A magnetic copper organic framework material as an efficient and recyclable catalyst for the synthesis of 1,2,3-triazole derivatives

In this study, a core–shell magnetic metal organic framework (MOF) catalyst was introduced based on Fe3O4 magnetic nanoparticles (MNPs) and copper organic frameworks. In this catalyst, Fe3O4 MNPs have been coated with MOFs in which copper was the inorganic nodes and 1,3,5-benzenetricarboxylic acid was the organic linkers. Then, the core–shell structures and catalytic efficiency have been confirmed properly and completely with various analyses such as FT-IR, TEM, SEM, TEM mapping, SEM mapping, EDX, PXRD, TGA, ICP and VSM. The Cu moieties in MOF and shell structures can catalyze the synthesis of 1,2,3-triazole derivatives with good to excellent yields in the presence of water as a green solvent. Moreover, this catalyst showed the high reusability due to the super paramagnetic properties.

www.nature.com/scientificreports/ oxygen that are the elements of Fe 3 O 4 MNPs, sulfur and particularly carbon, and copper are existed that are the main elements of shell structures. These outcomes approve the successful formation of core-shell structures. EDX analysis was also performed to study again the elemental analysis. So, this analysis was investigated for both bare Fe 3 O 4 and core-shell Fe 3 O 4 @HKUST-1 MNPs (Fig. 7). As can be seen in the first pattern ( Fig. 7a) correspond to Fe 3 O 4 MNPs, the iron and oxygen are presented, while in the second pattern (Fig. 7b), in addition to Fe and O, some new elements related to shell structures including sulfur, carbon and more importantly copper are observed.
It is known that the TGA analysis is a significant factor to confirm the core-shell structures and evaluate the thermal stability of the samples (Fig. 9). As shown in Fig. 9a, the Fe 3 O 4 MNPs have high thermal stability due to the iron oxide structures and only 9.958% of sample's weight has been decreased after increase the temperature to 500 °C. It can be attributed to the decomposition of hydroxyl functional groups on the surface of MNPs or remove of some waters or organic solvents remained in the sample. Interestingly, the TGA graph of Fe 3 O 4 @HKUST-1 MNPs showed more reduction in the weight (about 22.176%, Fig. 9b). The difference between this weigh loss with previous one is about 12% that can be assigned to the decomposition of shell structures 59 . Figure 10 shows magnetic properties of the Fe 3 O 4 and core-shell MNP structures at room temperature in the range of + 15,000 to −15,000 Oe. Thus, the VSM plot of Fe 3 O 4 MNPs exhibited the superparamagnetic properties with high saturation magnetization about 85 emu g −1 (Fig. 10, black graph). It is noteworthy, this magnetic property was reduced to about 65 emu g −1 after coating the MNPs with MOF shell structures (Fig. 10, red graph) 60 . These outcomes approve the successful synthesis of catalyst and it is in agreement with TEM, XRD and TGA results.
It is essential to obtain the amount of copper in the samples. Thereby, its amount in both fresh and reused catalyst (after five times reuse) has been estimated by ICP analysis. According to the ICP results, the weight www.nature.com/scientificreports/ percentage of Cu in the fresh and reused catalyst were 3.512 and 3.497 wt%, respectively. This analysis strongly confirmed the presence of copper in MOF structures (in accordance with EDX and SEM mapping observations) and also shows the leaching of Cu and shell structures is negligible amount that can be ignored. After complete characterization the catalyst structure, the catalyst efficiency has been investigated for the synthesis of 1,2,3-triazole derivatives from the three component condensation reaction of different alkyl halides, various phenylacetylene and sodium azide. To this end, initially, the reaction of benzyl bromide, phenylacetylene and sodium azide has been selected as a model reaction by taking into account several important factors such as amount of catalyst, effect of solvent and temperature (Table 1). Hence, at first step, the reaction was carried out without the catalyst under the solvent-free conditions or water as a green solvent (entries 1 and 2). As expected, with solvent-free conditions and without the catalyst, the reaction did not have any desirable product (entry 1) and the amount of product was trace in water (entry 2). With adding the catalyst to the reaction mixture, the yield of the reaction has been increased gradually (entries 3-6). The best amount of catalyst was obtained 30 mg (1.8 mol%) (entry 5). After find the optimum amount of the catalyst, the reaction was examined in the presence of different solvents that such as THF, DMF, MeCN, MeOH, EtOH, H 2 O and solvent-free conditions (entries 7-12). The highest and lowest amount of 1,2,3-triazole compound were obtained in the presence of water and solvent-free condition, respectively (entries 5 and 12). The last step was study the effect of temperature on model reaction (entries [13][14][15]. Therefore, the model reaction was carried out at different temperatures like 25, 50, 100 and 120 °C. The best temperature was 100 °C (reflux condition) and lower and higher temperature was not satisfying. So, the best condition was the using of water as a green solvent under reflux condition and 30 mg (1.8 mol%) of catalyst (entry 5).  www.nature.com/scientificreports/ In the second step and after finding the optimized reaction condition, the generality of this research was investigated in the reaction of different alkyl and benzyl halides with sodium azide and various phenyl acetylene and also in the attendance of 30 mg (1.8 mol%) of Fe 3 O 4 @HKUST-1 catalyst and water as a green solvent at 100 °C (Table 2). It is worth mentioning that, benzyl halides (entries 1-8) reacted better compared to alkyl halides (entries 9-11) on the basis of yield of the reaction and gave the product with highest amounts of yield. On the other hand, the phenylacetylene derivatives with no substituent (entries 1, 5, 6, and 8) or with electronwithdrawing group (entry 13) have better yield of the reaction compared to electron-donating groups (entries 12, 14 and 15). After that, in order to investigate the catalyst efficiency, the effects of bare MOF (HKUST-1) without the core (Fe 3 O 4 ) (entry 16) and some Cu salts like Cu(OAc) 2 and CuCl 2 (entries 17 and 18) have been tested in the model reaction under optimized conditions. As is evident, the yields of the reaction in presence of HKUST-1, copper acetate and copper chloride were 87, 83 and 80% respectively that they are a little bit lower than Fe 3 O 4 @ HKUST-1 which can be attributed to the nano structures of the final catalyst.
According to the literature 61,62 , a suggested reaction mechanism for the 1,3-dipolar cycloaddition reaction in the attendance of Fe 3 O 4 @HKUST-1 catalyst was proposed (Fig. 11). As mentioned before in the shell structure, the copper (II) was existed that it can be acted as a Lewis acid and catalyzed the synthesis of 1,2,3-triazole    Our catalyst exhibited high catalytic stability in repeated model reaction. On this basis, after finalization the model reaction, the Fe 3 O 4 @HKUST-1 catalyst was separated from the reaction mixture by an external magnet and washed several times with DMF and acetone, dried in vacuum oven at 50 °C for 12 h and reused in the next model reaction. It can catalyze the synthesis of 1,2,3-triazole derivatives with high isolated yield and after five time reusing the catalyst, the yield of the reaction decreased very low that it can be ignored (Fig. 12). These observations showed the structure of catalyst and especially shell structures stay without change during the reaction and probably no leaching of Cu and MOF materials has been occurred during the reaction.
Hot filtration test was also performed to scrutiny the stability of catalyst. In this regard, the model reaction of benzyl bromide (1.0 mmol), sodium azide (1.2 mmol) and phenyacetylene (1.0 mmol) has been carried out in the presence of optimum amount of catalyst (1.8 mol%) and water under reflux condition for 60 min. After www.nature.com/scientificreports/ progress the reaction for approximately 50%, the Fe 3 O 4 @HKUST-1 catalyst has been separated from the reaction mixture with an external magnet and then, the reaction performed for another 60 min. In interesting notice, without the catalyst, the reaction was not carried out that it was monitored by TLC (Fig. 13). A good agreement with ICP results and shows that no leaching of Cu or MOF shell structures have been happened during the 1,3-dipolar cycloaddition reaction. Also, to elucidate the stability of catalyst, after five cycles in the model reaction, any structural changes of catalyst were studied by FT-IR, SEM and ICP techniques. It is clearly evident from the FT-IR spectrum of the 5th reused catalyst that no significant changes in the frequencies, intensities and shapes of absorption bands were observed (Fig. S1). Moreover, the morphology and size of 5th reused catalyst has been investigated bey SEM technique (Fig. S2). The SEM image of resued catalyst (Fig. S2b) was aproximately similar with the SEM image of fersh catalyst (Fig. S2a) and there are not any significant differences in size and morphlogy. Besides, as mentioned in previous sections, the ICP-OES analysis showed that the amount of Cu in reused catalyst is 3.497 wt% that the decrease is very low and it can be ignored. Based on this valuable obtained data, no significant leaching of MOF was obsedrved from the surface of Fe 3 O 4 NPs.
To show the merit of present study compared to previously reported ones by using copper-based catalyst, the effect of our magnetic CuMOF catalyst has been compared with other Cu catalysts in the reaction of benzyl bromide, sodium azide and phenylacetylene (Table 3). Up to now, different homogeneous and heterogeneous Cu catalysts have been used for the azide-alkyne cycloaddition reaction (entries 1-8), but some of them suffer from long reaction time (entries 1-5), using hazardous solvent and reaction conditions (entries 1,3,4 and 7) and more importantly problems to reuse the catalyst (entries 1-3, and 5). Due to the heterogeneous nature and magnetic  www.nature.com/scientificreports/ properties of our catalyst, it can be separated from the reaction mixture by a simple external magnet and it can catalyze the 1,3-diplar cycloaddition reaction in shorter reaction time and greener condition (use water, entry 9).

Conclusion
In summary, a new magnetic MOF catalyst based on copper has been described for the synthesis of 1,2,3-triazole derivatives via the three component condensation reaction of various benzyl/alkyl halides, sodium azide and different phenyl acetylene derivatives. However, this reaction has been carried out with various homogeneous and heterogeneous Cu catalysts and also this reaction is famed to Cu azide-alkyne cycloaddition reaction, but this study is the first report for the use of magnetic CuMOF in the azide-alkyne cycloaddition reaction. Surprisingly, this catalyst can catalyze the synthesis of 1,2,3-triazole derivatives in short reaction time, good to excellent yields and more importantly in the presence of water as a green and environmentally friendly solvent.

Experimental
General. All 55 , and then, the surface of these MNPs has been modified by mercaptoacetic acid and finally, these modified MNPs  www.nature.com/scientificreports/ have been coated with HKUST-1 MOF by a versatile layer-by-layer assembly method and using copper acetate and 1,3,5-benzenetricarboxylic acid (H3-BTC) (Fig. 1) 56 .
General procedure for the synthesis of products 4a-k. To a mixture of phenyl acetylene derivatives (1.0 mmol), benzyl/alkyl halide (1.0 mmol) and sodium azide (1.2 mmol), in 10 mL water, 30 mg (1.8 mol%) of Fe 3 O 4 @HKUST-1 catalyst was added and refluxed for the time mentioned in Table 2. The progress of the reaction was monitored by TLC and upon the completion the reaction, the reaction mixture was diluted with ethyl acetoacetate and the Fe 3 O 4 @HKUST-1 catalyst was separated by an external magnet. Next, the organic part was separated from the water and it was dried on anhydrous Na 2 SO 4 and after solvent evaporation, the final products have been purified by recrystallization from ethanol to obtain the compounds 4a-k. www.nature.com/scientificreports/