.1, 53.6, 57.9, 61.5, 129.1, 131.1, 136.2,
147.2, 201.1. HRMS m/z (ESI) calcd for C53H94ICuN4 [cation]2+
488.2904, found 488.2909.
1-(4-Bromobenzyl)-4-(4-ethylphenyl)-1H-1,2,3-triazole (7i).
1
White solid; H NMR (CDCl3): 1.25 (t, 3 H, J = 7.6 Hz), 2.67
(q, 2 H, J = 7.6 Hz), 5.52 (s, 2 H), 7.17 (d, 2 H, J = 8.4 Hz),
7.24 (d, 2 H, J = 8 Hz), 7.50–7.52 (m, 2 H), 7.63 (brs, 1 H),
7.71 (d, 2 H, J = 8.4 Hz). 13C NMR (CDCl3): 15.6, 28.8, 53.6,
119.3, 123.0, 125.8, 127.9, 128.4, 129.8, 132.4, 133.9, 144.7.
HRMS m/z (ESI) calcd for C17H17BrN3 [M+H]+ 342.0600,
found 342.0595.
Typical procedure for the three component click-reaction
catalyzed by complex 5a
Organic bromide (1.0 mmol), NaN3 (1.2 mmol), alkyne (1.2
mmol), catalyst 5a (0.05 mmol) and water (2.0 mL) were
introduced to a vial fitted with a screw cap. The reaction was
carried out at room temperature and monitored by TLC. After
completion of the reaction, 20 mL of water was added to the
vial and the mixture was stirred for 10 min to precipitate the
product completely, which was collected by suction filtration
and washed with 10 mL of water several times affording the
desired triazole. All the products can be obtained with NMR
purity by this procedure.
1-(4-Bromobenzyl)-4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazole
1
(7j). White solid; H NMR (CDCl3): 1.33 (s, 9 H), 5.52 (s, 2
H), 7.16 (d, 2 H, J = 8.4 Hz), 7.43 (d, 2 H, J = 8.4 Hz), 7.51 (m, 2
H), 7.65 (brs, 1 H), 7.73 (d, 2 H, J = 8.4 Hz). 13C NMR (CDCl3):
31.3, 34.7, 53.5, 119.3, 122.9, 125.5, 125.8, 127.4, 129.6, 131.9,
132.3, 133.8, 151.5. HRMS m/z (ESI) calcd for C19H20BrN3Na
[M+Na]+ 392.0733, found 392.0715.
2-(1-(4-(tert-Butyl)benzyl)-1H-1,2,3-triazol-4-yl)propan-2-ol
1
(7k). White solid; H NMR (CDCl3): 1.32 (s, 9 H), 1.61 (s, 6
H), 5.47 (s, 2 H), 7.22 (d, 2 H, J = 8.4 Hz), 7.35 (brs, 1 H), 7.40
(d, 2 H, J = 8.0 Hz). 13C NMR (CDCl3): 30.5, 31.4, 34.8, 54.3,
68.5, 126.2, 128.2, 131.3, 152.2, 155.7. HRMS m/z (ESI) calcd
for C16H23N3NaO [M+Na]+ 296.1733, found 296.1723.
Recyclability study
All the recycling operations were carried out in a 25 mL Schlenk
tube under argon atmosphere. After the completion of the fresh
reaction performed as above typical procedure in the presence
of 2 mol% of 5a for 24 h, the reaction mixture was extracted with
ether (4 ¥ 20 mL) to remove the starting substrate and product,
and the residual aqueous catalyst phase could be reused for the
next run after addition of fresh reactants. The organic extracts
were combined and purified to give the desired triazole 7a.
2-(1-(4-(tert-Butyl)benzyl)-1H-1,2,3-triazol-4-yl)pyridine (7l).
brown solid; 1H NMR (CDCl3): 1.31 (s, 9 H), 5.55 (s, 2 H), 7.20–
7.23 (m, 1 H), 7.28 (d, 3 H, J = 8.8 Hz), 7.40 (dd, 2 H, J = 7.2,
2.0 Hz), 7.75–7.79 (m, 1 H), 8.04 (brs, 1 H), 8.18 (d, 1 H, J = 8.0
Hz), 8.53 (d, 1 H, J = 4.8 Hz). 13C NMR (CDCl3): 31.4, 34.8,
54.4, 121.2, 123.3, 126.3, 128.3, 131.2, 152.2. HRMS m/z (ESI)
calcd for C18H20N4Na [M+Na]+ 315.1586, found 315.1574.
NMR and HRMS data of new compounds
1-(4-(tert-Butyl)benzyl)-4-(p-tolyl)-1H-1,2,3-triazole
(7m).
1-Benzyl-4-(4-ethylphenyl)-1H-1,2,3-triazole
(7c). White
White solid; 1H NMR (CDCl3): 1.31(s, 9 H), 2.36 (s, 3 H), 5.53
(s, 2 H), 7.20 (d, 2 H, J = 7.2 Hz), 7.25 (d, 2 H, J = 8.4 Hz), 7.40
(d, 2 H, J = 6.8 Hz), 7.65 (brs, 1 H), 7.69 (d, 2 H, J = 7.6 Hz).
13C NMR (CDCl3): 21.4, 31.4, 34.8, 54.1, 125.7, 126.2, 128.0,
129.6, 131.8, 132.5, 138.1, 139.6, 152.0. HRMS m/z (ESI) calcd
for C20H24N3 [M+H]+ 306.1970, found 306.1947.
solid; 1H NMR (CDCl3): 1.24 (t, 3 H, J = 7.6 Hz), 2.66 (q, 2 H,
J = 7.6 Hz), 5.57 (s, 2 H), 7.22–7.30 (m, 2 H), 7.31 (d, 2 H, J =
2.4 Hz), 7.36–7.41 (m, 3 H), 7.63 (brs, 1 H), 7.72 (d, 2 H, J = 8.4
Hz). 13C NMR (CDCl3): 15.5, 28.7, 54.2, 125.7, 128.0, 128.3,
128.7, 129.1, 131.6, 134.8, 144.4, 148.3. HRMS m/z (ESI) calcd
for C17H18N3 [M+H]+ 264.1495, found 264.1489.
1-(4-(tert-Butyl)benzyl)-4-(4-(tert-butyl)phenyl)-1H-1,2,3-
1
1-Benzyl-4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazole
(7d).
triazole (7n). White solid; H NMR (CDCl3): 1.31 (s, 9 H),
1
White solid; H NMR (CDCl3): 1.33 (s, 9 H), 5.57 (s, 2 H),
7.28–7.30 (m, 2 H), 7.38 (d, 2 H, J = 7.2 Hz), 7.42 (d, 2 H, J = 8.0
Hz), 7.65 (brs, 1 H), 7.74 (d, 2 H, 8.0 Hz). 13C NMR (CDCl3):
31.3, 34.7, 54.3, 125.5, 125.8, 127.6, 128.0, 128.3, 128.8, 129.1,
134.7, 151.4. HRMS m/z (ESI) calcd for C19H21N3Na [M+Na]+
314.1628, found 314.1615.
1.33(s, 9 H), 5.54 (s, 2 H), 7.22–7.43 (m, 7 H), 7.78 (brs, 2 H).
13C NMR (CDCl3): 31.4, 34.8, 54.2, 125.5, 125.9, 126.2, 128.0,
128.9, 131.8, 132.4, 134.9, 151.4, 152.0. HRMS m/z (ESI) calcd
for C23H30N3 [M+H]+ 348.2434, found 348.2413.
1-(4-(tert-Butyl)benzyl)-4-(4-ethylphenyl)-1H-1,2,3-triazole
(7p). White solid; 1H NMR (CDCl3): 1.23 (t, 3 H, J = 7.6 Hz),
1.31 (s, 9 H), 2.65 (q, 2 H, J = 7.6 Hz), 5.52 (s, 2 H), 7.21–7.25
(m, 4 H), 7.38–7.40 (m, 4 H), 7.62 (brs, 1 H), 7.71 (d, 2 H, J = 8.0
Hz). 13C NMR (CDCl3): 15.6, 28.8, 31.4, 34.7, 54.0, 119.4, 125.8,
126.1, 128.0, 128.1, 128.4, 128.9, 131.8, 144.4, 152.0. HRMS
1-(4-Bromobenzyl)-4-phenyl-1H-1,2,3-triazole (7g). White
solid; 1H NMR (CDCl3): 5.53 (s, 2 H), 7.18 (d, 2 H, J = 8.4 Hz),
7.31–7.43 (m, 3 H), 7.52 (d, 2 H, J = 8.4 Hz), 7.67 (brs, 1 H), 7.80
(d, 2 H, J = 7.2 Hz). 13C NMR (CDCl3): 53.7, 119.6, 123.1, 125.8,
3444 | Green Chem., 2011, 13, 3440–3445
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m/z (ESI) calcd for C42H50N6Na [2M+Na]+ 661.3995, found
661.3973.
Fu¨rstner, Organometallics, 2004, 23, 280–287; (e) M. Mayr, M. R.
Buchmeiser and K. Wurst, Adv. Synth. Catal., 2002, 344, 712–719.
4 (a) D. B. Bagal, Z. S. Qureshi, K. P. Dhake, S. R. Khan and B. M.
Bhanage, Green Chem., 2011, 13, 1490–1494; (b) P. Li, L. Wang, Y.
Zhang and M. Wang, Tetrahedron Lett., 2008, 49, 6650–6654.
5 H. Yang, X. Han, G. Li and Y. Wang, Green Chem., 2009, 11, 1184–
1193.
4-((4-(p-Tolyl)-1H-1,2,3-triazol-1-yl)methyl)benzonitrile (7q).
White solid; 1H NMR (CDCl3): 2.29 (s, 3 H), 5.55 (s, 2 H), 7.14
(d, 2 H, J = 8.0 Hz), 7.29 (d, 2 H, J = 8.0 Hz), 7.57–7.63 (m, 5 H).
13C NMR (CDCl3): 21.3, 53.4, 112.7, 118.2, 119.6, 125.7, 127.4,
128.4, 129.6, 132.9, 138.4, 140.1, 148.7. HRMS m/z (ESI) calcd
for C17H15N4 [M+H]+ 275.1291, found 275.1280.
6 H. Zhou, Y. M. Wang, W. Z. Zhang, J. P. Qu and X. B. Lu, Green
Chem., 2011, 13, 644–650.
7 (a) H. Yang, Y. Wang, Y. Qin, Y. Chong, Q. Yang, G. Li, L. Zhang
and W. Li, Green Chem., 2011, 13, 1352–1361; (b) S. Wittmann, A.
Scha¨tz, R. N. Grass, W. J. Stark and O. Reiser, Angew. Chem., Int.
Ed., 2010, 49, 1867–1870; (c) K. V. S. Ranganath, J. Kloesges, A. H.
Scha¨fer and F. Glorius, Angew. Chem., Int. Ed., 2010, 49, 7786–7789.
8 (a) M. N. Liu and O. Reiser, Org. Lett., 2011, 13, 1102–1105; (b) J.
Choi, H. Y. Yang, H. J. Kim and S. U. Son, Angew. Chem., Int.
Ed., 2010, 49, 7718–7722; (c) B. Karimi and P. F. Akhavan, Chem.
Commun., 2009, 3750–3752; (d) S. J. Connon, A. M. Dunne and S.
Blechert, Angew. Chem., Int. Ed., 2002, 41, 3835–3838.
4-((4-(4-Ethylphenyl)-1H-1,2,3-triazol-1yl)methyl)benzoni-
1
trile (7r). White solid; H NMR (CDCl3): 1.25 (t, 3 H, J =
7.6 Hz), 2.67 (q, 2 H, J = 7.6 Hz), 5.64 (s, 2 H), 7.25 (d, 1 H,
J = 8.4 Hz), 7.37 (d, 2 H, J = 8.4 Hz), 7.63–7.74 (m, 6 H).
13C NMR (CDCl3): 15.6, 28.8, 53.6, 112.9, 118.3, 119.5, 125.9,
127.6, 128.5, 129.9, 132.7, 133.0, 140.1, 144.9. HRMS m/z (ESI)
calcd for C18H17N4 [M+H]+ 289.1448, found 289.1439.
9 (a) K. H. Shaughnessy, Chem. Rev., 2009, 109, 643–710, and reference
therein.
4-((4-(4-(tert-Butyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)
10 (a) S. Roy and H. Plenio, Adv. Synth. Catal., 2010, 352, 1014–1022;
(b) A. Azua, S. Sanz and E. Peris, Organometallics, 2010, 29, 3661–
3664; (c) C. Fleckenstein, S. Roy, Leuthau and H. Plenio, Chem.
Commun., 2007, 2870–2872; (d) S. H. Hong and R. H. Grubbs, J.
Am. Chem. Soc., 2006, 128, 3508–3509; (e) M. an der Heiden and H.
Plenio, Chem.–Eur. J., 2004, 10, 1789–1797.
11 H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem., Int. Ed.,
2001, 40, 2004–2021.
12 (a) M. Meldal and C. W. Tornøe, Chem. Rev., 2008, 108, 2952–3015;
(b) J. E. Moses and A. D. Moorhouse, Chem. Soc. Rev., 2007, 36,
1249–1262; (c) J. F. Lutz, Angew. Chem., Int. Ed., 2007, 46, 1018–
1025.
1
benzonitrile (7s). Yellow solid; H NMR (CDCl3): 1.33 (s, 9
H), 5.52 (s, 2 H), 7.16 (d, 2 H, J = 8.4 Hz), 7.43 (d, 2 H, J =
8.0 Hz), 7.50 (d, 2 H, J = 8.4 Hz, 7.66 (brs, 1 H), 7.74 (d, 2 H,
J = 8.0 Hz). 13C NMR (CDCl3): 31.4, 34.8, 53.6, 119.3, 123.0,
125.5, 125.9, 127.6, 129.7, 132.0, 132.4, 134.0, 148.5, 151.5.
HRMS m/z (ESI) calcd for C20H21N4 [M+H]+ 317.1766, found
317.1782.
1,3-Bis(1-benzyl-1H-1,2,3-triazol-4-yl)benzene (7u). White
1
solid; H-NMR (CDCl3): 5.55 (s, 4 H), 7.29–7.43 (m, 11 H),
13 (a) F. W. Li and T. S. A. Hor, Chem.–Eur. J., 2009, 15, 10585–10592;
(b) V. O. Rodionov, S. I. Presolski, S. Gardinier, Y. H. Lim and M. G.
Finn, J. Am. Chem. Soc., 2007, 129, 12696–12704; (c) V. O. Rodionov,
S. I. Presolski, D. D´ıaz, V. V. Fokin and M. G. Finn, J. Am. Chem.
Soc., 2007, 129, 12705–12712; (d) T. R. Chan, R. Hilgraf, K. B.
Sharpless and V. V. Fokin, Org. Lett., 2004, 6, 2853–2855; (e) W. G.
Lewis, F. G. Magallon, V. V. Fokin and M. G. Finn, J. Am. Chem.
Soc., 2004, 126, 9152–9153.
7.73–7.78 (m, 4 H), 8.17 (s, 1 H). 13C NMR (CDCl3): 54.5, 123.0,
125.5, 128.3, 129.0, 129.3, 129.5, 131.0, 134.6. HRMS m/z (ESI)
calcd for C24H21N6 [M+H]+ 398.1822, found 398.1803.
Acknowledgements
14 F. Wang, H. Fu, Y. Jiang and Y. Zhao, Green Chem., 2008, 10, 452–
We are grateful to the National Natural Science Foundation of
China (21002106 and 21133011) and the Chinese Academy of
Science for financial support.
456.
15 N. Moitra, J. J. E. Moreau, X. Cattoe¨n and M. Wong Chi Man,
Chem. Commun., 2010, 46, 8416–8418.
16 (a) S. Diez-Gonzalez, E. C. Escudero-Adan, J. Benet-Buchholz, E.
D. Stevens, A. M. Z. Slawin and S. P. Nolan, Dalton Trans., 2010, 39,
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47, 8881–8884; (d) S. Diez-Gonzalez, E. D. Stevens and S. P. Nolan,
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