Copper(ii) complexes supported by click generated mixed NN, NO, and NS 1,2,3-triazole based ligands and their catalytic activity in azide-alkyne cycloaddition

Article abstract of DOI:10.1039/c4dt00323c

The preparation and characterization of four new copper(ii) complexes supported by click generated mixed NN, NO, and NS 1,2,3-triazoles are reported. The four complexes display a 1:2 copper/ligand ratio and give monomeric units in the solid state. Crystal structures demonstrate that depending on the flexibility of the ligand NX (X = O, N, S) pendant arm, the coordination environment around the metal center can feature square planar or octahedral geometries. All four complexes are catalytically active at room temperature in a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction using sodium ascorbate as a reducing agent and water-ethanol as a solvent mixture. Complex 8 supported by the NS ligand displayed the best catalytic performance of the series allowing for the easy and high yielding preparation of a variety of mono-, bis- and tris-1,2,3-triazoles under low catalyst loadings.

Full text of DOI:10.1039/c4dt00323c

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Copper(II) complexes supported by click generated
mixed NN, NO, and NS 1,2,3-triazole based ligands
and their catalytic activity in azide–alkyne
cycloaddition†
Cite this: Dalton Trans., 2014, 43,
7069
Daniel Mendoza-Espinosa,a Guillermo Enrique Negrón-Silva,*a Deyanira Ángeles-Beltrán,a
Alejandro Álvarez-Hernández,b Oscar R. Suárez-Castillob and Rosa Santillánc
The preparation and characterization of four new copper(II) complexes supported by click generated
mixed NN, NO, and NS 1,2,3-triazoles are reported. The four complexes display a 1 : 2 copper/ligand
ratio and give monomeric units in the solid state. Crystal structures demonstrate that depending on the
flexibility of the ligand NX (X = O, N, S) pendant arm, the coordination environment around the metal
center can feature square planar or octahedral geometries. All four complexes are catalytically active at
room temperature in a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction using sodium
ascorbate as a reducing agent and water–ethanol as a solvent mixture. Complex 8 supported by the
NS ligand displayed the best catalytic performance of the series allowing for the easy and high yielding
preparation of a variety of mono-, bis- and tris-1,2,3-triazoles under low catalyst loadings.
Received 29th January 2014,
Accepted 24th February 2014
DOI: 10.1039/c4dt00323c
www.rsc.org/dalton
Functionalized 1,2,3-triazole derivatives have emerged as
interesting ligands for transition metals and organometallic
Introduction
Transition metal catalysis is a key instrument for both acade- species due to their potential to act as N donors.5 A wide range
mia and industry as it provides an efficient and sustainable of mono-, bis-, tris-, and polydentate ligands containing the
pathway to organic synthesis and the preparation of fine 1,2,3-triazole skeleton has been synthesized and studied for
chemicals.1 Because most of the transition metal catalyses are their coordination chemistry.6 The preparation of this type of
based on precious and highly expensive metal sources, an ligands has become more accessible due to the discovery of
intensive quest for their replacement with cheaper and readily the 1,3-dipolar Cu(I) catalyzed alkyne–azide cycloaddition
available metals is an important topic currently.2 Ligand (CuAAC) reaction which yields 1,4-disubstituted 1,2,3-tria-
design has emerged as the most powerful tool in transition zoles.7 This multicomponent one-pot process offers great
metal catalysis, as fundamental features such as activity, advantages such as simplicity, reliability and high atom
selectivity, and stability can be tuned taking advantage of the economy. Ligands synthesized through the CuAAC reaction
steric and electronic properties of the ligands that coordinate have found extensive use in coordination chemistry recently.8
to the metal centers.3 Consequently, a great deal of efforts has Their corresponding metal complexes have been studied for
been directed to the discovery, tailoring, and development of their electron transfer and magnetic properties,9 and used as
new ligands for metal based catalysis.4
metallo-supramolecular assemblies10 and as homogeneous
catalysts.11
Development of hybrid NX triazole (X = N, O, S) ligands has
attracted recent attention due to the enhanced coordination
capability offered by the heteroatom pair of electrons which is
available for donation to the metal center.12 Due to the pro-
spective bi- or multidentate coordination of the mixed NX (X =
N, S) triazoles, the stability and catalytic properties of the
metal derivatives are usually improved when compared to
monodentate systems.13
aDepartamento de Ciencias Básicas, Universidad Autónoma Metropolitana-
Azcapotzalco, Avenida San Pablo No. 180, México D.F. 02200, México.
E-mail: gns@correo.azc.uam.mx; Fax: +52-55-5318-9000; Tel: +52-5318-9593
bÁrea Académica de Química, Universidad Autónoma de Hidalgo,
Carretera Pachuca-Tulancingo Km 4.5, Mineral de la Reforma, Hidalgo, México
cDepartamento de Química, CINVESTAV-IPN, Apdo. Postal 14-740,
México D.F. 07000, México
†Electronic supplementary information (ESI) available: Sample 1H and 13C NMR
As part of our interest in developing the coordination
chemistry of various click-derived ligands and exploring the
application of the respective metal complexes, we present
for mono-, bis- and tris-1,2,3-triazoles prepared by the CuAAC process. CCDC
974373–974375 for complexes 5, 6, and 8. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c4dt00323c
This journal is © The Royal Society of Chemistry 2014
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herein the synthesis and characterization of four new copper(II)
complexes of the form [Cu(L)2Cl2] supported by click syn-
thesized mixed NN, NO, and NS 1,2,3-triazole ligands. Solid
state characterizations are presented to illustrate the effect of
the heteroatom of the triazole N-pendant arm in the coordi-
nation environment of the metal center. The four new com-
plexes showed activity as catalysts in the CuAAC process using
sodium ascorbate as a reducing agent. The complex supported
by the mixed NS triazole displayed the best catalytic perform-
ance of the series, allowing for easy and high yielding prepa-
ration of a variety of mono-, bis- and tris-1,2,3-triazoles under
low catalyst loadings.
Results and discussion
Synthesis and characterization
Scheme 2 Synthesis of complexes 5–8.
The substituted 1,2,3-triazoles used as ligands in this work
were prepared through a Cu(I) catalysed process as described
in the literature.14,15 The click reaction of the appropriate
alkyne and sodium azide in the presence of 4-chlorobenzyl
chloride, Cu(OAc)2·5H2O and sodium ascorbate provided
ligands 1–4 in good yields (Scheme 1).
Stirring of ligands 1–4 with equimolar amounts of
CuCl2·5H2O in methanol or ethanol at room temperature
yielded blue precipitates in the case of ligands 1 and 2 and
green precipitates in the case of 3 and 4. The copper(II) com-
plexes were purified by filtration and washing with cold metha-
nol. Under the above reaction conditions, we were expecting
complexes with ligand/copper 1 : 1 ratios and with the [Cu[L]-
Cl2] formula (Scheme 2). However, the low yields (∼25%) and
the large amount of residual copper chloride indicated incom-
plete consumption of the starting materials. As no NMR data
were available (paramagnetic complexes), elemental analyses
were obtained, and the results unveiled a 2 : 1 ligand/metal
ratio for all the complexes (Scheme 2).
Having confirmed the actual ligand/metal ratio of the syn-
thesized complexes, we modified the reaction conditions by
using two equivalents of the ligand and stirring for 12 h. The
precipitates were formed, and the yields of the isolated pro-
ducts were increased in a range of 71 to 82%. Complexes 5–8
were characterized by melting point, FT-IR and UV-vis. The
thermogravimetric (TG) curves over 25–800 °C for complexes
5–8 are given in Fig. 1. Complexes 5 and 6 are stable up to 191
and 198 °C respectively, while 7 and 8 maintain its original
composition up to 251 and 215 °C. A steady decline until
Fig. 1 TGA curves for 5–8.
reaching a residual weight for 5–8 is observed in the range of
∼600 to 650 °C. As noted in Fig. 1, all the complexes display
similar thermal decomposition patterns.
In order to gain further insight into the copper(II) complex
structures, we focused next on the preparation of X-ray quality
single crystals. Complex 5 was crystallized by slow evaporation
of a concentrated DCM solution at room temperature and the
solid state structure is depicted in Fig. 2. Complex 5 crystallizes
Fig. 2 ORTEP drawing of complex 5. Hydrogen atoms have been
omitted for clarity. Thermal ellipsoids are shown at the 50% probability
level.
Scheme 1 Synthesis of mixed ligands 1–4.
7070 | Dalton Trans., 2014, 43, 7069–7077
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Fig. 3 ORTEP drawing of complex 6. Hydrogen atoms are omitted for
clarity. Thermal ellipsoids are shown at the 50% probability level.
Fig. 4 Molecular structure of complex 8 shown to illustrate atom con-
nectivity. Hydrogen atoms are omitted for clarity.
ˉ
in a triclinic P1 space group as a monomeric unit and con-
firms the 1 : 2 metal/ligand ratio previously assumed. The
copper(II) center is coordinated to a single nitrogen of each of
the two 1,2,3-triazole ligands with N(1)–Cu(1) and N(1A)–Cu(1)
bond distances of 1.9976(16) Å and to two chlorine atoms with
Cu(1)–Cl(1) and Cu(1)–Cl(1A) bond distances of 2.2504(5) Å. An
overall square planar geometry around the metal center is
observed. Interestingly, the O(1) and O(1A) atoms are located
far away from the Cu(1) center [3.1570 Å] deterring a possible
bidentated coordination of each 1,2,3-triazole ligand.
triazole ligand displays a bidentate coordination through the
N(1) and S(1) atoms providing a hexacoordinated copper
center with an overall octahedral geometry. The five membered
ring formed by the S(1), C(9), C(10), N(1) and Cu(1) atoms also
resembles the envelope shape displayed in complex 6.
The d9 electronic configuration of the metal center does
not affect the almost perfect square planar geometry in
complex 5 (torsion angle of 0.03°). However, in complexes 6
and 8, a tetragonal compression due to the Jahn–Teller effect
is appreciable due to the elongation of the bonds in the z-axis
drawn by the apical chlorine atoms (z-out distortion).
Single crystals of complex 6 were prepared by diethylether
vapour diffusion into
a
chloroform saturated solution.
ˉ
Complex 6 crystallized in the triclinic P1 spatial group as a
monomeric unit, and the solid state structure is shown in
Fig. 3. The copper center presents a coordination number of
six with an octahedral geometry. Each triazole ligand coordi-
nates the metal center in a bidentate fashion through the N(1),
O(1) and N(1A)–O(1A) atoms and the two chlorine atoms com-
plete the coordination sphere at the apical positions. The
highly symmetric structure of 6 features in a C2 axis drawn
through the two Cl(1)–Cu(1)–Cl(1A) atoms. The Cu(1)–N(1) and
Cu(1)–N(1A) bond lengths are 1.9902(16) Å and the Cu(1)–O(1)
and Cu(1)–O(1A) bond distances are 2.2701(6) Å, falling all in
the standard distances for triazole complexes.16 The bidentate
fashion of the 1,2,3-triazole ligands in complex 6 may be
related to the more rigid structure and proximity of the ArO-
moiety instead of the more flexible ArCH2O-moiety displayed
in complex 5. The Cu(1) center forms a five-membered ring
with O(1), C(10), C(9) and N(1) with an overall conformation
best described as an envelope.
Although the crystal structure of complex 7 could not be
achieved, its structure can be correlated to 8 based on the fol-
lowing arguments. The hard and soft (Lewis) acid and bases
concept indicates that the Cu(II)–S and Cu(II)–N interactions
are stronger than Cu(II)–O. This feature enforces the idea that
complexes 7 and 8 display a bidentate coordination fashion
towards the metal center. In ligands 1–4, there are distinct
structural differences because of the lone pair on X to the
aryl–π system interactions; this leads to the monodentate N-
bonding in 5 whereas in 6–8, the conformation about the C–X–
C(aryl) has a preferred planar orientation facilitating the X–Cu(II)
interaction. This effect will be even more pronounced in
ligand 3 due to the role of the N-aryl lone pair in π-aryl–C(6)
interaction. Additionally, the hardness of the ((aryl)C)–X (X =
O, N or S) will be different from the possible CH2–O–CH2 to
copper.
Despite the various attempts to crystallize complexes 7 and
8, we were not able to obtain appropriate X-ray quality
samples. The best set of single crystals for complex 8 was
obtained by slow evaporation of a methanol solution at room
temperature yielding needle shaped green samples. Although
full refinement could not be obtained due to the crystal
quality,17 the molecular structure and the atom connectivity of
complex 8 (Fig. 4) are unambiguous and allow its discussion
and solid state comparison. Complex 8 resembles the mole-
cular structure of 6 featuring a monomeric unit that presents a
C2 axis drawn through the Cl(1)–Cu(1)–Cl(1A) atoms. Each
CuAAC activity of complexes 5–8
Copper(I) complexes of 1,2,3-triazoles are potential catalysts for
the [2 + 3] cycloaddition reaction between azides and alkynes
(CuAAC). In recent years, several hybrid NS ligands have been
tested as catalysts for click reactions showing an improved per-
formance compared to standard monodentate systems such as
triazoles, phosphines, and imidazoles.12,13 Knowing that our
copper(II) complexes could be reduced with sodium ascorbate
to render Cu(I) active species, we decided to use these in situ
generated catalysts for the preparation of monotriazoles.
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Scheme 3 Catalytic performance of complexes 5–8 in the synthesis of
monotriazole I. *Isolated yield.
Scheme 4 Catalytic performance of complexes 5–8 in the synthesis of
bistriazole II. *Isolated yield.
As a first target, we tested complexes 5–8 in the three com-
ponent preparation of I and we compared their performance
with the previously reported methodology that employed
Cu(OAc)2·5H2O as the metal source.
As depicted in Scheme 3, complexes 7 and 8 showed the
best catalytic performance of the series and they even improve
the reported literature procedure yield (88 and 95% yields,
respectively). Complexes 5–8 displayed good solubility in water
and ethanol mixture, and inert conditions were not required.
The reactions proceeded smoothly at room temperature in all
cases and the amount of sodium ascorbate necessary for good
click reaction performance was only 5 mol%. The synthesized
1,2,3-triazole can be easily purified by a chromatographic
column on silica gel using DMC and methanol (99 : 1) and the
presence of the catalyst 1,2,3-triazole ligand represents no
problem during purification.
Fig. 5 Formation of II under the catalytic 5–8 (determined by GC-MS).
Pleased by these results, we decided to challenge the capa-
bilities of complexes 5–8 in the preparation of bis-1,2,3-tria-
zoles of type II. Using similar reaction conditions to those
reported for the synthesis of II,15 we carried out the CuAAC
reaction of 1,3-bis(prop-2-ynyloxy) benzene with sodium azide
in the presence of benzyl chloride and 5 mol% of the catalyst.
We observed that the performance of complexes 7 and 8 was
better than those of Cu(OAc)2·5H2O under similar reaction con-
ditions (Scheme 4).
catalysts’ stability toward ligand/product exchange reactions
was imperative.
Table 1 shows the results of the reactions of 5–8 with tria-
zoles I and II in an ethanol–water (4 : 1) solvent mixture. The
reactions were performed at room temperature stirring equi-
molar amounts of the catalyst and the respective triazole for
16 h, and purification of products was performed by column
The formation of bis-triazole II under the catalytic 5–8 is
shown in Fig. 5. Conversions after four reaction hours are
similar for all the catalysts. Nevertheless, as the reaction time
increases, the higher efficiency of catalyst 8 is appreciable
reaching conversions up to 90% in 10 h and full conversion
in 12 h.
Table 1 Ligand exchange reactions of 5–8 with triazoles I and II
Catalyst Triazole Ligand : yielda (%) Triazole Ligand : yielda (%)
On the basis of the kinetic data and the isolated yields of I
and II, the catalytic performance of the complexes reported in
this paper can be ordered as 5 < 6 < 7 < 8. To get more insights
into the factors leading to catalytic performance and bearing
in mind that 1,2,3-triazoles were prepared from complexes
5
6
7
8
I
I
I
I
1 : 49
2 : 32
3 : 19
4 : 9
II
II
II
II
1 : 61
2 : 39
3 : 25
4 : 12
a Based on the theoretical amount of ligand contained in the original
that contain the same type of ligands, the study of the complex.
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Table 2 Ligand exchange reactions of reduced 5–8 with triazoles I
and II
Catalyst Triazole Ligand : yielda (%) Triazole Ligand : yielda (%)
5
6
7
8
I
I
I
I
1 : 55
2 : 41
3 : 25
4 : 13
II
II
II
II
1 : 66
2 : 48
3 : 31
4 : 17
a Based on the theoretical amount of ligand contained in the original
complex.
chromatography. The results indicate the amount of released
ligand that was originally contained in the copper catalyst.
Two main aspects from the data of Table 1 can be settled.
First, the ligand displacement percentages of complex 5 are
larger from the series reaching up to 61% with triazole II.
Second, the exchange percentages in 5–8 are larger with II,
likely due to a chelate effect exerted by the bis-triazole.
Remarkably, the amount of released ligand 4 from complex 8
is not larger than 12% in both cases.
Scheme 5 The range of substrates catalysed by complex 8.
As the active catalysts for the click process are obtained
after reduction with sodium ascorbate, we studied ligand
exchange reactions using this in situ reduced “Cu(I)” species.
Table 2 shows the ligand displacement percentages obtained
after the reaction of the reduced 5–8 with triazoles I and II.
According to the ligand displacement percentages shown in
Table 2, the reduced species are slightly more unstable in solu-
tion than the parent complexes 5–8. Nonetheless, their overall
solution behaviour is similar, displaying the reduced complex
5 as the more labile while the reduced complex 8 features the
higher stability of the series (no more than 17% of ligand
displacement).
With the overall results, it is arguable that the stability of
the metal complex in solution is a key factor in the catalytic
performance of 5–8. For instance, complex 5 that in the solid
state displayed monodentate coordination and allowed easier
ligand exchange in solution results in the less effective catalyst.
In contrast, the lesser ligand exchange observed in complexes
6–8 increases the conversion to products due to a more
effective coordination capacity and solution stability. Parti-
cularly, the sulphur atom, being the largest and softer of the
heteroatoms, results in a highly stable complex in solution
which provides the best catalytic copper species of the series.
After establishing that complex 8 (NS mixed ligand) was the
most efficient catalyst of the series, we decided to perform next
a substrate screening. As observed in Scheme 5, complex 8 is
capable of catalysing the formation of a series of mono-, bis-
and tris-1,2,3-triazoles featuring a variety of functional groups
and topologies.
increases to 3 mol% (1.5 mol% of catalyst per triazole unit),
and 18 to 24 h of stirring at room temperature is necessary to
reach yields from 68 to 79%. It is important to mention that
even 1,2,3-triazoles based on biologically active thymine and
uracil compounds can be prepared.
The most challenging part of the substrate screening
involved the preparation of a tris-1,2,3-triazole based on phloro-
glucinol. In this trial, 5 mol% of the catalyst and the reducing
agent and 24 h of stirring at room temperature gave the highly
functionalized product in 82% isolated yield.
A plausible reaction mechanism for the synthesis of 1,2,3-
triazoles using complex 8 is depicted in Scheme 6. Once 8 is
reduced to Cu(I) with sodium ascorbate, the mechanism is
probably started by the coordination of the alkyne to the soft
cationic Cu(I) center in a η2 mode. The metal enhanced acidity
of the –CH group in the alkyne moiety favours its deprotona-
tion by one of the copper coordinated 1,2,3-triazole ligands
resulting in the formation of a triazolium salt and the gen-
eration of a Cu(I)–acetylide complex. The in situ formed organic
azide then coordinates to the highly electrophilic cationic
Cu(I)–acetylide complex, and the cycloaddition takes place
through the formation of a five membered ring metallo-cycle
which after rearrangement yields a copper–triazolide inter-
mediate. The subsequent protonation of the triazolide moiety
by the triazolium salt releases the desired 1,2,3-triazole and
regeneration of the active catalyst takes place to finish the
cycle.
The optimized synthesis of monotriazoles required only
1 mol% of the catalyst and the respective reducing agent, and
no longer than 12 h was necessary to achieve good to excellent
yields (82–92%). In the case of the preparation of bis-triazoles,
the amount of the catalyst and the reducing agent only
Conclusions
We have reported the synthesis and characterization of
four new copper(II) complexes supported by click synthesized
mixed NX (X = N,O,S) 1,2,3-triazoles. The crystal structures of
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Scheme 6 Proposed reaction mechanism of complex 8 in the click process.
complexes 5, 6, and 8 display monomeric units and a ligand– IR spectra were recorded on a Bruker Alpha FT-IR/ATR spectro-
metal ratio of 2 : 1. Complex 5 presents a square planar geome- meter. UV-vis analyses were obtained with an Agilent 8453
try around the metal center while complexes 6 and 8 feature Spectrophotometer. Elemental analyses were obtained with a
octahedral coordination environments. For complexes 6 and 8 Thermo Finnegan CHNSO-1112 apparatus. All thermograms
the triazole ligands coordinate the metal center in a bidentate were performed in a SDTQ600 equipment at 20 °C min−1 from
fashion forming a five membered metallacycle with an envel- room temperature to 700 °C under a nitrogen flow of 5 mL
ope-like conformation. The four copper(II) complexes were min−1 using an alumina pan. GC-MS analyses were performed
reduced with sodium ascorbate and then tested in the CuAAC in an Agilent GC model HP 5890 coupled with a mass detector
reaction.
model 5973. X-Ray diffraction analyses were collected in an
Complexes 5–7 show moderate to good catalytic activity in Agilent Gemini Diffractometer using Mo Kα radiation (l =
the synthesis of mono- and bis-triazoles while complex 8 (sup- 0.71073 Å). Data were integrated, scaled, sorted, and averaged
ported by a NS mixed triazole) provided the best catalytic per- using the CrysAlisPro software package. The structures were
formance of the series allowing for the synthesis of a variety of solved using direct methods using SHELX 97 and refined by
mono-, bis- and tris-1,2,3-triazoles under low catalyst loadings. full matrix least squares against F2.18 All nonhydrogen atoms
The present catalytic studies are appealing because the prepa- were refined anisotropically. The position of the hydrogen
ration of 1,2,3-triazoles could be achieved from a series of com- atoms was kept fixed with common isotropic display para-
plexes that contain click produced ligands as well. The use of meters. The crystallographic data and some details of the data
mixed NX 1,2,3-triazoles as ligands for various transition collection and refinement are given in Table 3. The programs
metals and their catalytic applications are under investigation ORTEP19 and POV-Ray20 were used to generate the X-ray struc-
in our laboratory currently.
tural diagrams pictured in this article.
Synthesis of complexes 5–8
Experimental section
General information
Complex 5. A 3 mL methanol solution of copper chloride
pentahydrate (54 mg, 0.318 mmol) was added slowly to a solu-
Commercially available reagents and solvents were used as tion of ligand 1 (200 mg, 0.637 mmol) in 5 mL of methanol
received. Ligands 1–4 were synthesized as reported in the lit- and the reaction turned blue immediately. The reaction was
erature.14,15 Flash column chromatography was performed on stirred for 12 h at room temperature and a blue precipitate
Kieselgel silica gel 60 (230–400 mesh). Melting points were appeared. The solid was collected by vacuum filtration and
determined on a Fisher–Johns apparatus and are uncorrected. washed three times with 2 mL portions of cold (0 °C)
7074 | Dalton Trans., 2014, 43, 7069–7077
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methanol. A final washing with diethyl ether and vacuum
drying yielded the title product as a blue solid in 77% yield
Table 3 Crystallographic data and summary of data collection and
structure refinement
(0.245 mmol, 187 mg). Mp = 156–158 °C. FT-IR/ATR νmax cm−1
:
5
6
3161, 3215, 3168, 3042, 3000, 2974, 2788, 2633, 2122, 1675,
1612, 1584, 1488, 1457. UV/vis (MeOH) λmax/nm (ε/dm3 mol−1
cm−1): 254 (5.63 × 103), 317 (3.14 × 103), 455 (1.34 × 102).
Found: C, 53.41; H 4.17, N 14.98. Calc. for: C34H34Cl4CuN8 C,
53.73; H 4.51, N 14.74.
Formula
Fw
Cryst syst
Space group
T (K)
a (Å)
b (Å)
c (Å)
α (°)
β (°)
C
34H32Cl4CuN6O2
C32H28Cl4N6O2
733.94
762.00
Triclinic
Triclinic
ˉ
ˉ
P1
P1
293(2)
293(2)
7.2326(3)
8.3664(4)
15.0156(5)
97.304(3)
102.771(3)
98.187(3)
865.186(6)
1
1.463
4.063
19 934
0.734
3441
0.0414
0.0350
0.0451
0.0899
0.0970
1.029
7.1710(3)
8.3954(3)
14.3714(5)
75.138(3)
81.275(3)
79.855(3)
818.01(5)
1
1.490
1.034
24 061
0.937
2861
0.0527
0.0335
0.0394
0.1226
0.1297
1.045
Complex 8. A 3 mL methanol solution of copper chloride
pentahydrate (54 mg, 0.316 mmol) was added slowly to a solu-
tion of ligand 2 (200 mg, 0.633 mmol) in 5 mL of methanol
and the reaction turned green immediately. The reaction was
stirred for 12 h at room temperature and a green precipitate
appeared. The solid was collected by vacuum filtration and
washed three times with 2 mL portions of cold (0 °C) metha-
nol. A final washing with diethyl ether and vacuum drying
yielded the title product as a blue solid in 82% yield
(0.259 mmol, 198 mg). Samples for X-ray diffraction were
obtained by the slow evaporation of a concentrated methanol
γ (°)
V (Å3)
Z
dcalc/g cm−3
μ (mm−1
)
Refl collected
Tmin/Tmax
Nmeasd
[Rint
]
R [I > 2σ(I)]
R (all data)
Rw[I > 2σ(I)]
Rw (all data)
GOF
solution of the product. Mp = 191–193 °C. FT-IR/ATR νmax cm−1
:
3129, 3079, 3058, 3020, 2927, 1998, 1974, 1581, 1558, 1488,
1438, 1408, 1346, 1256, 1228. UV/vis (MeOH) λmax/nm (ε/dm3
mol−1 cm−1): 275 (5.98 × 103), 311 (3.45 × 103), 459 (1.82 × 102).
Found: C, 50.30; H 3.68, N 11.00. Calc. for: C32H28Cl4CuN6S2 C,
50.17; H 3.68, N 10.97.
methanol. A final washing with diethyl ether and vacuum
drying yielded the title product as a blue solid in 71% yield
(0.226 mmol, 172 mg). Single crystals were obtained by slow
General procedure for the CuAAC catalysis trials
evaporation of
a concentrated ethanol solution. Mp =
165–167 °C. FT-IR/ATR νmax cm−1: 3149, 3115, 3058, 3032,
2997, 2940, 2882, 2863, 2846, 1655, 1573, 1483, 1469, 1454.
UV/vis (MeOH) λmax/nm (ε/dm3 mol−1 cm−1): 269 (6.62 × 103)
323 (1.25 × 103) 456 (2.60 × 102). Found: C, 53.42; H 4.26, N
11.07; calc. for: C34H32Cl4CuN6O2 C, 53.59; H, 4.23, N 11.03.
Complex 6. A 3 mL methanol solution of copper chloride
pentahydrate (57 mg, 0.333 mmol) was added slowly to a solu-
tion of ligand 2 (200 mg, 0.667 mmol) in 5 mL of methanol
and the reaction turned blue immediately. The reaction was
stirred for 12 h at room temperature and a blue precipitate
appeared. The solid was collected by vacuum filtration and
washed three times with 2 mL portions of cold (0 °C) metha-
nol. A final washing with diethyl ether and vacuum drying
yielded the title product as a blue solid in 74% yield
(0.246 mmol, 181 mg). Single crystals were obtained by diethyl
ether vapour diffusion into a concentrated chloroform solution
of the product. Mp = 177–179 °C. FT-IR/ATR νmax cm−1: 3150,
3112, 3064, 1597, 1584, 1495, 1455, 1386, 1334, 1289, 1232.
UV/vis (MeOH) λmax/nm (ε/dm3 mol−1 cm−1): 250 (6.20 × 103)
328 (4.18 × 103) 453 (1.18 × 102). Found: C, 52.22; H 3.96, N
11.73. Calc. for: C32H28Cl4CuN6O2 C, 52.37; H, 3.85, N 11.45.
Complex 7. A 3 mL methanol solution of copper chloride
pentahydrate (55 mg, 0.319 mmol) was added slowly to a solu-
tion of ligand 2 (200 mg, 0.639 mmol) in 5 mL of methanol
and the reaction turned green immediately. The reaction was
stirred for 12 h at room temperature and a green precipitate
appeared. The solid was collected by vacuum filtration
and washed three times with 2 mL portions of cold (0 °C)
Monotriazole preparation. To a 20 mL round-bottom flask
equipped with a magnetic stirrer were charged the appropriate
catalyst and sodium L-ascorbate in equal mole percentages.
After addition of 7 mL of a mixture of EtOH–H2O (4 : 1 v/v), the
resulting suspension was stirred for five minutes at room
temperature. Subsequently, 1.14 mmol of the ligand,
1.40 mmol of sodium azide, and 1.40 mmol of benzyl chloride
were added to the reaction mixture, which was stirred for 12 h
at room temperature. 5 mL of H2O was added to the reaction
mixture and the precipitate was filtered off, washed thoroughly
with H2O, petroleum ether, and dried under vacuum. The
crude products were purified by column chromatography, and
their characterization is consistent with the literature
reports.14,15,21,22
Bis-triazole preparation. To a 20 mL round-bottom flask
equipped with a magnetic stirrer were charged the catalyst and
sodium L-ascorbate in equal mole percentages (according to
Scheme 4). After addition of 5 mL of a mixture of EtOH–H2O
(4 : 1 v/v), the resulting suspension was stirred for five minutes
at room temperature. Subsequently, 0.70 mmol of the alkyne,
1.54 mmol of sodium azide, and 1.54 mmol of benzyl chloride
were added to the reaction mixture, which was stirred at room
temperature (refer to Scheme 4 for reaction times). 5 mL of
H2O was added to the reaction mixture and the precipitate was
filtered off, washed thoroughly with H2O, petroleum ether,
and dried under vacuum. The crude products were purified by
column chromatography and their characterization is consist-
ent with the literature reports.14,15,23
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Dalton Transactions
Tris-triazole preparation. To a 20 mL round-bottom flask
equipped with magnetic stirrer were charged 16 mg
Application of Transition Metal Catalysis, in Drug Discovery
and Development: An Industrial Perspective, ed. M. L. Crawley
and B. M. Trost, Wiley, Germany, 1st edn, 2012, ch. 3,
vol. 1, pp. 97–163; (c) J. Hagen, Industrial Catalysis: A practi-
cal Approach, Wiley-VCH, Germany, 2nd edn, 2006, ch. 3,
vol. 1, pp. 59–80.
2 (a) F. Jaouen, E. Proietti, M. Lefevre, R. Chenitz,
J.-P. Dodelet, G. Wu, H. T. Chung, C. M. Johnston and
P. Zelenay, Energy Environ. Sci., 2011, 4, 114; (b) R. Bashyam
and P. Zelenay, Nature, 2006, 443, 63; (c) F. Studt, F. Ablid-
Pedersen, T. Bligaard, R. Z. Sorensen, C. H. Christensen
and J. K. Norskov, Science, 2011, 320, 1320; (d) G. Wu,
K. L. More, C. M. Johnston and P. Zelenay, Science, 2011,
332, 443.
3 (a) W. Wang, G. B. Hammond and B. Xu, J. Am. Chem. Soc.,
2012, 134, 5697; (b) C. Gunanatan and D. Milstein, Top.
Organomet. Chem., 2011, 37, 55; (c) A. Pfaltz and W. J. Dury III,
Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 5723; (d) K. Omatsu,
M. Ito, T. Kuneida and T. Ooi, Nat. Chem., 2012, 4, 473;
(e) J. J. Miller and M. S. Sigman, J. Am. Chem. Soc., 2007,
129, 2752.
4 (a) C. J. ÓBrien, E. A. B. Kantchev, G. A. Chass, N. Hadei,
A. C. Hopkinson, M. G. Organ, D. H. Setiadi, T.-H. Tang
and D.-C. Fang, Tetrahedron, 2005, 61, 9723; (b) P. J. Chirik
and K. Weighardt, Science, 2010, 327, 5967; (c) R. H. Crabtree,
New J. Chem., 2011, 35, 18; (d) G. Chelucci, Coord. Chem.
Rev., 2013, 257, 1887; (e) J. Klosin and C. R. Landis,
Acc. Chem. Res., 2007, 40, 1251.
5 (a) B. Happ, D. Escudero, M. D. Hager, C. Friebe, A. Winter,
H. Görls, E. Altuntas, L. Gonzalez and U. S. Schubert,
J. Org. Chem., 2010, 75, 4025; (b) F. Saleem, G. K. Rao,
A. Kumar, G. Mukherjee and A. K. Singh, Organometallics,
2013, 32, 3595; (c) N. Segaud, J.–N. Rebilly, K. Senechal-
David, R. Guillet, L. Billon, J.-P. Baltaze, J. Farjon,
O. Reinaud and F. Banse, Inorg. Chem., 2013, 52, 691;
(d) J. D. Crowley and E. L. Gavey, Dalton Trans., 2010, 39,
4035.
6 See for example: (a) C. Maeda, S. Yamaguchi, C. Ikeda,
H. Shinokubo and A. Osuka, Org. Lett., 2008, 10, 549;
(b) K. M. Mullen and M. J. Gunter, J. Org. Chem., 2008, 73,
3336; (c) C. Richardson, C. M. Fitchett, F. R. Keene and
P. J. Steel, Dalton Trans., 2008, 2534; (d) D. Schweinfurth,
K. I. Hardcastle and U. H. F. Bunz, Chem. Commun., 2008,
2203; (e) Y. Li, J. C. Huffman and A. H. Flood, Chem.
Commun., 2007, 2692; (f) T. L. Mindt, H. Struthers,
L. Brans, T. Anguelov, C. Scheweinsberg, V. Maes,
D. Tourwé and R. Schibli, J. Am. Chem. Soc., 2006, 128,
15096; (g) C. Camp, S. Dorbes, C. Picard and E. Benoist,
Tetrahedron Lett., 2008, 49, 1979; (h) T. Ziegler and
C. Hermann, Tetrahedron Lett., 2008, 49, 2166.
a
(0.021 mmol, 5 mol%) of complex 8 and 4 mg (0.021 mmol,
5 mol%) of sodium L-ascorbate. After addition of 10 mL of a
mixture of EtOH–H2O (4 : 1 v/v), the resulting suspension was
stirred for five minutes at room temperature. Subsequently,
107 mg (0.42 mmol) of 1,3,5-tris(prop-2-ynyloxy)benzene,
90 mg (1.39 mmol) of sodium azide, and 0.16 mL (1.39 mmol)
of benzyl chloride were added to the reaction mixture, which
was stirred for 24 h at room temperature. 10 mL of H2O was
added to the reaction mixture and the precipitate was filtered
off, washed thoroughly with H2O, petroleum ether, and dried
under vacuum. The crude product was purified by column
chromatography (CH2Cl2–MeOH 96 : 4 v/v) and its characteri-
zation is consistent with the literature.14,24
Ligand exchange reactions. To a 20 mL round-bottom flask
equipped with a magnetic stirrer were charged 0.5 mmol of
the copper complex and stoiquiometric amounts of the
respective triazole I or II. After addition of 10 mL of a mixture
of EtOH–H2O (4 : 1 v/v) the resulting suspension was stirred for
16 h at room temperature. The resulting mixture was extracted
with DCM, dried over MgSO4 and dried under vacuum. The
residue was purified by column chromatography starting with
100% CH2Cl2 and gradually increasing the polarity of the
eluent by adding MeOH. The purified triazoles were character-
ized by 1H and compared to the synthesized ligands 1–4.
Ligand exchange reactions with reduced complexes. To a
20 mL round-bottom flask equipped with a magnetic stirrer
were charged 0.5 mmol of the copper complex and 0.55 mmol
of sodium ascorbate. 10 mL of a mixture of EtOH–H2O (4 : 1
v/v) was added and the resulting suspension was stirred for
15 min. 0.5 mmol of triazole I or II was added to the catalyst
solution and the reaction was stirred for 16 h at room tempera-
ture. The resulting mixture was extracted with DCM, dried over
MgSO4 and dried under vacuum. The residue was purified by
column chromatography starting with 100% CH2Cl2 and
gradually increasing the polarity of the eluent by adding
MeOH. The purified triazoles were characterized by 1H and
compared to the synthesized ligands 1–4.
Acknowledgements
We are grateful to Consejo Nacional de Ciencia y Tecnología,
CONACyT (project 181448). DME also acknowledges “Beca de
Retencion” (application 192049) sponsored by CONACyT and
UAM-Azcapotzalco. DME, GNS, DAB, AAH and ORSC wish to
acknowledge the SNI for the distinction and the stipend
received.
7 (a) V. V. Rostostev, L. G. Green, V. V. Fokin and
K. B. Sharpless, Angew. Chem., Int. Ed., 2002, 41, 2596;
(b) J. E. Hein and V. V. Fokin, Chem. Soc. Rev., 2010, 39,
1302.
8 (a) J. D. Crowley and D. A. McMorran, Top. Heterocycl.
Chem., 2012, 28(31), 84; (b) O. Fleishel, N. Wu and
Notes and references
1 See for example: (a) W. Keim, in Transition Metals for
Organic Synthesis, ed. M. Beller and C. Bolm, Wiley VCH,
Germany, 2nd edn, 2004, ch. 1, vol. 1, pp. 15–25; (b) J. Yin,
7076 | Dalton Trans., 2014, 43, 7069–7077
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Paper
A. Petitjean, Chem. Commun., 2010, 46, 8454; 14 D. Mendoza-Espinosa, G. E. Negron-Silva, L. Lomas-
(c) B. M. J. M. Suijkerbuijk, B. N. H. Aerts, H. P. Dijkstra,
M. Lutz, A. L. Spek, G. van Koten and R. J. M. Klein
Gebbink, Dalton Trans., 2007, 1273.
9 (a) P. M. Guha, H. Phan, J. S. Kinyon, W. S. Brotherton,
K. Sreenath, J. T. Simmons, Z. Wang, R. J. Clark,
Romero, A. Gutierrez-Carrillo and D. Soto-Castro, Synthesis,
2013, 2431.
15 D. Mendoza-Espinosa, G. E. Negron-Silva, L. Lomas-
Romero, A. Gutierrez-Carrillo and R. Santillan, Synth.
Commun., 2013, 44, 807.
N. S. Dalal, M. Shatruk and L. Zhu, Inorg. Chem., 2012, 51, 16 (a) S. V. Voitekhovich, J. V. Filippova, A. G. Sukhanova,
3465; (b) M. Ostermeier, M.-A. Berlin, R. M. Meudnert,
S. Demeshko, F. Meyer, C. Limberg and S. Hecth,
Chem.–Eur. J., 2010, 16, 10202.
A. S. Lyakhov, L. S. Ivashkevish, G. T. Sukhanov and
Y. V. Grigoriev, Inorg. Chem. Commun., 2012, 24, 77;
(b) G. E. Kostakis, P. Xydias, E. Nordlander and
J. C. Plakatouras, Inorg. Chim. Acta, 2012, 383, 327;
(c) G. F. Manbeck, W. W. Brennessel, W. W. Evans,
M. Christopher and R. Eisenberg, Inorg. Chem., 2010, 49,
2834; (d) J. D. Crowley, P. H. Bandeen and L. R. Hanton,
Polyhedron, 2010, 29, 70.
10 (a) B. Schulze, C. Friebe, S. Hoeppener, G. M. Pavlov,
A. Winter, M. D. Hager and U. S. Schubert, Macromol.
Rapid Commun., 2012, 33, 597; (b) G. Aromi, L. A. Barrios,
O. Robeau and P. Gamez, Coord. Chem. Rev., 2011, 255,
485; (c) A. Noor, J. E. M. Lewis, S. A. Cameron, S. C. Moratti
and J. D. Crowley, Supramol. Chem., 2012, 24, 492; 17 Data for complex 8: C32H28Cl4CuN6S2; fw 766.06; space
(d) J. E. M. Lewis, C. J. McAdam, M. G. Gardiner and
J. D. Crowley, Chem. Commun., 2013, 49, 3398.
group C2/c; a = 31.1631(10), b = 13.4153(5), c = 8.5786(3),
β = 101.437(3); V = 3515.2(2); Z = 4; d = 1.448 Mg m−3; μ =
1.076 mm−1. Data were collected in an Agilent Gemini
Diffractometer using Mo Kα radiation (λ = 0.71073 Å). Data
were integrated, scaled, sorted, and averaged using the
CrysAlisPro software package. The structures were solved
using direct methods, using SHELX 97 and refined by full
matrix least squares against F2. The final refinement para-
meters R1 [I > 2σ(I)] = 0.1664, and wR2 = 0.4696.
11 See for example: (a) Y. Chen, W. Yan, N. G. Akhmedov and
X. Shi, Org. Lett., 2010, 12, 344; (b) E. Armadio, A. Scrivanti,
M. Bortoluzzi, M. Bertoldini, V. Beghetto, U. Matteoli and
G. Chessa, Inorg. Chim. Acta, 2013, 405, 188; (c) E. Amadio,
A. Scrivanti, G. Chessa, U. Matteoli, V. Beghetto,
M. Bertoldini, M. Rancan, A. Dolmella, A. Venzo and
R. Bertani, J. Organomet. Chem., 2012, 716, 193;
(d) D. Schweinfurth, C.-Y. Su, S.-C. Wei, P. Braunstein and 18 G. M. Sheldrick, SHELXS-97, Program for Crystal Structure
B. Sarkar, Dalton Trans., 2012, 41, 12984; (e) D. Canseco-
Solution and Refinement; Institut Für Anorganishe Chemie,
Gonzalez, A. Gniewek, M. Szulmanowicz, H. Mueller-Bunz,
Göttingen, Germany, 1998.
A. M. Trzeciak and M. Albrecht, Chem.–Eur. J., 2012, 18, 19 L. J. Farrugia, J. Appl. Crystallogr., 1997, 30, 565.
6055; (f) D. Wang, Y. Zhang, A. Harris, L. N. S. Gautam, 20 POV RAY, v. 3.5, Persistence of Vision Raytracer Pty. Ltd,
Y. Cheng and X. Shi, Adv. Synth. Catal., 2011, 353,
2584.
Williamston, Victoria Australia, 2002, retrieved from http://
www.povray.org
12 (a) S.-Q. Bai, L. L. Hoh and T. S. A. Hor, Inorg. Chem., 21 X. Creary, A. Anderson, C. Brophy, F. Crowell and Z. Funk,
2009, 48, 1207; (b) S.-Q. Bai, L. Yang, J.-L. Zuo and J. Org. Chem., 2012, 77, 8756.
T. S. A. Hor, Dalton Trans., 2013, 42, 11319; (c) X. Han, 22 B. R. Buckley, S. E. Dann and H. Heaney, Chem.–Eur. J.,
Z. Weng, D. J. Young, G.-X. Jin and T. S. A. Hor, Dalton
Trans., 2014, 43, 1305.
13 (a) L. Yang, Z. Wang, S.-Q. Bai and T. S. A. Hor, Dalton
Trans., 2013, 42, 9437; (b) S.-Q. Bai, A. M. Yong, J. J. Hu,
D. J. Young, X. Zhang, Y. Zong, J. Xu, J. L. Zuo
2010, 16, 6278.
23 G. E. Negron-Silva, R. Gonzalez-Olvera, D. Angeles-Beltran,
N. Maldonado-Carmona, A. Espinoza-Vazquez, M. E. Palomar-
Pardave, M. A. Romero-Romo and Rosa Santillan, Mole-
cules, 2013, 18, 4613.
and T. S. A. Hor, CrystEngComm, 2012, 14, 961; 24 H. Lopez-Ruiz, J. E. de la Cerda-Pedro, S. Rojas-Lima,
(c) J. D. Crowley and P. H. Bandeen, Dalton Trans., 2010,
39, 612.
I. Perez-Perez, B. V. Rodriguez-Sanchez, R. Santillan and
O. Coreño, ARKIVOC, 2013, iii, 139.
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 7069–7077 | 7077