Cu-Kojic Acid Complex Anchored to Functionalized Silica-MCM-41: A Promising Regioselective and Reusable Nanocatalyst for Click Reaction.

Cu-Kojic acid (KA) complex anchored to functionalized silica-MCM-41 was synthesized via the process of postgrafting and introduced as an effective, new, reusable, and thermally resistant heterogeneous nanocatalyst for the clean synthesis of 1H-1,2,3-triazoles from Click reaction of 2-(azidomethyl)-5-benzyloxy-4-pyrone and azido Kojic acid with a variety of terminal alkynes in excellent yields. The structure of nanocatalyst was analyzed by ICP, BET, XRD, EDS, SEM, TGA, TEM, and FT-IR techniques.

Introduction

Metal nanoparticles have been widely used for catalyn class="Chemical">sis, energy storage, drug delivery, conversion devices, and photonics due to their extremely small dimensions, large surface area, facile recovery, and high specific surface area.[1] Recently, many studies on the heterogeneity of homogeneous catalysts have been more widely considered. It is generally due to the advantages of reusing expensive catalysts, simple filtering, and easy separation of catalysts and products.[2−5] One of the most ideal approaches for developing new heterogeneous catalysts is anchoring solid-based homogeneous materials.[4] Inorganic solids such as silica-MCM and SBA are so important. They are mainly made up of reactive Si–OH silanol groups. Silica has particular advantages such as large surface area, considerable thermal and chemical stability, and large pores to the guest metal–ligand complex.[3,6−8]

Mobile Crystalline Material (MCM-41) of the family n class="Mutation">M41S is prepared by a liquid templating mechanism and hydrothermal synthesis.[9−14] This material exhibits significant features such as uniform shapes and nanopores with proper sizes. These nanopores are well ordered to possess array hexagonal channels.[15,16] They are an interesting molecular sieve to use in catalysis due to the good thermic stability, homogeneous pores, and large surface area. The features of silica-MCM-41 are improved by incorporating other functional groups by deposition of active species in the silica walls or the internal surface of the material.

The performance of the metal ions in the structure of functionalized n class="Chemical">silica atoms as active redox or acid sites makes them usable in a variety of catalytic organic reactions.[17,18] The ordered mesoporous silicone wall framework can be modified both post synthesis and directly by many methods. This indicates that the features of the active generated sites are controllable and vary according to the synthetic methods.[19−21] Since they are anchor sites for coupling agents of silane or metal species, many of the steps to modify include Si–OH silanol groups of mesoporous silica.[22,23]

Kojic acid (KA), an n class="Chemical">organic acid, is a fungal secondary metabolite formed biologically by several microorganisms of Aspergillus, Acetobacter, and Penicillium by using different substrates such as starch, sucrose, glucose, etc.[24] Many KA derivatives are known as attractive compounds in pharmaceutical chemistry because of their high reactivity, accessibility, and potential in biological assay.[25,26]

Considering that the heterocyclic n class="Chemical">1H-1,2,3-triazole derivatives are structures with various properties (biological, chemical, and technical), utilizing the selective, efficient, and new catalytic systems for the production of 1H-1,2,3-triazole compounds is an important issue in the pharmaceutical industry.[27−29] Lately, the Click reaction between a terminal alkyne and organic azide (CuAAC) has been found to have many uses in organic synthesis.

In addition, Cu-catalyzed n class="Gene">AAC is selective to 1,4-disubstituted 1H-triazoles products.[30−32] Moreover, copper (CuIII, CuII, CuI, and CuO) is one of the best options for optimal and efficient activation of organic reactions with transition metal elements. It has many advantages, such as low cost and high frequency. It can easily form coordinated heteroatoms as well as π-bonds to produce intermediates of organic metals.[33−35]

In 2016, we reported a new series of 1H-1,2,3-triazole compounds containing KA motif by the n class="Chemical">CuAAC in the presence of CuI as a homogeneous catalyst. The prepared derivatives were indicated their antioxidant activity.[36] This process suffers from one or some disadvantages such as tedious workup, harsh reaction conditions, and longer reaction times. Thus, we became concerned in the development of a clean, efficient, simple, excellent yielding, and eco-friendly method utilizing a novel catalyst for the synthesis of triazoles. Based on this, the CuII complex on Kojic acid-functionalized nanosilica-MCM-41 has been immobilized. Then, it is used as an excellent regioselective nanocatalyst in the production of 1,4-disubstituted 1H-triazoles by the Click reaction of azido-KA and 2-(azidomethyl)-5-benzyloxy-4-pyrone with terminal alkynes in ethanol/water (1:1) and EG as clean solvents, respectively.

Results and Discussion

In continuation of our recent research in the field of production of new recoverable heterogeneous catalysts for the production of heterocyclic derivatives,[21,37] it was decided to synthesize a new heterogeneous nanocatalyst (n class="Chemical">silica-MCM-41-CPTMS-Kojic acid-Cu) and study its application in the formation of 1,4-disubstituted 1H-triazoles by the Click reaction. The anchored nanocatalyst design and construction steps are presented in Scheme .

Scheme 1

Synthesis of Silica-MCM-41-KA-Cu

Nanocatalyst Characterization

Cu complex anchored to nanoporous n class="Chemical">silica-MCM-41 was completely analyzed by TEM, SEM, ICP, EDS, TGA, XRD, and FT-IR techniques. As seen in the curves (a and b) in Figure , FT-IR analyses of the synthesized nanocatalyst are separately done in the first and final steps of preparation. Figure a shows that the absorption peaks at 1084, 958, 802, and 463 cm–1 corresponded to the symmetric and asymmetric stretching vibrations (Si–O–Si) of the MCM-41 mesoporous structure. The peak at 3436 cm–1 corresponded to the stretching mode of the hydroxyl (O–H) agents. Figure b shows stretching modes at1569 cm–1 (C–O) and 1625 cm–1 (C=O) and stretching vibrations of Cu–Cl at 794 cm–1, indicating that the support of Cu-KA on MCM-41-CPTMS-KA hybrid materials has been done successfully.

Figure 1

FT-IR spectra of (a) MCM and (b) MCM-CPTMS-KA-Cu.

The regular morphology of samples was proved by comparing the SEM microimages of MCM and n class="Chemical">MCM-CPTMS-KA-Cu in Figure a,b and Figure c, respectively. From Figure c, it can be seen that with surface modification of MCM, the morphological changes are not noticeable and the morphology of surface silica-MCM-41 is preserved. Figure d,e indicates the TEM photographs of the prepared MCM and MCM-CPTMS-KA-Cu, respectively. There is good agreement between TEM photographs and XRD patterns. Also, a much orderly hexagonal arrangement of the nanopore structure is depicted in this study.

Figure 2

SEM micrographs of (a, b) silica-MCM-41 and (c) silica-MCM-41-CPTMS-KA-Cu. TEM photographs of (d) silica-MCM-41 and (e) silica-MCM-41-CPTMS-KA-Cu.

SEM micrographs of (a, b) silica-MCM-41 and (c) n class="Chemical">silica-MCM-41-CPTMS-KA-Cu. TEM photographs of (d) silica-MCM-41 and (e) silica-MCM-41-CPTMS-KA-Cu.

The EDX spectra and elemental SEM mapping of the silica-MCM-41-CPTMS-KA-Cu complex are presented in Figure . It can be seen from n class="Chemical">curve (a) that O (42.52%) and Si (57.48%) elements have been detected in MCM. The curve (b) displays the existence of C, O, Si, and Cu elements in functionalized MCM with relative mass percentages of 46.72, 26.43, 14.34, and 12.52%, respectively. The exact amount of Cu anchored to the mesoporous silica measured by ICP-OES is 8.9%.

Figure 3

EDS results of (a) silica-MCM-41 and (b) silica-MCM-41-CPTMS-KA-Cu. SEM mapping of (c–g) silica-MCM-41-CPTMS-KA-Cu.

EDS results of (a) silica-MCM-41 and (b) n class="Chemical">silica-MCM-41-CPTMS-KA-Cu. SEM mapping of (c–g) silica-MCM-41-CPTMS-KA-Cu.

The assessment of weight changes of modified silica-MCM-41 was performed by thermogravimetric analysis (TGA). Figure A displays the TGA curves for silica-MCM-41 (a) and silica-MCM-41-CPTMS-KA-Cu (b). Based on the TGA plots, the first slight weight loss is associated with desorption of chemically and physically adsorbed organic solvents and water inside hydroxyl groups (−OH) on the nanocatalyst surface and the pore channels, which is observed at temperatures below 200 °C. The next large weight loss is related to the thermal decomposition of covalent-bonded silanol groups (Si–OH) and organic agents at temperatures of 500–800 and 200–500 °C, respectively. The differential thermal analysis (DTA) curve of MCM-41-CPTMS-KA-Cu presented in Figure B displays the removal of adsorbed organic solvents and water.

Figure 4

(A) TGA analysis of silica-MCM-41 (a) and silica-MCM-41-CPTMS-KA-Cu (b). (B) DTA thermograms of silica-MCM-41-CPTMS-KA-Cu.

(A) TGA analysis of n class="Chemical">silica-MCM-41 (a) and silica-MCM-41-CPTMS-KA-Cu (b). (B) DTA thermograms of silica-MCM-41-CPTMS-KA-Cu.

The XRD patterns of silica-MCM-41 and n class="Chemical">silica-MCM-41-CPTMS-KA-Cu at the small angle are illustrated in Figure . The XRD patterns indicate an intense reflection peak at 2θ = 2.39° assigned to the d100 plane and weak reflection peaks at 2θ = 4.07° and 4.70° related to d110, and d200, respectively. These can be assigned to the hexagonal arrangement framework of silica-MCM-41 and silica-MCM-41-CPTMS-KA-Cu. As depicted, after the modification stages, a significant reduction in the intensity of the diffraction was seen, which might be due to some changes in the wall width or the distinction in the scattering contrast of the walls and pores of silicate structure and complex. These results confirm that the synthesis of the nanocatalyst has occurred on the internal nanopore channels of silica-MCM-41.

Figure 5

XRD patterns of (a) silica-MCM-41 and (b) silica-MCM-41-CPTMS-KA-Cu.

XRD patterns of (a) silica-MCM-41 and (b) n class="Chemical">silica-MCM-41-CPTMS-KA-Cu.

Using the n class="Gene">BET technique, the N2 adsorption–desorption isotherms are applied to determine the textural properties of silica-MCM-41 and silica-MCM-41-CPTMS-KA-Cu, where the samples are depicted in Figure . As evident in Table , by comparing the surface features such as SBET (BET surface), DBJH (pore diameter), Vtotal (total nanopore volume), and wall width of these samples, it can be proved that metal copper was anchored to the internal surface of silica-MCM-41. Strong reasons for this conclusion are the wall diameter value increases of silica-MCM-41-CPTMS-KA-Cu, specific surface area, and nanopore volume decrease.

Figure 6

N2 desorption and adsorption isotherms of MCM-41 and MCM-41-KA-Cu.

Table 1

Textural Parameters of MCM-41 and MCM-41-KA-Cu Measured by N2 Sorption Isotherms

sample	SBET (m2/g)	pore diameter by BJH method (nm)	pore volume (cm3/g)	wall diameter (nm)
MCM-41	890	2.9	1.14	1.08
MCM-41-KA-Cu	345	1.5	0.54	2.2

N2 desorption and adsorption isotherms of n class="Chemical">MCM-41 and MCM-41-KA-Cu.

Regioselective Silica-MCM-41-CPTMS-KA-Cu-Catalyzed Production of 1,4-Disubstituted 1,2,3-Triazole Compounds 3a–3j

After construction of nanocatalyst and confirmation of its scaffold by different analyses, we focused on finding a n class="Chemical">simple, efficient, eco-friendly procedure for the synthesis of triazoles 3a–3j in the presence of silica-MCM-41-CPTMS-KA-Cu as a recyclable and efficient mesoporous catalyst. First, to create favorable conditions, a model reaction of phenylacetylene 2 and azide compounds 1a and 1b in the presence of different amounts of MCM-CPTMS-KA-Cu using various solvents and temperatures was selected. The results of screening experiments were tabulated (Tables and 3). In the case of compound 3a, the favorable result was obtained using phenylacetylene (2.0 mmol) and azide (0.5 mmol) in the presence of MCM-41-CPTMS-KA-Cu (3 mg) in EtOH/H2O (1:1) (5 mL) as a solvent under reflux (Table , entry 13). In the case of compound 3f, with the same ratio of material and catalyst, the favorable result was found in ethylene glycol (EG) solvent at 100 °C (Table , entry 11).

Table 2

Effect of Different Factors (mol % of Nanocatalysts, Temperatures, and Solvents)a on the Synthesis of 3a

entry	catalyst (mg)	solvent	temperature (°C)	time (min)	yield (%)b
1	3	CH3CN	rt	200	trace
2	3	CH3CN	reflux	200	10
3	3	EtOAc	reflux	200	40
4	3	EG	rt	200	20
5	3	EG	100	120	80
6	3	CH3CN/H2O (1:1)	reflux	200	15
7	3	acetone/H2O (1:1)	reflux	70	94
8	3	THF/H2O (1:1)	reflux	45	96
9	3	MeOH/H2O (1:1)	reflux	60	95
10	3	EG /H2O (1:1)	100	60	98
11	3	EtOH/H2O (1:1)	rt	60	70
12	1	EtOH/H2O (1:1)	reflux	45	96
13	3	EtOH/H2O (1:1)	reflux	30	98
14	5	EtOH/H2O (1:1)	reflux	30	95

Reaction conditions: phenylacetylene (2.0 mmol), azide (0.5 mmol).

Isolated yields.

Table 3

Effect of Different Factors (mol % of Nanocatalysts, Temperature, and Solvents)a on the Synthesis of 3f

entry	catalyst (mg)	solvent	temperature (°C)	time (min)	yield (%)b
1	3	CH3CN	rt	200	trace
2	3	CH3CN	reflux	200	5
3	3	EtOAc	reflux	200	trace
4	3	CH3CN/H2O (1:1)	reflux	200	10
5	3	acetone/H2O (1:1)	reflux	200	70
6	3	THF/H2O (1:1)	reflux	200	trace
7	3	MeOH/H2O (1:1)	reflux	200	50
8	3	EtOH/H2O (1:1)	reflux	200	60
9	3	EG	rt	200	50
10	3	EG	100	15	98
11	3	EG /H2O (1:1)	100	60	98
12	1	EG	100	30	96
13	5	EG	100	30	95

Reaction conditions: phenylacetylene (2.0 mmol), azide (0.5 mmol).

Isolated yields.

Reaction conditions: phenylacetylene (2.0 mmol), n class="Chemical">azide (0.5 mmol).

Reaction conditions: phenylacetylene (2.0 mmol), n class="Chemical">azide (0.5 mmol).

After optimizing experiments, the reaction of various terminal alkynes with n class="Chemical">azide compounds 1a and 1b were done. Results displayed in Table indicated that different terminal alkynes could react with compounds 1a and 1b smoothly and give compounds 3a–3e and 3f–3j in excellent yields.

Table 4

Silica-MCM-41-CPTMS-KA-Cu-Catalyzed Clean Preparation of 1,4-Disubstituted Triazoles

The possible mechanistic pathway is shown in Scheme for the production of 3a–3j.[38−41] To produce n class="Chemical">diynes (4), it is plausible that a Glaser-type reaction (CuII-catalyzed oxidative dimerization of terminal alkynes (2)) may be done to create the active CuI species that catalyzes the Click reaction. The alkyne 2 reacts with the CuI nanocatalyst to obtain Cu (I)-acetylide (A), followed by coordination with the organo-azides (1a and 1b) to afford a dicopper complex (B). Next, the C–N covalent bond forms between the end N atom of the coordinated −N3 and the β-C atom of Cu (I)-acetylide, producing intermediate C. Then, reductive elimination of C leads to the triazolyl 5-cuprated intermediate D. Finally, corresponding to fast protonolysis, the final product (3) is obtained and regenerates the CuI -nanocatalyst.

Scheme 2

Plausible Proposed Mechanism for the Construction of Triazoles (3) Catalyzed Using the Silica-MCM-41-CPTMS-KA-Cu Nanocatalyst

To illustrate the importance of this research, we carried out a comparative study of the efficiency, reactivity, and capability of silica-MCM-41-CPTMS-KA-CuII nanocatalyst in the Click reaction of n class="Chemical">azides (1a and 1b) and terminal alkynes with some formerly reported catalysts (Table ). The reviews demonstrate that our procedure is comparable with other reported catalytic systems in terms of yields of the products, reaction time, and temperatures. In addition to this, the present nanocatalyst is more effective than the others due to some important benefits such as easy synthesis, eco-friendliness, stability, and recyclability of the nanocatalyst. It should be noted that the synthesized compounds have antioxidant activity.[36]

Table 5

Comparison of the Activity of MCM-CPTMS-KA-CuII with Other Reported Catalysts for the Production of 1,4-Disubstituted Triazoles in the Literature[36,42−45]

Isolated yields.

Hot Filtration Test and Recoverability of the Catalyst

To test the leaching of copper in the reaction mixture and the heterogeneity of the nanocatalyst, we carried out hot filtration for the synthen class="Chemical">sis of triazoles derivative with azide compounds 1a and 1b and phenylacetylene. In this test, we obtained the product yield in half the reaction time of 54%. Next, the reaction was repeated and in half the reaction time, the nanocatalyst was separated and the filtrate was allowed to react further. We found that, after this hot filtration, no further reaction was observed. The reaction yield in this stage was 54%, approving the leaching of copper was negligible.

The recyclability of heterogeneous nanocatalysts is one of the main advantages for different applications (commercial, medicinal, etc.). To investigate the recovery and reusability of silica-MCM-41-CPTMS-KA-Cu, this nanocatalyst was studied in the Click reaction of n class="Chemical">azide compounds 1a and 1b with phenylacetylene as a model reaction under optimized reaction conditions (Figure ). After the reaction for each run, the nanocatalyst was rapidly and simply separated by centrifugation from the solution reaction and washed three times with DI-H2O and ethanol. Next, the nanocatalyst was applied in the subsequent reaction. The MCM-41-CPTMS-KA-Cu was reapplied for at least six times without any considerable copper leaching and reduction in its activity (Figure ). However, a slight decrease in yield was observed after each reaction cycle, which can be attributed to the fact that in each recovery period, a small part of the catalyst is lost. According to ICP-OES analysis, negligible Cu was detected in the reaction solution up to the six runs. Also, the amount of Cu has been measured based on ICP-OES technique for unused nanocatalyst (8.9%) and after six runs (8.5%). In addition, the recovered nanocatalyst after six runs was assessed by FT-IR (Figure ), SEM (Figure ), and TEM instruments (Figure ). These analyses for the recycled nanocatalyst proved that the nanocatalyst can be reapplied in six recycles without any appreciable change in the mesoporosity of the silicate scaffold.

Figure 7

Recycling of MCM-41-KA-Cu in the synthesis of triazole derivatives.

Figure 8

FT-IR spectrum of recovered silica-MCM-41-CPTMS-KA-Cu.

Figure 9

SEM microimage of recovered silica-MCM-41-CPTMS-KA-Cu.

Figure 10

TEM microimage of recovered silica-MCM-41-CPTMS-KA-Cu.

Recycling of MCM-41-KA-Cu in the synthen class="Chemical">sis of triazole derivatives.

Conclusions

In the current study, we successfully den class="Chemical">signed a novel mesoporous metal Cu complex (silica-MCM-41-CPTMS-KA-Cu) and characterized its scaffold by different analytical techniques. It was applied as a nanostructured catalyst in the clean preparation of 1,2,3-triazolic 1,4-disubstituted compounds through the Click reaction of azide compound based on Kojic acid with various terminal alkynes. The important benefits of this nanosize particle catalyst system are the easy synthesis, low reaction times, recoverability of the nanocatalyst and high stability, green conditions, simple workup, high yields of products, and easy purification.

Experimental Section

Materials and Instruments

All utilized solvents and chemical material were provided from Aldrich, Fluka, and Merck Chemical Companies. The FT-IR spectra of prepared compounds were confirmed by Pills made from KBr on a NEXUS 670 instrument (Urmia Univern class="Chemical">sity, Urmia, Iran). Spectral data of 1H (300 MHz) and 13C NMR (75 MHz) were collected one to one utilizing a BRUKER NMR instrument (Urmia University, Urmia, Iran). Nanocatalyst morphology was found by SEM technique using a FESEM TESCAN MIRA3 and Zeiss EM10C TEM analysis (Daypetronic Company, Tehran, Iran). The TGA digital thermographic analysis was confirmed using the a Shimadzu DTG-60 (Kurdistan University, Sanandaj, Iran). The EDX of the nanoparticle was collected by a FESEM TESCAN MIRA3 (Daypetronic Company, Tehran, Iran, and University of Kurdistan, Sanandaj, Iran). The XRD patterns were obtained using a Panalytical X’Pert Pro system (Daypetronic Company, Tehran, Iran). The copper percentage was evaluated using the ICP-OES technique (Tarbiat Modares University, Tehran, Iran). TLC was utilized to check the reaction on SIL G/UV 254 silica gel plates.

Preparation of Nano-Silica-MCM-41

In a typical method, to a stirring solution of 2 M NaOH (1.75 mL) and deionized n class="Chemical">water (240 mL) at 80 °C, 0.5 g of cetyltrimethylammonium bromide (1.37 mmol) was added. After homogenization of the solution, tetraethyl orthosilicate TEOS (2.5 mL) was added dropwise to the solution reaction to give a white slurry. Then, the slurry solution was refluxed for 2 h. The filtered product was washed several times with deionized water, followed by drying at 90 °C. Then, to remove residual cetyltrimethylammonium bromide, the resulting product was calcinated at 550 °C for 5.5 h. Eventually, the silica-MCM-41 was obtained.

Preparation of MCM-41-CPTMS

A stirring solution of 2.5 g of 3-chloropropyltrimethoxysilane (n class="Chemical">CPTMS) and 2.4 g of silica-MCM-41 powder was refluxed in n-hexane (48 mL) under N2 gas for 24 h. The resulting filtered solid was washed four times with hexane and then dried in an oven to achieve silica-MCM-41-CPTMS.

Preparation of Silica-MCM-41-CPTMS-Kojic Acid

A solution of 1 g of silica-MCM-41-Cl, 1 g of n class="Chemical">Kojic acid, and 0.3 g of NaOH in 12 mL of methanol/water (10:1) was stirred for 20 h under reflux. Next, the resulting product was washed four times with water and then with methanol, followed by drying for 10 h at 60 °C.[46]

Preparation of Silica-MCM-41-CPTMS-KA-Cu

The functionalized silica-MCM-41-n class="Chemical">Kojic acid (3 g) and CuCl2·2H2O (1.5 g) in acetone (50 mL) were stirred at room temperature for 25 h. Eventually, the filtered grayish-yellow sediment was washed four times with acetone and then dried in vacuum at 50 °C for 10 h. Therefore, the silica-MCM-41-CPTMS-KA-Cu heterogeneous nanocatalyst is obtained.

General Method for the Synthesis of 1,4-Disubstituted 1,2,3-Triazole Compounds 3a–3j

To a solution of 2 mmol of terminal alkyne and 0.5 mmol of n class="Chemical">azide compounds 1a and 1b, respectively, in ethanol/water (1:1) and EG, silica-MCM-41-CPTMS-KA-Cu (3 mg) was added. The reaction was controlled by TLC. After completing the reaction, the catalyst was filtered, washed with DI-H2O and ethanol, dried, and saved for the next runs (Tables and 2). In the case of compounds 3a–3e, the reaction solvent was evaporated by a rotary set under reduced pressure. The final precipitates were recrystallized from MeOH/CH3CN (1:1). In the case of compounds 3f–3j, cold water was added to the reaction to form precipitates. The filtered product was washed with water, followed by drying in a vacuum. The final product was recrystallized from EtOH, affording triazole derivatives in excellent yields. The resulting products from this reaction were analyzed by 13C and 1H NMR and FT-IR spectrophotometers and corresponded to formerly reported cases (see the Supporting Information).