JP2001198454A - Semi-automatic synthesizer and rotator for stirring - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a semi-automatic synthesizer, capable of supplying a plurality of fluid chemicals without mixing the chemicals by a relatively simple piping configuration, and a rotator for stirring, capable of efficiently stirring a high viscosity solution. SOLUTION: This semi-automatic synthesizer has at least a reaction vessel, a solvent tank, a plurality of chemical tanks each storing a chemical, a first line connecting the reaction vessel with the solvent tank, second lines connecting a plurality of the chemical tanks to the first line independently, valves each disposed at the connection part or in its vicinity for connecting the first line to each of the second lines, and a means for controlling the valves so that any one of the second lines is communicated with the first line. In the semi-automatic synthesizer, the piping configuration is simplified by unifying the feed lines supplying the chemicals to the reaction vessel into the first line. The rotator for stirring comprises at least a support and a three or more rotation members, which are mounted to the support so as to rotate while coming into contact with the bottom of the reaction vessel.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a semi-automatic synthesis apparatus for reacting a plurality of fluid medicines, and more particularly, to controlling the supply of a fluid medicine and a solvent to a reaction vessel, stirring the reaction vessel,
Operations such as pressure adjustment and temperature adjustment can be performed automatically,
In particular, the present invention relates to a semi-automatic synthesis apparatus in which the piping configuration is simplified by unifying the supply line of the drug to the reaction vessel.

Another aspect of the present invention relates to a stirring rotor that can efficiently stir a high-viscosity solution and can be suitably used in the semi-automatic synthesis apparatus of the present invention.

[0003]

2. Description of the Related Art In recent years, semi-automatic synthesis apparatuses for synthesizing various compounds using a computer have been developed, and a series of synthesis operations such as drug addition and temperature control have been developed. , Agitation, pH adjustment, cleaning of the apparatus, etc. are continuously performed. When reacting a plurality of fluid medicines using such an automatic synthesizer, how to connect a plurality of medicine tanks storing the medicines to the reaction container becomes a problem.

[0004] Each of the chemical tanks and the reaction vessel are directly connected,
In the case where the number of drug supply lines is equal to the number of drugs, piping becomes complicated and the device becomes large, taking up space for installation and
The cost is high. In addition, when increasing or decreasing the number of medicines, there is a problem that the external connection parts of the reaction container must be replaced in accordance with the number of medicine supply lines.

On the other hand, when a plurality of drug tanks are connected to a reaction vessel using a single drug supply line, different drugs are mixed inside the line, and it is not possible to grasp an accurate drug supply amount.
There is a problem that the reaction becomes inaccurate. Also, depending on the combination of drugs, a reaction occurs in the supply line,
There is a risk of blockage.

[0006] In addition, a small-sized device capable of controlling the reaction process through instructions from a computer as well as nitrogen replacement in a reaction vessel, addition of a plurality of agents, strong stirring, temperature control, pressure control, and detection and recording of variables of the reaction process. Since there is no semi-automatic synthesizer and the experimenter assembles and uses a thermostat, stirrer, etc. by himself, it is troublesome, and appropriate temperature control corresponding to rapid exothermic reaction and endothermic reaction, and high viscosity solution Is not necessarily achieved.

Accordingly, an object of the present invention is to provide a drug supply system for supplying a plurality of fluid drugs to a reaction vessel without mixing them one by one by a relatively simple piping configuration, a replacement system using an atmosphere gas in the reaction vessel, A stirrer, pressure control,
An object of the present invention is to provide a semi-automatic synthesis apparatus in which temperature control is integrated.

[0008]

Means for Solving the Problems As a result of intensive studies in view of the above-mentioned object, the present inventors have found that in a semi-automatic synthesis apparatus for supplying a plurality of fluid medicines to a reaction vessel one by one, a plurality of medicine tanks and a reaction vessel are connected. The piping configuration to be connected, a first line that connects the reaction vessel and the solvent tank, a second line that independently connects a plurality of drug tanks to the first line, the first line, and the second line. A valve provided at or near each connection of the second line, and means for controlling the valve such that one of the second lines communicates with the first line (hereinafter referred to as “medicine supply Control section ")
With a relatively simple piping configuration,
The present inventors have found that a plurality of chemicals can be supplied to a reaction vessel without mixing, and have reached the present invention.

That is, in the semi-automatic synthesis apparatus of the present invention, as shown in FIG. 1, all the chemical tanks (A to E) are finally connected to the first line 101 via the second line 102. A chemical supply line directly connected to the reaction vessel is integrated into the first line 101. In the present invention, since the number of drug supply lines connected to the reaction container can be reduced to one, the apparatus can be simplified and downsized, and the manufacturing cost can be reduced.

Further, every time one kind of drug is supplied, a sufficient amount of solvent is supplied to the first line to wash out the remaining drug into the reaction vessel, thereby supplying an accurate amount of drug, It is possible to prevent different medicines from being mixed inside the first line.

The present invention can also provide a more practical semi-automatic synthesizer by satisfying the following conditions.

(1) It is preferable that a three-way valve is used as the valve, and the valve is disposed at each connection between the first line and the second line. Further, it is preferable to use the same shape for each chemical tank, second line and valve, and to arrange the valve in series. As a result, the number of drug tanks can be easily increased or decreased by simply adding / removing the set of the drug tank, the second line, the three-way valve, and the first line for extension, so that various reactions can be performed. can do.

(2) The semi-automatic synthesis apparatus preferably has a rotating magnetic field device provided at the lower part of the reaction vessel, and a stirring rotor placed in the reaction vessel and rotated by the action of the rotating magnetic field device. .

(3) As the stirring rotor, a stirring rotor having at least a support and three or more rotating members attached to the support so as to rotate in contact with the bottom surface of the reaction vessel is used. Preferably, it is used. The support is preferably made of a soft magnetic material. It is preferable that an opening, a stirring member, and a pair or more permanent magnets whose magnetic poles face in opposite directions are provided on the support to increase the stirring efficiency. The stirring rotor can be rotated as desired without providing a rotating shaft on the rotor itself, and is easy to handle, and the rotating member reduces friction between the rotor and the bottom of the container. Do not damage container. Further, it has a feature that it can be stably installed in a round bottom reaction vessel.

(4) It is preferable that the means for moving the reaction vessel in the vertical and horizontal directions be provided so that the reaction vessel and the lid can be detachably attached while the position of the lid of the reaction vessel is fixed. . When removing the lid from the reaction vessel, it is common to move the lid, but since various connecting parts such as pipes and tubes are fitted to the lid,
Poor workability. Such a problem can be solved by moving the reaction vessel itself in the vertical and horizontal directions.

(5) It is preferable that the entire surface of the back surface of the reaction vessel lid except for the hole for the external connection port is covered with a chemical resistant seal. As described above, since various connecting parts such as pipes and tubes are fitted to the lid material, it is necessary to remove the lid material for each reaction and wash the solvent and reactants adhering to the back surface of the lid material. Has poor workability. Such a problem can be solved by previously covering the back surface of the lid member with a seal having a hole for an external connection port, removing the seal, washing and reattaching the seal after each reaction.

(6) The semi-automatic synthesizing device comprises: a rotation speed adjusting unit for changing the rotation speed of the rotating magnetic field; a temperature adjusting unit for maintaining the temperature inside the reaction vessel within a certain range; It is preferable to have a pressure adjusting section to be held inside.

(7) The semi-automatic synthesizing apparatus has a rotational speed, a viscosity,
It is preferable to have a variable detection unit for detecting data such as a change in calorific value. By measuring the change in the reaction solution as the reaction progresses, the progress of the reaction can be estimated, and it is useful for elucidating the reaction mechanism.

(8) The semi-automatic synthesis apparatus preferably has a control device for controlling the supply amounts of the drug and the solvent, the rotation speed of the rotating magnetic field, and the temperature and pressure in the reaction vessel through instructions from a computer.

[0020]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In a preferred embodiment of the present invention, as shown in FIG. 1, a semi-automatic synthesizer comprises: [A] a drug supply device (a solvent tank 11, a drug tank 12, a first line 101, a second line 101); Line 102, valve 15, pump 16) [B] Reactor (casing 2, reaction vessel 3, rotating magnetic field unit 4, temperature control unit 5, pressure control unit 6, stirring rotor 7, temperature / pressure / stirring Variable detection unit for rotation speed, rotation torque, viscosity, etc.) [C] Control unit (computer, operation control box,
A drug supply controller, a rotating magnetic field controller, a temperature controller, and a pressure controller.

Hereinafter, each component of the present invention will be described with reference to the accompanying drawings, but the present invention is not limited to the embodiments of these drawings.

[A] Drug Supply Device In the present invention, the drug supply device 1 comprises at least a solvent tank, a plurality of drug tanks for storing each drug, a first line connecting the reaction container and the solvent tank, A second line that independently connects the plurality of drug tanks to the first line, and a valve provided at or near each connection between the first line and the second line. The opening and closing of the valve is controlled by the medicine supply control unit such that one of the second lines communicates with the first line.

In the preferred embodiment shown in FIG. 1, the drug supply device 1 comprises a solvent tank 11, a plurality of drug tanks 12 for storing each drug, and a plurality of catalyst tanks 14 for storing each catalyst.
A first line 101 and a third line 103 connecting the reaction vessel 3 and the solvent tank 11; and a second line connecting each of the chemical tanks 12 to the first line 101 independently. 102, a fourth line 104 that independently connects each of the catalyst tanks 14 to the third line 103, and a connection portion between the first line 101 and each of the second lines 102 and the A three-way valve 15 provided at the connection between the third line 103 and each of the fourth lines 104
And a pump 16, a two-way valve 17, and a check valve 18 provided downstream of the first line and the third line.

The first line 101 and the second line 102 are chemical supply lines, and the third line 103 and the fourth line 104 are catalyst supply lines. The third line 103 is the first line 101, and the fourth line 104 is the second line 102, except for whether the sample flowing through the line is a drug or a catalyst. Since they are substantially the same, the description of the third line and the fourth line will be omitted below, but the description of the first line and the second line will be all the same for the third line and the fourth line. Applicable.

In the present invention, since all drug tanks are connected to the first line via the second line,
The drug supply line directly connected to the reaction vessel is integrated with the first line. By unifying the medicine supply line, the problem that the number of pipes increases according to the kind of the medicine can be solved.

The three-way valve 15 provided at the connection between the first line and each of the second lines comprises a solvent inflow valve 151, a drug inflow valve 152 and an outflow valve 153. When one of the solvent inflow valve 151 and the drug inflow valve 152 is open, the other is in a closed state, and the opening and closing are switched by a switch. Outflow valve 153 is always open. As the three-way valve 15,
Three-way solenoid valves are preferred. Note that one of the second lines
Instead of the three-way valve 15, a combination of a plurality of valves may be used as long as a means for connecting one to the first line can be secured. For example, a valve on the first line and a valve on the second line are provided near the connection between the first line and the second line, so that one of the two valves is in an open state. Opening and closing may be controlled.

On the first line, a pump 16 for transferring a medicine / solvent is provided. Besides pumps,
Other transfer means capable of controlling the flow rate can be used without particular limitation. For example, the position of the liquid level between the solvent and the drug
A method of adjusting the flow rate of the solvent / drug by setting the flow rate higher than 3 and allowing the solvent / drug to fall naturally and providing a flow rate control valve.

At steady state, all three-way valves are
1 is open and the first line is filled with solvent. At the time of drug supply, the drug inflow valve 152 of the three-way valve connected to the target drug tank is opened, and a type of drug is transferred from the drug tank 12 to the reaction container 3 through the second line 102 and the first line 101. .

For example, when supplying a medicine from the medicine tank C, the medicine inflow valve 152 of the three-way valve connected to the medicine tanks A, B, D and E is kept open while the medicine inflow of the three-way valve connected to the medicine tank C is kept open. Only valve 152 opens. Therefore, only the medicine C is transferred to the reaction vessel 3 through the first line 101. After supplying a predetermined amount of the medicine, the solvent inflow valve 151 is opened again to flow the solvent, the medicine C remaining in the first line is washed away, and the state is restored to a steady state. The amount of the solvent required for washing is calculated by calculating the space inside the first line, and is set to a sufficient amount so that substantially no drug remains.
With the above operation procedure, the supply of the medicine C is completed. When supplying the medicines from the medicine tanks A, B, D and E, the same operation procedure is followed.

As described above, each time one kind of drug is supplied, it is necessary to wash the first line to prevent mixing of the drugs. The initial solvent volume is calculated by subtracting the solvent of the washing from the solvent volume. As the piping material, it is preferable to use a fluororesin tube or a fluororesin lining tube from the viewpoint of preventing the inside of the piping from being washed by the medicine and improving the cleanability of the inside of the piping.

In the case of a reaction using a catalyst, it is preferable to separate the catalyst supply line from the chemical supply line. When a plurality of catalysts are used, a third line 103 and a fourth line 104 are provided as catalyst lines as shown in FIG.

The drug supply control section controls the opening and closing of the three-way valve 15 and the flow rate of the pump 16 in accordance with a drug supply program in which an operation procedure for synthesizing a target compound is stored.
Control the supply of each chemical and catalyst. When the temperature or the pressure inside the reaction vessel exceeds the safe value, the drug supply control unit stops the pump 16 to temporarily stop the supply of the drug until the temperature and the pressure drop to the safe values.

Next, a case where the number of medicine tanks is increased or decreased will be described. As shown in FIG. 2, when a new medicine tank E is added to the apparatus including the medicine tanks A to D, the medicine tank E, the second line 102, the three-way valve 15, and the first line 101 for extension are used. Are added as one set. If you want to remove unnecessary drug tanks, please use the drug tank 12, the second line
The set 102, the three-way valve 15, and the first line 101 for extension may be removed.

It is preferable that the second line and the valve connected to each drug tank have the same shape. By making the valve dead space the same and arranging the valves in series, the number of drug tanks can be increased by simply adding / removing the set of drug tank, second line, three-way valve and first line for extension. Can be easily increased or decreased,
It can respond to various reactions.

[B] Reactor [1] Housing As shown in FIG. 3, the housing 2 supports the reaction vessel 3 and protects the rotating magnetic field device 4 and the like. The housing 2 may have any shape, for example, a columnar shape, a cubic shape, or the like. As shown in FIG. 4, the housing 2 is fixed on the lifter 23 with screws, and wheels 25 are provided on the lower surface of the lifter so that the lifter 23 can move on the rail 24 in the horizontal direction. After completion of the reaction, the housing 2 is moved downward by the lifter 23 while the position of the reaction vessel lid member 32 is fixed by the clamp 36, and then the reaction vessel 3 is removed from the lid part 32 by moving the rail 24 laterally. .

Rubber feet 22 are provided at four corners on the lower surface of the support plate of the rail 24 to absorb vibration. The housing 2 is made up of two or more parts and is fixed with screws or the like so that the internal components such as the rotating magnetic field device 4 can be easily maintained. For example, as shown in FIG. 4, the housing 2 includes two U-shaped members 21a and 21b, which are screwed.

Further, by attaching one or more shafts or the like to the housing and fixing the reaction container 3 to the shaft with a member such as a power clamp, the reaction container 3 and the housing 2 are integrally fixed, and The displacement of the reaction vessel due to the above may be prevented.

[2] Reaction Vessel The reaction vessel 3 is inserted into an opening on the upper surface of the housing 2 as shown in FIG. Although the shape of the reaction vessel 3 is not particularly limited, a cylindrical shape or a round bottom cylindrical shape is particularly preferable. In the present invention, in order to control the temperature of the reaction solution, the reaction vessel 3 is preferably made of a metal material having a high heat conduction rate, such as stainless steel or aluminum. A flange portion 3 a is formed on the upper surface of the reaction vessel 3, and is joined to a flange portion 32 a of a lid member 32 via a packing 31. The packing 31 is preferably made of a heat / chemical resistant synthetic resin / rubber such as fluororesin, fluororubber, silicon rubber, butyl rubber, and the like.

The cover 32 is fixed by a clamp 36. The lid member 32 has an external connection port such as an insertion port for the backflow condenser 33a and the thermometer 33b, an atmosphere gas inflow line 6a, a vacuum line 6b, a connection port for the drug line 101 and the catalyst line 103, and a thermometer 33b. The two-way valves 33a`, 17, 62, and 63 are connected to all the external connection ports except the insertion ports (the check valves 67 and 1 are further provided for the atmosphere gas inflow line, the chemical line, and the catalyst line).
8) is provided. During the reaction, the two-way valve 33a`, 17, 62, 6
By closing 3, operation under pressure is possible.

When the inside of the reaction vessel 3 is under reduced pressure,
The lid member 32 is pressed against the flange portion 3a of the reaction vessel 3 by the atmospheric pressure, and the reaction vessel 3 is naturally sealed. However, in order to normally keep the reaction vessel 3 in a sealed state, as shown in FIG. The lid member 32 and the reaction container 3 are joined together using the power clip 34 or a single ring-shaped power clamp.

As shown in FIG. 5, the back surface of the cover material except for the hole 32b for the external connection port is made of fluorine rubber, silicon rubber, or the like, as shown in FIG. It is preferable to cover with a seal 37 having chemical resistance such as. The seal 37 can be used many times by removing, washing, and reattaching it after the completion of the reaction.
As shown in FIG. 7, in the case of a lid material of a type to be inserted into the reaction vessel, the inside of the side surface 32c of the lid material also has a chemical resistant seal 37.
It is preferable to cover with. The chemical resistant seal is
Use one that can be easily attached and detached and does not fall off during the reaction.

[3] Rotating Magnetic Field Apparatus As the rotating magnetic field apparatus 4 that can be preferably used,
A type that rotates a magnet using a motor (motor-type rotating magnetic field device 40) and a type that creates a rotating magnetic field by sequentially moving the magnetic poles of a plurality of electromagnets arranged on the circumference in one direction (electromagnetic rotating magnetic field device) 41).
Hereinafter, each will be described.

(A) Motor-type rotating magnetic field device The motor-type rotating magnetic field device 40 is, as shown in FIG.
A horizontal support 401 fixed to the bottom surface of the rotary shaft, a rotary shaft 405 penetrating through the through hole 402 of the support 401, and rotatably fixed by bearings 403 and 404, and a pulley 406 fixed to the tip of the rotary shaft. , Two or more permanent magnets 407 fixed on the upper surface of the pulley 406 substantially symmetrically with respect to the rotation axis,
08 and a motor 409 connected to a pulley 406.

A through hole 402 is provided in the upper frame 401a and the intermediate frame 401b of the support body 401.
2, a rotating shaft 405 penetrates, and a pulley 4
06 is fixed. Because of the vibration caused by the high-speed rotation of the pulley 406, the support 401 needs to be firmly fixed to the housing 2. In the example of FIG. 9, the lower frame 401c of the support 401 is fixed to the bottom surface of the housing 2 by welding or the like.

The rotating shaft 405 passes vertically through the through hole 402 of the support 401, and a pulley 406 is provided at its tip with bearings 403, 40
It is rotatably fixed by 4.

As shown in FIG. 10, the ball bearing 403
Is fixed to the upper frame 401a of the support body 401, and the inner circumference is fixed to the rotating shaft 405. The outer periphery of the bearing 404 is fixed to the intermediate frame 401b of the support 401, and the inner periphery is fixed to the rotating shaft 405. Due to the strong permanent magnet of the rotor 7, the rotating shaft 405 and the pulley 406 are attracted upward. However, if only the ball bearing 403 is used, the rotating shaft 405 is attracted by a slight imbalance of the attracting force of the rotor 7. Eccentric force works,
There is a problem that the frictional force increases and the rotation speed does not increase. So we use ball bearings 403 and 404 at the same time,
By eliminating the horizontal deviation of the rotating shaft 405, the rotating shaft 4
05 can be rotated stably. The bearing is not limited to a ball bearing, and various known bearings can be used.

As shown in FIG. 9, the pulley 406 is
The motor 4 is fixed coaxially to the tip of
It is connected to a pulley 409a fixed to the tip of 09.
The pulley 406 is preferably made of a soft magnetic material so that it can act as a yoke when the permanent magnet is fixed.

A permanent magnet 407 is fixed on the upper surface of the pulley 406 symmetrically with respect to the rotation axis. The number of the permanent magnets 407 is preferably an even number, and the permanent magnets 407 are alternately arranged so that the opposite magnetic poles face upward. As permanent magnet materials, KS magnet, N
KS magnets, ferrite magnets, rare earth magnets, etc., are preferred, but rare earth magnets are preferred from the viewpoint of high magnetic flux density.
Nd-Fe-B based rare earth magnets are preferred. The magnetic flux of the permanent magnet 407 exerts an attractive force and a repulsive force on the permanent magnet fixed to the rotor 7.

The motor 409 rotates a pulley 406 to which a permanent magnet 407 is fixed via a pulley 409a fixed to an upper end thereof and a belt 408. As the motor 409, either an AC motor or a DC motor can be used. In the example of FIG. 9, the motor 409 is installed vertically,
b is fixed to the upper frame 401a of the support 401. A power supply to the motor, an on / off switch, a switch for switching a current direction, an indicator lamp indicating on / off of the switch, a device for controlling the number of rotations of the motor, and the like can be appropriately arranged inside or outside the housing 2. it can.

(B) Electromagnet type rotating magnetic field device The electromagnet type rotating magnetic field device 41 includes a horizontal support plate 412 fixed to the bottom surface of the housing 21 as shown in FIG. Consists of eight coils 411 arranged at intervals,
The coil 411 is arranged such that the magnetization direction thereof is directed to the center of the circumference.

The coil 411 is connected to a rotation speed control unit 44 having a power supply device. One of the coils facing each other has an N pole and the other has an S pole as shown in FIGS. 12 (a) and 12 (b). A rotating magnetic field is created by passing a current through the coil and periodically moving the positions of the north and south poles by 45 °. In FIG. 12, two N poles and two S poles are provided, but one N pole and one S pole may be provided. In FIG. 12, the number of coils is eight, but the number of coils is not limited as long as the number is four or more.

(C) Control of Rotating Magnetic Field In order to stir at a speed desired by the user, it is preferable to make the rotating speed of the rotating magnetic field variable. The rotating magnetic field control unit includes a normal current or voltage variable power supply, a rotation speed setting unit 42, a rotation speed detection unit 43, and a rotation speed control unit 44. The rotation number detecting unit measures the actual rotation number of the rotor 7 in the reaction vessel by using a rotation number detecting magnet 75 attached to the rotor 7 or the like.
The rotation speed control unit 44 constantly compares the rotation speed set by the user with the rotation speed setting unit 42 with the rotation speed measured by the rotation speed detection unit 43, and if they do not match, the power supply device increases or decreases the current or voltage. To instruct.

[4] Temperature Control Unit The temperature control unit heats and / or cools the reaction vessel 3 so that the temperature of the reaction solution becomes a desired value. FIG. 3 and FIG. 13, which is a cross-sectional view taken along line FF of FIG. 3, show an example of the temperature control unit. In the example of FIG. 13, the heating means comprises an electric heater 51, and the cooling means comprises a cooling device 52 comprising a Peltier element, a radiator 54, and a fan 55. The temperature controller is a thermometer 33
b, an on / off switch, a switch 57 for selecting a heating unit and a cooling unit, and a temperature setting unit 58, and their operations are controlled by a temperature control unit 59.

As shown in FIG. 3, in order to quickly transfer heat to the reaction vessel 3, a heat conductor 53 having a hollow portion 53a opening upward is formed in contact with the upper surface of the housing. The upper half of the heat conductor 53 is a cylindrical body, and the lower half is a rectangular solid. Holes 53b for inserting the bar-shaped electric heater 51 are formed in the lower rectangular body at each corner.
The opening of the hollow portion 53a is located below the opening on the upper surface of the housing, and the reaction vessel 3 is inserted into the hollow portion 53a through the opening of the housing. The heat conductor 53 is made of a metal material having a high heat conduction rate, such as aluminum, so that heat in the reaction vessel 3 can be quickly diffused or heat can be transferred in the reaction vessel 3.

The electric heater 51 is inserted into a hole 53 b provided in the heat conductor 53, and performs heating according to an instruction from the temperature controller 59. The three cooling devices 52 are fixed to the side surfaces of the heat conductor 53 with an adhesive or the like. The cooling device 52 is instructed by the temperature controller 59.
Is applied to the Peltier element, and the heat of the heat conductor 53 is carried by the Peltier element.

A radiator 54 made of aluminum fins is fixed to the surface of each Peltier element, and dissipates the heat carried from the heat conductor 53. In addition, outside air enters through a ventilation hole 26 (see FIG. 13) provided on a side surface of the housing, and is discharged from the fan 55 through a radiator 54 by a fan 55 provided on the side surface of the housing. Due to this ventilation, heat on the Peltier element is quickly transferred to the outside of the device.

FIG. 14 shows a system block diagram of the temperature controller. The temperature control unit 59 includes a thermometer 33 placed in the reaction vessel 3.
The temperature of the reaction solution measured in b is compared with the temperature set by the user.If the temperature of the reaction solution is lower than the set temperature and the selection switch 57 is set to heating or automatic control, the electric heater 51 is turned on. Instruct to heat. On the other hand, if the temperature of the reaction solution is higher than the set temperature and the selection switch 57
Is set to cooling or automatic control, the cooling device 52
And instruct the fan 55 to operate.

In the present invention, the cooling device is not limited to the Peltier device, and various known cooling means can be used. For example, there is a method of introducing a refrigerant cooled by an external cooling device to cool the reaction device.

Further, there is provided a means for displaying the reaction solution temperature measured by the thermometer 33b and / or the temperature set by the user on a display device, and / or an external output means for outputting a digital signal or an analog signal outside the reaction device. be able to. With these output means, a set temperature as a reaction condition and a temperature history accompanying the progress of the reaction can be recorded manually or automatically.

[5] Pressure Adjusting Unit The pressure adjusting unit 6 is composed of a pressurizing unit by the atmospheric gas supply line 6a and a depressurizing unit by the vacuum line 6b, and keeps the pressure inside the reaction vessel within a predetermined range set by the user. It is controlled by the pressure controller to maintain it.

FIG. 15 shows a system block diagram of the pressure adjusting section 6. The pressure gauge 61 detects the pressure inside the reaction vessel 3, and when the pressure exceeds a predetermined value, the valve 62 of the vacuum line is opened to reduce the pressure. When the pressure is less than the predetermined value, the valve 63 of the atmospheric gas supply line is opened and automatically adjusted to maintain the pressure near the normal pressure.

In the atmosphere gas supply line 6a, the atmosphere gas supply pressure is adjusted by the pressure regulating valve 64, and the needle valve
The atmosphere gas supply flow rate is finely adjusted by 65, and the atmosphere gas flow rate is measured by the flow meter 66. The check valve 67 prevents the reaction solution in the reaction vessel from flowing back into the atmosphere gas supply line when the supply pressure of the atmosphere gas is lower than the inside of the reaction vessel 3.

Means for displaying the pressure inside the reaction vessel measured by the pressure gauge 61 and / or the pressure within a predetermined range set by the user on a display device and / or an external device for outputting a digital signal or an analog signal outside the reaction device. Output means can be provided. With these output means, it is possible to manually or automatically record a set pressure as a reaction condition and a pressure history accompanying the progress of the reaction.

[6] Stirring Rotor In the semi-automatic synthesis apparatus of the present invention, a known stirring rotor can be used without any particular limitation. The stirring rotator 7 is placed in the reaction vessel 3 placed on the rotating magnetic field device 4, and is rotated by the rotating magnetic field to perform stirring.

In the case where the reaction solution has a high viscosity, see JP-A-11-137.
It is preferable to use a bearing-type stirring rotor described in No. 990 or a rotor having a plurality of rotating members. Such a stirring rotor can be rotated as desired without providing a rotating shaft on the rotor itself, is easy to handle, and can be stirred under vacuum, pressure, high temperature, and the like. Easy to do.

A rotor having a plurality of rotating members is newly developed by the present inventors for stirring a high-viscosity solution. The rotor is attached to at least the support and the support so as to rotate in contact with the bottom surface of the reaction vessel.
And more than one rotating members.

The rotor of the present invention is characterized in that it has excellent stirring efficiency, hardly damages the reaction vessel, and can be suitably used for a round-bottom reaction vessel. In addition, JP-A-11-1
Unlike the bearing type stirring rotor described in 37990, there is no need to attach a bearing to the center of the rotor,
There is an advantage that it is easy to secure an opening for promoting up and down flow at the center of the support, and the stirring efficiency can be improved.

Hereinafter, the rotor of the present invention will be described with reference to examples.

(1) First Embodiment As shown in FIG. 16, the stirring rotor 7 of the first embodiment comprises a support 71 having an opening 71b, and four rotating members fixed to the support 71. Consists of 72.

(A) Support The support 71 has a function of maintaining the balance of the rotor 7 and a function as a yoke when magnetized by the magnetic field of the rotating magnetic field device 4. In FIGS. 16 (a), (b) and (c), the support 71
Is a rectangular plate having two projections 71a on the lower surface and an opening 71b penetrating in the vertical direction, but the shape of the support is not limited to this. Shape, a plate shape such as a polygonal plate shape, or a U-shape. Further, the side surface may be inclined for the purpose of controlling the flow.

The material of the support 71 is not particularly limited as long as it is a soft magnetic material. From the viewpoint of strength and chemical resistance, a metal having chemical resistance and soft magnetism such as soft magnetic stainless steel is preferable. Further, another soft magnetic metal such as an iron alloy may be coated with a chemically resistant resin such as a fluororesin.

When stirring a high-viscosity liquid, it is better to make the support 71 heavier to some extent in order to ensure rotational stability.

By providing the opening 71b in the support,
Since the liquid above and below the support 71 flows through the opening 71b during the stirring, the stirring efficiency can be increased. As long as a space for fixing the rotating member 72 can be secured, the opening 71b
May be as large as possible. The edge of the opening 71b may be a vertical surface, but may be an inclined surface to promote the up and down flow of the liquid.

Since the stirring rotor of the first embodiment does not have a permanent magnet, it can be used even in a high temperature environment, particularly at a temperature of 120 ° C. or higher. When the permanent magnet is not provided, it is necessary to make the shape of the support 71 as long as possible, such as a rectangle, a rhombus, and an ellipse, so as to function as a yoke. However, the width A of the support is 20% or more of the maximum length B of the support. Elongating the support beyond the range is not preferable because rotation becomes unstable.

In order to get closer to the magnetic field of the rotating magnetic field device 4 for driving the rotor, it is preferable to lower the lower surface of the support 71 as low as possible. In the example of FIG. 16, the position of the lower surface of the support is lowered by providing two lower protrusions 71a on the support 71. Assuming that the distance from the lower surface of the support 71 to the bottom surface of the reaction vessel in which the rotor 7 is placed is d, d is preferably 5 mm or less. The lower limit of d is 0.5 mm. d
If the diameter is smaller than 0.5 mm, the support 71 may collide with the bottom surface 3b of the reaction vessel, which is not preferable.

(B) Rotating Member The rotating member 72 includes a rotating body such as a wheel and a ball, and components for rotatably holding the rotating body. Rotating member
By using 72, the friction between the rotor and the container bottom surface is reduced, and the rotor can be smoothly rotated.
The number of rotating members is not particularly limited as long as it is an integer of 3 or more.

The rotating member is attached to the support so as to rotate in contact with the bottom surface of the reaction vessel. In the first embodiment, as shown in FIG.
Are arranged on a circle around the rotation axis Z. The rotating members are preferably arranged at equal intervals on the circumference. The rotation axis Z preferably passes through the center of gravity G of the rotor 7, but may slightly deviate from the center of gravity G as long as the rotor can rotate stably. In order to stabilize the rotation, it is preferable that the diameter W of the circumference where the rotating member is disposed is set to 20% or more of the maximum length B of the support 71.

In the first embodiment shown in FIG. 16, a caster is used as the rotating member 72, but a known rotating member other than a rotating member using wheels or balls can be used without particular limitation. Hereinafter, specific examples of the rotating member 72 will be described.

FIG. 17A shows a state in which the wheel 721 is held through the wheel shaft 722 and the wheel shaft 722 is supported by the bearings 723a and 723b.
It is a rotating member sandwiched between. Fluoro rubber tires 724 are attached to wheels 721 to prevent damage to the bottom of the reaction vessel.
Has been fitted. The screw 725 allows the rotating member 72 to be
Fixed to.

FIG. 17 (b) shows a rotating member in which both sides of a wheel 721 are held between two wheel shafts 722. In order not to damage the bottom of the reaction vessel, the ground surface of the wheel 721 is curved.

FIG. 17 (c) shows a part of the rotating member shown in FIG. 17 (a) cut obliquely to fix the wheel 721 at an angle. Such a wheel can be preferably used especially when a round bottom reaction vessel is used. The rotor can be stabilized by tilting the angle of the wheel so that it is perpendicular to the curved surface of the round bottom container.

FIG. 18A shows an example of a rotating member using a ball 726 as a rotating body. The support body 723 has four legs 727, and the ends of each leg are slightly curved inward as shown in FIGS. 726 is loosely fitted. The support 723 supports the wheel shaft 722, and the wheel 721 is in contact with the ball 726. Since the wheel 721 rotates in reverse with the rotation of the ball 726, friction can be reduced, and the ball can be smoothly rotated in one direction.

(2) Second Embodiment As shown in FIG. 19, the stirring rotor 7 of the second embodiment comprises a support 71, four rotating members 72 fixed to the support 71,
Two or more permanent magnets 73 symmetrically fixed to the lower surface of the support 71
And a U-shaped stirring member 74 and a rotation speed measuring magnet 75.

(A) Support The support 71 of the second embodiment is a support 71 for fixing the rotating member.
One side recess 71a, a central opening 71b through which liquids above and below the support 71 penetrate and flow, two lower surface protrusions 71c for fixing the permanent magnet 73 with screws, and a U-shaped stirring member 74. It consists of a disk having an upper surface groove 71d for fixing.

(B) Rotating Member In the second embodiment, the rotating member shown in FIG. 17B is used as the rotating member 72, but the present invention is not limited to this.

(C) Permanent magnet The permanent magnet 73 is fixed substantially symmetrically with respect to the rotation axis of the support 71. The number of the permanent magnets 73 is preferably an even number, and it is preferable that the permanent magnets 73 are fixed to the support 71 so that the magnetization directions are perpendicular. The permanent magnets are arranged so that the opposite magnetic poles face downward alternately, for example, as shown in FIG. 22, such that the lower surface of one permanent magnet is an N pole and the lower surface of the other permanent magnet is an S pole. Place and fix the permanent magnet.

In the case of stirring the high viscosity solution, it is preferable to use a strong permanent magnet for the rotor magnet. As such permanent magnets, KS magnets, NKS magnets, FeCrO
Magnets, ferrite magnets, rare earth magnets, etc.
Rare earth magnets are preferred from the viewpoint of high magnetic flux density.

In order to stir a liquid having a high stirring resistance such as a high viscosity solution, it is preferable to use an ultra high performance sintered magnet as the permanent magnet 73. As such an ultra-high performance sintered magnet,
Rare earth permanent magnets such as Nd-based and Sm-based magnets are exemplified. _{Specifically, Nd 2 Fe 14 B, Sm} (Co-Fe-Cu-Zr) 7, Sm (Co-Fe-Cu) 7,
Sm-Pr-Co ₅ , sintered SmCo _{5 and the} like can be mentioned. A preferred permanent magnet is Nd ₂ Fe ₁₄ B.

In the second embodiment, as shown in FIGS. 20 (b) and 20 (c), a screw hole is formed in the permanent magnet 73, and the permanent magnet 73 is fixed to the lower surface convex portion 71c of the support with the screw 77. However, the method of fixing the permanent magnet is not limited to this.

For example, FIG. 21 shows the individual permanent magnets 73a, 73
b are box-shaped casings 78a and 78b each made of a chemical-resistant metal or resin (supported by welding or a chemical-resistant adhesive, etc.)
An example in which the inner permanent magnet 73 is prevented from coming into contact with the stirring solution by being hermetically closed by being fixed to the lower surface of the magnet 71 in a hermetically sealed state). FIG. 22 shows an example in which the support 71 and the permanent magnet 73 fixed to the lower surface thereof are completely covered with the chemical-resistant resin layer 79.

Coating methods for the chemical resistant resin include coating,
Examples include electrostatic coating and electrodeposition coating. Preferred chemical resistant resins are one or more selected from the group consisting of fluororesins, polyethylene resins, melamine resins, epoxy resins, urethane resins, polyamide resins, and other thermosetting resins. Particularly preferred chemical resistant resin is a baking fluororesin paint containing a polymer such as ethylene tetrafluoride, ethylene trifluoride chloride, vinyl fluoride, vinylidene fluoride and propylene hexafluoride as a main component. Commercially available fluororesin paints include Blue Armor (manufactured by Du Pont), Aflon COP (manufactured by Asahi Glass Co., Ltd.) and the like. By using the fluororesin paint for baking, excellent chemical resistance can be imparted to the permanent magnet, and it can be widely used for a rotor for organic synthesis reaction.

(D) Stirring Member In the second embodiment, the shape of the stirring member 74 is a U-shaped bar, but the length of the bar is not particularly limited. In addition, the shape of the stirring member is not particularly limited, and may be an arbitrary shape such as a plate shape or a propeller shape.

Further, the stirring member may protrude from the support 71. Further, the stirring member may be provided on any of the upper surface, the lower surface, and the side surface of the support.

(E) Rotation speed measuring magnet When measuring the viscosity of the reaction solution by measuring the rotation speed of the stirring rotor, a magnet 75 for measuring the rotation speed is provided on the stirring rotor 7 and the magnet 75 is provided. What is necessary is just to measure rotation of an external sensor. The position of the rotation speed measuring magnet is not particularly limited.

(3) Third Embodiment As shown in FIG. 23, the stirring rotator 7 of the third embodiment comprises supports 71A and 71B, four rotating members 72, and
It comprises a pair of permanent magnets 73 joined to 1B, two stirring members 74 attached to the side of the support 71A, and four wheels 76 attached to the upper surface of the support 71A.

(A) Support As shown in FIG. 24, the support has two detachable parts.
71A and 71B, both of which are fixed by screws 77.

On the support 71A, facing the wall surface of the reaction vessel.
By attaching the four wheels 76, collision when rotating the rotor is reduced, and the inner wall of the reaction vessel is hardly damaged. As the wheel 76, a wheel fitted with a tire 724 made of fluoro rubber shown in FIG. 17 (a) is used. A groove having the same width as the rotating member 72 and the stirring member 74 is slightly carved on the side surface of the support 71A, and the rotating member 72 and the stirring member 74 are firmly fixed.

The support 71B holds a pair of permanent magnets 73, and is inserted into the opening of the support 71A. Since the support 71B can be moved up and down by changing the position of the screw 77, the distance between the permanent magnet 73 and the rotating magnetic field device 4 can be easily finely adjusted.

In the third embodiment, the opening 71 of the support is provided.
Since b is provided as large as possible, the stirring efficiency can be further improved.

(B) Stirring member In the third embodiment, two bars are attached to the side surface of the support as a stirring member. The stirring member 74 is provided at the support opening 71b.
And does not hinder the vertical movement of the fluid, so that the stirring efficiency can be improved.

The number of stirring members is arbitrary, but is preferably an even number in consideration of the rotational balance of the rotor 7. The material of the stirring member is not particularly limited as long as it has chemical resistance, but a chemical-resistant metal such as stainless steel is preferable.

(4) Fourth Embodiment As shown in FIG. 26, the stirring rotor 7 of the fourth embodiment comprises a support 71 and four rotating members 7 attached at an angle.
2 and a pair of permanent magnets 73 joined to the lower surface of the support.
And four L-shaped stirring members 7 attached to the upper surface of the support
Consists of four.

The fourth embodiment is characterized in that the rotating member 72 is attached to the support 71 while being inclined. When the rotating member is inclined as shown in FIG. 27, stability is improved when the rotating member is installed in the reaction vessel 3 having a round bottom. The inclination angle of the rotating member 72 is
What is necessary is just to set according to the curvature of a round bottom container.

In the fourth embodiment, the rotating member is inclined by cutting the mounting surface of the rotating member 72 on which the support 71 is obliquely cut. The method of providing the inclination is not limited to this,
For example, the mounting surface of the rotating member of the support 71 may be cut diagonally.

In the example shown in FIG. 26, the shape of the stirring member is an L-shaped material. However, the shape of the stirring member is not particularly limited, and may be inclined, or any shape such as a propeller shape. be able to.

With respect to the configuration other than the above, the stirring rotor of the fourth embodiment may be the same as that of the second or third embodiment.

(5) Fifth Embodiment In a fifth embodiment shown in FIG. 28, the support 71 is made of a horizontal plate member, and a pair of at least one stirring member 74 projecting axially symmetrically from the center of the plate member. Is formed. In the example of FIG. 28,
Although the stirring member 74 and the support 71 are integrally formed,
The shape of the stirring member can be any shape such as a propeller shape in addition to a plate shape. Further, the length of the stirring member is not limited. By providing the stirring member 74 on the support 71, the rotor can be made compact, and the center of gravity becomes lower than when the rotor is provided on the upper part, so that the stability is increased. Regarding the structure other than the support 71 and the stirring member 74, the rotor 7 of the fifth embodiment may be the same as any one of the first to fourth embodiments.

(6) Sixth Embodiment In the sixth embodiment shown in FIGS. 29 (a), (b), and (c), three circular openings 71b arranged at equal intervals on a circular support 71 are provided. Is provided. The edge 71 b ′ of the opening is formed as an inclined surface to promote the up and down flow of the support 71. With the opening 72,
During the stirring, the liquid above and below the support 71 flows through the opening 71b, and the stirring efficiency can be increased. Permanent magnet 73
The opening 71b may be made as large as possible, as long as a space for fixing is secured. The opening 71b of the support 71
Regarding other structures, the rotor of the sixth embodiment may be the same as any one of the first to fifth embodiments.

[7] Variable Detector (1) Detection of Rotation Speed When a motor-type rotating magnetic field device is used, the rotation speed can be detected by measuring the rotation speed of the motor 409. For example, a method of attaching a marker to the rotating shaft and counting the reflected light of the marker with an optical sensor, a method of providing a small generator on the rotating shaft to generate an alternating current, and counting the frequency, and the like can be mentioned.

When an electromagnet type rotating magnetic field device is used, the number of revolutions is detected by measuring the number of revolutions of the rotor 7. For example, there is a method in which a magnet 75 is provided in a part of the rotor 7 and the rotation of the magnet is counted by the rotation number detecting unit 43 outside the reaction vessel. The position where the rotation speed measuring magnet 75 is provided is
There is no particular limitation.

[0111] Such a rotational speed measuring device is commercially available, and when a commercially available product is used, the rotational speed can be easily detected.

(2) Detection of Torque When a motor-type rotating magnetic field device is used, by measuring the torque of the motor 409 or the rotating torque of the rotating shaft 405,
As described below, the viscosity of the reaction solution can be estimated.
The torque output means includes a torque sensor and a torque output means. The torque sensor is disposed between the drive shaft and the load shaft. FIGS. 30A and 30B show two arrangement examples. In the example of FIG. 30a, the torque sensor 400 is disposed between the motor 409 and the pulley 409a. In the example of FIG. 30b, the motor 409 is arranged below the rotating disk 406 ', and the gearbox 409d and the torque sensor 400 are arranged between the motor 409 and the rotating disk 406'.

The torque output means is the torque sensor 400
And / or means for displaying the output torque value on a display device and / or outputting the torque value as a digital signal or an analog signal outside the reactor. With these output means, the torque value can be recorded manually or automatically.

The torque sensor normally connects the drive shaft and the load shaft with a torsion bar, measures the phase difference between the drive shaft and the load shaft before and after the torsion bar, and converts it into torque. In the present invention, the torque sensor and the torque output means are not particularly limited, and a known product such as a commercially available product can be used.

(3) Detection of Viscosity of Reaction Solution The viscosity of the reaction solution is estimated from the torque of the rotating magnetic field device 4 based on the viscosity of the reaction solution. By measuring the change in the viscosity of the reaction solution as the reaction progresses, the progress of the reaction can be estimated, and it is useful for elucidating the reaction mechanism.

The means for measuring viscosity has a computer which can be inputted from the torque output means. When the torque output means of the rotating magnetic field device 4 outputs an analog signal, the analog signal is input to a computer via an A / D converter. Conversely, when the torque output means outputs a digital signal, the signal can be directly connected and input to a digital input / output port such as a serial port or a parallel port of the computer.

The viscosity of the reaction solution is measured according to the following procedure. (a) First, select a plurality of standard solutions having different viscosities.
The viscosity range of the standard solution should cover the variation range of the viscosity of the reaction solution.

(B) Next, the standard solution is stirred under the same conditions as the reaction solution, and the torque number of the rotating magnetic field device at that time is input. The conditions mentioned here include the stirring speed, the set temperature, and the atmosphere. Thus, the binary number indicating the relationship between the torque and the viscosity is obtained by associating the input torque number with the viscosity of the standard solution.

(C) The reaction to be measured is performed, and the torque history of the rotating magnetic field device is input.

(D) Using the binary array showing the relationship between the torque and the viscosity obtained in (b) above, calculate the viscosity of the torque of the reaction solution by a known numerical analysis method. By performing this for all of the reaction torque history, the viscosity history of the reaction solution is obtained.

The viscosity history of the obtained reaction solution can be output to a display, a printer or the like by a known method. According to the above-described procedure, the change in viscosity of the reaction can be easily measured.

(4) Detection of Caloric Fluctuation Due to Reaction The caloric fluctuation is estimated by approximately calculating the calorific value generated by the exothermic reaction or the caloric value absorbed by the endothermic reaction. Examples of the exothermic organic reaction that generates a considerable amount of heat include polymerization of vinyl monomers such as styrene and vinyl acetate, and acrylic monomers such as acrylic esters, acrylonitrile, and acrylic acid. In large reactors,
Incorrect prediction of the reaction heating value makes it impossible to control the temperature by cooling during the exothermic reaction, leading to serious accidents. Therefore, the fact that the calorific value of the chemical reaction can be experimentally measured at the time of sample synthesis is an index that allows a marginal temperature control when transferring to mass production at a factory. By the measuring means of the present invention, the calorific value fluctuation of the organic reaction can be easily obtained from the temperature of the reaction solution, and can be used as a guide for the safety of the organic reaction and the design conditions of the reaction apparatus.

The means for measuring the change in the calorific value of the reaction has a computer which can be inputted from the external output means of the temperature control means.
The computer here refers to a computer system having an input device such as a keyboard, a storage device such as a memory and a floppy disk drive, and an output device such as a monitor display and a printer, in addition to a calculation unit including a CPU. When the external temperature output means outputs an analog signal, the analog signal is input to a computer via an A / D converter. Conversely, when the external temperature output means outputs a digital signal, the signal can be directly connected to a digital input / output port such as a serial port or a parallel port of the computer and input. Hereinafter, three cases of an exothermic reaction, an endothermic reaction, and an exothermic and endothermic reaction will be described respectively.

(I) Exothermic reaction (a) Principle The balance of the change in the amount of heat per unit time in the reaction vessel can be expressed by the following equation. dQ / dt = dQr / dt + dQcv / dt, where Q is the amount of heat in the reaction vessel, Qr is the amount of heat (having a negative value) out of the reaction vessel, and Qcv is the amount of heat generated by the reaction. Since the change in the amount of heat in the reaction vessel appears as a change in the temperature, the above equation can be rewritten as follows. C · M · dT / dt = dQr / dt + dQcv / dt where C represents the specific heat of the reaction solution, and M represents the weight of the reaction solution.

The dQr / dt corresponds to the cooling rate of the reactor, and is affected by the characteristics of the reactor, the outside air temperature, the specific heat of the reaction solution, the weight, etc., and is difficult to obtain theoretically. However, if cooling is performed using a reference solution that has the same specific heat and weight as the reaction solution and does not generate or absorb heat, Qcv in the above equation becomes 0, and dQr / dt can be obtained experimentally.

(B) Calculation of calorific value (a) First, specific heat C and weight M of the reaction solution are input to a computer as initial conditions. The specific heat C of the reaction solution can be easily obtained by a known method. In the present invention, it is assumed that the specific heat of the reaction solution does not change much.

(B) An organic reaction is carried out at a predetermined set temperature Tset by using the above reaction apparatus, and the reaction temperature history of the organic reaction is inputted. At this time, in the temperature control means, the selection switch 47 is set to cooling or automatic control so that only the cooling device operates. Since the reaction is only an exothermic reaction, the temperature in the course of the reaction does not become lower than the set temperature Tset. The reaction temperature history obtained here is a binary array consisting of the reaction elapsed time and the temperature of the reaction solution at that time.

(C) Next, a reference solution having substantially the same specific heat as the reaction solution is selected. The type of the reference solution is not particularly limited as long as it does not generate heat or endotherm, but if the content of the solvent in the reaction solution is overwhelmingly large, it is considered that the specific heat of the solvent is almost the same as the reaction solution. It can be used as a solution. If the reaction solution after the reaction does not further generate or absorb heat, it can be used as a reference solution.

Using a reference solution having the same weight as the reaction solution, a reference solution heated to a temperature higher than the maximum value Tmax of the temperature change range in the reaction temperature history is put into the reactor, and the reaction is performed under substantially the same conditions as in the organic reaction. Cool to the set temperature Tset and enter the cooling temperature history. The cooling temperature history obtained here is a binary array consisting of the elapsed cooling time and the temperature of the reference solution at that time.

(D) The cooling temperature history, specific heat C, and weight M
Is used, the cooling rate Vcool at an arbitrary temperature T within the range of the set temperatures Tset to Tmax is calculated by the following equation: Vcool (T) = dQr / dt = C · M · dT / dt (where t Is the elapsed cooling time, and T is the temperature of the reference solution corresponding to the above-mentioned t.). Vcool (T) obtained here is a function of the temperature T, and is a binary array consisting of the normal temperature T and the cooling rate Vcool (having a negative value) at that temperature.

Note that dT / dt is a rate of change (decrease rate) of the temperature T during an arbitrary cooling elapsed time, and can be easily obtained from the numerical value of the cooling temperature history by a known numerical analysis method such as a numerical differentiation method.

(E) Finally, the reaction temperature history and the cooling rate Vco
Using ol, specific heat C, and weight M, the exothermic rate dQcv / dt 'of the reaction is determined by the following equation: dQcv / dt' = Vcool (T ') + C.M.dT' / d
t '(where, t' represents the elapsed time of the reaction, and T 'represents the temperature of the reaction solution corresponding to the above-mentioned t'; the integration range of the time t 'is from the start to the end of the reaction). Note that dT '/ dt' is a rate of change of the reaction solution temperature T 'during an arbitrary reaction elapsed time, and can be easily obtained by a known numerical analysis method. The calorific value of the reaction is obtained by numerically integrating the heat generation rate dQcv / dt '.

(Ii) In the case of endothermic reaction In the case of endothermic reaction, the balance of heat change per unit time in the reaction vessel can be expressed by the following equation. dQ / dt = dQh / dt + dQev / dt where, Q is the amount of heat in the reaction vessel, Qh is the amount of heat entering the reaction vessel from the outside, and Qev is the amount of heat absorbed by the reaction (having a negative value). For the same reason as in the case of the exothermic reaction, if a reference solution having the same specific heat and weight as the reaction solution and neither exothermic nor endothermic is used, Qev in the above equation becomes 0, and dQh / dt can be experimentally obtained. it can.

Among the procedures for calculating the amount of heat absorbed, the following are performed: (a) a procedure for inputting the specific heat C and the weight M of the reaction solution; (b) an organic reaction is carried out at a predetermined set temperature Tset using the above-mentioned reaction apparatus. The procedure for inputting the reaction temperature history of the organic reaction is the same as the procedures (a) and (b) for calculating the calorific value described above, and the other procedures will be described below.
However, the selection switch 47 in the temperature control means is set to heating or automatic control so that only the heating device operates.

(C ') Procedure for calculating the calorific value After selecting a reference solution having substantially the same specific heat as the reaction solution in the same manner as in (c), using the reference solution having the same weight as the reaction solution, The reference solution cooled to a temperature lower than the minimum value Tmin of the temperature change range in the temperature history is put into the reactor, heated to the set temperature Tset under substantially the same conditions as the organic reaction, and the heating temperature history is input. The heating temperature history obtained here is a binary array consisting of the elapsed heating time and the temperature of the reference solution at that time.

(D ') The heating temperature history, specific heat C, and weight M
Is used, the heating rate Vheat at an arbitrary temperature T within the range of the set temperatures Tset to Tmin is calculated by the following equation: Vheat (T) = dQh / dt = C · M · dT / dt (where t Represents the elapsed time of heating, and T represents the temperature of the reference solution corresponding to the above t.). Vheat (T) obtained here is a function of the temperature T, and is a binary array composed of the normal temperature T and the heating rate Vheat at that temperature. As described above, dT / dt can be easily obtained by a known numerical analysis method.

(E ') Finally, the reaction temperature history and the heating rate V
Using the heat, the specific heat C, and the weight M, the endothermic rate dQev / dt 'of the reaction is obtained by the following equation: dQev / dt' = Vheat (T ') + C ・ M ・ dT' / d
t '(where, t' represents the elapsed time of the reaction, and T 'represents the temperature of the reaction solution corresponding to the above-mentioned t'; the integration range of the time t 'is from the start to the end of the reaction). Note that dT '/ dt' can be determined by a known numerical analysis method. Endothermic velocity dQev
The reaction endotherm is obtained by numerically integrating / dt '.

(Iii) Exothermic and Endothermic Reaction In the case where both an exothermic reaction and an endothermic reaction are present in the reaction process, the above procedures (a), (b), (c), (c ′), (d) ), (D ') and the following procedure (e ") to calculate the calorific value fluctuation,
The selection switch 47 in the temperature control means is set to automatic control.

(E ″) From the reaction temperature history, the cooling rate Vcool, the heating rate Vheat, the specific heat C, and the weight M, the rate of change in the calorific value of the reaction dQ / dt ′: dQ / dt ′ = F (T ′) + C ・ M ・ dT '/ dt' where F (T ') = Vcool (T') when T> Tset, F (T ') = 0 when T = Tset, and T <Tset In this case, F (T ′) = Vheat (T ′), t ′ represents the reaction elapsed time, T ′ represents the temperature of the reaction solution corresponding to the above t ′, and the integration range of the time t ′ is from the start to the end of the reaction. Note that dT '/ dt' can be obtained by a known numerical analysis method, and the calorific value fluctuation rate dQ / dt '.
By numerically integrating, the calorific value fluctuation of the reaction can be obtained.

The obtained calorific value Qcv, endothermic amount Qev and calorific value variation Q of the reaction can be output to a display, a printer or the like by a known method.

According to the above-described procedure, the change in the amount of heat due to the reaction can be determined with considerable accuracy, and the measurement can be performed at the same time when the reaction is carried out in the reaction apparatus of the present invention. Can be. The heat of reaction is an important factor in considering the safety of the organic reaction and the design conditions of the reactor.

[C] Controller The controller is composed of a computer and an operation control box.
It has a rotating magnetic field control unit, a temperature control unit 59, and a pressure control unit. The controller controls the supply amounts of the drug and the solvent, the rotation speed of the rotating magnetic field, and the temperature and pressure in the reaction vessel through instructions from a computer.

FIG. 31 shows the relationship between the drug supply device, the reaction device, and the control device. For the synthesis of the target compound, the procedure input by the user is transmitted from the computer through the operation control box to the drug supply device and the reaction device, and the operation is controlled. Also, the number of rotations detected from the variable detection unit,
Data such as viscosity and calorific value fluctuations are fed back to the computer through the operation control box to grasp the status of the reaction on the screen and record the data on the computer.

[D] Method of Using Semi-Automatic Synthesis Apparatus First, the stirring rotor 7 is gently put into the reaction vessel 3, the reaction vessel 3 and the lid 32 are firmly fixed with the power clip 34, and the inside of the vessel is evacuated. . Next, by the medicine supply device 1,
The initial solvent from which the solvent amount of the washing has been subtracted flows into the reaction vessel 3.

Thereafter, the magnetic field of the rotating magnetic field device 4 is rotated, the rotor 7 in the reaction vessel 3 is rotated, bubbling with the atmospheric gas is started, and the temperature of the reaction vessel 3 is raised. In accordance with the drug supply program for synthesizing the target compound, the control device weighs in the drug and the catalyst while instructing the opening / closing of the three-way valve 15 and the flow rate of the pump 16. During the reaction, the control device controls the pressure and temperature so that the pressure and temperature inside the reaction vessel 3 do not exceed the safe values. When the temperature or the pressure inside the reaction vessel rises rapidly, the supply of the drug is automatically stopped until the temperature or the pressure drops.

When the completion of the reaction is confirmed from the reaction time, the viscosity of the reaction solution and the like, the bubbling and stirring with the atmospheric gas are stopped. The power clip 34 is removed, the housing 2 is moved by the lifter and the rail, the reaction container is removed from the lid material, and the reaction product in the reaction container is collected.

Although the present invention has been described in detail with reference to the accompanying drawings, the present invention is not limited thereto, and various modifications can be made without departing from the spirit of the present invention.

[0148]

As described above in detail, the semi-automatic synthesizing apparatus of the present invention has a relatively simple piping structure because a plurality of chemical tanks are finally connected to the first line via the second line. Thereby, a plurality of drugs can be supplied to the reaction container without mixing. The semi-automatic synthesis apparatus of the present invention, in which a stirrer, pressure control, and temperature control are integrated,
Very useful for reactions with multiple fluidic agents.

Further, the stirring rotor of the present invention can be rotated as desired without providing a rotating shaft on the rotor itself, and can be easily handled and the stirring efficiency can be improved. Moreover, since the reaction vessel is hardly damaged, it can be suitably used for the semi-automatic synthesis apparatus of the present invention.

[Brief description of the drawings]

FIG. 1 is a schematic diagram showing an example of a semi-automatic synthesis apparatus of the present invention.

FIGS. 2A and 2B are diagrams showing addition of a drug tank to the drug supply device, and are schematic diagrams of (a) before adding a drug tank and (b) after adding a drug tank.

FIG. 3 is a partial sectional side view of a peripheral portion of a reaction vessel of the semi-automatic synthesis apparatus of the present invention.

FIG. 4 is an exploded perspective view showing an example of a housing of the semi-automatic synthesis device of the present invention.

FIG. 5 is a bottom view showing an example of a lid member of a reaction container.

FIG. 6 is a cross-sectional side view showing an example of a lid member of a reaction container.

FIG. 7 is a bottom view showing another example of the lid material of the reaction container.

FIG. 8 is a cross-sectional side view showing another example of the lid member of the reaction vessel.

FIG. 9 is a partial cross-sectional side view showing an example of a motor-type rotating magnetic field device.

FIG. 10 is a partially enlarged cross-sectional view illustrating an example of a ball bearing of a motor-type rotating magnetic field device.

FIG. 11 is a plan view showing an example of an electromagnet type rotating magnetic field device.

FIG. 12 is a plan view showing an example of a coil arrangement of the electromagnet type rotating magnetic field device.

FIG. 13 is a sectional view taken along line FF of FIG. 3;

FIG. 14 is a system block diagram illustrating an example of a temperature control unit.

FIG. 15 is a system block diagram illustrating an example of a pressure adjusting unit.

FIG. 16 is a view showing a rotor according to the first embodiment, and FIG.
It is a top view, (b) side view, (c) bottom view.

FIG. 17 is an enlarged sectional view showing three examples of a rotating member using wheels.

FIG. 18 is a view showing an example of a rotating member using a ball, in which (a) is a perspective view, (b) is a front view, (c) is a side view, and (d) is a bottom view.

FIG. 19 is a perspective view showing a rotor according to a second embodiment.

FIG. 20 is a diagram showing a rotor according to a second embodiment, and (a)
It is a top view, (b) side view, (c) bottom view.

FIG. 21 is a partial side view showing an example of a box casing of a rotor.

FIG. 22 is a sectional view showing an example of a rotor coated with a chemical resistant resin.

FIG. 23 is a perspective view showing a rotor according to a third embodiment.

FIG. 24 is an exploded perspective view showing a rotor according to a third embodiment.

FIG. 25 is a view showing a rotor according to a third embodiment, and (a)
It is a top view, (b) side view, (c) bottom view.

FIG. 26 is a diagram showing a stirring rotor according to a fourth embodiment, in which (a) is a plan view, (b) is a side view, (c) is a bottom view, and (d) is a CC cross-sectional view.

FIG. 27 is a sectional view showing a stirring rotor according to a fourth embodiment, which is installed in a round bottom reaction vessel.

FIG. 28 is a perspective view showing a rotor according to a fifth embodiment.

FIG. 29 is a view showing a rotor according to a sixth embodiment;
It is a top view, (b) side view, (c) bottom view.

FIG. 30 is a partial sectional side view showing two examples of a motor-type rotating magnetic field device provided with a rotating torque meter.

FIG. 31 is a schematic diagram showing the relationship between a drug supply device, a reaction device, and a control device.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 ... Drug supply apparatus 101 ... 1st line 102 ... 2nd line 103 ... 3rd line 104 ... 4th line 11 ... Solvent tank 12 ... Drug Tank 14 ・ ・ ・ Catalyst tank 15 ・ ・ ・ Three-way valve 151 ・ ・ ・ Solvent inflow valve 152 ・ ・ ・ Chemical inflow valve 153 ・ ・ ・ Outflow valve 16 ・ ・ ・ Pump 17 ・ ・ ・ Two-way valve 18 ・ ・ ・ Reverse Stop valve 2 ... Housing 21, 21a, 21b ... Housing 22 ... Rubber feet 23 ... Lifter 24 ... Rail 25 ... Wheel 26 ... Vent 3 ... Reaction Container 3a ・ ・ ・ Flange part 31 ・ ・ ・ Packing 32 ・ ・ ・ Lid 32a ・ ・ ・ Flange part 32b ・ ・ ・ External connection port 33c ・ ・ ・ Lid side part 33 ・ ・ ・ External connection parts 33a ・ ・ ・Backflow condenser 33b ・ ・ ・ Temperature meter 34 ・ ・ ・ Power clip 35 ・ ・ ・ Shaft 36 ・ ・ ・ Clamp 37 ・ ・ ・ Seal 4 ・ ・ Rotating magnetic field device 40 ・ ・ ・ Motor type rotating magnetic field device 400 ..Torque sensors 401, 401a, 401b, 401c ... Supports 403, 404 ... Bearing 405 ... Rotating shaft 406 ... Pulley 406 '... Rotating disk 407 ... Permanent magnet 408・ Belt 409 ・ ・ ・ Motor 409a ・ ・ ・ Pulley 409b ・ ・ ・ Screw 409c ・ ・ ・ Gear box 41 ・ ・ ・ Electromagnetic rotating magnetic field device 411 ・ ・ ・ Coil 412 ・ ・ ・ Support plate 42 ・ ・ ・ Rotation speed setting Unit 43 ・ ・ ・ Rotation speed detection unit 44 ・ ・ ・ Rotation speed control unit 5 ・ ・ ・ Temperature control unit 51 ・ ・ ・ Electric heater 52 ・ ・ ・ Cooling device 53 ・ ・ ・ Heat conductor 53a・ ・ ・ Hole 54 ・ ・ ・ Heat radiator 55 ・ ・ ・ Fan 56 ・ ・ ・ On / Off switch 57 ・ ・ ・ Selection switch 58 ・ ・ ・ Temperature setting means 59 ・ ・ ・ Temperature controller 6 ・ ・ ・ Pressure adjustment Part 6a ・ ・ ・ Atmospheric gas supply line 6b ・ ・ ・ Vacuum line 61 ・ ・ ・ Pressure gauge 62, 63, 68 ・ ・ ・ Two-way valve 64 ・ ・ ・ Pressure regulating valve 65 ・ ・ ・ D Idle valve 66 ・ ・ ・ Flow meter 67 ・ ・ ・ Check valve 69 ・ ・ ・ Speedometer 7 ・ ・ ・ Rotator for stirring 71 ・ ・ ・ Support 72 ・ ・ ・ Rotating member 721 ・ ・ ・ Wheel 722 ・ ・ ・Wheel axle 723, 723a, 723b ... bearing 724 ... tire 725 ... screw 726 ... ball 727 ... leg 73 ... permanent magnet 74 ... stirring member 75 ... rotation speed Measurement magnet 76 ・ ・ ・ Wheel 77 ・ ・ ・ Screw 78 ・ ・ ・ Box type casing 79 ・ ・ ・ Chemical resistant resin

Claims (26)

[Claims] 1. A semi-automatic synthesis apparatus for supplying a plurality of fluid medicines to a reaction vessel, wherein at least the reaction vessel, a solvent tank, a plurality of medicine tanks storing each medicine, and the reaction vessel and the solvent tank are connected. The first line to do
A second line that independently connects the plurality of drug tanks to the first line, and a valve provided at or near a connection between the first line and each of the second lines, Means for controlling the valve so that any one of the second lines communicates with the first line. 2. The semi-automatic synthesis apparatus according to claim 1, wherein a plurality of catalyst tanks, a third line connecting the reaction vessel and the solvent tank independently of the first line, and A fourth line that independently connects the catalyst tanks to the third line, a valve provided at or near each connection between the third line and each of the fourth lines, Means for controlling the valve so that any one of the fourth lines communicates with the third line. 3. The semi-automatic synthesizer according to claim 1, wherein the valve is a three-way valve, and a connection between the first line and the second line and / or a third line and a fourth line. A semi-automatic synthesizing device, which is provided at a connection part of a line. 4. The semi-automatic synthesizing apparatus according to claim 1, wherein a rotating magnetic field device provided at a lower portion of the reaction vessel, and a rotating magnetic field device placed in the reaction vessel and operated by the rotating magnetic field device. A semi-automatic synthesizing apparatus comprising: a rotating rotor. 5. The semi-automatic synthesis apparatus according to claim 4, wherein the rotor is at least a support and three or more rotating members attached to the support so as to rotate in contact with the bottom surface of the reaction vessel. And a semi-automatic synthesizing apparatus. 6. The semi-automatic synthesizing apparatus according to claim 5, wherein a pair of permanent magnets whose magnetic poles face in opposite directions are provided on the support. 7. The semi-automatic synthesizing apparatus according to claim 6, wherein said permanent magnet is sealed by a box-shaped casing. 8. The semi-automatic synthesizing apparatus according to claim 6, wherein the permanent magnet is coated with a chemical resistant resin. 9. The semi-automatic synthesizing apparatus according to claim 5, wherein the support has an opening. 10. The semi-automatic synthesis apparatus according to claim 5, wherein said rotor has a stirring member. 11. The semi-automatic synthesizing apparatus according to claim 4, wherein said rotating magnetic field device has a speed changing means for changing a rotation speed of a rotating magnetic field. 12. The semi-automatic synthesis apparatus according to claim 1, further comprising a temperature control unit having a unit for heating and / or cooling the reaction vessel. 13. The semi-automatic synthesis apparatus according to claim 1, wherein said means for measuring the pressure inside the reaction vessel, means for reducing the pressure inside the reaction vessel, and means for pressurizing the inside of the reaction vessel. A semi-automatic synthesizing apparatus, comprising: 14. The semi-automatic synthesizing apparatus according to claim 1, further comprising means for supporting said reaction vessel movably in the vertical and horizontal directions. 15. The semi-automatic synthesis apparatus according to claim 1, wherein the reaction container has a lid having a plurality of external connection ports, and a back surface of the lid is provided with the external material. A semi-automatic synthesis apparatus characterized by being covered with a removable chemical-resistant seal except for a connection port. 16. The semi-automatic synthesizing apparatus according to claim 4, further comprising means for detecting a rotation speed of said rotor. 17. The semi-automatic synthesizing apparatus according to claim 4, wherein said rotating magnetic field device further comprises means for measuring a rotational torque and outputting the measured torque to a computer. 18. The semi-automatic synthesis apparatus according to claim 17, further comprising means for measuring the viscosity of the reaction solution.
Means for measuring the viscosity of the reaction solution, using a plurality of standard solutions having different viscosities, means for determining the relationship between rotational torque and viscosity, and using the obtained relationship between the rotational torque and viscosity, the reaction solution Means for determining the viscosity of the reaction solution from the rotational torque of the semi-automatic synthesis apparatus. 19. The semi-automatic synthesizing apparatus according to claim 12, further comprising a means for measuring a variation in the calorific value of the reaction, wherein the means for measuring the variation in the calorific value of the reaction has substantially the same specific heat as that of the reaction solution. A means for determining the heating rate and / or cooling rate of the reaction apparatus using a reference solution having the same weight as the reaction solution, and using the obtained heating rate and / or cooling rate to obtain a calorific value change from a temperature change over time of the reaction. A semi-automatic synthesis apparatus comprising: means for calculating a speed; and means for calculating a calorific value variation of a reaction from the calorific value variation speed. 20. The semi-automatic synthesis apparatus according to claim 1, wherein the supply amounts of the drug and the solvent are:
A semi-automatic synthesis apparatus, wherein a rotation speed of a rotating magnetic field and a temperature and a pressure in the reaction vessel are controlled by a control device through an instruction from a computer. 21. A stirring rotor rotated by the action of a rotating magnetic field, comprising at least a support and three or more rotating members attached to the support so as to rotate in contact with the bottom surface of the reaction vessel. A stirring rotor, characterized in that: 22. The stirring rotor according to claim 21, wherein a pair of at least one permanent magnet whose magnetic poles face in opposite directions is provided on the support. 23. The stirring rotor according to claim 22, wherein the permanent magnet is sealed by a box-shaped casing. 24. The stirring rotor according to claim 22, wherein the permanent magnet is coated with a chemical resistant resin. 25. The stirring rotor according to any one of claims 21 to 24, wherein the support has an opening. 26. The stirring rotor according to claim 21, wherein the rotor has a stirring member.