JP2007326066A - Reaction apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a reaction apparatus capable of efficiently carrying out diffusion rate-controlling reaction and quickly stopping the proceeding of the reaction at proper timing. <P>SOLUTION: The reaction apparatus comprises a diffusing and mixing reaction part for introducing at least two or more kinds of reagents into a mixing channel 18 with a micro cross-sectional surface area and mixing the reagents by molecular diffusion and a reaction stopping part 20 for stopping the reaction by stirring and mixing the mixed reagents from the mixing reaction part and a reaction stopping chemical. After being mixed in the mixing reaction part by molecular diffusion in the mixing channel with a micro cross-sectional surface area, the reagents are mixed with the reaction stopping chemical in the reaction stopping part to quickly stop the reaction. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a reaction apparatus, and more particularly, to a reaction apparatus for flow reaction for performing organic chemical synthesis such as high-speed diffusion reaction, explosive reaction, and exothermic reaction.

Currently, there is a microreactor as shown in FIG. 14 as a device for performing chemical synthesis with high efficiency. The microreactor introduces the reaction reagents A and B from the introduction channels 100a and 100b to the mixing channel 102 having a microchannel cross-sectional area of 0.05 mm ² or less, for example, and mixes the reaction reagent and performs chemical synthesis. By using mixing by molecular diffusion, high speed, high yield, high selectivity, high reaction temperature controllability, and the like can be obtained.

  However, in such a conventional microreactor, when carrying out a diffusion-controlled reaction in which the target product is changed to a byproduct at high speed, the target product is a byproduct in the micromixing channel of the microreactor. Therefore, the target product cannot be obtained efficiently. In addition, in diffusion-controlled reactions such as explosive reactions, it is necessary to stop the reaction at an optimum time after mixing the reagents.

In order to cope with such problems, the following measures can be considered when the diffusion-controlled reaction is performed in a microreactor.
The microreactor shown in FIG. 15 is provided with a second mixing channel 102b having a large channel cross-sectional area after a first mixing channel 102a having a micro channel cross-sectional area. In this microreactor, mixing using high-speed molecular diffusion is performed in the micro flow channel of the first mixing flow channel 102a, and then the mixed product is guided to the second mixing flow channel 102b having a relatively large cross-sectional area, whereby molecules Reduces the diffusion rate and suppresses the formation of by-products. However, in this method, since a by-product is continuously generated at a low speed in the second mixing channel, it is impossible to reliably stop the reaction, and as a result, the yield of the target product is reduced. Lower. In addition, since the second mixing channel has a large cross-sectional area (volume), the residence time becomes long, and the generation of by-products may be promoted.

  In the microreactor shown in FIG. 16, a reaction stoppage agent introduction flow path 104 is joined to a mixing flow path 102 having a micro flow path cross-sectional area, and a reaction stop flow path 106 is provided downstream thereof. In this microreactor, mixing is performed by high-speed molecular diffusion in the microchannel of the mixing channel 102, and then a reaction terminator E is introduced at an optimum position according to the target diffusion-controlled reaction, and side reactions and side products are generated. It suppresses things.

  The problem with this method is that it is necessary to study the method of introducing the reaction terminator E. As shown in FIGS. 17 (a) and 17 (b) and FIGS. 18 (a) and 18 (b), it is necessary to design appropriately from which direction the reaction terminator is introduced to stop / suppress side reactions. If this is the case, the reaction cannot be stopped reliably.

  In addition, when the reaction termination process (reactant species) by the reaction terminator is a reaction-controlled reaction, it is necessary to install a very long reaction stop channel to stop the reaction. There is no guarantee that the reaction will be stopped within the range of the reaction stop channel. Therefore, there is a high possibility that the target product cannot be obtained in high yield. In addition, an increase in the flow path length leads to an increase in pressure loss, and it is necessary to use a higher-pressure liquid feeding device, which has a demerit that energy efficiency is lowered. In addition, this method needs to know in advance whether the chemical reaction process for stopping the reaction is diffusion-controlled or reaction-controlled, and is extremely inflexible.

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a reaction apparatus capable of efficiently performing a diffusion-controlled reaction and quickly stopping the progress at an appropriate timing. .

  In order to achieve the above object, the reaction apparatus according to claim 1, wherein at least two or more kinds of reagents are introduced into a micro cross-sectional area mixing flow path, and a mixing reaction section that mixes the reagents by molecular diffusion, and the diffusion mixing. It is arranged downstream of the reaction part, and has a reaction stop part for stirring and mixing the mixed reagent from the diffusion mixing reaction part and the reaction stop agent to stop the reaction.

  In the first aspect of the present invention, the reagent is mixed by molecular diffusion in the micro cross-sectional area mixing channel in the mixing reaction portion, and then the reaction stopping agent is stirred and mixed in the reaction stopping portion to quickly stop the reaction. .

According to a second aspect of the present invention, the reaction apparatus according to the first aspect is characterized in that the mixed reaction portion and the reaction stop portion are formed between flat plate members facing each other.
In the invention described in claim 2, the mixing reaction part and the reaction stop part are formed between the flat plate members facing each other, and the whole is compact and has a good sealing property.

According to a third aspect of the present invention, there is provided the reaction apparatus according to the second aspect of the invention, wherein the mixed reaction section can change the shape and / or size of the flow path by changing one of the flat plate-like members. It is characterized by that.
In invention of Claim 2, it can respond to various reaction by preparing the flat member which formed the required flow-path structure, and replacing this.

According to a fourth aspect of the present invention, there is provided the reaction apparatus according to any one of the first to third aspects, wherein an outlet channel that opens on an axis is formed in the reaction stop portion, and the outlet channel is opened. A narrow portion for preventing fluid from flowing out in a short circuit is formed between the portion and the surface of the rotor facing the portion.
In the third aspect of the present invention, the narrow portion formed between the opening of the outlet channel and the surface of the rotor facing the opening prevents the fluid from flowing out in a short-circuit, and high stirring efficiency is achieved. Achieved.

  According to the first to third aspects of the invention, it is possible to provide a reaction apparatus capable of efficiently carrying out the diffusion-controlled reaction and quickly stopping the progress at an appropriate timing.

Embodiments of the present invention will be described below with reference to the drawings.
1 to 3 show an external view and a mechanism sectional view of a first embodiment of a reaction apparatus according to the present invention. This reaction apparatus is configured inside a cover 10 and a bottom plate 12 which are a pair of flat members formed in a substantially disc shape.

  The cover 10 and the bottom plate 12 are joined via the packing 14, and the raw material reagent introduction channels 16 a and 16 b (two in this example) between them, a micro-channel mixing channel 18 formed by joining them, and A stirring and mixing chamber 20 on the downstream side is formed. The mixing flow path 18 constitutes a diffusion mixing reaction part, and the stirring and mixing chamber 20 constitutes a reaction stop part. In this embodiment, the introduction flow paths 16a and 16b are formed in a groove shape on the upper surface of the bottom plate 12, and are inserted into the cover 10 to communicate with the introduction port 22. The introduction port 22 is connected to the reagent via the tube 24 and the like. Contact the source.

  A rotor 26 is disposed in the stirring and mixing chamber 20 and is remotely driven by a magnetic drive unit 28 disposed adjacent to the cover 10. In addition to the mixing flow path 18, the stirring and mixing chamber 20 is provided with a stop drug introduction flow path 30 for introducing a reaction stop drug and a discharge flow path 34 for deriving a product after the reaction. The stop medicine supply source and the storage container (not shown) are communicated via the outlet port 35 and the tube 24. For the cover 10, the bottom plate 12, the packing 14, the rotor 26, and other components, at least the wetted parts are those that have corrosion resistance against organic reagents. The cover 10, the bottom plate 12, and the packing 14 are integrated by a method such as screwing.

  In this embodiment, the stirring and mixing chamber 20 is formed in a cylindrical shape coaxial with these by forming recesses in the cover 10 and the bottom plate 12 respectively. The introduction channels 16a and 16b are formed so as to extend in the circumferential direction from the introduction port so as to extend in the radial direction so that the mixing channel 18 extends at the intersection with the mixing channel 18. Further, the mixing channel 18 and the stopping agent introduction channel 30 are arranged at a predetermined angle (90 degrees in this example) in a horizontal plane. By arranging the flow paths in this way, the overall shape can be made compact, but the shapes of the introduction flow paths 16a and 16b and the mixing flow path 18 are not limited thereto.

  For example, as shown in FIGS. 4A to 4C, the introduction flow paths 16a and 16b are formed by changing the portion where the introduction flow paths 16a and 16b join the mixing flow path 18 from a T shape to a Y shape. It is possible to adjust the length L of the mixing flow path 18 without changing the overall arrangement. For example, by forming the introduction channels 16a and 16b and the mixing channel 18 on the bottom plate 12 side, the bottom plate 12 having a distance L suitable for various reactions is prepared in advance, and a bottom plate suitable for the reaction to be performed is prepared. By attaching, various reactions can be performed easily. In addition, in FIG.4 (d), the horizontal part of the introduction flow paths 16a and 16b is formed in linear form, and there exists an advantage which is easy to process.

  In the example of FIG. 2, each of the mixing channel 18 and the stopping agent introduction channel 30 is one, but as shown in FIGS. The channel 30 may be connected to the stirring and mixing chamber 20. The stop medicine introduction flow path 30 and the discharge flow path 34 are opened to the respective ports via the inside of the cover 10. What is necessary is just to set the optimal number of each flow path according to the chemical reaction made into implementation.

The cross-sectional area of the mixing channel 18 is 0.1 mm ² or less, preferably 0.05 mm ² or less, more preferably 0.01 mm ² or less. Further, when the width of the mixing channel 18 is W and the depth is H, it is preferable that W ≦ H. In addition, after satisfy | filling the conditions of the said flow-path cross-sectional area, the W / H becomes smaller, the intermolecular distance in molecular diffusion mixing becomes short, and the reactivity improves. W / H is 0.2 or less, preferably 0.1 or less, more preferably 0.05 or less. The cross-sectional area of the reaction terminator introduction flow path 30 is preferably larger than the cross-sectional area of the mixing flow path 18, 1.5 times or more, preferably 10 times or more, and more preferably 100 times or more.

  By reducing the actual volume of the stirring and mixing chamber 20 (the volume of the stirring and mixing chamber 20 minus the volume of the rotor 26 body), the adoption of stirring can be increased and the reaction can be stopped for a short time. . The actual volume is desirably 0.3 mL or less, preferably 0.05 mL or less, more preferably 0.01 mL or less.

  As the material of the rotor 26, for example, a magnetic material or a metal coated with a material having characteristics of an organic-resistant reagent such as tetrafluoroethylene polymer, ceramic, and glass is used. As shown in FIGS. 6A to 6F, the shape of the rotor 26 can be selected as appropriate, such as a cylindrical shape, a rectangular parallelepiped shape, a football shape, a disk shape, a spherical shape, a starfish shape, and an impeller shape. In this embodiment, it has a cross shape extending radially in four directions.

  In this embodiment, as shown in FIG. 7, the gap between the rotor 26 and the ceiling wall of the mixing chamber forms a narrow portion g between the outlet channel 34. As a result, the mixing chamber becomes a semi-enclosed space, and even if strong convection occurs by the rotor 26, a situation in which the unmixed fluid flows in a short circuit to the outlet channel 34 is avoided, resulting in sufficient agitation. After mixing, the reagent whose reaction has stopped reliably flows out.

  The magnetic drive unit 28 is connected to an electric motor (motor) 36 that is rotationally driven by an AC or DC power source, a controller having a function of controlling the rotational speed of the electric motor 36, and an output shaft of the electric motor 36, and a permanent magnet 38 is mounted thereon. It is constituted by a disk 40. Here, when the electric motor 36 is operated, the disk 40 on which the permanent magnet 38 is mounted rotates, and the rotor 26 (which incorporates a magnetic body) rotates along with the operation. The magnetic drive unit 28 for driving the rotor 26 is installed and fixed to the upper portion of the cover 10 by screws or the like, but may be installed below the bottom plate 12 as a matter of course.

The operation of the reactor according to the first embodiment configured as described above will be described below.
First, the reaction reagent is introduced into the introduction flow paths 16a and 16b through a port formed in the cover 10 through the tube 24 using a pump for feeding a chemical solution such as a syringe pump. In addition, the reaction terminator is introduced into the reaction terminator introduction channel through a port formed in the cover 10 by using, for example, a pump for feeding a chemical solution such as a syringe pump.

  The introduced reaction reagent merges into the mixing channel 18 via the introducing channels 16a and 16b, and is mixed and reacted by molecular diffusion while flowing the distance L in the mixing channel 18 having a small cross-sectional area. The liquid containing the product after the reaction flows into the stirring and mixing chamber 20 that communicates with the mixing channel 18.

  On the other hand, the introduced reaction terminator flows into the stirring and mixing chamber 20 via the introduction channel 30. In the stirring and mixing chamber 20, the mixed reagent containing the product and the reaction stopping agent are uniformly mixed by forced stirring by the rotating operation of the rotor 26, and the reaction is stopped. The reagent containing the target product after stopping the reaction is output from the outlet port through the joint and the tube 24 through the outlet channel. The introduction flow rate of the reaction terminator is at least twice the total flow rate of the reaction reagent, preferably at least 10 times, more preferably at least 20 times.

As described above, in the reaction apparatus of this embodiment, in the diffusion-controlled reaction, high-speed mixing using molecular diffusion is realized in the mixing channel 18 having a micro-channel cross-sectional area, and at the same time, a minute actual volume is stirred. By rapid mixing using forced stirring with a reaction terminator in the mixing chamber 20, it is possible to stop the generation of side reactions and by-products at an appropriate timing.
That is, it is possible to completely stop the generation of the by-product D in the following reaction example.
A + B → C + D (A, B: Reagent C: Target product D: By-product)
According to the present invention,
A + B → C + D + E + F + ... (A, B: Reagent C: Target product D ~: By-product)
As for the diffusion-controlled reaction of the type that changes continuously to different by-products at a high speed continuously, the distance (L) of the mixing channel 18 is adjusted to the target reaction with the highest yield of C. By designing so that it can be obtained, it is possible to stop the generation of by-products and to effectively obtain the target product C at high speed and high yield, as described above.

  The present invention is also useful in a reaction in which mixing of A + B with the reaction reagents A and B has explosive properties. For example, if the distance L of the mixing channel 18 is set to be extremely small, the mixture is led to the stirring and mixing chamber 20 immediately after mixing, and the reaction is stopped rapidly by the reaction stopping agent in the stirring and mixing chamber 20, an explosive reaction can be performed extremely safely It becomes possible to carry out.

  In the above embodiment, the shape of the reaction apparatus is circular, but it may be rectangular as shown in FIG. 8, and can be appropriately set according to the shape and number of flow paths and other conditions. .

  FIG. 9 shows still another embodiment of the present invention, in which a temperature control device 42 for controlling the temperatures of the introduction channels 16a and 16b and the stirring and mixing chamber 20 as a unit is installed. The temperature control device 42 adjusts the output of the heater 44 based on the heater (or cooler) 44 installed below the bottom plate 12, the temperature sensor 46 embedded in the bottom plate 12, and the output of the temperature sensor 46. A controller 48 is provided. Of course, the heater 44 may be installed in another location, or a heat medium may be introduced.

  FIG. 10 shows still another embodiment of the present invention, and a heater (or a cooler) that individually controls the temperatures of the introduction flow paths 16a and 16b, the stirring and mixing chamber 20, and the stop drug introduction flow path 30. 44a, 44b, 44c and a temperature sensor (not shown) are installed. It is preferably used when the temperature for reacting reagents differs from the temperature for stopping the reaction. As the configuration for controlling the individual heaters (or coolers) 44a and 44b, an appropriate one can be adopted as in the previous embodiment.

  FIG. 11 shows still another embodiment of the present invention, which is provided with means for adjusting the supply rate of the reaction terminator. That is, a separation and purification device 50 that separates and removes the reaction terminator from the liquid mixture on the downstream side of the stirring and mixing chamber 20, an analysis device 52 that analyzes the components of the liquid containing the target product after separation, Based on the output, a controller 54 is provided for controlling the number of revolutions of the reaction stopping liquid feed pump 53 so that an optimum reaction achievement rate can be obtained. As the analyzer 52, an appropriate means is adopted depending on the target of the reaction product, and examples thereof include a pH meter having a quick response and a device for directly analyzing product components such as a chromatography device. Of course, other parameters such as the speed of the reaction reagent supply pump, the reaction temperature, the rotational speed of the rotor 26, and the like may be controlled based on the data of the analyzer 52.

  12 and 13 show still another embodiment of the present invention, in which a plurality of reaction and reaction stop processes are combined to constitute one overall process. In FIG. 12, the cover 10 is omitted. In this embodiment, three mixing channels and three stirring and mixing chambers are combined. That is, the reagents A and B flow from the introduction flow paths 16a and 16b and react in the first mixing flow path 18a to generate the intermediate product H, and merge with the reaction terminator C in the first stirring and mixing chamber 20a. To stop the reaction. Reagents E and F flow from the introduction flow paths 16e and 16f, react in the second mixing flow path 18b, generate an intermediate product I, and stir and mix with the reaction terminator G in the second stirring and mixing chamber 20b. To stop the reaction. These are separated by the first and second separation / purification devices 50a and 50b, respectively, and then merged with another reagent J in the third mixing channel 18c that merges with the introduction channel 16j, and further reacted. To produce the target product M. This is stirred and mixed with the reaction terminator K in the third stirring and mixing chamber 20c to stop the reaction, and after the reaction terminator is separated by the third separation and purification device 50c, it is discharged.

  Thus, the reaction apparatus of this invention can respond to various continuous reactions by combining appropriately. Such a composite reaction apparatus may be formed between the pair of covers 10 and the bottom plate 12, or may be configured by arranging a plurality of units on an appropriate substrate. In this way, by adopting an integrated configuration, an apparatus capable of stable operation can be designed in a compact manner without using piping such as the tube 24.

すなわち、拡散混合部に、
A: 1M 2,6 Diisopropylphenol 1M 1,3 Dimethoxybenzene/Pyridine
B: neat Acetic Anhydride
の供給流体をシリンジにより供給し、反応停止部には、飽和炭酸水素ナトリウムを供給した。 Using the reactor having the shape shown in FIGS. 1 and 2, acetylation reaction of diisopropylphenol as shown in the following formula was performed.

That is, in the diffusion mixing section,
A: 1M 2,6 Diisopropylphenol 1M 1,3 Dimethoxybenzene / Pyridine
B: neat Acetic Anhydride
The supply fluid was supplied by a syringe, and saturated sodium hydrogen carbonate was supplied to the reaction stopper.

The dimensions of each part of the apparatus are as follows.
Diffusion mixing unit dimensions: width 0.3mm, depth 2.0mm, length 12mm
Reaction stop part: Introduction channel width 2.0mm, depth 2.0mm, length 12mm
Reaction stop chamber actual volume 0.2mL
Rotor speed 2000rpm
The flow rate conditions were set as follows, and the yield immediately after product derivation was compared with the yield after standing (15 min).
Flow rate conditions Reagent (A, B) flow rate: 0.007mL / min
Reaction stopping agent flow rate: 0.07mL / min

The results are shown below. Here, if the reaction stop function does not function, the product yield after standing is larger than the product yield immediately after derivation.
<Result 1: 20 ° C>
Product yield immediately after derivation = 5%
Product yield after standing = 5%
→ The reaction stop is functioning.
<Result 2: 60 ° C>
Product yield immediately after derivation = 15%
Product yield after standing = 15%
→ The reaction stop is functioning.
From the above, it can be seen that the reaction stop, which is the purpose of the reaction apparatus according to the present invention, is reliably performed.

It is a figure which shows the external appearance of the reaction apparatus of one embodiment of this invention. It is a figure which shows the flow path and stirring stirring chamber of the reaction apparatus of embodiment of FIG. It is a figure which shows the cross section of the reactor of embodiment of FIG. (A)-(d) is a figure which shows the modification of an introduction flow path and a mixing flow path. (A)-(c) is a figure which shows other embodiment of a flow path and a stirring mixing chamber. (A)-(f) is a figure which shows the various modifications of a rotor. It is a figure which shows the cross section of a stirring mixing chamber. It is a figure which shows the external appearance of the reaction apparatus of other embodiment of this invention. It is a figure which shows the cross section of the reaction apparatus of other embodiment of this invention. It is a figure which shows the modification regarding a temperature control apparatus. It is a figure which shows the reaction apparatus of other embodiment which has an analyzer. It is an external view of a combination type reactor. It is a top view of a combination type reaction apparatus. It is a figure which shows an example of the conventional reaction apparatus. It is a figure which shows the other example of the conventional reactor. It is a figure which shows the further another example of the conventional reaction apparatus. It is a figure which expands and shows the principal part of the conventional reactor. It is a figure which shows the other example of the conventional reactor.

Explanation of symbols

10 Cover 12 Bottom plate 14 Packing 16a, 16b Introduction flow path 18, 18a-18c Mixing flow path (diffusion mixing reaction part)
20, 20a-20c stirring and mixing chamber (reaction stop unit)
DESCRIPTION OF SYMBOLS 22 Introduction port 24 Tube 26 Rotor 28 Magnetic drive part 30 Stop medicine introduction flow path 32 Stop medicine introduction port 34 Derivation flow path 35 Derivation port 36 Electric motor 38 Permanent magnet 40 Disk 42 Temperature control apparatus 44, 44a-44c Heater 46 Temperature Sensor 48 Controller 50, 50a to 50c Separation and purification device 52 Analysis device 53 Liquid feed pump 54 Controller

Claims (4)

A diffusion mixing reaction section for introducing at least two kinds of reagents into the micro cross-sectional area mixing flow channel and mixing the reagents by molecular diffusion;
A reaction apparatus, comprising: a reaction stopping unit that is disposed downstream of the diffusion mixing reaction unit and stops the reaction by stirring and mixing the mixed reagent from the diffusion mixing reaction unit and the reaction terminator.   The reaction apparatus according to claim 1, wherein the mixing reaction part and the reaction stop part are formed between flat plate members facing each other.   The reaction apparatus according to claim 2, wherein the mixing reaction section can change the shape and / or size of the flow path by changing one of the flat plate-like members. An outlet channel that opens on the axis is formed in the reaction stop portion, and fluid is prevented from flowing out in a short circuit between the opening portion of the outlet channel and the surface of the rotor facing the outlet channel. The reaction apparatus according to any one of claims 1 to 3, wherein a narrow portion is formed.

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