Research Article pubs.acs.org/journal/ascecg
Polyacrylonitrile Fiber Supported N‑Heterocyclic Carbene Ag(I) As Efficient Catalysts for Three-Component Coupling and Intramolecular 1,3-Dipolar Cycloaddition Reactions under Flow Conditions Jian Cao,† Gang Xu,† Pengyu Li,† Minli Tao,†,‡ and Wenqin Zhang*,†,‡ †
Department of Chemistry, School of Science, Tianjin University, No.135 Yaguan Road, Haihe Education Park, Tianjin, 300350, People’s Republic of China ‡ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), No. 92 Weijin Road, Nankai District, Tianjin 300072, People’s Republic of China S Supporting Information *
ABSTRACT: A series of recoverable and reusable N-heterocyclic carbene silver complexes supported on polyacrylonitrile fiber were prepared and characterized. Their catalytic performances in three-component coupling reactions of aldehydes, amines, and alkynes (A3 coupling) to synthesize propargylamines were evaluated. The catalysts were also used to prepare fused triazoles in one-pot reactions with excellent yields and diastereoselectivities. In these reactions, the substrates underwent A3 coupling followed by intramolecular 1,3-dipolar cycloaddition. The above reactions were also successfully performed in a continuous-flow process, and sustainable, modular, and efficient syntheses of propargylamines and fused triazoles were achieved. KEYWORDS: Polyacrylonitrile fiber, Continuous-flow process, N-heterocyclic carbene silver, Three components coupling, 1,3-Dipolar cycloaddition
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INTRODUCTION Continuous-flow microreactors and their applications in chemical synthesis are an effective alternative strategy to conventional batch-based regimes.1−4 There are generally two ways to introduce catalysts into microreactors. One method is to dissolve a homogeneous catalyst directly into the reaction mixture; the other is to immobilize the catalyst on solid supports. The drawbacks to homogeneous catalysts are the cost of the catalyst and the need for its removal from the products.2,5 The combination of immobilized catalysts and flow chemistry is a promising way to avoid these problems. In fact, such systems have been used industrially for decades in the form of packed-bed reactors. When adapted to microreactors, the catalyst particles must be appropriately scaled for the microreactor with dimensions of 10−1000 μm.6 Typically, lightly cross-linked organic supports are not appropriate for use in microreactors, because they clog the device, causing irreproducibility and high back-pressures.7,8 To circumvent these problems, novel supports are needed for microfluidic systems.9 Polyacrylonitrile fiber (PANF) is a common and inexpensive commercial material which can be easily woven into different shapes. In addition, it has large specific surface areas and abundant −CN groups which can be © 2017 American Chemical Society
transformed into various other functional groups. For example, quaternary ammoniums,10 ionic liquids,11 and amines12 have all been introduced into PANFs to catalyze various reactions. Transition metal complexes of N-heterocyclic carbenes (NHCs) have been subjected to extensive investigations because of their successful applications in coordination chemistry and catalysis.13−15 Among these complexes, NHC silver complexes (NHC-Ag) have received special attention due to their structural diversity and their wide range of applications including being effective carbene transfer agents and having good biological activities.16 However, in contrast to numerous other transition metal NHC catalysts which have been used in various reactions, the use of silver NHC complexes as catalysts is severely limited.17,18 The three-component reaction of an aldehyde, an amine, and an alkyne (A3 coupling)19−21 represents an important approach for the synthesis of propargylamines, which are recurrent moieties in biologically active compounds and are valuable intermediates. Homogeneous catalysts such as copper,22−27 Received: January 11, 2017 Revised: March 4, 2017 Published: March 8, 2017 3438
DOI: 10.1021/acssuschemeng.7b00103 ACS Sustainable Chem. Eng. 2017, 5, 3438−3447
Research Article
ACS Sustainable Chemistry & Engineering Scheme 1. Preparation of Modified Fibers
Figure 1. XPS of (a) survey scan of PANF-NHC-Ag 4b and (b) Ag 3d spectrum for PANF-NHC-Ag 4b.
silver,28−33 gold,34,35 and other metals36 have been applied to A3 coupling reactions. However, during the course of the reaction, most of these catalytic systems suffer from a loss of the costly or hazardous catalysts. In order to achieve recyclable catalysts, Ag(I) and Cu(I) in ionic liquids have been developed by Li et al.29 and Park et al.,37 respectively. Kidwai et al.38 reported gold nanoparticles as reusable catalysts, and Corma et al.39 developed CeO2 and ZrO2-stabilized Au(III) as efficient catalysts for A3 coupling reactions. MCM-41-supported gold,40 hydroxyapatite-supported copper,41 heteropolyacid-supported silver,42 polystyrene-supported Ag,43,44 and AgY zeolite45 have also been successfully used to catalyze A3 coupling reactions under heterogeneous conditions. The 1,3-dipolar cycloaddition reaction between an alkyne and an azide developed by Huisgen46 has become a very popular reaction. The resulting five-membered ring is found in a large number of compounds that possess biological activities.47 In addition, 1,3-dipolar cycloaddition reactions that make use of silver salt catalysts have attracted a great deal
of attention. 18,48,49 In 2011, McNulty and co-workers discovered the synthetically useful Ag(I)-catalyzed reaction of azides with alkynes.50 More recently, Chen et al. reported the catalyst-free synthesis of fused triazoles via a 1,3-dipolar cycloaddition reaction.36,51 Herein, we report the synthesis and application of a novel PANF supported N-heterocyclic carbine silver complex (PANF-NHC-Ag; Scheme 1). The resulting materials were highly active to catalyze A3 coupling and subsequent 1,3dipolar cycloaddition reactions in continuous-flow process. The small volumes used by microreactors enable the safe use of highly toxic or explosive reactants, i.e., azides.3,52 To the best of our knowledge, this is the first example of fiber-supported metal carbene used as a catalyst in flow chemistry.
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RESULTS AND DISCUSSION Preparation of PANF-NHC-Ag Catalysts. The synthesis of propargylamines began with the preparation of the PANFNHC-Ag catalysts. The protocols for preparing these catalysts 3439
DOI: 10.1021/acssuschemeng.7b00103 ACS Sustainable Chem. Eng. 2017, 5, 3438−3447
Research Article
ACS Sustainable Chemistry & Engineering
amination, the ester carbonyl carbon peak disappears, and a new signal from the amide carbon appears at around 176.8 ppm. In addition, intense carbon signals from the NHC moieties can be seen at around 136.9 and 129.9 ppm for 4b. The UV−vis spectra of aminated PANF, NHC-Ag and PANF-NHC-Ag are shown in Figure S2. The NHC-Ag (3b) displays UV−vis absorbance at 357 nm, which is due to an extended conjugation in the ligand.57 After immobilizing the NHC-Ag derivative into the aminated PANF, PANF-NHC-Ag fibers have almost the same characteristic spectra at 357 nm. These results indicate that the NHC-Ag is successfully immobilized into the aminated PANF. The FTIR spectra of PANF and the modified fibers are shown in Figure S3. The FTIR spectrum of PANF (Figure S3a) has a characteristic CN peak at 2230 cm−1 and a CO peak from the ester moiety at 1730 cm−1.58,59 This confirms that PANF is a copolymer of acrylonitrile and methyl acrylate. Comparing the FTIR spectrum of aminated PANF (Figure S3b) with that of PANF, the most striking changes are the disappearance of the 1730 cm−1 peak, the weakening of the 2230 cm−1 peak, and the appearance of a broad absorption peak at 3450−3250 cm−1 which is due to the amide N−H stretching vibration.59 These changes suggest that most of the ester groups and some of the CN groups were transformed to amide bonds when the ethylenediamine was introduced. The FTIR of PANF-NHC-Ag (Figure S3d) exhibits a new absorption peak at 720 cm−1 which is due to the existence of Ag(I) and the NHC complex (Figure S3c). The crystalline structures of the modified and original fibers were also investigated by X-ray diffraction (XRD). The XRD spectrum of PANF (Figure S4a) shows an intense reflection peak at 2θ = 17° which corresponds to the (100) diffraction of the hexagonal lattice formed by the parallel close packing of the molecule rods.60 This indicates that PANF adopts a stiff rodlike conformation due to the intermolecular repulsions between the nitrile groups. The XRD peak at 2θ = 17° is weaker in the modified fibers (Figure S4b,c), which indicates that only part of the crystalline phase of the fiber has changed after the modifications. The elemental analysis of PANF, aminated PANF, and PANF-NHC-Ag are shown in Table S2. After the modification, the amount of carbon decreases significantly in all the samples. The amount of nitrogen decreases significantly in PANF-NHCAg when the NHC-Ag is introduced. The changes confirm the composition of the modified fibers. The swelling of a modified fiber is essential in microfluidic applications where the fiber comes in contact with organic solvents.8,61,62 In this work, a continuous flow process was used where organic solvents were continuously injected into the system. These solvents diffused into the fibers leading to changes in the fiber shapes. The extent of fiber swelling (G) was calculated using the following equation:63
mainly involve the transesterification of the aminated PANF and NHC-Ag esters (Scheme 1). The aminated PANF was prepared from PANF and ethylenediamine.12 Imidazolium salts 2 were obtained by reacting imidazoles 1 with methyl chloroacetate. The succeeding reaction between Ag2O and the imidazolium salts 2 gave the desired NHC-Ag esters 3 in good yield. Subsequent treatment of 3 with the aminated PANF at reflux in acetonitrile afforded PANF-NHC-Ag 4. The extent of modification was measured directly by determining the weight gain according to the following equation: weight gain = [(W2 − W1)/W1] × 100%, where W1 and W2 are the weights of the aminated PANF and the PANF-NHC-Ag, respectively. To investigate the influence of substituted groups of NHCs, a series of PANF-NHC-Ag catalysts (4a, 4b, and 4c) were synthesized. Characterization of PANF-NHC-Ag Catalysts. The PANF-NHC-Ag fibers were analyzed using scanning electron microscopy (SEM) in order to examine both the general morphology and microscopic fine structure of the material. As shown in Figure S1, the PANF-NHC-Ag fibers (4a, 4b, and 4c) are thicker and the surfaces are coarser than that of PANF. The surface of PANF-NHC-Ag is relatively rough and porous with granular flakes, which are the result of the introduction of NHC-Ag. X-ray photoelectron spectroscopy (XPS) was utilized to study the chelating mechanism and the elemental composition of 4b. The full survey spectrum of 4b (Figure 1a) shows principal energy levels for O 1s, N 1s, Ag 3d, C 1s, and Cl 2p at 536.20, 403.76, 370.19, 376.17, 287.41, and 200.96 eV. The high resolution Ag 3d spectrum of PANF-NHC-Ag (Figure 1b) can be deconvoluted into two groups’ peaks which correspond to Ag(I) (374.28 and 368.25 eV) and Ag(0) (372.98 and 367.02 eV; oxidation states of Ag, see Supporting Information Table S1).53,54 Solid-state 13C NMR (Figure 2) was also used to characterize the modified fibers. The pure PANF has the following characteristic peaks: the backbone carbon peak is at around 29.7 ppm; the cyano carbon peak is centered at 122.1 ppm, and the ester carbonyl carbon peak is at 174.5 ppm.55,56 After
G=
Ws(t ) − Wd Wd
(1)
where Wd is the weight of the dry fibers, Ws is the weight of the swollen fibers, and t is the swelling time (swelling experiments, see Supporting Information). The swelling ratios (G) of the modified fibers in various solvents at different times (t) are shown in Figure S5. The swelling ratios in all the organic solvents are lower than those in water. The swelling ratios of
Figure 2. Solid-state 13C NMR of PANF, aminated PANF, and PANFNHC-Ag (4a, 4b, 4c). 3440
DOI: 10.1021/acssuschemeng.7b00103 ACS Sustainable Chem. Eng. 2017, 5, 3438−3447
Research Article
ACS Sustainable Chemistry & Engineering
done for 10 consecutive cycles, and the activity remained virtually unchanged (Figure S6). The silver content in the clear filtrates was less than 1.0 ppm, which implies that the supported catalyst is stable enough. The thermal properties of the fibers were investigated with thermogravimetry (TG) and differential scanning calorimeter (DSC). For PANF-NHC-Ag, it was observed that no significant degradation occurred before 200 °C (Figures S7, S8, and S9). To gain more insight into the catalytic performance and recyclability of PANF-NHC-Ag, kinetic studies of the A3 coupling reaction on the synthesis of 8e were performed. As can be seen from Figure 3, when 1 mol % of PANF-NHC-Ag (4b) was used as the catalyst system, the conversion of the A3 coupling reaction proceeded to 95% within 1 h (initial 0.5 h turnover frequency (TOF), 152/h). The TOF of NHC-Ag (3b) could reach 90/h during the first 30 min under such a system. These results indicated that the supported catalyst demonstrated an enhanced catalytic activity as compared with its homogeneous counterpart. Moreover, the kinetic curves of the recovered PANF-NHC-Ag for the first cycles were analogous to that of the original catalyst system (initial 0.5 h TOF, 144/h), demonstrating the excellent stability and recyclability of PANF-NHC-Ag. Interestingly, along with the growth of recycling number, the reaction rate reached a stable state after the second cycle (initial 0.5 h TOF, 130/h). Multicomponent synthetic reactions performed in one pot play a significant role in modern synthetic chemistry. These reactions have higher atom economy and selectivity, and they facilitate the construction of more diverse and complex molecules.66 With the catalysis of PANF-NHC-Ag, starting materials 5 (R1 = H), 6 (R2 = H), and (S)-2-azidomethylpyrrolidine (9) were refluxed in CH3CN (Table 3). In this case, the A3 coupling products were not isolated. They underwent a cascade intramolecular 1,3-dipolar cycloaddition reaction to provide a fused triazole in good yield (11a: 87%). With this result in hand, other fused triazoles were then synthesized under identical reaction conditions. As shown in Table 3, the corresponding fused triazoles were obtained in moderate yields (75−83%) and excellent diastereoselectivities (>99/1; as determined by 1H NMR spectroscopy).51 Compared with catalyst-free reactions,36,51 the reaction catalyzed by PANFNHC-Ag was evidently shortened from 12 to 2 h, and the reaction temperature was evidently lowered from 100 °C (in DMF) to 82 °C (in refluxed acetonitrile). The Catalytic Activity of PANF-NHC-Ag under Flow Conditions. A microfluidic system was then assembled using these optimized conditions as shown in Figure 4. The experimental setup consisted of a stainless steel column loaded with the PANF-NHC-Ag catalyst and an HPLC pump67 used to feed the reactor with a solution of reaction mixture. Initially, the modified fiber was cut into pieces of 0.1−0.5 cm. However, the reactor column could not be thoroughly filled with the fibrous catalyst pieces, which caused an irreproducibility result in use. But small particles will lead to high pressure drops.68 So the fiber was cooled with liquid nitrogen and ground into particles of about 1−5 μm (Figure S1e). A back-pressure regulator (BPR) and an ice−water cooling bath were placed after the reactor column to prevent boiling of the solvent.69,70 The preparation of 8a was initially used to examine the effectiveness of PANF-NHC-Ag for a flow-chemistry reaction. The device was operated with a loading of 1.0 g of 4b (functionality = 0.75 mmol/g). A stock solution containing the substituted alkyne 5 (1.2 M), aldehyde 6 (1.2 M), and amine 7 (1 M) in CH3CN was pumped at 60 °C. Flow rates were
PANF-NHC-Ag (4b) in various organic solvents were between 10% and 18% at equilibrium. The Catalytic Activity of PANF-NHC-Ag to A3Coupling and Intramolecular 1,3-Dipolar Cycloaddition Reactions. The catalytic activity of the modified fibers with different substituted groups for the A3 coupling reaction was investigated. The A3 coupling of isobutyraldehyde, phenylacetylene, and pyrrolidine was used as the model reaction. The reaction proceeded smoothly at 60 °C with all three catalysts to give yields of 78−92% (Table 1, entry 1, 2, 3). Since 4b has the highest yield, it was chosen for further investigations. Table 1. Optimization Studies for A3 Coupling Reactiona
entry
catalyst
temp (°C)
solvent
yield (%)
1 2 3 4 5 6 7 8 9 10 11 12 13
4a 4b 4c No catalyst 4b 4b 4b 4b 4b 4b 4b 4bb 4bc
60 60 60 60 reflux 60 60 60 60 25 60 60 60
CH3CN CH3CN CH3CN CH3CN CH2Cl2 Toluene MeOH EtOAc H2O CH3CN no solvent CH3CN CH3CN
78 92 85
