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Challenging the scope of continuous, gas-phase reactions with supported ionic liquid phase (SILP) catalysts—Asymmetric hydrogenation of methyl acetoacetate
Applied Catalysis A: General 399 (2011) 35–41
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Applied Catalysis A: General journal homepage: www.elsevier.com/locate/apcata
Challenging the scope of continuous, gas-phase reactions with supported ionic liquid phase (SILP) catalysts—Asymmetric hydrogenation of methyl acetoacetate Eva Öchsner a , Martin J. Schneider a , Carolin Meyer a , Marco Haumann b , Peter Wasserscheid a,∗ a b
Lehrstuhl für Chemische Reaktionstechnik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, D-91058 Erlangen, Germany Chemical Reaction Engineering, Friedrich-Alexander-University Campus Busan, 1276 Jisa-Dong, Gangseo-Gu, Busan 618-230, Republic of Korea
a r t i c l e
i n f o
Article history: Received 5 January 2011 Received in revised form 8 March 2011 Accepted 18 March 2011 Available online 26 March 2011 Keywords: Asymmetric catalysis Hydrogenation Ionic liquids Ketones Supported catalysts SILP
a b s t r a c t In the last years Supported Ionic Liquid Phase (SILP) catalysis has attracted growing interest for continuous gas phase reactions. The concept combines in a unique manner the advantages of traditional homogeneous and heterogeneous catalysis by making use of the extremely low vapor pressure of an ionic liquid film on support. In this way, continuous gas phase reactions with macroscopically solid but microscopically homogeneous catalyst materials have been successfully realized. However—so far—continuous gas-phase SILP catalysis has only been demonstrated for reactions with relatively simple selectivity problems (such as, regioselectivity, chemoselectivity). This study demonstrates the successful application of a SILP catalyst in continuous gas phase asymmetric hydrogenation. The hydrogenation of methyl acetoacetate (MAA) is presented using an immobilized dibromo[3-(2,5-(2R,5R)-dimethylphospholanyl1)-4-di-o-tolylphosphino-2,5-dimethylthio-phene]-ruthenium (Ru1Br2 ) catalyst. © 2011 Elsevier B.V. All rights reserved.
1. Introduction In 2002, Mehnert et al. for the first time published the immobilization of a transition metal catalyst in a thin film of ionic liquid immersed on a porous inorganic support [1], a concept for which the term “Supported Ionic Liquid Phase” (SILP) catalysis was coined shortly after [2]. Since then, the concept to apply solids coated with an ionic liquid layer as catalyst has attracted steeply growing scientific interest as evidenced by a number of recent reviews on the topic [3]. SILP catalyst materials make use of the fact that many transition metal complexes dissolve well in ionic liquids [4]. To prepare a SILP catalyst, the resulting ionic catalyst solution is dispersed over the high internal surface area of a porous support. Due to the very good wettability of ionic liquids on typical inorganic supports and as a result of strong capillary forces, the thus formed material is a dry solid that still contains the ionic catalyst solution in the form of a thin liquid film in its pores. Consequently, the dissolved catalyst still acts microscopically as a homogeneously dissolved complex in its uniform ionic liquid environment. Macroscopically, however, a solid SILP material is obtained that can be processed in reactor concepts traditionally applied in heterogeneous catalysis, e.g. fixed-bed reactors. A particular strength of the SILP catalyst concept compared to traditional organic/ionic
∗ Corresponding author. Tel.: +49 9131 85 27420; fax: +49 9131 85 27421. E-mail address: [email protected] (P. Wasserscheid). 0926-860X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.apcata.2011.03.038
liquid biphasic catalysis is the large specific exchange surface between the reactant flow and the ionic catalyst solution. Together with typical IL film thicknesses in the lower nanometer range (depending on IL loading and support pore structure) catalytic materials are obtained that provide very short diffusion distances for the reactants through the relatively viscous ionic catalyst solution. In reviewing the recent development of SILP catalyst applications, it is obvious that almost all examples showing long-term active and selective systems were obtained by applying the SILP material in contact with a continuous gas flow of reactants. In this way successful examples of hydroformylation [5], methanol carbonylation [6], hydroamination [7], hydrogenation [8] and ultralow temperature water–gas shift reaction [9] have been achieved. In contrast, the original concept of Mehnert and a number of later publications [10] where the SILP material is contacted with a liquid reaction mixture exhibited intrinsic problems regarding catalyst stability. The latter concern (a) the lack of stability of the liquid film on the support vs. mechanical removal by convection, (b) the leaching of the very thin IL film into the liquid reaction phase and (c) the leaching of the applied transition metal complex into the liquid reaction phase. While the first aspect might be solved by clever support selection, the other two require modifications of the support or addition of ionic tags to the chiral ligand. One attempt to overcome these limitations is the covalent linkage of ionic species to the support [11]. However, this implicates considerable additional synthetic effort to make the SILP slurry system suitable for effective recycling.
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Scheme 1. Hydrogenation of methyl acetoacetate using dibromo[3-(2,5-(2R,5R)-dimethylphospholanyl-1)-4-di-o-tolylphosphino-2,5-dimethyl-thiophene]ruthenium as catalyst.
This contribution describes our recent efforts to explore the applicability and scope of continuous gas-phase SILP catalysis for the asymmetric hydrogenation of prochiral ketones. This reaction is important to produce optically pure alcohols that are applied as building blocks in the production of pharmaceuticals and fine chemicals [12,13]. Traditionally, the reaction is carried out in organic solvents using chiral transition metal complexes [14,15]. Typically, complexes of precious metals, such as Ru, Rh or Ir, are applied together with chiral ligands obtained from multi-step syntheses. Thus, efficient concepts and strategies are highly desirable to recover these expensive catalysts from the reaction mixture [16–18]. In the last decade, many different strategies have been developed to immobilize chiral catalyst complexes for asymmetric hydrogenation to enable easy catalyst recycling and re-use options. Important examples include the covalent anchoring of chiral complexes on polymers [19], silica [20], zirconium phosphonate supports [21], and immobilization concepts with large [22] or polymerized ligands [23]. Furthermore, concepts for a non-covalent immobilization of chiral metal complexes by ion exchange [24] and embedding in membranes [25] are noteworthy. An alternative strategy for the recycling of catalysts for asymmetric hydrogenation is immobilization in a liquid–liquid biphasic system. Water [26], fluorinated phases [27], and ionic liquids (ILs) [28] have been successfully used as immobilization phases. SILP catalysis has only recently been applied to asymmetric hydrogenation in three reported examples dealing with the hydrogenation of 2-cyclohexen-1-one, 1,3-cyclooctadiene and methyl acetoacetate (MAA). All these examples have been studied in slurry phase reactions using the solvents isopropanol, diethyl ether, toluene, or hexane [29]. Moreover, the hydrogenation of acetophenone using either isopropanol [13] or hexane [30] as solvents has been reported. Recently, SILP catalysts have also been used in combination with supercritical carbon dioxide for the enantioselective hydrogenation of dimethyl itaconate [31]. Our paper focuses on the continuous, gas phase, SILP catalyzed, asymmetric hydrogenation of methyl acetoacetate to methyl hydroxybutyrate (see Scheme 1). It builds on our recently reported work on the liquid phase hydrogenation of MAA in mixtures of methanol and ionic liquids [32]. Particular challenges of transferring asymmetric hydrogenation reactions into continuous gas phase systems concern the very unusual reaction conditions (in our case T > 100 ◦ C and residence times < 3 s) that are linked to this synthetic concept. While a continuous gas phase operation provides various advantages over batch-wise processing, it is, however, linked to certain restrictions. All feedstocks and products have to be volatile at reaction conditions. The partial pressure of the reactants has to be low enough in order to avoid condensation in the catalyst bed and therefore high throughput for high-boiling reactants is an issue.
The applied SILP catalyst material consisted of a thin film of 1ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide on silica gel 30 with dibromo[3-(2,5-(2R,5R)-dimethylphospholanyl1)-4-di-o-tolylphosphino-2,5-dimethyl-thiophene]ruthenium dissolved as catalyst therein. Such bidentate ligand modified Ru-complexes are known from the literature to exhibit excellent performance when dissolved in protic solvents such as methanol [33]. Generally, the applied SILP catalysts contained 0.38 mass% Ru dissolved in an ionic liquid volume that corresponded to 80% of the silica pore volume. 2. Experimental 2.1. Chemicals All chemicals were handled using standard Schlenk techniques. Commercially available chemicals were used without further purification. For catalyst preparation, [bis(2methylallyl)(1,5-cyclooctadiene)ruthenium (II)] from Acros and 3-(2,5-(2R,5R)-dimethylphospholanyl-1)-4-di-o-tolylphosphino2,5-dimethylthiophene 1 from Evonik Degussa GmbH were used. The hydrobromic acid (48%) was purchased from Fluka. Commercial dry methanol and acetone from Acros (both 99.9%, water content less than 50 ppm) were used. The silica gel 30 (particle size 0.2–1 mm, pore volume 0.37 cm3 g−1 , Merck KGaA) and silanized silica gel 60 (particle size 0.063–0.2 mm, pore volume 0.54 cm3 g−1 , Merck KGaA) were used as support materials (see Supporting information Table S-1 for further support characterization). The ionic liquid [EMIM][NTf2 ] (H2 O < 500 ppm, Cl− < 100 ppm, Merck KGaA) was used for SILP preparation. For the miniplant runs the carrier gas helium (purity: 4.6) and hydrogen (purity: 5.0) from Linde AG and methyl acetoacetate (purity: 99%) from Aldrich was used. During some experiments—marked with “Oxisorb guard bed for He and H2 ”—the gases were contacted with an OXISORB® (Messer Industriegase GmbH, guaranteed final impurities of oxygen <5 ppm) guard bed prior to addition to the reactor to avoid contamination of the catalyst with oxygen. 2.2. Catalyst preparation The catalyst was prepared in situ according to literature [34]. A mixture of one equivalent of [bis(2-methylallyl)(1,5cyclooctadiene)ruthenium (II)] and two equivalents of the ligand 1 were placed in a Schlenk flask under argon atmosphere. Dry acetone (5 mL) and a methanolic solution (0.29 M) of hydrobromic acid (0.33 mL) were added and the solution was stirred 30 min at room temperature. This solution was heated to 30 ◦ C in an oil bath and the solvent was removed under high vacuum over 1 h. The catalyst dibromo[3-(2,5-(2R,5R)-dimethylphospholanyl-1)-4-
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Fig. 1. Flow scheme of our continuous asymmetric hydrogenation reactor setup equipped with two different reactors: Berty reactor (G) and tubular reactor (H).
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di-o-tolylphosphino-2,5-dimethyl-thiophene]ruthenium (Ru1Br2 ) was obtained as a brown solid powder. To synthesize the SILP catalyst, Ru1Br2 was dissolved in 15 mL dry and degassed methanol. Afterwards the porous support and the ionic liquid were added to the catalyst solution and the mixture was stirred under argon for 90 min. In the next step the solvent methanol was removed by high vacuum treatment and an impregnated support was obtained. The SILP system was stored under argon atmosphere until further use in continuous experiments. 2.3. Continuous gas phase experiments The continuous gas phase experiments were carried out in a fixed bed reactor plant equipped with a Berty-type reactor [35] and a tubular reactor (see Fig. 1). In the Berty reactor (95 mL volume), a gas phase circulation (loop flow) is generated by a turbine on top of the reactor vessel and intensively contacted with the solid SILP catalyst in the reactor. The reactor has been originally developed for kinetic measurements of classical heterogeneous catalysts because of its CSTR-like gradient-free concentration profile. The applied tubular reactor was 30 cm long and had a reaction volume of 35 mL. 1 g of the SILP catalyst was filled into the Berty reactor (G) or in the tubular reactor (H) under helium atmosphere and the complete rig was flushed with helium. The rig was pressurized with 10 bar helium and left under pressure for 15 min while monitoring the pressure. If no pressure drop was observed, the reactor was heated to reaction temperature under a continuous flow of helium. Helium and hydrogen were fed into the rig via mass flow controllers (MFC (A) and (B), Bronkhorst F-201CV-200-RAD-11V/F-201CV-200-RAD-33-V). The carrier gas helium was used to evaporate the substrate MAA in a CEM (controlled evaporation and mixing)-unit (F) (Bronkhorst) and to flush the top section of the Berty reactor. MAA and MeOH were taken from a reservoir in the liquid state and fed into the CEM-unit via LIQUI-flows (D, E) (D: Bronkhorst L13-RAD-11-K-10S, E: Bronkhorst L13V02RAD-11-K-10S). In order to ensure proper mixing, the preheated hydrogen and helium–MAA flows were combined in a mixing unit, which consisted of a 7 mm Swagelok filter filled with glass wool. The gas mixture could then either enter the Berty reactor (G), or enter the tubular reactor (H), or exit the system via a bypass. After the reactor, the gas mixture passed a 7 m filter in order to avoid contamination of the pressure valve with solid particles. A back-pressure regulator valve (I) was used to maintain the desired reaction pressure and outlet gas flow. After the regulator valve the reactants were condensed (J) and samples were collected at regular intervals in an auto-sampler (K). The collected samples were diluted with diethyl ether and afterwards directly analyzed via gas chromatography on a Varian 3900 equipped with a Lipodex E column (length 25 m, inner diameter 0,25 mm, temperature program: 80 ◦ C–20 min isotherm, 80 ◦ C → 200 ◦ C, 10 ◦ C/min, 200 ◦ C–10 min isotherm, carrier gas: 0.4 mL/min helium, detector: FID, 250 ◦ C).
Fig. 2. Conversion vs. time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—variation of IL loading. (Reaction conditions: Berty reactor; L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), 0.38 wt.% Ru, 125 ◦ C, 10 bar, 5000 rpm, 200 NmL/min He, 75 NmL/min H2 , 0.25 g/h MAA, = 2.4 s.)
It is highly noteworthy that the use of the ionic liquid film on the support was found to be absolutely essential to realize any catalytic hydrogenation in the system. By just impregnating the silica with the same Ru-precursor/ligand without ionic liquid, no catalytic activity was observed. Additionally, it was even found that a relatively high degree of pore filling ˛ (˛ = ionic liquid volume/pore volume) with the ionic liquid is beneficial, probably to protect the catalyst from unfavorable chemical interaction with the support surface. High ˛ values result in higher maximum conversions (e.g. ˛ = 1, X = 32.4%) and a slightly shortened activation phase. This result also indicates that rising ionic loading ˛ does not seem to cause visible mass transport limitation effects, a fact that is correlated to the relatively slow catalytic reaction. In contrast to the conversion profiles, the enantiomeric excess profile in the stable phase is not affected by a different IL-loading (ee in the range of 82–85%). After 30 h time-on-stream (TOS) slight changes in enantioselectivity were observed, comparing the different IL loadings. With these first experiments it became evident that the SILP catalyst concept is in principle able to promote asymmetric hydro-
3. Results and discussion The results of our initial hydrogenation runs to test the influence of ionic liquid loading in the Berty reactor are presented in Figs. 2 and 3. In all these experiments, the conversion and ee vs. time-on-stream showed comparable profiles. During the initial activation process conversion and enantiomeric excess increase steadily. The activation process is followed by a period of stable catalytic operation, concerning both selectivity and activity. Subsequently, a deactivation period, in which the enantiomeric excess and conversion decrease and the chiral catalyst degrades over time, is observed.
Fig. 3. ee vs. Time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—variation of IL loading. (Reaction conditions: L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), 0.38 wt.% Ru, 125 ◦ C, 10 bar, 5000 rpm, 200 NmL/min He, 75 NmL/min H2 , 0.25 g/h MAA, = 2.4 s.)
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Table 1 NH3 -TPD measurement of the applied supports. Support
Surface aciditya (mol/g)
Silica 60 (silanized) Silica 30 (calcinated) Silica 30 (dried)
43.23 159.16 276.35
a
Determined by NH3 temperature programmed desorption.
genation in a continuous gas-phase reaction with reasonable enantiomeric excess at 125 ◦ C. The moderate conversions of around 30% have to be rated in the light of the very short catalyst contact time of only 2.4 s (!) in these experiments. Encouraged by these initial results, we investigated in the next step the influence of different silica based support materials characterized by different surface acidities. Table 1 shows the analysis of surface acidity of the applied support materials as determined by NH3 -TPD measurements. The lowest acidity was found for silanized silica in which surface Si–OH groups have been modified by treatment with dichloro-dimethyl-silane. The calcinated silica showed a significantly reduced amount of Si–OH groups compared to dried silica. In the calcinated sample, a large proportion of the Si–OH groups had been removed during the calcination process. The SILP system with the silanized silica support showed low catalytic activity (XMax = 5.8%; see Supporting information, Fig. S-1). In contrast, SILP catalysts immobilized on calcinated or dried silica resulted in better conversions (calcinated SiO2 : XMax = 17.7%, dried SiO2 : XMax = 20.4%). Additionally, the catalyst activation time was significantly shortened by using non-calcinated silica instead of the calcinated support (19 h TOS for full activation vs. 27 h TOS). Wolfson et al. [36] described the positive influence of acids on the catalytic activity of Ru-based asymmetric hydrogenation of MAA and postulated a modification of the general catalytic cycle originally described by Noyori et al. [34,37]. The modified catalytic cycle involves protonation of the carbonyl group of the substrate by an acid prior to hydride insertion. Furthermore, it was stated that the presence of acidic solids in the reaction mixture could enhance the reaction in aprotic solvents. We assume that in our case the acidic Si–OH groups enhance the catalytic activity of the Ruthenium catalyst in the same manner. The enantioselectivity was also influenced by the acidity of the support material in a certain range. Use of the silanized silica support reduced the ee in the time range of stable activity to 70% compared to ee = 85% for calcinated SiO2 (see Supporting information, Fig. S-2). The SILP catalyst with dried silica showed an ee of 80% in the stable activity phase. Further experiments focused on the catalyst activation time and the influence of hydrogen pre-treatment. In this context, a SILP catalyst was flushed with hydrogen for 16 h prior to addition of the MAA substrate. Remarkably, the catalyst activation could indeed be shortened from 27 h to 20 h in this way (see Supporting information, Fig. S-3). This finding hints for an acceleration of the catalyst activation process in a hydrogen saturated system. This accelerated activation process can be explained by the postulated reaction mechanisms of Noyori and Ohkuma [37] and Wolfson et al. [36]. The latter include the conversion of the Ru-dihalide catalyst precursor to the Ru-hydride by reaction with hydrogen followed by elimination of HX. This activation step should be accelerated in a hydrogen saturated SILP-system The following experiments aimed for a better understanding of the reasons for the observed catalyst deactivation in our continuous experiments. To exclude the rather unlikely option that the active Ru-complex leaves the SILP material via the gaseous product phase by sublimation, condensed samples from the continuous reactor were analyzed by inductive coupled plasma-atom emission spec-
Fig. 4. Conversion vs. time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—influence of the additive methanol. (Reaction conditions: Berty reactor; L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), ionic liquid loading ˛ = 0.8, 0.38 wt.% Ru, 125 ◦ C, 10 bar, 5000 rpm, 200 NmL/min He, 75 NmL/min H2 , 0.125 g/h MAA, 0.152 g/h MeOH, = 2.4 s, oxisorb guard bed for He and H2 .)
troscopy (ICP-AES). No leaching of Ru (catalyst), P (ligand) and S (ligand and ionic liquid) was detected in the liquid product (detection limit: 1 ppm). Additionally, leaching of the Br-ligand (resulting in a stability-loss of the transition metal complex) was investigated. During one experiment the product stream was passed through an acidic aqueous solution of silver nitrate, but no precipitation of AgBr was observed. As another potential reason for the observed deactivation behavior, the accumulation of organic compounds or side-products in the SILP catalyst was considered. Analysis of the product stream by means of gas chromatography and mass spectroscopy (GC–MS) indicated the formation of high-boiling side-products such as transesters and aldol adducts in traces. However, largely deactivated SILP catalysts (after 60 h TOS) showed no re-activation after vacuum treatment for 8 h (see Supporting information, Fig. S-4). Accordingly, side-product formation is not the only reason for the observed deactivation. Furthermore, the influence of the reaction temperature on the stability of the SILP catalyst was tested, because the applied transition metal catalyst Ru1Br2 has been originally designed for lower reaction temperatures in liquid phase reactions (50–80 ◦ C) [33]. Noteworthy, time to full activation of the SILP catalyst was strongly depending on the reaction temperature, with 31 h time-on-stream for 125 ◦ C, but 63 h for 105 ◦ C (see Supporting information, Fig. S-5). The period of stable catalytic operation was significantly increased at lower reaction temperatures (35 h TOS at 105 ◦ C compared to 10 h TOS at 125 ◦ C); on the other hand a lower maximum conversion was observed. Remarkably, enantiomeric excess was up to 88% at 105 ◦ C and decreased very slowly over TOS (still 80% ee after 140 h TOS; see Supporting information, Fig. S-6). Ru1Br2 is known to exhibit particularly high activities in alcoholic and protic solvents, especially in methanol [34c]. Additionally, methanol increases the hydrogen solubility in the thin ionic liquid film. Therefore we expected an increase in activity and enantioselectivity by continuously co-feeding of gaseous methanol into our reactor system (for details see Experimental Part). The corresponding conversion/ee vs. time-on-stream profiles of the continuous experiments in the Berty reactor at 125 ◦ C are presented in Figs. 4 and 5.
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Fig. 5. ee vs. Time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—influence of the additive methanol. (Reaction conditions: Berty reactor; L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), ionic liquid loading ˛ = 0.8, 0.38 wt.% Ru, 125 ◦ C, 10 bar, 5000 rpm, 200 NmL/min He, 75 NmL/min H2 , 0.125 g/h MAA, 0.152 g/h MeOH, = 2.4 s, oxisorb guard bed for He and H2 .)
In the experiment with added methanol, catalyst activation was much faster and a higher activity in the period of stable catalytic operation was obtained (XMax = 87.3%). This confirms that the presence of MeOH shows the same activating effects than previously reported for the reaction in organic solvents [34c]. However, the period of stable catalytic operation (in both cases 10 h) was not extended by added methanol. Surprisingly, the decrease in activity with the alcoholic additive is smoother and catalytic activity is observed up to a TOS of 160 h (X = 5.7%). Unexpectedly, the enantiomeric excess is not improved by adding methanol. Additional experiments were carried out at 105 ◦ C to realize longer catalyst stability and higher ee’s. At this temperature, experiments in the Berty reactor (G in Fig. 1) and in the tubular reactor (H in Fig. 1) were compared. The reason for this reactor comparison was our suspicion that the broad residence time distribution (RTD) of the Berty reactor, which is identical to the RTD of an ideal tank reactor, could lead to preferred formation of higher boiling consecutive reaction products (such as transesterification products). The
Fig. 6. Conversion vs. time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—influence of reactor type and the additive methanol. (Reaction conditions: L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), ionic liquid loading ˛ = 0.8, 0.38 wt.% Ru, 105 ◦ C, 10 bar, 5000 rpm (Berty), 200 NmL/min He, 75 NmL/min H2 , 0.125 g/h MAA, 0.152 g/h MeOH, = 2.4 s, oxisorb guard bed for He and H2 .)
Fig. 7. ee vs. Time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—influence of reactor type and temperature. (Reaction conditions: L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), ionic liquid loading ˛ = 0.8, 0.38 wt.% Ru, 105 ◦ C, 10 bar, 5000 rpm (Berty), 200 NmL/min He, 75 NmL/min H2 , 0.125 g/h MAA, 0.152 g/h MeOH, = 2.4 s, oxisorb guard bed for He and H2 .)
latter may fill and block the open pore volume of our SILP catalyst material. Figs. 6 and 7 show the direct comparison of the continuous gas phase hydrogenation in the tubular reactor vs. the same experiments at 105 ◦ C in the Berty reactor. Indeed, a very positive effect of the plug flow reactor on the catalyst stability was observed. After 35 h TOS full catalyst activation was achieved and stable catalytic operation over at least 70 h was realized. Thus, for more than 100.000 residence times 70% conversion (XMax = 74%) with 75–80% ee could be realized at 105 ◦ C reaction temperature. During the total reaction time of the experiment in the tubular reactor a total turnover number of the catalyst of 2500 was achieved. 4. Conclusion In conclusion, we have successfully extended the scope of the SILP catalyst concept to continuous gas phase reaction with a complex, ligand influenced enantioselectivity. In detail, we have demonstrated for the first time a continuous, gas phase, asymmetric hydrogenation reaction. In the hydrogenation of methyl acetoacetate using Ru1Br2 in 1-ethyl-3-methylimidazolium bis(trifluoromethyl-sulfonyl)imide on silica 30, an enantiomeric excess in the range of 65–82% ee could be obtained for more than 100 h time-on-stream continuous operation (experiment at 105◦ in the plug flow reactor). Moreover, it was demonstrated, that the ionic liquid film on the support is absolutely essential for catalytic activity in the system and a relatively high degree of pore filling with the ionic liquid is beneficial. The catalyst activation times can be shortened by using non-calcinated silica instead of the calcinated support and by hydrogen pre-treatment. The combination of thermal degradation of the SILP catalyst and the formation of high-boiling side-products were identified as the main threats for catalyst stability. By changing the reactor from a back-mixed Bertytype to a tubular reactor, the accumulation of side-products in the SILP catalyst could be significantly reduced and much higher catalyst stability was observed. Remarkably, our continuous gas phase hydrogenation has been achieved for a substrate of relatively low volatility by using helium as carrier gas in the reactor. Based on these results, we expect that the use of SILP catalyst technology in continuous gas phase reactions can be in principal transferred to any substrate that has enough vapor pressure to be analyzed by gas chromatography. SILP catalyst materials in continuous gas-phase contact offer a very sim-
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ple way of catalyst/product separation and allow application of well-known catalytic systems without additional synthetic effort for ligand modification. The finding of this study that even complex ligand induced selectivities can be tackled by this continuous gas-phase technology should open further fields of application. Acknowledgements We gratefully thank Dr. Renat Kadyrov (Evonik Degussa GmbH) for fruitful discussions on ligand selection and for providing ligand samples. The authors acknowledge support by the Federal Ministery of Education and Research (BMBF), the Deutsche Forschungsgemeinschaft within the Erlangen Excellence Cluster “Engineering of Advanced Materials and SYNFLOW within the EU’s Seventh Framework Programme“. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.apcata.2011.03.038. References [1] C.P. Mehnert, R.A. Cook, N.C. Dispenziere, M. Afeworki, J. Am. Chem. Soc. 124 (2002) 12932–12933. [2] (a) A. Riisager, P. Wasserscheid, R. van Hal, R. Fehrmann, Catal. Lett. 90 (2003) 149–153; (b) A. Riisager, P. Wasserscheid, R. van Hal, R. Fehrmann, J. Catal. 219 (2) (2003) 452–455. [3] (a) P. Tundo, A. Perosa, Chem. Soc. Rev. 36 (2007) 532–550; (b) Y. Gu, G. Li, Adv. Synth. Catal. 351 (2009) 817–847; (c) S. Werner, M. Haumann, P. Wasserscheid, Annu. Rev. Chem. Biomol. Eng. 1 (2010) 203–230; (d) C. Van Doorslaer, J. Wahlen, P. Mertens, K. Binnemans, D. De Vos, Dalton Trans. 39 (2010) 8377–8390. [4] P. Wasserscheid, P.S. Schulz, T. Welton (Eds.), Ionic Liquids in Synthesis, 2nd ed., Wiley-VCH, Weinheim, 2007, pp. 369–463. [5] (a) A. Riisager, R. Fehrmann, S. Flicker, R. van Hal, M. Haumann, P. Wasserscheid, Angew. Chem. Int. Ed. 44 (2005) 815–819; (b) A. Riisager, R. Fehrmann, M. Haumann, P. Wasserscheid, Eur. J. Inorg. Chem. (2006) 695–706; (c) A. Riisager, R. Fehrmann, M. Haumann, B.S.K. Gorle, P. Wasserscheid, Ind. Eng. Chem. Res. 44 (2005) 9853–9859; (d) A. Riisager, R. Fehrmann, M. Haumann, P. Wasserscheid, Top. Catal. 40 (1–4) (2006) 91–102; (e) M. Haumann, K. Dentler, J. Joni, A. Riisager, P. Wasserscheid, Adv. Synth. Catal. 349 (3) (2007) 425–431. [6] A. Riisager, B. Jørgensen, P. Wasserscheid, R. Fehrmann, Chem. Commun. (2006) 994–996. [7] O. Jimenez, T.E. Müller, C. Sievers, A. Spirkl, J.A. Lercher, Chem. Commun. (2006) 2974–2976. [8] M. Ruta, G. Laurenczy, P.J. Dyson, L. Kiwi-Minsker, J. Phys. Chem. C 112 (2008) 17814–17819. [9] S. Werner, N. Szesni, A. Bittermann, M.J. Schneider, P. Härter, M. Haumann, P. Wasserscheid, Appl. Catal. A 377 (2010) 70–75.
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[10] (a) H. Hagiwara, Y. Sugawara, T. Hoshi, T. Suzuki, Chem. Commun. (2005) 2942; (b) H. Hagiwara, K.H. Ko, T. Hoshi, T. Suzuki, Chem. Commun. (2007) 2838; (c) C. Brochwitz, A. Feldhoff, U. Kunz, M. Vaultier, A. Kirschning, Lett. Org. Chem. 3 (2006) 442. [11] (a) C.P. Mehnert, Chem. Eur. J. 11 (2005) 50–56; (b) B. Gadenne, P. Hesemann, J.J.E. Moreau, Chem. Commun. (2004) 1768–1769. [12] T. Ohkuma, H. Ooka, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 117 (9) (1995) 2675–2676. [13] L.-L. Lou, X. Peng, K. Yu, S. Liu, Catal. Commun. 9 (2008) 1891–1893. [14] W. Tang, X. Zhang, Chem. Rev. 103 (2003) 3029–3069. [15] W.S. Knowles, Angew. Chem. Int. Ed. 41 (2002) 1998–2007 (nobel lecture). [16] M. Heitbaum, F. Glorius, I. Escher, Angew. Chem. Int. Ed. 45 (2006) 4732–4762. [17] A.F. Trindade, P.M.P. Gois, C.A.M. Afonso, Chem. Rev. 109 (2009) 418–514. [18] J.M. Fraile, J.I. Graci, J.A. Mayoral, Chem. Rev. 109 (2009) 360–417. [19] (a) D.J. Bayston, J.L. Fraser, M.R. Ashton, A.D. Baxter, M.E.C. Polywka, E. Moses, J. Org. Chem. 63 (1998) 3137–3140; (b) T. Ohkuma, H. Takeno, Y. Honda, R. Noyori, Adv. Synth. Catal. 343 (2001) 369–375. [20] (a) P.N. Liu, J.G. Deng, Y.Q. Tu, S.H. Wang, Chem. Commun. (2004) 2070–2071; (b) B. Kesanli, W. Lin, Chem. Commun. (2004) 2284–2285. [21] A. Hu, H.L. Ngo, W. Lin, J. Am. Chem. Soc. 125 (2003) 11490–11491. [22] C. Köllner, B. Pugin, A. Togni, J. Am. Chem. Soc. 120 (1998) 10274–10275. [23] R.T. Halle, E. Schulz, M. Spagnol, M. Lemaire, Tetrahedron Lett. 41 (2000) 3323–3326. [24] W.P. Hems, P. McMorn, S. Riddel, S. Watson, F.E. Hancock, G.J. Hutchings, Org. Biomol. Chem. 3 (2005) 1547–1550. [25] D. Tas, C. Thoelen, I.F.J. Vankelecom, P.A. Jacobs, Chem. Commun. (1997) 2323–2324. [26] S. Zeror, J. Collin, J.C. Fiaud, L.A. Zouioueche, J. Mol. Catal. A: Chem. 256 (2006) 85–89. [27] E. de Wolf, B.-J. Deelman, in: J.G. de Vries, C.J. Elsevier (Eds.), Handbook of Homogeneous Hydrogenation, Wiley-VCH, Weinheim, 2007, pp. 1377–1388. [28] P. Wasserscheid, P. Schulz, in: J.G. de Vries, C.J. Elsevier (Eds.), Handbook of Homogeneous Hydrogenation, Wiley-VCH, Weinheim, 2006, pp. 1389–1421. [29] A. Wolfson, I.F.J. Vankelecom, P.A. Jacobs, Tetrahedron Lett. 44 (2003) 1195–1198. [30] K.L. Fow, S. Jaenicke, T.E. Müller, C. Sievers, J. Mol. Catal. A: Chem. 279 (2008) 239–247. [31] U. Hintermair, T. Höfener, T. Pullmann, G. Franciò, W. Leitner, ChemCatChem 2 (2010) 150–154. [32] (a) E. Öchsner, K. Schneiders, K. Junge, M. Beller, P. Wasserscheid, Appl. Catal. A 364 (1–2) (2009) 8–14; (b) T. Floris, P. Kluson, M.J. Muldoon, H. Pelantova, Catal. Lett. 134 (2010) 279–287. [33] (a) R. Kadyrov, Chim. Oggi 26 (5) (2008) 41–42; (b) R. Kadyrov, J. Tarabocchia, M.L. Prunier (Eds.), Catalysis of Organic Reactions, CRC Press, Boca Raton, 2009, pp. 211–216; (c) R. Kadyrov, R.M. Koenigs, C. Brinkmann, D. Voigtlaender, M. Rueping, Angew. Chem. Int. Ed. 48 (2009) 7556–7559. [34] (a) R. Noyori, T. Ohkuma, M. Kitamura, H. Takaya, N. Sayo, H. Kumobayashi, S. Akutagawa, J. Am. Chem. Soc. 109 (1987) 5856–5858; (b) M. Kitamura, T. Ohkuma, S. Inoue, N. Sayo, H. Kumobayashi, S. Akutagawa, T. Ohta, H. Takaya, R. Noyori, J. Am. Chem. Soc. 110 (1988) 629–631. [35] J.M. Berty, Chem. Eng. Prog. 70 (5) (1974) 78–84. [36] A. Wolfson, I.F.J. Vankelecom, S. Geresh, P.A. Jacob, J. Mol. Catal. A: Chem. (2004) 21–26. [37] (a) R. Noyori, T. Ohkuma, Angew. Chem. Int. Ed. 40 (2001) 40–73; (b) R. Noyori, M. Kitamura, T. Ohkuma, Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 5356–5362.
Contents lists available at ScienceDirect
Applied Catalysis A: General journal homepage: www.elsevier.com/locate/apcata
Challenging the scope of continuous, gas-phase reactions with supported ionic liquid phase (SILP) catalysts—Asymmetric hydrogenation of methyl acetoacetate Eva Öchsner a , Martin J. Schneider a , Carolin Meyer a , Marco Haumann b , Peter Wasserscheid a,∗ a b
Lehrstuhl für Chemische Reaktionstechnik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, D-91058 Erlangen, Germany Chemical Reaction Engineering, Friedrich-Alexander-University Campus Busan, 1276 Jisa-Dong, Gangseo-Gu, Busan 618-230, Republic of Korea
a r t i c l e
i n f o
Article history: Received 5 January 2011 Received in revised form 8 March 2011 Accepted 18 March 2011 Available online 26 March 2011 Keywords: Asymmetric catalysis Hydrogenation Ionic liquids Ketones Supported catalysts SILP
a b s t r a c t In the last years Supported Ionic Liquid Phase (SILP) catalysis has attracted growing interest for continuous gas phase reactions. The concept combines in a unique manner the advantages of traditional homogeneous and heterogeneous catalysis by making use of the extremely low vapor pressure of an ionic liquid film on support. In this way, continuous gas phase reactions with macroscopically solid but microscopically homogeneous catalyst materials have been successfully realized. However—so far—continuous gas-phase SILP catalysis has only been demonstrated for reactions with relatively simple selectivity problems (such as, regioselectivity, chemoselectivity). This study demonstrates the successful application of a SILP catalyst in continuous gas phase asymmetric hydrogenation. The hydrogenation of methyl acetoacetate (MAA) is presented using an immobilized dibromo[3-(2,5-(2R,5R)-dimethylphospholanyl1)-4-di-o-tolylphosphino-2,5-dimethylthio-phene]-ruthenium (Ru1Br2 ) catalyst. © 2011 Elsevier B.V. All rights reserved.
1. Introduction In 2002, Mehnert et al. for the first time published the immobilization of a transition metal catalyst in a thin film of ionic liquid immersed on a porous inorganic support [1], a concept for which the term “Supported Ionic Liquid Phase” (SILP) catalysis was coined shortly after [2]. Since then, the concept to apply solids coated with an ionic liquid layer as catalyst has attracted steeply growing scientific interest as evidenced by a number of recent reviews on the topic [3]. SILP catalyst materials make use of the fact that many transition metal complexes dissolve well in ionic liquids [4]. To prepare a SILP catalyst, the resulting ionic catalyst solution is dispersed over the high internal surface area of a porous support. Due to the very good wettability of ionic liquids on typical inorganic supports and as a result of strong capillary forces, the thus formed material is a dry solid that still contains the ionic catalyst solution in the form of a thin liquid film in its pores. Consequently, the dissolved catalyst still acts microscopically as a homogeneously dissolved complex in its uniform ionic liquid environment. Macroscopically, however, a solid SILP material is obtained that can be processed in reactor concepts traditionally applied in heterogeneous catalysis, e.g. fixed-bed reactors. A particular strength of the SILP catalyst concept compared to traditional organic/ionic
∗ Corresponding author. Tel.: +49 9131 85 27420; fax: +49 9131 85 27421. E-mail address: [email protected] (P. Wasserscheid). 0926-860X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.apcata.2011.03.038
liquid biphasic catalysis is the large specific exchange surface between the reactant flow and the ionic catalyst solution. Together with typical IL film thicknesses in the lower nanometer range (depending on IL loading and support pore structure) catalytic materials are obtained that provide very short diffusion distances for the reactants through the relatively viscous ionic catalyst solution. In reviewing the recent development of SILP catalyst applications, it is obvious that almost all examples showing long-term active and selective systems were obtained by applying the SILP material in contact with a continuous gas flow of reactants. In this way successful examples of hydroformylation [5], methanol carbonylation [6], hydroamination [7], hydrogenation [8] and ultralow temperature water–gas shift reaction [9] have been achieved. In contrast, the original concept of Mehnert and a number of later publications [10] where the SILP material is contacted with a liquid reaction mixture exhibited intrinsic problems regarding catalyst stability. The latter concern (a) the lack of stability of the liquid film on the support vs. mechanical removal by convection, (b) the leaching of the very thin IL film into the liquid reaction phase and (c) the leaching of the applied transition metal complex into the liquid reaction phase. While the first aspect might be solved by clever support selection, the other two require modifications of the support or addition of ionic tags to the chiral ligand. One attempt to overcome these limitations is the covalent linkage of ionic species to the support [11]. However, this implicates considerable additional synthetic effort to make the SILP slurry system suitable for effective recycling.
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Scheme 1. Hydrogenation of methyl acetoacetate using dibromo[3-(2,5-(2R,5R)-dimethylphospholanyl-1)-4-di-o-tolylphosphino-2,5-dimethyl-thiophene]ruthenium as catalyst.
This contribution describes our recent efforts to explore the applicability and scope of continuous gas-phase SILP catalysis for the asymmetric hydrogenation of prochiral ketones. This reaction is important to produce optically pure alcohols that are applied as building blocks in the production of pharmaceuticals and fine chemicals [12,13]. Traditionally, the reaction is carried out in organic solvents using chiral transition metal complexes [14,15]. Typically, complexes of precious metals, such as Ru, Rh or Ir, are applied together with chiral ligands obtained from multi-step syntheses. Thus, efficient concepts and strategies are highly desirable to recover these expensive catalysts from the reaction mixture [16–18]. In the last decade, many different strategies have been developed to immobilize chiral catalyst complexes for asymmetric hydrogenation to enable easy catalyst recycling and re-use options. Important examples include the covalent anchoring of chiral complexes on polymers [19], silica [20], zirconium phosphonate supports [21], and immobilization concepts with large [22] or polymerized ligands [23]. Furthermore, concepts for a non-covalent immobilization of chiral metal complexes by ion exchange [24] and embedding in membranes [25] are noteworthy. An alternative strategy for the recycling of catalysts for asymmetric hydrogenation is immobilization in a liquid–liquid biphasic system. Water [26], fluorinated phases [27], and ionic liquids (ILs) [28] have been successfully used as immobilization phases. SILP catalysis has only recently been applied to asymmetric hydrogenation in three reported examples dealing with the hydrogenation of 2-cyclohexen-1-one, 1,3-cyclooctadiene and methyl acetoacetate (MAA). All these examples have been studied in slurry phase reactions using the solvents isopropanol, diethyl ether, toluene, or hexane [29]. Moreover, the hydrogenation of acetophenone using either isopropanol [13] or hexane [30] as solvents has been reported. Recently, SILP catalysts have also been used in combination with supercritical carbon dioxide for the enantioselective hydrogenation of dimethyl itaconate [31]. Our paper focuses on the continuous, gas phase, SILP catalyzed, asymmetric hydrogenation of methyl acetoacetate to methyl hydroxybutyrate (see Scheme 1). It builds on our recently reported work on the liquid phase hydrogenation of MAA in mixtures of methanol and ionic liquids [32]. Particular challenges of transferring asymmetric hydrogenation reactions into continuous gas phase systems concern the very unusual reaction conditions (in our case T > 100 ◦ C and residence times < 3 s) that are linked to this synthetic concept. While a continuous gas phase operation provides various advantages over batch-wise processing, it is, however, linked to certain restrictions. All feedstocks and products have to be volatile at reaction conditions. The partial pressure of the reactants has to be low enough in order to avoid condensation in the catalyst bed and therefore high throughput for high-boiling reactants is an issue.
The applied SILP catalyst material consisted of a thin film of 1ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide on silica gel 30 with dibromo[3-(2,5-(2R,5R)-dimethylphospholanyl1)-4-di-o-tolylphosphino-2,5-dimethyl-thiophene]ruthenium dissolved as catalyst therein. Such bidentate ligand modified Ru-complexes are known from the literature to exhibit excellent performance when dissolved in protic solvents such as methanol [33]. Generally, the applied SILP catalysts contained 0.38 mass% Ru dissolved in an ionic liquid volume that corresponded to 80% of the silica pore volume. 2. Experimental 2.1. Chemicals All chemicals were handled using standard Schlenk techniques. Commercially available chemicals were used without further purification. For catalyst preparation, [bis(2methylallyl)(1,5-cyclooctadiene)ruthenium (II)] from Acros and 3-(2,5-(2R,5R)-dimethylphospholanyl-1)-4-di-o-tolylphosphino2,5-dimethylthiophene 1 from Evonik Degussa GmbH were used. The hydrobromic acid (48%) was purchased from Fluka. Commercial dry methanol and acetone from Acros (both 99.9%, water content less than 50 ppm) were used. The silica gel 30 (particle size 0.2–1 mm, pore volume 0.37 cm3 g−1 , Merck KGaA) and silanized silica gel 60 (particle size 0.063–0.2 mm, pore volume 0.54 cm3 g−1 , Merck KGaA) were used as support materials (see Supporting information Table S-1 for further support characterization). The ionic liquid [EMIM][NTf2 ] (H2 O < 500 ppm, Cl− < 100 ppm, Merck KGaA) was used for SILP preparation. For the miniplant runs the carrier gas helium (purity: 4.6) and hydrogen (purity: 5.0) from Linde AG and methyl acetoacetate (purity: 99%) from Aldrich was used. During some experiments—marked with “Oxisorb guard bed for He and H2 ”—the gases were contacted with an OXISORB® (Messer Industriegase GmbH, guaranteed final impurities of oxygen <5 ppm) guard bed prior to addition to the reactor to avoid contamination of the catalyst with oxygen. 2.2. Catalyst preparation The catalyst was prepared in situ according to literature [34]. A mixture of one equivalent of [bis(2-methylallyl)(1,5cyclooctadiene)ruthenium (II)] and two equivalents of the ligand 1 were placed in a Schlenk flask under argon atmosphere. Dry acetone (5 mL) and a methanolic solution (0.29 M) of hydrobromic acid (0.33 mL) were added and the solution was stirred 30 min at room temperature. This solution was heated to 30 ◦ C in an oil bath and the solvent was removed under high vacuum over 1 h. The catalyst dibromo[3-(2,5-(2R,5R)-dimethylphospholanyl-1)-4-
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Fig. 1. Flow scheme of our continuous asymmetric hydrogenation reactor setup equipped with two different reactors: Berty reactor (G) and tubular reactor (H).
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di-o-tolylphosphino-2,5-dimethyl-thiophene]ruthenium (Ru1Br2 ) was obtained as a brown solid powder. To synthesize the SILP catalyst, Ru1Br2 was dissolved in 15 mL dry and degassed methanol. Afterwards the porous support and the ionic liquid were added to the catalyst solution and the mixture was stirred under argon for 90 min. In the next step the solvent methanol was removed by high vacuum treatment and an impregnated support was obtained. The SILP system was stored under argon atmosphere until further use in continuous experiments. 2.3. Continuous gas phase experiments The continuous gas phase experiments were carried out in a fixed bed reactor plant equipped with a Berty-type reactor [35] and a tubular reactor (see Fig. 1). In the Berty reactor (95 mL volume), a gas phase circulation (loop flow) is generated by a turbine on top of the reactor vessel and intensively contacted with the solid SILP catalyst in the reactor. The reactor has been originally developed for kinetic measurements of classical heterogeneous catalysts because of its CSTR-like gradient-free concentration profile. The applied tubular reactor was 30 cm long and had a reaction volume of 35 mL. 1 g of the SILP catalyst was filled into the Berty reactor (G) or in the tubular reactor (H) under helium atmosphere and the complete rig was flushed with helium. The rig was pressurized with 10 bar helium and left under pressure for 15 min while monitoring the pressure. If no pressure drop was observed, the reactor was heated to reaction temperature under a continuous flow of helium. Helium and hydrogen were fed into the rig via mass flow controllers (MFC (A) and (B), Bronkhorst F-201CV-200-RAD-11V/F-201CV-200-RAD-33-V). The carrier gas helium was used to evaporate the substrate MAA in a CEM (controlled evaporation and mixing)-unit (F) (Bronkhorst) and to flush the top section of the Berty reactor. MAA and MeOH were taken from a reservoir in the liquid state and fed into the CEM-unit via LIQUI-flows (D, E) (D: Bronkhorst L13-RAD-11-K-10S, E: Bronkhorst L13V02RAD-11-K-10S). In order to ensure proper mixing, the preheated hydrogen and helium–MAA flows were combined in a mixing unit, which consisted of a 7 mm Swagelok filter filled with glass wool. The gas mixture could then either enter the Berty reactor (G), or enter the tubular reactor (H), or exit the system via a bypass. After the reactor, the gas mixture passed a 7 m filter in order to avoid contamination of the pressure valve with solid particles. A back-pressure regulator valve (I) was used to maintain the desired reaction pressure and outlet gas flow. After the regulator valve the reactants were condensed (J) and samples were collected at regular intervals in an auto-sampler (K). The collected samples were diluted with diethyl ether and afterwards directly analyzed via gas chromatography on a Varian 3900 equipped with a Lipodex E column (length 25 m, inner diameter 0,25 mm, temperature program: 80 ◦ C–20 min isotherm, 80 ◦ C → 200 ◦ C, 10 ◦ C/min, 200 ◦ C–10 min isotherm, carrier gas: 0.4 mL/min helium, detector: FID, 250 ◦ C).
Fig. 2. Conversion vs. time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—variation of IL loading. (Reaction conditions: Berty reactor; L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), 0.38 wt.% Ru, 125 ◦ C, 10 bar, 5000 rpm, 200 NmL/min He, 75 NmL/min H2 , 0.25 g/h MAA, = 2.4 s.)
It is highly noteworthy that the use of the ionic liquid film on the support was found to be absolutely essential to realize any catalytic hydrogenation in the system. By just impregnating the silica with the same Ru-precursor/ligand without ionic liquid, no catalytic activity was observed. Additionally, it was even found that a relatively high degree of pore filling ˛ (˛ = ionic liquid volume/pore volume) with the ionic liquid is beneficial, probably to protect the catalyst from unfavorable chemical interaction with the support surface. High ˛ values result in higher maximum conversions (e.g. ˛ = 1, X = 32.4%) and a slightly shortened activation phase. This result also indicates that rising ionic loading ˛ does not seem to cause visible mass transport limitation effects, a fact that is correlated to the relatively slow catalytic reaction. In contrast to the conversion profiles, the enantiomeric excess profile in the stable phase is not affected by a different IL-loading (ee in the range of 82–85%). After 30 h time-on-stream (TOS) slight changes in enantioselectivity were observed, comparing the different IL loadings. With these first experiments it became evident that the SILP catalyst concept is in principle able to promote asymmetric hydro-
3. Results and discussion The results of our initial hydrogenation runs to test the influence of ionic liquid loading in the Berty reactor are presented in Figs. 2 and 3. In all these experiments, the conversion and ee vs. time-on-stream showed comparable profiles. During the initial activation process conversion and enantiomeric excess increase steadily. The activation process is followed by a period of stable catalytic operation, concerning both selectivity and activity. Subsequently, a deactivation period, in which the enantiomeric excess and conversion decrease and the chiral catalyst degrades over time, is observed.
Fig. 3. ee vs. Time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—variation of IL loading. (Reaction conditions: L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), 0.38 wt.% Ru, 125 ◦ C, 10 bar, 5000 rpm, 200 NmL/min He, 75 NmL/min H2 , 0.25 g/h MAA, = 2.4 s.)
E. Öchsner et al. / Applied Catalysis A: General 399 (2011) 35–41
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Table 1 NH3 -TPD measurement of the applied supports. Support
Surface aciditya (mol/g)
Silica 60 (silanized) Silica 30 (calcinated) Silica 30 (dried)
43.23 159.16 276.35
a
Determined by NH3 temperature programmed desorption.
genation in a continuous gas-phase reaction with reasonable enantiomeric excess at 125 ◦ C. The moderate conversions of around 30% have to be rated in the light of the very short catalyst contact time of only 2.4 s (!) in these experiments. Encouraged by these initial results, we investigated in the next step the influence of different silica based support materials characterized by different surface acidities. Table 1 shows the analysis of surface acidity of the applied support materials as determined by NH3 -TPD measurements. The lowest acidity was found for silanized silica in which surface Si–OH groups have been modified by treatment with dichloro-dimethyl-silane. The calcinated silica showed a significantly reduced amount of Si–OH groups compared to dried silica. In the calcinated sample, a large proportion of the Si–OH groups had been removed during the calcination process. The SILP system with the silanized silica support showed low catalytic activity (XMax = 5.8%; see Supporting information, Fig. S-1). In contrast, SILP catalysts immobilized on calcinated or dried silica resulted in better conversions (calcinated SiO2 : XMax = 17.7%, dried SiO2 : XMax = 20.4%). Additionally, the catalyst activation time was significantly shortened by using non-calcinated silica instead of the calcinated support (19 h TOS for full activation vs. 27 h TOS). Wolfson et al. [36] described the positive influence of acids on the catalytic activity of Ru-based asymmetric hydrogenation of MAA and postulated a modification of the general catalytic cycle originally described by Noyori et al. [34,37]. The modified catalytic cycle involves protonation of the carbonyl group of the substrate by an acid prior to hydride insertion. Furthermore, it was stated that the presence of acidic solids in the reaction mixture could enhance the reaction in aprotic solvents. We assume that in our case the acidic Si–OH groups enhance the catalytic activity of the Ruthenium catalyst in the same manner. The enantioselectivity was also influenced by the acidity of the support material in a certain range. Use of the silanized silica support reduced the ee in the time range of stable activity to 70% compared to ee = 85% for calcinated SiO2 (see Supporting information, Fig. S-2). The SILP catalyst with dried silica showed an ee of 80% in the stable activity phase. Further experiments focused on the catalyst activation time and the influence of hydrogen pre-treatment. In this context, a SILP catalyst was flushed with hydrogen for 16 h prior to addition of the MAA substrate. Remarkably, the catalyst activation could indeed be shortened from 27 h to 20 h in this way (see Supporting information, Fig. S-3). This finding hints for an acceleration of the catalyst activation process in a hydrogen saturated system. This accelerated activation process can be explained by the postulated reaction mechanisms of Noyori and Ohkuma [37] and Wolfson et al. [36]. The latter include the conversion of the Ru-dihalide catalyst precursor to the Ru-hydride by reaction with hydrogen followed by elimination of HX. This activation step should be accelerated in a hydrogen saturated SILP-system The following experiments aimed for a better understanding of the reasons for the observed catalyst deactivation in our continuous experiments. To exclude the rather unlikely option that the active Ru-complex leaves the SILP material via the gaseous product phase by sublimation, condensed samples from the continuous reactor were analyzed by inductive coupled plasma-atom emission spec-
Fig. 4. Conversion vs. time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—influence of the additive methanol. (Reaction conditions: Berty reactor; L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), ionic liquid loading ˛ = 0.8, 0.38 wt.% Ru, 125 ◦ C, 10 bar, 5000 rpm, 200 NmL/min He, 75 NmL/min H2 , 0.125 g/h MAA, 0.152 g/h MeOH, = 2.4 s, oxisorb guard bed for He and H2 .)
troscopy (ICP-AES). No leaching of Ru (catalyst), P (ligand) and S (ligand and ionic liquid) was detected in the liquid product (detection limit: 1 ppm). Additionally, leaching of the Br-ligand (resulting in a stability-loss of the transition metal complex) was investigated. During one experiment the product stream was passed through an acidic aqueous solution of silver nitrate, but no precipitation of AgBr was observed. As another potential reason for the observed deactivation behavior, the accumulation of organic compounds or side-products in the SILP catalyst was considered. Analysis of the product stream by means of gas chromatography and mass spectroscopy (GC–MS) indicated the formation of high-boiling side-products such as transesters and aldol adducts in traces. However, largely deactivated SILP catalysts (after 60 h TOS) showed no re-activation after vacuum treatment for 8 h (see Supporting information, Fig. S-4). Accordingly, side-product formation is not the only reason for the observed deactivation. Furthermore, the influence of the reaction temperature on the stability of the SILP catalyst was tested, because the applied transition metal catalyst Ru1Br2 has been originally designed for lower reaction temperatures in liquid phase reactions (50–80 ◦ C) [33]. Noteworthy, time to full activation of the SILP catalyst was strongly depending on the reaction temperature, with 31 h time-on-stream for 125 ◦ C, but 63 h for 105 ◦ C (see Supporting information, Fig. S-5). The period of stable catalytic operation was significantly increased at lower reaction temperatures (35 h TOS at 105 ◦ C compared to 10 h TOS at 125 ◦ C); on the other hand a lower maximum conversion was observed. Remarkably, enantiomeric excess was up to 88% at 105 ◦ C and decreased very slowly over TOS (still 80% ee after 140 h TOS; see Supporting information, Fig. S-6). Ru1Br2 is known to exhibit particularly high activities in alcoholic and protic solvents, especially in methanol [34c]. Additionally, methanol increases the hydrogen solubility in the thin ionic liquid film. Therefore we expected an increase in activity and enantioselectivity by continuously co-feeding of gaseous methanol into our reactor system (for details see Experimental Part). The corresponding conversion/ee vs. time-on-stream profiles of the continuous experiments in the Berty reactor at 125 ◦ C are presented in Figs. 4 and 5.
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E. Öchsner et al. / Applied Catalysis A: General 399 (2011) 35–41
Fig. 5. ee vs. Time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—influence of the additive methanol. (Reaction conditions: Berty reactor; L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), ionic liquid loading ˛ = 0.8, 0.38 wt.% Ru, 125 ◦ C, 10 bar, 5000 rpm, 200 NmL/min He, 75 NmL/min H2 , 0.125 g/h MAA, 0.152 g/h MeOH, = 2.4 s, oxisorb guard bed for He and H2 .)
In the experiment with added methanol, catalyst activation was much faster and a higher activity in the period of stable catalytic operation was obtained (XMax = 87.3%). This confirms that the presence of MeOH shows the same activating effects than previously reported for the reaction in organic solvents [34c]. However, the period of stable catalytic operation (in both cases 10 h) was not extended by added methanol. Surprisingly, the decrease in activity with the alcoholic additive is smoother and catalytic activity is observed up to a TOS of 160 h (X = 5.7%). Unexpectedly, the enantiomeric excess is not improved by adding methanol. Additional experiments were carried out at 105 ◦ C to realize longer catalyst stability and higher ee’s. At this temperature, experiments in the Berty reactor (G in Fig. 1) and in the tubular reactor (H in Fig. 1) were compared. The reason for this reactor comparison was our suspicion that the broad residence time distribution (RTD) of the Berty reactor, which is identical to the RTD of an ideal tank reactor, could lead to preferred formation of higher boiling consecutive reaction products (such as transesterification products). The
Fig. 6. Conversion vs. time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—influence of reactor type and the additive methanol. (Reaction conditions: L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), ionic liquid loading ˛ = 0.8, 0.38 wt.% Ru, 105 ◦ C, 10 bar, 5000 rpm (Berty), 200 NmL/min He, 75 NmL/min H2 , 0.125 g/h MAA, 0.152 g/h MeOH, = 2.4 s, oxisorb guard bed for He and H2 .)
Fig. 7. ee vs. Time-on-stream profiles of the SILP catalyzed MAA hydrogenation in a continuous gas-phase reaction—influence of reactor type and temperature. (Reaction conditions: L/Ru = 2:1, [EMIM][NTf2 ], silica 30 (0.2–1 mm), ionic liquid loading ˛ = 0.8, 0.38 wt.% Ru, 105 ◦ C, 10 bar, 5000 rpm (Berty), 200 NmL/min He, 75 NmL/min H2 , 0.125 g/h MAA, 0.152 g/h MeOH, = 2.4 s, oxisorb guard bed for He and H2 .)
latter may fill and block the open pore volume of our SILP catalyst material. Figs. 6 and 7 show the direct comparison of the continuous gas phase hydrogenation in the tubular reactor vs. the same experiments at 105 ◦ C in the Berty reactor. Indeed, a very positive effect of the plug flow reactor on the catalyst stability was observed. After 35 h TOS full catalyst activation was achieved and stable catalytic operation over at least 70 h was realized. Thus, for more than 100.000 residence times 70% conversion (XMax = 74%) with 75–80% ee could be realized at 105 ◦ C reaction temperature. During the total reaction time of the experiment in the tubular reactor a total turnover number of the catalyst of 2500 was achieved. 4. Conclusion In conclusion, we have successfully extended the scope of the SILP catalyst concept to continuous gas phase reaction with a complex, ligand influenced enantioselectivity. In detail, we have demonstrated for the first time a continuous, gas phase, asymmetric hydrogenation reaction. In the hydrogenation of methyl acetoacetate using Ru1Br2 in 1-ethyl-3-methylimidazolium bis(trifluoromethyl-sulfonyl)imide on silica 30, an enantiomeric excess in the range of 65–82% ee could be obtained for more than 100 h time-on-stream continuous operation (experiment at 105◦ in the plug flow reactor). Moreover, it was demonstrated, that the ionic liquid film on the support is absolutely essential for catalytic activity in the system and a relatively high degree of pore filling with the ionic liquid is beneficial. The catalyst activation times can be shortened by using non-calcinated silica instead of the calcinated support and by hydrogen pre-treatment. The combination of thermal degradation of the SILP catalyst and the formation of high-boiling side-products were identified as the main threats for catalyst stability. By changing the reactor from a back-mixed Bertytype to a tubular reactor, the accumulation of side-products in the SILP catalyst could be significantly reduced and much higher catalyst stability was observed. Remarkably, our continuous gas phase hydrogenation has been achieved for a substrate of relatively low volatility by using helium as carrier gas in the reactor. Based on these results, we expect that the use of SILP catalyst technology in continuous gas phase reactions can be in principal transferred to any substrate that has enough vapor pressure to be analyzed by gas chromatography. SILP catalyst materials in continuous gas-phase contact offer a very sim-
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ple way of catalyst/product separation and allow application of well-known catalytic systems without additional synthetic effort for ligand modification. The finding of this study that even complex ligand induced selectivities can be tackled by this continuous gas-phase technology should open further fields of application. Acknowledgements We gratefully thank Dr. Renat Kadyrov (Evonik Degussa GmbH) for fruitful discussions on ligand selection and for providing ligand samples. The authors acknowledge support by the Federal Ministery of Education and Research (BMBF), the Deutsche Forschungsgemeinschaft within the Erlangen Excellence Cluster “Engineering of Advanced Materials and SYNFLOW within the EU’s Seventh Framework Programme“. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.apcata.2011.03.038. References [1] C.P. Mehnert, R.A. Cook, N.C. Dispenziere, M. Afeworki, J. Am. Chem. Soc. 124 (2002) 12932–12933. [2] (a) A. Riisager, P. Wasserscheid, R. van Hal, R. Fehrmann, Catal. Lett. 90 (2003) 149–153; (b) A. Riisager, P. Wasserscheid, R. van Hal, R. Fehrmann, J. Catal. 219 (2) (2003) 452–455. [3] (a) P. Tundo, A. Perosa, Chem. Soc. Rev. 36 (2007) 532–550; (b) Y. Gu, G. Li, Adv. Synth. Catal. 351 (2009) 817–847; (c) S. Werner, M. Haumann, P. Wasserscheid, Annu. Rev. Chem. Biomol. Eng. 1 (2010) 203–230; (d) C. Van Doorslaer, J. Wahlen, P. Mertens, K. Binnemans, D. De Vos, Dalton Trans. 39 (2010) 8377–8390. [4] P. Wasserscheid, P.S. Schulz, T. Welton (Eds.), Ionic Liquids in Synthesis, 2nd ed., Wiley-VCH, Weinheim, 2007, pp. 369–463. [5] (a) A. Riisager, R. Fehrmann, S. Flicker, R. van Hal, M. Haumann, P. Wasserscheid, Angew. Chem. Int. Ed. 44 (2005) 815–819; (b) A. Riisager, R. Fehrmann, M. Haumann, P. Wasserscheid, Eur. J. Inorg. Chem. (2006) 695–706; (c) A. Riisager, R. Fehrmann, M. Haumann, B.S.K. Gorle, P. Wasserscheid, Ind. Eng. Chem. Res. 44 (2005) 9853–9859; (d) A. Riisager, R. Fehrmann, M. Haumann, P. Wasserscheid, Top. Catal. 40 (1–4) (2006) 91–102; (e) M. Haumann, K. Dentler, J. Joni, A. Riisager, P. Wasserscheid, Adv. Synth. Catal. 349 (3) (2007) 425–431. [6] A. Riisager, B. Jørgensen, P. Wasserscheid, R. Fehrmann, Chem. Commun. (2006) 994–996. [7] O. Jimenez, T.E. Müller, C. Sievers, A. Spirkl, J.A. Lercher, Chem. Commun. (2006) 2974–2976. [8] M. Ruta, G. Laurenczy, P.J. Dyson, L. Kiwi-Minsker, J. Phys. Chem. C 112 (2008) 17814–17819. [9] S. Werner, N. Szesni, A. Bittermann, M.J. Schneider, P. Härter, M. Haumann, P. Wasserscheid, Appl. Catal. A 377 (2010) 70–75.
41
[10] (a) H. Hagiwara, Y. Sugawara, T. Hoshi, T. Suzuki, Chem. Commun. (2005) 2942; (b) H. Hagiwara, K.H. Ko, T. Hoshi, T. Suzuki, Chem. Commun. (2007) 2838; (c) C. Brochwitz, A. Feldhoff, U. Kunz, M. Vaultier, A. Kirschning, Lett. Org. Chem. 3 (2006) 442. [11] (a) C.P. Mehnert, Chem. Eur. J. 11 (2005) 50–56; (b) B. Gadenne, P. Hesemann, J.J.E. Moreau, Chem. Commun. (2004) 1768–1769. [12] T. Ohkuma, H. Ooka, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 117 (9) (1995) 2675–2676. [13] L.-L. Lou, X. Peng, K. Yu, S. Liu, Catal. Commun. 9 (2008) 1891–1893. [14] W. Tang, X. Zhang, Chem. Rev. 103 (2003) 3029–3069. [15] W.S. Knowles, Angew. Chem. Int. Ed. 41 (2002) 1998–2007 (nobel lecture). [16] M. Heitbaum, F. Glorius, I. Escher, Angew. Chem. Int. Ed. 45 (2006) 4732–4762. [17] A.F. Trindade, P.M.P. Gois, C.A.M. Afonso, Chem. Rev. 109 (2009) 418–514. [18] J.M. Fraile, J.I. Graci, J.A. Mayoral, Chem. Rev. 109 (2009) 360–417. [19] (a) D.J. Bayston, J.L. Fraser, M.R. Ashton, A.D. Baxter, M.E.C. Polywka, E. Moses, J. Org. Chem. 63 (1998) 3137–3140; (b) T. Ohkuma, H. Takeno, Y. Honda, R. Noyori, Adv. Synth. Catal. 343 (2001) 369–375. [20] (a) P.N. Liu, J.G. Deng, Y.Q. Tu, S.H. Wang, Chem. Commun. (2004) 2070–2071; (b) B. Kesanli, W. Lin, Chem. Commun. (2004) 2284–2285. [21] A. Hu, H.L. Ngo, W. Lin, J. Am. Chem. Soc. 125 (2003) 11490–11491. [22] C. Köllner, B. Pugin, A. Togni, J. Am. Chem. Soc. 120 (1998) 10274–10275. [23] R.T. Halle, E. Schulz, M. Spagnol, M. Lemaire, Tetrahedron Lett. 41 (2000) 3323–3326. [24] W.P. Hems, P. McMorn, S. Riddel, S. Watson, F.E. Hancock, G.J. Hutchings, Org. Biomol. Chem. 3 (2005) 1547–1550. [25] D. Tas, C. Thoelen, I.F.J. Vankelecom, P.A. Jacobs, Chem. Commun. (1997) 2323–2324. [26] S. Zeror, J. Collin, J.C. Fiaud, L.A. Zouioueche, J. Mol. Catal. A: Chem. 256 (2006) 85–89. [27] E. de Wolf, B.-J. Deelman, in: J.G. de Vries, C.J. Elsevier (Eds.), Handbook of Homogeneous Hydrogenation, Wiley-VCH, Weinheim, 2007, pp. 1377–1388. [28] P. Wasserscheid, P. Schulz, in: J.G. de Vries, C.J. Elsevier (Eds.), Handbook of Homogeneous Hydrogenation, Wiley-VCH, Weinheim, 2006, pp. 1389–1421. [29] A. Wolfson, I.F.J. Vankelecom, P.A. Jacobs, Tetrahedron Lett. 44 (2003) 1195–1198. [30] K.L. Fow, S. Jaenicke, T.E. Müller, C. Sievers, J. Mol. Catal. A: Chem. 279 (2008) 239–247. [31] U. Hintermair, T. Höfener, T. Pullmann, G. Franciò, W. Leitner, ChemCatChem 2 (2010) 150–154. [32] (a) E. Öchsner, K. Schneiders, K. Junge, M. Beller, P. Wasserscheid, Appl. Catal. A 364 (1–2) (2009) 8–14; (b) T. Floris, P. Kluson, M.J. Muldoon, H. Pelantova, Catal. Lett. 134 (2010) 279–287. [33] (a) R. Kadyrov, Chim. Oggi 26 (5) (2008) 41–42; (b) R. Kadyrov, J. Tarabocchia, M.L. Prunier (Eds.), Catalysis of Organic Reactions, CRC Press, Boca Raton, 2009, pp. 211–216; (c) R. Kadyrov, R.M. Koenigs, C. Brinkmann, D. Voigtlaender, M. Rueping, Angew. Chem. Int. Ed. 48 (2009) 7556–7559. [34] (a) R. Noyori, T. Ohkuma, M. Kitamura, H. Takaya, N. Sayo, H. Kumobayashi, S. Akutagawa, J. Am. Chem. Soc. 109 (1987) 5856–5858; (b) M. Kitamura, T. Ohkuma, S. Inoue, N. Sayo, H. Kumobayashi, S. Akutagawa, T. Ohta, H. Takaya, R. Noyori, J. Am. Chem. Soc. 110 (1988) 629–631. [35] J.M. Berty, Chem. Eng. Prog. 70 (5) (1974) 78–84. [36] A. Wolfson, I.F.J. Vankelecom, S. Geresh, P.A. Jacob, J. Mol. Catal. A: Chem. (2004) 21–26. [37] (a) R. Noyori, T. Ohkuma, Angew. Chem. Int. Ed. 40 (2001) 40–73; (b) R. Noyori, M. Kitamura, T. Ohkuma, Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 5356–5362.