Synthetic reaction device

Abstract

The utility model relates to a synthetic reaction device suitable for carbamazepine bromide. The synthetic reaction device comprises a reaction kettle, a solid feeder, a condenser, a solvent receiving tank, a buffer tank and a pipeline system, the reaction kettle, the solid feeder, the solvent receiving tank and the buffer tank are provided with discharging pipes and control valves, the pipeline system is properly provided with a control valve, two working modes of backflow gas absorption and evaporation solvent gas absorption are switched through a valve switch, and the solid feeder can slowly add solids into a reaction system. According to the utility model, the feeding speed of solid materials can be controlled, and two working modes of reflux gas absorption and evaporation solvent gas absorption can be quickly and conveniently switched.

Description

Technical Field

[0001] The utility model belongs to the technical field of drug synthesis equipment, and specifically relates to a synthesis reaction device, which is especially suitable for the synthesis reaction of carbamazepine bromide. Background Art

[0002] Carbamazepine and oxcarbazepine are important anti-epileptic drugs, listed in the national basic medical insurance drug catalog, and are mainly used in the treatment of epilepsy, diabetes insipidus and peripheral neuropathy. The chemical name of carbamazepine bromide is iminostilbenecarbonyl chloride, which is an important intermediate in the synthesis of carbamazepine and oxcarbazepine.

[0003] In industry, the synthesis of carbamazepine bromide is to put iminodibenzyl, chlorobenzene and triphosgene into a reactor, heat and reflux to produce chloroformylation reaction to obtain chlorobenzene solution of iminodibenzyl chloride, and release a large amount of hydrogen chloride and phosgene at the same time; then put dibromohydantoin and initiator into the chlorobenzene solution of iminodibenzyl chloride and heat to carry out bromination reaction, then evaporate chlorobenzene at high temperature and dehydrobrominate to obtain carbamazepine bromide, and release a large amount of hydrogen bromide and a small amount of bromine vapor during the reaction. After the reaction is completed, methanol is added, stirred and filtered to obtain carbamazepine bromide.

[0004] At present, there are two problems in the synthesis reaction of carbamazepine bromide:

[0005] 1) The bromination reaction of iminodibenzyl chloride and dibromohydantoin is a free radical reaction. After initiation, the reaction is very violent and the temperature rises rapidly (the temperature rises to more than 50°C within 3 minutes, and the reaction temperature can rise to more than 130°C). It is very easy to be dangerous and the reaction is difficult to control; 2) The chloroformylation reaction and bromodehydrobromination are carried out in the same kettle. The chloroformylation is heated and refluxed to produce a large amount of hydrogen chloride and phosgene, which require gas absorption. The bromodehydrobromination reaction produces a large amount of hydrogen bromide and a small amount of bromine, which also requires gas absorption. This requires the reaction device to be able to quickly and conveniently switch between the two working modes of reflux gas absorption and solvent evaporation gas absorption. The reaction temperature is high and the material is highly corrosive, which is difficult to meet with the existing general reaction devices. Based on this, this application was developed. Utility Model Content

[0006] The utility model aims to overcome the defects of the prior art and provide a synthesis reaction device, which is particularly suitable for the synthesis reaction of carbamazepine bromide and has a good effect.

[0007] In order to achieve the above objectives, the utility model provides the following technical solutions:

[0008] A synthetic reaction device for carbamazepine bromide, comprising a reactor, a condenser, a solvent receiving tank and a buffer tank, wherein the reactor is provided with a solid feeder and a reflux diverter, wherein the reflux diverter is in the shape of a cylinder with upper and lower openings, and a reflux port is provided on the side wall of the reflux diverter, and the reflux port extends inwardly to form a reflux channel;

[0009] The reflux port of the reflux splitter pipe is connected to the lower connection port of the condenser through a pipeline, the upper connection port of the condenser is connected to the inlet of the solvent receiving tank through a pipeline, the outlet of the solvent receiving tank is connected to the inlet of the buffer tank through a pipeline, and the outlet of the buffer tank is connected to the tail gas absorption tower through a pipeline (the tail gas absorption tower contains sodium hydroxide solution to decompose phosgene and absorb hydrogen chloride and hydrogen bromide);

[0010] The lower connection port of the condenser is connected to the inlet of the solvent receiving tank through a pipeline, and the upper connection port of the condenser is communicated with the upper opening of the reflux diversion pipe through a pipeline.

[0011] Specifically, the reactor cover is connected with a solid feeder. The solid feeder includes a main body that is generally large at the top and small at the bottom, a screw shaft is arranged in the main body, a spiral screw is arranged on the screw shaft, a motor is connected to the top of the screw shaft, and the motor is connected to a transmission for controlling the speed; a feed port is arranged at the upper part of the main body, a connecting port is arranged at the bottom of the main body and the connecting port extends into the reactor, and a control valve is arranged on the connecting port outside the reactor. Solid materials are put into the solid feeder through the feed port, and the motor drives the screw to rotate through the transmission and the screw shaft to provide power, and the solid materials are slowly added to the reactor through the control valve. The transmission can adjust the screw speed, and then adjust the solid feeding speed, so as to avoid adding the solid reaction raw materials to the reactor at one time, causing the reaction to be too intense. After the feeding is completed, the control valve is closed to prevent the solvent vapor from entering the solid feeder when the solvent is evaporated at high temperature.

[0012] Furthermore, the reactor is fixed on the operating table through a support, and a stirring device and a temperature measuring device are arranged in the reactor, and a motor is connected to the top of the stirring device. A vacuum connection port and a feeding interface are arranged on the reactor cover of the reactor. The vacuum connection port is generally used for pumping liquid materials into the reactor.

[0013] Specifically, the reactor is a jacketed reactor, and a side wall of the reactor is provided with a connection port for the inlet and outlet of a heating or cooling medium.

[0014] Furthermore, a discharge port is provided at the bottom of the reactor, and a first discharge control valve is installed at the discharge port.

[0015] Furthermore, a discharge pipe is provided at the bottom of the solvent receiving tank, and a second discharge control valve is provided on the discharge pipe.

[0016] Furthermore, a sewage pipe is provided at the bottom of the buffer tank, and a third discharge control valve is provided on the sewage pipe.

[0017] During actual operation, the reaction kettle, solvent receiving tank and buffer tank are installed on the operating table through supports so that the discharge port, discharge pipe and sewage pipe are at a certain height from the ground to facilitate discharge.

[0018] In the device of the utility model, the connecting pipe, the control valve, the one-way valve, etc. constitute a pipe system, and the appropriate switch of the control valve can realize the switching between the reflux gas absorption and the evaporation solvent gas absorption working modes. Further preferably, a control valve is provided on the pipe connecting the reflux port of the reflux shunt pipe with the lower connecting port of the condenser, a control valve is provided on the pipe connecting the upper connecting port of the condenser with the inlet of the solvent receiving tank, and a one-way valve is provided on the pipe connecting the outlet of the buffer tank to the tail gas absorption tower. A control valve is provided on the pipe connecting the lower connecting port of the condenser with the inlet of the solvent receiving tank, and a control valve is provided on the pipe connecting the upper connecting port of the condenser with the upper opening of the reflux shunt pipe.

[0019] The device described in the utility model includes a reactor, a solid feeder, a condenser, a solvent receiving tank, a buffer tank and a pipeline system. The reactor, the solid feeder, the solvent receiving tank and the buffer tank are equipped with a discharge pipe and a control valve. The control valve is appropriately installed in the pipeline system. The two working modes of reflux gas absorption and evaporation solvent gas absorption are switched by the valve switch. The solid feeder can slowly add solids to the reaction system. The surfaces of all equipment in contact with the materials of this device are required to be acid-resistant and corrosion-resistant, and the equipment before the condenser must be high temperature resistant. The reactor can be lined with quartz glass, the reflux diversion pipe and the pipeline in front of the solvent receiving tank are made of glass, the sealing gasket is made of high temperature and corrosion resistant materials such as polytetrafluoroethylene, and the pipeline after the solvent receiving tank can be made of PPR pipe, PVC pipe, etc.

[0020] Compared with the prior art, the utility model achieves the following beneficial effects:

[0021] 1) The reactor is equipped with a solid feeder, which can slowly add solids to the reaction system. The feeding rate can be controlled by setting a transmission. The solid material is put into the solid feeder through the feed port. The motor drives the screw to rotate through the transmission and the screw shaft to provide power, and the solid material is slowly added to the reactor through the control valve. The transmission can adjust the screw speed, and then adjust the solid feeding speed, to avoid adding solid reaction materials to the reactor at one time, causing the reaction to be too violent.

[0022] 2) The pipeline system consists of connecting pipelines, control valves and one-way valves. Appropriate switching of the control valves can realize the switching between the reflux gas absorption and evaporation solvent gas absorption working modes. The one-way valve can prevent the gas absorption liquid from flowing back. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic diagram of the overall structure of the synthesis reaction device of the utility model;

[0024] Figure 2 The schematic diagram of the structure of the reflux shunt pipe is shown in the figure, with a cross-sectional view on the left and an axonometric view on the right;

[0025] Figure 3 This is a schematic diagram of the structure of the solid feeder. DETAILED DESCRIPTION

[0026] The following will be combined with the drawings in the embodiments of the utility model to clearly and completely describe the technical solutions in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, not all of them. Based on the embodiments in the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model. Example

[0027] like Figures 1 to 3 As shown, the utility model provides a synthetic reaction device suitable for carbamazepine bromide, which includes a reactor 1, a condenser 16, a solvent receiving tank 3, a buffer tank 4 and a pipeline system. The reactor 1 is fixed on the operating table through a support 5. A solid feeder 12 and a reflux shunt pipe 23 are arranged on the reactor cover 2 of the reactor 1. The reflux shunt pipe 23 is generally in the shape of a cylinder with upper and lower openings. A reflux port 23-4 is opened on the side wall of the reflux shunt pipe 23, and the reflux port 23-4 extends inward to form a reflux channel 23-3;

[0028] The reflux port 23-4 of the reflux splitter 23 is connected to the lower connection port of the condenser 16 through a pipeline, the upper connection port of the condenser 16 is connected to the inlet of the solvent receiving tank 3 through a pipeline, the outlet of the solvent receiving tank 3 is connected to the inlet of the buffer tank 4 through a pipeline, and the outlet of the buffer tank 4 is connected to the tail gas absorption tower through a pipeline (the tail gas absorption tower contains sodium hydroxide solution to decompose phosgene and absorb hydrogen chloride and hydrogen bromide);

[0029] The lower connection port of the condenser 16 is connected to the inlet of the solvent receiving tank 3 through a pipeline, and the upper connection port of the condenser 16 is connected to the upper opening 23-2 of the reflux diversion pipe 23 through a pipeline. The condenser 16 is provided with a cooling water inlet 18 and a cooling water outlet 17.

[0030] The reactor cover 2 of the reactor 1 is connected with a solid feeder 12 . Figure 3It is a structural schematic diagram of a solid feeder. The solid feeder 12 includes a body 12-1 which is generally large at the top and small at the bottom, a screw 12-2, a screw shaft 12-3, a feed port 12-4, a second motor 12-5, a transmission 12-6, a connection port 12-7, and a control valve 12-8. A screw shaft 12-3 is provided in the body 12-1, a spiral screw 12-2 is provided on the screw shaft 12-3, the top of the screw shaft 12-3 is connected to the second motor 12-5, and the second motor 12-5 is connected to a transmission 12-6 for controlling the speed; a feed port 12-4 is provided on the upper part of the body 12-1, a connection port 12-7 is provided at the bottom of the body 12-1 and the connection port extends into the reactor 1, and a control valve 12-8 is provided on the connection port outside the reactor 1. When adding solid materials to the reactor 1, the control valve 12-8 is opened. Solid materials are put into the solid feeder 12 through the feed port 12-4, and the second motor 12-5 drives the screw 12-2 to rotate through the transmission 12-6 and the screw shaft 12-3 to provide power, and the solid materials are slowly added to the reactor 1 through the control valve 12-8. The transmission 12-6 can adjust the speed of the screw 12-2, and then adjust the solid feeding speed to avoid adding the solid reaction raw materials to the reactor 1 at one time to cause too intense reaction. After the feeding is completed, the control valve 12-8 is closed to prevent the solvent vapor from entering the solid feeder 12 when the solvent is evaporated at high temperature.

[0031] The reactor 1 is fixed on the operating table through the support 5. The reactor 1 is provided with a stirring device 8 and a temperature measuring device 9. The top of the stirring device 8 is connected to a first motor 15. The motor 15 provides power for the stirring device 8. The stirring device 8 and the temperature measuring device 9 can adopt conventional structures in the field, such as ordinary commercially available stirrers, thermometers, etc., because their structures are not the innovation of the utility model, they are not repeated here. The reactor cover 2 of the reactor 1 is provided with a vacuum connection port 13 and a feeding interface 14. The reactor 1 is a jacketed reactor, and the side wall of the reactor 1 is provided with a first connection port 6 and a second connection port 7 for heating or cooling medium to enter and exit. The bottom of the reactor 1 is provided with a discharge port 10, and the discharge port 10 is installed with a first discharge control valve 11. The bottom of the solvent receiving tank 3 is provided with a discharge pipe 19, and the discharge pipe 19 is provided with a second discharge control valve 20. The bottom of the buffer tank 4 is provided with a sewage pipe 21, and the sewage pipe 21 is provided with a third discharge control valve 22. In actual operation, the reaction kettle 1, the solvent receiving tank 3, and the buffer tank 4 are installed on the operating table so that the discharge port 10, the discharge pipe 19, and the sewage pipe 21 are at a certain height from the ground to facilitate discharge.

[0032] In the device of the utility model, a first control valve 26 is provided on the pipeline connecting the reflux port 23-4 of the reflux shunt pipe 23 and the lower connection port of the condenser 16, a second control valve 27 is provided on the pipeline connecting the lower connection port of the condenser 16 and the inlet of the solvent receiving tank 3, and a one-way valve 28 is provided on the pipeline connecting the outlet of the buffer tank 4 to the tail gas absorption tower. A third control valve 25 is provided on the pipeline connecting the upper connection port of the condenser 16 and the inlet of the solvent receiving tank 3, and a fourth control valve 24 is provided on the pipeline connecting the upper connection port of the condenser 16 and the upper opening 23-2 of the reflux shunt pipe 23.

[0033] In the device of the utility model, the pipeline system includes a first connecting pipeline a, a second connecting pipeline b, a third connecting pipeline c, a fourth connecting pipeline d, a fifth connecting pipeline e, a sixth connecting pipeline f, a seventh connecting pipeline g, an eighth connecting pipeline h, a ninth connecting pipeline i, a tenth connecting pipeline j, an eleventh connecting pipeline k and a first control valve 26, a second control valve 27, a third control valve 25, a fourth control valve 24 and a one-way valve 28, etc. Appropriate switching of the control valves can realize switching between the two working modes of reflux gas absorption and evaporation solvent gas absorption, and the one-way valve 28 can prevent the absorption liquid from flowing back.

[0034] In the present invention, all surfaces of equipment in contact with materials are required to be acid-resistant and corrosion-resistant, and the equipment in front of the solvent receiving tank 3 is required to be high temperature resistant. The reactor 1 can be lined with quartz glass, the reflux diversion pipe 23 and the first connecting pipe a, the second connecting pipe b, the third connecting pipe c, the fourth connecting pipe d, the fifth connecting pipe e, the sixth connecting pipe f, the seventh connecting pipe g, the eighth connecting pipe h, the ninth connecting pipe i and the first, second, third and fourth control valves are made of glass, the sealing gasket is made of high temperature and corrosion resistant materials such as polytetrafluoroethylene, and the tenth connecting pipe j and the eleventh connecting pipe k can be made of corrosion resistant materials such as PPR pipes and PVC pipes.

[0035] The control valve not mentioned in the utility model is in a closed state during use. In addition, since the reaction system pipeline is composed of glass and cannot withstand excessive pressure, the entire reaction system is balanced with the atmosphere through the gas absorption tower and the pipeline system.

[0036] In the device of the utility model, when the chloroformylation reaction is carried out in the reactor 1, chlorobenzene, iminodibenzyl and triphosgene are put into the reactor 1 through the feeding interface 14, and the feeding port 14 is covered. The first control valve 26 and the third control valve 25 are opened, the stirring device 8 is turned on, and the heating is turned on (that is, the heating medium steam is input into the reactor jacket through the first connecting port 6 and the second connecting port 7 on the side wall of the reactor 1). After the reaction starts, the reaction liquid refluxes and generates a large amount of hydrogen chloride gas, phosgene and chlorobenzene vapor, which enter the condenser 16 with cooling water through the reflux channel 23-3, the reflux port 23-4, the sixth connecting pipe f, and the fifth connecting pipe e of the reflux diverter 23 (the cooling water enters the condenser 16 through the cooling water inlet 18 and the cooling water outlet 17). The cooled chlorobenzene liquid returns to the reactor 1 through the fifth connecting pipe e, the sixth connecting pipe f, the reflux port 23-4 and the reflux channel 23-3 of the reflux diverter 23, and the non-condensable hydrogen chloride and phosgene enter the tail gas absorption tower for absorption through the fourth connecting pipe d, the eighth connecting pipe h, the ninth connecting pipe i, the tenth connecting pipe j, the eleventh connecting pipe k, and the one-way valve 28. This line is mainly used for reflux gas absorption.

[0037] In the utility model device, when the bromination and dehydrobromination reaction is carried out in the reactor 1, the initiator and a small amount of dibromohydantoin are put into the reactor 1 through the feeding interface 14, and the remaining dibromohydantoin is put into the solid feeder 12 through the feeding port 12-4. The feeding interface 14 and the feeding port 12-4 are covered, and stirring is started. The fourth control valve 24 and the second control valve 27 are opened, and the reaction liquid is heated by water vapor (the heating medium water vapor can be input into the reactor jacket through the first connecting port 6 and the second connecting port 7 on the side wall of the reactor 1), and the heating steam is turned off after the reaction is initiated. The control valve 12-8 and the second motor 12-5 are opened, and the dibromohydantoin in the solid feeder 2 is slowly added to the reactor 1 through the control valve 12-8 under the action of the screw 12-2. The speed of the screw 12-2 can be controlled by the transmission 12-6, and then the feeding speed is controlled to make the reaction proceed smoothly. After the feeding is completed, the control valve 12-8 and the second motor 12-5 are closed, and the heating is turned on to evaporate the chlorobenzene and dehydrobromine. The generated chlorobenzene vapor and hydrogen bromide enter the condenser 16 through the main channel 23-1, the upper opening 23-2, the first connecting pipe a, the second connecting pipe b, the third connecting pipe c, and the fourth connecting pipe d of the reflux diverter 23. The condensed chlorobenzene liquid and hydrogen bromide enter the solvent receiving tank 3 through the pipeline fifth connecting pipe e, the seventh connecting pipe g, and the ninth connecting pipe i. Hydrogen bromide enters the tail gas absorption tower through the tenth connecting pipe j, the eleventh connecting pipe k, and the one-way valve 28. The function of the buffer tank 4 is to prevent a small amount of sodium hydroxide solution from flowing back into the reaction system. After the chlorobenzene is evaporated, the heating is turned off to cool down, methanol is added, and stirred to obtain a slurry of carbamazepine bromide and methanol mixed, which is discharged through the discharge port 10 and the first discharge control valve 11, and the carbamazepine bromide is filtered. The recovered chlorobenzene is discharged through the discharge pipe 19 and the second discharge control valve 20. This line is mainly used for evaporative solvent gas absorption.

[0038] In the description of the present invention, the indicated orientation or position relationship is based on the orientation or position relationship shown in the accompanying drawings, which is only for the convenience of describing the present invention and simplifying the description, and does not indicate or imply that the device or element referred to must have a specific orientation. Therefore, it cannot be understood as a limitation on the present invention.

[0039] Although the embodiments of the present invention have been shown and described, and although the present invention is designed for the production of carbamazepine bromide, it is understandable to those skilled in the art that various changes, modifications, substitutions and variations may be made to these embodiments without departing from the principles and spirit of the present invention, all of which are within the scope of protection of the present invention.

Claims

1. A synthesis reaction device, characterized in that: It includes a reactor, a condenser, a solvent receiving tank and a buffer tank. The reactor is provided with a solid feeder and a reflux diverter. The reflux diverter is in the shape of a cylinder with upper and lower openings. A reflux port is provided on the side wall of the reflux diverter and the reflux port extends inward to form a reflux channel. The reflux port of the reflux splitter pipe is connected to the lower connection port of the condenser through a pipeline, the upper connection port of the condenser is connected to the inlet of the solvent receiving tank through a pipeline, the outlet of the solvent receiving tank is connected to the inlet of the buffer tank through a pipeline, and the outlet of the buffer tank is connected to the tail gas absorption tower through a pipeline; The lower connection port of the condenser is connected to the inlet of the solvent receiving tank through a pipeline, and the upper connection port of the condenser is communicated with the upper opening of the reflux diversion pipe through a pipeline.

2. The synthesis reaction device according to claim 1, characterized in that: The solid feeder comprises a main body which is generally larger at the top and smaller at the bottom. A screw shaft is arranged in the main body, a spiral screw is arranged on the screw shaft, a motor is connected to the top of the screw shaft; the motor is connected to a transmission for controlling the speed; a feed port is arranged at the top of the main body, a connecting port is arranged at the bottom of the main body and the connecting port extends into the reactor, and a control valve is arranged on the connecting port outside the reactor.

3. The synthesis reaction device according to claim 1, characterized in that: The reactor is provided with a stirring device and a temperature measuring device, and the top of the stirring device is connected with a motor.

4. The synthesis reaction device according to claim 3, characterized in that: The reactor is provided with a vacuum connection port and a feeding interface.

5. The synthesis reaction device according to claim 3, characterized in that: The reactor is a jacketed reactor, and a side wall of the reactor is provided with a connection port for the inlet and outlet of a heating or cooling medium.

6. The synthesis reaction device according to claim 3, characterized in that: A discharge port is provided at the bottom of the reactor, and a first discharge control valve is installed at the discharge port.

7. The synthesis reaction device according to claim 1, characterized in that: A discharge pipe is arranged at the bottom of the solvent receiving tank, and a second discharge control valve is arranged on the discharge pipe.

8. The synthesis reaction device according to claim 1, characterized in that: A sewage discharge pipe is provided at the bottom of the buffer tank, and a third discharge control valve is provided on the sewage discharge pipe.

9. The synthesis reaction device according to claim 1, characterized in that: A control valve is provided on the pipeline connecting the reflux port of the reflux diversion pipe and the lower connecting port of the condenser, a control valve is provided on the pipeline connecting the upper connecting port of the condenser and the inlet of the solvent receiving tank, and a one-way valve is provided on the pipeline connecting the outlet of the buffer tank to the tail gas absorption tower.

10. The synthesis reaction device according to claim 1, characterized in that: A control valve is provided on the pipeline connecting the lower connection port of the condenser with the inlet of the solvent receiving tank, and a control valve is provided on the pipeline communicating with the upper connection port of the condenser and the upper opening of the reflux diversion pipe.

Images