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. 2019 Dec 23;5(1):394–405. doi: 10.1021/acsomega.9b02904

Nanofibrils of a CuII-Thiophenyltriazine-Based Porous Polymer: A Diverse Heterogeneous Nanocatalyst

Sudipta K Kundu †, Anirban Kayet †, Ramlal Baidya †, Lanka Satyanarayana ‡, Dilip K Maiti †,*
PMCID: PMC6964281  PMID: 31956787

Abstract

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Herein, we report knitting of a thiophenyltriazine-based porous organic polymer (TTPOP) with high surface area and high abundance of nitrogen and sulfur sites, synthesized through a simple one-step Friedel–Crafts reaction of 2,4,6-tri(thiophen-2-yl)-1,3,5-triazine and formaldehyde dimethyl acetal in the presence of anhydrous FeCl3, and thereafter grafting of Cu(OAc)2·H2O in the porous polymer framework to achieve the potential catalyst (CuII-TTPOP). TTPOP and CuII-TTPOP were characterized thoroughly utilizing solid-state 13C-CP MAS NMR, Fourier transform infrared, wide-angle powder X-ray diffraction, thermogravimetric analysis, and X-ray photoelectron spectroscopy and surface imaging by transmission electron microscopy and field emission scanning electron microscopy. The porosity of the nanomaterials was observed in the surface imaging and verified through conducting N2 gas adsorption techniques. Keeping in mind the tremendous importance of C-C and C-N coupling and cyclization processes, the newly synthesized CuII-TTPOP was employed successfully for a wide range of organic catalytic transformations under mild conditions to afford directly valuable diindolylmethanes and spiro-analogues, phthalimidines, propargyl amines, and their sugar-based chiral compounds with high yields using readily available substrates. The highly stable new heterogeneous catalyst showed outstanding sustainability, robustness, simple separation, and recyclability.

Introduction

The porous organic polymers (POPs) are attractive materials with multipurpose applications in gas storage and separation,1−4 catalytic supports,5,6 chemical sensing,7 and energy storage,8 owing to their larger surface area, low skeleton density, and high chemical and thermal tolerance. The greatly enhanced surface area and porosity, installation of functionality for binding substrates and metal ions, and developing innovative chemical activities through the fabrication of nanomaterials are the essential parameters for heterogeneous catalysis, and controlling these parameters is a novel target to the research professionals of academia and industry to achieve selective organic transformations. During the last few decades, many works have been focused on synthesis of various POPs, such as hyper-cross-linked polymers (HCPs),9,10 polymers of intrinsic microporosity (PIMs),11 conjugated microporous polymers (CMPs),12 crystalline triazine-based frameworks (CTFs),13 metal-organic frameworks (MOFs),14,15 and covalent organic frameworks (COFs),16 in addition to the traditional porous materials, such as zeolites,17 porous amine-modified silicas,17 and activated porous carbons.18 Among these porous materials, the amorphous POPs are ideal host matrices to encapsulate various active metal ions in heterogeneous catalysis because of their unprecedented intrinsic structural features, such as the availability of suitable binding sites in the polymer frameworks comprising nonhydrolyzable carbon backbones, high surface areas, porosities, and thermal and hydrothermal stabilities present in the POP supports. These features render POPs potentially advantageous over COFs and MOFs as a suitable platform for the development of new-generation heterogeneous catalysts. Our main aims of designing and synthesizing porous materials are to achieve remarkably enhanced porosities and heightened surface areas, and these highly attractive properties are expected to find innovative applications in nanoscience and nanotechnology such as in absorption and storage of useable voluminous volatile materials, electromagnetic wave absorption materials, asymmetric supercapacitors, automotive exhaust purifiers, sensing lethal health hazards of varied phases, fabricating nanoelectronic devices of unparalleled sensitivity, and highly efficient heterogeneous catalysis for diverse organic syntheses.19 Herein, we successfully investigated synthesis, fabrication, characterization, imaging, adsorption, and heterogeneous catalysis of CuII-based nano-POPs.

Due to obvious advantages, the heterogeneous catalysis has gained much attention over homogeneous catalysis for most of the fundamental reactions, such as cyclic carbonate formation, nucleophilic addition, hetero-Diels–Alder and 1,3-dipolar cycloaddition, alkyne hydration, rearrangement, oxidation, reduction, coupling reaction, photocatalysis, C(sp3)–H borylation, and alkene hydroformylation.20 In general, the single-metal sites are incorporated into polymers of heterogeneous catalysts, where the porosity makes the active sites easily accessible and may lead to enhanced catalytic selectivity based on which substrates can preferentially be reached and smoothly react with the catalytic sites. Due to the inbuilt covalent-bonded network, one could anticipate that POPs might become more suitable scaffolds than the other porous materials to anchor metal ions and therefore emerge as versatile and efficient organic supports as heterogeneous catalysts. It also allows easy recovery of the occluded guests and providing stabilization of the guest under reaction conditions. Due to low cost, easy availability, and diverse catalytic activities under different conditions, copper compounds have attracted much attention in organic synthesis. Recently, Liu’s group synthesized a porous organic polymer bifunctionalized with triazine and thiophene moieties and employed for removal of Cu(II) ions from water through adsorption.21 Inspired by this work, we have synthesized, fully characterized, and grafted the triazinothiophene-nano-POP with Cu(II)-species for development of its innovative catalytic properties. Gratifyingly, during the screening of fundamental C-C/C-N coupling and cyclization catalysis, we found diverse catalytic activities of the CuII-TTPOP for C-N and C-C coupled dual cyclization under mild conditions to valuable diindolylmethane analogues (4, eq. i, Scheme 1), three-component coupling to highly substituted propargyl amines (7, eq. ii), and three-partner annulation to phthalimidines (9, eq. iii).

Scheme 1. CuII-TTPOP-Catalyzed C-C/C-N Coupled Reactions.

Scheme 1

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The diindolylmethanes contain an indole moiety, and they could serve as advanced intermediates for the synthesis of numerous bioactive molecules.22−24 Recently, these heterocycles have been considered as attractive synthetic targets possessing diverse biological properties such as antibacterial,25 antifungal,26 antiandrogenic,27 anticancer,28 and anti-implantation activities.29 They are also known to act as growth-promoting agents and carbonic anhydrase II inhibitors30 as well as dyes and colorimetric sensors.31 It should be noted that the classical method for the synthesis of diindolylmethanes involved the Friedel–Craft reaction of indoles and carbonyl compounds using homogeneous catalysis.32 The indolization of 2-ethynylanilines followed by functionalization has been found as an alternative efficient route for achieving substituted indoles using transition metal catalysts.33 Very recently, varieties of diindolylmethanes have been synthesized via cycloisomerization of 2-alkynyl anilines followed by C3-functionalization in one pot.32b To the best of our knowledge, there is not a single report on the synthesis of diindolylmethanes employing 2-ethynylaniline (a precursor of indole) by using a heterogeneous catalyst. Most of the routes to diindolylmethanes were performed through the electrophilic substitution reaction of indoles or their precursors with carbonyl compounds using homogeneous catalysis.32 On the other hand, propargyl amines were also synthesized previously employing Cu-, Ag-, Zn-, and Ru-salts and complexes as homogeneous catalysts.34 For instance, synthesis of propargyl amines was established through one-pot three-component reactions among aldehydes, amines, and alkynes (A3-coupling) using homogeneous catalysts such as CuPF6-i-Pr-pybox-diPh,34a CuO nanoparticles,34b Cu(OTf)2,34c RuCl3-CuCl,34f and Ag(IPr)2]PF6.34h Apart from this, the use of AgOAc catalyst to couple terminal alkynes,34e ZnEt2 carboxylic acid promoter,34g and Zn(OTf)234i for the reaction among terminal alkynes and imines at high temperature was reported. Phthalimidines are important heterocyclic scaffolds from a synthetic prospect and are found widely in complex natural products35 and drug molecules.36 They have become attractive synthetic objects owing to their broad range of biological profile, such as antipsychotic,37 antiulcer,38 antiviral,39 anesthetic,40 antihypertensive,41 anti-inflammatory,42 antileukemic,43 and vasodilatory44 activities. Due to the broad spectrum of the biological profile of substituted phthalimidines, their synthesis is very much important. Although aldimines have been extensively studied for their synthesis,45 there is not a single report on the synthesis of these heterocycles employing a heterogeneous catalyst.

Herein, we have synthesized a thiophenyltriazine-based porous organic polymer (TTPOP) through the Friedel–Crafts reaction of 2,4,6-tri(thiophen-2-yl)-1,3,5-triazine and formaldehyde dimethyl acetal in the presence of anhydrous FeCl3 and thereafter grafting of Cu(OAc)2·H2O in the porous polymer framework to achieve the potential catalyst CuII-TTPOP. TTPOP and CuII-TTPOP were characterized thoroughly by employing the following techniques: wide-angle powder XRD, thermogravimetric analysis (TGA), field emission (FE) SEM, transmission electron microscopy (TEM), Fourier transform infrared, N2 adsorption/desorption isotherms, solid-state cross-polarization magic angle spinning 13C NMR, and X-ray photoelectron spectroscopy (XPS). The newly synthesized CuII-TTPOP was employed successfully for a wide range of organic catalytic transformations under mild conditions to afford directly valuable diindolylmethanes and spiro-analogues, phthalimidines, propargyl amines, and their sugar-based chiral compounds with high yields and high recyclability using readily available substrates. To the best of our knowledge, the heterogeneous catalysis was never attempted before the contribution of this study to synthesize the unique classes of valuable diindolylmethanes and spiro-analogues, phthalimidines, and propargyl amines.

Experimental Section

Materials and Characterization Techniques

2-Thiophenecarbonitrile and formaldehyde dimethyl acetal were purchased from Sigma-Aldrich, India. Ethylene dichloride and trifluoromethanesulfonic acid were purchased from Spectrochem, India. Anhydrous ferric chloride was obtained from Merck, India. Powder X-ray diffraction (PXRD) patterns were recorded on a desktop X-ray diffractometer (Rigaku-Miniflex II) with Cu Kα (λ = 0.15406 nm) radiation. N2 adsorption–desorption isotherms of polymer materials were obtained using Micromeritics ASAP 2020 at 77 K. Prior to the gas adsorption studies, the samples were degassed at 403 K under high vacuum conditions for 8 h. Specific surface areas were calculated from the adsorption data using Brunauer–Emmett–Teller (BET) methods. Transmission electron microscopy (TEM) images of the polymer samples were taken using a Tecnai G2 F20 instrument. A Jeol JEM 6700F field emission scanning electron microscope was used for the determination of the morphology of the polymers. Thermogravimetric analysis of the polymers was carried out on Netzsch STA 449 C coupled with Netzsch QMS 403 C under a continuous flow of air with a heating/cooling rate of 10 °C min–1. The solid-state MAS NMR spectra of the samples were taken in a Bruker Ascend 400 spectrometer. Cu loading in the sample was estimated using a PerkinElmer Optima 2100 DV inductively coupled plasma mass spectroscope (ICP-MS). X-ray photoelectron spectroscopy (XPS) analysis was carried out by a SPECS I3500 plus spectrometer using a Mg X-ray source. Unless otherwise stated, reactions were performed in oven-dried glassware fitted with rubber septa and were stirred with Teflon-coated magnetic stirring bars. Liquid reagents and solvents were transferred via a syringe using standard Schlenk techniques. Acetonitrile, dichloromethane (DCM), and 1,2-ethylene dichloride (EDC) were distilled over calcium hydride. All other solvents and reagents were used as received unless otherwise noted. Reaction temperatures above 25 °C refer to the oil bath temperature. Thin layer chromatography was performed using silica gel 60 F-254 precoated plates (0.25 mm) and visualized by UV irradiation, anisaldehyde stain, and other stains. Silica gel of particle size 100–200 mesh was used for column chromatography. Melting points were recorded on a digital melting point apparatus from Jyoti Scientific (AN ISO 9001:2000) and are uncorrected. 1H and 13C NMR spectra were recorded using a 300/400 MHz spectrometer with 13C operating frequencies of 75/100 MHz. Chemical shifts (δ) are reported in ppm relative to the residual solvent CDCl3 signal (δ = 7.24 for 1H NMR and δ = 77.0 for 13C NMR) and DMSO-d6 signal (δ = 2.47 for 1H NMR and δ = 39.4–40.6 for 13C NMR). Data for 1H NMR spectra are reported as follows: chemical shift (multiplicity, number of hydrogen and coupling constants). Abbreviations are as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br (broad). High-resolution mass spectrometry (HRMS) data was recorded on a Q-tof-micro quadruple mass spectrophotometer using acetonitrile as solvent.

Synthesis of 2,4,6-Tri(thiophen-2-yl)-1,3,5-triazine

To a stirred solution of 2-thiophenecarbonitrile (A) (1.0915 g, 10 mmol) in 25 mL of dry dichloromethane was added trifluoromethanesulfonic acid (1.501 g, 10 mmol) under ice-cool conditions. The mixture was stirred for 36 h at room temperature under an Ar atmosphere. After the removal of the solvent under reduced pressure, the residue was neutralized with aqueous NaHCO3. The formed precipitate was collected by filtration; then washed with water, methanol, acetone, and hexane in this order; and dried under vacuum to afford 2,4,6-tri(thiophen-2-yl)-1,3,5-triazine with 85% yield.

Synthesis of Thiophenyltriazine-Based Porous Organic Polymer

The monomer 2,4,6-tri(thiophen-2-yl)-1,3,5-triazine (1 mmol, 0.32 g) and formaldehyde dimethyl acetal (6 mmol, 0.53 mL) were dissolved in anhydrous 1,2-dichloroethane (DCE, 20 mL) in a 50 mL round-bottom flask for 10 min. To this solution, anhydrous ferric chloride (8 mmol, 1.3 g) was added under an argon atmosphere. The resulting reaction mixture was heated to 80 °C for 24 h under constant stirring. After cooling to room temperature, the crude product was collected by filtration and repeatedly washed with methanol until the filtrate was nearly colorless. The product was further purified by Soxhlet extraction in methanol for 24 h. Finally, the product was dried at 120 °C under vacuum to provide TTPOP, a brown solid, in a good yield of ∼96% (Scheme 2).

Scheme 2. Synthesis of CuII-TTPOP.

Scheme 2

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Grafting of Cu(II) Ions in the Interior Cavities of the TTPOP

In a typical synthetic procedure, 100 mg of TTPOP in methanol (10 mL) was sonicated for 15 min. Then, Cu(OAc)2·H2O (90 mg) was added and again sonicated for 15 min. Then, it was refluxed for 24 h, filtered, washed with methanol and acetone till the filtrate became colorless, and dried at 80 °C for overnight to obtain our CuII-TTPOP catalyst (1) (Scheme 2).

General Procedure for the Synthesis of Diindolylmethanes

To a well-stirred solution of carbonyl compounds 2 (0.5 mmol) and 2-alkynyl anilines 3 (1.0 mmol) in chloroform was added the CuII-TTPOP (containing 5 mol % Cu), and the reaction mixture was stirred at room temperature for 4–8 h. After complete consumption of the starting material (as indicated by TLC), the reaction mixture was filtered and washed with chloroform two times. Then, the organic solvent was removed under reduced pressure to get a crude residue, which was further purified by silica gel column chromatography using 100–200 mesh silica gel to get pure DIMs 4 with 80–90% yields.

General Procedure for Synthesis of Propargyl Amines

To a well-stirred solution of aromatic aldehydes 2 (0.5 mmol) and aromatic amines 5 (0.525 mmol) in chloroform was added CuII-TTPOP (containing 5 mol % Cu), and the reaction mixture was stirred at room temperature for 2 h. After 2 h, phenyl acetylenes 6 (0.55 mmol) were added dropwise into the reaction mixture and then the reaction mixture was further stirred at room temperature for an additional 8–10 h. After completion of the reaction (as indicated by TLC), the reaction mixture was filtered and washed with chloroform twice and the organic layer was dried under reduced pressure to get a residue. The residue was purified by silica gel column chromatography over 100–200 mesh silica gel to get pure propargyl amines 7 with high yield (85–90%).

General Procedure for the Synthesis of Phthalimidines

To a well-stirred solution of 2-formyl methyl benzoates 8 (0.5 mmol) and aromatic amines 5 (0.525 mmol) in chloroform was added CuII-TTPOP (containing 5 mol % Cu), and the reaction mixture was stirred at room temperature for 2 h. After 2 h, phenylacetylene 6a (0.55 mmol) was added dropwise into the reaction mixture, and the reaction mixture was further stirred at room temperature for additional 20–22 h. After completion of the reaction (as indicated by TLC), the reaction mixture was filtered and washed with chloroform twice and the organic layer was dried under reduced pressure to get a residue. The residue was purified by silica gel column chromatography over 100–200 mesh silica gel to get pure phthalimidines 9 with 83–86% yields.

Results and Discussion

Synthesis of CuII-TTPOP

The reaction sequences toward synthesizing the CuII-TTPOP involve the treatment of 2-thiophenecarbonitrile with trifluoromethanesulfonic acid (CF3SO3H) in dichloromethane (DCM) followed by heating with formaldehyde dimethyl acetal [CH2(OMe)2] in the presence of anhydrous FeCl3 catalyst in 1,2-dichloroethane (DCE) to afford the polymer TTPOP. Finally, it was grafted with Cu(II) ions utilizing copper acetate monohydrate salt [Cu(OAc)2·H2O] under refluxing methanol to obtain the desired catalyst, CuII-TTPOP (Scheme 2).

Imaging TTPOP and CuII-TTPOP Materials

The fibrous networks for both the TTPOP and CuII-TTPOP catalyst are clearly observed through field emission scanning electron microscopy (FESEM) imaging of the samples prepared by the drop cast method (Figure 1). From field emission scanning electron microscopy (FESEM) images, the width of the fibers of TTPOP was in the range of 20–35 nm (Figure 1a and inset Figure 1b). Gratifyingly, on grafting of Cu(II) to TTPOP, the porous and fibrous network is retained in the nano-range. However, due to the incorporation of Cu(OAc)2·H2O in the binding sites of TTPOP, a small increase in the width of the fibers was observed (Figure 1c) ranging 35–45 nm (inset Figure 1d). The FESEM image of CuII-TTPOP (inset Figure 1d) clearly shows that good crystallinity arises after Cu(II) grafting to TTPOP. It is also confirmed by the TEM image analyses of the TTPOP (Figure 2a), which exhibits formation of bundles of ultralong nanofibrils. The width of these fibers is in the range of 20–30 nm. Imaging of the bundles of CuII-TTPOP nanofibrils had established the existence of an excellent crystalline morphology.

Figure 1.

Figure 1

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FESEM images of TTPOP (a, b) and CuII-TTPOP(c, d).

Figure 2.

Figure 2

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TEM images of TTPOP (a) and CuII-TTPOP (b); their thermogravimetric analysis (c) and wide-angle powder XRD (d).

Thermogravimetric Analysis

Thermogravimetric analyses of TTPOP and CuII-TTPOP nanomaterials have been carried out to understand the thermal stability of these materials (Figure 2c). The black line of metal-free TTPOP indicates that the polymer is thermally stable up to 350 °C and a minimum weight loss of 11% had taken place due to the removal of adsorbed water or trapped solvents at the porous networks.46 The major weight loss started from 350 °C temperature, whereas weight loss started for CuII-TTPOP (red line) much earlier (300 °C). Thus, with a rise in temperature, the polymer might start a sharp decomposition due to thermal cleavage of C-C, C-N, and C-S bonds. On the other hand, the TGA plot of CuII-TTPOP shows that above 300 °C temperature, the sharp weight loss occurred due to the burning of the organic framework.

Wide-Angle Powder X-ray Diffraction

The wide-angle powder XRD pattern (Figure 2d) of TTPOP shows a single broad peak in the range of 15–30°, indicating the amorphous nature of the hyper-cross-linked polymer. However, after Cu(II) grafting in the polymer, it reveals some distinct sharp peaks along with a broad peak.

FTIR Study

The presence of triazine and thiophene aromatic residues is confirmed by recording FTIR spectra of both the polymer-based TTPOP and CuII-TTPOP nanomaterials (Figure 3). The spectrum of TTPOP showed two adsorption bands at 1507 and 1399 cm–1, which represent the aromatic C-N stretching and “breathing” modes in the triazine units, respectively.47 The adsorption bands at 1660 cm–1 (C=C bond stretching) and 820 cm–1 (C-S bond stretching) confirm the presence of a thiophene residue in the nanofibril polymer networks. From the spectra (Figure 3) of CuII-TTPOP and reused CuII-TTPOP, we have seen the small positive shift of adsorption bands of the aromatic C-N stretching and “breathing” modes in the triazine units and C-S bond stretching in CuII-TTPOP and reused CuII-TTPOP to the higher value. These results indicate the coordination of Cu(II) ions by N and S binding sites in the polymer frameworks.

Figure 3.

Figure 3

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FTIR analysis of TTPOP, CuII-TTPOP, and reused catalyst after six consecutive cycles.

N2 Adsorption–Desorption Isotherm

The porosity of polymer-based TTPOP and CuII-TTPOP nanomaterials is investigated by N2 adsorption–desorption analysis at 77 K (Figure 4a,b). The nitrogen sorption isotherms of both TTPOP and CuII-TTPOP nanomaterials exhibit a rapid uptake below the relative pressure at P/Po = 0.1, which suggests the presence of microporosity inside the polymers. The sorption profiles show a typical type I isotherm, which is the characteristic of microporous materials. The Brunauer–Emmett–Teller (BET) surface areas of TTPOP and CuII-TTPOP are 466 and 395 m2 g–1, respectively. The existence of a hysteresis loop in the high-pressure region in the isotherms could be attributed to the presence of an interparticle void space or originating because of deformation and swelling of the polymeric network upon gas adsorption.48 The pore size distributions (PSDs) of the nanomaterials are calculated employing the nonlocal density functional theory (NLDFT) method, which is shown in the inset of the corresponding figures. The pore size distribution of the TTPOP and CuII-TTPOP nanofibrils using the carbon slit-pore model at 77 K exhibited unimodal porosity with extra-large micropores centered at 1.55 and 1.50 nm, respectively, which signifies the presence of supermicropores in these polymer-based materials.

Figure 4.

Figure 4

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N2 sorption isotherms and PSDs (inset) calculated from the NLDFT method (a) for TTPOP and (b) for CuII-TTPOP. Filled circles represent adsorption, and empty circles represent desorption points. (c) Solid-state 13C-CP MAS NMR of TTPOP and CuII-TTPOP.

Solid-State 13C-CP MAS NMR

The structural integrity of these porous materials, TTPOP and CuII-TTPOP, is established from solid-state 13C-CP MAS NMR (Figure 4c). The signal at 14 ppm can be attributed to CH3 of acetates and at 28 ppm to the carbon (CH2) that is connected with two aromatic thiophene residues. The signals at 58 and 68 ppm can be assigned to a few free methoxy groups and methoxy groups bearing terminal carbon, respectively. The signal at 138 ppm can be assigned to aromatic carbons of the thiophene ring, and the signal at 168 ppm is attributed to the most deshielded carbon atoms of the triazine ring.

ICP-MS and XPS Analyses

The Cu content in CuII-TTPOP was 2.76 wt % as determined by the ICP-MS analysis technique. Further, the presence of copper in CuII-TTPOP has also been confirmed by the Cu 2p XPS spectrum (Figure 5c). The XPS measurement was employed to elucidate the oxidation state of copper and to show the coordination of copper ions by N and S binding sites of the polymer. XPS survey spectra (Figure 5d) of CuII-TTPOP demonstrate that in addition to the binding energy peaks at 532.05, 398.90, 283.98, 227.74, 164.85, and 163.85 eV corresponding to the O 1s, N 1s, C 1s, S 2s, S 2p1/2, and S 2p3/2 respectively, there are another two peaks at 953.75 and 933.80 eV that are attributed to the Cu 2p1/2 and Cu 2p3/2 binding energies, respectively. The binding energy peak of N 1s (shown in Figure 5a) centered at 398.5 eV signifies the presence of free N sites of the triazine moieties in the pure TTPOP. However, the positive shift of the binding energy for N 1s to a higher value centered at 398.9 eV and also the positive shift of binding energies for both S 2p1/2 and S 2p3/2 (shown in Figure 5b) to the higher values in the CuII-TTPOP indicate that here copper(II) ions are strongly coordinated by both N and S binding sites of the triazine moieties in CuII-TTPOP. The XPS spectrum of Cu 2p indicates the +2 oxidation state of Cu in the CuII-TTPOP material.49 During comparison of the XPS spectra of Cu 2p of CuII-TTPOP and Cu(OAc)2·H2O,49c we have seen a negative shift of binding energies of Cu 2p1/2 and Cu 2p3/2 to a lower value. This may be due to the shifting of electron density from N and S sites to Cu(II) ions in the CuII-TTPOP. These can be attributed to the strong interaction between the polymer network and Cu(II) ions in the CuII-TTPOP material.

Figure 5.

Figure 5

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XPS spectra: (a) N 1s and (b) S 2p of TTPOP and CuII-TTPOP; (c) Cu 2p; and (d) survey of CuII-TTPOP.

Heterogeneous Nanocatalysis for Direct Construction of Valuable Diindolylmethanes

In the present study, we have chosen a model C-C/C-N coupled cyclization reaction for the synthesis of diindolylmethanes employing unprotected 2-ethynyl anilines and aldehydes. At the very outset, we started our initial development of the cascade reaction through screening different catalysts to ultimately finding out the most efficient catalytic system. The reaction of benzaldehyde (2a) and 2-ethynylaniline (3a) in the presence of the metal-free TTPOP nanomaterial in ethylene dichloride (EDC) at room temperature could not afford the desired diindolylmethane (4a, entry 1, Table 1) and even at elevated temperature (80 °C). To our delight, the reaction was completed in 4 h at 80 °C on employing CuII-TTPOP as the catalyst (5 mol %), and the desired product 4a was obtained with 78% yield (entry 3). The reaction was studied at ambient temperature using EDC, CH2Cl2, and CHCl3 (entries 4–6), and the yield was improved to 90% in CHCl3 with a little slower reaction rate (6 h). However, attempts with other polymer-based CuII catalysts such as Cu(II)@SiO2, Cu(II)@C, and Cu(II)@polystyrene to furnish 4a were successful with moderate yields (51–56%) and relatively slower reaction rate (12 h, entries 7–9). Next, we screened the solvent effect on the reaction with aprotic polar (entries 10–14) and nonpolar solvents (entries 15 and 16), and, unfortunately, these were not compatible with the cascade cyclization process. Catalyst loading for the reaction was optimized to 5 mol % (entries 6, 17, and 18).

Table 1. Development of Cascade Cyclization to Diindolylmethanea.

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entry catalyst solvent temperature (°C) time (h) 4a, yieldb (%)
1 TTPOP EDC 25 24 NRc
2 TTPOP EDC 80 24 NRc
3 CuII-TTPOP EDC 80 4 78
4 CuII-TTPOP EDC 25 6 84
5 CuII-TTPOP CH2Cl2 25 6 85
6 CuII-TTPOP CHCl3 25 6 90
7 Cu(II)@SiO2 CH2Cl2 25 12 51
8 Cu(II)@C CH2Cl2 25 12 56
9 Cu(II)@polystyrene CH2Cl2 25 12 50
10 CuII-TTPOP CH3CN 25 12 NRc
11 CuII-TTPOP THF 25 12 30d
12 CuII-TTPOP Et2O 25 12 NRc
13 CuII-TTPOP dioxane 25 12 NRc
14 CuII-TTPOP DMF 25 6 NRc
15 CuII-TTPOP toluene 25 12 <10d
16 CuII-TTPOP benzene 25 12 NRc
17 CuII-TTPOP (7) CHCl3 25 6 91e
18 CuII-TTPOP (3) CHCl3 25 12 70f
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a

Reactions were carried out using benzaldehyde (2a, 0.5 mmol) and 2-ethynylaniline (3a, 1 mmol) in the presence of CuII-TTPOP (5 mol % Cu) (2.76 wt % copper present in the CuII-TTPOP nanomaterials, measured by AAS analysis).

b

Yield of the isolated product after column purification.

c

No reaction when performed without copper.

d

Unreacted 2a and 3a were recovered.

e

Reaction using 7 mol % CuII-TTPOP.

f

Reaction using 3 mol % CuII-TTPOP.

Having optimized conditions in hand (entry 6, Table 1), we explored the scope of the reaction with a wide range of functionalized substrates (Scheme 3). The cascade cyclization reaction was successfully investigated utilizing various aryl-, naphthyl-, and heteroaromatic aldehydes as well as cyclic ketones under the developed reaction conditions. Interestingly, the functionalized aromatic aldehydes (2b–d) worked efficiently in this electrophilic substitution reaction, affording the diindolylmethane (4b–d) in excellent yields (87–90%). Thiophenyl aldehyde 2e and a cyclic ketone 2f also served as good substrates in this protocol and afforded the desired products 4e and 4f with 85 and 80% yields, respectively. We also explored the scope of the reaction employing 4-nitro benzaldehyde (2b) and a variety of 2-alkynyl anilines (3b–f) having aromatic as well as aliphatic groups at the alkyne end under the optimized condition to obtain corresponding diindolylmethanes 4g–k with 80–90% yield. Later on, the cycloisomerization followed by C3-functionalization reaction was also carried out with differently substituted 2-alkynyl anilines (3g–k) and 4-nitro benzaldehyde (2b) under the standard conditions (entry 7, Table 1). Gratifyingly, substituted 2-(phenylethynyl) anilines 3g–k containing Cl, Br, CH3, and CF3 functionality on the aromatic ring of 2-iodoaniline also served as good substrates, leading to the formation of 4l–p (Scheme 3). The structures of the diindolylmethanes (4a–p) were unambiguously established by comparing the NMR data with reported compounds.32 One of our main aims to develop the strategies under mild conditions is building of valuable sugar-based chiral compounds decorated with multiple chiral centers. To our delight, the carbohydrate aldehydes 2g and 2h efficiently served as good substrates to achieve corresponding chiral diindolylmethanes 4q and 4r.

Scheme 3. Synthesized Diindolylmethanes.

Scheme 3

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Dual Role of Nanocatalyst

With the aim of gaining some insight into the reaction mechanism, we performed some control experiments (Scheme 4) in which we monitored the reaction employing a mixture of 4-nitro benzaldehyde (2b) and 2-ethynylaniline (3a) or 2b and indole (8) in the absence and presence of our nanocatalyst (CuII-TTPOP) at room temperature in CHCl3 (Scheme 4). It was noticed that compound 4b was not formed at all in the absence of the catalyst even after 24 h (path a and path b); rather, only the starting materials (2b, 3a, and 8) were recovered solely. However, as expected, in the presence of catalyst (1), the diindolylmethane (4b) was formed with 89–90% yield (paths c and d). On the other hand, on continuing the reaction up to 2 h, indole (8) was isolated in a significant amount (40%) along with the desired product 4b (40%) (path e). The aforementioned results clearly suggested that the reaction proceeds through indole 8 and the catalyst might have a dual role for activating both the carbonyl and alkyne moieties.

Scheme 4. Control Experiments to Evaluate the Role of CuII-TTPOP.

Scheme 4

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Synthesis of Propargyl Amine and Phthalimidine Synthon

To explore the diverse applicability of the nanocatalyst CuII-TTPOP, we examined its catalytic activities for the synthesis of substituted propargyl amines and phthalimidines via multicomponent reactions (MCR).50 Owing to their broad spectrum of biological and pharmacological profiles,51−53 the syntheses of substituted propargyl amines became an active research area.32 They have also been considered as important chemical building blocks, particularly for the synthesis of nitrogen-containing compounds, such as allylamines, pyrroles, pyrrolidines, and oxazoles.54 The most commonly used approach for the synthesis of propargyl amines is the A3-coupling under catalytic conditions utilizing aldehydes, amines, and alkynes.34a Other important strategies involved the amination of propargyl derivatives including propargyl phosphates, esters, halides, triflates, and oxyphosphonium salts.55 Most of the methods to synthesize propargyl amines have been performed under homogeneous catalysis only. Therefore, the synthesis of propargyl amines employing heterogeneous catalysis is highly desirable because it offers several advantages over homogeneous catalysis. Keeping this goal in our mind, we were first intended to synthesize propargyl amine, and our development of the A3-coupling reaction among 4-chloro benzaldehyde (2g), 4-methoxyphenylamine (5a), and phenylacetylene (6a) was investigated at room temperature and the desired product N-(1-(4-chlorophenyl)-3-phenylprop-2-ynyl)-4-methoxyaniline (7a) was not formed at all in the presence of TTPOP even at elevated temperature in chloroform (entries 1 and 2; Table 2). To our delight, the desired propargyl amine (7a) was isolated with 45–90% yields in chloroform in the presence of CuII-TTPOP, Cu(II)@SiO2, Cu(II)@C, and Cu(II)@polystyrene (entries 3–6). Next, we turned our attention toward the solvent study for the A3-coupling reaction (entries 7–17), which showed CHCl3 as the best reaction medium to afford propargyl amine 7a with 90% yield (entry 3). The catalyst loading was optimized to 5 mol % (entries 5, 18, and 19) under the reaction conditions. We explored the scope of the A3-coupling reaction (Scheme 5) under optimized reaction conditions (entry 3, Table 2), and corresponding functionalized propargyl amines (7b–f) were furnished with synthetically viable yields (85–90%). After getting success in the synthesis of electronically different propargyl amines (7a–f), we were further interested to extend the A3-coupling strategy for the direct synthesis of phthalimidines employing the nanocatalyst CuII-TTPOP. At this end, we envisioned the alkynylation followed by the Mannich lactamization reaction in the presence of the heterogeneous catalyst. Gratifyingly, the new A3-coupling reaction among methyl benzoate-2-carboxaldehyde (8), aromatic amines (5), and alkynes (6) afforded the desired phthalimidines (9a–d, Scheme 6) with high yield (83–85%) under the mild conditions.

Table 2. Developing A3-Coupling Reactiona.

graphic file with name ao9b02904_0012.jpg

entry catalyst (5 mol %) solvent temperature (°C) time (h) 7a, yieldb (%)
1 TTPOP CHCl3 25 24 NRc
2 TTPOP CHCl3 40 24 NRc
3 CuII-TTPOP CHCl3 25 12 90
4 Cu(II)@SiO2 CHCl3 25 18 45
5 Cu(II)@C CHCl3 25 18 45
6 Cu(II)@polystyrene CHCl3 25 18 50
7 CuII-TTPOP CH2Cl2 25 12 85
8 CuII-TTPOP DCE 25 12 55
9 CuII-TTPOP CH3CN 25 24 NRc
10 CuII-TTPOP EtOH 25 24 20d
11 CuII-TTPOP MeOH 25 24 20d
12 CuII-TTPOP THF 25 24 30d
13 CuII-TTPOP Et2O 25 24 NDe
14 CuII-TTPOP dioxane 25 24 NRc
15 CuII-TTPOP benzene 25 24 NRc
16 CuII-TTPOP toluene 25 24 20d
17 CuII-TTPOP DMF 25 24 NRc
18 CuII-TTPOP CHCl3 25 12 90f
19 CuII-TTPOP CHCl3 25 12 72g
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a

Reactions were carried out using 4-chloro benzaldehyde (2g, 0.5 mmol), 4-methoxyphenylamine (5a, 0.5 mmol), and phenylacetylene (6a, 0.6 mmol) in the presence of CuII-TTPOP (5 mol %).

b

Yield of the isolated product after purification by silica gel column chromatography.

c

No reaction when performed without copper.

d

Unreacted aldimine was recovered.

e

Not detected.

f

Reaction using 7 mol % CuII-TTPOP.

g

Reaction using 3 mol % CuII-TTPOP.

Scheme 5. Synthesized Propargyl Amines.

Scheme 5

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Scheme 6. Synthesized Phthalimidines.

Scheme 6

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Recyclability and Heterogeneous Nature of the Catalyst CuII-TTPOP

For a heterogeneous catalyst, it is important to examine its ease of separation from the reaction mixture, recoverability, and reusability. The reusability of the CuII-TTPOP catalyst was investigated for the synthesis of diindolylmethane (4a) from benzaldehyde (2a) and 2-ethynylaniline (3a) under optimized reaction conditions (entry 6, Table 1). After the first catalytic cycle, the catalyst was recovered by centrifugation of the reaction mixture, subsequently washing with methanol followed by acetone, and drying at 100 °C temperature for 1 h before its use in the next cycle. The performance of the recovered catalyst for the representative reaction was examined up to a six successive runs with a very low loss of catalytic activity. The yield was 88% for the particular reaction at the sixth run (Figure 6). The same technique was employed for the synthesis of propargyl amine (7a, Table 2) and phthalimidines (9a, Scheme 6) under the optimized reaction conditions. The low loss of catalytic activity may be due to the blocking of some active sites with organic reagents during the course of a catalytic reaction. To explain this, we have carried out N2 adsorption–desorption isotherm studies of the reused catalyst after the 6th cycle (Figure 7a). The decrease in BET surface area (395–348 m2 g–1) led us to explain the fact that the accumulation of external materials hinders N2 adsorption in pore space (reduction of pore volume from 0.432 to 0.368 cm3/g).

Figure 6.

Figure 6

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Reusability test of the CuII-TTPOP heterogeneous catalyst.

Figure 7.

Figure 7

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(a) N2 sorption, (b) FESEM image, (c) 13C-CP MAS NMR, and (d) Cu 2p XPS spectrum of the reused CuII-TTPOP catalyst after the 6th catalytic cycle. Herein, all of the characterizations of reused catalyst were performed after the 6th catalytic cycle of the reaction to diindolylmethane (4a), synthesized from benzaldehyde (2a) and 2-ethynylaniline (3a) under optimized reaction conditions (entry 6, Table 1).

To check mechanical stability of the CuII-TTPOP nanocatalyst after the 6th catalytic cycle, we have characterized the reused CuII-TTPOP nanocatalyst. SEM image analysis of the CuII-TTPOP nanocatalyst (Figure 7b) after the 6th catalytic run indicates that there is no change in the morphology of the catalyst during the course of the catalytic run. 13C solid-state CP MAS NMR analysis (Figure 7c) reveals that the structural integrity of organic functional groups in the nanoporous polymer backbone was retained. XPS spectrum of the Cu 2p region (Figure 7d) of reused CuII-TTPOP nanocatalyst signifies that the +2 oxidation state of Cu remains unchanged after the catalytic reaction. All of these analyses show that our newly developed nanocatalyst is stable with the preservation of the structural integrity of organic functional groups in the porous polymer backbone under the proposed aforesaid reaction conditions. To determine whether the synthesis of diindolylmethane analogues (4) with the CuII-TTPOP catalyst is indeed heterogeneous in nature, we have performed the leaching test (Experimental Section) by considering benzaldehyde and 2-ethynylaniline as the model substrates under optimized reaction conditions. After 2 h, 55% conversion was attained. The reaction was continued for an additional 4 h with the filtrate only after separating the CuII-TTPOP catalyst by centrifugation. However, no progress in conversion was observed. The atomic absorption spectroscopy (AAS) technique was employed to verify whether any leaching of copper takes place during the course of catalytic reaction. The result indicates that the Cu content in the filtrate was below the detection limit of the instrument. The Cu content in the CuII-TTPOP catalyst after the 6th catalytic cycle was found to be 2.73 wt %, as determined by ICP-MS analysis, which is still analogous to that of the fresh one (2.76 wt %). This study clearly established that almost no Cu leaching occurred during the course of reactions and that our catalyst is truly heterogeneous in nature.

Conclusions

In conclusion, we have synthesized, fabricated, and fully characterized CuII-grafted 2,4,6-tri(thiophen-2-yl)-1,3,5-triazine-based nanofibrils with a microporous organic polymer network. The existence of porosity in the nanomaterials was confirmed through SEM imaging and the N2 adsorption study. The new CuII-TTPOP porous nanomaterials were employed successfully for a wide range of catalytic C-C/C-N coupling and cyclization under mild conditions to afford valuable propargyl amines, phthalimidines, diindolylmethanes, and spiro- and sugar-based chiral analogues. The heterogeneous and porous nanocatalyst showed excellent sustainability, robustness, recoverability, recyclability, simple separation, and negligible leaching of Cu(II). This is an important addition to the existing homogeneous catalytic methods and opens up a new avenue in heterogeneous catalysis.

Acknowledgments

Financial support of SERB (S.K.K.) (PDF/2017/000735), D.S. Kothari, UGC (A.K.) (No. F.4-2/2006 (BSR)/CH/16-17/0058), CSIR (JRF to R.L.B.), SERB (No. EMR/2017/005028), and CSIR (02(0250)/15/EMRII) for research funding as well as CAS-V, UGC, and CRNN, CU, for instrument facilities are gratefully acknowledged.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.9b02904.

  • Detailed experimental procedures, leaching test, spectroscopic data, and 1H and 13C NMR spectra (PDF)

Author Contributions

§ S.K.K., A.K., and R.B. contributed equally to the work.

The authors declare no competing financial interest.

Supplementary Material

ao9b02904_si_001.pdf (5.1MB, pdf)

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