JP4285256B2 - Method for carrying out chemical reaction and microchannel structure therefor - Google Patents

Description

  The present invention relates to a microchannel structure suitable for performing chemical / physical operations such as liquid feeding, mixing, chemical reaction, separation and the like in a microchannel, a method for performing a chemical reaction using the microchannel structure, and a microchannel for the same. The present invention relates to a channel structure.

The phase transfer catalyst accelerates the reaction between components dissolved in each phase by going back and forth between an organic phase and an aqueous phase that are insoluble in each other. As an example of a phase transfer catalyst, a reaction system using a quaternary ammonium salt will be described as an example. In Figure 1, CN as nucleophilic anion (15) ^- in the use and exchange an alkyl halide (16) to (R-X) to a nitrile (17) (R-CN) reaction, quaternary ammonium salts (18) a (Q + ^{X -)} illustrates the concept of reaction mechanism when used as a phase transfer catalyst a. A reaction system of an aqueous phase containing Na ⁺ CN ⁻ composed of a nucleophilic anion (15) and a nonpolar organic phase containing (R—X) which is an alkyl halide (16) which is an organic substrate that reacts with the aqueous phase. The phase transfer catalyst quaternary ammonium salt (18), (Q ⁺ X ⁻ ), is an aqueous phase nucleophilic anion (15) (CN ⁻ ) and a halogen anion (38) that forms an ion pair with itself. By exchanging (X ⁻ ), nucleophilic anion (15) (CN ⁻ ) is transferred to the organic phase where the reaction takes place to promote the reaction. After the reaction, an ion pair is formed with (X ⁻ ) which is the released halogen anion (38), and again becomes (Q ⁺ X ⁻ ) which is a quaternary ammonium salt (18) to return to the aqueous phase. repeat. As phase transfer catalysts, phosphonium salts, crown ethers, cryptands, dialkyl polyoxyethylene oxides and the like are generally known in addition to quaternary ammonium salts. In addition, the reaction efficiency of the reaction system using the phase transfer catalyst depends on how efficiently the phase transfer catalyst can move between the phases, and the phase transfer efficiency of the phase transfer catalyst depends on the catalyst phase and the reaction phase. The larger the specific interface area, the better the shorter the diffusion distance of the interphase transfer touch.

  The above example is an example of a two-phase phase transfer catalytic reaction. Recently, the phase transfer catalyst becomes insoluble in both the organic phase and the aqueous phase under a specific reaction condition, and exists as a third liquid phase. Reaction processes have been attempted (see, for example, Non-Patent Document 1).

  In the above example, as shown in FIG. 12, the phase transfer catalyst phase (41) is the third phase, and the organic phase (2) and the aqueous phase (1) are not directly in contact with each other so as not to contact each other. To carry out the reaction. A special Lamond stirrer (42) is used for stirring. In this way, reactants dissolved in both phases can be reacted while the organic phase and the aqueous phase are separated, and the selectivity can be increased, and the reaction rate can be rapidly increased even at a reaction temperature near room temperature. It has been reported that it is possible to perform a periodic operation in which an organic phase containing a reaction product is extracted and an organic phase containing a reaction product is newly added to react again. For example, polyethylene glycol (average molecular weight 3000) is used as the phase transfer catalyst, dodecane is used as the organic solvent, potassium hydroxide is used as the aqueous phase, and the phase transfer catalyst phase is arranged between the organic phase and the aqueous phase to form three phases. However, in the example where benzyl butyl ether was synthesized from benzyl chloride and butanol in an organic solvent, the rate of ether formation in the three-phase system was 7 times faster than that in the two-phase system, and the organic phase was brought into contact with the aqueous phase. The selectivity was 0.6, while the reaction was carried out so as to avoid contact between the organic phase and the aqueous phase using a stationary three-phase batch reaction with an ultrasonic transmitter. It has been reported that the selectivity at that time was as high as 0.9 (for example, see Non-Patent Document 1).

  However, in general, in a reaction vessel such as a test tube, a beaker, or a reaction kettle, the arrangement of each phase is determined by the specific gravity of each phase or is mixed with other phases due to the philicity, so that a phase transfer catalyst is included. It is extremely difficult to position the three phases between the organic phase and the aqueous phase. In addition, it is very practical to use by scaling up, such as designing a special stirrer to stir so that each phase does not mix, or stirring so as not to break the interface of each phase due to vibration. difficult. Furthermore, since it is difficult to take out or replace each phase separately, there is a problem that it is difficult to continuously perform the reaction.

"Development of next-generation chemical reaction process technology Development of multi-phase catalytic reaction process technology 2001 technical report", Chemical Technology Strategy Organization, May 2001, pages 13-43

  The object of the present invention has been proposed in view of such a conventional situation, and in a reaction using a phase transfer catalyst in a microchannel, an organic phase fluid, an aqueous phase fluid, and a fluid containing a phase transfer catalyst are used. In conducting chemical reactions, the phase of the fluid containing the phase transfer catalyst is placed between the phase of the organic phase fluid and the phase of the aqueous phase fluid, or the reaction is continuously carried out by stirring so that each phase does not suspend. And a method for carrying out a chemical reaction suitable for easily separating / recovering and reusing a fluid including an organic phase fluid, an aqueous phase fluid, and a phase transfer catalyst, and a microchannel structure therefor. .

  In order to solve the above problems, the present invention introduces an organic phase fluid containing a chemical reaction raw material and an aqueous phase fluid and a fluid containing a phase transfer catalyst into a microchannel, and the fluid causes a laminar flow in the microchannel. A fluid containing the phase transfer catalyst is sent in a layer between the organic phase fluid and the aqueous phase fluid, and the chemical reaction raw material generates a chemical reaction in the microchannel. In order to carry out such a chemical reaction, three or more inlets for introducing a fluid, an introduction channel communicating with them, and a fluid introduced and communicated with the introduction channel A micro-channel structure having a micro-channel, a three- or more-exhaust channel for branching out of the micro-channel and separating and discharging the fluid, and a discharge port communicating with them, Fluid progression at or near the boundary between fluids By using a microchannel structure having a microchannel in which a partition wall having a height equal to or less than the channel depth is disposed discontinuously along the direction of the fluid, The present invention has finally been completed.

  Hereinafter, the present invention will be described in detail.

In recent years, a fluid is introduced into a microchannel using a microchannel structure having a microchannel having a length of about several centimeters on a glass substrate of several cm square and a width and depth of sub-μm to several hundred μm. Research that conducts chemical reactions is attracting attention. In such a microchannel, an efficient chemical reaction can be performed without performing a special stirring operation due to the rapid diffusion of molecules due to the effect of a short intermolecular distance and a large specific interfacial area in a microspace. For example, as shown in FIG. 2, an aqueous phase (1) and an organic phase (2) in which raw materials are dissolved are introduced into a Y-shaped microchannel, and the organic phase and the aqueous phase formed at the Y-shaped merged portion are introduced. Reaction occurs at fluid boundary (3). In general, there are almost all cases where the Reynolds number is smaller than 1 in a microscale flow path, and a laminar flow state as shown in FIG. 2 is obtained unless the flow velocity is significantly increased. Moreover, since the diffusion time is proportional to the square of the width (9) of the microchannel, the smaller the microchannel width (9), the more the mixing proceeds by molecular diffusion without actively mixing the reaction solution. , Reaction and extraction are likely to occur. In addition, as shown in FIG. 3, if the fluid outlet (12) of the microchannel is also Y-shaped, the water phase and the organic phase can be separated relatively easily. Extraction and separation operations are performed between the liquid phases.
<Chemical reaction method>
The method for carrying out a chemical reaction of the present invention utilizes the characteristics of the microchannel, and introduces an organic phase fluid containing a chemical reaction raw material and an aqueous phase fluid and a fluid containing a phase transfer catalyst into the microchannel, The fluid containing the phase transfer catalyst is sent in a layer between the organic phase fluid and the aqueous phase fluid while the fluid maintains a laminar flow in the microchannel, and the chemical reaction raw material is microflowed. It causes a chemical reaction in the road.

  Here, the organic phase fluid containing a chemical reaction raw material used in the present invention refers to a raw material introduced into a microchannel to obtain a target reaction product and a medium for dissolving the raw material. The contained fluid is introduced from the microchannel separately from the aqueous phase fluid containing the chemical reaction raw material and the fluid containing the phase transfer catalyst, and causes a chemical reaction in the microchannel. The organic solvent used in the organic phase fluid is not particularly limited as long as it does not depart from the object of the present invention. In general, alcohols such as methanol, ethanol and butanol, esters such as ethyl acetate and butyl acetate, dibutyl ether and the like Organic solvents such as linear ethers and cyclic hydrocarbons such as toluene, hexane, and cyclohexane are used.

  The aqueous phase fluid containing a chemical reaction raw material used in the present invention refers to a raw material introduced into a microchannel and a medium for dissolving the raw material in order to obtain a target reaction product. It is introduced from the microchannel separately from the organic phase fluid containing the chemical reaction raw material and the fluid containing the phase transfer catalyst, and causes a chemical reaction in the microchannel. The solvent used in the aqueous phase fluid may be water such as cold water or warm water, and may be an organic solvent added as long as it does not depart from the object of the present invention.

  The fluid containing a phase transfer catalyst used in the present invention refers to a raw material introduced into a microchannel and a medium for dissolving the raw material to obtain a target reaction product, and the fluid containing these reaction raw materials is a chemical reaction. The organic phase fluid containing the raw material and the aqueous phase fluid are introduced separately from the microchannel and cause a chemical reaction in the microchannel. The organic solvent used in the fluid containing the phase transfer catalyst is not particularly limited as long as it does not depart from the object of the present invention, but an alcoholic organic solvent such as methanol or ethanol is generally used. Furthermore, as the phase transfer catalyst, those generally used can be adopted as long as they do not deviate from the object of the present invention. For example, N- (4-trifluoromethylbenzyl) cinconium bromide, n -Ammonium salt phase transfer catalyst such as octyldimethylammonium bromide, cinchondium chloride, or the like, or 12-crown-4, 15-crown-5, 18-crown-6, dibenzo-18-crown-6, dicyclohexyl- Crown ether phase transfer catalysts such as 18-crown-6, acyclic compounds having similar functions to crown ether compounds such as polyethylene glycol and polyvinyl alcohol, and the above ammonium phase transfer catalysts, crown ether phase transfer catalysts, Crown ether compounds and similar machines Among the acyclic compound having the mixtures thereof of any two or more different. By using a mixture of two or more different phase transfer catalysts, for example, the effect of facilitating the transfer of an initiator such as alkali to the organic phase and simultaneously improving the selectivity of the optically active substance can be achieved. can get.

  The chemical reaction raw material contained in the organic phase fluid and the aqueous phase fluid used in the present invention means that the chemical reaction raw material used can be substantially dissolved in each of the organic phase fluid and the aqueous phase fluid, and is included in the organic phase fluid. The chemical reaction raw material and the chemical reaction raw material contained in the aqueous phase fluid may be combined in such a way as to allow a chemical reaction by the action of the phase transfer catalyst. For example, N- (4-trifluoromethylbenzyl) cinconium bromide as a phase transfer catalyst, phenalside and isobutyraldehyde dissolved in an organic phase fluid, and lithium hydroxide dissolved in an aqueous phase fluid as a chemical reaction raw material Can be given as examples of combinations. These are appropriately determined depending on the target product, reaction efficiency, solubility of raw materials, and the like.

  The organic phase fluid, the aqueous phase fluid containing the chemical reaction raw material, and the fluid containing the phase transfer catalyst are introduced into the micro flow channel, and these fluids maintain the laminar flow in the micro flow channel and include the phase transfer catalyst. The fluid forms a layer between the organic phase fluid containing the chemical reaction raw material and the aqueous phase fluid containing the chemical reaction raw material. These fluids are fed while the chemical reaction raw material causes a chemical reaction in the microchannel. It is. Needless to say, the present invention can be applied to all reactions using a phase transfer catalyst. For example, a hydrolysis reaction, a cyano substitution reaction, an aldol reaction, an alkylation reaction, a daltzen reaction using a phase transfer catalyst. Examples include condensation, epoxidation reaction, asymmetric aldol reaction, asymmetric alkylation reaction, asymmetric darzen condensation, asymmetric epoxidation reaction and the like.

  As described above, the present invention makes it possible to reduce the specific gravity and lyophilicity of each fluid by utilizing the characteristics of the micro flow channel that can easily form a laminar flow without substantially intermingling the introduced fluid. The phase transfer catalyst phase can be disposed between the organic phase and the aqueous phase without depending on the liquid phase, and the fluid containing the phase transfer catalyst can be used to convert the organic phase fluid containing the chemical reaction raw material and the chemical reaction raw material. By forming a layer between the water-phase fluid and the water-phase fluid, the reactant (chemical reaction raw material) dissolved in both fluids is allowed to react without causing direct contact between the organic-phase fluid and the water-phase fluid. Can be implemented. In addition, as described above, in the microchannel, the rapid diffusion of molecules due to the short intermolecular distance and the effect of a large specific interfacial area enables efficient chemical reaction without special stirring operation. Without mixing with fluid stirrers or vibrations, the fluids containing the phase transfer catalyst, the organic phase fluid containing the chemical reaction raw material, and the aqueous phase fluid containing the chemical reaction raw material are kept in contact with each other without mixing the fluids. The reaction can proceed promptly.

  In addition, the chemical reaction carrying out method of the present invention is to carry out a chemical reaction while maintaining a laminar flow in the micro flow channel as described above. However, the micro flow channel then divides the flow channel (also referred to as a separation unit). ), A fluid containing a phase transfer catalyst, an organic phase fluid containing a chemical reaction raw material, and an aqueous phase fluid containing a chemical reaction raw material can be separated and discharged. By doing so, as described later, each used fluid can be used again for a chemical reaction, and an expensive material such as a phase transfer catalyst can be recovered and reused.

  The method for carrying out a chemical reaction according to the present invention has the above-described features. More specifically, the method for carrying out a chemical reaction includes three or more inlets for introducing a fluid, an introduction channel communicating with them, and the introduction. A micro-channel for flowing a fluid to be introduced and communicating with the channel, three or more discharge channels for branching from the micro-channel and separating and discharging the fluid, and a discharge port communicating with them And a method for performing a chemical reaction using a micro-channel structure having: a fluid containing a phase transfer catalyst is introduced from at least one inlet, and from at least one other inlet An organic phase fluid containing a chemical reaction raw material is introduced, and an aqueous phase fluid containing a chemical reaction raw material is introduced from at least one additional inlet. As described above, the fluid used in the present invention is introduced from three or more inlets, and the fluid containing the phase transfer catalyst is changed into the organic phase fluid containing the chemical reaction raw material and the chemical reaction raw material while maintaining the laminar flow in the micro flow path. By arranging them between the aqueous phase fluids containing the chemical reaction, the chemical reaction can be efficiently performed, and each fluid can be separated and discharged even after the chemical reaction.

  Furthermore, after performing the chemical reaction in the micro flow channel, one or two or more fluids selected from the group consisting of an organic phase fluid, an aqueous phase fluid, and a fluid containing the phase transfer catalyst are supplied to the separation unit of the discharge channel. Then, after separation, each fluid can be reintroduced from a predetermined introduction port, and the reaction efficiency is further improved. By doing so, it is possible to continuously react by recovering and reusing an expensive phase transfer catalyst, or by recovering and reusing an organic phase or an aqueous phase with unreacted substances. is there.

Moreover, said microchannel is a channel generally having a width of 500 μm or less and a depth of 300 μm or less. The width and depth of the introduction channel and the discharge channel are not particularly limited, but may be the same width and depth as the microchannel. The sizes of the introduction port and the discharge port are not particularly limited, but may generally be about 0.1 to several mm in diameter.
<Microchannel structure>
A microchannel structure for use in the method for carrying out a chemical reaction according to the present invention includes three or more inlets for introducing a fluid, an introduction channel communicating with the inlets, a communication channel with the introduction channel, and the introduction channel. A micro-channel structure having a micro-channel for flowing a fluid, three or more discharge channels branching from the micro-channel and separating and discharging the fluid, and a discharge port communicating with them A micro flow in which a partition wall having a height equal to or less than a flow path depth is disposed discontinuously with respect to the fluid traveling direction along the fluid traveling direction at or near the boundary between the fluids It has a road.

  A reintroduction flow path for guiding at least one separated fluid from a discharge port to the introduction port; a pump communicating with the reintroduction flow path and sending fluid; and the reintroduction flow It is preferable to further include a reservoir tank that communicates with the path and temporarily stores fluid.

  Hereinafter, the fine channel structure of the present invention will be described in more detail with reference to the drawings.

  As described above, when two or more kinds of fluids are introduced into the microchannel, laminar flows are formed relatively easily, and boundaries between the two fluids are formed. However, the boundaries between the two or more kinds of fluids are further stabilized. In order to make it easy to separate from other fluids with which the fluid is in contact at the branching portion that is held at the branching path from the minute channel to the discharge channel, as shown in FIG. Alternatively, a partition wall (7) discontinuous with respect to the fluid direction and having a height equal to or less than the channel depth is formed on the bottom surface (36) of the microchannel (5) in the vicinity thereof along the fluid traveling direction. May be. Here, discontinuous means that the place where the partition wall (7) is present and the place where the partition wall (7) is absent are alternately arranged at an arbitrary interval with respect to the fluid traveling direction (26). In general, it is necessary to repeat contact and isolation between fluids many times in a micro flow channel (5) having a width of several μm to several hundred μm and a length of several cm to several tens of cm. Is preferably about 1 μm to 1000 μm, and the ratio between where the partition wall (7) is present and where the partition wall (7) is not present It is more preferable that the sum of the areas is equal to the sum of the areas where the fluid and the fluid contact each other where there is no partition wall (7). By using a structure having such a flow path, a fluid containing a phase transfer catalyst (hereinafter sometimes simply referred to as “catalyst fluid”) and an organic phase fluid containing a chemical reaction raw material (hereinafter simply referred to as “organic”). And a water phase fluid (hereinafter, simply referred to as “water”) containing a chemical reaction raw material are separated very well and each fluid is recovered and used again for a chemical reaction. And an efficient chemical reaction can be carried out.

  The microchannel structure according to the present invention has three or more for branching from the microchannel and discharging the fluid on the rear side of the microchannel when viewed from the liquid feeding direction after the chemical reaction in the microchannel. The discharge flow path and the discharge port communicating with them are provided. This discharge flow path has a branch portion at the communication portion between the micro flow path and the discharge flow path, and the laminar flow in the micro flow path is separated at the branch portion. Further, a reintroduction flow path for guiding at least one separated fluid from the discharge port to the introduction port is provided. The reintroduction channel is for guiding at least one of the separated catalyst fluid, organic fluid, and water, and the reintroduction channel communicates with any one or any of the above-described introduction ports through the discharge port. is doing. The reintroduction channel further includes a micropump that is in communication with the reintroduction channel and supplies a fluid, and a reservoir tank that is in communication with the channel and temporarily stores the fluid. You may have. By adopting such a structure, it is possible to continuously reuse an expensive phase transfer catalyst continuously, or to continuously introduce a fluid that has been left behind for a chemical reaction to the introduction port. As a result, an efficient chemical reaction can be carried out.

  Moreover, said microchannel is a channel generally having a width of 500 μm or less and a depth of 300 μm or less. The width and depth of the introduction channel and the discharge channel are not particularly limited, but may be the same width and depth as the microchannel. The sizes of the introduction port and the discharge port are not particularly limited, but may generally be about 0.1 to several mm in diameter.

  As a means for introducing the fluid, liquid feeding may be performed using a liquid feeding pump (4) installed outside the microchannel structure (28) as shown in FIG. In addition, the method of introducing the fluid discharged from the discharge port B (23) through the predetermined introduction port B (20) again is to put the fluid to be fed by the liquid feed pump (4) in advance as shown in FIG. The container B (10) may be returned through a capillary tube (40) or the like. As another form, as shown in FIG. 6, a reservoir tank (13) for storing fluid and a micropump (14) for feeding fluid are embedded in the microchannel structure (28), and the reservoir Fluid from the tank (13) by the micropump (indicated as MP in FIG. 5) (14) is sent to the inlet B (20) and discharged from the outlet B (23) through the microchannel (5). The fluid may be returned to the reservoir tank (13) again through the recovery channel (27) provided in the microchannel structure (28), and the fluid may be fed again by the micropump (14). . If the reservoir tank (13) has a capacity that does not deplete the fluid in the reservoir tank (13) even if the fluid is fed to the entire microchannel (5), the reservoir tank (13) is sized. There is no particular limitation. The width and depth of the recovery channel (27) are not particularly limited, but may be the same width and depth as the microchannel (5).

  The microchannel substrate having the microchannels constituting the microchannel structure as described above is made of, for example, glass, quartz, ceramic, silicon, or a substrate material such as metal or resin by machining, laser processing, etching, or the like. Can be manufactured by direct processing. Further, when the substrate material is ceramic or resin, it can also be manufactured by molding using a mold such as a metal having a channel shape.

  In general, the microchannel substrate has a microchannel structure in which a cover body having a small hole having a diameter of about several millimeters is laminated and integrated at a position corresponding to the inlet and outlet that communicate with the microchannel. Use as a body. As a method for joining the cover body and the micro-channel substrate, when the substrate material is ceramics or metal, soldering or adhesive is used, or when the substrate material is glass, quartz, or resin, it is a hundred to several hundreds of degrees A bonding method suitable for each substrate material is used, such as thermal bonding by applying a load at a high temperature, or when the substrate material is silicon, by activating the surface by washing and bonding at room temperature.

  According to the present invention, the following effects can be obtained.

  According to the method for carrying out a chemical reaction of the present invention, the catalyst fluid, the organic fluid, and the aqueous phase fluid are introduced from separate inlets provided in the microchannel structure of the present invention, and the organic fluid and the aqueous phase fluid are in direct contact with each other. The catalyst fluid is arranged between the organic fluid and the water phase fluid so that one side of the catalyst fluid is the organic fluid and the other side is the water phase fluid while maintaining the boundary between each fluid. The chemical reaction is carried out by contacting along the direction, and the catalyst fluid, organic fluid and aqueous phase fluid are separated and discharged from separate outlets, without depending on the specific gravity or philicity of each layer The catalyst fluid can be placed between the organic phase and the aqueous phase and sent to carry out a chemical reaction.

  Further, by using a mixture of two or more different phase transfer catalysts, for example, it is possible to facilitate the transfer of an initiator such as alkali to the organic phase and to simultaneously improve the selectivity of the optically active substance. Obtainable.

  In addition, as described above, in the microchannel, due to the rapid diffusion of molecules due to the short intermolecular distance and the effect of a large specific interfacial area, an efficient chemical reaction can be performed without performing a special stirring operation by the chemical reaction execution method according to the present invention. Therefore, the reaction can proceed quickly without mixing each phase while maintaining the interfaces of the catalyst fluid, organic fluid, and water phase fluid, without stirring by a special stirrer or vibration. it can.

  Further, by applying the chemical reaction execution method of the present invention, each phase is introduced by reintroducing at least one of the separated catalyst fluid, organic fluid, and aqueous phase fluid from the predetermined introduction port. Since it can be recovered and discarded or reused independently, the expensive phase transfer catalyst can be reused repeatedly, or the fluid that has been left behind for the chemical reaction in the fluid that has undergone the chemical reaction is introduced into the inlet. As a result, an efficient chemical reaction can be carried out.

  Further, in the microchannel structure for carrying out the chemical reaction of the present invention, the partition wall having a height equal to or less than the channel depth is formed along the fluid traveling direction at or near the boundary between the fluids. A microchannel structure having microchannels discontinuously arranged with respect to the traveling direction of the catalyst, and having such a channel makes it possible to form a catalyst fluid, an organic fluid, and an aqueous phase fluid. Can be separated very well and each fluid can be recovered and used again for chemical reactions.

  The microchannel structure according to the present invention further includes a reintroduction channel for guiding at least one of the catalyst fluid, the organic fluid, and the aqueous phase fluid separated and discharged at the discharge port from the discharge port to the introduction port. The re-introduction channel may further include a pump that communicates with the re-introduction channel and feeds fluid, and a reservoir tank that communicates with the channel and temporarily stores the fluid. In addition, it is possible to re-use the expensive phase transfer catalyst for continuous reaction, or continuously introduce the chemical reaction raw material remaining in the chemical reaction fluid. It can be reintroduced into the mouth, and as a result, an efficient chemical reaction can be carried out.

  Hereinafter, embodiments of the present invention will be described in detail. Needless to say, the present invention is not limited to these examples, and can be arbitrarily changed without departing from the scope of the invention.

As an example, a microchannel structure (28) as shown in FIG. 7 and FIG. 8 showing the AA ′ section in FIG. 7 and FIG. 9 showing the BB ′ section was manufactured. The shape of the micro channel has three inlets and three outlets, and the inlet channel (30) communicating with each inlet (11) and the outlet channel (31) communicating with each outlet (12). ) Was used as a microchannel (5) branched into three in a ψ-shape. The formed microchannel (5) has a width of 150 μm, a depth of 20 μm, and a length of 300 mm. Further, as shown in FIG. 4, a partition wall (7 μm high, 50 μm long, 5 μm wide) at a position of about 50 μm and about 100 μm from one side surface of the flow channel so that the width direction of the flow channel is divided into three. ) At intervals of 200 μm. The flow path is 70mm
A microchannel substrate (6) was produced by forming a Pyrex (registered trademark) substrate of × 38 mm × 1 mm (thickness) by general photolithography and wet etching. A Pyrex (registered trademark) substrate of the same size, in which small holes (35) having a diameter of 0.6 mm are provided by mechanical processing means at positions corresponding to three inlets (11) and three outlets (12). The micro flow path (5) was sealed by bonding by heat fusion as the cover body (29) to form a micro flow path structure.

Using this microchannel structure, a mixture of N- (4-trifluoromethylbenzyl) cinchoninium bromide and 1% polyethylene glycol (PEG200) shown in FIG. 10 was used as a phase transfer catalyst. Then, 1-phenacyl-1,2-epoxy-4-methylpentane, which is an optically active epoxy ketone, was synthesized by an asymmetric Durzens reaction between isobutyraldehyde and aromatic ketone, phenalside. In addition, as an index of the optical activity of this product, enantioselectivity shown in the following (formula 1) was used as both indicating the difference in the abundance between the R isomer and the S isomer, which are optical isomers. In addition, R and S of (Formula 1) show the production amount of R body and S body, respectively.
Enantioselectivity = (R−S) / (R + S) (Formula 1)
As a catalyst fluid, a mixture of N- (4-trifluoromethylbenzyl) cinchoninium bromide (53.4 mg, 0.1 mmol) and 1% polyethylene glycol (PEG200) was dissolved in ethanol. As the organic fluid, phenalside (154.5 mg, 1.0 mmol) and isobutyraldehyde (0.14 ml, 1.5 mmol) were dissolved in dichloroethane at room temperature. As an aqueous phase fluid, potassium hydroxide (2.0 mmol) was dissolved in water. Catalyst fluid is introduced from the central inlet B (20) of the microchannel structure shown in FIG. 7, organic fluid is introduced from the inlet A (19), and aqueous fluid is introduced from the inlet C (21). When the liquid is fed at a rate of 5 μL / min, the organic fluid, the catalyst fluid, and the water phase fluid can form a three-phase laminar flow in the microchannel, and the organic fluid can be fed from the discharge port A (22). The catalyst fluid could be separated and discharged from the outlet B (23) and the aqueous phase fluid from the outlet C (24) very well. The reaction temperature was 4 ° C. by placing the microchannel structure in a thermostat. The reaction time in the microchannel when the liquid was fed into the microchannel at a liquid feeding speed of 5 L / min was about 4 seconds.

  The discharged organic fluid was extracted with diethyl ether, and the obtained organic fluid was washed with saturated saline, followed by filtration and evaporation of the solvent in order to obtain a crude product. Flash column chromatography (hexane: diethyl ether = The desired epoxy ketone was obtained by separation and purification in 15: 1). The yield of the obtained epoxy ketone was 75% with respect to the raw material N- (4-trifluoromethylbenzyl) cinconium bromide, and the enantioselectivity was 69 (%).

  Further, when the separated catalyst fluid was recovered, 90% of the transferred phase transfer catalyst could be recovered.

  Furthermore, when the reaction was carried out by introducing again from the introduction port of the microchannel structure together with the new organic fluid and aqueous phase fluid, the target epoxy ketone could be obtained again by the same extraction method as above, The yield was 75% with respect to the raw material N- (4-trifluoromethylbenzyl) cinchoninium bromide, and the enantioselectivity was 69 (%).

Comparative example

  As a comparative example, a sample bottle having a diameter of 5 cm and a height of 10 cm was used. As in the case of Example 1, as a phase transfer catalyst, N- (4-trifluoromethylbenzyl) cinchoninium bromide and 1% shown in FIG. An optically active epoxy ketone was synthesized by an asymmetric Durzence reaction of isobutyraldehyde and an aromatic ketone, phenalside, using a mixture of polyethylene glycol (PEG200).

  The catalyst fluid was a mixture of N- (4-trifluoromethylbenzyl) cinchoninium bromide (53.4 mg, 0.1 mmol) and 1% polyethylene glycol (PEG 200) dissolved in ethanol. As the organic fluid, phenalside (154.5 mg, 1.0 mmol) and isobutyraldehyde (0.14 ml, 1.5 mmol) were dissolved in dichloroethane at room temperature. As an aqueous phase fluid, potassium hydroxide (2.0 mmol) was dissolved in water. When 40 ml each of the organic fluid, the aqueous phase fluid, and the catalytic fluid are put into the sample bottle, the phase transfer catalytic phase is mixed with the organic phase and the aqueous phase to form two phases, and the organic fluid, the aqueous phase fluid, and the catalytic fluid are mixed. Three phases could not be formed.

  The sample bottle was placed in a thermostatic bath and stirred at 4 ° C. for 72 hours to carry out the reaction by suspending the reaction solution in the sample bottle, and then the reaction was stopped by adding 1N hydrochloric acid. After the reaction was stopped, the reaction solution in the sample bottle separated into two phases, but the phase transfer catalyst could not be recovered. The reaction solution after the reaction was extracted with diethyl ether, and the obtained organic phase was washed with saturated brine, filtered and evaporated to obtain a crude product. Flash column chromatography (hexane: diethyl ether = The target epoxy product was obtained by separating and purifying in 15: 1). The yield of the obtained epoxy ketone was 75% with respect to the raw material N- (4-trifluoromethylbenzyl) cinconium bromide, and the enantioselectivity was 69 (%).

It is a figure which shows an example of the reaction system using a phase transfer catalyst. It is a conceptual diagram which shows the laminar flow in a Y-shaped microchannel. It is a conceptual diagram which shows the laminar flow in a double Y-shaped microchannel. It is a conceptual diagram which shows the example which formed the discontinuous partition wall located in the fluid boundary in the bottom face of a microchannel. It is a conceptual diagram which shows the means to liquid-feed with the liquid feed pump installed outside the microchannel structure. It is a conceptual diagram which shows the means to liquid-feed with the micro pump which embedded the fluid inside the microchannel structure. It is the microchannel structure used in the example. It is A-A 'sectional drawing (enlargement) in the microchannel structure of FIG. It is B-B 'sectional drawing (enlargement) in the microchannel structure of FIG. It is the phase transfer catalyst used in the Example. It is the synthesis | combination of the optically active epoxy ketone by the asymmetrical Darzens reaction of isobutyraldehyde and phenalside in an Example. It is the figure which showed an example which makes it exist between an organic fluid and an aqueous phase fluid so that a catalyst fluid may be made into a 3rd phase, and an organic fluid and an aqueous phase fluid may not contact directly.

Explanation of symbols

1: Water phase fluid 2: Organic fluid 3: Fluid boundary 4: Liquid feed pump 5: Microchannel 6: Microchannel substrate 7: Partition wall 8: Container A
9: Width of microchannel 10: Container B
11: inlet 12: outlet 13: reservoir tank 14: micropump 15: nucleophilic anion 16: alkyl halide 17: nitrile 18: quaternary ammonium salt 19: inlet A
20: Inlet B
21: Inlet C
22: Discharge port A
23: Discharge port B
24: Discharge port C
25: Upper surface 26: Fluid traveling direction 27: Recovery flow path 28: Micro flow path structure 29: Cover body 30: Introduction flow path 31: Discharge flow path 32: Container C
33: Container D
34: Side surface 35: Small hole 36: Bottom surface 37: Depth of minute flow path 38: Halogen anion 39: Width of fluid boundary 40: Capillary tube 41: Catalytic fluid 42: Lamond stirrer

Claims (6)

An organic phase fluid containing a chemical reaction raw material and an aqueous phase fluid and a fluid containing a phase transfer catalyst are introduced into a micro flow channel, and the fluid containing the phase transfer catalyst is maintained in a laminar flow in the micro flow channel. Is a chemical reaction execution method in which a liquid is sent in a layer between the organic phase fluid and the aqueous phase fluid, and the chemical reaction raw material causes a chemical reaction in a microchannel, Three or more introduction ports and introduction flow passages communicating with them, a micro flow passage for communicating the introduction flow passage and flowing the introduced fluid, a branch from the fine flow passage, and separating and discharging the fluid A partition wall having a height equal to or less than the depth of the channel along the fluid traveling direction at or near the boundary between the fluids. Microchannels discontinuously arranged in the direction of fluid flow A fluid containing phase transfer catalyst is introduced from at least one inlet, the organic phase fluid is introduced from at least one other inlet, and at least one further A method for carrying out a chemical reaction, wherein the aqueous phase fluid is introduced from an introduction port . The method for carrying out a chemical reaction according to claim 1, wherein the phase transfer catalyst comprises two or more different phase transfer catalysts. The method for carrying out a chemical reaction according to claim 1 or 2, wherein the fluid containing the organic phase fluid, the aqueous phase fluid and the phase transfer catalyst is separated and discharged. One or two or more fluids selected from the group consisting of the organic phase fluid, the aqueous phase fluid and the fluid containing the phase transfer catalyst are reintroduced through predetermined inlets of each fluid after separation. The method for carrying out a chemical reaction according to claim 3 . Three or more inlets for introducing a fluid, an introduction channel communicating with the inlets, a micro channel for communicating the introduction channel and flowing the introduced fluid, a branch from the micro channel, and A micro-channel structure having three or more discharge channels for separating and discharging a fluid and a discharge port communicating with the three or more channels, and a fluid traveling direction at or near the boundary between the fluids along the partition wall of the channel depth less height according to any one of claims 1 to 4, characterized by having a fine channel which is arranged discontinuously with respect to the traveling direction of the fluid A microchannel structure for use in a method for carrying out a chemical reaction. A reintroduction channel for guiding the separated at least one fluid from a discharge port to the introduction port, a pump that communicates with the reintroduction channel and feeds the fluid, and the reintroduction channel The microchannel structure for use in the method for carrying out a chemical reaction according to claim 5 , further comprising a reservoir tank that communicates with the fluid tank and temporarily stores fluid.

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