Encapsulation of Homogeneous Catalysts in ... - ACS Publications

This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Encapsulation of Homogeneous Catalysts in Porous Polymer Nanocapsules Produces FastActing Selective Nanoreactors Sergey A. Dergunov,*,† Alibek T. Khabiyev,‡ Sergey N. Shmakov,† Mariya D. Kim,† Nasim Ehterami,§ Mary Clare Weiss,§ Vladimir B. Birman,⊥ and Eugene Pinkhassik*,† †

Department of Chemistry, University of Connecticut, 55 North Eagleville Rd, Storrs, Connecticut 06269-3060, United States Kazakh National Research Technical University, 22 Satpayev St., Almaty 050013, Kazakhstan § Department of Chemistry, Saint Louis University, 3501 Laclede Avenue, St. Louis, Missouri 63103, United States ⊥ Department of Chemistry, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130, United States ‡

S Supporting Information *

ABSTRACT: Nanoreactors were created by entrapping homogeneous catalysts in hollow nanocapsules with 200 nm diameter and semipermeable nanometerthin shells. The capsules were produced by the polymerization of hydrophobic monomers in the hydrophobic interior of the bilayers of self-assembled surfactant vesicles. Controlled nanopores in the shells of nanocapsules ensured long-term retention of the catalysts coupled with the rapid flow of substrates and products in and out of nanocapsules. The study evaluated the effect of encapsulation on the catalytic activity and stability of five different catalysts. Comparison of kinetics of five diverse reactions performed in five different solvents revealed the same reaction rates for free and encapsulated catalysts. Identical reaction kinetics confirmed that placement of catalysts in the homogeneous interior of polymer nanocapsules did not compromise catalytic efficiency. Encapsulated organometallic catalysts showed no loss of metal ions from nanocapsules suggesting stabilization of the complexes was provided by nanocapsules. Controlled permeability of the shells of nanocapsules enabled sizeselective catalytic reactions. KEYWORDS: polymer nanocapsules, homogenous catalysis, immobilization, nanoreactors, nanopores, vesicles

C

surface. Multiple attempts to overcome these limitations, such as placement of the catalysts in the fibers, metal−organic frameworks, magnetic nanoparticles, or dendrimers, highlight the difficulties of the practical use of homogeneous catalysts and the need for innovative methods to immobilize homogeneous catalysts.15−21 Recent progress in facilitating practical applications of existing homogeneous catalysts has been driven by the development of new materials for the immobilization of catalysts. Encapsulation of catalysts is an attractive option highlighted by the recent emergence of yolk− shell nanoparticle-based nanoreactors.22−25 Most shells containing entrapped metal nanoparticles were based on ceramic or similar materials due to typical fabrication methods, such as etching the shell in core−shell structures. A handful of studies reported the entrapment of metal nanoparticle catalysts in hollow carbon and polymer shells.26−28 Although these

ombining the advantages of homogeneous and heterogeneous catalysis has motivated numerous investigations since the development of viable homogeneous catalysts.1,2 Ideal catalytic processes exhibit efficient and diverse reactions (characteristic of homogeneous catalysis) and ease of separation of the reaction products from the catalyst with a simple technical setup (characteristic of heterogeneous catalysis). Immobilization of the homogeneous catalysts permits continuous-flow processes as opposed to batch processes that necessitate recovery of the catalysts.3,4 Recent progress in the flow chemistry makes the continuous processes especially attractive.5−12 Despite the obvious need, fundamental options for the immobilization of homogeneous catalysts are still limited. The main approaches have been the attachment of a catalyst to a surface and conducting catalytic reactions in biphasic systems.13,14 Current immobilization methods have intrinsic limitations, including performing a reaction on the interface, stringent requirements for the high stability of catalysts, need for the elaborate synthetic design of ligands for covalent attachment to the surface, and difficulties with asymmetric reactions due to steric hindrance at the © 2016 American Chemical Society

Received: October 6, 2016 Accepted: November 15, 2016 Published: November 15, 2016 11397

DOI: 10.1021/acsnano.6b06735 ACS Nano 2016, 10, 11397−11406

Article

www.acsnano.org

Article

ACS Nano

Figure 1. Schematic representation of a nanoreactor containing homogeneous catalysts entrapped in porous polymer nanocapsules.

catalysts but large enough to allow a rapid flow of reactants and products in and out of the capsule. For the vast majority of synthetically useful organic reactions, the difference in size between typical catalysts and substrates or products is only a fraction of a nanometer. Perfect pores should have controlled sizes and narrow size distribution. To enable rapid flow, shells should have high pore density and small thickness. The chemistry of shells should permit facile entrapment of catalysts, and the resulting capsule/catalyst constructs should be compatible with a broad range of solvents. In this work, we investigate vesicle-templated polymer nanocapsules as a platform that satisfies these requirements. We have recently developed a vesicle-templated approach to the synthesis of polymer nanocapsules having single-nanometer thick shells with programmed-size pores that showed size-selective permeability in the desired range for the entrapment of homogeneous catalysts.44−48 To form nanocapsules, hydrophobic monomers and cross-linkers are loaded into the hydrophobic interior of bilayers of catanionic surfactant vesicles or liposomes. Uniform nanopores are imprinted by using poreforming templates that are codissolved with the monomers in the bilayer and removed after the formation of nanocapsules.45,46 Varying the size, composition, and number of pore-forming templates controls the size, chemical environment, and density of nanopores in the shells.44,45,49 Crosslinked porous polymer shells are stable in different organic solvents. These capsules are capable of long-term retention of molecules larger than the pore size and permit ultrafast transport of molecules smaller than pores.44,46,48,50−52 We used these semipermeable hollow nanocapsules for catch and release of organic molecules and for creation of optical nanosensors and yolk−shell nanoreactors containing entrapped metal nanoparticles.22,44,51,53

materials are suitable for the encapsulation of metal nanoparticles with typical dimensions between 10 and 100 nm, they are not likely to be viable for the encapsulation of the vast majority of homogeneous catalysts with a typical size range between 1 and 2 nm. In fact, reports on achieving size-selective transformations due to selective permeability of the shells highlighted the challenge of controlling the pore size and often resulted in hindered diffusion through the shells.29,30 Until recently, the creation of nanoreactors containing common homogeneous catalysts has not been feasible due to the lack of suitable materials for the fabrication of shells with appropriate permeability characteristics. Previous attempts of immobilizing enzymes in polymer microcapsules emphasized this difficulty. Leaching of enzymes and hindered flow of substrates and products as evidenced by the increased Michaelis−Menten constant have been reported as typical confounding problems.31−35 Reports on permeability control in polymer capsules produced by layer-by-layer assembly showed successful longterm retention of molecules with molecular weights exceeding 5000.35−37 The vast majority of widely used homogeneous catalysts are much smaller with typical molecular weights in the 300−1100 range.38,39 In polymersomes, another example of polymer capsules, the permeability was successfully controlled by the insertion of bacterial porins, enabling the assembly of enzyme-based nanoreactors but limiting the processes to aqueous solutions.40−42 Other attempts to create semipermeable capsules showed difficulties with long-term retention of medium-sized molecules. For example, organic−inorganic hybrid vesicles created with a siloxane layer showed release of polyethylene glycol molecules with the molecular weight up to 1500.43 An ideal shell material for nanoreactors should have pores that are small enough to retain most common homogeneous 11398


Article

ACS Nano

Figure 2. Synthesis and characterization of vesicle-templated nanoreactors. (A) Schematic representation of the preparation procedure of vesicles and nanocapsules: surfactants and monomers are mixed in an aqueous solution of catalysts or ligands producing self-assembled vesicles containing monomers and cross-linkers in the hydrophobic interior of bilayers. Polymerization followed by the removal of the surfactant scaffold and nonentrapped catalysts yields a suspension of polymer nanocapsules with entrapped catalysts. Inclusion of poreforming templates in the bilayer before the polymerization can control the size of nanopores. (B) Size distribution (solid lines) and autocorrelation function (open circles) of vesicles before and after polymerization determined by dynamic light scattering (DLS) in aqueous solution. SEM (C) and TEM (D) images of nanocapsules after polymerization and template removal. (SDBS:CTAT = 80:20), 1% (w/v) solution of surfactants. Ratio of monomers/surfactants = 2:1.

investigate the effect of encapsulation of structurally diverse catalysts of representative sizes that promote different wellknown and synthetically useful reactions in a broad spectrum of conditions, e.g., solvents ranging from nonpolar (toluene) to highly polar (water) and temperatures ranging from ambient to 140 °C. Polymer nanocapsules containing entrapped catalysts were prepared by the directed assembly method using controlled polymerization of hydrophobic monomers in the interior of bilayers of self-assembled vesicles.47 When mixed with hydrophobic acrylate monomers, butyl methacrylate (BMA), and ethylene glycol dimethacrylate (EGDMA), aqueous solutions of cetyltrimethylammoium bromide or tosylate (CTAB or CTAT) and sodium dodecylbenzenesulfonate (SDBS) form vesicles containing monomers in the hydrophobic interior of bilayers (Figure 2A).47,61 The formation of vesicles was confirmed by DLS, SANS, and SAXS as described previously.47,61,62 Polymerization of monomers followed by removal of the surfactant scaffold resulted in the formation of hollow polymer nanocapsules (Figure 2C, D; Figure S1B, C). Other monomers, e.g., styrene derivatives, can be used to form nanocapsules.45−48 Transmission and scanning electron microscopy (TEM and SEM) images showed spherical structures with narrow size distribution (Figure 2C, D; Figure S1B, C) consistent with previously reported nanocapsules templated by liposomes and surfactant vesicles.46,47,62 The average size of nanocapsules isolated after the polymerization of monomers and measured by SEM and TEM was identical to the average size of vesicles observed by DLS (Figure 2B; Figure 1SA). The

Herein, we demonstrate successful creation of fast-acting and size-selective nanoreactors by entrapment of representative homogeneous catalysts in porous hollow polymer nanocapsules. Encapsulation of catalysts did not compromise their performance as evidenced by the identical reaction rates shown by entrapped and free catalysts. In addition, we show that sizeselective permeability through the nanopores in the shells of nanocapsules resulted in size-selective catalytic reactions.

RESULTS AND DISCUSSION Our primary goals were to create nanoreactors by entrapping homogeneous catalysts in hollow polymer capsules with porous nanometer-thin shells (Figure 1) and to test the hypothesis that encapsulation of homogeneous catalysts would not negatively affect the reaction rates. To investigate this idea, we fabricated a series of encapsulated catalysts and evaluated their performance and long-term retention within nanocapsules. We used five model catalysts with different structures: p-(diphenylmethylpiperidine)-pyridine (DPMPP, 1) that catalyzes the acylation of alcohols; a pincer-type catalyst 254−57 that was shown to be extremely efficient for the Suzuki, Sonogashira, and Heck crosscoupling reactions; a Verkade’s superbase, proazaphosphatrane (3), functionalized with Pd(OAc)2 that is known as a versatile catalyst for the Suzuki cross-coupling reactions;58 a 4,4′,4″,4‴(porphine-5,10,15,20-tetrayl)tetrakis(benzenesulfonic acid) tetrasodium salt (MnTPPSNa, 4), known as an efficient catalyst for the assembly of phenoxazine derivatives from 2-aminophenols;59 and 5,10,15,20-tetra-p-tolyl-21H,23H-porphine (MnTTPCl, 5), shown as a potent catalyst in the epoxidation of alkenes.60 We chose these model reactions in order to 11399


Article

ACS Nano capsules preserved their spherical shape upon drying, consistent with high degree of cross-linking. We measured the amount of catalysts inside the nanocapsules to establish reference data for quantitative evaluation of the performance of catalysts and to measure their long-term retention within nanocapsules. An entrapped DPMPP 1 was characterized by 1H NMR spectroscopy. We used atomic absorption (AA) spectroscopy to measure the amount of encapsulated organometallic catalysts 2 and 3. In this method, an aliquot of nanocapsule suspension, taken after the separation of unentrapped catalyst, was vaporized in an AA instrument, and the amount of metal was determined using a calibration curve. Our previous data showed no leakage of medium-sized molecules (MW > 500 D) from porous nanocapsules for more than four years.45,46,48,50 To evaluate the long-term retention of catalysts in this study, a suspension of nanocapsules containing entrapped catalyst molecules was incubated at ambient conditions upon constant agitation. Similar tests were performed at elevated temperatures to simulate aging and/or harsh reaction conditions, such as reflux in high boiling solvents. An aliquot of a suspension was taken at regular intervals from each sample (daily for the first week, then weekly for two months). This aliquot was passed through a PTFE syringe filter (0.2 μm) to remove nanocapsules. The supernatant was collected and analyzed with AA spectroscopy. No escape of the palladium ions was observed under different conditions. Due to the detection limit of the AA method, we would have observed the release of as little as 0.05% of the catalyst. As reported previously, this catalyst is not prone to the formation of palladium nanoparticles under typical reaction conditions.44,45 In agreement with previous reports, we found no evidence of nanoparticle formation. Likewise, the amount of entrapped porphyrins was evaluated by UV−vis and fluorescence spectroscopy. Since nonmetalated porphyrins differ from metalated ones in absorbance and fluorescence spectra, loss of metal ions or porphyrin molecules would have immediately revealed itself in spectroscopic measurements. Long-term observations of entrapped porphyrins showed no change compared with initial samples. These data suggest high long-term stability of the encapsulated catalysts, and the kinetic data described below are entirely due to the catalytic reaction happening inside the nanocapsules. We evaluated the effect of the encapsulation on the kinetics of the catalytic reactions by performing a series of experiments comparing the conversion of substrate in the presence of encapsulated and free catalysts. In all cases, solutions of free catalysts were prepared so as to match the total amount of the catalysts in the nanocapsules using measurements described above. In these experiments, the amount of catalysts in the nanocapsules was determined by independent measurements. Then, the solution of a free catalyst was prepared to match this concentration. The progress of reaction was monitored using 1 H NMR for the acylation of alcohols, GC-MS for the coupling and epoxidation reactions, and UV−vis spectroscopy for the heterocycle formation. In the acylation of alcohols catalyzed by DPMPP, we compared the reactions catalyzed by the free and encapsulated catalysts throughout the conversion of most of the substrate. The kinetics of the reactions were identical within the measurement error (Figure 3, Table 1S)). The same results were obtained with different amounts of catalysts. The

Figure 3. Comparison of kinetics of reactions catalyzed by encapsulated and free organocatalyst. DPMPP catalyzes acylation of alcohols. The reactions were performed in air at 20 °C. The yield of products was determined by NMR (Figure S2). Reaction of methanol with acetic anhydride was monitored with NMR using free and encapsulated DPMPP at the same concentration. At each catalyst/substrate ratio, the rates of reactions catalyzed by free (empty circles, triangles, and squares) and encapsulated catalysts (solid circles, triangles, and squares) were identical.

encapsulation clearly did not have any negative effect on the overall reaction kinetics (Figure S3). In a similar way, we performed the Suzuki coupling reactions between phenylboronic acid and different aryl halides (Figure 4; Table 2S). In these reactions, we monitored the formation of the biphenyl product at regular intervals during the standard reaction time (60 min). In each case, we observed the same reaction kinetics for free and encapsulated catalysts. In addition, we monitored the supernatant for the presence of any potential fragments of the pincer catalyst or formation of byproducts such as biphenyl-2,6-diamine reported previously.57 None of the experiments showed the escape or degradation of the entrapped catalyst. This finding suggests that catalyst stayed inside the nanocapsules and the Pd−C bond remained intact during catalysis. We also examined the Sonogashira coupling reaction between a terminal alkyne (ethynyl benzene) and a series of aryl halides.54 We performed the reactions under standard conditions (140 °C, 5 min) and compared the yields of the reactions catalyzed by free and encapsulated catalysts. Due to an inherently different reactivity of the substrates, the yields at the reaction end point varied widely for different substrates. These variations allowed us to compare the performance of free and entrapped catalysts at different reaction end points ranging from less than 10% to more than 50% conversion. In all cases, the yields for the reactions catalyzed by either free or encapsulated catalysts were identical (Figure 5; Table 3S). To expand the utility of polymer nanocapsules as a platform for nanoreactors, we investigated two other reactions: a formation of a heterocycle and an epoxidation. We chose a coupling of an aminophenol into a derivative of phenoxazine to demonstrate the assembly of a complex structure from small components and due to broad utility of phenoxazine derivatives. This reaction can be catalyzed in water by a sulfonated porphyrin metalated with manganese. The coupling 11400


Article

ACS Nano

Figure 4. Suzuki coupling reactions of different aryl halides with phenylboronic acid catalyzed by free (empty dots) and encapsulated (solid dots) catalysts. Reaction conditions: aryl halide (1 mmol), PhB(OH)2 (1.5 mmol), K3PO4 (2 mmol), toluene (6 mL), and catalyst (0.0004 mol %). The reactions were performed in air at 100 °C. Catalysts: (A−C) [Pd(Cl)(C6H3(NHP(piperidinyl)2)2] and (D−F) Pd(OAc)2 in combination with ligand P(t-PrNCH2CH2)3N. Conversion was determined by GC-MS, based on aryl halide (Figures S7−S9). Substrates: (A, D) bromobenzene, (B, E) p-nitro bromobenzene, and (C, F) 4-bromoanisole.

spectroscopy (Figure S3). The yield of APX in both reactions was the same (Figure 6). Epoxidation of aklenes is another synthetically useful reaction that is catalyzed by a range of porphyrin-based catalysts. Here, we examined the epoxidation of styrene using sodium periodate as an oxidant in acetonitrile/water mixture. Again, the yields in reactions catalyzed by a free and encapsulated catalyst were identical (Figure 6). The five reactions described above showed identical performance for free and encapsulated catalysts examined with different substrates and captured at different conversion end points. The reactions were conducted in five different solvents (toluene, chloroform, acetonitrile/water mixture, ethylene glycol, and water) at temperatures ranging from ambient to 140 °C and represented a broad spectrum of synthetically useful transformations. We conclude that the encapsulation of homogeneous catalysts did not negatively impact the reaction rate. In other words, the catalytic conversion was not hindered by the diffusion of substrates or products through the pores of nanocapsules. The immediate implication of these findings is that one can retain the same catalytic efficiency, as in the reactions with free catalysts, but simplify the separation of the reaction products from the catalysts. We believe that this observation alone is a substantial milestone in the development of the nanoreactors incorporating homogeneous catalysts. In laboratory experiments, simple filtration or decantation of nanocapsules via mild centrifugation (1−3 min at 1000−2000g) was sufficient to separate the nanoreactors from the reaction mixture. Due to the ease of functionalization of shells, nanocapsules can be readily immobilized in a highly permeable matrix, e.g., fibers, to enable continuous-flow processes.

Figure 5. Sonogashira coupling reactions of aryl halides with ethynylbenzene catalyzed by free (patterned bars) and encapsulated (empty bars) catalysts. Reaction conditions: aryl halide (2 mmol), ethynylbenzene (3 mmol), K3PO4 (2 mmol), ethylene glycol (4 mL); catalyst was added to aryl halide in ethylene glycol, and the reactions were performed at 140 °C. Catalyst: [Pd(Cl)(C6H3(NHP(piperidinyl)2)2]. Conversion determined after 5 min of reaction by GC/MS, based on aryl halide (Figures S10 and S11). Substrates: (A) iodobenzene, (B) bromobenzene, (C) p-nitrobromobenzene, and (D) 4-bromoanisole.

of 2-aminophenol was conducted at ambient conditions for 4.5 h using free and encapsulated catalyst. The yield of product 2aminophenoxazin-3-one (APX) was determined using UV−vis 11401


Article

ACS Nano

Figure 6. Reactions catalyzed by free (patterned bars) and encapsulated (empty bars) manganese porphyrins. Reaction conditions of oxidative coupling (A): A mixture of OAP (2.7 mmol), MnTPPSNa (13 μmol), and H2O2 (10 mmol) in water (30 mL) was stirred at room temperature and pH 8 for 4.5 h. The yield of APX was determined spectrophotometrically (Figure S5). Reaction conditions of olefin epoxidation (B): A mixture of styrene (2 mmol), MnTTPCl catalyst (6.5 μmol), imidazole (0.4 mmol) in acetonitrile (20 mL), and NaIO4 (4 mmol) in 10 mL H2O was heated at 77 °C for 3 h. The yield of epoxide was determined by GC/MS.

Figure 7. Selective reaction achieved by the size-selective access of substrates into nanoreactors in the Suzuki coupling reactions of aryl halides with phenylboronic acid. The membrane itself shows permeability to small substrates, whereas larger substrates do not react inside polymer nanocapsules. Conversion was determined after 120 min of reaction by GC/MS, based on aryl halide with encapsulated (empty bars) and free (patterned bars) catalyst. Substrates: I, bromobenzene; II, p-nitro bromobenzene; III, 2bromodibenzothiophene; and IV, 9-bromoanthracene. Concentration of catalyst for I and II was 0.0004 mol %, and for III and IV: 0.001 mol %. Space-filling models illustrate the smallest dimension for the catalysts, phenylboronic acid, and aryl halides.

To take advantage of controlled permeability of prepared nanoreactors, we investigated size-selective reactions enabled by the programmed nanopores in the walls of nanocapsules. Size selectivity is particularly important in reactions that use mixed feedstock, e.g., linear vs branched isomers or selective transformation of one diastereomer in a mixture,63,64 and in combinatorial reactions65−67 that facilitate selective acquisition of libraries of molecules produced by modular assembly.68 In these experiments, we performed a Suzuki coupling between aryl bromide substrates with different cross sections and phenylboronic acid. Space-filling models of the substrates and the catalyst are shown on Figure 7. As reported previously,45 the use of pore-forming templates in the synthesis of nanocapsules allows us to control the size of the pores in the nanocapsule shells so that molecules bigger than the pore size remain entrapped, while the molecules smaller than the pores diffuse freely in and out of nanocapsules. The effective pore size in the shells of nanocapsules was determined with permeability assays measuring the efflux of molecules with different smallest dimensions (Figure S6). To test the hypothesis that size-selective permeability of nanocapsule shells would translate into the size-selective catalytic reactions, we chose two aryl bromide substrates69 that are similar in size to phenylboronic acid (approximately 0.8 nm)70 and two substrates that are slightly larger (approximately 1.2 nm).71−73 The expectation was that the catalyst having the smallest dimension of approximately 1.7 nm57 (Figure 7) would remain entrapped. The smaller substrates are expected to enter the capsule, while larger substrates should not be able to pass

through the pores; therefore no coupling reaction should be observed. For each substrate, we ran the reaction for a standard amount of time (120 min) and determined the yield of the product of the coupling reaction by GC/MS. In control experiments, the reaction was performed using free catalyst with the same total amount in solution as the encapsulated catalyst. For small substrates, the yield of the coupled product was the same for encapsulated and free catalysts (Figure 7). In contrast, large substrates formed the coupled product in the presence of free catalyst but not in the presence of nanocapsules containing entrapped catalysts (Figure 7). These observations confirm that the pores in the nanocapsule shells indeed provide selective permeability that translates into the size-selective catalytic reactions.

CONCLUSIONS This study investigated the performance of homogeneous catalysts entrapped in hollow polymer nanocapsules with nanometer-thin shells and uniform nanopores. Multiple experiments employing diverse catalysts, transformations, and reaction conditions, i.e., broad range of solvents and temperatures, showed identical reaction rates for free and encapsulated catalysts. These results confirmed that the encapsulation did not compromise the catalytic activity and that the polymerization process did not deactivate catalysts encapsulated in the cross-linked vesicles. An important implication of these findings is the ability to immobilize homogeneous catalysts in 11402


Article

ACS Nano

of catalyst solutions. CTAT stock solution was equilibrated at 40 °C for 30 min. Samples were prepared by mixing the stock solutions at 80:20 volume ratios corresponding to 80:20 weight ratio of SDBS to CTAT, and after brief vortexing, the solutions were not subjected to any type of mechanical agitation and were additionally equilibrated at the room temperature during 1 h or/and were extruded 5 times at 25 °C through a track-etched polyester Nucleopore membrane (Sterlitech) with 0.2 μm pore size using a Lipex stainless steel extruder (Northern Lipids). Synthesis of Nanocapsules Using Thermal Initiation. The sample prepared as described above was purged with nitrogen, and the thermostat was set to 40 °C. Following the polymerization, a solution of NaCl (0.02 mL of 3 N) in methanol (10 mL) was added to the reaction mixture to precipitate the nanocapsules. The nanocapsules were separated from the reaction mixture and purified by repeated centrifugation and resuspension steps using methanol (3 drops of NaCl (3 M, 0.02 mL) were added to aid precipitation). Acylation Reaction Inside Nanocapsules. One equiv of methanol, 1.5 equiv of the auxiliary base (triethylamine), and 3 equiv of acetic anhydride were added together to 1 mL of CDCl3 suspension of nanocapsules with entrapped catalyst with a known amount of TMS as the internal standard. Samples were analyzed using 1 H NMR spectroscopy. General Procedure for Suzuki Cross-Coupling Reactions of Aryl Halides with Phenylboronic Acid. Newly purchased or freshly recrystallized phenylboronic acid (183 mg, 1.5 mmol), powdered anhydrous K3PO4 (424 mg, 2.0 mmol), and toluene (4.0 mL) were mixed in a round-bottom flask. The mixture was vigorously stirred and heated up to 100 °C. Then the aryl halide (1.0 mmol) and the correct amount of catalyst (free or entrapped into nanocapsules) were added as a toluene solution (2.0 mL) via syringe. Samples taken from the reaction mixture were diluted with methylene chloride, passed through a PTFE syringe filter, and analyzed by GC/MS. At the end of the reaction, the mixtures were allowed to cool to room temperature, passed through PTFE syringe filter, and then analyzed for the residual Pd content. General Procedure for Sonogashira Cross-Coupling Reactions of Aryl Halides with Alkynes. All Sonogashira cross-coupling reactions were carried out without rigorous exclusion of air and moisture. Ethylene glycol was of reagent grade (98%) or better and was used as received. Newly purchased phenyl acetylene (330 mg, 3 mmol), powdered anhydrous K3PO4 (467 mg, 2.0 mmol), and ethylene glycol (5.0 mL) were mixed in a round-bottom flask. The mixture was vigorously stirred and heated up to 140 °C. Then the aryl halide (2.0 mmol) and the correct amount of catalyst (free or entrapped into nanocapsules) were added as an ethylene glycol solution (1.0 mL) via syringe. Samples taken from the reaction mixture were diluted with ethyl acetate, passed through PTFE syringe filter, and analyzed by GC/MS. At the end of the reaction, mixtures were allowed to cool to room temperature, passed through PTFE syringe filter, and then analyzed for residual Pd content. LCMS Analyses. Analyses were done on a Shimadzu Single Quad LCMS-2010EV with ESI modes using a Nova-Pak C18 reverse phase column (150 mm × 3.9 mm i.d., 4 μm, Waters, Ireland) for separations. NMR Measurements. A JEOL 270 NMR spectrometer was used to collect data for all kinetics experiments using tetramethylsilane as an internal standard (δ = 0 ppm). Measurements were taken at regular time intervals to determine the conversion of monomers. Signals at 3.45 and 3.65 ppm (hydrogens attached to methyl groups of methanol and ester) were used to monitor the reaction. Varian DirectDrive 500 MHz spectrometer was used for measurement of DPMPP catalyst inside nanocapsules. A Bruker 400 MHz Broadband NMR spectrometer was used to collect data for all of the prepared compounds. A Shimadzu GC-MS QP2010S was used to collect molecular fragmentation information for Suzuki and Sonogashira C−C coupling reactions. Atomic absorption experiments were carried out on GBC 908AA instrument equipped with a graphite furnace.

nanocapsules without any loss of the reaction efficiency. Sizeselective permeability of shells of nanocapsules permitted the creation of size-selective nanoreactors. Substrates larger than the pore size did not show noticeable conversion, while substrates smaller than the pores underwent unhindered transformations. An investigation of stability of nanoreactors showed no measurable leaching of catalysts or metal ions from the nanocapsules. Due to the ease of controlling the pore size and surface chemistry of the shells, we anticipate that encapsulation of homogeneous catalysts in polymer nanocapsules will be readily adaptable to a broad range of catalysts and reagents as well as diverse strategies for the immobilization of nanocapsules. Nanocapsules are synthesized from inexpensive materials using a simple and scalable method, further enhancing the utility of the nanoreactor platform. In addition to establishing encapsulation in polymer nanocapsules as a viable method for immobilization of homogeneous catalysts, this study sets the stage for further enhancements of catalytic activity enabled by the confinement of the catalysts in the nanocapsules. For example, controlling the microenvironment of nanocapsules, increasing local concentration of either the catalysts or substrates inside the nanocapsules, or coencapsulating multiple catalysts for cascade reactions will likely result in dramatic increase in overall efficiency of catalytic processes.

EXPERIMENTAL SECTION Concurrent Loading of Monomers into Surfactant Vesicles Using UV-Initiator. To prepare stock solutions, SDBS (100 mg) and CTAT (100 mg) were mixed in separate vials with t-BMA (32 μL, 0.19 mmol), BMA (32 μL, 0.19 mmol), EGDMA (32 μL, 0.17 mmol), GPA (5.9 mg, 0.02 mmol), initiator 2,2-dimethoxy-2-phenylacetophenone (3 mg, 0.01 mmol), and CHCl3 (100 μL). The CHCl3 was evaporated using a stream of purified argon to form a surfactant−monomer film on the wall of a culture tube. The film was further dried under vacuum for 10 min to remove traces of CHCl3. Each mixture was hydrated in 10 mL of catalyst solution. Each stock solution was equilibrated at 40 °C for 30 min. Samples were prepared by mixing the stock solutions at 80:20 volume ratios corresponding to 80:20 weight ratio of SDBS to CTAT and were additionally equilibrated at room temperature for 1 h. After brief vortexing, the solutions were not subjected to any type of mechanical agitation. Synthesis of Nanocapsules Using UV-Initiation. The sample prepared as described above was irradiated for 1.5 h with UV light (λ = 254 nm) in a photochemical reactor (10 lamps, 32W each; the distance between the lamps and the sample was 10 cm) using a quartz tube with path length of light of approximately 3 mm. Following the polymerization, a solution of NaCl (0.02 mL of 3N) in methanol (10 mL) was added to the reaction mixture to precipitate the nanocapsules. The nanocapsules were separated from the reaction mixture and purified by repeated centrifugation and resuspension steps using methanol (3 drops of NaCl (3M, 0.02 mL) were added to aid precipitation), water−methanol mixture, and water as washing solutions. Concurrent Loading of Monomers into Surfactant Vesicles for Thermal Initiation of Polymerization. To prepare stock solutions, SDBS (100 mg) was mixed with t-BMA (32 μL, 0.19 mmol), BMA (32 μL, 0.19 mmol), EGDMA (32 μL, 0.17 mmol), GPA (5.9 mg, 0.02 mmol), initiator lauroyl peroxide (2 mg, to make 4 × 10−4 M concentration after mixing), and CHCl3 (100 μL). CTAT (100 mg) was mixed with t-BMA (32 μL, 0.19 mmol), BMA (32 μL, 0.19 mmol), EGDMA (32 μL, 0.17 mmol), GPA (5.9 mg, 0.02 mmol), activator MDA (2.5 mg, to make 2 × 10−4 M concentration after mixing), and CHCl3 (100 μL). The CHCl3 was evaporated using a stream of purified argon to form a surfactant−monomer film on the wall of a culture tube. The film was further dried under vacuum for 10 min to remove traces of CHCl3. Each mixture was hydrated in 10 mL 11403


Article

ACS Nano

(11) Wegner, J.; Ceylan, S.; Kirschning, A. Flow Chemistry − a Key Enabling Technology for (Multistep) Organic Synthesis. Adv. Synth. Catal. 2012, 354, 17−57. (12) Adamo, A.; Beingessner, R. L.; Behnam, M.; Chen, J.; Jamison, T. F.; Jensen, K. F.; Monbaliu, J.-C. M.; Myerson, A. S.; Revalor, E. M.; Snead, D. R.; Stelzer, T.; Weeranoppanant, N.; Wong, S. Y.; Zhang, P. On-Demand Continuous-Flow Production of Pharmaceuticals in a Compact, Reconfigurable System. Science 2016, 352, 61−67. (13) Genna, D. T.; Wong-Foy, A. G.; Matzger, A. J.; Sanford, M. S. Heterogenization of Homogeneous Catalysts in Metal−Organic Frameworks Via Cation Exchange. J. Am. Chem. Soc. 2013, 135, 10586−10589. (14) Román-Martínez, M. C.; Salinas-Martínez de Lecea, C. Heterogenization of Homogeneous Catalysts on Carbon Materials. In New and Future Developments in Catalysis; Suib, S. L., Ed.; Elsevier: Amsterdam, 2013; pp 55−78. (15) Corma, A.; Garcia, H. Silica-Bound Homogenous Catalysts as Recoverable and Reusable Catalysts in Organic Synthesis. Adv. Synth. Catal. 2006, 348, 1391−1412. (16) Dondoni, A.; Massi, A. Asymmetric Organocatalysis: From Infancy to Adolescence. Angew. Chem., Int. Ed. 2008, 47, 4638−4660. (17) Yusop, R. M.; Unciti-Broceta, A.; Johansson, E. M. V.; SánchezMartín, R. M.; Bradley, M. Palladium-Mediated Intracellular Chemistry. Nat. Chem. 2011, 3, 239−243. (18) Mehnert, C. P.; Cook, R. A.; Dispenziere, N. C.; Afeworki, M. Supported Ionic Liquid Catalysis − a New Concept for Homogeneous Hydroformylation Catalysis. J. Am. Chem. Soc. 2002, 124, 12932− 12933. (19) Krause, J. O.; Nuyken, O.; Wurst, K.; Buchmeiser, M. R. Synthesis and Reactivity of Homogeneous and Heterogeneous Ruthenium-Based Metathesis Catalysts Containing Electron-Withdrawing Ligands. Chem. - Eur. J. 2004, 10, 777−784. (20) Hlatky, G. G. Heterogeneous Single-Site Catalysts for Olefin Polymerization. Chem. Rev. 2000, 100, 1347−1376. (21) Shylesh, S.; Schünemann, V.; Thiel, W. R. Magnetically Separable Nanocatalysts: Bridges between Homogeneous and Heterogeneous Catalysis. Angew. Chem., Int. Ed. 2010, 49, 3428−3459. (22) Jia, Y.; Shmakov, S. N.; Register, P.; Pinkhassik, E. Size-Selective Yolk-Shell Nanoreactors with Nanometer-Thin Porous Polymer Shells. Chem. - Eur. J. 2015, 21, 12709−12714. (23) Huang, X.; Guo, C.; Zuo, J.; Zheng, N.; Stucky, G. D. An Assembly Route to Inorganic Catalytic Nanoreactors Containing Sub10-Nm Gold Nanoparticles with Anti-Aggregation Properties. Small 2009, 5, 361−365. (24) Liu, J.; Qiao, S. Z.; Budi Hartono, S.; Lu, G. Q. Monodisperse Yolk−Shell Nanoparticles with a Hierarchical Porous Structure for Delivery Vehicles and Nanoreactors. Angew. Chem., Int. Ed. 2010, 49, 4981−4985. (25) Liu, J.; Qiao, S. Z.; Chen, J. S.; Lou, X. W.; Xing, X.; Lu, G. Q. Yolk/Shell Nanoparticles: New Platforms for Nanoreactors, Drug Delivery and Lithium-Ion Batteries. Chem. Commun. 2011, 47, 12578− 12591. (26) Kamata, K.; Lu, Y.; Xia, Y. Synthesis and Characterization of Monodispersed Core−Shell Spherical Colloids with Movable Cores. J. Am. Chem. Soc. 2003, 125, 2384−2385. (27) Lou, X. W.; Archer, L. A.; Yang, Z. Hollow Micro-/ Nanostructures: Synthesis and Applications. Adv. Mater. 2008, 20, 3987−4019. (28) Shmakov, S. N.; Pinkhassik, E. Simultaneous Templating of Polymer Nanocapsules and Entrapped Silver Nanoparticles. Chem. Commun. 2010, 46, 7346−7348. (29) Shchukin, D. G.; Sukhorukov, G. B. Nanoparticle Synthesis in Engineered Organic Nanoscale Reactors. Adv. Mater. 2004, 16, 671− 682. (30) Antipov, A. A.; Sukhorukov, G. B.; Fedutik, Y. A.; Hartmann, J.; Giersig, M.; Möhwald, H. Fabrication of a Novel Type of Metallized Colloids and Hollow Capsules. Langmuir 2002, 18, 6687−6693. (31) Winterhalter, M.; Hilty, C.; Bezrukov, S. M.; Nardin, C.; Meier, W.; Fournier, D. Controlling Membrane Permeability with Bacterial

ASSOCIATED CONTENT S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.6b06735. Materials and Methods Figures S1−S11 Tables S1−S3 (PDF)

AUTHOR INFORMATION Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Sergey A. Dergunov: 0000-0001-6668-6445 Eugene Pinkhassik: 0000-0003-1429-0435 Author Contributions

S.A.D., S.N.S., V.B.B., and E.P. designed the experiments. S.A.D. took the lead in implementing the experimental design. S.A.D., A.T.K., S.N.S., M.D.K., N.E., and M.C.W. performed the experiments. E.P. conceived the project, designed the experiments, and coordinated the research and writing of the manuscript. Notes

The authors declare no competing financial interest.

ACKNOWLEDGMENTS This work was supported by the National Science Foundation (CHE-1522525, CHE-1316680, and CHE-1012951). SEM and TEM studies were performed using the facilities in the UConn/ FEI Center for Advanced Microscopy and Materials Analysis (CAMMA). REFERENCES (1) McMorn, P.; Hutchings, G. J. Heterogeneous Enantioselective Catalysts: Strategies for the Immobilisation of Homogeneous Catalysts. Chem. Soc. Rev. 2004, 33, 108−122. (2) Hagen, J., Industrial Catalysis: A Practical Approach. In Industrial Catalysis, 2nd ed.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2006; p 525. (3) Newman, S. G.; Jensen, K. F. The Role of Flow in Green Chemistry and Engineering. Green Chem. 2013, 15, 1456−1472. (4) Vural Gursel, I.; Noel, T.; Wang, Q.; Hessel, V. Separation/ Recycling Methods for Homogeneous Transition Metal Catalysts in Continuous Flow. Green Chem. 2015, 17, 2012−2026. (5) Jang, M.; Czoschke, N. M.; Lee, S.; Kamens, R. M. Heterogeneous Atmospheric Aerosol Production by Acid-Catalyzed Particle-Phase Reactions. Science 2002, 298, 814−817. (6) Glasnov, T. N.; Findenig, S.; Kappe, C. O. Heterogeneous Versus Homogeneous Palladium Catalysts for Ligandless Mizoroki−Heck Reactions: A Comparison of Batch/Microwave and Continuous-Flow Processing. Chem. - Eur. J. 2009, 15, 1001−1010. (7) Sellin, M. F.; Webb, P. B.; Cole-Hamilton, D. J. Continuous Flow Homogeneous Catalysis: Hydroformylation of Alkenes in Supercritical Fluid-Ionic Liquid Biphasic Mixtures. Chem. Commun. 2001, 781−782. (8) Newton, S.; Carter, C. F.; Pearson, C. M.; de C. Alves, L.; Lange, H.; Thansandote, P.; Ley, S. V. Accelerating Spirocyclic Polyketide Synthesis Using Flow Chemistry. Angew. Chem., Int. Ed. 2014, 53, 4915−4920. (9) McQuade, D. T.; Seeberger, P. H. Applying Flow Chemistry: Methods, Materials, and Multistep Synthesis. J. Org. Chem. 2013, 78, 6384−9. (10) Pastre, J. C.; Browne, D. L.; Ley, S. V. Flow Chemistry Syntheses of Natural Products. Chem. Soc. Rev. 2013, 42, 8849−8869. 11404


Article

ACS Nano Porins: Application to Encapsulated Enzymes. Talanta 2001, 55, 965− 971. (32) Nasseau, M.; Boublik, Y.; Meier, W.; Winterhalter, M.; Fournier, D. Substrate-Permeable Encapsulation of Enzymes Maintains Effective Activity, Stabilizes against Denaturation, and Protects against Proteolytic Degradation. Biotechnol. Bioeng. 2001, 75, 615−618. (33) Patterson, D. P.; Prevelige, P. E.; Douglas, T. Nanoreactors by Programmed Enzyme Encapsulation inside the Capsid of the Bacteriophage P22. ACS Nano 2012, 6, 5000−5009. (34) Ariga, K.; Ji, Q.; Mori, T.; Naito, M.; Yamauchi, Y.; Abe, H.; Hill, J. P. Enzyme Nanoarchitectonics: Organization and Device Application. Chem. Soc. Rev. 2013, 42, 6322−6345. (35) Sakr, O. S.; Borchard, G. Encapsulation of Enzymes in Layer-byLayer (Lbl) Structures: Latest Advances and Applications. Biomacromolecules 2013, 14, 2117−2135. (36) Renggli, K.; Baumann, P.; Langowska, K.; Onaca, O.; Bruns, N.; Meier, W. Selective and Responsive Nanoreactors. Adv. Funct. Mater. 2011, 21, 1206−1205. (37) Donath, E.; Sukhorukov, G. B.; Caruso, F.; Davis, S. A.; Möhwald, H. Novel Hollow Polymer Shells by Colloid-Templated Assembly of Polyelectrolytes. Angew. Chem., Int. Ed. 1998, 37, 2201− 2205. (38) van Leeuwen, P. W. N. M. Homogeneous Catalysis: Understanding the Art; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2004; p 407. (39) Cole-Hamilton, D. J. Homogeneous Catalysis - New Approaches to Catalyst Separation, Recovery, and Recycling. Science 2003, 299, 1702−1706. (40) Che, H.; van Hest, J. C. M. Stimuli-Responsive Polymersomes and Nanoreactors. J. Mater. Chem. B 2016, 4, 4632−4647. (41) Peters, R. J. R. W.; Louzao, I.; van Hest, J. C. M. From Polymeric Nanoreactors to Artificial Organelles. Chemical Science 2012, 3, 335−342. (42) Vriezema, D. M.; Comellas Aragonès, M.; Elemans, J. A. A. W.; Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M. Self-Assembled Nanoreactors. Chem. Rev. 2005, 105, 1445−1490. (43) Yasuhara, K.; Kawataki, T.; Okuda, S.; Oshima, S.; Kikuchi, J. -i. Spontaneously Formed Semipermeable Organic-Inorganic Hybrid Vesicles Permitting Molecular Weight Selective Transmembrane Passage. Chem. Commun. 2013, 49, 665−667. (44) Dergunov, S. A.; Durbin, J.; Pattanaik, S.; Pinkhassik, E. PhMediated Catch and Release of Charged Molecules with Porous Hollow Nanocapsules. J. Am. Chem. Soc. 2014, 136, 2212−5. (45) Dergunov, S. A.; Pinkhassik, E. Functionalization of Imprinted Nanopores in Nanometer-Thin Organic Materials. Angew. Chem., Int. Ed. 2008, 47, 8264−8267. (46) Dergunov, S. A.; Kesterson, K.; Li, W.; Wang, Z.; Pinkhassik, E. Synthesis, Characterization, and Long-Term Stability of Hollow Polymer Nanocapsules with Nanometer-Thin Walls. Macromolecules 2010, 43, 7785−7792. (47) Kim, M. D.; Dergunov, S. A.; Pinkhassik, E. Directed Assembly of Vesicle-Templated Polymer Nanocapsules under near-Physiological Conditions. Langmuir 2015, 31, 2561−2568. (48) Dergunov, S. A.; Miksa, B.; Ganus, B.; Lindner, E.; Pinkhassik, E. Nanocapsules with ‘‘Invisible’’ Walls. Chem. Commun. 2010, 46, 1485−1487. (49) Danila, D. C.; Banner, L. T.; Karimova, E. J.; Tsurkan, L.; Wang, X. Y.; Pinkhassik, E. Directed Assembly of Sub-Nanometer Thin Organic Materials with Programmed-Size Nanopores. Angew. Chem., Int. Ed. 2008, 47, 7036−7039. (50) Maclin, A. Q.; Kim, M. D.; Dergunov, S. A.; Pinkhassik, E.; Lindner, E. Small-Volume Ph Sensing with a Capillary Optode Utilizing Dye-Loaded Porous Nanocapsules in a Hydrogel Matrix. Electroanalysis 2015, 27, 733−744. (51) Dergunov, S. A.; Pinkhassik, E. Synergistic Co-Entrapment and Triggered Release in Hollow Nanocapsules with Uniform Nanopores. J. Am. Chem. Soc. 2011, 133, 19656−19659.

(52) Ehterami, N.; Dergunov, S. A.; Ussipbekova, Y.; Birman, V. B.; Pinkhassik, E. Catalytic Ship-in-a-Bottle Assembly within Hollow Porous Nanocapusles. New J. Chem. 2014, 38, 481−485. (53) Kim, M. D.; Dergunov, S. A.; Lindner, E.; Pinkhassik, E. DyeLoaded Porous Nanocapsules Immobilized in a Permeable Polyvinyl Alcohol Matrix: A Versatile Optical Sensor Platform. Anal. Chem. 2012, 84, 2695−2701. (54) Bolliger, J. L.; Frech, C. M. Highly Convenient, Clean, Fast, and Reliable Sonogashira Coupling Reactions Promoted by Aminophosphine-Based Pincer Complexes of Palladium Performed under Additive- and Amine-Free Reaction Conditions. Adv. Synth. Catal. 2009, 351, 891−902. (55) Bolliger, J. L.; Frech, C. M. The 1,3-Diaminobenzene-Derived Aminophosphine Palladium Pincer Complex {C6h3[Nhp(Piperidinyl)2]2pd(Cl)} − a Highly Active Suzuki−Miyaura Catalyst with Excellent Functional Group Tolerance. Adv. Synth. Catal. 2010, 352, 1075−1080. (56) Bolliger, J. L.; Blacque, O.; Frech, C. M. Rationally Designed Pincer-Type Heck Catalysts Bearing Aminophosphine Substituents: Pdiv Intermediates and Palladium Nanoparticles. Chem. - Eur. J. 2008, 14, 7969−7977. (57) Bolliger, J. L.; Blacque, O.; Frech, C. M. Short, Facile, and HighYielding Synthesis of Extremely Efficient Pincer-Type Suzuki Catalysts Bearing Aminophosphine Substituents. Angew. Chem., Int. Ed. 2007, 46, 6514−6517. (58) Kingston, J. V.; Verkade, J. G. Synthesis and Characterization of R2pn = P(Ibunch2ch2)3n: A New Bulky Electron-Rich Phosphine for Efficient Pd-Assisted Suzuki-Miyaura Cross-Coupling Reactions. J. Org. Chem. 2007, 72, 2816−22. (59) El-Khalafy, S. H.; Hassanein, M. Oxidation of 2-Aminophenol with Molecular Oxygen and Hydrogen Peroxide Catalyzed by Water Soluble Metalloporphyrins. J. Mol. Catal. A: Chem. 2012, 363−364, 148−152. (60) Naik, R.; Joshi, P.; Umbarkar, S.; Deshpande, R. K. Polystyrene Encapsulation of Manganese Porphyrins: Highly Efficient Catalysts for Oxidation of Olefins. Catal. Commun. 2005, 6, 125−129. (61) Dergunov, S. A.; Richter, A. G.; Kim, M. D.; Pingali, S. V.; Urban, V. S.; Pinkhassik, E. Synergistic Self-Assembly of Scaffolds and Building Blocks for Directed Synthesis of Organic Nanomaterials. Chem. Commun. 2013, 49, 11026−11028. (62) Kim, M. D.; Dergunov, S. A.; Richter, A. G.; Durbin, J.; Shmakov, S. N.; Jia, Y.; Kenbeilova, S.; Orazbekuly, Y.; Kengpeiil, A.; Lindner, E.; Pingali, S. V.; Urban, V. S.; Weigand, S.; Pinkhassik, E. Facile Directed Assembly of Hollow Polymer Nanocapsules within Spontaneously Formed Catanionic Surfactant Vesicles. Langmuir 2014, 30, 7061−7069. (63) Hagemeyer, A.; Jandeleit, B.; Liu, Y.; Poojary, D. M.; Turner, H. W.; Volpe, A. F., Jr; Henry Weinberg, W. Applications of Combinatorial Methods in Catalysis. Appl. Catal., A 2001, 221, 23−43. (64) Hackman, B. M.; Lombardi, P. J.; Leighton, J. L. Highly Diastereo- and Enantioselective Reagents for Aldehyde Crotylation. Org. Lett. 2004, 6, 4375−4377. (65) Quebatte, L.; Scopelliti, R.; Severin, K. Combinatorial Catalysis with Bimetallic Complexes: Robust and Efficient Catalysts for AtomTransfer Radical Additions. Angew. Chem., Int. Ed. 2004, 43, 1520− 1524. (66) Serra, J. M.; Corma, A.; Farrusseng, D.; Baumes, L.; Mirodatos, C.; Flego, C.; Perego, C. Styrene from Toluene by Combinatorial Catalysis. Catal. Today 2003, 81, 425−436. (67) Menger, F. M.; Ding, J.; Barragan, V. Combinatorial Catalysis of an Elimination Reaction. J. Org. Chem. 1998, 63, 7578−7579. (68) Burello, E.; Rothenberg, G. Optimal Heck Cross-Coupling Catalysis: A Pseudo-Pharmaceutical Approach. Adv. Synth. Catal. 2003, 345, 1334−1340. (69) Prasad, P. N.; Stevens, E. D. Chemical Perturbation and Lattice Instability in Molecular Crystals. J. Chem. Phys. 1977, 66, 862−867. (70) Feulner, H.; Linti, G.; Nöth, H. Beiträge Zur Chemie Des Bors, 206. Darstellung Und Strukturelle Charakterisierung Der P-Formylbenzolboronsäure. Chem. Ber. 1990, 123, 1841−1843. 11405


Article

ACS Nano (71) Myers, A. W.; Jones, W. D. Steric and Electronic Effects on the Insertion of a Rhodium Phosphine Complex into the C−S Bond of Substituted Dibenzothiophenes. Homogeneous Model for the Hydrodesulfurization Process. Organometallics 1996, 15, 2905−2917. (72) Khorasani, S.; Botes, D. S.; Fernandes, M. A.; Levendis, D. C. A Single-Crystal-to-Single-Crystal Diels-Alder Reaction with Mixed Topochemical and Topotactic Behaviour. CrystEngComm 2015, 17, 8933−8945. (73) Hauw, C. Structure Cristalline De L’ethyl 9-Bromo 10Anthracene. Acta Crystallogr. 1960, 13, 100−104.

11406


Encapsulation of Homogeneous Catalysts in ... - ACS Publications

Recommend Documents