Copper was immobilized onto carboxymethyl cellulose, nanofibrillated cellulose, TEMPO-nanofibrillated cellulose, and lignin. The lignocellulosic frames were used with the aim of providing an effective support for catalyst copper and allowing its further reutilization. Each organic support was successful and effective in the coupling of copper with the exception of lignin. These complexes were used as heterogeneous catalysts to produce 1-benzyl-4-phenyl-1H-
The “Huisgen click” reaction refers to an azide-alkyne 1,3-dipolar cycloaddition. This reaction has many useful applications for drug discovery [
Copper (Cu) based catalyst for the “Huisgen click” reaction has received significant attention during the last decade due to its versatile reactivity and much lower cost compared with noble metals, such as Pd and Rh. The rate of this copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is increased by a factor of 107 relative to the purely thermal process [
In general catalytic metal particles have been immobilized on solid supports that include the following: silica, alumina, zirconia, ceria, zeolites, glass fibers, and synthetic polymers [
Reddy et al. used the same procedure and materials as Yu et al. to create the Cu(0)-cellulose catalyst and had similar results in their catalyst formations, with Cu 2P X-ray photoelectron spectroscopy (XPS) spectra peaks around 932.7 eV. However, inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis in both studies show that Yu et al.’s Cu(0)-cellulose had almost double the amount of copper compared to Reddy et al.’s at 0.730 mmol/g and 0.368 mmol/g, respectively [
Koga et al. created a cellulose-supported Cu(I) catalyst using 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) nanofibrillated cellulose (TNFC). The azide-alkyne pair of benzyl azide and phenyl acetylene reacted in an aqueous solution of sodium ascorbate containing the Cu(I)-TNFC catalyst; the copper content of the catalyst used in the reaction was 10
Zhong et al. in 2013 used carboxymethyl cellulose (CMC) to immobilize copper that displayed excellent antimicrobial properties against
Sodium carboxymethyl cellulose (Na-CMC) with average molecular weight of 90,000 g/mol was purchased from Sigma-Aldrich, USA; nanofibrillated cellulose (NFC), 2.8 wt%, from the University of Maine, USA; TEMPO-nanofibrillated cellulose (TNFC) gel, 0.96 wt%, from Forest Products Laboratory, USA; lignin, alkali from Sigma-Aldrich, USA; copper sulfate pentahydrate (CuSO4·5H2O) from Fisher Scientific, USA; sodium borohydride (NaBH4), 0.5 M, from Acros, USA; ethanol (reagent alcohol, 95%) from Sigma-Aldrich, USA; tert-butanol (99.5%) from Acros, USA; benzyl azide (94%) from Alfa Aesar, England; phenyl acetylene (98%) from Alfa Aesar, England; sodium cyanoborohydride (NaBH3CN) from Sigma-Aldrich, USA.
Sodium carboxymethyl cellulose (Na-CMC) (1 g) was suspended in deionized water (49 mL). After that, CuSO4 (aqueous, 15 mL, 0.1 M) was added dropwise to the solution under constant stirring. Once all the CuSO4 had been added, mixing immediately ceased, and the solution rested for 14 h. Sodium borohydride (aqueous, 10 mL, 0.5 M) was added slowly under constant stirring over 30 min in order to reduce the oxidation state of copper [
Nanofibrillated cellulose (NFC) gel (1 g, 2.8 wt%) was suspended in deionized water (10 mL). After that, CuSO4 (aqueous, 4 mL, 0.1 M) was then added dropwise to the solution under constant stirring for 1 h. Sodium borohydride (aqueous, 3 mL, 0.5 M) was added as a reducer. Once added, the suspension underwent constant stirring for 30 min.
TEMPO-nanofibrillated cellulose gel (5 mL, 0.96 wt%) was suspended in deionized water (10 mL). After that, CuSO4 (aqueous, 4 mL, 0.1 M) was then added dropwise to the solution under constant stirring for 1 h. Next, to reduce the oxidation state of copper, sodium borohydride (aqueous, 3 mL, 0.5 M) was added and stirred for another 30 min.
Lignin (1 g) was suspended in deionized water (10 mL). After that, CuSO4 (aqueous, 4 mL, 0.1 M) was then added dropwise to the solution under constant stirring for 1 h. Lastly, sodium borohydride (aqueous, 3 mL, 0.5 M) was added slowly and then stirred with the suspension for 30 min to ensure all the copper had been reduced.
Each suspension was then centrifuged and the upper liquid layer was removed. The solids that remained were then redispersed in water (50 mL) and centrifuged again at 8000 rpm for 5 min. The upper clear solution was removed, and ethanol (25 mL) was mixed with the solid in the bottom of the vial. The vial was centrifuged again at 8000 rpm for 5 min, and the upper clear solution was subsequently removed. Ethanol was again mixed, and, after waiting for two hours upon mixing, the solution was centrifuged at 8000 rpm for 5 min. The upper liquid was then removed. This process was repeated using tert-butanol. The solid that remained from each suspension was then stored in a vacuum for 2 days to prevent oxidation and to allow the tert-butanol to dry. After the solids were dried under vacuum, they were placed in a freeze-dryer for 3 days [
Sodium cyanoborohydride (aqueous, 3.3 mM, 30 mL) was used to pretreat Cu-CMC (6 mg), Cu-NFC (11 mg), Cu-TNFC (14 mg), and Cu-lignin (200 mg)—all separately—at 70°C for 20 min prior to performing the CuAAC reaction. For the CuAAC reaction, benzyl azide (125
Illustration of the CuAAC of benzyl azide and phenylacetylene to produce 1,4-BPT, where [A]: benzyl azide, [B]: phenylacetylene, and [C]: 1-benzyl-4-phenyl-1H-
This process was then repeated using Cu-CMC and scaled up by a factor of 5 in order to reduce human error. In addition to scale-up, the recovered catalyst was reused twice for the same reaction to analyze catalytic decay.
This scaled-up process was also repeated using Cu-CMC in 30 mL of acetonitrile, a common solvent medium for CuAAC, instead of 30 mL of water. This was done to compare with other literature, as water is not typically used as the solvent in this CuAAC since copper easily dissolves in water. However, water is a very desirable reaction medium due to its abundance and environmental sustainability.
The copper loading on each catalyst support was determined using Varian Vista-PRO CCD simultaneous inductively coupled plasma-optical emission spectroscopy (ICP-OES) (Palo Alto, USA). In order to prepare these samples for ICP-OES, 30 mg of each catalyst was dissolved in 1 mL of nitric acid (71 wt%). When the solid complexes were completely dissolved, the solution was diluted with 99 mL of deionized water and 15 mL of this solution was then used for ICP-OES analysis.
The oxidation state of copper on each catalyst was determined using Physical Electronics VersaProbe 5000 X-ray Photoelectron Spectroscopy (XPS) system with a monochromatic Aluminum K
The solid product from the CuAAC reaction was dissolved in deuterochloroform and nuclear magnetic resonance (1H NMR) measurements were taken using a 400 MHz Agilent Technologies NMR, Model Number 400/54/ASP. Data analysis was performed using Agilent Technologies Software VNMRJ, Version 2.4, Revision A.
The yield of each reaction was determined in the following equation:
ICP-OES analysis calculated the amount of copper on each catalyst. Three samples of each complex were used in order to gain an accurate knowledge of the loading of copper onto each organic support. Figure
Amount of copper per gram of catalyst on each hybrid material.
Yu et al. used microcrystalline cellulose as the platform to attach copper, and the copper loading onto the microcrystalline cellulose only resulted in 0.730 mmol Cu/g catalyst [
As determined from XPS the state of oxidation was Cu(I) for all complexes. There were strong peaks around 931-932 and 950-951 with a weak satellite peak between the two around 943. This weak satellite peak was the determining factor for the oxidation state because it is unique to the Cu(I) oxidation state only. Figure
XPS spectra of Cu-CMC.
The reaction time was outstanding for each catalyst, with each reaction reaching completion in 15 minutes. Compared to Koga et al.
Yield information of each CuAAC using different catalysts.
Catalyst proposed | 1,4-BPT yield (mg) | Yield percentage |
---|---|---|
Cu-CMC | 131 | 56% |
Cu-NFC | 85 | 36% |
Cu-TNFC | 136 | 58% |
Cu-lignin | 90 | 39% |
One thing to note as well is that the Cu-lignin was irrecoverable from the reaction. It appears to have dissolved in the aqueous layer.
Table
Results of CuAAC using and reusing Cu-CMC.
Catalyst use | Reaction time | Yield percentage |
---|---|---|
1 | 10 min | 45% |
2 | 20 min | 43% |
3 | 150 min | 38% |
These results show that the first reuse of the catalyst is still very effective as the reaction time was still very fast, only increasing by 10 minutes. However, after reusing the catalyst once again, the reaction time increased greatly to 150 min suggesting the catalyst is not be reused more than once.
The low yields could be due to the extraction and purification process of the product, as there is much room for human error in this procedure. When using an internal standard of 1,4-dimethoxy benzene, NMR analysis showed yields of over 80% 1,4-BPT. This indicates that improvements can be made to purification in order to isolate the entire desired product that is formed.
The results of the 1H NMR analysis from Cu-CMC as catalyst were as follows:
NMR results for material produced from procedure used in this research.
The reaction completely favors the formation of 1,4-substituted triazoles as well, differing from the thermal reaction which often results in a mixture of 1,4-substitued and 1,5-substituted triazoles [
Considering that the highest yields in water as media were for Cu-CMC and Cu-TNFC, they were tested in acetonitrile to evaluate differences. The results in this regard are presented in Table
Yield information using acetonitrile as reaction medium.
Catalyst proposed | 1,4-BPT yield (mg) | Yield percentage |
---|---|---|
Cu-CMC | 1070 | 91% |
Cu-TNFC | 872 | 74% |
Cu-cellulose was easily prepared using CMC, NFC, TNFC, and lignin. These complexes were then used as catalysts in the CuAAC between benzyl azide and phenylacetylene to produce 1,4-BPT. Water and acetonitrile as media for the reaction were used. In water media, the catalysts, with the exception of lignin, were easy to recover, displaying the low hazardous impact the reaction has on the environment. The reaction was complete in 15 minutes for each copper complex, showing the excellent catalytic ability of each heterogeneous catalyst. Cu-CMC and Cu-TNFC displayed the highest yields and were subsequently used as catalysts when acetonitrile was utilized as media for the reaction. The reaction in this case needed longer time to be completed and the yield resulted higher for Cu-CMC. Based on the process used to fabricate the hybrid Cu-cellulose materials, CMC appears to be the best support for copper of the four organic compounds used as it held the most copper due to its higher number of Na-carboxyl groups and yielded one of the highest amounts of 1,4-BPT. Further investigation will be directed on the improvement of copper attachment on the lignocellulosic raw material for the specific application in the catalysis field.
1-Benzyl-4-phenyl-1H-1,2,3-triazole
Carboxymethyl cellulose
Copper azide-alkyne cycloaddition
2,2,6,6-Tetramethylpiperidine-1-oxyl radical
Nanofibrillated cellulose
TEMPO-nanofibrillated cellulose
Inductively coupled plasma atomic emission spectroscopy
Inductively coupled plasma-optical emission spectrometry
Nuclear magnetic resonance
Thin layer chromatography
X-ray photoelectron spectroscopy.
The authors declare that they have no conflicts of interest.
This work was supported by the USDA National Institute of Food and Agriculture, McIntire-Stennis, 1007636-WVA00119, “Advanced Applications for Nanomaterials from Lignocellulosic Sources.”