JPH0669360B2 - Liquid-liquid heterophasic reactor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention is a liquid-liquid heterophasic reaction system in which a continuous multi-stage reaction is carried out while stirring and mixing these different phases, and at the same time as the reaction, these different phases are continuously mixed in a reactor. The present invention relates to a reaction device for efficiently separating a product to efficiently obtain a product.

[Conventional technology and its problems]

Most chemical reactions in the chemical industry are heterophasic (gas-
Liquid, gas-solid, liquid-solid, liquid-liquid, solid-solid), and there are many useful reactions in one of them, liquid-liquid heterophasic reaction. For example, hydrolysis of fats and oils by lipase, modification of fats and oils, synthesis reaction of fats and oils and various ester synthesis reactions, and various peptide synthesis reactions found in synthesis of artificial sweetener aspartame using protease,
Alternatively, a nitration reaction, a sulfonation reaction, an alkylation reaction and the like of an organic compound may be mentioned. In order to improve the reaction efficiency, these heterophasic reactions are generally carried out as a fine emulsion, and after reaching a predetermined reaction rate, the reaction is stopped and then the reaction product is separated into each phase to produce a product. It is a batch operation to collect. In addition, the raw material is continuously supplied,
It is possible to carry out a continuous reaction, but in this case an additional step of separating the emulsion is required in addition to the reactor.

Thus, in a reaction in a liquid-liquid heterophasic dispersion system that does not dissolve in each other, it is necessary to separate the reaction system into respective phases again after the reaction, and as a method, generally, stationary separation, centrifugation, or Membrane separation and the like can be mentioned. However, if these separation steps are combined after the reaction, the system becomes complicated and the cost becomes heavy, which is a problem in industrialization.

The present inventors have already reported that liquids in enzyme or microbial reactions
In a liquid heterophasic system reaction, a continuous reaction method has been proposed in which a high reaction rate can be maintained while simultaneously separating products (Japanese Patent Application No. 61-122994). However, usually, most of chemical reactions and biochemical reactions are reactions in which the reaction rate decreases as the reaction rate increases, and the reaction rate can be expressed by a decreasing function of the reaction rate. In such a reaction, a tubular reactor is more efficient than a completely mixed reactor, particularly when a continuous reaction is performed while maintaining a high reaction rate. That is, even in Japanese Patent Application No. 61-122994,
In order to maintain a high reaction rate, the reaction rate becomes slow, so a long residence time is required, and a large reaction volume is required to ensure the production rate. Also, in the case of a complete mixing type reactor, by connecting several reactors in series and making it a multi-stage type, the disadvantage to the tubular reactor can be overcome considerably, but a large number of reactors are required and the system becomes complicated, and it becomes practical. It is not preferable for conversion.

[Means for solving problems]

In order to solve the above problems, the inventors of the present invention have proposed Japanese Patent Application No.
The reaction can be carried out efficiently without losing the characteristic of the reaction method according to No. 122994, that is, the characteristic that two phases are separated at the same time as the reaction, and in addition, taking into account those characteristics due to the difference in the type of reactor as described above. As a result of extensive studies for the purpose of developing a reactor, one tank of reaction was obtained by providing a partition plate having a structure in which the light liquid phase and the heavy liquid phase can move up and down at appropriate speeds. We have developed an efficient reactor that can carry out a series multi-stage reaction continuously.

That is, according to the present invention, a partition plate having a hole divides the partition into two or more compartments above and below, each compartment is provided with an inner wall for partitioning inside and outside, and an agitator is attached to the inner compartment. In the uppermost compartment, a heavy liquid phase inlet and a light liquid phase overflow outlet are provided in the upper part, and in the lowermost compartment, a light liquid phase inlet is provided below the stirrer. It is intended to provide a liquid-liquid heterophasic reactor of two liquid phases which are insoluble or hardly soluble and have different specific gravities, each having a heavy liquid phase outlet provided in a lowermost compartment.

According to the present invention, in a reactor in which a light liquid phase and a heavy liquid phase are separated into upper and lower layers, the light liquid phase and the heavy liquid phase are separated from each other while leaving a portion where the light liquid phase and the heavy liquid phase are immiscible. By mixing in the vicinity, the light liquid phase and the heavy liquid phase as the reaction raw materials,
Alternatively, in a reactor capable of converting a reaction raw material existing in a light liquid phase and / or a heavy liquid phase into a product and removing a product existing in an immiscible part of the light liquid phase and / or the heavy liquid phase. Provided is an apparatus capable of performing a continuous multistage reaction by dividing a light liquid phase and a heavy liquid phase in a reactor into a plurality of stages by a partition plate having a structure capable of moving up and down at appropriate speeds.

Therefore, according to the present invention, a more compact reactor can be realized in a two-phase heterophasic system reaction, and a very excellent reaction method capable of simultaneously separating two phases together with the reaction can be established.

The present invention will be described in more detail with reference to the drawings showing a preferred embodiment of the present invention by taking as an example a liquid-liquid two-phase system reaction of an aqueous solution as a heavy liquid phase and a non-aqueous solution phase having a smaller specific gravity than water as a light liquid phase. To do. Liquid-liquid 2 represented by A + B → C + D (A and B are reaction raw materials and C and D are products respectively. Now, A and C are water-soluble and B and D are water-insoluble) as a reaction example. The phase reaction will be described with reference to FIG. FIG. 1 is an example of a reactor having the features of the present invention. From the bottom of the reactor 1, 2 is an aqueous phase, and 3, 4 and 5 are divided into three compartments by a partition plate 27 having holes in the reaction section.
The larger the number of compartments, the more efficient it is, but the device becomes complicated and expensive. Therefore, 2 to 10 are preferable. In each part divided into partition plates, the non-aqueous solution phase and the water phase are made into a fine emulsion to perform an efficient reactor, so here, the two phases are mixed by a helical screw type stirring blade 25 having a draft tube 8. To do. 6 is a non-aqueous solution (light liquid) phase. As shown in Fig. 1, if baffles 10 and 22 are provided at the top and bottom of the reactor, respectively, the liquids at the top and bottom of the reactor are prevented from being completely mixed, and the non-aqueous phase and the water phase are prevented. It is preferable because a part in the state where and are separated can be formed.

The reaction raw material A (aqueous phase) and the reaction raw material B (non-aqueous solution phase) are pumped into the reactor from the reaction raw material (aqueous phase) storage tank 16 and the reaction raw material (non-aqueous solution phase) storage tank 17 at a constant ratio.
With 19,18, water (heavy liquid phase) inlet 28 and non-aqueous solution (light liquid phase) inlet 9 are charged. The water and the non-aqueous solution may be charged in either a cocurrent or countercurrent manner, but it is usually preferable to charge them in a countercurrent manner.

As a partition plate that divides the inside of the reactor, one that has as little mixing as possible of the upper and lower liquids that bound the partition plate, on the other hand, if the non-aqueous solution and water are continuously supplied, those that have a moving speed commensurate with their supply speed Used. That is, it is most preferable that the respective liquid phases move up and down by the supply rates of the non-aqueous solution and water. The shape and material of the partition plate are not particularly limited as long as they satisfy the above conditions, and for example, perforated plate trays, bubble cap trays, bubble trays, etc. used in a shelf column for distillation, extraction, etc. In this case, stainless steel, glass, ceramics, synthetic polymers, etc. are used as the material.

In the uppermost compartment, a non-aqueous solution (light liquid phase) overflow port 29,
A water (heavy liquid phase) outlet 30 is provided in the lowermost compartment, and D and C generated from each outlet are taken out.

Since the product of the present invention can be separated at the same time as the reaction, it is possible to perform not only batch operation but also continuous reaction or semi-continuous reaction in which the reaction raw materials are continuously extracted while continuously extracting the product. Is. In addition, by partitioning the reactor in multiple stages with partition plates to prevent complete mixing of the liquid, an efficient reaction can be performed, shortening the reaction time, reducing the reactor size, and increasing the product concentration. Become.

When the draft tube 8 and the stirring blade 25 as shown in FIG. 1 are used as the inner wall, the diameter of the draft tube is not particularly limited and may be determined according to the intended reaction. A diameter of 90% is preferably used. In addition, the rotation speed of the stirring blade was such that the lower layer in the reactor was well rolled up to cause mixing in the vicinity of the interface between the non-aqueous solution phase and the aqueous phase, and the non-aqueous solution phase and the aqueous phase were formed in the upper and lower parts of the reactor. It may be set so that the part that does not mix remains.

The filler 7 may be used as shown in FIG. In this case, the form of the filler is not particularly limited,
Raschig rings, dressing rings, berl saddles, interlocks saddles, which are commonly used as fillers,
You may fill with a filling material such as a pole ring or a cylindrical net. The material is not particularly limited, and metal, porcelain, plastic, or the like can be used.

The use of the filler enhances the contact efficiency between the aqueous phase and the non-aqueous solution phase, and in a system using a catalyst or a biocatalyst such as an enzyme or a microorganism, the contact efficiency between the catalyst and the reaction raw material is increased. Reaction can be performed. However, if these conditions are satisfied without using the filler, it is not necessary to use the filler in particular.

When using this reactor to carry out reactions using ordinary chemical catalysts or biocatalysts such as enzymes and microorganisms, the catalysts used for these reactions are efficiently retained in the reactor, but the water phase or May dissolve slightly in the aqueous phase.
Therefore, it is preferable to concentrate and recover these catalysts in consideration of efficient use of these catalysts and influence on the quality of products.

In the present invention, the term "catalyst" means not only ordinary chemical catalysts but also all catalysts including biocatalysts such as enzymes and microorganisms.

In order to efficiently concentrate and recover the catalyst, static separation, centrifugation,
A method such as membrane separation can be used, but it is preferable to use an ultrafiltration membrane for continuous separation. The ultrafiltration membrane to be used is not particularly limited in terms of material, shape, etc. as long as it does not pass the catalyst used in the reaction, and cellulose acetate membrane, polyacrylonitrile membrane is used for recovering the one dissolved in the aqueous phase side. A hydrophilic material such as a polysulfone membrane or a polyamide membrane can be preferably used, and a polypropylene material, a polyethylene membrane, a Teflon membrane or the like having a hydrophobic material can be used to collect the material dissolved in the non-aqueous phase. Can be preferably used. Furthermore, a membrane made of an inorganic material such as porous glass or porous ceramic can be preferably used for membrane separation of any of a water phase and a non-aqueous solution phase. Further, regarding the shape, any shape such as a flat film shape, a tubular shape, a spiral shape, a hollow fiber shape can be used. The molecular weight cut-off of the ultrafiltration membrane depends on the catalyst used in the reaction, as long as it has a pore size that can prevent the permeation of these catalysts, and is not particularly limited, but generally about 3000 to 50,000. preferable. The aqueous phase or non-aqueous solution phase containing no catalyst may be continuously extracted by ultrafiltration, and the concentrated solution of the catalyst may be continuously or semi-continuously returned to the reaction system.

If most of the catalyst is retained in the reactor and its dissolution in the aqueous phase or non-aqueous solution phase can be ignored, it is not necessary to separate these catalysts by ultrafiltration. It is also possible to fill the catalyst immobilized on the insoluble carrier in advance by various methods, and in this case also, the catalyst recovery step by ultrafiltration is not necessary. Alternatively, it is also possible to omit the ultrafiltration step and add a fresh catalyst corresponding to the catalyst component dissolved in the aqueous phase or the non-aqueous solution phase.

By using such a method, it is possible to retain the catalyst in the reactor and efficiently recover and reuse the catalyst without performing a special pretreatment. The catalyst may be retained by adsorption or the like without any special pretreatment, or may be filled with a catalyst (supported catalyst, immobilized biocatalyst, etc.) that has been insolubilized in advance by various methods, or There is a method such as using in a free state without using a packing, and which method is to be used may be appropriately selected depending on the characteristics of the catalyst, reaction conditions and the like.

The feature of the present invention is that the upper and lower two layers in the reactor are mixed in the vicinity of the interface to carry out the reaction, and the reaction is performed while leaving the immiscible parts in the upper layer part and the lower layer part in the reactor. In a reactor that can take out the light liquid phase and the heavy liquid phase independently, it prevents the liquid in the reactor from being completely mixed in the reactor, and the light liquid phase and the heavy liquid phase move at the same speed as each supply speed. By providing a partition plate having a possible structure, it is possible to carry out an efficient reaction, that is, a series multi-stage reaction can be continuously performed in a single tank reactor. Therefore, the products can be simultaneously obtained while continuously adding the reaction raw materials.
Further, since the reaction can be continuously performed, the concentration of each product in the reactor can be kept constant.

The method of the present invention can be applied to various reactions in a liquid-liquid heterophasic system of a light liquid phase and a heavy liquid phase, the hydrolysis reaction of fats and oils by the above lipase, the synthesis of triglyceride by lipase, the transesterification reaction of triglyceride, Alternatively, a synthetic reaction of a peptide with a protease such as the synthesis of artificial sweetener aspartame (aspartyl phenylalanine methyl ester) from carbobenzyloxy-1-aspartic acid and γ-phenylalanine methyl ester by thermolysin, or these biosynthesis In addition to the reaction, it is widely applicable to reactions in a liquid-liquid two-phase system such as nitration reaction of organic compounds, sulfonation reaction and alkylation reaction, but is not limited thereto.

〔Example〕

Examples of the present invention will be described below, but the present invention is not limited to these examples.

Example-1 The case of hydrolyzing fats and oils with an enzyme using the method of the present invention will be described. In this case, the reaction substances are fat and water, the enzyme is lipase, and the reaction products are fatty acid and glycerin. The present inventors have already found that when hydrolyzing fats and oils using lipase, the product glycerin greatly contributes to the stability of lipase. According to the research conducted by the present inventors, when the glycerin concentration in the aqueous phase in the reaction system is within the range of 10 to 40% by weight, the enzyme is stabilized and the hydrolysis of fats and oils preferably proceeds. The method of the present invention makes it easy to keep the concentrations of various components constant in each stage divided into partition plates in the reactor, and therefore is preferably applied to hydrolysis of fats and oils by lipase. That is, the glycerin concentration in the water phase can be controlled while maintaining a high oil and fat decomposition rate by appropriately adjusting the supply ratio of the oil and fat and the water phase.

FIG. 1 shows an example of a preferred embodiment system of the present invention. First, soybean oil was hydrolyzed by lipase by the reaction system shown in FIG. In the hydrolysis of fats and oils with lipase, in FIG. 1, 9 is a fats and oils supply nozzle, 11 is a fatty acid solution storage tank, 14 is a glycerol aqueous solution membrane treatment storage tank, 15 is a glycerin water storage tank, 16 is a water storage tank, and 17 is a fats and oils storage tank.

1 reaction mixture of 1kg of decomposed fatty acid (fatty acid content 85%) of enzymatically decomposed soybean oil, 1kg of 15wt% glycerin water and 2g of lipase (320000 units / g) produced from Candida cylindracee was added to the reaction vessel 30 The reaction was carried out while maintaining the temperature at ℃. The ratio of the diameter of the reaction tank and the diameter of the draft tube 8 is 1
It is 0: 6. As the stirring blade, a ribbon type blade 25 as shown in FIG. 1 was used, and stirring was performed at a peripheral speed of about 0.5 m / sec. 50 g from the oil / fat storage tank 17 to the reaction tank 1 by the pump 18.
The soybean oil (fatty acid content 0%) was continuously supplied from the nozzle 9 at the bottom of the reaction tank at a flow rate of / HR, and the water storage tank 16 was preliminarily charged with 15 wt% glycerin water. 15 wt% glycerin water was continuously supplied from the upper part of the reactor at a flow rate of HR. That is, the oil phase and the water phase were fed into the reactor respectively so that the average residence time of the oil phase and the water phase was 20 hours. By dividing the reaction tank into three stages with partition plates, an efficient hydrolysis reaction can be performed without complete mixing. Further, by providing baffle plates 10 and 22 at the upper and lower portions of the reaction tank, respectively, fatty acid containing almost no water or glycerin water containing almost no oil can be obtained on the upper side 6 and the lower side 2. In this way, the fatty acid is continuously extracted by overflow from the light liquid phase overflow port 29 by the amount of the soybean oil supplied, and the glycerin water is continuously extracted from the outlet 30 at the bottom of the reaction tank by the pump 20 and once stored in the storage tank 14 After being stored in, the enzyme dissolved in the aqueous phase was concentrated and recovered by the ultrafiltration membrane 13, and the amount of glycerin water extracted was
The reaction was carried out while adjusting so as to be 50 g / HR. In this example, a polyacrylonitrile membrane (molecular weight cut-off of 30,000) was used as an ultrafiltration membrane to semi-continuously concentrate the enzyme and then returned to the reaction tank.

The reaction was continued while continuously supplying soybean oil and an aqueous glycerin solution and continuously extracting a fatty acid solution and an aqueous glycerin solution using such a reactor.

After 20 hours (equal to the average residence time in the reaction tank), the reaction solution was sampled from the 3rd part, 4th part and 5th part of the reaction tank 1, and the acid value and saponification value of each oil phase were measured. Moreover, the glycerin concentration of each aqueous phase was measured. Acid value of part 3 = 155, saponification value = 198, Acid value of part 4 = 181, saponification value = 1
An acid value = 190 and a saponification value = 200 in the 99,5 portion were obtained. When the hydrolysis rate was calculated from the following formula, the hydrolysis rates of the 3,4,5 parts were 78%, 91%, and 95%, respectively.

In addition, the glycerin concentration in the 3,4,5 part is 24%,
It was 16.4% and 15.4%. The decomposition rate of the portion 5 is equal to the decomposition rate of the fatty acid solution obtained in the fatty acid solution storage tank 11,
The glycerin concentration in the aqueous phase of the portion 3 is equal to the glycerin concentration of the glycerin aqueous solution in the glycerin aqueous solution storage tank 15.

Similarly, when the decomposition rate and glycerin concentration of each part of the reaction vessel were measured 40 hours, 60 hours, 80 hours, and 100 hours after the start of soybean oil supply, it was as shown in Table 1.

Even after 100 hours of continuous reaction, the enzyme was not inactivated at all, the decomposition rate of soybean oil was 92 to 95%, and the glycerin concentration in the aqueous phase was 23 to 24%.

On the other hand, the water content in the fatty acid solution storage tank 11 during dissolution of the fatty acid was 0.5% or less. In addition, the glycerin water that passed through the ultrafiltration membrane was glycerin water with good quality. Thus, it was found that by using this reaction system, the reaction and the product can be separated at the same time, and the enzyme can be efficiently recovered and reused to maintain a high decomposition rate.

Comparative Example-1 Here, soybean oil was continuously hydrolyzed using a reaction tank having no partition plate for dividing the reaction tank used in Example-1 into multiple stages in the reaction tank.

1 kg of decomposed fatty acid (85% fatty acid content) obtained by enzymatically decomposing soybean oil in a reaction tank in advance, 1 kg of 20 wt% glycerin water, and lipase produced from Candida cylindracee (320000 units /
g) 2 g was added and the reaction was carried out while maintaining the reaction tank at 30 ° C. The ratio of the diameter of the reaction tank to the diameter of the draft chirp is 10: 6. Ribbon type blades are used for the stirring blades and the peripheral speed is 0.5m /
Stirring was performed for seconds.

Soybean oil was supplied from the lower part of the reaction tank at a flow rate of 50 g / HR, and water was supplied from the upper part at a flow rate of 25 g / HR to carry out a continuous reaction. That is, the soybean oil was fed into the reaction vessel so that the average residence time of the soybean oil was 20 hours and the glycerin concentration in the aqueous phase was maintained at about 20%.

In this way, the fatty acid produced in the same manner as in Example-1 was continuously withdrawn by overflow, and the sweet water was continuously removed from the system after the enzyme dissolved in the aqueous phase was recovered by the ultrafiltration membrane. I pulled it out.

The hydrolysis rate of soybean oil and the glycerin concentration at each reaction time were measured and the results are shown in Table 2.

Thus, the enzyme was not deactivated even after the continuous reaction for 100 hours, but the decomposition rate of soybean oil was 85 to 86%, which is lower than that of Example-1.

Example-2 Using the same apparatus as in Example-1, the initially charged soybean oil decomposition solution, the 15 wt% glycerin aqueous solution and the enzyme charge were also the same as in Example-1, and the soybean oil supply was the same as in Example-1. 50
g / HR, and changed the supply amount of the 15 wt% glycerin aqueous solution to 25 g / HR. That is, the average residence time of the aqueous phase was 40 hours. In this way, soybean oil was continuously hydrolyzed. The lipolysis rate and glycerin concentration in each part of the reaction tank for each reaction time are shown in Table 3.

It was found that by adjusting the supply speed of the aqueous phase in this way, high-concentration glycerin water can be obtained while maintaining a high decomposition rate.

[Brief description of drawings]

 FIG. 1 is a schematic diagram showing an example of the reaction apparatus of the present invention. DESCRIPTION OF SYMBOLS 1 ... Reaction tank 2 ... Heavy liquid phase part 3-5 ... Reaction part, 6 ... Light liquid phase part, 7 ... Filler 8 ... Draft tube 9 ... Reaction raw material (light liquid phase) inlet 10 ... Upper baffle plate 11 ... Product (light liquid phase) storage tank 12 Cough 13 Ultrafiltration membrane 14 Product (heavy liquid phase) membrane processing storage tank 15 Product (heavy liquid phase) storage tank 16 Reaction raw material (heavy liquid phase) storage tank 17 ... Reactant (light liquid phase) storage tank 18-21 ... Pump 22 ... Lower baffle plate 23-24 ... Valve 25 ... Stirring blade 26 ... Stirring motor 27 ... Reaction tank partition plate 28 ... Heavy liquid phase inlet 29 ... Product (light liquid phase) overflow port 30 ... Product (heavy liquid phase) outlet

Claims (1)

[Claims] 1. A partition plate having a hole divides the partition into two or more compartments above and below. Each compartment is provided with an inner wall for partitioning the inside and the outside, and an agitator is attached to the inner compartment. In the uppermost compartment, a heavy liquid phase inlet and a light liquid phase overflow outlet are provided in the upper part, and in the lowermost compartment, a light liquid phase inlet is provided below the stirrer. A liquid-liquid heterophasic reactor of two liquid phases having different specific gravities, which are insoluble or hardly soluble in each other, provided with a heavy liquid phase outlet in a lowermost compartment.