Regioselective Synthesis of 1 , 2 , 3-Triazoles Catalyzed Over ZnO Supported Copper Oxide Nanocatalyst as a New and Efficient Recyclable Catalyst in Water

The CuO/ZnO nanocatalysts are reported as efficient and recyclable catalysts for the regioselective synthesis of 1,2,3triazoles from benzyl halides and terminal alkynes in water. The catalysts are synthesized by a co-precipitation method and characterized by BET surface area, XRD, SEM, TEM and EDS analysis. The effect of CuO loading, catalyst amount and solvent was investigated. The catalyst can be recovered by a simple filtration and applied in consecutive runs with no loss of activity.


Introduction
Nowadays, synthesis of 1,2,3-triazoles has received considerable attention because of their wide range of applications. 11,2,3-Triazoles are five-membered nitrogen heterocyclic compounds that have been broadly applied in various research fields including synthetic organic, medicinal, materials, and biological chemistry. 2These compounds are useful building blocks in the chemistry, resistant to moisture, oxygen, light, and also metabolism in the body. 3In addition, 1,2,3-triazoles are used as dyes, corrosion inhibition agents, photostabilizers, and photographic materials. 4The main method for the synthesis of 1,2,3-triazoles is the Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. 5This reaction has been the model for click reactions which was introduced by Kolb and Sharpless in 2001.However, there are some catalytic reactions for the synthesis of 1,2,3-triazole derivatives.][24][25] Recently, nanocatalysts have been extensively studied as competitive substitutes to the usual catalysts due to their comparable performance. 26Particularly, application of nano-metal oxides as catalysts in organic synthesis has been improved because of their significant characteristics.The recyclability of catalysts is an additional advantage of these catalysts. 27e have been putting our efforts towards the design and development of nanocatalysts.0][31] Moreover, as a part of our current research on the development of new routes to prepare heterocyclic systems, [32][33][34][35] the performance of CuO/ZnO nanocatalysts in the click synthesis of 1,2,3-triazoles from benzyl halides and terminal alkynes in water was investigated (Scheme 1).

Results and Discussion
The catalysts are synthesized by a co-precipitation method and characterized by BET surface area, XRD, SEM, TEM and EDS analysis.Figure 1, shows the XRD analysis of ZnO and 20CuO/ZnO samples.
There are several peaks attributed to ZnO at a wide range of 2θ = 31.7,34.3, 36.3, 47.3, 56.4,62.8, 66.2, 67.8, 69.0, 72.5 and 76.9 degrees which are characteristics of (100), (002), ( 101), ( 102), ( 110), ( 103), ( 200), ( 112 1, the ZnO crystallite size is about 23 and 12 nm for ZnO support and 20CuO/ZnO catalyst, respectively.Also, the average crystallite size of CuO in the catalyst is about 8 nm.The structural properties of prepared samples are presented in Table 1. The BET surface area of ZnO support is 53 m 2 /g, and as 20 wt% CuO is loaded on the support, the surface area increases to 89 m 2 /g.As shown in Table 1, after CuO loading on ZnO the pore volume of 20CuO/ZnO increases, while its pore size decreases, simultaneously.The N 2 adsorption/desorption profiles for ZnO and 20CuO/ZnO samples are shown in Figure 2a.According to the IUPAC classification, these isotherms can be categorized as type IV at the borderline with type II, with a type H3 hysteresis loop.This isotherm indicates the presence of mesopores with a pore size distribution continuing into the macropore domain 36 (Figure 2b).In addition, the type H3 hysteresis is usually observed on solids containing aggregates or agglomerates of some particles leading to slit-shaped pores, with nonuniform size and/or shape.Furthermore, the reflection point on ZnO occurs at around P/P 0 = 0.86, and by an increase of CuO it shifts to a lower value of around 0.8 for 20CuO/ZnO.These results suggested the smaller mesopores in the samples containing Cu content.Furthermore, higher amounts of N 2 -adsorption on 20CuO/ZnO nanocatalyst can be related to mesopores with higher pore volume.These results are consistent with the average pore size and pore volume of the samples shown in Table 1.
Figure 3 shows the SEM analysis of ZnO and 20Cu-O/ZnO.
The ZnO micrograph (Figure 3a) exhibits an aggregation of nano-slit-like particles.However, the morphology of the catalyst after Cu loading is changed drastically.As can be seen, incorporation of Cu into the ZnO has a significant effect on the morphology of the catalyst.The 20CuO/ZnO sample exhibits an agglomerate of nanoparticles with a particle size of about 38 nm in diameter.Figure 4a shows TEM image and CuO particle size distribution of 20CuO/ZnO.CuO nanoparticles are highly dispersed on the catalyst surface.Figure 4a-inset picture exhibits the CuO nanoparticle size distribution, by an average CuO particle size of about 4.4 nm.The HRTEM ima- a Ioslated pure products.b Products were characterized by comparison of their spectroscopic data and melting points with those reported in the literature. 19,35 of 20CuO/ZnO is shown in Figure 4b.The reflections with d-spacing values of 0.282 and 0.252 nm correspond to ZnO (100) and CuO (111 -) lattice planes.
For the optimization of reaction conditions, various parameters such as CuO loading, catalyst amount and solvent were investigated.Initially, the reaction between ben-zyl bromide, phenylacetylene and sodium azide, in the presence of the catalyst as a model reaction was investigated (Scheme 1).The perofrmance of various CuO/ZnO nanocatalysts containing 5, 10 and 20 wt.% CuO in the synthesis of 1,2,3-triazoles were investigated.As shown in Table 2, with an increase of CuO content, the activity of Albadi et al.: Regioselective Synthesis of 1,2,3-Triazoles Catalyzed Over ... the catalysts increases, and the 20CuO/ZnO showed the highest yield of reaction (about 92%), in a relatively short reaction time (20 min).Also, in the presence of ZnOblank and CuO-bulk no produsts were obtained.These results demonstrated the effect of CuO nanoparticles on the synthesis of 1,2,3-triazoles.Also, it should be noted that no product was obtained in the absence of the catalyst (blank test) under these reaction condition.
Table 3 shows that the best results was achieved by the reaction of benzyl bromide, phenylacetylene and sodium azide (1: 1: 1.1 mol/ratio) in the presence of 0.07 g of the catalyst in water as the solvent under reflux condition (Table 3).The other solvents such as ethanol, methanol, CH 3 CN, and CH 2 Cl 2 resulted in lower yields.
The activity of various terminal alkynes and benzyl halides under optimized conditions is summarized in Table 4.It is clear that a substitution with electron withdrawing or electron donating groups on the phenyl rings did not have a significant effect on the result of the reaction.It should be noted that the corresponding triazoles were obtained with high yields and regioselectivities.Moreover, the obtained products can be isolated by a simple filtration and recrystallized from a mixture of ethanol/water (3: Furthermore, the recyclability of the catalyst for the reaction of benzyl bromide and phenylacetylene under optimized conditions was investigated.After completion of each reaction, the spent catalyst was recovered by filtration.Then it was washed with hot ethanol, dried and used for the next run.The recovered catalyst showed a sustained performance after 5 consecutive runs with no loss of activity.Also, the results demonstrated high selectivity and high yields of corresponding products in the five consecutive runs (Table 5).2θ = 10-80° using Cu Ká radiation.The specific surface area of samples was determined by nitrogen adsorptiondesorption using BET method, using an automated gas adsorption analyzer (Tristar 3020, Micromeritics).The morphology of the catalyst was investigated comprehensively by scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HRTEM) techniques using a HITACHI S-4160 instrument, as well as JEOL JEM-2100 (200 kV) microscope equipped with an EDS analytical system.

1. Preparation of the Catalyst
The CuO/ZnO catalysts containing 5 to 20 wt.% CuO, were prepared by co-precipitation method.A Na 2 CO 3 H 2 O solution was added drop-wise into an approperiate mixture of 0.03 M Cu(NO 3 ) 2 3H 2 O and Zn(NO 3 ) 3 6H 2 O solutions under continuous mixing.The slurry was kept at pH 8.5 for 15 min at 65 °C, then filtered and washed with deionized water.The precipitates were dried for 12 h at 100 °C followed by calcination at 300 °C for 3 h.The final catalyst is denoted as xCuO/Zn-O where x is the weight percent of the copper oxide in the catalyst.

2. General Procedure
A mixture of benzyl halide (1 mmol), terminal alkyne (1 mmol), sodium azide (1.1 mmol), and proper amount of the catalyst was stirred in water under reflux condition for the appropriate time (Table 3).After reaction completion, the mixture was cooled, filtered and added to hot ethanol.The filtrate was evaporated and dried.Then, the obtained solid was recovered in a hot ethanol/water (3:1 v/v) and the catalyst was washed with hot ethanol, dried and applied for consecutive runs.

Conclusion
In this research CuO/ZnO nanocatalysts as efficient recyclable catalysts were introduced for the click synthesis of 1,2,3-triazoles under reflux conditions in water.The catalysts demonstrated a satisfactory yield of about 88% after 5 consecutive runs, with sustained activity.Clean procedure, easy work-up, short reaction time and high yields of corresponding products make this method an attractive procedure for the synthesis of 1,2,3-triazoles.

Acknowledgement
We are thankful to research council of Behbahan Khatam Alanbia University of Technology for the support of this work.

Experimental
Chemicals were purchased from Merck.Products were characterized by comparison of their spectroscopic data ( 1 H NMR, 13 C NMR and IR) and physical properties with those reported in the literature.NMR spectra were recorded in DMSO-d 6 or CDCl 3 on a Bruker Avance DPX 500 and 400 MHz spectrometers.IR spectra were recorded on a BOMEMMB-Series 1998 FT-IR spectrometer.All yields refer to isolated products.The Bruker AXS D8 advanced diffractometer carried out the XRD analysis of the catalyst.The sample was scanned over the range of

Table 1 :
Structural properties of prepared samples.
SampleCrystallite Size a (nm) S BET Pore volume Pore Size D CuO D ZnO (m 2 /g) (cm 3 /g) (nm) a Average CuO crystal size calculated by XRD.

Table 3 .
Optimization of the reaction conditions.
a Reflux conditions.b Isolated pure products.
a Ioslated pure products.