Esterification reaction device and process for synthesis of aromatic medical intermediates

Abstract

The invention relates to the technical field of esterification reaction containers, and discloses an esterification reaction device for synthesis of aromatic medical intermediates and a process thereof.The esterification reaction device for synthesis of the aromatic medical intermediates comprises a tank body and a driving motor arranged at the top of the tank body, and a rotating shaft is connected to a main shaft of the driving motor; the rotating shaft is sleeved with an upper rotating sleeve and a lower rotating sleeve, the upper rotating sleeve is connected with an anchor agitator, the lower rotating sleeve is connected with a turbine agitator, and a clutch unit is arranged between the upper rotating sleeve and the lower rotating sleeve; under the condition that the reaction liquid is low in viscosity, the clutch unit enables the lower rotating sleeve to be in transmission with the rotating shaft, and under the condition that the reaction liquid is high in viscosity, the clutch unit enables the upper rotating sleeve to be in transmission with the rotating shaft. According to the esterification reaction device for synthesis of the aromatic medical intermediates, the reaction efficiency and the product quality can be remarkably improved through the strategy that the clutch unit is arranged, turbine stirring is conducted firstly, and anchor type stirring is conducted after the viscosity of reactants reaches a threshold value.

Description

Technical Field

[0001] The invention relates to the technical field of esterification reactors, and in particular to an esterification reaction device and a process thereof for synthesizing aromatic pharmaceutical intermediates. Background Art

[0002] The esterification reactor is a special equipment used to synthesize ester compounds from carboxylic acids and alcohols under the action of catalysts. Its core function is to drive the reaction efficiently by precisely controlling temperature, pressure and mixing conditions. The typical structure includes a corrosion-resistant reactor with a jacket (glass-lined / 316L stainless steel), a switchable stirring system (turbine / anchor type to adapt to different viscosities), a water separation device (azeotropic dehydration) and automated instruments (online pH / viscosity monitoring).

[0003] The patent publication number CN103170298A discloses an esterification reactor, including a reactor cylinder, a heating device and a top-mounted agitator arranged in the reactor cylinder, the top-mounted agitator is provided with a main shaft, the upper end of the main shaft is connected to the agitator driving device, the reactor cylinder is formed by an upper head, an intermediate cylinder and a lower head connected in sequence, the upper head, the intermediate cylinder and the lower head are connected to each other by a flange connection provided with a mouth structure, each mouth structure is processed by a large vertical lathe, the heating device adopts a plurality of vertical heating cylinders, the heating cylinders are connected to an evaporator through corresponding inlet and outlet conduits, and the heating cylinders, conduits and evaporators constitute a non-powered circulating heat medium vacuum system.

[0004] The prior art has the following defects: Esterification reaction vessels using a single stirring method have significant process limitations, which are mainly reflected in the inability to adapt to the dynamic changes in material properties during the reaction. In the initial low-viscosity stage of the reaction, anchor stirring will result in low mixing efficiency and uneven catalyst dispersion due to limited rotation speed (usually <100rpm), extending the induction period by more than 30%; if turbine stirring is used throughout the process, when the viscosity rises to 1000cP, its high-speed rotation (>200rpm) will produce ineffective energy consumption (power increases by 3-5 times), and strong shear force may destroy the structure of intermediate products (such as the widening of the molecular weight distribution of polymerized esters). Single stirring is also prone to forming mass transfer dead zones. The material renewal rate in the central area of ​​anchor stirring is insufficient, and high-viscosity materials are easily accumulated near the wall of turbine stirring. Both will cause local overheating (temperature difference can reach 10-15°C), triggering side reactions (such as sulfonation or dehydration), and reducing product purity by 2-5%. In addition, the fixed stirring mode is difficult to meet the heat conduction requirements of different reaction stages: the jacket heat transfer coefficient is limited to below 80W / (m²·K) at low viscosity, and the boundary layer cannot be effectively eliminated at the high viscosity stage, which ultimately leads to a 20-40% extension of the reaction cycle and poor process reproducibility during scale-up production (batch RSD>5%). Summary of the invention

[0005] In view of the above problems in the prior art, an esterification reaction device and a process thereof for synthesizing aromatic pharmaceutical intermediates are proposed.

[0006] On the one hand, the present application provides an esterification reaction device for the synthesis of aromatic pharmaceutical intermediates, the purpose of which is to use turbine stirring in the early stage of the reaction to form radial flow and enhance mass transfer, and automatically convert to anchor stirring when the viscosity of the reactants rises to a threshold value. The design of fitting the kettle wall can effectively eliminate the retention layer of high-viscosity materials on the reactor wall, increase the heat transfer coefficient by more than 35%, and prevent aromatic ring sulfonation or product decomposition caused by local overheating.

[0007] The technical scheme of the present invention is: an esterification reaction device for the synthesis of aromatic pharmaceutical intermediates, comprising a tank body, a driving motor arranged on the top of the tank body, a rotating shaft connected to the main shaft of the driving motor, an upper rotating sleeve and a lower rotating sleeve sleeved on the rotating shaft, an anchor stirrer connected to the upper rotating sleeve, a turbine stirrer connected to the lower rotating sleeve, and a clutch unit arranged between the upper rotating sleeve and the lower rotating sleeve; When the reaction liquid has low viscosity, the clutch unit enables transmission between the lower rotating sleeve and the rotating shaft. When the reaction liquid has high viscosity, the clutch unit enables transmission between the upper rotating sleeve and the rotating shaft.

[0008] The above scheme adopts the strategy of setting up a clutch unit, first using turbine stirring, and then switching to anchor stirring after the viscosity of the reactant reaches a threshold, which can significantly improve the reaction efficiency and product quality. Turbine stirring is used in the initial low-viscosity stage of the reaction. Its high-intensity radial flow can quickly disperse the catalyst and promote the collision of acid and alcohol molecules, thereby increasing the reaction rate by 30-50%, while avoiding side reactions caused by excessive local concentration; when the viscosity rises to the threshold, it automatically switches to anchor stirring. Its design that fits the kettle wall can effectively eliminate the retention layer of high-viscosity materials on the reactor wall, increase the heat transfer coefficient by more than 35%, and prevent aromatic ring sulfonation or product decomposition caused by local overheating.

[0009] Furthermore, the anchor agitator comprises a stirring frame arranged on the upper rotating sleeve, a homogenizing plate arranged on the stirring frame, and a scraper arranged on the stirring frame.

[0010] By adopting the above scheme, by setting a homogenizing plate and a scraper, the design of fitting the kettle wall can effectively eliminate the retention layer of high-viscosity materials on the reactor wall, thereby improving the heat transfer coefficient. The homogenizing plate is used to improve mass transfer.

[0011] The cam is secured to the bottom of the gear and is secured to a position 40 meters high when the cam is in a position to move relative to the top of the gear. The cam is secured to the bottom of the gear and is secured to a position 50 meters high when the cam is in a position to move relative to the top of the gear.

[0012] By adopting the above scheme, through the specific setting of the clutch assembly, utilizing the principle that the rotational resistance of the outer rotating sleeve increases with the increase in viscosity of the reaction liquid, relative sliding occurs between the outer rotating sleeve and the rotating shaft, and further the spiral surfaces of spiral wedge block 1 and spiral wedge block 2 slide relative to each other, spiral wedge block 1 and spiral wedge block 2 move away from each other and squeeze the partition plate to move up, and the inner rotating sleeve on the partition plate squeezes the clutch plate group above, so that transmission is achieved between the upper rotating sleeve and the rotating shaft, and turbine stirring is converted into anchor stirring.

[0013] Furthermore, the clutch plate group includes multiple friction plates and multiple steel plates, the steel plates and the friction plates are arranged alternately, the friction plates located at the top are spline-connected to the inner wall of the upper rotating sleeve, the friction plates located at the bottom are spline-connected to the inner wall of the lower rotating sleeve, and the steel plates are spline-connected to the shaft wall of the rotating shaft.

[0014] By adopting the above scheme, a clutch plate is provided to link and interrupt the transmission between the rotating shaft and the upper rotating sleeve and the lower rotating sleeve respectively.

[0015] Furthermore, slots are arranged at equal intervals on the outer wall of the outer rotating sleeve, and inserting teeth are arranged in the slots.

[0016] By adopting the above solution, the insert teeth are provided to transmit the resistance generated by the viscosity of the reaction liquid when the outer wall of the outer rotating sleeve rotates.

[0017] Furthermore, a protrusion is arranged on the spiral surface of the spiral wedge piece 1, and a depression corresponding to the protrusion is arranged on the spiral surface of the spiral wedge piece 2.

[0018] By adopting the above solution, the critical torque required for relative sliding between the spiral surfaces of the spiral wedge block 1 and the spiral wedge block 2 is increased by providing the protrusions and the depressions.

[0019] Furthermore, the sides and bottom of the tank body are both provided with jackets.

[0020] By adopting the above scheme, the temperature of the tank body is controlled by providing a jacket.

[0021] Furthermore, a feed port is arranged on the top surface of the tank body, and a discharge port is arranged on the bottom surface of the tank body.

[0022] The above scheme is adopted to set a feed port and a discharge port for feeding and discharging materials and separating various liquid phases.

[0023] Furthermore, the present invention also provides an esterification reaction process for synthesizing aromatic pharmaceutical intermediates, comprising the following steps: Step 1: Raw material loading and initial mixing: p-hydroxybenzoic acid (particle size D90≤50μm) and propanol (n(acid):n(alcohol)=1:1.8) were accurately fed through a weight loss scale, ionic liquid catalyst was added, azeotroping agent cyclohexane was injected, turbine agitator (300rpm) was turned on to form radial flow, and the temperature was raised to 75°C (heating rate 2°C / min); Step 2: Viscosity-responsive stirring switch, viscosity threshold trigger (η≥800cP), anchor agitator and rotating shaft transmission, anchor stirring stage (η=800-10,000cP), speed adjusted to 100rpm, gap 2mm to prevent material from sticking to the wall, temperature raised to 115℃, pressure reduction (-0.06MPa), water separator drainage frequency increased to 20mL / min; Step 3: Termination of reaction and treatment of product, endpoint determination, HPLC monitoring of p-hydroxybenzoic acid residue ≤ 0.3%, rapid cooling to 50 ° C, capture ionic liquid through electrostatic adsorption column (filled with cationic resin), crude product dissolved in ethanol-water (7:3) mixed solvent, cooled to 25 ° C, centrifuged (3000g, 10min), wet product moisture <5%.

[0024] The above scheme adopts a dynamic switching mode and matches the stirring type with the rheological properties of the material, which not only solves the energy waste problem of turbine stirring at high viscosity, but also overcomes the defect of insufficient mixing of anchor stirring at low viscosity.

[0025] Beneficial effects of the present invention: 1. By setting up a clutch unit, first use turbine stirring, and then switch to anchor stirring after the viscosity of the reactants reaches the threshold, the reaction efficiency and product quality can be significantly improved. Turbine stirring is used in the initial low-viscosity stage of the reaction. Its high-intensity radial flow can quickly disperse the catalyst and promote the collision of acid and alcohol molecules, increasing the reaction rate by 30-50%, while avoiding side reactions caused by excessive local concentrations; when the viscosity rises to the threshold, it automatically switches to anchor stirring. Its design that fits the kettle wall can effectively eliminate the retention layer of high-viscosity materials on the reactor wall, increase the heat transfer coefficient by more than 35%, and prevent aromatic ring sulfonation or product decomposition caused by local overheating.

[0026] 2. Through the specific setting of the clutch assembly, using the principle that the rotational resistance of the outer rotating sleeve increases with the increase in viscosity of the reaction liquid, relative sliding occurs between the outer rotating sleeve and the rotating shaft, and further the spiral surfaces of spiral wedge block 1 and spiral wedge block 2 slide relative to each other, spiral wedge block 1 and spiral wedge block 2 move away from each other and squeeze the partition plate to move up, and the inner rotating sleeve on the partition plate squeezes the clutch plate group above, so that transmission is achieved between the upper rotating sleeve and the rotating shaft, and turbine stirring is converted into anchor stirring. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 It is a three-dimensional diagram of the esterification reaction device used for the synthesis of aromatic pharmaceutical intermediates of the present invention; Figure 2 It is a top view of the esterification reaction device for synthesizing aromatic pharmaceutical intermediates of the present invention; Figure 3 For the present invention Figure 2 Sectional view at AA; Figure 4 This is a front view of the bottom structure of the rotating shaft in the esterification reaction device for the synthesis of aromatic pharmaceutical intermediates of the present invention; Figure 5 For the present invention Figure 4 A half-cutaway perspective view of the structure; Figure 6 For the present invention Figure 4 Sectional view at the middle BB; Figure 7 For the present invention Figure 4 Top view of the structure; Figure 8 For the present invention Figure 7 Sectional view at CC; Fig. 9 It is a stereoscopic diagram of spiral wedge block 1 and spiral wedge block 2 in the esterification reaction device for synthesizing aromatic pharmaceutical intermediates of the present invention; Fig.10 For the present invention Fig. 9 Exploded diagram of Fig.11 It is an exploded view of a clutch plate assembly in an esterification reaction device for synthesizing aromatic pharmaceutical intermediates of the present invention; Fig.12 For the present invention Figure 8 A cross-sectional view of spiral wedge block 2 after rotation relative to spiral wedge block 1.

[0028] In the figure: 1. Tank body; 2. Driving motor; 3. Rotating shaft; 4. Upper rotating sleeve; 5. Lower rotating sleeve; 6. Turbine agitator; 7. Stirring frame; 8. Homogenizing plate; 9. Scraper; 10. Partition plate; 11. Outer rotating sleeve; 12. Inner rotating sleeve; 13. Clutch plate group; 14. Spring; 15. Spiral wedge block 1; 16. Spiral wedge block 2; 17. Friction plate; 18. Steel plate; 19. Slot; 20. Gear; 21. Protrusion; 22. Depression; 23. Jacket; 24. Feed inlet; 25. Discharge outlet; 26. Anchor agitator. DETAILED DESCRIPTION

[0029] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the accompanying drawings.

[0030] Example 1, reference Figure 1-12 , which is the first embodiment of the present invention, provides an esterification reaction device for the synthesis of aromatic pharmaceutical intermediates, including a tank body 1, a driving motor 2 arranged on the top of the tank body 1, a rotating shaft 3 is connected to the main shaft of the driving motor 2, an upper rotating sleeve 4 and a lower rotating sleeve 5 are sleeved on the rotating shaft 3, an anchor agitator 26 is connected to the upper rotating sleeve 4, a turbine agitator 6 is connected to the lower rotating sleeve 5, and a clutch unit is arranged between the upper rotating sleeve 4 and the lower rotating sleeve 5; when the reaction liquid has low viscosity, the clutch unit enables the lower rotating sleeve 5 to transmit the power to the rotating shaft 3, and when the reaction liquid has high viscosity, the clutch unit enables the upper rotating sleeve 4 to transmit the power to the rotating shaft 3.

[0031] In this embodiment, a liquid feeding valve is also provided on the top of the tank body 1, which is a stainless steel butterfly valve, and alcohol raw materials (such as ethylene glycol) are accurately injected through a metering pump. The valve body is installed at an angle of 45° to avoid splashing of droplets; a special tube for catalyst injection is a Hastelloy capillary (Φ8mm), which penetrates 1 / 3 below the liquid surface to achieve directional injection to prevent local excessive concentration; a temperature sensor sleeve extends to the center of the reaction zone, with built-in PT100 and infrared dual probes, and a temperature measurement error of ≤±0.3℃; a pressure balance port is connected to a two-stage safety system, which is directly connected to the atmosphere through an activated carbon filter in the normal pressure stage, and is switched to a bursting disc (0.35MPa bursting pressure) after boosting; a sampling valve is a sanitary sterile design, equipped with an online viscometer and a micro HPLC to achieve closed-loop quality control; a sight glass light group, composed of an LED cold light source and corrosion-resistant borosilicate glass, supplemented by a 360° rotating camera, can monitor the operating status of the anchor agitator 26.

[0032] In this embodiment, the outer diameter and inner diameter of the upper rotating sleeve 4 and the lower rotating sleeve 5 are the same, the inner diameters of the upper rotating sleeve 4 and the lower rotating sleeve 5 are larger than the outer diameter of the rotating shaft 3, and there is a gap between the lower end of the upper rotating sleeve 4 and the upper end of the lower rotating sleeve 5. In order to make the upper rotating sleeve 4 and the lower rotating sleeve 5 rotate coaxially with the rotating shaft 3 while maintaining the gap between the lower end of the upper rotating sleeve 4 and the upper end of the lower rotating sleeve 5, a plurality of shaft steps with a diameter equal to the inner diameter of the upper rotating sleeve 4 and the lower rotating sleeve 5 are arranged on the shaft wall of the rotating shaft 3, and a plurality of convex rings matching the shaft steps are arranged on the inner walls of the upper rotating sleeve 4 and the lower rotating sleeve 5, and the convex rings are mounted on the shaft steps through thrust bearings.

[0033] By setting up a clutch unit, the strategy of first turbine stirring and then switching to anchor stirring after the viscosity of the reactant reaches the threshold can significantly improve the reaction efficiency and product quality. Turbine stirring (200-400rpm) is used in the initial low viscosity stage of the reaction. Its high-intensity radial flow can quickly disperse the catalyst and promote the collision of acid and alcohol molecules, thereby increasing the reaction rate by 30-50%, while avoiding side reactions caused by excessive local concentration; when the viscosity rises to the 800cP threshold, it automatically switches to anchor stirring (60-80rpm). Its design that fits the kettle wall can effectively eliminate the retention layer of high-viscosity materials on the reactor wall, increase the heat transfer coefficient by more than 35%, and prevent aromatic ring sulfonation or product decomposition caused by local overheating. This dynamic switching mode solves the energy waste problem of turbine stirring at high viscosity (power consumption is reduced by 40%) by matching the stirring type with the rheological properties of the material, and overcomes the defect of insufficient mixing of anchor stirring at low viscosity, shortening the reaction endpoint time by 20% and increasing the product purity from 99.2% to 99.7%. In addition, the scraping effect significantly reduces the risk of coking and extends the equipment cleaning cycle by 3 times, making it particularly suitable for the production of heat-sensitive, high-value-added pharmaceutical intermediates such as parabens.

[0034] Reference Figure 3 The anchor stirrer 26 includes a stirring frame 7 arranged on the upper rotating sleeve 4 , a homogenizing plate 8 arranged on the stirring frame 7 , and a scraper 9 arranged on the stirring frame 7 .

[0035] By arranging the homogenizing plate 8 and the scraper 9, the design of fitting the reactor wall can effectively eliminate the retention layer of high-viscosity materials on the reactor wall, thereby improving the heat transfer coefficient. The homogenizing plate 8 is used to improve mass transfer.

[0036] Reference Figure 5The clutch unit includes a partition plate 10 disposed between the upper rotating sleeve 4 and the lower rotating sleeve 5. The partition plate 10 has a hole in the center and the sliding sleeve is disposed on the rotating shaft 3. The partition plate 10 is closely attached to the outer walls of the upper rotating sleeve 4 and the lower rotating sleeve 5 and symmetrically extends with an outer rotating sleeve 11. The partition plate 10 is symmetrically extended with an inner rotating sleeve 12 in the inner cavity of the upper rotating sleeve 4 and the lower rotating sleeve 5. The two ends of the inner rotating sleeve 12 are respectively abutted with a group of clutch plate groups 13. The clutch plate group 13 located at the top connects the upper rotating sleeve 4 and the rotating shaft 3, and the clutch plate group 13 located at the bottom connects the upper rotating sleeve 4 and the rotating shaft 3. The clutch plate group 13 connects the lower rotating sleeve 5 and the rotating shaft 3. A limit ring is provided on the side of each clutch plate group 13 away from the inner rotating sleeve 12. A spring 14 is abutted between the lower rotating sleeve 5 and the partition plate 10. A spiral wedge block 15 is provided on the partition plate 10. A spiral wedge block 2 16 is provided in the lower rotating sleeve 5. The spiral surfaces of the spiral wedge block 15 and the spiral wedge block 2 16 are fitted together. When the inner rotating sleeve 12 squeezes the clutch plate group 13, the clutch plate group 13 is in a linkage state, and the other clutch plate group 13 is in a disconnected state.

[0037] In this embodiment, the spring 14 is arranged to apply a resistance to the upward movement of the partition plate 10, so that when the viscosity of the reaction liquid has not reached a threshold value, the inner rotating sleeve 12 is always pressed against the clutch plate group 13 below, and the partition plate slides vertically in the gap between the upper rotating sleeve 4 and the lower rotating sleeve 5. When the partition plate is close to the lower rotating sleeve 5, the clutch plate group 13 below is compressed, and when the partition plate is close to the upper rotating sleeve 4, the clutch plate group 13 above is compressed, and the spring 14 is compressed.

[0038] Through the specific setting of the clutch assembly, using the principle that the rotational resistance of the outer rotating sleeve 11 increases with the increase in viscosity of the reaction liquid, relative sliding occurs between the outer rotating sleeve 11 and the rotating shaft 3, and further the spiral surfaces of the spiral wedge 15 and the spiral wedge 2 16 slide relative to each other, the spiral wedge 15 and the spiral wedge 2 16 move away from each other and squeeze the partition plate 10 to move upward, the inner rotating sleeve 12 on the partition plate 10 squeezes the clutch plate group 13 above, so that transmission is achieved between the upper rotating sleeve 4 and the rotating shaft 3, and the turbine stirring is converted into anchor stirring.

[0039] Reference Fig.11 The clutch plate group 13 includes a plurality of friction plates 17 and a plurality of steel plates 18. The steel plates 18 and the friction plates 17 are arranged alternately. The friction plates 17 located at the top are spline-connected to the inner wall of the upper rotating sleeve 4, and the friction plates 17 located at the bottom are spline-connected to the inner wall of the lower rotating sleeve 5. The steel plates 18 are spline-connected to the shaft wall of the rotating shaft 3. Both sides of the friction plates 17 are provided with friction bosses with equal spacing, and the surfaces of the friction bosses are subjected to high friction treatment.

[0040] The clutch plate is provided to link and interrupt the transmission between the rotating shaft 3 and the upper rotating sleeve 4 and the lower rotating sleeve 5 respectively.

[0041] Reference Figure 6Slots 19 are arranged at equal intervals on the outer wall of the outer rotating sleeve 11 , and inserting teeth 20 are arranged in the slots 19 .

[0042] In this embodiment, the insert teeth 20 are used to increase the rotation resistance of the outer rotating sleeve 11. The depth of the insert teeth 20 can be freely selected. Insert teeth 20 of different depths correspond to the viscosity threshold value of relative rotation between the outer rotating sleeve 11 and the rotating shaft 3. The lower the depth of the insert teeth 20, the smaller the viscosity threshold value.

[0043] The insert teeth 20 are provided to transmit the resistance generated by the viscosity of the reaction liquid when the outer wall of the outer rotating sleeve 11 rotates.

[0044] Reference Fig.10 A protrusion 21 is provided on the spiral surface of the spiral wedge 15, and a depression 22 corresponding to the protrusion 21 is provided on the spiral surface of the spiral wedge 2 16.

[0045] By providing the protrusion 21 and the recess 22, the critical torque required for relative sliding between the spiral surfaces of the spiral wedge 15 and the spiral wedge 16 is increased. When the torque applied to the outer rotating sleeve 11 exceeds the critical value, relative sliding occurs between the spiral surfaces of the spiral wedge 15 and the spiral wedge 16. The sliding friction force is smaller than the static friction force, and the spiral wedge 15 and the spiral wedge 16 will quickly rotate away from each other.

[0046] Reference Figure 1 The side and bottom of the tank body 1 are both provided with a jacket 23. By providing the jacket 23, the tank body 1 is temperature controlled.

[0047] Reference Figure 1 The top surface of the tank body 1 is provided with a feed port 24, and the bottom surface of the tank body 1 is provided with a discharge port 25. The feed port 24 and the discharge port 25 are provided for feeding and discharging and separation of various liquid phases. The feed port 24 is flange-connected and equipped with a quick-opening blind plate for batch feeding of solid acid raw materials.

[0048] Reference Figure 8 and Fig.12The working principle of the present invention is as follows: when the esterification reaction starts, the viscosity of the reactants is low, the partition plate 10 is pressed against the lower rotating sleeve 5 under the action of the spring 14, the lower end of the inner rotating sleeve 12 connected to the partition plate 10 squeezes the clutch plate group 13 below, the lower rotating sleeve 5 and the rotating shaft 3 are driven, and the turbine agitator 6 rotates actively at this time; when the viscosity of the reactants increases to a critical value η≥800cP as the reaction proceeds, the outer rotating sleeve 11 and the rotating shaft 3 are driven by the principle that the rotation resistance of the outer rotating sleeve 11 increases with the increase of the viscosity of the reaction liquid, so that the outer rotating sleeve 11 and the rotating shaft 3 are driven by the outer rotating sleeve 11. Relative sliding occurs between the rotating shafts 3, and further, the spiral surfaces of the spiral wedge block 15 and the spiral wedge block 2 16 slide relative to each other, and the spiral surfaces of the spiral wedge block 15 and the spiral wedge block 2 16 change from full fit to partial fit, and the spiral wedge block 15 and the spiral wedge block 2 16 move away from each other and squeeze the partition plate 10 to move upward, and the inner rotating sleeve 12 on the partition plate 10 squeezes the clutch plate group 13 above, and the multiple friction plates 17 and steel plates 18 in the clutch plate group 13 squeeze each other, so that transmission is transmitted between the upper rotating sleeve 4 and the rotating shaft 3, and the turbine stirring is converted into anchor stirring.

[0049] Example 2, reference Figure 1-12 , which is the second embodiment of the present invention, provides: an esterification reaction process for the synthesis of aromatic pharmaceutical intermediates, using an esterification reaction device for the synthesis of aromatic pharmaceutical intermediates, comprising the following steps: Step 1: Raw material loading and initial mixing, p-hydroxybenzoic acid (particle size D90≤50μm) and propanol (n(acid):n(alcohol)=1:1.8) were accurately fed through a weight loss scale, ionic liquid catalyst was added, azeotroping agent cyclohexane was injected, turbine stirrer 6 (300rpm) was turned on to form radial flow, and the temperature was raised to 75°C (heating rate 2°C / min); Step 2: Viscosity responsive stirring switching, viscosity threshold trigger (η≥800cP), anchor stirrer 26 and rotating shaft 3 drive, anchor stirring stage (η=800-10,000cP), speed adjusted to 100rpm, gap 2mm (to prevent material from sticking to the wall), temperature raised to 115℃, pressure reduction (-0.06MPa), water separator drainage frequency increased to 20mL / min; Step 3: Termination of reaction and treatment of product, endpoint determination, HPLC monitoring of p-hydroxybenzoic acid residue ≤ 0.3%, rapid cooling to 50 ° C, capture ionic liquid through electrostatic adsorption column (filled with cationic resin), crude product dissolved in ethanol-water (7:3) mixed solvent, cooled to 25 ° C, centrifuged (3000g, 10min), wet product moisture <5%.

[0050] By adopting a dynamic switching mode and matching the stirring type with the rheological properties of the material, it not only solves the energy waste problem of turbine stirring at high viscosity, but also overcomes the defect of insufficient mixing of anchor stirring at low viscosity.

[0051] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. An esterification reaction device for synthesizing aromatic pharmaceutical intermediates, comprising a tank body (1), a driving motor (2) arranged on the top of the tank body (1), a rotating shaft (3) connected to the main shaft of the driving motor (2), characterized in that: An upper rotating sleeve (4) and a lower rotating sleeve (5) are sleeved on the rotating shaft (3); the upper rotating sleeve (4) is connected to an anchor stirrer (26); the lower rotating sleeve (5) is connected to a turbine stirrer (6); and a clutch unit is provided between the upper rotating sleeve (4) and the lower rotating sleeve (5); When the reaction liquid has low viscosity, the clutch unit enables transmission between the lower rotating sleeve (5) and the rotating shaft (3); when the reaction liquid has high viscosity, the clutch unit enables transmission between the upper rotating sleeve (4) and the rotating shaft (3).

2. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 1, characterized in that: The anchor stirrer (26) comprises a stirring frame (7) arranged on the upper rotating sleeve (4), a homogenizing plate (8) arranged on the stirring frame (7), and a scraper (9) arranged on the stirring frame (7).

3. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 1, characterized in that: The clutch unit comprises a partition plate (10) arranged between an upper rotating sleeve (4) and a lower rotating sleeve (5), the partition plate (10) having a hole at its center and a sliding sleeve arranged on the rotating shaft (3), the partition plate (10) being closely attached to the outer walls of the upper rotating sleeve (4) and the lower rotating sleeve (5) and symmetrically extending with an outer rotating sleeve (11), the partition plate (10) being symmetrically extending with an inner rotating sleeve (12) in the inner cavities of the upper rotating sleeve (4) and the lower rotating sleeve (5), the two ends of the inner rotating sleeve (12) being respectively abutted with a group of clutch plate groups (13), the clutch plate group (13) located at the upper end being connected to the upper rotating sleeve (4) and the rotating shaft (3), and the clutch plate group (13) located at the lower end being connected to the upper rotating sleeve (4) and the rotating shaft (3), The clutch plate group (13) connects the lower rotating sleeve (5) and the rotating shaft (3); a limit ring is provided on the side of each clutch plate group (13) away from the inner rotating sleeve (12); a spring (14) is abutted between the lower rotating sleeve (5) and the partition plate (10); a spiral wedge block 1 (15) is provided on the partition plate (10); a spiral wedge block 2 (16) is provided in the lower rotating sleeve (5); the spiral surfaces of the spiral wedge block 1 (15) and the spiral wedge block 2 (16) are in contact with each other; when the inner rotating sleeve (12) presses the clutch plate group (13), the clutch plate group (13) is in a linked state, and the other clutch plate group (13) is in a disconnected state.

4. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 3, characterized in that: The clutch plate group (13) comprises a plurality of friction plates (17) and a plurality of steel plates (18), wherein the steel plates (18) and the friction plates (17) are arranged alternately, the friction plates (17) located at the top are spline-connected to the inner wall of the upper rotating sleeve (4), the friction plates (17) located at the bottom are spline-connected to the inner wall of the lower rotating sleeve (5), and the steel plates (18) are spline-connected to the shaft wall of the rotating shaft (3).

5. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 3, characterized in that: Slots (19) are arranged at equal intervals on the outer wall of the outer rotating sleeve (11), and insert teeth (20) are arranged in the slots (19).

6. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 3, characterized in that: The spiral surface of the spiral wedge piece 1 (15) is provided with a protrusion (21), and the spiral surface of the spiral wedge piece 2 (16) is provided with a recess (22) corresponding to the protrusion (21).

7. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 1, characterized in that: The sides and bottom of the tank body (1) are both provided with jackets (23).

8. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 1, characterized in that: The top surface of the tank body (1) is provided with a material inlet (24), and the bottom surface of the tank body (1) is provided with a material outlet (25).

9. An esterification reaction process for the synthesis of aromatic pharmaceutical intermediates, using the esterification reaction device for the synthesis of aromatic pharmaceutical intermediates as claimed in claim 1, characterized in that: The following steps are involved: Step 1: Raw material loading and initial mixing: p-hydroxybenzoic acid (particle size D90 ≤ 50 μm) and propanol (n (acid): n (alcohol) = 1:1.8) were accurately fed through a weight loss scale, an ionic liquid catalyst was added, and an azeotropic agent cyclohexane was injected. The turbine stirrer (6) (300 rpm) was turned on to form a radial flow, and the temperature was raised to 75°C (heating rate 2°C / min); Step 2: Viscosity responsive stirring switching, viscosity threshold trigger (η≥800cP), anchor stirrer (26) and rotating shaft (3) transmission, anchor stirring stage (η=800-10,000cP), speed adjusted to 100rpm, gap 2mm to prevent material from sticking to the wall, temperature raised to 115°C, pressure reduction (-0.06MPa), water separator drainage frequency increased to 20mL / min; Step 3: Termination of reaction and treatment of product, endpoint determination, HPLC monitoring of p-hydroxybenzoic acid residue ≤ 0.3%, rapid cooling to 50 ° C, capture ionic liquid through electrostatic adsorption column (filled with cationic resin), crude product dissolved in ethanol-water (7:3) mixed solvent, cooled to 25 ° C, centrifuged (3000g, 10min), wet product moisture <5%.

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