ARTICLE pubs.acs.org/IECR
Efficient Oxidative Dehydrogenation of Lactate to Pyruvate Using a Gas-Liquid Micro Flow System Toshiya Yasukawa,† Wataru Ninomiya,† Ken Ooyachi,† Nobuaki Aoki,‡ and Kazuhiro Mae*,‡ † ‡
Corporate Research Laboratories, Mitsubishi Rayon Co., Ltd., 20-1 Miyuki-Cho, Otake, Hiroshima 739-0693, Japan Department of Chemical Engineering, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan ABSTRACT: An efficient production of pyruvate by the oxidative dehydrogenation of lactate is achieved using a micro flow system based on gas-liquid slug flow. In this micro flow system, oxidizing agents and acetonitrile solutions of lactates and vanadium species are used, and lactate is converted into the corresponding pyruvate. For reasons of atom economy and enhanced mass transfer of oxygen into the liquid phase, due to internal circulation flow within slugs, molecular oxygen is the preferred agent. In a catalyst screening, vanadium oxytrichloride (VOCl3) gave the highest pyruvate yield. A continuous system is developed, consisting of the following two processes using T-shaped mixers: the mixing of an acetonitrile solution of lactate with that of VOCl3 and the injection of oxygen gas into the solution mixture. Compared with the conventional batch system, the oxidative dehydrogenation of lactate to the corresponding pyruvate proceeds more effectively using this micro flow system.
1. INTRODUCTION Pyruvates, including pyruvic acid and its derivatives such as pyruvate esters, are used as intermediates of perfume, food additives, and electronic materials.1 They are also attractive as raw materials for various bioactive substances such as antivirus and anticancer drugs.2 However, the production of pyruvic acid is still based on the conventional reaction scheme through dehydrative decarboxylation of tartaric acid, as shown in Figure 1.3,4 Although this reaction provides pyruvic acid in good yield, it has a serious disadvantage in that it requires excess KHSO4 as the decarboxylation agent. Therefore, a new process with high atom efficiency for the production of pyruvic acid would be preferable. Catalytic reactions for the synthesis of pyruvate from lactic acid and/or its ester as raw materials have also been proposed (Figure 1). These reactions were examined in both gas and liquid phases. In gas phase reactions, various solid catalysts have been used: binary oxides containing molybdenum such as Fe2O3-MoO3 and TeO2-MoO3,5 vanadium oxide species,6 and iron phosphate.7-9 These processes achieve high yields of pyruvate from lactate. However, besides the requirement for vaporizing lactate at high temperature, a reaction temperature above 473 K is also needed, increasing running costs. In liquid phase reaction with solid catalysts such as Pd-metal alloys supported on activated carbon, oxidative dehydrogenation of lactate takes place under milder conditions compared to those of the gas phase reaction. The reaction temperature is decreased to less than 363 K.10,11 However, the liquid phase reaction has the disadvantage that the required precious metal catalysts are expensive. As discussed above, from the viewpoint of effective production of pyruvate, reaction at low temperature with an inexpensive catalyst would be desirable. Oxidative dehydrogenation of lactate ester catalyzed by vanadium species under homogeneous conditions would be a promising candidate process for our requirements because the reaction temperature is below 373 K. Since the r 2011 American Chemical Society
Figure 1. Reaction scheme for pyruvate production.
yield of the corresponding pyruvate ester depends on the dissolved oxygen concentration in the liquid phase, efficient transfer of oxygen into the liquid phase containing the substrate is essential for high productivity. For intensified mass transfer between these two phases, we employ gas-liquid slug flow in a microreactor. Slug flow can enhance the contact efficiency between the gas and liquid phases due to the large specific surface areas and circulation flow in slugs. The internal circulation flow renews the solute concentration at the interface of the two phases. The flow also preserves the difference between the concentration at the interface and that at equilibrium. This difference is the enhanced driving force for the mass transfer.12 Micromixers with simple channel shapes such as T-shaped and Y-shaped mixers are used for stable formation of slug flow.12-15 However, in this reaction system, since the reaction mixture is a homogeneous solution, the development of a separation and Received: October 8, 2010 Accepted: February 16, 2011 Revised: November 24, 2010 Published: March 02, 2011 3858
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Figure 3. Reaction scheme of ethyl pyruvate formation from ethyl lactate.
Table 1. Effect of Oxidizing Agenta
Figure 2. Reaction mechanism of vanadium catalytic cycle.
recovery process for the catalyst and material is required. Therefore, we need to enhance the yield of desired product for this homogeneously catalyzed reaction. Because oxygen gas can be used with a vanadium catalyst and slug flow in microchannels to oxidize lactate, it is expected to be suitable for efficient production of pyruvate. In this study, we propose a microreactor system based on gasliquid slug flow for the efficient production of pyruvate ester from lactate ester. Lactate esters are obtained from lactic acid by esterification with various alcohols. Lactic acid is mainly synthesized by fermentation of glucose, and it should be separated and purified from the fermentation solution, which contains various organic compounds. However, as the boiling point of lactic acid is very high, distillation is ineffective for separation. As an alternative procedure, the transformation of lactate into its esters and subsequent separation is preferable. Therefore, lactate esters are also valuable compounds in examining the effective transformations of lactate into other useful chemicals. Our reaction scheme is shown in Figure 1. We applied a gas-liquid slug flow microreactor system to the oxidative dehydrogenation of lactate esters to pyruvate esters, mainly ethyl lactate to ethyl pyruvate. This system was optimized by the screening of catalyst species and oxidizing agents. Using these results, we compared the micro flow system with the batch reaction and demonstrated superior performance of the micro flow system.
2. REACTION MECHANISM The reaction mechanism of the oxidative dehydrogenation of secondary alcohols with a vanadium catalyst is shown in Figure 2.16-18 In the first step, a vanadium species reacts with both alcohol (ethyl lactate) and oxygen to form VO2Cl species. The initial species of vanadium is VOCl3, and it is transformed into VO2Cl after the reaction with ethyl lactate and O2. However, VO2OH resulting from ligand exchange with H2O is also a possible product, and this reaction would cause the deactivation of the catalyst. An active species such as vanadium alkoxide is formed as a key intermediate for production of the carbonyl compound. The pyruvate ester and a dihydroxyvanadium species (V(OH)2Cl) are subsequently generated via β-hydrogen elimination. The low valence vanadium species V(OH)2Cl is reoxidized to high valence VO2Cl by an oxidizing agent, with evolution of H2O. The high valence vanadium species is then ready to react again with the secondary alcohol to regenerate vanadium alkoxide. On the basis of this catalytic cycle, the
conversion of 1a (%)b
yield of 2a (%)c
air (1 atm) O2 (1 atm)
23 50
21 31
TBHPe
40
39
entry
oxidizing agent
1-1 1-2 1-3d a
VOCl3: 0.13 mmol; MS-3A: 1.0 g, oxidizing agent, at room temperature, for 20 min. b Determined by gas chromatography. c Determined by isolated yield. d Carried out under N2. e TBHP (2 mmol).
oxidizing agent has the following two roles: formation of the active vanadium species from the initial vanadium compound and reoxidation of the low valence vanadium species to form the high valence one. The reaction rate, r, depends on the concentrations of secondary alcohol and dissolved oxygen. r ¼ k½alcohola ½O2 b
ð1Þ
where k is the rate constant. This equation shows that the achievement of high productivity requires maintaining high concentrations of both alcohol and dissolved oxygen.
3. EXPERIMENTAL SECTION 3.1. Batch Reaction. First, a typical batch reaction procedure is described. Figure 3 shows the scheme for the main process in the batch reaction. A mixture of ethyl lactate (EL, 1a) and vanadium catalyst was stirred in acetonitrile under oxygen, air, or nitrogen to produce ethyl pyruvate (EP, 2a). EL (2 mmol, Wako Pure Chemical), vanadium oxychloride (VOCl3, 0.13 mmol, Wako Pure Chemical), molecular sieve-3A (MS-3A, 1.0 g, Wako Pure Chemical), and dry acetonitrile (10 mL, KANTO CHEMICAL) as a solvent were mixed in a 50 mL conical flask at room temperature (298 K). The role of MS-3A is to keep the reaction mixture dry, because the vanadium species hydrolyze slowly in the presence of molecular H2O produced during the reaction. The liquid in the flask was stirred at 450 rpm. Using this setup, the oxidizing agent was screened first; air (Table 1, entry 1-1), pure oxygen (entry 1-2), and tert-butyl hydroperoxide (TBHP; entry 1-3) were tested. When oxygen in air or pure oxygen gas was used as the oxidizing agent, the atmospheric gas in the flask was substituted for air or pure oxygen with an aspirator and a balloon filled with air or pure oxygen, respectively. When the liquid oxidizing agent TBHP was used, the balloon was filled with nitrogen. The interfacial area between the gas and liquid phases was 18-20 cm2. The reaction time under air was 20 min (entry 1-1) and that under oxygen was 20 min (entry 1-2). The reaction time in the presence of TBHP as oxidizing agent was also 20 min (entry 1-3). Next, vanadium species as catalysts were screened (Figure 4). Vanadium oxychloride was the first candidate (Table 2, entry 2-1). The experimental conditions were the same as those of 3859
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Figure 4. Reaction scheme of ethyl pyruvate formation from ethyl lactate, using various vanadium species as catalysts.
Figure 5. Reaction scheme for the formation of various pyruvates from lactates, using the optimum oxidizing agent and catalyst.
Table 3. Pyruvate Yield for VOCl3 Catalyzed Oxidation of Lactate Ester or Lactic Acida
Table 2. Results of Oxidation of 1a to 2a Catalyzed by Various Vanadium Compoundsa
entry
amount of V-species conversion of 1a yield of 2a entry
catalyst
b
(mmol)
(%) 50
2-1
VOCl3
0.13
2-2
b
(%) 31c
VO(acac)2
0.1
8
5
2-3d,e VO(acac)2
0.1
36
35
2-4f
19
VO(acac)2
0.1
26
2-5f,g VO(acac)2
0.1
31
22
2-6
VO(OEt)3
0.1
9
5
2-7f 2-8
VO(OEt)3 V2O5
0.1 0.05
19 9
2-9
H4PMo11VO40
0.1
30
yield of 2 (%)b
substrate 1
3-1
R = Me
1b
3-2
R = Et
1a
49 56
3-3 3-4
R = i-Pr R = n-Bu
1c 1d
72 59
3-5c
R=H
1e
28d
a
VOCl3: 0.13 mmol; MS-3A: 1.0 g; O2: 1 atm; at room temperature; and reaction time: 40 min. b Determined by isolated yield. c The reaction time was 20 min. d Determined by HPLC.
17 trace not detected
2-10f none
2
trace
2-11h none
3
trace
a
MS-3A: 1.0 g; O2: 1 atm; at room temperature; and reaction time: 20 min. b Determined by gas chromatography. c Determined by isolated yield. d Carried out under N2. e Added m-CPBA (2 mmol). f Added m-CPBA (0.1 mmol). g The reaction time was 45 min. h Added TBHP (2 mmol).
entry 1-2. When solid vanadium species vanadyl acetylacetonate (VO(acac)2) was used with organic peroxide m-chloroperbenzoic acid (m-CPBA) as oxidizing agent, the balloon was filled with pure oxygen or nitrogen (entries 2-2-2-5). When solid vanadium species vanadium oxytriethoxide (VO(OEt)3) was used as a catalyst with m-CPBA as oxidizing agent, the balloon was filled with pure oxygen (entries 2-6 and 2-7). When typical vanadium species vanadium(V) oxide (V2O5) or molybdovanadophosphoric acid (H4PMo11VO40) were used, the balloon was filled with pure oxygen (entries 2-8 and 2-9). For comparison, the reaction without any catalyst was also performed using 0.1 mmol of m-CPBA (entry 2-10) and 2 mmol of TBHP (entry 2-11) as the oxidizing agents. In the screenings of the oxidizing agents and the vanadium species, the reactions were quenched by addition of distilled water (10 mL). For removal of catalyst, EL and EP in the reaction mixture were then extracted with ethyl acetate (10 mL). The conversion of EL and the yield of EP were both determined by gas chromatography (GC-2014 equipped with FID detector and DB-FFAP column, Shimadzu). The isolated yield of 2a was determined. Compound 2a was isolated by column chromatography with silica gel (Wako gel) using a mixture of hexane and ethyl acetate (hexane/ethyl acetate ratio range of 13-20 (v/v)) as the eluent (Table 2, entry 2-1). In addition, using the optimum oxidizing agent and catalyst, the oxidations of various lactate esters were carried out at room temperature for 40 min (Figure 5; Table 3, entries 3-1-3-4). Isolated yields of corresponding pyruvates 2a-2d were determined.
Figure 6. Experimental setup for micro flow reaction.
In the case of lactic acid as starting material, the pyruvic acid yield at room temperature for 20 min was determined by HPLC (entry 3-5). 3.2. Flow Reaction. Figure 6 shows the micro flow reaction system. The system consists of two mixing zones. In the first mixing zone, the acetonitrile solution of EL and the acetonitrile solution containing the vanadium catalyst screened in the previous section were supplied to a union tee and mixed in the union tee. In the second mixing zone, this solution was mixed with pure oxygen gas, and gas-liquid slug flow formed in the reaction zone. The flow reaction conditions were as follows: in the first mixing zone, EL solution (0.2 M) and VOCl3 solution (0.02 M) were supplied by HPLC pumps (each flow rate was 1 mL/min) to a 1/ 16 union tee (inner diameter: 1.3 mm, Swagelok). In the flow reaction with the EL and VOCl3 solution slurry, because the slurry was not provided stability with a pump, MS-3A was not used as a dehydration agent. The reaction temperature was room temperature adjusted to 298 K. The channel length of the first mixing zone (reactor) was 300 mm, and the channel inner diameter (i.d.) was 1.0 or 0.5 mm. For this mixing zone, we refer to the system including the channel of i.d. 1.0 mm as flow reaction 1 and the channel of i.d. 0.5 mm as flow reaction 2. In the second mixing zone, oxygen gas was injected into the mixed solution of EL and VOCl3 in a 1/16 union tee (inner diameter: 1.3 mm). The flow rate of oxygen gas was 2 cm3/min. The channel length of the second mixing zone was 5-20 m, and the channel inner diameter was 1.0 mm. In these conditions, we observed the formation of gas-liquid slug flow. The initial slug lengths of the two liquid phases were 5.0-6.0 mm. At the end of the reactor, the reaction mixture was trapped in a 10 mL vial 3860
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Industrial & Engineering Chemistry Research containing water. The conversion of EL and the yield of EP were determined by the same method as that for the batch reaction. The reaction mixture was also analyzed by GC/MS (GC-1700, EI, Shimadzu). Ethyl pyruvate, acetic acid, and unreacted ethyl lactate were detected in this analysis. However, in all reactions, the amount of acetic acid was less than 1 mol % of the total molar amount of ethyl lactate and ethyl pyruvate. By-products via hydrolysis of ethyl ester, such as lactic acid, pyruvic acid, and ethanol were not detected. Therefore, the conversion of lactate was approximately equal to the yield of the corresponding pyruvate. In other words, the selectivity of ethyl pyruvate was nearly 100%. In addition to ethyl lactate, the reactions of other lactate esters such as methyl lactate, i-propyl lactate, and n-butyl lactate were also carried out. The channel i.d. was 1.0 mm. The second mixing zone length was 50 m, and the residence time was in the range of 9.6-14.4 min. These reactions were catalyzed by VOCl3 with pure oxygen as the oxidizing agent and were carried out at room temperature. In each reaction using lactate esters as a starting material, high pyruvate yield was achieved.
4. RESULTS AND DISCUSSION 4.1. Batch Reaction. Table 1 summarizes the results of the oxidation reaction of lactate 1a catalyzed by VOCl3 using various oxidizing agents. When the reaction of 1a with 0.13 mmol of VOCl3 was carried out under an atmospheric pressure of pure oxygen at room temperature for 20 min, the yield of pyruvate 2a increased compared with that under air (entries 1-2 and 1-1). This tendency is expressed as eq 1. Because the oxygen partial pressure in entry 1-2 was higher than that in entry 1-1, the dissolved O2 concentration in entry 1-2 was also higher than that in entry 1-1. As a result, the activity in entry 1-2 was higher than that in entry 1-1. When TBHP under nitrogen was used instead of pure oxygen as the oxidizing agent, the yield and selectivity of 2a increased (entry 1-3). These results show that both pure oxygen and organic peroxide are effective for the catalytic cycle of EL to EP with VOCl3, and the yield of 2a is enhanced with increasing concentration of dissolved oxidizing agent. With respect to atom efficiency and the safety aspects of storage, pure oxygen is superior to TBHP. The results of the oxidation reaction of 1a catalyzed by various vanadium compounds with oxidizing ability are shown in Table 2. VOCl3 and pure oxygen proved the most suitable in these screenings, because the pyruvate productivity of the reaction catalyzed by VOCl3 is higher than that using the other catalysts and pure oxygen is useful in the VOCl3 catalytic reaction. When the reaction was carried out using 0.1 mmol of vanadyl acetylacetonate (VO(acac)2) as the catalyst under oxygen, the activity decreased (entry 2-2). However, in the presence of a stoichiometric amount (2 mmol) of m-chloroperbenzoic acid (m-CPBA), pyruvate 2a was formed in high yield (35%, entry 2-3). Moreover, the addition of a catalytic amount (0.1 mmol) of m-CPBA (entries 2-4 and 2-5) increased the productivity of EP catalyzed by VO(acac)2. These results indicate that the structural change of the vanadium compound from the initial species to the active one is necessary for starting the catalytic cycle. When VO(acac)2 was used as the catalyst, m-CPBA was a more effective oxidizing agent than dissolved molecular oxygen in terms of the structural change of vanadium species discussed above. Meanwhile, each oxidizing agent was effective for reoxidation of low valence vanadium. However, on the basis of these results, the more efficient catalyst for the reoxidation of low valence
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Figure 7. Comparison of performance between flow and batch reactions at room temperature. b Flow reaction 1; ( batch reaction using pure oxygen as oxidizing agent.
vanadium species is still unclear. We assume that the ratedetermining step is the reoxidation of low valence vanadium. Therefore, m-CPBA is more effective than dissolved molecular oxygen for this step. The catalytic performance of vanadium oxytriethoxide (VO(OEt)3) under pure oxygen (entries 2-6 and 2-7) was almost the same as that of VO(acac)2. In these experiments, catalysts were partially precipitated in the reaction mixture. Since VO(OEt)3 is unstable in the presence of water, it reacted with water generated by oxidative dehydrogenation or included as an impurity in the solvent. As discussed above, we consider that m-CPBA is more suitable than pure oxygen for the structural change of vanadium species such as VO(OEt)3. We also expect that the mechanism of the structural change into the active species would be different from the case of VO(acac)2 as catalyst, because the initial oxidation numbers of VO(acac)2 and VO(OEt)3 are different. Typical oxidizing agents such as vanadium(V) oxide (V2O5) and molybdovanadophosphoric acid (H4PMo11VO40) could not catalyze oxidation of 1a (entries 2-8 and 2-9). The reaction mixture with V2O5 was a heterogeneous solution and that with H4PMo11VO40 was homogeneous. As the colors of the reaction mixture remained unchanged, no alkoxy vanadium complex was formed with lactate 1a by the vanadium species. Although lactate 1a was converted in the case of H4PMo11VO40, decomposition of 1a mainly occurred due to the strong acidic property of the catalyst. Almost no reaction proceeds under pure oxygen in the absence of vanadium species, as shown in Table 2 (entries 2-10 and 2-11). In these cases, no byproduct via oxidative decomposition was detected by GC-MS. On the basis of these results, a reaction system catalyzed by VOCl3 with an oxidizing agent seems to be superior in atom efficiency and the safety aspects of storage suggest that pure oxygen is the most suitable. Table 3 shows the results of the oxidation reactions of various lactates (1a-e) catalyzed by VOCl3. For various lactic esters (1a-d), the corresponding pyruvic esters (2a-d) were synthesized with good yields (entries 3-1-3-4). The reaction of lactic acid (1e) resulted in a relatively low yield (28%). In this case, no lactic acid was detected in the end product (entry 3-5). This result indicates that the rates of side reactions such as decarboxylation are faster than that of the main reaction. Our results suggest that the optimized reaction conditions are effective for lactate esters as starting species. 4.2. Flow Reaction. Figure 7 shows the results of flow reaction 1, of which the specifications are listed in Table 1 (the internal diameter of the first mixing zone is 1 mm). The EP yield of flow reaction 1 was higher than that of the batch reaction in spite of 3861
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Figure 8. Effects of inner diameter of the first mixing zone. b Flow reaction 1, inner diameter of the first mixing zone: 1 mm; 2 Flow reaction 2, inner diameter of the first mixing zone: 0.5 mm.
the short reaction time. This result suggests that the observed activity of the flow reaction is enhanced in comparison with that of the batch reaction. This increased activity should be attributed to the high concentration of dissolved oxygen. Such high concentration of oxygen is achieved by gas-liquid slug flow in a flow reactor demonstrating large gas-liquid interface area and rapid mass transfer between the two phases through internal circulation flow inside slugs. In the batch reaction, the gas-liquid interface area per unit volume of reaction mixture was 196.25 mm2/ mL. In contrast, that in the flow reaction was 363.59 mm2/mL. Moreover, the renewal of the gas-liquid interface area accelerates the mass transfer between the two phases.19-22 Thus, the superiority of productivity in the flow reaction is clearly explained by the large gas-liquid interface area and the internal circulation flow in each segment. Furthermore, the catalytic species was not affected by molecular H2O produced during the reaction in a short reaction period. Figure 8 summarizes the results of flow reactions 1 and 2. When the residence time in the first mixing zone was less than 33 s for flow reaction 1, no pyruvate was produced. This result suggested the existence of an induction period before formation of pyruvate. The induction period of flow reaction 2 was shorter than that of flow reaction 1. The smaller inner diameter of the first mixing zone of flow reaction 2 resulted in accelerated mixing of EL and VOCl3 solutions compared with flow reaction 1. Therefore, we assume that incomplete mixing of EL and VOCl3 solutions caused the long induction period. The slope of EP yield against reaction time for flow reaction 2 is comparable with that for flow reaction 1. These results suggest that the rate-determining step is this mixing step, in which VOCl3 is transformed into the active species. Unfortunately, because this period is essential for the formation of the key intermediates such as the alkoxyvanadium species, accelerating mixing between EL and the VOCl3 solution would not eliminate it. Figure 9 shows the results of the syntheses of the corresponding pyruvates from the various lactate esters using the micro flow system. The yields of the pyruvates are higher than 50%, which is superior to those obtained by the batch reaction. Therefore, the gas-liquid slug flow microreactor system is useful for the syntheses of various pyruvates from lactate esters. Even near the exit of the second mixing zone, the gas-liquid slugs were clearly maintained. These results show that high conversion of lactate is achieved using a long length tube and maintaining gasliquid slug flow. Finally, the advantages of the micro flow system are summarized. Because of a large contact interface area for gas and liquid phases and circulation flow inside slugs, gas-liquid slug flow in a microchannel accelerates mass transfer between the two phases.
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Figure 9. Oxidation of various lactate esters to corresponding pyruvates at room temperature. The second mixing zone length was 50 m, and the residence time ranges from 9.6 to 14.4 min. O Methyl pyruvate (2b), b ethyl pyruvate (2a), 0 i-propyl pyruvate (2c), and 9 n-butyl pyruvate (2d).
The accelerated mass transfer enables a high dissolved gas concentration and enhanced activity. In addition, as a result of the mixing intensification in the first mixing zone, the induction period is shortened. Therefore, the overall activity in the micro flow system is much higher than that in the conventional batch system. Moreover, the result was obtained at room temperature, which is much lower than the temperature required for the batch syntheses. Low temperature synthesis leads to the development of an industrial process with reduced energy consumption.
5. CONCLUSION For developing an efficient process of pyruvate production from lactate, we propose a liquid phase catalytic reaction with vanadium species and a flow system based on gas-liquid slug flow. First, using the batch reaction, the oxidizing agents and the catalysts were screened. Both molecular oxygen and organic peroxide were effective as oxidizing agents. However, on the basis of the results of the oxidizing agent screening and from the viewpoint of atom economy, we suggest oxygen as the preferred oxidizing agent. In the catalyst screening, VOCl3 gave the highest pyruvate conversion and yield. Using the screened oxidizing agent and catalyst, a micro flow system based on gas-liquid slug flow was examined. The reactor system included two T-shaped mixers: one was for mixing substrate with catalyst solution and the other was for generating slug flow by adding oxygen. The proposed system is easy to set up, since the tubing and joints are commercially available. The induction period is shortened by the rapid mixing in the first mixing zone. The reaction is also accelerated by enhancement of mass transfer of oxygen in the slug flow. Therefore, the overall activity in the micro flow system is much higher than that of a conventional batch system. In addition, the oxidation of ethyl pyruvate using oxygen gas in the flow reactor system efficiently proceeds at room temperature, which is lower than that applied in the conventional syntheses. Low temperature synthesis enables the development of an industrial process with reduced energy consumption. The usefulness of this micro reaction system has also been demonstrated for several different lactates. From these results, the proposed micro flow reactor system enables efficient production of pyruvates at moderate temperatures using an inexpensive catalyst. ’ AUTHOR INFORMATION Corresponding Author
*Tel.: þ81 75 383 2668. Fax: þ81 75 383 2658. E-mail:
[email protected]. 3862
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’ ACKNOWLEDGMENT The authors gratefully acknowledge the financial support of the New Energy and Industrial Technology Development Organization (NEDO) through the project entitled “Development of Fundamental Technologies for Green and Sustainable Chemical Processes Project”. ’ REFERENCES
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(20) Irandoust, S.; Andersson, B. Simulation of Flow and Mass Transfer in Taylor Flow Through a Capillary. Comput. Chem. Eng. 1989, 13, 519–526. (21) Kashid, M. N.; Gerlach, I.; Goetz, S.; Franzke, J.; Acker, J. F.; Platte, F.; Agar, D. W.; Turek, S. Internal Circulation within the Liquid Slugs of a Liquid-Liquid Slug-Flow Capillary Microreactor. Ind. Eng. Chem. Res. 2005, 44, 5003–5010. (22) Song, H.; Chen, D. L.; Ismagilov, R. F. Reactions in Droplets in Microfluidic Channels. Angew. Chem., Int. Ed. 2006, 45, 7336–7356.
(1) Corma, A.; Iborra, S.; Velty, A. Chemical Routes for the Transformation of Biomass into Chemicals. Chem. Rev. 2007, 107, 2411–2502. (2) Iida, T.; Ohira, Y. 7-Fluoro-2,3-didehydrosialic acid and intermediate for synthesis thereof. WO1995032955, December 7, 1995. (3) Erlenmeyer, E. Verhalten der Glycerins€aure und der Weins€aure gegen wasserentziehende Substanzen. Ber. Dtsch. Chem. Ges. 1881, 14, 320–323. (4) Howard, F. Pyruvic Acid. Org. Syn. Coll. 1941, 1, 475–476. (5) Sugiyama, S.; Shigemoto, N.; Masaoka, N.; Sugetoh, S.; Kawami, H.; Miyaura, K.; Hayashi, H. Vapor-Phase Oxidation of Ethyl Lactate to Pyruvate over Various Oxide Catalysts. Bull. Chem. Soc. Jpn. 1993, 66, 1542–1547. (6) Sovorov, B. V.; Rafikov, S. R.; Kagarlitskii, A. D. The Oxidative Ammonolysis of Organic Compounds. Russ. Chem. Rev. 1965, 34, 657–668. (7) Ai, M.; Ohdan, K. Effects of Differences in the Structures of Iron Phosphates on the Catalytic Action in the Oxidative Dehydrogenation of Lactic Acid to Pyruvic Acid. Appl. Catal., A 1997, 165, 461–465. (8) Ai, M.; Ohdan, K. Oxidation by Iron Phosphate Catalyst. J. Mol. Catal. A 2000, 159, 19–24. (9) Ai, M. Catalytic Activity of Iron Phosphate Doped with a Small Amount of Molybdenum in the Oxidative Dehydrogenation of Lactic Acid to Pyruvic Acid. Appl. Catal., A 2002, 234, 235–243. (10) Tsujino, T.; Ohigashi, S.; Sugiyama, S.; Kawashiro, K.; Hayashi, H. Oxidation of Propylene Glycol and Lactic Acid to Pyruvic Acid in Aqueous Phase Catalyzed by Lead-Modified Palladium-on-Carbon and Related Systems. J. Mol. Catal. 1992, 71, 25–35. (11) Sugiyama, S.; Kikumoto, T.; Tanaka, H.; Nakagawa, K.; Sotowa, K.; Maehara, K.; Himeno, Y.; Ninomiya, W. Enhancement of Catalytic Activity on Pd/C and Te-Pd/C During the Oxidative Dehydrogenation of Sodium Lactate to Pyruvate in an Aqueous Phase Under Pressurized Oxygen. Catal. Lett. 2009, 131, 129–134. (12) Okubo, Y.; Maki, T.; Aoki, N.; Khoo, T. H.; Ohmukai, Y.; Mae, K. Liquid-Liquid Extraction for Efficient Synthesis and Separation by Utilizing Micro Spaces. Chem. Eng. Sci. 2008, 63, 4070–4077. (13) Trachsel, F.; G€unther, A.; Khan, S.; Jensen, K. F. Measurement of Residence Time Distribution in Microfluidic Systems. Chem. Eng. Sci. 2005, 60, 5729–5737. (14) Song, H.; Tice, J. D.; Ismagilov, R. F. A Microfluidic System for Controlling Reaction Networks in Time. Angew. Chem., Int. Ed. 2003, 42, 768–772. (15) Aoki, N.; Tanigawa, S.; Mae, K. A New Index for Precise Design and Advanced Operation of Mass Transfer in Slug Flow. Chem. Eng. J., in press (Available online, doi:10.1016/j.cej.2010.07.071). (16) Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.; Kawamura, T.; Uemura, S. Oxovanadium Complex-Catalyzed Aerobic Oxidation of Propargylic Alcohols. J. Org. Chem. 2002, 67, 6718–6724. (17) Kirihara, M.; Ochiai, Y.; Takizawa, S.; Takahata, H.; Nemoto, H. Aerobic Oxidation of R-Hydroxycarbonyls Catalysed by Trichlorooxyvanadium: Efficient Synthesis of R-Dicarbonyl Compounds. Chem. Commun. 1999, 1387–1388. (18) Bonchio, M.; Bortolini, O.; Conte, V.; Primon, S. Aerobic Oxidation of Isopropanol Catalysed by Peroxovanadium Complexes: Mechanistic Insights. J. Chem. Soc., Perkin Trans. 2001, 2, 763–765. (19) Qian, D.; Lawal, A. Numerical Study on Gas and Liquid Slugs for Taylor Flow in a T-Junction Microchannel. Chem. Eng. Sci. 2006, 61, 7609–7625. 3863
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