Preparation of ruthenium azido complex containing a Tp ligand and ruthenium-catalyzed cycloaddition of organic azides with alkynes in organic and aqueous media: Experimental and computational studies

Article abstract of DOI:10.1016/j.jorganchem.2014.09.038

The catalytic activity of a series of ruthenium azido complexes containing Tp ligands has been evaluated for the cycloaddition of terminal alkynes and azides to give selectively 1,5-disubstituted 1,2,3-triazoles. The complex Tp(PPh₃)(EtNH₂)RuN₃ (2, Tp = HB(pz)₃, pz = pyrazolyl) was found to be an effective catalyst for the cycloaddition reactions. In the presence of complex 2, azides reacted with a range of terminal alkynes containing various functionalities to selectively produce 1,5-disubstituted 1,2,3-triazoles. Theoretical calculations support the proposed mechanism.

Full text of DOI:10.1016/j.jorganchem.2014.09.038

Journal of Organometallic Chemistry 774 (2014) 57e60
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Preparation of ruthenium azido complex containing a Tp ligand and
ruthenium-catalyzed cycloaddition of organic azides with alkynes in
organic and aqueous media: Experimental and computational studies
Tsang-Hsiu Wang, Feng-Ling Wu, Guan-Ru Chiang, Sheng-Ting He, Yih-Hsing Lo*
Department of Applied Physics and Chemistry, University of Taipei, Taipei 10048, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
The catalytic activity of a series of ruthenium azido complexes containing Tp ligands has been evaluated
for the cycloaddition of terminal alkynes and azides to give selectively 1,5-disubstituted 1,2,3-triazoles.
The complex Tp(PPh3)(EtNH2)RuN3 (2, Tp ¼ HB(pz)3, pz ¼ pyrazolyl) was found to be an effective catalyst
for the cycloaddition reactions. In the presence of complex 2, azides reacted with a range of terminal
alkynes containing various functionalities to selectively produce 1,5-disubstituted 1,2,3-triazoles. Theo-
retical calculations support the proposed mechanism.
Received 12 August 2014
Received in revised form
6 September 2014
Accepted 9 September 2014
Available online 15 October 2014
© 2014 Elsevier B.V. All rights reserved.
Keywords:
Tp
Azideealkyne cycloaddition
Ruthenium azido
Click chemistry
Introduction
Results and discussion
Organic azides (Nꢀ3 ) are synthetically useful reagents [1]. Among
many transformations, perhaps the most significant one is the
[3þ2] cycloaddition reactions with acetylenes to synthesize tri-
azoles [2]. Triazoles are nitrogen heteroarenes which have found a
range of important applications in the agricultural and pharma-
ceutical industries [3]. Analogously, metal-coordinated azido li-
gands can also undergo [3þ2] cycloaddition reactions with
carbonecarbon and carboneheteroatom multiple bonds,
frequently under very mild conditions [4e11]. Although such re-
actions are studied extensively in synthetic organic chemistry,
dipolar cycloaddition reactions of azide coordinated metal com-
plexes are relatively unexplored. A few reports appeared on
cycloaddition of alkynes to metal azido complexes in recent years
[5c,12]. Herein, the catalytic activity of a series of ruthenium azido
complexes containing Tp ligands has been evaluated for the
cycloaddition of terminal alkynes and azides to give selectively 1,5-
disubstituted 1,2,3-triazoles. Theoretical calculations support the
proposed mechanism.
Synthesis of new ruthenium azido complex
The new ruthenium azido complex Tp(PPh3)(EtNH2)RuN3 (2,
Tp ¼ HB(pz)3, pz ¼ pyrazolyl) can be readily prepared from
Tp(PPh3)2RuN3 (1). Facile ligand substitution is observed when the
neutral ruthenium azido complex 1 is treated with EtNH2, yielding
the amine-substituted ruthenium azido complex 2 (Scheme 1). The
azido complex 2 is soluble in polar solvents such as CH2Cl2, CHCl3,
and acetone, moderately soluble in diethyl ether, and stable in so-
lution and in air. The IR spectrum of the complex exhibits a strong
band at 2044 cmꢀ1 due to the terminal azido group, and the 31P
NMR spectrum of 2 displays a singlet resonance at
d 46.1 assigned
to the triphenylphosphine groups. Bright yellow crystals were ob-
tained by slow diffusion of n-hexane into a CH2Cl2 solution of 2 at
0 ꢁC for 96 h, and the molecular structure of 2 has been determined
by X-ray diffraction analysis [13]. An ORTEP diagram is shown in
Fig.1, and selected bond distances and angles are given in the figure
caption. The environment about the ruthenium metal center cor-
responds to a slightly distorted octahedron, and the bite angle of
the Tp ligand produces an average NeRueN angle of 86.5ꢁ, only
slightly distorted from 90ꢁ.
* Corresponding author. Tel.: þ886 2 2311 3040x3111; fax: þ886 2 2389 7641.
E-mail address: yhlo@utaipei.edu.tw (Y.-H. Lo).
http://dx.doi.org/10.1016/j.jorganchem.2014.09.038
0022-328X/© 2014 Elsevier B.V. All rights reserved.

58
T.-H. Wang et al. / Journal of Organometallic Chemistry 774 (2014) 57e60
properties of these ruthenium complexes were investigated using
the cycloaddition of benzyl azide and phenylacetylene as the pro-
totypical reaction. In the screening experiments, a mixture of
benzyl azide and phenylacetylene (1/1.5 or 1/2 equiv) in toluene
was heated at 80 ꢁC for 24 h in the presence of 2 mol % of a
ruthenium complex (with respect to the limiting reagent benzyl
azide) to afford the 1,5-disubstituted-1,2,3-triazoles (5) in high
yields (Table 1). The resulting reaction mixture or the isolated
product was then analyzed by 1H NMR. In the 1H NMR spectrum of
5, two singlet resonances appear at 5.51 and 7.72 attributed to
CH2Ph and CH, respectively. The most active catalyst is complex 2.
While the product distribution is independent of these solvents, the
conversion decreases from 80% (toluene) to benzene (69%) and THF
(35%). These reactions processes are in sharp contrast to the for-
mation of 5 from benzyl azide and phenylacetylene in benzene at
80 ꢁC for 2 h in the presence of 1 mol % of the catalyst
Cp*(PPh3)2RuCl.
Scheme 1. Synthesis of new ruthenium azido complex.
Cycloaddition of alkynes and organic azides in organic and aqueous
media
Since the complex 2 has some solubility in polar solvents, the
click reactions were attempted in water. Chemical reactions in
aqueous medium are of growing importance because of many po-
tential advantages, such as alleviation of environmental problems
associated with the use of organic solvents [17]. Surprisingly,
phenylacetylene could be coupled with benzyl azide in water with
regioselectivity essentially identical with that observed in organic
medium.
To evaluate the scope of this new ruthenium-catalyzed process
with respect to the alkyne component, reactions of benzyl azide
with several alkynes were carried out. Complete consumption of
the benzyl azide at the end of the reaction was confirmed by 1H
NMR analysis. A selection of examples is presented in Table 1.
Characteristic spectroscopic data of compounds 5e9 consist of a
Fig. 1. An ORTEP drawing of 2 with thermal ellipsoids shown at the 50% probability
level. Selected distances [Å] and angles [ꢁ]: Ru(1)eN(10) 2.147(3), R(1)eN(7) 2.137(3),
Ru(1)eN(1) 2.119(2), Ru(1)eN(3) 2.085(2), Ru(1)eN(5) 2.077(3), N(7)eN(8) 1.197(4),
N(8)eN(9) 1.180(5); N(1)eRu(1)eN(3) 85.68(9), N(3)eRu(1)eN(5) 89.62(10), N(3)e
Ru(1)eN(7) 92.95(11).
strongly deshielded CH2Ph resonance as a singlet at d 5.5 0.2 ppm
in the 1H NMR spectrum.
Selection of catalysts
In contrast to the click reactions promoted by copper, the
ruthenium complex Cp*(PPh3)2RuCl was reported to catalyze the
cycloaddition reaction of terminal alkynes with alkyl azides in
refluxing benzene to afford exclusively the 1,5-disubstituted-1,2,3-
triazoles [14]. On the other hand, we have reported the first
example that dimerization of alkynes with the ruthenium azido
complex instead of ruthenium chloride complex to give (E)-enynes
carried out in organic and aqueous media [15]. Therefore, ruthe-
nium azido complex was a logical choice in our search for a new
catalyst of click reaction. The catalytic properties of several ruthe-
nium complexes containing Tp ligands were examined. The struc-
tures of these ruthenium azido complexes are shown in Scheme 2.
Most of the complexes (1, 3 and 4) are known [16]. The catalytic
Mechanistic considerations
A detailed mechanism for the click reactions mediated by the 2
system is not yet clear, as the intermediates of the click reactions
have not been identified. It has been established that click reactions
mediated by the very similar precursor Tp(PPh3)(tBuNC)RuN3
proceeds through the coupling of an alkyne and an azide ligands
[18]. It is very likely that the present formation of enynes may
involve a similar mechanism (Scheme 3). The displacement of the
spectator ligands (EtNH2, PPh3) produces the activated intermedi-
ate A, which is converted, via the oxidative coupling of an alkyne
and an azide, to the intermediate B. The intermediate B then un-
dergoes ligand substitution releasing the aromatic triazole product
Scheme 2. Ruthenium azido complex.

T.-H. Wang et al. / Journal of Organometallic Chemistry 774 (2014) 57e60
59
Table 1
Experimental procedures
Preparation of 1,5-disubstituted-1,2,3-triazoles via Ru-catalyzed cycloadditions of
benzyl azide with alkynes.
General procedure
All manipulations were performed under nitrogen using
vacuum-line, drybox, and standard Schlenk techniques.
CH3CN and CH2Cl2 were distilled from CaH2 and diethyl ether
and THF from Na/ketyl. All other solvents and reagents were of
reagents grade and were used without further purification. NMR
Entry
Cat.
R1
Solvent
Conversion (%)
spectra were recorded on
300 MHz (1H), 121.5 MHz (31P), 267.45 MHz (11B) or 75.4 MHz
13C) using SiMe4, BF3$Et2O or 85% H3PO4 as standard or on an
a Bruker AC-300 instrument at
1
2
3
4
5
6
7
8
1
2
3
4
2
2
2
2
2
2
2
Ph (5)
Ph (5)
Ph (5)
Ph (5)
Toluene
Toluene
Toluene
Toluene
Water
Toluene
Water
Toluene
Water
74
80
50
62
80
82
81
82
79
72
96
(
Avance 500 FT-NMR spectrometer. FAB mass spectra were
recorded on a JEOL SX-102A spectrometer. Elemental analyses
and X-ray diffraction studies were carried out at the Regional
Center of Analytical Instrument at National Taiwan Normal
University.
Ph (5)
nBu (6)
nBu (6)
tBu (7)
9
10
11
tBu (7)
C(O)OMe (8)
(CH3)3Si (9)
Toluene
Toluene
Synthesis of new ruthenium azido complex
To a solution of 1 (0.20 g, 0.23 mmol) in 30 mL of THF was added
10 mL of CH3CH2NH2. The solution was stirred for 22 h, the color
changed from yellow to orange yellow, and then the solution was
filtered through Celite. Solvent of the filtrate was removed under
vacuum and the residue was washed with n-hexane to give 2
and regenerating the catalyst 2. Interestingly, the intermediate A is
transformed to B via the oxidative coupling of an alkyne and PhN3,
not N3. We have examined computationally using DFT at the B3LYP/
LANL2DZ level of theory [19,20] to study the reaction energies of
the entry 10. Intermediate A is converted to the intermediate B, this
step is calculated to be ꢀ45.9 kcal/mol at 298 K. Intermediate A is
converted to the intermediate C by [3þ2] cycloaddition, this step is
calculated to be 34.9 kcal/mol at 298 K. This is why the terminal
alkyne coupling PhN3, not N3. On the other hand, unlike
Cp*(PPh3)2RuCl, click reactions by the complex 2 was carried in
protic solvents such as H2O. At present, the mechanism of click
reactions can only be speculated upon. Further work is in progress
and will be reported in a forthcoming paper.
(0.14 g, 90% yield). Spectroscopic data for 2: IR (KBr, cmꢀ1):
n
(BeH)
2473 (br),
n d 7.81 (d,
(N3) 2044 (vs). 1H NMR (acetone-d6):
JHeH ¼ 2.1 Hz, 1H, Tp), 7.80 (d, JHeH ¼ 2.1 Hz, 1H, Tp), 7.63 (d,
JHeH ¼ 2.1 Hz, 1H, Tp), 7.56e7.08 (m, Ph), 6.88 (1H, Tp), 6.71 (1H,
Tp), 6.75 (1H, Tp), 6.01 (t, JHeH ¼ 2.1 Hz, 1H, Tp), 5.94 (t,
JHeH ¼ 2.1 Hz, 1H, Tp), 5.83 (t, JHeH ¼ 2.1 Hz, 1H, Tp), 2.87 (q,
JHeH ¼ 7.2 Hz, 2H, NCH2), 2.11 (br, 2H, NH2), 1.18 (q, JHeH ¼ 7.2 Hz,
3H, NCH2CH3). 31P NMR (acetone-d6):
d 46.1. MS (FAB) m/z: 662.1
(Mþ), 619.3 (Mþ ꢀ CH3CH2NH2), 577.1 (Mþ ꢀ CH3CH2NH2, N3). Anal.
Scheme 3. Mechanistic considerations.

60
T.-H. Wang et al. / Journal of Organometallic Chemistry 774 (2014) 57e60
Calcd for C29H31BN10PRu (663.16): C, 52.58; H, 4.72; N, 21.14. Found:
C, 52.61; H, 4.71; N, 21.09.
Appendix A. Supplementary material
CCDC 992330 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
General procedure for 2 catalyzed cycloadditions
A mixture of benzyl azide (0.50 mmol), alkyne R1eC^CeR2
(0.60 mmol) and 2 (2 mol %) in 10 mL solvent was heated at 80 ꢁC
for 24 h. The progress of the reaction was monitored by 1H NMR.
In most cases the benzyl azide was completely consumed at the
end of the reaction. The solvent was removed under vacuum and
the product was purified by silica gel chromatography. The
unreacted alkyne and traces of side products were first eluted out
with hexane, followed by 1/1 hexane/ether. The pure 1,5-
disubstututed triazole product was then obtained by elution
with ether.
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(CDCl3):
d
7.72 (s, 1H), 7.36e7.26 (m, 8H), 7.01 (t, 2H, JHeH ¼ 3.6 Hz),
5.51 (s, 2H). 13C NMR (CDCl3):
d 138.36, 135.56, 133.31, 133.25,
129.61, 129.08, 128.91, 128.21, 127.21, 126.93, 51.85. EI-MS: m/z 236
[M þ 1].
For 1-benzyl-5-butyl-1H-1,2,3-triazole (6, R1
¼
nBu): 1H NMR
(CDCl3):
d
7.38 (s, 1H), 7.26e7.17 (m, 3H), 7.08 (t, 2H, JHeH ¼ 3.8 Hz),
5.42 (s, 2H), 2.42 (t, 2H, JHeH ¼ 7.8 Hz), 1.46e1.37 (m, 2H), 1.27e1.15
(m, 2H), 0.77 (t, 3H, JHeH ¼ 7.2 Hz). 13C NMR (CDCl3):
d 138.01,
135.59, 133.06, 133.01, 129.46, 128.78, 127.62, 52.13, 30.42, 23.35,
22.69, 14.16. EI-MS: m/z 216 [M þ 1].
For 1-benzyl-5-(tert-butyl)-1H-1,2,3-triazole (7, R1 ¼ tBu): 1H
NMR (CDCl3):
d 7.11 (s, 1H), 7.03e6.84 (m, 3H), 6.75 (d, 2H,
JHeH ¼ 7.0 Hz), 5.41 (s, 2H), 0.97 (s, 9H). 13C NMR (CDCl3):
d 146.03,
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(8,
7.96 (s, 1H), 7.31e7.26 (m, 5H),
161.2, 139.30, 133.60,
R1 ¼ C(O)OMe): 1H NMR (CDCl3):
d
5.58 (s, 2H), 3.84 (s, 3H). 13C NMR (CDCl3):
d
€
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1-benzyl-5-(trimethylsilyl)-1H-1,2,3-triazole
(9,
R1 ¼ (CH3)3Si): 1H NMR (CDCl3):
d
7.38e7.50 (m, 5H), 5.61 (s, 2H),
0.12 (s, 9H). 13C NMR (CDCl3):
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Conclusions
[13] Crystallographic data for 2:
C
29H32BN10PRu,
M
¼
663.50, Orthorhombic,
Complex 2 effectively catalyzes the cycloaddition of terminal
alkynes and azides to give selectively 1,5-disubstituted 1,2,3-
triazoles. The catalyst is reasonably air stable and can tolerate a
number of functional groups, which allows for its use in organic
and aqueous media.
a ¼ 8.5910(3) Å, b ¼ 17.7915(6) Å, c ¼ 19.9364(7) Å,
a
¼ 90ꢁ,
b
¼ 90ꢁ,
g
¼ 90ꢁ,
V ¼ 3047.21(18) Å3, T ¼ 200(2), space group P 212121, Z ¼ 4, 17,422 re-
flections collected, 5335 unique (R(int) ¼ 0.0256) which were used in all
calculations, R1 ¼ 0.0256 for I > 2
s, The final wR2 was 0.0256 (all data).
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G. Jia, J. Am. Chem. Soc. 127 (2005) 15998.
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Acknowledgment
We gratefully acknowledge the financial support from the Na-
tional Science Council of Taiwan (NSC 103-2113-M-845-001), the
project of the specific research fields in the University of Taipei,
Taiwan.