A polymer supported Cu(i) catalyst for the 'click reaction' in aqueous media

Article abstract of DOI:10.1039/c4dt02962c

Polymer stabilized monovalent copper has been synthesized using an in situ chemical transformation route and was characterized by means of different microscopic, optical and surface characterization techniques, which offered information about the chemical structure of the polymer and the morphology of the complex. The supramolecular material, Cu(i)-poly(2-aminobenzoic acid), denoted Cu(i)-pABA, showed catalytic activity for the cycloaddition reaction between terminal alkynes and azides to synthesize 1,2,3-triazoles with excellent yields. The catalyst was recovered from the reaction mixture and recycled several times without an appreciable loss of catalytic activity. The whole strategy was done under ambient conditions and in the presence of water as a solvent.

Full text of DOI:10.1039/c4dt02962c

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Table of content:
Cu(I)-polymer composite recyclable catalyst for the azide-alkyne cycloaddition reaction at
room temperature in aqueous medium.

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Polymer supported Cu(I) catalyst for ‘click reaction’ in aqueous media
Rafique Ul Islam,a Abu Taher,a Meenakshi Choudhary,a Michael J Witcomb,b Kaushik
Mallick a*
a Department of Chemistry, University of Johannesburg, P.O. Box 524, Auckland Park 2006,
South Africa,
b DST/NRF Centre of Excellence in Strong Materials, University of the Witwatersrand,
Private Bag 3, WITS 2050, South Africa.
* Address correspondence to kaushikm@uj.ac.za
Polymer stabilized monovalent copper has been synthesized using an in-situ chemical
transformation route and was characterized by means of different microscopic, optical and
surface characterization techniques, which offered the information about the chemical
structure of polymer and the morphology of the complex. The supramolecular material,
Cu(I)−poly(2-aminobenzoic acid), Cu(I)-pABA, showed the catalytic activity for the
cycloaddition reaction between terminal alkynes and azides to synthesize 1,2,3-triazoles with
excellent yields. The catalyst was recovered from the reaction mixture and recycled for
several times without appreciable loss of catalytic activity. The whole strategy was done
under ambient condition and in presence of water as a solvent.
Keywords: Cu(I)−poly(2-aminobenzoic acid), azide-alkyne cycloaddition, click reaction,
multicomponent reaction.
Introduction
Catalysis by metal ions is a powerful method of accelerating a large number of organic
reactions.1 An example of a carbon-carbon bond formation reaction is where enantioselective
carboalkoxylation of alkynes has been reported catalyzed by gold(I) complexes.2 Further, a
palladium (II) catalyst system, in the presence of 1,2-bis(diphenylphosphino) ethane as the
ligand, has been found to be an efficient catalyst for the N-alkylation of amines using
alcohols under solvent-free conditions.3 In addition to these, metal ion catalyzed organic
transformation reactions utilizing a one-pot process have gained increasing interest as the
molecular complexity is rapidly generated without the need for the isolation of intermediates
resulting in enhanced efficiency and sustainability.4-6 Au(I)/Rh(I) dual catalyst system has
been reported for the consecutive synthesis of β‑disubstituted ketones and asymmetric 1,4-
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addition,7 while poly (3-aminoquinoline) stabilized Pd(I) has been found to act as a catalyst
for a Sonogashira cross-coupling reaction for aryl and heteroaryl of iodides and bromides.8
The participation of metal ions in biological reactions has also been demonstrated. For
example, in the presence of O2, Fe(III) or Cu(II), and an appropriate electron donor, a number
of enzymatic and non-enzymatic oxygen free radical-generating systems have been reported
to catalyze the oxidative modification of proteins.9
Cu(I) catalyzed azide-alkyne cycloaddition (AAC) or Click reaction continues to be of much
interest10 since it offers the opportunity to chemists to connect two potentially complex
building blocks under mild conditions.11 The cycloaddition between an azide and a terminal
or internal alkyne to give a 1,4- or 1,5-disubstituted 1,2,3-triazole, was developed by Rolf
Huisgen.12 The lack of regioselectivity and the requirement of high temperature were the
major drawbacks of the reaction. The copper(I) catalysts could facilitate the cycloaddition in
a regiospecific manner to give only 1,4-disubstituted triazoles and was reported by
Sharpless10 and have attracted significant attention due to their application in the synthesis of
pharmaceutical, agrochemical, dye, corrosion inhibitor, biochemical, polymer and other
functional materials. This reaction has thus been extensively applied to the synthesis of
macromolecules13 and to the functionalization of biomolecules.14 AAC reaction has been
reported using the catalyst in the form of Cu(I) salt,15 CuSO4-ascorbate system,16
immobilized Cu(I) onto polymers17 or zeolite,18 copper nanoparticles,19 metallic copper
turnings,20 nanostructured copper oxide21 and all of the above copper based catalysts have
successfully demonstrated the activity for the title reaction.
The present paper reports on a single-step oxidative polymerization reaction of 2-
aminobenzoic acid using copper sulphate as an oxidizing agent, which results in the
formation of a Cu(I)-poly(2-aminobenzoic acid), Cu(I)-pABA, complex. Special attention has
been paid to characterizing the metallo-macromolecule complex by spectroscopic techniques.
The as-prepared material showed a high catalytic activity towards azide-alkyne 1,3-dipolar
cycloaddition reactions carried out at room temperature, in the presence of water as a solvent,
under aerated conditions yielding catalytic efficiency over several cycles. Polymers show the
potential benefit as a stabilizer of the catalyst for a wide range of applications.22-24 The
advantage of a polymer as a stabilizer results from its robustness as well as flexibility.25
2

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Materials and methods
Materials: Unless otherwise mentioned, all chemicals and reagents used for this study were
of analytical grade and were used as received. Ultra-pure water (specific resistivity >
17Mꢀcm) was used in these experiments.
Synthesis of the Cu(I)−poly(2-aminobenzoic acid), Cu(I)-pABA, complex: In a typical
experiment, 0.10 g of 2-aminobenzoic acid was dissolved in 25 mL Milli-Q water (60oC) in a
beaker. To this, 10 mL of CuSO4, 5H2O solution (10−2 mol dm−3, dissolved in
dimethylformamide, DMF) was added slowly under continuous stirring conditions. During
the addition, the solution took on a green colourization, while at the end; a dark green
precipitation was formed at the bottom of the beaker. The entire reaction was performed at
room temperature upon open atmosphere condition. The material was allowed to settle for 10
min after which 5 ꢀL of the colloidal solution was taken from the bottom of the conical flask
and pipetted onto lacey, carbon-coated, nickel mesh grids for TEM examination. Subsequent
to the TEM study, the same grids were sputter coated with a conducting layer a few
nanometres thick of Au-Pd and viewed by scanning electron microscopy (SEM). The
required amount of material was used for UV-vis and Raman spectroscopy studies. The
remaining portion of the compound was dried under vacuum at 60 oC and used for XRD and
XPS measurements as well as for studies of the catalytic properties.
Procedure for the synthesis of phenyl azide, benzyl azide and 2-bromo benzyl azide:
Phenyl azide: Sodium azide (0.78 g, 12 mmol, 1.2 equiv.) and CuSO4.5H2O (2.5 g, 10 mmol,
1.0 equiv.) were added in a round bottom flask in presence of methanol (15 mL). To this
phenyl boronic acid (1.22 g, 10 mmol, 1.0 equiv.) was added under vigorous stirring
conditions at room temperature. The resulting mixture was concentrated under reduced
pressure and the residue was extracted with hexane producing a yellow liquid.
Benzyl azide: Benzyl bromide (2.0 mL, 16.84 mmol, 1.0 equiv.) was dissolved in DMSO (40
mL). Sodium azide (1.64 g, 25.26 mmol, 1.5 equiv.) was added as solid and the reaction was
stirred overnight at room temperature. Water was added slowly to the reaction mixture and
the product was extracted using diethyl ether. The combined diethyl ether layer was washed
with brine, dried over anhydrous sodium sulphate and the solvent was removed under
reduced pressure to yield benzyl azide.
2-Bromo benzyl azide: 2-Bromo benzyl bromide (2.5 g, 10 mmol, 1.0 equiv.) was dissolved
in DMSO (40 mL). Sodium azide (0.975 g, 15 mmol, 1.5 equiv.) was added as solid and the
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reaction was stirred overnight at room temperature. Water was added slowly to reaction
mixture and the product was extracted using diethyl ether. The combined diethyl ether layer
was washed with brine, dried over anhydrous sodium sulphate and the solvent was removed
under reduced pressure to yield 2-bromobenzyl azide.
General procedure for the cyclo-addition reaction between azide and terminal alkyne:
Alkyne (1 equiv.) and azide (1 equiv.) were added in the presence of water (5 mL) in a 25 mL
round bottom flask. To this solution, 1 equivalent of triethylamine (TEA) and 10 mg of
Cu(I)-pABA catalyst (0.01 mol % of Cu) were added. The reaction mixture was stirred at
room temperature for 3-5 h and the reaction was monitored using thin layer chromatography
technique. After completion, the reaction mixture was filtered and the residue was washed
with methanol. Methanol was evaporated from the filtrate and the latter was extracted using
ethyl acetate and subsequently dried over anhydrous sodium sulphate. The combined organic
layer was then concentrated under vacuum to give the corresponding triazoles and purified by
column chromatography. Compounds were confirmed by comparison with the spectroscopic
data described in the relevant literature.
General procedure for the one-pot, multicomponent azide-alkyne cycloaddition: The
above mentioned procedure was followed using an alkyl halide 5 (1 equiv.), NaN3 (1 equiv.)
and an alkyne 2 (1 equiv.) in the presence of water (10 mL), triethylamine (1 equiv.) and
catalyst (0.01 mol % of Cu) for the cycloaddition reaction in a single pot for 7 h.
Characterization techniques: SEM studies were performed in a FEI FEG Nova 600
Nanolab operating at 2–10 kV. TEM investigations were undertaken at 120 kV in a Philips
CM200 TEM equipped with a LaB6 source. An ultrathin window energy-dispersive X-ray
spectrometer and a Gatan Imaging Filter (GIF) attached to the microscope were used to
determine the chemical composition of the samples. The UV-vis spectra were recorded using
a Shimadzu UV-1800 UV-VIS spectrophotometer with a quartz cuvette. Raman spectra were
acquired using the green (514.5 nm) line of an argon ion laser as the excitation source. Light
dispersion was undertaken via the single spectrograph stage of a Jobin–Yvon T64000 Raman
spectrometer. The X-ray diffraction (XRD) patterns were recorded on a Shimadzu XD-3A X-
ray diffractometer operating at 20 kV using Cu-Kα radiation (k = 0.1542 nm). The
measurements were performed over a diffraction angle range of 2θ = 20o to 70o. The X-ray
photoelectron spectra were collected in an ultra-high vacuum chamber attached to a Physical
Electronics PHI 560 ESCA/SAM system. Nitrogen adsorption-desorption isotherms were
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measured with a Quadra-Sorb S1 apparatus at 77 K. The surface areas were calculated by the
Brunauer–Emmett–Teller (BET) method, and the pore size distribution was calculated from
the desorption branch using the Barett-Joyner-Halenda (BJH) theory. The Thermo Scientifc
XSERIES-2 Quadrupole Inductively Coupled Plasma Mass Spectrometer (ICP-MS)
1
instrument was used to calculate the copper concentration due to leaching process. H NMR
and 13C NMR spectra were recorded on Bruker Ultrashield 400 (400 MHz for 1H and
100 MHz for 13C{1H} in CDCl3).
Results and discussion:
Formation mechanism of the Cu(I)-pABA complex:
The Cu(I)-pABA composite complex was prepared by using an in-situ polymerization and
composite formation technique26 in which the formation of the polymer and Cu(I) took place
simultaneously. During the addition of copper sulphate to 2-aminobenzoic acid, the oxidative
polymerisation of aminobenzoic acid occurred to form poly-(aminobenzoic acid), pABA,
while at the same time, the Cu(II) salts reduced to Cu(I). Further reduction of Cu(I) to Cu(0)
nanoparticles was not facilitated probably because the co-ordination of the Cu(I) with the
chain nitrogen of the pABA forms an energetically more stable N→Cu(I) type of bond but
the exact structure of Cu(I)-pABA has not been established yet. The results of the following
characterization techniques support the above statements.
Characterization of the Cu(I)-pABA complex:
Microscopic property: The SEM image (Figure 1A) illustrates the fiber-like morphology of
the Cu(I)-pABA complex. A similar morphology was obtained when the ratio of copper
sulphate to 2-aminobenzoic acid was altered. Various sizes and dimensions of the fibers were
seen within the branch of the polymer. Focusing the high intensity electron beam on the
sample was not able to distort the structure suggesting a high level of rigidity of the polymer.
The TEM image (Figures 1B) shows the internal microstructure of the polymer. It should be
noted that further reduction of Cu(I) species to Cu(0) is possible during TEM observations if
the sample is exposed to the electron beam for an extended period or when the beam is
focussed onto a given area. The viewing conditions were chosen here such that this reduction
did not occur. The surface of the samples was found to be smooth while there was no
evidence of the presence of copper nanoparticles within or on the polymer. To confirm this,
X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) measurements were
undertaken. Energy-dispersive X-ray (EDX) spectra was obtained from the electron beam
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being focused onto the Cu(I)-pABA sample and yielded copper X-ray peaks situated at the
binding energies of 0.85, 8.05, and 8.95 keV belong to CuL1, CuKα, and CuKβ, respectively.
The representative EDX Spectra for Cu(I)-pABA sample is available in Electronic
Supplementary Information Fig. S1 (ESI). The Ni peak is derived from the TEM support
grid.
Surface analysis: The XRD pattern of polyaniline and the derivatives generally varies as a
consequence of the nature of the synthesis route, solvent utilized for the synthesis, the
oxidation state and the chain length of the polymer.27 In the present study, the XRD pattern of
Cu(I)-pABA (Figure 2A) confirmed the crystalline character of the poly (2-aminobenzoic
acid), and showing no indication of the formation of metallic copper. The XRD pattern of
pABA is available in Electronic Supplementary Information Fig S2 (ESI). The XPS spectrum
(Figure 2B) shows a single Cu 2p3/2 peak at 933.40 eV, which suggests the presence of Cu(I)
in the sample.28 XPS analysis also confirmed that 1.06 wt% Cu was present on the surface of
the polymer matrix.
Optical characterization: The UV-vis spectrum of Cu(I)-pABA complex is shown in Figure
3A. A shoulder-like appearance at 330 nm corresponds to the π−π* transition of the
benzenoid rings, an inter-band transition. Again, in the present study, within the range
between 400−700 nm, the resultant complex material showed a broad absorption spectra with
an absorption peak at 500 nm and this behaviour might be due to the combined effect of (a)
polaron–bipolaron transition, that shows the absorption band within the range of 400–440 nm
and (b) benzenoid to quinoid excitonic transition.29,30 The position of the excitonic peak is
sensitive to the nature of the counter-ions, the solvent and to the chemical structure of the
polymer.31
Figure 3B shows a typical Raman spectrum recorded from the Cu(I)-pABA supramolecular
material. In the 1700 and 1000 cm−1 range the bands derived from Raman spectra involve the
poly-(aminobenzoic acid) oxidation state. The spectrum of polymer reveals C–C stretching
deformation bands of benzene ring at 1602 and 1575 cm−1, which are characteristic of the
semiquinone structure.32,33 Another peak appeared at 1500 cm−1 corresponds to the N–H
bending deformation band as a result of the interaction of the Cu(I) with nitrogen. Three
prominent peaks at 1390, 1427 and 1450 cm−1 correspond to the C–N•+ stretching modes, the
intensity of the peak at 1390 cm−1 confirming the high concentration of these species present
in the polymer. The bands between 1200–1300 cm−1 can be assigned to C–N stretching
modes. The position of the benzene C–H bending deformation band at 1175 cm−1 is again
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characteristic of the reduced and semiquinone structures. The above mentioned bands
indicate the presence of both quinoid and benzenoid structures in poly-(aminobenzoic acid).
Gas adsorption property: According to Figure 4, the nitrogen adsorption and desorption
isotherms of Cu(I)-pABA possess a type II isotherm with a typical H3-type hysteresis loop
according to the IUPAC (International Union of Pure and Applied Chemistry) classification.
The corresponding pore size distribution curve by the Barrett-Joyner-Halenda (BJH) method
demonstrates that the pore diameters are in the range from 25 to 35 nm (inset, Figure 4). The
BET surface area of the sample was calculated to be 7.8 m2.g–1.
Catalytic property of the Cu(I)-pABA supramolecular composite: The Cu(I)-pABA
composite material was used as an catalyst for 1,3-dipoar cycloaddition for the synthesis of
di-substituted 1,2,3-triazoles using benzyl azide, 1a, with phenyl acetylene, 2a, at room
temperature in the presence triethyl amine (Et3N) under different solvent conditions such as
dichloromethane, chloroform, toluene, ethanol, methanol and water (Table 1). Before that the
thermal stability of the catalyst was measured using differential scanning calorimetry (DSC)
technique. The DSC thermogram shows the superior thermal stability of the Cu(I)-pABA in
comparison with pure polymer (pABA). Details DSC study is available in Electronic
Supplementary Information Fig S3 (ESI). In the absence of Cu(I)-pABA, there was no sign of
the formation of the product 1-benzyl-4-phenyl-1H-1,2,3-triazole (3a) (entry 1). Using Cu(I)-
pABA as a catalyst, the desired coupled product has been achieved with varying yields
(entries 2-6) in presence of different solvents (dichloromethane, chloroform, toluene, ethanol,
methanol and water). The combination of methanol, methanol-water (1:1) and water alone
(entries 3-5) gave the highest product conversion among all the solvents tested in Table 1.
Further optimization of the reaction was performed by varying the catalyst loading. The best
result was achieved when the catalyst concentration was 0.01 mol% of Cu in methanol /
methanol-water (1:1) / water used as a solvent (Table 1, entries 3−5). Increasing the amount
of catalyst concentration by a factor of 10, no further improvement in the product yield was
recorded (Table 1, entry 6). Further to the above, the reaction between benzyl azide with
phenyl acetylene was also carried out in the absence of Et3N and in the presence of the
catalyst (Cu(I)-pABA) to determine the significance of Et3N in the reaction. We observed
that the most appropriate reaction conditions in which our catalyst performed efficiently was
in the environment of Et3N−H2O. The product, 1-benzyl-4-phenyl-1H-1,2,3-triazole (3a), was
characterised by spectroscopic methods and found to be identical with that reported one.34 As
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a consequence of the above results, by considering both an economic and an environmental
aspect, it was decided to use only water as a solvent for the rest of the study.
Based on the above optimized reaction conditions, we explored the versatility of the catalyst
for the 1,3-dipolar cycloaddition of structurally diverse azides and alkynes, and the results are
summarized in Tables 2 and 3. All the substrates produced the expected cycloaddition
product with very good to excellent yields and selectivity.
It was found that a yield of 98% of the cycloaddition product, 1-benzyl-4-phenyl-1H-1,2,3-
triazole, has been obtained for the coupling between benzyl azide and phenylacetylene (Table
2, entry 1). The coupling of phenyl azide with phenylacetylene (Table 2, entry 6) resulted the
product, 1, 4-diphenyl-1H-1,2,3-triazole, with the yield of 97%. To achieve a comparable
yield value for the coupling product between benzyl azide with phenylacetylene and phenyl
azide with phenylacetylene, a longer reaction time was required for the later and that can be
explained in terms of an adjacent steric crowding effect due to the presence of benzene ring.
The coupling between ethyl propiolate with benzyl and phenyl azide (Table 2, entries 2 and
7) produced 90% of the products (ethyl 1-benzyl-1H-1,2,3-triazole-4-carboxylate, 3b, and
ethyl 1-phenyl-1H-1,2,3-triazole-4-carboxylate, 3g) has been obtained within 3 and 5 hours
of reaction duration respectively. The structure of the compound 3g has been identified by the
single crystal X-ray crystallography35 as shown in Figure 5. When prop-2-yn-1-ol was
coupled with benzyl azide (Table 2, entry 3), a decrease in yield (84%) has been observed of
the cycloaddition product. Coupling between 1-ethynyl-4-(trifluoromethoxy) benzene and
benzyl azide produced the cycloaddition product, 1-benzyl-4-(4-(trifluoromethoxy)phenyl)-
1H-1,2,3-triazole, with a yield of 86% (Table 2, entry 4). The presence of electron donating
group in the alkynes does not have much effect towards the yield of cycloaddition product.
Cycloaddition reaction between 1-ethynyl-4-methoxybenzene with both benzyl and phenyl
azide produced 87 and 86% yield, respectively (Table 2, entries 5 and 8) within 3 and 5 hours
of reaction duration respectively. The coupling between phenyl acetylene and 1-azido-4-
methoxybenzene produced the cycloaddition product, 1-(4-methoxyphenyl)-4-phenyl-1H-
1,2,3-triazole, with a yield of 95% (Table 2, entry 9). Almost identical amount of
cycloaddition product, 1-(naphthalen-1-yl)-4-phenyl-1H-1,2,3-triazole, has been obtained
when phenyl acetylene reacted with 1-azidonaphthalene, (Table 2, entry 10), within 5h of
reaction duration. The cycloaddition of 2-bromobenzyl azides with different alkynes (Table
3, entries 1-5) shows an identical reactivity trend to that found for the benzyl azide (Table 2,
entries 1-5).
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The recyclability of the catalyst: After identified water as the suitable solvent for the above
reactions, we investigated the scaling up of the title reaction and the recyclability of the
Cu(I)-pABA catalyst using benzyl azide and phenylacetylene as reactants. We increased ten
fold the amount of both the catalyst and the reactants, and performed the experiment under
the previous reaction conditions. After the first run, the product was extracted with ethyl
acetate and the residual catalyst was reused four times under the same conditions. The results
indicated that the used material was also active as a catalyst without a significant loss of
catalytic performance (Figure 6A). At the end of the fifth cycle, a yield of 83% of the coupled
product has been achieved. The catalyst was characterized by TEM at the conclusion of the
first cycle. The presence of the copper nanoparticles was clearly noted (dark spots with wide
size distribution, 10−40 nm, Figure 6B, some of them are circled). In the case of
nanoparticles, the surface of the particles is considered to be more reactive as a catalyst as the
surface area to volume ratio of the catalyst particles increases significantly as its size
decreases to the nano level. In the present scenario, the results of the catalytic activity studies
during the recycling process did not show any noticeable effect of nanoparticles in terms of
yield or time for the completion of the reaction, which implies that both Cu(I) and the copper
nanoparticle species were almost equally active as a catalyst for cycloaddition reaction. It is
also important to mention that ICP-MS (inductively coupled plasma mass spectrometry)
analysis did not provide any indication for the leaching of copper species at any stage of the
recyclability study of the catalyst. The gradual decrease of the yield with recycling was
mainly due to the loss of catalyst species during the washing process. For each subsequent
cycle, the fresh reaction mixture had a lower amount of copper present in the catalyst which
affected the yield.
Cycloaddition reaction using a one-pot multicomponent system: For many organic
transformations, the reaction sequences are not as efficient as enzymatic reactions in terms of
selectivity and also from an economic point of view. The ideal reaction strategy for the
preparation of structurally complex substances would involve sequences in which stereo-
controlled formation of bonds occur in a single step starting from simple, readily available
materials. As a result, great attention has been given to the development of multicomponent
reactions. In the present work, we also directed our attention towards the one-pot, three-
component Click reaction (Table 4) in which the azide-alkyne cycloaddition products were
generated in-situ from their precursor, aryl bromides, sodium azide and alkyne, by deleting
one step. The Cu(I)-pABA catalyst again performed well as a catalyst in water in the
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presence of triethyl amine to give the desired products (Table 4, entries 1−10) in good to
excellent isolated yields ranging from 85-94% with a longer period of reaction time (7 hours)
to complete.
Kinetic study of the cycloaddition reaction: The kinetic study of the title reaction, in the
o
presence of a Cu(I)-pABA catalyst (0.01 mol% Cu) at room temperature (25 C) using H2O
as a solvent for the period of seven hours, has been performed for (a) benzyl azide with
phenyl acetylene in the presence of triethyl amine, (b) benzyl azide with phenyl acetylene in
the absence of triethyl amine and (c) for the three component system, benzyl bromide,
sodium azide and phenyl acetylene in the presence of triethyl amine (Figure 7). From this
graph, it is clear that a higher conversion was achieved when triethyl amine was used as a
base for both (a) and (c). For (a), about 97% cycloaddition product was recorded in 180 min
whereas only a 55% cycloaddition product was obtained within the same time period for (b).
For (b), the rate of the reaction was retarded due to the absence of the base. For the reaction
with the multicomponent system (curve c), a steady conversion of the reactants was observed
resulting in around 93% of cycloaddition product in 390 min. No further increase in
conversion was indicated after an additional 30 mins. From Figure 7, curve b, it is clear that
in the absence of the base, the induction time of the reaction was longer so there was no
indication of product formation in the first 30 min whereas in (a) and (c) no such induction
period was observed when triethyl amine was used in the reaction. In absence of a base 76%
of cycloaddition product has been achieved clearly indicates the importance of base for a
Click reaction to obtain a higher yield.
The most accepted mechanistic pathway for the Cu(I)-pABA catalysed cycloaddition reaction
is illustrated in Scheme 1. Since Cu(I) is considered to be the most active species for this
reaction, the mechanism thus involves the formation of a Cu(I)-acetylidine complex through
the coordination with alkyne followed by the addition with the azide group to give 1,2,3-
triazole. It is worth to mention that, under the standard reaction conditions, all the reactions
were highly regioselective towards 1,4-disubstituted triazoles. Simple workup operations
involving filtration, solvent evaporation and/or column chromatography techniques were
applied, furnishing the corresponding 1,2,3-triazoles with excellent isolated yields and
selectivity irrespective of nature of the substrates.
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Conclusions:
In summary, the present study illustrates the feasibility and the applicability of utilizing a
Cu(I)-pABA composite material, synthesized from the precursors of Cu(II) sulphate and (2-
aminobenzoic acid), to catalyse azide-alkyne cycloaddition at room temperature in the
presence of water. The process is environment friendly and uses an easily available solvent to
produce excellent yields. Moreover, the execution of the reaction was performed easily using
a one-pot, multicomponent strategy to provide the target 1,2,3-triazoles with excellent yields
and selectivity. The recyclability of the catalyst without the loss of significant efficiency
together with the scope for the scaling up of the reaction indicates the potential of the
material as an efficient catalyst.
Acknowledgement:
The authors (RUI, AT, MC and KM) acknowledge financial support from the Research
Committee and the Faculty of Science of the University of Johannesburg. MJW gratefully
thanks the National Research Foundation (NRF), South Africa for financial support.
References:
1
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Figure Captions:
Figure: 1
Representative (A) SEM and (B) TEM image of the Cu(I)-pABA complex. No evidence of
the formation of copper nanoparticles was seen from the TEM image.
Figure: 2
XRD pattern (A) indicates the crystalline character of the polymer and no indication of the
presence of metallic copper. The XPS analysis (B) shows a single Cu 2p3/2 peak at 933.40 eV
that corresponds to the presence of Cu(I) species in the sample.
Figure: 3
The UV-vis spectrum (A) of the Cu(I)-pABA complex with a shoulder-like appearance at
330 nm corresponds to the π−π* transition of the benzenoid rings whereas the
polaron/bipolaron transition is positioned at about 400 nm. In the Raman spectrum (B) two
high intensity peaks at 1602 and 1575 cm−1 reveal the C–C deformation bands of benzenoid
unit whereas the benzene C–H bending deformation band at 1175 cm−1 indicates the presence
of quinoid rings.
Figure: 4
Nitrogen adsorption and desorption isotherms and pore size distribution of the Cu(I)-pABA
composite (in-set).
Figure: 5
ORTEP diagram of compound 3g.
Figure: 6
(A) The histogram from the recyclability study of the Cu(I)-pABA catalytic system shows
that the used material was active as a catalyst without a significant loss of catalytic
performance. At the end of the fifth cycle, a yield of 83% of the coupled product was
achieved. (B) The TEM image of the used catalyst at the end of the first cycle reveals the
formation of copper nanoparticles (some of them are indicated within circles) with a wide
range of size distribution, 10−40 nm.
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Figure: 7
Kinetic study of the azides and alkynes cyclo-addition reactions for (a) benzyl azide with
phenyl acetylene in the presence triethyl amine, (b) benzyl azide with phenyl acetylene in the
absence of triethyl amine and (c) three-component system, benzyl bromide, sodium azide and
phenyl acetylene in the presence triethyl amine using the Cu(I)-pABA catalyst (0.01 mol% of
Cu) at room temperature for a period of 7 hours.
Scheme caption:
Scheme: 1
Proposed mechanism of the azide-alkyne cycloaddition reaction.
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Scheme: 1
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: Solvent and catalyst optimization Studies.a
Catalyst
Table 1
Ph
Bn N
Ph
+
Bn N3
N
Solvent
N
3a
1a
2a
Time (h) Yield(%)
Catalyst conc. (mol% of Cu)
Solvent
Entry
DCM/ CHCl3/
Toluene/ EtOH/
MeOH/ H2O
Cu-pABA (0.0)
1
24
-
DCM/ CHCl3/
Toluene/ EtOH
81-86
2
Cu-pABA (0.01)
3-5
3
4
Cu-pABA (0.01)
Cu-pABA (0.01)
3
3
97
97
MeOH
MeOH : H2O (1:1)
5
Cu-pABA (0.01)
3
97
H2O
MeOH/ MeOH:H2O/
H2O
3
97
6
Cu-pABA (0.1)
a Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol) and triethyl amine (1.0 mmol)
at room temperature.
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Cu(I)-pABA catalyzed azide-alkyne cycloaddition of benzyl and phenyl azides with
Table 2:
different alkynes.a
Ar
Catalyst
R
N
N
Ar N3
+
R
N
2a-e
1a-d
3a-j
, Ar = Benzyl (Bn)
a
b, Ar = Phenyl (Ph)
, Ar = 4-OMePh (Ar')
c
d, Ar = 1-Naphthyl (Nap)
Alkynes (2)
Azides (1)
Products (3)b,c
Yields (%)
98
Entry
1
Bn
Bn
N
N
a
a
a
N
O
O
90
84
a
2
3
4
N
N
O
b
O
N
b
Bn
OH
a
N
OH
c
c
N
N
Bn
Bn
N
N
OCF3
a
a
OCF3
86
87
97
N
d
d
N
N
5
OCH3
OCH3
N
e
e
Ph
N
6
7
8
b
N
a
f
N
Ph
O
O
O
N
N
b
90
86
O
g
b
N
Ph
N
b
OCH3
OCH3
N
N
h
e
Ar'
N
9
c
95
91
N
i
N
a
a
Nap
N
10
d
N
j
N
a All reactions were carried out in water in the presence of the Cu(I)-pABA catalyst (0.01 mol% Cu) and
triethyl amine base (1 equiv.) at room temperature.
b Reactions with benzyl azides ( ) were under taken for 3 h.
1a
c Reactions with aryl azides (
) were under taken for 5 h.
1b, 1c, 1d
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Cu(I)-pABA catalyzed azide-alkyne cycloaddition of 2-bromobenzyl azides with different
Table 3:
alkynesa
Catalyst
R
N3
N
N
+
R
N
Br
Br
1c
4a-e
2a-e
Entry
1
Alkynes ( )
Products ( )
Yields (%)
98
2
4
N
N
a
b
c
Br
a
N
N
O
O
O
O
N
N
2
3
91
90
Br
b
c
OH
N
OH
N
Br
N
N
4
5
90
88
OCF3
OCF3
N
Br
N
d
d
N
N
OCH3
OCH3
Br
N
e
e
a All reactions were carried out in water in the presence of the Cu(I)-pABA catalyst (0.01 mol% Cu) and
triethyl amine base (1 equiv.) at room temperature for 3 h.
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Azide-alkyne cycloaddition using a polymer composite catalyst.a
Table 4:
R1
catalyst
R
N
R1 Br
+ NaN3
+ R
2a-e
N
3a-e, 4a-e
N
5 a,b
R1 = Ph
R1 = o-BrPh
a,
b,
Entry
Products (3,4)
Yields (%)b
93
3a
3b
3c
3d
3e
1
2
3
4
90
86
90
87
5
6
94
93
92
88
85
4a
4b
7
8
9
4c
4d
4e
10
aAlkyl halide (1 equiv.), NaN (1 equiv.), alkyne (1 equiv.) and Cu(I)-
5
2
3
pABA catalyst (0.01 mol% Cu), triethyl amine (1 equiv) at room temperature.
b All reactions were caried out over a period of 7 h.
24