JP2006225726A - Method for producing chemical substance by electrochemical reaction - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To improve the yield of electrochemical reaction. <P>SOLUTION: In the method for producing a chemical substance, electrochemical reaction is performed using a microreactor characterized in that a flow passage provided with one or more pairs of a working electrode and a counter electrode is present, the interelectrode distance between each working electrode and each counter electrode is ≤200 μm, and a partition is provided between each working electrode and each counter electrode. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for producing a chemical substance using a microreactor having an electrode in a member. More specifically, in the fields of chemistry, biochemistry, agriculture, forestry, medical care, food industry, pharmaceutical industry, environmental conservation, etc., in particular, the use of a flow reactor that is useful as a chemical synthesis, chemical analysis and biochemical reactor Related to the manufacturing method.

Electrochemical reactors are roughly classified into batch type and flow type. A batch type electrochemical reactor performs an electrochemical oxidation-reduction reaction on the surface of an electrode by inserting at least a pair of electrodes into a container filled with an electrolytic solution and applying a voltage to the electrodes. A flow-type electrochemical reactor is one in which an electrolytic solution is circulated through a flow path provided with at least a pair of electrodes, and a voltage is applied to the electrodes to continuously perform an electrochemical oxidation-reduction reaction. Conventional electrochemical reactors, both batch type and flow type, have been put into practical use industrially, but the distance between electrodes is several tens to several centimeters away, so in order to flow the necessary amount of current It was necessary to increase the voltage or increase the supporting electrolyte concentration. Since the amount of power consumption is the product of the current value and the voltage value, there is a problem that increasing the voltage increases the amount of power consumption or increases the amount of heat generated and the amount of by-products. On the other hand, in order to reduce the electrical resistance of the electrolytic solution, a method of increasing the supporting electrolyte concentration may be taken. However, there are problems such as many supporting electrolytes are expensive and the amount of by-products derived from the supporting electrolyte increases. In addition, conventional electrochemical reactors with an internal volume of 1 m ³ to several tens m ³ are generally used in order to increase the production volume. When the internal volume is large in this way, it is difficult to remove heat generated during the electrolytic reaction, and there is a problem that unnecessary side reactions are likely to occur.

  The microreactor is a device having a minute flow path, and is used for chemical reaction, minute analysis, drug development, genome / DNA analysis tool and the like. A microreactor is characterized by extremely high heat exchange efficiency and precise temperature control since the entire apparatus is smaller than a conventional reactor. Therefore, even with reactions that generate a large amount of heat, there is a risk of runaway or explosion, reactions that require precise temperature control, or reactions that require rapid heating or cooling, precise control can be easily performed using a microreactor. There is an advantage that it is possible. In addition, when a plurality of compatible liquids or gases are mixed by providing a branch in a minute flow path, they can be mixed instantaneously because the diffusion distance is short. Therefore, mixing at a more ideal mixing ratio is possible, and undesirable side reactions can be suppressed. In addition, since the reaction is performed in a minute space, the interface per unit volume of the fluid, for example, the liquid / liquid interface between the water-insoluble solvent and water, or the area of the solid / liquid interface between the liquid and the vessel wall, Become very large. Therefore, the mass transfer through the interface and the contact area with the heterogeneous catalyst are increased, so that the reaction can be performed efficiently. Furthermore, since the volume of the reactor is very small, the amount and cost of the sample (reaction reagent, sample, etc.) used for the reaction can be reduced, and the reaction scale can be reduced to the limit of the analysis capability of the product. Waste can be suppressed and the burden on the environment can be reduced.

  In the production of substances using microreactors, it has been studied to perform so-called numbering up, in which a large number of microreactors are produced in parallel, instead of scaling up to increase the size of the reactor as in the past. In the conventional scale-up, in order to mass-produce substances developed in laboratory flasks, after conducting a small test of several liters and a medium test of several hundred liters, an actual plant with a scale of several meters is designed. It takes a lot of cost, labor, and time, and it is not uncommon for yield to deteriorate due to scale-up. On the other hand, in the numbering up in the microreactor, it is considered that a large number of the same microreactors are produced in parallel, so that production can be easily increased and products of the same quality can be produced.

Electrochemical reaction microreactors have many reports for analytical applications (see, for example, Patent Documents 1 and 2). However, there are very few examples of using a microreactor for chemical substance production (see, for example, Patent Documents 3 to 6). Moreover, Japanese Patent Application Laid-Open No. 2003-172736 is substantially intended for DNA PCR reactions and electrophoresis, and is not intended for chemical substance production. Japanese Patent Application Laid-Open No. 2003-117409 is not suitable for chemical substance production because it uses plastics as a material for a reactor. In addition, US Pat. No. 6,607,655 discloses an example of chemical production using a microreactor, but a space formed by two electrodes and a slit by sandwiching an insulating film having a slit between the electrodes. The reaction solution is injected into the tank and the electrochemical reaction is carried out. In the examples of the patent, as the insulating film, a material having high chemical resistance such as polyimide is used, but the durability against the electrochemical reaction is not sufficient, and the material is sufficiently durable for this purpose. Some materials are not known. Japanese Patent Application Laid-Open No. 2004-66169 reports a microchemical device that performs an electrochemical reaction in a micro space made of a carbon material obtained by carbonizing and baking a thermosetting resin molded product. Carbonized and fired carbon materials are not suitable for mass production because they have poor dimensional stability and tend to cause abnormal shrinkage and warpage. In addition, by sandwiching an ion conductive film between the anode and the cathode, it is said that ions can be conducted without mixing the reaction solution between the two electrodes, but the ion conductive film absorbs the solvent and swells. However, there are many problems such as the fact that the minute space is pressed by swelling of the membrane, and in some cases, the reaction solution cannot be flown by blocking.
JP 2004-239781 A JP2003-4752 JP 2003-172736 A JP 2003-117409 A US Pat. No. 6,607,655 JP 2004-66169 A

  An object of the present invention is to improve the yield of an electrochemical reaction.

  As a result of intensive studies to solve the above problems, the present inventors have completed the following invention. That is, the present invention has a flow path having a pair of electrodes of the working electrode and the counter electrode, the distance between the working electrode and the counter electrode is 200 μm or less, and a partition is provided between the working electrode and the counter electrode. A method for producing a chemical substance by performing an electrochemical reaction using a microreactor.

    According to the present invention, the yield of electrochemical reaction can be improved.

  Hereinafter, the present invention will be described in detail.

  In the present invention, the microreactor is an apparatus for chemical reaction / material production utilizing a phenomenon in a micro space centered on a width of several μm to several hundreds of μm produced by using a micro processing technique or the like. The size of the entire apparatus is not necessarily small.

  In the microreactor used in the present invention, the distance between the working electrode and the counter electrode is 200 μm or less. The distance between the electrodes is more preferably 100 μm or less, and particularly preferably 50 μm or less. If the distance between the electrodes becomes too large, there may be a problem that the electric resistance of the reaction solution increases and the power consumption increases. Furthermore, if a supporting electrolyte is added or increased for the purpose of lowering electric resistance, a step of separating the supporting electrolyte after the reaction may be required, or the manufacturing cost may increase due to the use of an expensive supporting electrolyte.

  A partition wall is provided between the electrodes of the microreactor used in the present invention. The partition wall is provided for the purpose of suppressing diffusion so that a compound generated at the working electrode and the counter electrode diffuses to the opposite electrode and is not subjected to an oxidation reaction or a reduction reaction again. The material of the partition is not particularly limited as long as the partition can be processed between the electrodes. For example, when the substrate is processed with silicon, the partition wall may be processed at the same time when the groove is formed, and when the substrate is not excellent in workability like silicon, a thick film resist (for example, You may process a groove | channel and a partition using SU-8 MicroChem company). The partition wall must have a gap through which ions for energization pass. The shape of the void is not particularly limited. For example, the wall may have a through-hole, or the wall may have a fine hole such as a porous wall. From the above viewpoint, a shape having a slit in the wall is preferable. The porosity of the void provided in the wall is preferably 1% or more and 80% or less, and more preferably 10% or more and 60% or less. The porosity can be determined from the ratio of the cross-sectional area of the entire partition provided between the electrodes to the cross-sectional area of the entire partition.

  The microreactor used in the present invention has a channel having a pair of electrodes of a working electrode and a counter electrode having a distance between electrodes of 200 μm or less, and a reaction liquid on one end of the channel on the working electrode side and the counter electrode side. Two or more branched flow channels for supplying the reaction solution are connected, and the other end is connected to two or more branched flow channels for separating the reaction solution on the working electrode side and the counter electrode side, respectively. If it is, it will not specifically limit. For example, a groove is formed on an insulating substrate such as glass using a thick film resist (for example, SU-8 MicroChem), and a pair of electrodes are provided in the groove using vapor deposition or sputtering techniques. Thereafter, a lid may be covered with an insulating substrate such as glass, and a reaction solution may be injected into the flow path so that an electrochemical reaction can be performed. Here, the shape of the flow path is not particularly limited, and may be linear or curved.

  In addition, a groove is formed on the silicon substrate whose surface has been oxidized to enhance the insulating property using an etching technique, and a pair or more electrodes are provided in the groove using an evaporation or sputtering technique. It is also possible to cover the substrate with a conductive substrate and inject a reaction solution into this flow path so that an electrochemical reaction can be performed. Here, the shape of the flow path is not particularly limited, and may be linear or curved. The method of covering the silicon substrate with glass is preferable because anodic bonding is simple and excellent in adhesion.

  The flow path of the microreactor used in the present invention is preferably formed using a photolithography technique. Photolithographic technology allows easy microfabrication, and can be freely designed in two dimensions. Also, mass production technology has been established, so microreactors can be supplied at low cost. There are many merits such as being possible.

  One end of a flow path having electrodes of a microreactor used in the present invention is connected to a flow path branched into two or more for supplying a reaction solution to the working electrode side and the counter electrode side, and the other end Two or more branched flow paths for separating the reaction solution on the working electrode side and the counter electrode side must be connected to each other. The supply-side flow path branched into two or more enables supply of reaction liquids having different components on the working electrode side and the counter electrode side at different flow rates. Further, the discharge-side flow path branched into two or more enables separation and discharge while suppressing mixing of chemical components generated on the working electrode side and the counter electrode side to a minimum. The connection angle of the branched flow path with respect to the flow path provided with the electrode is not particularly limited, but is preferably 5 ° to 120 °, more preferably 10 ° to 90 °. If this connection angle is 5 ° or less, the distance until the flow path is completely separated becomes too long and wasteful, which is not preferable. If it is 120 ° or more, it depends on the flow rate, but due to a small pressure difference of the pump. This is not preferable because vibration occurs on the liquid surface. In addition, the connection angle of two or more branched flow paths with respect to the flow path including the electrodes may be symmetric or asymmetric.

  The length of the flow path of the microreactor used in the present invention is not particularly limited, and may be appropriately designed in consideration of the reaction solution concentration, the reaction solution flow rate, the current density, the current efficiency, and the like.

  The electrode material of the microreactor used in the present invention is not particularly limited as long as power is supplied. For example, metals such as palladium, platinum, rhodium, iridium, nickel, gold, tungsten, niobium, cadmium, manganese, thallium, lead, mercury, and carbon materials such as glassy carbon, spectroscopic grade graphite, pyrolytic graphite, and carbon cloth And those powders dispersed in xylene wax, epoxy resin, silicone rubber, Nujol or the like can be used. In addition, when the metal is deposited by vapor deposition or sputtering, a thin film such as chromium or titanium may be deposited as a base in order to improve adhesion to the substrate. Carbon may be coated with a paste in which carbon powder is dispersed in an adhesive material on the surface of the metal electrode. Similarly, a hydrocarbon compound is coated on the surface of the metal electrode and thermally decomposed under reduced pressure. Pyrolytic graphite may also be used.

  The electrochemical reaction performed in the present invention is not particularly limited. Electrochemical reactions are broadly divided into oxidation reactions and reduction reactions. Particularly in the organic compound electrochemical reactions, functional group conversion type, addition type, insertion type, substitution type, exchange type, elimination type, dimerization type, Examples thereof include a cross-dimerization type, a cyclization type, a multimerization type, a cleavage type, a metallization type, an asymmetric synthesis type, and the like. Electrochemical reactions are broadly divided into direct methods in which the substrate is oxidized and reduced by transferring electrons between the reaction substrate and the electrode, and indirect methods using an electron transfer carrier called a mediator. There is no particular limitation. Similarly, the reaction substrate used in the present invention is not limited to an organic compound and an inorganic compound, and is not particularly limited.

  The reaction substrate for the electrochemical reduction dimerization reaction performed in the present invention is not particularly limited. Examples thereof include compounds having a carbon-carbon double bond such as maleic acid, succinic acid, dimethylmaleic acid, dimethyl succinic acid and acrylonitrile, and compounds having a carbon-oxygen double bond such as ketones and aldehydes. These reaction substrates may be reacted in the same kind or in different kinds.

  The solvent that can be used in the present invention is not particularly limited as long as it can supply protons. For example, water, methanol, ethanol, n-propanol, isopropanol, 1,2-ethanediol, acetic acid, hydrochloric acid and the like can be used, and a single solvent may be used or a mixed solvent may be used. As the solvent to be mixed, the above-mentioned solvents may be used, and acetonitrile, dimethylformamide, propylene carbonate, dimethyl sulfoxide, formamide, 2-pyrrolidone, pyridine, tetramethylurea, ethylenediamine, nitromethane, nitrobenzene, hexane, dichloromethane, chloroform, etc. should be used. Can do.

In the present invention, a supporting electrolyte may be used, and is not particularly limited as long as it can be dissolved in the reaction solution to have conductivity. Since the supporting electrolyte acts as an ion in the solvent, it is a salt combined with an anion and a cation that are easily ionized. Examples of the cation include alkali metal ions such as Li ⁺ , Na ⁺ , K ⁺ , Rb ⁺ , and Cs ⁺ , ammonium ions, tetramethylammonium ions, tetraethylammonium ions, tetra (n-propyl) ammonium ions, tetra (i−). And quaternary alkyl ammonium such as propyl) ammonium ion, tetra (n-butyl) ammonium ion, and tetra (n-hexyl) ammonium ion. Examples of anions include halogen ions such as Cl ⁻ , Br ⁻ and I ⁻ , acetate ions, sulfate ions, nitrate ions, perchlorate ions, BF ₄ ⁻ , PF ₆ ⁻ , bis (trifluoromethanesulfonyl) imide, bis ( 1,1,2,2,3,3,3-heptafluoro-1-propanesulfonyl) imide, bis (1,1,2,2,3,3,4,4,4-nonafluoro-1-butanesulfonyl) ) Imido and various sulfonate ions.

  The inlet of the channel of the microreactor used in the present invention may be connected to a supply device for introducing a fluid into the channel from the outside, and a small pump may be built in the channel. The supply means for introducing the fluid into the microreactor from the outside is not particularly limited. For example, supply from various pumps, a method of pumping, a method of using a difference in gravity, or a container compressed to a high pressure Or the like can be used. Specific examples of pumps include 1) a syringe pump that pushes fluid in a cylinder with a piston, and 2) a reciprocating pump that increases pressure using a reciprocating motion of a piston or plunger, such as a piston pump or a diaphragm pump, 3) Rotating pumps that rotate gears and rollers such as gear pumps and peristaltic pumps, confine fluid in gaps and push it to transport, and 4) Rotary fluids such as volute pumps and diffuser pumps that rotate by rotating blades and pressurize by centrifugal force Centrifugal pumps that increase the pressure, and other generally known pumps.

  The hydraulic equivalent diameter of the flow path of the microreactor used in the present invention is preferably 1 μm or more and 2000 μm or less, more preferably 10 μm or more and 1000 μm or less, and particularly preferably 20 μm or more and 500 μm or less. When the hydraulic equivalent diameter of the microreactor flow path is 1 μm or less, the pressure loss is extremely large and the treatment amount is remarkably reduced. This is not preferable because the temperature control becomes difficult because the temperature control becomes difficult, and it is preferable. Absent. The hydraulic equivalent diameter mentioned here can be expressed by (channel cross-sectional area × 4 ÷ wetting side length).

  The pre-treatment method and post-treatment method of the reaction solution used in the present invention are not particularly limited, but may be performed using a flow path having a hydraulic equivalent diameter similar to that of the microreactor used in the present invention.

  The microreactor used in the present invention may be equipped with a temperature control device. Here, the temperature control device is not particularly limited as long as it has a heating and cooling function and can be controlled to a predetermined temperature. However, a pipe through which a heat medium or a refrigerant flows, an electric heater, a Peltier element, etc. Can be mentioned. It is preferable to install the thermal control device near the reaction flow path because the temperature response is quick. The constituent material of the microreactor is preferably a material having high thermal conductivity. For example, metals such as copper, gold, aluminum, silver, nickel, iron, platinum, lead, tin, titanium, alloys such as stainless steel, hastelloy, brass, copper tungsten, aluminum nitride, silicon nitride, boron nitride, beryllium oxide , Etc., silicon, quartz, glass, diamond, sapphire, silicon carbide, and the like.

  EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited at all by these Examples.

Example 1
The microreactor was made by bonding a glass plate on a silicon substrate having grooves and electrodes formed inside the grooves. Specifically, it was created according to the following procedure.
1) Using an ICP etching technique on a silicon substrate, two grooves having a depth of 40 μm, a width of 100 μm, and a length of 100 mm are formed in a portion where an electrode is located, and a 10 μm square column is formed between the grooves at a pitch of 10 μm. A groove having a depth of 40 μm and a width of 100 μm was formed in the shape shown in FIG. 1 up to the reaction solution inlet and outlet.
2) Thermal oxidation was performed at 1000 ° C. in the presence of water vapor to form an insulating layer.
3) A photoresist was used to mask the portions other than the electrode position.
4) After forming a chromium layer of about 500 mm by sputtering technique, a platinum layer of about 2500 mm was formed.
5) The resist was dissolved, unnecessary metal layers were removed, and a pair of electrodes having a width of 80 μm and a distance between electrodes of 50 μm as shown in FIG. 2 was formed.
6) The silicon substrate on which the electrode was formed and the Pyrex glass with a hole for injecting the reaction solution were bonded using an anodic bonding technique.
7) Dicing was performed, and unnecessary portions were cut to complete the microreactor.

  A reaction solution (dimethyl maleate: 20 wt%, sodium acetate: 2 wt% / methanol) was injected from one inlet of the microreactor channel, and the electrode on the channel side was used as a cathode. A reaction solution (sodium acetate: 2 wt% / methanol) was injected from the other inlet of the microreactor channel, and the electrode on the channel side was used as an anode. The microreactor was mounted on a Peltier device and the temperature was controlled at 15 ° C. The reaction solution was fed at a flow rate of 10 μL / min using a syringe pump. The residence time on the electrode at this time was about 2.5 seconds. Using a potentio galvano stud (HSV-100 manufactured by Hokuto Denko), a voltage of 5 V was applied, and the discharged sample was quantitatively analyzed by gas chromatography. The yield of tetrabutylbutanecarboxylic acid, which is a dimer of dimethyl maleate, was 2.1 mol%.

(Comparative Example 1)
As shown in FIG. 3, the experiment was performed in the same manner as in Example 1 except that the microreactor in which the partition walls between the electrodes of the microreactor shown in Example 1 were removed was used. The yield of tetrabutylbutanecarboxylic acid was 1.1 mol%.

(Comparative Example 2)
In order to equalize the time required to pass through the flow path with electrodes using the reactor in which the distance between the electrodes of the microreactor shown in Example 1 is set to 500 μm, the flow rates of the two reaction liquids are each set to 63 μL / min. The experiment was performed in the same manner as in Example 1 except that. Tetrabutylbutanecarboxylic acid could not be detected by gas chromatography, and the yield of dimethyl succinate was 0.8 mol%.

(Example 2)
A microreactor having the same flow path shape was manufactured in the same manner as in the microreactor production process 4) shown in Example 1 except that nickel was sputtered instead of sputtering platinum. Further, the microreactor was subjected to electrolysis by applying a voltage while feeding a 0.10 M palladium chloride / 10% hydrochloric acid solution to the cathode-side channel and 10% hydrochloric acid to the anode-side channel at a flow rate of 10 μL / min. Then, palladium black was electrodeposited on the cathode.

  A reaction solution (phenylacetonitrile: 3.0 g, 20% hydrochloric acid: 30 mL, ethanol: 50 mL) was injected from one inlet of the microreactor channel, and the electrode on the channel side was used as a cathode. 10% hydrochloric acid was injected from the other inlet of the microreactor channel, and the electrode on the channel side was used as the anode. The microreactor was mounted on a Peltier device and the temperature was controlled at 15 ° C. The reaction solution was fed at a flow rate of 10 μL / min using a syringe pump. The residence time on the electrode at this time was about 2.5 seconds. Using a potentio galvano stud (HSV-100, manufactured by Hokuto Denko), a voltage of 5 V was applied, and the discharged sample was quantitatively analyzed by liquid chromatography. The yield of 2-phenylethylamine was 4.5 mol%.

(Comparative Example 3)
Except that the microreactor having the shape shown in Comparative Example 1 was used, the electrode was processed in the same manner as in Example 3 and the same experiment was performed. The yield of 2-phenylethylamine was 1.5 mol%.

(Comparative Example 4)
In order to equalize the time required to pass through the flow path with electrodes using the reactor in which the distance between the electrodes of the microreactor shown in Example 2 is 500 μm, the flow rates of the two reaction liquids are each set to 63 μL / min. The experiment was performed in the same manner as in Example 3 except that. 2-Phenylethylamine could not be detected by liquid chromatography.

1 is a schematic plan view of a microreactor according to an embodiment of the present invention. It is a fragmentary sectional view of the microreactor concerning one embodiment of the present invention. It is a fragmentary sectional view of the microreactor concerning one embodiment of the present invention.

Explanation of symbols

1. 1. Electrode part flow path 2. A flow path from the electrode part to the inlet and outlet. Inlet and outlet

Claims (3)

  There is a flow path including a pair of electrodes of a working electrode and a counter electrode, a distance between the working electrode and the counter electrode is 200 μm or less, and a partition wall is provided between the working electrode and the counter electrode A method for producing a chemical substance by carrying out an electrochemical reaction using a microreactor.   The method for producing a chemical substance according to claim 1, wherein the microreactor has a temperature control device. The method for producing a chemical substance according to claim 1 or 2, wherein the electrochemical reaction is a reduction dimerization reaction.

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