Microwave assisted azide-alkyne cycloaddition reaction using polymer supported Cu(i) as a catalytic species: A solventless approach

Article abstract of DOI:10.1039/c5ra04490a

A polymer supported copper(i) composite has been synthesized using a one-step chemical synthesis route under ambient conditions. The resultant material serves as an effective catalyst for a 1,3-dipolar cycloaddition reaction between terminal alkynes and a

Full text of DOI:10.1039/c5ra04490a

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DOI: 10.1039/C5RA04490A
Microwave assisted azide-alkyne cycloaddition reaction using polymer supported Cu(I)
as a catalytic species: A solvent less approach
Abu Taher, Debkumar Nandi, Rafique Ul Islam, Meenakshi Choudhary, Kaushik Mallick*
Department of Chemistry, University of Johannesburg, P.O. Box: 524, Auckland Park 2006,
South Africa.
*Corresponding author:kaushikm@uj.ac.za (K. Mallick)
ABSTRACT:
Polymer supported copper (I) composite has been synthesized using a oneꢀstep chemical
synthesis route under ambient condition. The resultant material serve as an effective catalyst
for 1,3ꢀdipolar cycloaddition reaction between terminal alkynes and azides to synthesize
1,2,3ꢀtriazoles with excellent yields using microwave irradiation technique in absence of any
solvent. The composite has also been found to an effective catalyst for the multicomponent
synthesis of 1,2,3ꢀtriazoles from organic halides, sodium azide and terminal alkynes under
the identical conditions as mentioned above.
KEYWORDS: azideꢀalkyne cycloaddition, multicomponent reaction, Cu(I) catalyst,
microwave synthesis
1. INTRODUCTION:
The copperꢀcatalyzed azideꢀalkyne cycloaddition reaction has become one of the most
important reactions for the preparation of 1,2,3ꢀtriazoles.1 The 1,2,3ꢀtriazoles are typical
nitrogenꢀcontaining heterocyclic molecules that have attracted interest due to their wide range
of applications in different biological activities.2 These molecules have pharmaceutical
applications for the development of new drugs3 and also important for industrial purpose for
the development of new materials4 as well as the designing of new catalysts.5 The
cycloaddition reaction as discovered by Huisgen6 and developed independently by Sharpless1
and Meldal7 using the copperꢀcatalysed reaction protocol with high regioselectivity.
Copper(I) is the recommended catalyst for azideꢀalkyne cycloaddition reaction, commonly
known as ‘Click reaction’,1,8 and most of the reaction protocols involved either by direct
addition of a Cu(I) salt or inꢀsitu reduction of Cu(II) by sodium ascorbate.1,9 In an effort to
achieve a reusable heterogeneous catalytic nature, Cu(I) catalysts have been immobilized
onto polymers10 or zeolite.11 Copper nanoparticles,12 copper turnings13 and nanostructured
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CuO14 have also successfully demonstrated as a catalyst for this reaction. Using Cu2O powder
as a source of catalytic Cu(I) species for azideꢀalkyne cycloaddition reactions results poor
yields.15 Efforts have also been made to enhance the catalytic efficiency of Cu2O by using
several surface modification techniques.16 Polymer coated Cu2O nanoparticles have been
reported as a catalyst for click reactions in water under physiological temperatures.17 Copper
nanoparticles have been produced from copper sulphate precursor using excess hydrazine as a
reducing agent and successfully used for cycloaddition reactions.10 Again, stoichiometric
amount hydrazine and copper acetate system was used for the synthesis Cu2O as a catalyst for
the title reaction.18 Nanoporous copper catalyst fabricated from Cu30Mn70 alloy, by applying a
deꢀalloying temperature, shows excellent catalytic activity for azideꢀalkyne cycloaddition
reactions.19
The demand of green and sustainable synthetic method is a significant challenge to the
chemical community. This objective can be achieved through the use of (i) aqueous synthetic
protocols and (ii) microwave technique which has been reported to reduce the reaction time
and increase the product yield.20 Microwave chemistry generally relies on the ability of the
reaction mixture to efficiently absorb microwave energy, taking the advantage of microwave
dielectric heating phenomena.21
The use of solid copper granules was found to be effective for the alkyneꢀazide cycloaddition
reaction as a catalyst when microwave energy was applied.22 Highly efficient cycloaddition,
between organic azides and terminal alkynes, has been reported under microwave irradiation
catalyzed by copper nanoparticles mounted within the pores of activated charcoal.23
A
microwaveꢀassisted synthesis of the 1,4ꢀdisubstituted 1,2,3ꢀtriazoles has been reported using
copper(I)ꢀcatalyzed threeꢀcomponent reaction in a completely regioselective manner.3 A oneꢀ
pot procedure for Cu(II)ꢀcatalyzed diazoꢀtransfer and subsequent Cu(I) catalyzed azideꢀ
alkyne cycloaddition has been reported for the generation of 1,4ꢀdisubstitutedꢀ1,2,3ꢀtriazoles
from amines using a microwave irradiation technique.24 A series of fluorescent 8ꢀ(1Hꢀ1,2,3ꢀ
triazolꢀ4ꢀyl)ꢀsubstituted adenosine derivatives were synthesized via Sonogashira crossꢀ
coupling reaction followed by copper catalyzed azideꢀalkyne cycloaddition chemistry
applying a microwave irradiation method.25
A polymer supported cuprous iodide catalyst as the source of Cu(I) has been reported26 for
the preparation of a small library of 1,4ꢀdisubstituted 1,2,3ꢀtriazoles which were obtained
with a very good yields in acetonitrile and dichloromethane solvent. The catalyst did not
show any significant leaching of copper and can be reused for a number of cycles without
decreased reaction yields.
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Inspired by the above report on the polymer based copper catalyst, we have synthesized
Cu(I)ꢀpoly(phenylenediamine), Cu(I)ꢀpPDA, complex using inꢀsitu polymerization and
composite formation (IPCF) route.27 During the polymerization process each step is
associated with a release of electron and that electron reduces the Cu2+ ion to form Cu+ ion.
The Cu+ ion binds with the chain nitrogen of the poly(phenylenediamine) which acts as the
catalytic centre in the polymerꢀmetal composite material. The polymer based copper
composite was used as catalyst for azideꢀalkyne cycloaddition reaction using a microwave
irradiation technique under solvent free condition. The advantage of a polymer as a stabilizer
of the catalyst is due to its robustness as well as flexibility28 and also shows the potential
benefit for wide range of applications.29 The copperꢀpolymer composite was characterized
using the spectroscopic and microscopic techniques.
2. EXPERIMENTAL PROCEDURE
2.1. Materials
Ultraꢀpure water (specific resistivity >17 Mꢀcm) was used to prepare the solution of CuSO4,
5H2O (10−2 mol dm−3). All the chemicals as well as the solvents were purchased for this study
were ‘used as received’ without further purification.
2.2. Characterization techniques
Scanning electron microscopy (SEM) studies were undertaken in a FEI FEG Nova 600
Nanolab at 5 kV. The UVꢀvis spectra were recorded using a Shimadzu UVꢀ1800, UVꢀVIS
spectrophotometer with a quartz cuvette. IR spectra were collected utilizing a Shimadzu
IRAffinityꢀ1 with a spectral resolution of 0.5 cmꢀ1. The XRD patterns were recorded on a
Shimadzu XDꢀ3A Xꢀray diffractometer operating at 20 kV using CuꢀKα radiation (k =
0.1542 nm). The measurements were performed over a diffraction angle range of 2θ = 20o to
80o. The XPS spectra were collected in an ultraꢀhigh vacuum chamber attached to a Physical
Electronics PHI 560 ESCA/SAM system. Nitrogen adsorptionꢀdesorption isotherms were
measured with a QuadraꢀSorb 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 BarettꢀJoynerꢀHalenda (BJH) theory. 1H NMR and 13C NMR
spectra were recorded on Bruker Ultrashield 400 (400 MHz for 1H and 100 MHz for 13C{1H}
in CDCl3).
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2.3. Synthesis:
2.3.1. Preparation of Cu(I)-pPDA composite catalyst:
In a typical experiment, 0.108g of oꢀphenylenediamine (PDA; 10−2 mol dm−3) was dissolved
in 10 mL methanol To this solution, 0.250 g of CuSO4.5H2O in 10 mL of water (10−2 mol
dm−3) was added slowly under continuous stirring conditions. During the addition, the
solution took on a green colour, while at the end, a greenish precipitation was formed at the
bottom of the conical flask. Entire reaction was performed at room temperature and under
open atmosphere. The material was allowed to settle for 30 min after which the colloidal
solution was taken from the bottom of the conical flask and pipetted onto lacey, carbonꢀ
coated, nickel mesh grids for scanning electron microscopy (SEM) study and the grid was
sputter coated with a conducting layer a few nanometres thick of AuꢀPd. The required
amount of material was used for UVꢀvis and Raman spectroscopy studies. The remaining
portion of the compound was dried under vacuum at 60 0C and used for XRD, XPS and BET
measurements as well as the studies for the microwave assisted azideꢀalkyne cycloaddition
reaction.
2.3.2. Procedure for azide-alkyne cycloaddition in presence of microwave radiation:
Azide, 1a or 1b (1mmol, 1.0 equiv.) and alkyne, 2(aꢀi), (1mmol, 1.0 equiv.) were taken in a
polytop vial in presence of triethylamine (0.14 mL, 1 mmol, 1.0 equiv.) and Cu(I)ꢀpPDA
(5mg of 0.05 mol % of Cu). The reaction mixture was exposed to microwave radiation for
10ꢀ60 seconds using a domestic microwave. To validate the domestic microwave approach,
we also have performed the experiment using a standard laboratory microwave (Anton Paar,
Multiwave PRO) with a power level of 600 W for 10ꢀ60 seconds. The reaction was
monitored using thin layer chromatography (TLC) technique. After completion of the
reaction, the reaction mixture was dissolved in dichloromethane and filtered. Filtrate was
concentrated under vacuum to give the corresponding triazoles and purified by column
chromatography technique. Compounds were confirmed by comparison with the
spectroscopic data described in the reported literatures. It is also important to mention that no
solvent was used for this reaction using a microwave irradiation technique.
2.3.3. General procedure for the one-pot, multicomponent azide-alkyne cycloaddition:
The above mentioned procedure (section: 2.3.2) was followed using benzyl bromide or oꢀ
bromobenzyl bromide, 4a or 4b, (1mmol, 1.0 equiv.), NaN3 (65 mg, 1moml, 1.0 equiv.) and
an alkyne, 2aꢀ2c, 2e or 2g (1mmol, 1.0 equiv.) in presence of triethylamine (0.14 mL, 1
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mmol, 1.0 equiv.) and Cu(I)ꢀpPDA (5mg of 0.05 mol % of Cu) for the oneꢀpot
multicomponent reaction. The reaction mixture was exposed to microwave radiation for 30ꢀ
60 seconds.
3. RESULTS AND DISCUSSION:
Characterization of the Cu(I)-pPDA composite:
The scanning electron microscopy (SEM) image (Figure 1A) shows the sphereꢀlike
morphology has been formed during the reaction between oꢀphenylenediamine and copper
sulphate. The diameter of the spheres is within the ranges from 100 to 300 nm. We have first
determined the optical properties of the microspheres by using UVꢀvisible and Infraꢀred
spectrophotometric techniques (Figure 1, B and C respectively). The electronic absorption
spectra of the polyaniline base and the polyaniline salt have been documented in the
literature. The absorption spectrum of the polyaniline base30 shows two distinct absorption
bands between 315ꢀ345 nm and 590ꢀ650 nm depending upon the method of preparation.
Polyaniline salt31 shows three absorption bands at 325ꢀ360 nm, 400ꢀ450 nm and 700ꢀ825 nm.
In the present study, the steady increase of absorption spectra with the absorption peaks at
435 and 700 nm indicates the gradual oxidation of oꢀphenylenediamine to form the pꢀPDA in
the presence of copper sulphate (Figure 1B). At the end of the polymerization process the
colour of the monomer, which is colourless (Figure 1B, left side cuvette), has changed to
green colour (Figure 1B, right side cuvette). The peak appeared at 435 nm is due to the
polaron/bipolaron transition whereas the band from 550 to 800 nm with the absorption peak
at 700 nm is responsible for the transition from the localized benzenoid highest occupied
molecular orbital to a quinoid lowest unoccupied molecular orbital that is, a benzenoidꢀtoꢀ
quinoid excitonic transition.32 In the IR spectra (Figure 1C), the bands at 1643 cm−1 can be
assigned to the C=C stretching vibration of the quinoid rings whereas a small peak at 1470
cm−1 can be attributed to the C=C stretching vibration of the benzenoid rings. The intensity of
the peak indicates the fully oxidized form of the polymer. The band at 1400 cm−1 corresponds
to the C−N stretching vibration on the aromatic ring. The peaks at 1112 and 1020 cm−1
correspond to the aromatic C−H inꢀplane bending vibration.
The XRD pattern of polyaniline and its derivatives generally varies and strongly depends on
the nature of the synthesis route used, solvent utilized for the synthesis, the oxidation state
and the chain length of the polymer.33 In the present study, the XRD pattern of Cu(I)ꢀpPDA
(Figure 2A) confirmed the crystalline character of the polyꢀphenylenediamine (pꢀPDA), and
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also showing no indication of the formation of metallic copper species. XPS technique was
employed to investigate the nature of copper present in the synthesized material. A broad
spectrum of Cu 2p3/2 is shown in Figure 2 (B) with a peak position at 932.50 eV. The coreꢀ
level Cu 2p3/2 spectrum was deconvoluted, and two peaks at 932.45 and 933.30 eV were
extracted which correspond to Cu (I) and Cu (II), respectively.34 XPS analysis was also
informed that the amount unreacted Cu (II) species in the sample is less than 10%.
Figure 3 shows the nitrogen adsorption and desorption isotherms of Cu(I)ꢀpPDA composite.
The graph resembles with a ‘type II’ isotherm with a typical H3ꢀtype of hysteresis loop
according to the IUPAC classification. The corresponding pore size distribution curve by the
BarrettꢀJoynerꢀHalenda (BJH) method demonstrates that the pore diameters are in the range
from 25 to 35 nm (inset, Figure 3). The BET surface area of the sample was calculated to be
11.2 m2g–1.
3.1. Cu(I)-pPDA as a catalyst for title reaction under microwave irradiation:
The copperꢀcatalyzed azideꢀalkyne cycloaddition (CuAAC), known as a ‘click reaction’, has
become one of the important reactions in pharmaceutical industry3, 35 for the preparation of
1,2,3ꢀtriazoles with high regioselectivity. The relevance of polymer as a support material of
the catalyst has been evolved dramatically in the field of organic chemistry.36 The synthesis
of organic compounds using polymerꢀsupported catalysts has been of great interest in recent
years, especially in connection with pharmaceutical research.37 The polymer has also been
used as a support matrix of the metal catalyst and applied for various organic synthesis and
coupling reactions.38 In our previous reports we have showed that the use of polymer
supported copper (I) as the catalyst for the azideꢀalkyne cycloaddition reaction took about 7h
to achieve a yield of 85ꢀ94% at room temperature for multicomponent system.39 The sluggish
reaction process may not be an attractive protocol for the title reaction and to counter this
problem we have hypothesized, and also influenced by other reference works,22,40 that the
microwave energy may increase the rate and efficiency of the reaction. To confirm this, we
have used Cu(I)ꢀpPDA composite as a catalyst for 1,3ꢀdipoar cycloaddition reaction for the
synthesis of diꢀsubstituted 1,2,3ꢀtriazoles using benzyl azide (1a), with phenyl acetylene (2a),
in the presence of triethylamine (Et3N) using microwave radiation (600 watt). After a short
irradiation (<10 sec) irradiation, a white solid product has been observed at the bottom of the
reaction container. The product was characterised by spectroscopic methods and found to be
identical with the reported one,41 1ꢀbenzylꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole (3aa), with an isolated
yield of 99%, (Table: 1, entry: 1). In the absence of Cu(I)ꢀpPDA, there was no sign of the
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formation of the above product. In this study we did not use any solvent so optimization of
solvent study was ruled out. We also found triethylamine (Et3N) played a good role as a base
so we prefer to use the same for rest of the cycloaddition reactions. It is also important to
mention that solid bases, such as, K2CO3, Na2CO3, K3PO4, Cs2CO3 are not suitable for the
present study presumably due to the liquid nature of Et3N serve the purpose of proton
abstraction from the alkynes more easily compare to the solid bases (K2CO3, Na2CO3, K3PO4
and Cs2CO3) as the reaction was performed under the solvent free condition. Encouraged by
the above result and based on the above standardized reaction conditions, we have explored
the versatility of the Cu(I)ꢀpPDA catalyst for the 1,3ꢀdipolar cycloaddition reaction, using
microwave energy, of benzyl azide with various structurally diverse alkynes and the results
are summarized in Table 1.
All the substrates produced the expected cycloaddition product with very good to excellent
yields and selectivity. When phenyl acetylene attached with and electron donating group
(−OCH3) the coupling reaction with benzyl azide forms 1ꢀbenzylꢀ4ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀ
1,2,3ꢀtriazole (3ab) with an isolated yield of 97% indicates a slight retardation of the reaction
as compared with phenyl acetylene (entry 2). Propargyl alcohol also forms the cycloaddition
product with benzylazide with an isolated yield of 92% (entry 3). The chain length of the
alcohol has an effect on the rate of the reaction where propargyl alcohol is bit faster in rate
for the cycloaddition reaction with benzyl azide than that of 3ꢀbutynꢀ1ꢀol (2d) (entry: 4).
Ester molecules, such as, methyl propiolate (2e) and ethyl propiolate (2f) were also
successfully participate for cycloaddition reaction with benzyl azide produced methyl 1ꢀ
benzylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (3ae) and ethyl 1ꢀbenzylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀ
carboxylate (3af) with the isolated yields of 90 and 91% at 34 and 38 sec respectively (entries
5 and 6). We have attempted the cycloaddition reaction using different terminal alkynes (1ꢀ
pentyne and 1ꢀ hexyne; 2g and 2f) with benzyl azide and more than 90% cyclo product has
been obtained within a minute during the exposure of the microwave irradiation (entries 7
and 8, respectively). We also have checked the performance of the catalyst for the
cycloaddition reaction between the bromoꢀderivatives of benzyl azide (oꢀbromo benzyl azide,
1b) and different alkynes (Table: 1, entries: 9ꢀ14). A similar kind of activity of the Cu(I)ꢀ
pPDA composite as a catalyst for the title reaction has been observed both for benzyl azide
(4a) and oꢀbromo benzyl azide (4b). It is also important to mention that the alkyne containing
heterocycle moiety, 3ꢀethynylthiophene, (Table: 1, entry: 14) also efficiently participate the
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cycloaddition reaction with oꢀbromo benzyl azide with the formation of 1ꢀ(2ꢀbromobenzyl)ꢀ
4ꢀ(thiophenꢀ3ꢀyl)ꢀ1Hꢀ1,2,3ꢀtriazole (3bi) when Cu(I)ꢀpPDA was used as a catalyst.
An interesting result has been obtained when the performance of a domestic microwave was
compared with a standard laboratory microwave, using the identical microwave radiation
power (600 watt) for the period of 10ꢀ60 seconds and the results are summarized in table 3. In
heterogeneous catalysis, the recyclability is an important parameter of the catalyst from the
economic point of view. The stability and performance of the catalyst was tested, for the
reaction mentioned in Table 1, entry 1, under the previous condition (Figure 4A). At the end
of the first cycle, catalyst was recovered using a centrifuge technique and the residual catalyst
was reused for another two times for the similar reaction. A yield of 98% of the coupled
product 3aa was achieved within 10 sec for the reaction between 1a and 2b. The recovered
catalyst was characterized by TEM at the end of the first cycle. The presence of the copper
nanoparticles was clearly noted, with a wide range of size distribution (40ꢀ150 nm), on the
polymer matrix (Figure 4B). Despite some loss of the catalyst during the filtration process the
yield percentage remained considerably good (94%) for the second cycle of the reaction. At
the end of the third cycle a moderate deactivation of the catalyst has been noticed with the
yield of 83% of the cycloaddition product. The results indicated that the used material was
also active as a catalyst without a significant loss of catalytic performance. It also important
to mention that the recovery of the catalyst is a serious challenge for the microwave assisted
reactions particularly for the polymer based catalyst.
3.2. Multicomponent ‘click’ reaction under microwave irradiation:
In chemistry, a multicomponent reaction where more than two reactants combine in a
sequential manner to give highly selective products that retain majority of the atoms of the
starting material. Many organic reactions and the reaction sequences have been developed for
the construction of structurally complex molecules. The ideal reaction strategies for
preparation of structurally complex substances would involve sequences in which the
formation of bonds occur in a single step starting from simple, readily available materials and
for that reason great attention has been given to the development of multicomponent
reactions (MCRs), because of their high degree of atom economy, their applications in
combinatorial chemistry, and diversity oriented synthesis.42 Reports have also been published
on enantioselective MCRs for the synthesis of stereoꢀchemically complex polycyclic
compounds.42ꢀ44 A microwaveꢀassisted threeꢀcomponent reaction was used to prepare a series
of 1,4ꢀdisubstitutedꢀ1,2,3ꢀtriazoles from corresponding alkyl halides, sodium azide, and
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alkynes by Cu(0)ꢀCuSO4 system.13 Cuꢀcatalysed formation of 5ꢀalkynylꢀ1,4ꢀdisubstitutedꢀ
1,2,3ꢀtriazoles has been reported through a multicomponent reaction pathway using organic
halides, terminal alkynes and sodium azide under ambient conditions.45
In this present work, we have used Cu(I)ꢀpPDA as a catalyst for a microwaveꢀassisted threeꢀ
component reaction to prepare a 1,4ꢀdisubstitutedꢀ1,2,3ꢀtriazoles from corresponding alkyl
halides (4a or 4b), sodium azide and alkynes (2aꢀ2c, 2e or 2g). The catalyst again performed
well to give the desired products (Table: 2, entries 1−5) with excellent isolated yields (85ꢀ
96%) for less than a minute from benzyl bromide, sodium azide and alkynes. Phenylacetylene
and methoxy substituted phenylacetylene produced 1ꢀbenzylꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole
(3aa, entry: 1) and 1ꢀbenzylꢀ4ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀ1,2,3ꢀtriazole (3ab, entry: 2) by
reacting with benzyl bromide and sodium azide with the isolated yields of 96 and 92 %
respectively. All other alkynes substituted with alcohol (entry 3) and ester (entry 4) as well as
the terminal alkyne (entry 5) produced the 1,2,3ꢀtriazole products 3 with excellent yield.
Again, microwaveꢀassisted threeꢀcomponent reaction using 2-bromobenzyl bromide, sodium
azide and alkynes yielded the similar kind of results as above and mentioned in Table 2
(entries: 6ꢀ10).
Both studies (mentioned in Table 1 and 2) showed the use of Cu(I)ꢀpPDA as a catalyst for the
formation of 1,4ꢀdisubstitutedꢀ1,2,3ꢀtriazole 3 in a very fast and efficient fashion by
microwave irradiation technique. Compared to regular heating, microwave irradiation
technique is an efficient and convenient approach for the synthesis of complex molecule from
their simple precursors. Under microwave irradiation, molecules rapidly change their
orientation that causes higher molecular friction, results a faster and more efficient reaction.
Again, microwave energy increases the bond vibration which causes the decrease of bond
dissociation energy also results rapid reaction rates with high yields.46, 47
The mechanistic pathway for the Cu(I) catalysed cycloaddition reaction is illustrated in
scheme 1. Since Cu(I) is considered to be the most active species for this reaction, the
catalytic cycle thus involves the formation of a Cu(0)ꢀacetylidine complex (i) through the
coordination with alkyne followed by the addition with the azide group to form an
intermediate (ii). The intermediate (ii) further forms the second intermediate (iii), which
subsequently forms the 1,2,3ꢀtriazole (iv) after the protonation and elimination reaction with
the regeneration of active catalyst.48 It is important to mentioning that under the microwave
reaction condition, both for the domestic and the standard laboratory microwave, all the
reactions were highly regioselective towards 1, 4ꢀdisubstituted triazoles.
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CONCLUSION:
In conclusion, an effective route for the synthesis of highly active and stable polyꢀ
phenylenediamine supported copper (I) catalyst has been described for the promoting 1,3ꢀ
dipolar cycloaddition reactions between terminal alkynes and azides to synthesis 1,2,3ꢀ
triazoles with excellent yields under microwave radiation technique. In addition, the organoꢀ
catalyst was also effective for the above cycloaddition reaction through a oneꢀstep
multicomponent pathway from organic halides, terminal alkynes and sodium azideto avoid
the handling of organic azides which are toxic and hazardous in nature. Microwave
irradiation technique for the current cycloaddition reactions dramatically decrease the time of
the reaction and that consequently increase the turnover number of the reaction. It is also
important to mention that the copper nanoparticles are also very active catalyst for the
microwave assisted 1,3ꢀdipolar cycloaddition reactions which was confirmed during the
recyclability study for the current experiment. The current study also confirms that
ACKNOWLEDGEMENTS
AT acknowledges financial support from the Faculty of Science and the Global Excellence
and Stature fellowship programme, University of Johannesburg. MC acknowledges financial
support from National Research Foundation, South Africa and also the Faculty of Science,
University of Johannesburg. The authors RUI and KM acknowledge financial support from
the Research Committee and the Faculty of Science of the University of Johannesburg.
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Figure Caption:
Figure: 1
(A) The SEM image of the Cu(I)ꢀpPDA composite material illustrates a sphereꢀlike
morphology with the diameter ranging from 100 to 300 nm. (B) The gradual increase of
absorption peaks at 435 and 700 nm indicate the steady polymerization of oꢀ
phenylenediamine. The peak appeared at 435 nm is due to the polaron/bipolaron transition
whereas the band from 550 to 800 nm with the absorption peak at 700 nm is responsible for
the transition from the localized benzenoid highest occupied molecular orbital to a quinoid
lowest unoccupied molecular orbital that is, a benzenoidꢀtoꢀquinoid excitonic transition. At
the end of the polymerization process the colour of the monomer, which is colourless, has
changed to green colour. (C) In the IR spectra, the bands at 1643 cm−1 can be assigned to the
C=C stretching vibration of the quinoid rings whereas a small peak at 1470 cm−1 can be
attributed to the C=C stretching vibration of the benzenoid rings. The intensity of the peak
indicates the fully oxidized form of the polymer.
Figure: 2
(A) XRD pattern indicates the crystalline nature of the polymer and also have no evidence of
metallic copper. In XPS analysis (B), the coreꢀlevel Cu 2p3/2spectrum with two peaks at
932.45 and 933.30 eV correspond to Cu (I) and Cu (II), respectively.
Figure: 3
Nitrogen adsorption and desorption isotherms of Cu(I)ꢀpPDA composite. The pore size
distribution curve demonstrates that the pore diameters are in the range from 25 to 35 nm
(inset).
Figure: 4
(A) The histogram, derived from the recyclability study of the Cu(I)ꢀpPDA catalyst, shows
that the used material is also active without a significant loss of catalytic performance. At the
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end of the first and second cycle a yield of 98% and 94% of the azideꢀalkyne cycloaddition
product has been obtained, whereas as a moderate deactivation of the catalyst has been
noticed during the third cycle with the yield of 83% of the cycloaddition product. (B) The
TEM image of the recovered catalyst at the end of the first cycle. The presence of the copper
nanoparticles was clearly noted, with a wide range of size distribution (40ꢀ150 nm), on the
polymer matrix.
Scheme Caption:
Scheme: 1
Catalytic cycle for the azide–alkyne cycloaddition reaction.
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Table 1. Microwave assisted Cu(I)ꢀpPDA catalyzed azideꢀalkyne cycloaddition of aryl azides
with different alkyne a
Entry
1
Azide Alkyne (2)
(1)
Product (3)b
Time
(sec)
10
Yield
(%)c
99
1a
2
15
97
1a
3
4
30
34
92
88
1a
1a
5
6
34
38
90
91
1a
1a
7
8
54
60
92
95
1a
2g
1a
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Table 1. Continueda
Entry Azide
Alkyne (2)
Product (3)b
Time Yield
(sec)
(1)
(%)c
9
12
98
1b
1b
10
15
98
OH
11
12
13
14
30
34
60
15
90
89
92
96
1b
1b
1b
1b
2c
O
O
N
N
3be
Br
N
aReaction conditions: Benzylazide 1 (1 mmol), alkyne 2 (1 mmol), triethylamine (1 mmol)
b
and 0.05 mol% Cu Cu(I)ꢀ
p
PDA (0.05 mol% of Cu; 5mg). All reactions were carried out in
microwave under solvent free condition. c Isolated yield.
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Table 2. Microwave assisted Cu(I)ꢀpPDA catalyzed one pot multicomponent alkyl bromideꢀ
alkyne cycloaddition a
Entry
Alkyl
Alkyne (2)
Product (3)b
Time (sec)
Yield (%)c
bromide (4)
1
2
30
38
50
58
60
30
38
50
58
60
96
92
86
85
80
94
91
83
84
78
4a
4a
4a
4a
4a
4b
4b
4b
4b
4b
2a
2b
2c
2e
2g
2a
2b
2c
2e
2g
3aa
3ab
3ac
3ae
3ag
3ba
3bb
3bc
3be
3bg
3
4
5
6
7
8
9
10
aReaction conditions: Benzylhalide 4 (1 mmol.), NaN3 (1 mmol), alkyne 2 (1 mmol),
triethylamine (1 mmol) and Cu(I)ꢀp
PDA catalyst(0.05 mol% of Cu; 5mg). bAll reactions were
carried out in microwave under solvent free condition. cIsolated yield.
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Table 3. Comparative yields obtained between domestic MW and laboratory MWa,b
Entry
Alkyl
azide/
bromide (2
or 4)
Alkyne (2) Product (3)
Time
(Sec)
Yield
(%)c
Yield
(%)d,e
(domestic (laboratory
MW)
MW)
1
2
3
4
5
10
15
50
58
60
99
99
1a
2a
2b
2c
2e
2g
3aa
3ab
3ac
3be
3ag
96
86
84
80
95
86
83
81
1b
4a
4b
4a
aReaction conditions: Benzylazide 1 (1 mmol), alkyne 2 (1 mmol), triethylamine (1 mmol)
and Cu(I)ꢀ PDA (5mg of 0.05 mol% Cu), or Benzylhalide 4 (1 mmol.), NaN3 (1 mmol),
p
alkyne 2 (1 mmol), triethylamine (1 mmol) and Cu(I)ꢀpPDA catalyst (5mg of 0.05 mol% Cu).
b All reactions were carried out in microwave under solvent free condition. c,d Isolated yields:
e
average after triplicate. [laboratory MW= Multiwave PRO, Anton Paar GmbH, Power: 600
W].
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Microwave assisted solvent less approach for azide-alkyne cycloaddition
254x190mm (96 x 96 DPI)