JP2917862B2 - Method for producing ester cyclic dimer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improved method for producing a cyclic dimer which is a raw material for the polymerization of polylactic acid, polyglycolic acid and other poly-α-hydroxycarboxylic acids.

[0002]

2. Description of the Related Art Biodegradable or degradable polymers in the natural environment have attracted attention from the viewpoint of environmental protection. In particular, polylactic acid, polyglycolic acid and the like are excellent in decomposability and physical properties, and their early practical use is desired. One of the conditions necessary for practical application and industrialization is that the raw material is supplied at high efficiency and at low cost. From lactide and glycolide, which are cyclic dimers of lactic acid and glycolic acid, polylactic acid and polyglycolic acid can be obtained with high efficiency by ring-opening polymerization. A manufacturing method is desired.

[0003] The cyclic dimers of α-hydroxycarboxylic acids such as lactic acid and glycolic acid are produced by heating and depolymerizing their (crude) polymers and oligomers in the presence of a catalyst. That is, rather than purifying and polymerizing lactic acid, glycolic acid, etc., a high-purity raw material obtained by polymerizing a low-purity raw material once to form an oligomer or a polymer and depolymerizing them is obtained.
By polymerizing the monomer, a polymer having a high molecular weight can be obtained with high efficiency, and this method is considered as a shortcut of industrialization.

As a method for producing an ester cyclic dimer by depolymerization of polylactic acid or polyglycolic acid, a method in which a reaction and a formed dimer are separated using a thin-film distillation apparatus is disclosed in Japanese Patent Application Laid-Open Publication No. HEI 7-1995. No. -5000091. In this publication, a method disclosed in European Patent Application Publication No. 264926 using a twin-screw extruder is introduced as a conventional technique. It is said that monomer can be produced.

However, when the technique disclosed in the above publication is examined in detail, the crude lactide obtained has a considerably low optical purity and is unsatisfactory as shown in the examples. That is, the L-form ratio of the obtained lactide was 90.8 to 92.5% (average 91.6%), and the impurity meso-lactide (L / D mixture) was 7.6% on average throughout the examples. , Also contains on average 0.8% of D-lactide. That is, racemization progresses considerably strongly in the depolymerization step.

[0006]

Needless to say, lactide and the like having high optical purity are desirable. In order to obtain a homopolymer having excellent crystallinity and heat resistance, the optical purity of lactide or the like is desirably 98% (99% by weight) or more. Even in the case of copolymerization, the raw material must have high purity (for example, 99% by weight or more) in order to stably obtain a product of a constant quality.
It is desirable that Crude lactide having a low L-form ratio has a problem in that the efficiency and yield in the purification step are low and the cost is disadvantageous. An object of the present invention is to provide an improved new method capable of producing an ester cyclic dimer having high optical purity with high efficiency.

[0007]

SUMMARY OF THE INVENTION The object of the present invention is to provide α
A method of depolymerizing a polymer or oligomer of hydroxycarboxylic acid (for example, lactic acid or glycolic acid) in the molten state in the presence of a depolymerization catalyst to form a cyclic dimer, and removing the cyclic dimer out of the reaction system in a gas phase , The formation of the dimer by depolymerization is reduced to 400 per liter of the reactant.
This is achieved by performing the reaction under reduced pressure in a reaction vessel containing a planar stirring device having an evaporation area of not less than ² cm ² .

In the present invention, the molecular weight of the raw material poly-α-hydroxycarboxylic acid is not particularly limited. In the conventional method, it is necessary to use a material having a low melt viscosity, and usually a material having a molecular weight of about 500 to 3000 is used. In the examples of the above publication, oligomers having a degree of polymerization of 10 to 20 (molecular weight of about 740 to 1300) are used. This is because high viscosity materials are difficult to handle in the thin film distillation method. In the method of the present invention, the raw material polymer may be an oligomer having a molecular weight of about 500 to 3,000, and a polymer having a higher molecular weight, for example, a molecular weight of about 30,000 or more can be used. This is because the thin-film distillation method does not have a stirrer, but the present invention uses a reaction vessel having a stirrer.

A feature of the present invention is to use a reaction vessel (reactor) incorporating a planar stirring device having a large evaporation area. In order to provide the stirrer with a large evaporation surface, the rotary motion of the drive shaft may cause the planar stirring element having a large surface area to alternately pass through both the liquid of the reactant and the space for evaporation. . Hereinafter, an apparatus used in the present invention will be described with reference to the drawings.

FIGS. 1 and 2 are explanatory diagrams showing specific examples of a reactor preferred for the present invention. FIG. 1 is a cross-sectional view of a reaction apparatus. In a reaction vessel 1, disk-shaped stirring elements 4 and 5 that are rotated by two drive shafts 2 and 3 are provided. The lower half of the container 1 has a reactant 6 and the upper half of the container is a space 7. Reference numeral 8 denotes a hole for supplying an inert gas or connecting to an exhaust (vacuum) system. Although not shown in the drawing, the container 1 and the like are heated by a suitable heating means, for example, electric heating, steam, or another gas or liquid heating medium. The rotational motion of the drive shafts 2 and 3 causes the disk-shaped stirring elements 4 and 5 to rotate, and the reactants 6 and 5 respectively.
And in the space 7 alternately. Stirring elements 4 and 5
(1) Accelerate the reaction by stirring the reactant 6; (2)
The heat from the heated reaction vessel 1 is effectively taken into the reactant by stirring, and (3) the reactant is moved in the upper space 7 in a state where the reactant is attached to the surface thereof in a film form. It acts to evaporate volatile components (such as lactide). By repeating the movement in the reactant 6 and the upper space 7, the volatile components in the reactant 6 evaporate and are led by an external vacuum system to, for example, an rectifier or an external recovery device having a condenser, and the lactide And a cyclic dimer such as glycolide. If the recovery unit has a high-performance multi-stage distillation (rectification) unit, a product with considerably high purity can be obtained. Otherwise, crude lactide and the like can be obtained. Product.

FIG. 2 is a plan view of the apparatus of FIG. The two drive shafts 2 and 3 are attached to the container 1, and the disk-shaped stirring elements 4, 5 and the screw-shaped stirring / liquid sending elements 9, 10 are rotated. 11 is a reactant inlet,
12 is an exit. The screws 9 and 10 act to stir and feed the reactants from the inlet to the outlet. Although these can be omitted, the inside of the reaction vessel 1 is depressurized, and in order to take out a reactant from the outlet 12 by, for example, a pump, any liquid feeding mechanism that applies back pressure to the pump or pressurization A mechanism is needed. In a closed system in which the outlet 12 is closed, such a liquid feeding mechanism is unnecessary. That is, even if the outlet is closed, the cyclic dimer and the like generated by the reaction are taken out of the system by a vacuum device, so that if the amount of the raw material corresponding to the amount taken out is supplied from the inlet, the reaction system is in a steady state. And the reaction proceeds stably.

On the other hand, when a part of the reactants is taken out at an appropriate speed and supplied again to the inlet of the reactor, the reaction system becomes a circulation system, and the reaction is performed more uniformly and steadily.
More extensive applications are possible. In such a circulatory system,
There is also an advantage that the depolymerization catalyst and additives are repeatedly used, so that their consumption can be reduced. In addition, in a closed system, long-term continuous operation cannot be performed because impurities in the reactants accumulate in the reaction vessel, but long-term continuous operation cannot be performed if reaction residues are continuously or intermittently taken out from the outlet of the reaction vessel. Becomes possible. Also, by adding a suitable solvent or diluent (eg, polyethylene glycol) and stabilizer (eg, antioxidant) to the reaction system, fluidity, reactivity, stability, etc. can be improved. Is advantageous.

The stirrer may be a single shaft. However, as shown in FIGS. 1 and 2, a two-shaft or multi-shaft stirrer in which a plurality of stirring elements are arranged so as to overlap or mesh with each other on two drive shafts is used as a container. Has a self-cleaning action that constantly removes substances adhering to the inner surface of the
It has the advantage that the device is less contaminated by deposits and can be operated stably for a long period of time, and is particularly preferable for the purpose of the present invention. The thin-film distillation apparatus does not have such a mechanical self-cleaning action, and may cause a problem in long-term continuous operation. In the depolymerization step, the generated cyclic dimer evaporates and is taken out of the system, so that considerable heat of evaporation is required. The main sources of this heat are conduction and infrared radiation from the container 1 and heat generated by stirring the reactants. Therefore, it is also preferable to appropriately provide fins and irregularities on the stirring element in order to improve the efficiency of stirring and conduction. Of course, increasing the rotational speed of the agitator can provide more heat to the reactants, and the method of the present invention has a wider range of applications.

One of the differences between the apparatus shown in FIGS. 1 and 2 and the cylindrical twin-screw extruder is that the volume of the reaction vessel can be extremely increased. Therefore, the reactant 6 can be reacted relatively slowly under mild conditions, that is, at a lower temperature, and a large-capacity apparatus suitable for industrial production can be obtained at a relatively low cost. The second difference is
The stirring element is planar. Therefore, the agitating element has a large surface area in comparison with its weight, and the reaction device has a large evaporation area and is high in efficiency and low in cost.

For the purposes of the present invention, a reaction (depolymerization)
Must be performed at a temperature as low as possible within a certain short time. Racemization occurs faster at higher temperatures.
Of course, the alteration (oxidation, coloring, etc.) of the reactants is more likely to occur at higher temperatures. For example, in the synthesis by depolymerization of polylactic acid, racemization occurs at 160 ° C. or higher and 220 ° C.
The above is remarkable. Therefore, the reaction temperature is preferably 220 ° C. or lower, particularly preferably 210 ° C. or lower, and most preferably 200 ° C. or lower. In the thin-film distillation method, the reaction time is extremely short (within 1 minute), so that the reaction temperature has to be set to a high temperature of 220 ° C. or more, so that the racemization proceeds and the optical purity of the product deteriorates. In the example of the above publication, the temperature of the thin film still is as high as 260 ° C. As a result, the L-form ratio of the product is about 92% by weight on average.
And low.

The reaction time need not be so short as long as the temperature is somewhat low. The average reaction time depends on the evaporation area.
It is preferably 0 minutes or less, 2 hours or less, particularly 1 hour or less at 210 ° C, and 5 hours or less, particularly 3 hours or less at 200 ° C.

The larger the surface area of the stirrer, the greater the desirability of evaporation. When the lower half of the reaction vessel is filled with reactants, the evaporation area can be approximated by the sum of half the surface area of the stirring device and the horizontal cross-sectional area in the middle of the reaction vessel. The ratio between the evaporation area and the volume of the reactant (unit liter) is hereinafter referred to as the effective evaporation area. In order to carry out the reaction with high efficiency, the effective evaporation area is required to be 200 cm ² / l or more,
cm ² / l or more is preferable, and 600 cm ² / l or more is most preferable. A planar stirring device, that is, a planar or curved surface, or those obtained by appropriately adding irregularities or deformation thereto, can obtain a larger evaporation area with a relatively simple structure as compared with a twin-screw extruder. For example, 2 cm
If they are arranged at intervals, the evaporation area can be increased to 500 cm ² / l or more. If, for example, a corrugated, grooved, spherical, fin-shaped or other unevenness is formed on the surface of a flat or curved element,
Further, the evaporation area can be increased to 1.5 times or more of the plane.

The shape of the stirrer or its element is arbitrary, but for example, a disc, a petal, a multi-leaf, a screw, or the like provided with holes, grooves, fins, and irregularities as appropriate are preferably used. The screw type has various applications such as a screw conveyor type as shown in FIG. 2 and a blade such as a ship propulsion device or an electric fan, but basically has a helical portion and has a spiral shape. It has a liquid function. FIG. 2 shows an example in which the two shafts rotate in the same direction. However, in the case of reverse rotation, screws in opposite directions may be combined.

FIG. 3 is a system diagram showing an embodiment of the present invention, which will be described below by taking lactic acid as an example. The same applies to α-hydroxycarboxylic acids other than lactic acid. The raw material lactic acid aqueous solution is supplied from a tank 21 to a concentrator 23 by a pump 22. Tanks 24 and 26 are for additives (antioxidants, catalysts, solvents, etc.), which are supplied by pumps 25 and 27 as needed. The concentrating device 23 is for evaporating the water content of the raw material and out of the system, and the reference numeral 28 is the taken water content. This concentration step is usually performed at 100 to 1
The reaction is performed at 50 ° C. and normal pressure, but can be performed under reduced pressure.
The lactic acid, which has been concentrated to almost zero moisture, is supplied to the first polymerization reactor 31 via a filter 30 by a pump 29 in a molten state. In the reaction device 31, for example, 300
150 to 16 under a slightly reduced pressure of about 100 Torr
At 0 ° C., lactic acid is dehydrated and condensed to form an oligomer. Reference numeral 32 denotes a vacuum (exhaust) device which includes a condenser or trap, a vacuum pump, and the like. Those polymerized in the reactor 31
It is sent to a second polymerization device 34 by a pump 33. The second reactor 34 is almost the same as the first reactor, but has a slightly higher degree of vacuum of 1 to 100 Torr. 35 is a vacuum device.

FIG. 3 shows an example in which polymerization is continuously performed in two reactors connected in series. However, three or more reactors may be used in multiple stages, and one reactor may be used. The batch operation may be performed intermittently. In this polymerization step, an oligomer having a molecular weight of polylactic acid of about 500 to 3000 is often produced. If the molecular weight is large, the melt viscosity is high, and it is difficult to handle at a low temperature. In the polymerization step, a polymerization catalyst may be used, but an oligomer can be obtained without a catalyst. If a catalyst is present, racemization may proceed, so it is preferable not to use a catalyst. In order to prevent the molecular weight from becoming excessive in this polymerization step, a polymerization inhibitor or a terminator may be used. That is, a monocarboxylic acid or monoalcohol having a boiling point of 100 ° C., particularly 150 ° C. or higher,
The degree of polymerization can be suppressed to 100 to 10 by adding, for example, 1 to 10 mol% of dicarboxylic acid, diol, hydroxide or carbonate of an alkali metal to lactic acid.

The oligomer obtained in the reactor 34 is sent to a first depolymerizer 37 by a pump 36. As the depolymerization device 37, for example, a reaction vessel having a planar stirring device shown in FIGS. 1 and 2 is used, and a depolymerization catalyst in a tank 38 is supplied by a pump 39. In the depolymerization device 37, the lactic acid oricomer or polymer reacts (depolymerizes) at a temperature of 180 to 220 ° C. and a degree of vacuum of 10 to 100 Torr in the presence of a catalyst to form a cyclic dimer, which evaporates and exits the reaction system. It is condensed by a condenser 41 via a provided rectification column 40 and is recovered as a lactide 43. Reference numeral 42 denotes a vacuum (exhaust) device, and reference numeral 44 denotes a high-boiling component, which is discarded or returned to the previous polymerization step or the like. The reactants of the depolymerizer 37 are sent to the second depolymerizer 46 by the pump 45. The second depolymerization device 46 is almost the same as the first depolymerization device 37, and the degree of vacuum is set high, for example, 1 to 10 Torr.
47 is a rectification column, 48 is a condenser, 49 is a vacuum device,
50 is the recovered lactide and 51 is a high boiling substance.

FIG. 3 shows an example in which two depolymerization reaction vessels 37 and 46 are connected in series. However, one or three or more reaction vessels may be arranged in series. A part of the reactants in the reaction vessel 46 is taken out by the pump 52, and when the valve 53 is closed and the valve 55 is opened, the reaction substance is returned to the reaction vessel 37 in the preceding stage to form a circulation system. If the valve 55 is closed and the valve 53 is opened, the reaction residue 54
Is taken out. When the pump 52 is stopped, the reaction vessel 46 is stopped.
Becomes a closed system.

Liquid sending pump 2 for connecting each process and the reaction apparatus
9, 33, 36, 45, and 52 may be continuous operation or intermittent operation, but continuous operation is preferable in terms of steadiness. It is also desirable to adjust and control the pumping speed of the pumps and the like so as to keep the amount of the reactants in each reaction vessel constant. In addition, a storage tank may be provided between each step of concentration, polymerization, and depolymerization of the raw materials, if necessary.

The average residence time (reaction time) of the reactants in the reactors 37 and 46 may be slightly longer when the reaction temperature is low, as described above. It is also preferable in terms of production efficiency. Factors governing the depolymerization rate are the type and amount of the catalyst, the temperature, the stirring speed of the reactants, the heat transfer speed, the degree of vacuum, and the effective evaporation area. In the present invention, the stirring speed, the heat transfer speed and the effective evaporation area can be made sufficiently large, so that the reaction temperature can be made relatively low and the reaction speed can be made relatively large.
High quality products can be obtained with high efficiency. Polymerization and depolymerization are equilibrium reactions, and it is believed that the same catalyst works in both reactions. The catalyst is not particularly limited, and any known or effective catalyst may be used.Metal tin, tin oxide, tin chloride, tin salts of organic acids, such as tin octylate, are preferably used, and For example, about 0.01 to 3%, particularly about 0.1 to 1% is often used. In addition, the reaction apparatus shown in FIGS. 1 and 2 can be preferably used also in the step of concentrating and polymerizing the raw materials. In the apparatus shown in FIG. 3, the reaction is continued in a state where the supply of the oligomer and the like is stopped by stopping the pump 36 at regular intervals (for example, every 10 days), and almost all of the oligomer and the like in the reaction vessels 37 and 46 are lactide. Then, the valve 55 is closed and the valve 53 is opened, the residue of the depolymerization reaction is taken out of the system, and a new catalyst and a fluidity improving agent (for example, polyethylene glycol) are supplied.

The method of the present invention can be applied to the recovery and reuse (recycling) of cyclic dimers from molded products such as polylactic acid and polyglycolic acid and scraps after use. That is, after removing the collected refuse such as molded products, they are crushed into small pieces, and are melted by, for example, a screw extruder, and are melted as shown in FIG.
May be supplied to the polymerization step or the depolymerization step. By adjusting the water content of the polymer pieces before melting, the molecular weight of the polymer after melting can be arbitrarily controlled, making it suitable for the reaction in those steps.

[0026]

EXAMPLES In the following examples,% and parts are by weight unless otherwise specified.

Example 1 L having an optical purity of 99.5% or more
-About 300 l of a 90% aqueous solution of lactic acid is supplied to a tank type reaction vessel having an anchor stirrer and having a capacity of 800 l, heated and concentrated at 135 ° C under atmospheric pressure for 3 hours, and stored in a storage tank. These two tanks correspond to the concentration device 23 in FIG. The concentrated lactic acid solution was supplied to a polymerization apparatus in which two reactors as shown in FIGS. The reaction apparatus was composed of 35 disc-type stirring elements having a diameter of 60 cm at intervals of 2 cm on one side (a total of 70 pieces), and a screw-type element (feed 5c).
m, 2 rotations) are arranged at two points on the entrance side and the exit side, and correspond to 31 and 34 in FIG. The effective volume of the lower half of the reactor is about 190 l, and the effective evaporation area when filled with the reactants is about 600 cm ² / l. First
The first reactor was at a temperature of 150 ° C. and a degree of vacuum of 100 Torr, and the second reactor was at a temperature of 155 ° C. and a degree of vacuum of 20 To.
rr and the rotation speed of the stirrer are both 15 rpm. The average molecular weight of the oligomer after polymerization was 2,200, and was continuously supplied to the next depolymerization step.

The depolymerization device is a device in which two devices having the same biaxial planar stirring device as the above polymerization device are connected in series, and corresponds to the reaction devices 37 and 46 in FIG. The first depolymerization reactor is at a temperature of 200 ° C., a degree of vacuum of 20 Torr,
The second depolymerization reactor has a temperature of 200 ° C and a degree of vacuum of 10To.
rr and the rotation speed of the stirrer are both 30 rpm. Second
Some of the reactants in the reactor are removed by pump 52, as in FIG. 3, and returned to the first reactor at a rate of 10 l / min. The speeds of the pumps 36 and 45 are adjusted so that the liquid levels of the reactants in the two depolymerization reactors are each 3 cm below the center of the stirring shaft. The catalyst used tin octylate for the reactants. The amount of the oligomer supplied to the depolymerizer is 3.32 l / min on average, and the average residence time of the reactants in the reaction vessel is about 2 hours. The conversion ratio of lactide obtained from the two condensers to the starting lactic acid was 93.1% of the theoretical value, and the L-form ratio was 98.5 (optical purity: 97.5%).
0)%. This is much better than the L-form ratio of lactide of about 92% in the examples of the above-mentioned Japanese Unexamined Patent Publication. According to the findings of the present inventors, when the L-form ratio is 97.5% or more, high-purity lactide having an L-form ratio of 99.5% or more can be easily obtained in a purification step by a recrystallization method. However, when the L-form ratio is 95% or less, it is extremely difficult to increase the L-form ratio by a recrystallization method using a solvent or the like.

Example 2 An experiment almost identical to that of Example 1 was performed.
This was performed using a depolymerization apparatus having a different surface area of the stirring element. The stirrer element is a disc-shaped, and has a concentric circular groove with a semicircular cross section of 1.6 mm in width and 0.8 mm in depth on the surface at a distance of 2 mm.
The surface area is 1.46 times that of a flat disk, and flat fins of 6 mm wide, 10 mm long and 3 mm thick are radially welded to the tip of the disk at 60 ° intervals to remove oligomers on the inner surface of the reaction vessel. The efficiency of heat transfer and stirring is increased by scraping (clearance 5 mm). The effective evaporation area of the reactor is about 880 cm ² / l and the rotation speed is 40
rpm. The temperature and pressure of the reaction vessel are the same as in Example 1. As a result, the supply rate of the oligomer to the depolymerization apparatus was 4.35 l / min, and the reaction rate of the depolymerization was about 1.31 times that of Example 1. The conversion to lactide was 93.3%, and the L-form ratio was 98.5%, which was almost the same as in Example 1. The molecular weight of the oligomer to be supplied from the polymerization step to the depolymerization step was 1960, and was slightly reduced due to an increase in the supply amount, but there was no particular problem.

[0030]

According to the present invention, a cyclic dimer having a high optical purity can be easily produced with high efficiency from an oligomer or polymer of poly-α-hydroxycarboxylic acid. Further, the reactor used in the present invention has the following major features: high efficiency, relatively simple structure, easy upsizing, low production cost, wide application range of raw materials, and stable operation. For this reason, the cost of lactide and glycolide to be produced was further reduced, and the possibility of practical use of the biodegradable polymer was further increased.

[Brief description of the drawings]

FIG. 1 is an explanatory cross-sectional view of a reactor incorporating a twin-screw agitator suitable for the present invention.

FIG. 2 is an explanatory plan view of the apparatus of FIG. 1;

FIG. 3 is a system diagram of an apparatus for continuously producing an ester cyclic dimer according to an embodiment of the present invention.

[Explanation of symbols]

1 reaction vessel 2 drive shaft
3 drive shaft 4 stirring element 5 stirring element
6 reactant 7 space 8 supply and exhaust holes
9 screw-type element 10 screw-type element 11 reactant inlet
12 Reactant outlet 21 Raw material (lactic acid etc.) tank 22 Metering pump
23 Concentrator 24 Additive tank (1) 25 Metering pump
26 additive tank (2) 27 measuring feeder 28 steam
29 liquid feed pump 30 filter 31 polymerization reactor (1)
32 exhaust device 33 liquid feed pump 34 polymerization reactor (2)
35 exhaust device 36 liquid feed pump 37 depolymerization device (1)
38 catalyst tank 39 metering pump 40 rectification tower
41 condenser 42 vacuum pump 43 products (lactide etc.)
44 High boiling point material 45 Liquid feed pump 46 Depolymerization equipment (2)
47 rectification column 48 condenser 49 vacuum pump
50 products (lactide, etc.) 51 high-boiling substances 52 liquid pump
53 valve 54 residue 55 valve
56 filters

────────────────────────────────────────────────── ─── Continuation of the front page (72) Eiichi Koseki, Inventor Eiichi Koseki, 1 Kuwaharacho, Nishinokyo, Nakagyo-ku, Kyoto Shimazu Works Sanjo Factory (56) References JP-A-63-123401 (JP, A) JP-A-7 −309863 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) C07D 319/12 CA (STN) REGISTRY (STN)

Claims (5)

(57) [Claims] 1. A method for depolymerizing a polymer or oligomer of α-hydroxycarboxylic acid in a molten state in the presence of a depolymerization catalyst to form a cyclic dimer, and removing the cyclic dimer out of the reaction system in a gas phase. A process for producing an ester cyclic dimer, wherein the dimer is produced by polymerization in a reaction vessel having a built-in planar agitator having an evaporation area of 400 cm ² or more per liter of a reactant. 2. The method according to claim 1, wherein the reaction temperature is 220 ° C. or lower. 3. The reaction vessel is filled with a reactant under the reaction vessel, and the space above is a space, and the stirring element is alternately passed through the lower reactant and the upper space by rotation of a horizontally provided drive shaft. 3. The method according to claim 1. 4. The stirring element according to claim 1, wherein said stirring element is at least one selected from the group consisting of a disc, a petal, a multi-leaf, a screw, and those provided with holes, grooves, fins and / or various irregularities.
4. A seed, at least a part of which has the function of sending reactants by rotary movement.
The described method. 5. The method according to claim 1, wherein a plurality of agitating elements are provided on the two drive shafts so as to overlap or mesh with each other, and rotate in the same or opposite directions to each other.