An esterification reaction device and process for synthesizing aromatic pharmaceutical intermediates

Abstract

The present invention relates to the technical field of esterification reaction vessels, and discloses an esterification reaction device and process for synthesizing aromatic pharmaceutical intermediates. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates comprises a tank body, a drive motor disposed on the top of the tank body, a rotating shaft connected to the main shaft of the drive motor, an upper rotating sleeve and a lower rotating sleeve sleeved on the rotating shaft, an anchor agitator connected to the upper rotating sleeve, a turbine agitator connected to the lower rotating sleeve, and a clutch unit disposed between the upper rotating sleeve and the lower rotating sleeve; when the viscosity of the reaction liquid is low, the clutch unit transmits the power between the lower rotating sleeve and the rotating shaft, and when the viscosity of the reaction liquid is high, the clutch unit transmits the power between the upper rotating sleeve and the rotating shaft. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates, by providing a clutch unit, adopts a strategy of first turbine stirring and then switching to anchor stirring after the viscosity of the reactant reaches a threshold, which can significantly improve reaction efficiency and product quality.

Description

Technical Field

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

[0002] An esterification reactor is a specialized device used to synthesize ester compounds from carboxylic acids and alcohols in the presence of a catalyst. Its core function is to drive the reaction efficiently through precise control of temperature, pressure, and mixing conditions. A typical structure includes a jacketed, corrosion-resistant reactor (glass-lined or 316L stainless steel), a switchable agitation system (turbine or anchor type to accommodate different viscosities), a water separator (azeotropic dehydration), and automated instrumentation (online pH / viscosity monitoring).

[0003] Patent publication number CN103170298A discloses an esterification reactor, comprising a reactor cylinder, a heating device and a top-mounted agitator arranged in the reactor cylinder, the top-mounted agitator being provided with a main shaft, the upper end of which is connected to a stirrer drive device, the reactor cylinder being composed of an upper head, an intermediate cylinder and a lower head connected in sequence, the upper head, the intermediate cylinder and the lower head being interconnected by flanges provided with a mouth structure, each of which is machined using a large vertical lathe, the heating device comprising a plurality of vertical heating cylinders, the heating cylinders being connected to an evaporator via corresponding inlet and outlet conduits, the heating cylinders, the conduits and the evaporator constituting a non-powered circulating heat medium vacuum system.

[0004] The existing technology has the following defects:

[0005] Esterification reaction vessels using a single agitation method have significant process limitations, primarily due to their inability to adapt to the dynamic changes in material properties during the reaction. During the initial, low-viscosity stage of the reaction, anchor agitation, due to its limited speed (typically <100 rpm), results in low mixing efficiency, uneven catalyst dispersion, and a prolonged induction period of over 30%. Furthermore, if turbine agitation is used throughout the reaction, once the viscosity reaches 1000 cP, its high speed (>200 rpm) results in inefficient energy consumption (power increases 3-5 times), while strong shear forces can disrupt the structure of intermediate products (e.g., broadening the molecular weight distribution of polymerized esters). Single agitation is also prone to forming mass transfer dead zones. The material turnover rate in the center of the anchor agitator is insufficient, while the near-wall surface of the turbine agitator is prone to accumulation of high-viscosity materials. Both can lead to localized overheating (temperature differences 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 in 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

[0006] In view of the above problems in the prior art, an esterification reaction device and process for the synthesis of aromatic pharmaceutical intermediates are proposed.

[0007] In one aspect of the present application, an esterification reaction apparatus for the synthesis of aromatic pharmaceutical intermediates is provided, the purpose of which is to use turbine stirring at the initial 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 the reactor wall can effectively eliminate the retention layer of high-viscosity materials on the reactor wall, thereby increasing the heat transfer coefficient by more than 35% and preventing aromatic ring sulfonation or product decomposition caused by local overheating.

[0008] The technical solution of the present invention is: an esterification reaction device for synthesizing aromatic pharmaceutical intermediates, comprising a tank body, a drive motor arranged on the top of the tank body, a rotating shaft connected to the main shaft of the drive 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;

[0009] 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.

[0010] Adopting this approach, by incorporating a clutch unit, initially employs turbine agitation, then switches to anchor agitation once the viscosity of the reactants reaches a threshold, significantly improving reaction efficiency and product quality. Turbine agitation is used during the initial, low-viscosity phase of the reaction. Its high-intensity radial flow rapidly disperses the catalyst and promotes collisions between acid and alcohol molecules, increasing the reaction rate by 30-50% while also avoiding side reactions caused by localized overconcentration. When the viscosity reaches a threshold, anchor agitation automatically switches to the reactor wall. Its contoured design effectively eliminates the retention layer of high-viscosity materials on the reactor wall, increasing the heat transfer coefficient by over 35% and preventing localized overheating that could lead to aromatic ring sulfonation or product decomposition.

[0011] Furthermore, the anchor agitator includes 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.

[0012] By adopting the above scheme, by setting a homogenizing plate and a scraper, the design of the scraper 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 is used to improve mass transfer.

[0013] The axle up and down groove at two ends embeds respectively in two guide rails up and down of being made up of the groove on the attachment piece, and the tooth on the attachment piece is meshed with tooth on upper sprocket wheel, the lower sprocket.

[0014] 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 as the viscosity of the reaction liquid increases, 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 upward, and the inner rotating sleeve on the partition plate squeezes the clutch plate group above, so that transmission is transmitted between the upper rotating sleeve and the rotating shaft, and the turbine stirring is converted into anchor stirring.

[0015] Furthermore, the clutch plate group includes multiple friction plates and multiple steel plates, and the steel plates and friction plates are arranged alternately. The friction plates located above are spline-connected to the inner wall of the upper rotating sleeve, the friction plates located below 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.

[0016] By adopting the above solution, 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.

[0017] Furthermore, slots are arranged at equal intervals on the outer wall of the outer rotating sleeve, and inserting teeth are arranged in the slots.

[0018] 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.

[0019] Furthermore, a protrusion is provided on the spiral surface of the spiral wedge piece 1, and a depression corresponding to the protrusion is provided on the spiral surface of the spiral wedge piece 2.

[0020] By adopting the above solution, by providing the protrusions and the depressions, the critical torque required for relative sliding between the spiral surfaces of the first spiral wedge and the second spiral wedge is increased.

[0021] Furthermore, the sides and bottom of the tank body are both provided with jackets.

[0022] By adopting the above solution, the temperature of the tank body is controlled by providing a jacket.

[0023] Furthermore, a feed port is provided on the top surface of the tank body, and a discharge port is provided on the bottom surface of the tank body.

[0024] The above solution is adopted to provide a feed port and a discharge port for feeding and discharging materials and separating various liquid phases.

[0025] Furthermore, the present invention also provides an esterification reaction process for synthesizing aromatic pharmaceutical intermediates, comprising the following steps:

[0026] 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 added using a loss-in-weight scale. An ionic liquid catalyst was added, and cyclohexane as an azeotropic agent was injected. The turbine agitator was turned on (300 rpm) to form a radial flow, and the temperature was raised to 75°C (heating rate 2°C / min).

[0027] Step 2: Viscosity-responsive stirring is switched. The viscosity threshold is triggered (η≥800 cP). The anchor agitator is driven by the rotating shaft. In the anchor stirring stage (η=800-10,000 cP), the speed is adjusted to 100 rpm, a 2 mm gap is set to prevent material from sticking to the wall, the temperature is raised to 115°C, the pressure is reduced (-0.06 MPa), and the drainage frequency of the water separator is increased to 20 mL / min.

[0028] Step 3: Termination of reaction and product treatment, endpoint determination, HPLC monitoring of p-hydroxybenzoic acid residue ≤ 0.3%, rapid cooling to 50 ° C, capture the ionic liquid through an electrostatic adsorption column (packed with cationic resin), the crude product is dissolved in a mixed solvent of ethanol and water (7:3), cooled to 25 ° C, and centrifuged (3000g, 10min), the moisture content of the wet product is <5%.

[0029] The above solution adopts a dynamic switching mode and matches the stirring type with the rheological characteristics 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.

[0030] Beneficial effects of the present invention:

[0031] 1. By setting up a clutch unit, the strategy of first using turbine stirring and then switching to anchor stirring when the viscosity of the reactants reaches a threshold can significantly improve reaction efficiency and product quality. Turbine stirring is used in the initial low-viscosity stage of the reaction. Its high-intensity radial flow quickly disperses the catalyst and promotes collisions between acid and alcohol molecules, increasing the reaction rate by 30-50% while avoiding side reactions caused by localized excessive concentrations. When the viscosity rises to the threshold, anchor stirring is automatically switched. Its design, which fits the reactor wall, effectively eliminates the retention layer of high-viscosity materials on the reactor wall, increasing the heat transfer coefficient by more than 35%, and preventing localized overheating that can cause aromatic ring sulfonation or product decomposition.

[0032] 2. Through the specific setting of the clutch assembly, the principle that the rotational resistance of the outer rotating sleeve increases with the increase of the viscosity of the reaction liquid is utilized, so that relative sliding occurs between the outer rotating sleeve and the rotating shaft. Further, the spiral surfaces of spiral wedge block 1 and spiral wedge block 2 slide relative to each other, and spiral wedge block 1 and spiral wedge block 2 move away from each other and squeeze the partition plate upward. 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

[0033] Figure 1 This is a perspective view of the esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to the present invention;

[0034] Figure 2 This is a top view of the esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to the present invention;

[0035] Figure 3 For the present invention Figure 2 Cross-sectional view at AA in the middle;

[0036] Figure 4 This is a front view of the bottom structure of the rotating shaft in the esterification reaction device for synthesizing aromatic pharmaceutical intermediates of the present invention;

[0037] Figure 5 For the present invention Figure 4 A half-section perspective view of the structure;

[0038] Figure 6 For the present invention Figure 4 Cross-sectional view at the middle BB;

[0039] Figure 7 For the present invention Figure 4 Top view of the structure;

[0040] Figure 8 For the present invention Figure 7 Cross-sectional view at CC;

[0041] Figure 9A perspective view of spiral wedge 1 and spiral wedge 2 in the esterification reaction device for synthesizing aromatic pharmaceutical intermediates of the present invention;

[0042] Figure 10 For the present invention Figure 9 Exploded diagram;

[0043] Figure 11 This is an exploded view of the clutch plate assembly in the esterification reaction device for synthesizing aromatic pharmaceutical intermediates of the present invention;

[0044] Figure 12 For the present invention Figure 8 Cross-sectional view of spiral wedge 2 after rotation relative to spiral wedge 1.

[0045] In the picture:

[0046] 1. Tank body; 2. Drive motor; 3. Rotating shaft; 4. Upper rotating sleeve; 5. Lower rotating sleeve; 6. Turbine agitator; 7. Mixing 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 port; 25. Discharge port; 26. Anchor agitator. DETAILED DESCRIPTION

[0047] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0048] 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, and a turbine agitator 6 is connected to the lower rotating sleeve 5, 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 causes transmission between the lower rotating sleeve 5 and the rotating shaft 3, and when the reaction liquid has high viscosity, the clutch unit causes transmission between the upper rotating sleeve 4 and the rotating shaft 3.

[0049] 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. Alcohol raw materials (such as ethylene glycol) are accurately injected through a metering pump. The valve body is installed at a 45° angle to avoid splashing of droplets; a special tube for catalyst injection is a Hastelloy alloy 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 a built-in PT100 and infrared dual probes, and a temperature measurement error of ≤±0.3°C; 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 switches to a bursting disc (0.35MPa bursting pressure) after boosting; the sampling valve is of sanitary and sterile design and is equipped with an online viscometer and a micro HPLC to achieve closed-loop quality control; the sight glass light group is composed of an LED cold light source and corrosion-resistant borosilicate glass, supplemented by a 360° rotating camera, which can monitor the operating status of the anchor agitator 26.

[0050] 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 diameter of the upper rotating sleeve 4 and the lower rotating sleeve 5 is 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 provided on the shaft wall of the rotating shaft 3, and a plurality of convex rings matching the shaft steps are provided 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.

[0051] By configuring a clutch unit, the system initially uses turbine stirring, then switches to anchor stirring once the viscosity of the reactants reaches a threshold, significantly improving reaction efficiency and product quality. Turbine stirring (200-400 rpm) is used during the initial, low-viscosity phase of the reaction. Its high-intensity radial flow rapidly disperses the catalyst and promotes collisions between acid and alcohol molecules, increasing the reaction rate by 30-50% while also preventing side reactions caused by localized overconcentration. When the viscosity reaches a threshold of 800 cP, the system automatically switches to anchor stirring (60-80 rpm). Its contoured design effectively eliminates the stagnant layer of high-viscosity materials on the reactor wall, improving the heat transfer coefficient by over 35% and preventing localized overheating that can lead to aromatic ring sulfonation or product decomposition. This dynamic switching mode, by matching the stirring type with the rheological properties of the material, addresses both the energy waste associated with turbine stirring at high viscosities (reducing power consumption by 40%) and the inadequate mixing associated with anchor stirring at low viscosities. This reduces the reaction endpoint time by 20% and increases 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.

[0052] Reference Figure 3The 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 .

[0053] 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.

[0054] Reference Figure 5 The clutch unit includes a partition plate 10 arranged 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 arranged on the rotating shaft 3. The partition plate 10 is symmetrically extended with an outer rotating sleeve 11 close to the outer wall of the upper rotating sleeve 4 and the lower rotating sleeve 5. 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, and a spiral wedge block 2 16 is provided in the lower rotating sleeve 5. The spiral surface of the spiral wedge block 15 and the spiral surface of the spiral wedge block 2 16 are in contact. When the inner rotating sleeve 12 squeezes 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.

[0055] In this embodiment, the spring 14 is configured to apply a resistance when the partition plate 10 moves upward, so that when the viscosity of the reaction liquid has not reached a threshold value, the inner rotating sleeve 12 always presses 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 approaches the lower rotating sleeve 5, the clutch plate group 13 below is compressed. When the partition plate approaches the upper rotating sleeve 4, the clutch plate group 13 above is compressed and the spring 14 is compressed.

[0056] Through the specific setting of the clutch assembly, utilizing the principle that the rotational resistance of the outer rotating sleeve 11 increases as the viscosity of the reaction liquid increases, 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, and 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 generated between the upper rotating sleeve 4 and the rotating shaft 3, and the turbine stirring is converted into anchor stirring.

[0057] Reference Figure 11The clutch plate group 13 includes multiple friction plates 17 and multiple steel plates 18. The steel plates 18 and friction plates 17 are arranged alternately. The upper friction plates 17 are spline-connected to the inner wall of the upper rotating sleeve 4, and the lower friction plates 17 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 treated with high friction.

[0058] 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.

[0059] Reference Figure 6 Slots 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.

[0060] In this embodiment, the insert teeth 20 are used to increase the rotational 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 at which relative rotation occurs between the outer rotating sleeve 11 and the rotating shaft 3. The lower the depth of the insert teeth 20, the lower the viscosity threshold.

[0061] 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.

[0062] Reference Figure 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.

[0063] By providing the protrusions 21 and the recesses 22, the critical torque required for relative sliding between the spiral surfaces of the spiral wedge 15 and the spiral wedge 2 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 2 16. The sliding friction force is less than the static friction force, and the spiral wedge 15 and the spiral wedge 2 16 will quickly rotate away from each other.

[0064] 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.

[0065] 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 materials and separating 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.

[0066] Reference Figure 8 and Figure 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, and the lower end of the inner rotating sleeve 12 connected to the partition plate 10 squeezes the clutch plate group 13 below, and the transmission is between the lower rotating sleeve 5 and the rotating shaft 3. At this time, the turbine agitator 6 rotates actively; 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 rotated according to the principle that the rotational resistance of the outer rotating sleeve 11 increases with the increase of the viscosity of the reaction liquid. Relative sliding occurs between the rotating shafts 3, and further the spiral surfaces of the spiral wedge 15 and the spiral wedge 2 16 slide relative to each other, and the spiral surfaces of the spiral wedge 15 and the spiral wedge 2 16 change from full fit to partial fit, and the spiral wedge 15 and the spiral wedge 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.

[0067] Example 2, reference Figure 1-12 , which is a second embodiment of the present invention, provides: an esterification reaction process for synthesizing aromatic pharmaceutical intermediates, using an esterification reaction device for synthesizing aromatic pharmaceutical intermediates, comprising the following steps:

[0068] 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 added using a loss-in-weight scale. An ionic liquid catalyst was added, and cyclohexane as an azeotropic agent 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).

[0069] Step 2: Viscosity-responsive stirring is switched. The viscosity threshold is triggered (η≥800 cP). The anchor agitator 26 is driven by the rotating shaft 3. In the anchor stirring stage (η=800-10,000 cP), the speed is adjusted to 100 rpm, the gap is 2 mm (to prevent material from sticking to the wall), the temperature is raised to 115°C, the pressure reduction is turned on (-0.06 MPa), and the drainage frequency of the water separator is increased to 20 mL / min.

[0070] Step 3: Termination of reaction and product treatment, endpoint determination, HPLC monitoring of p-hydroxybenzoic acid residue ≤ 0.3%, rapid cooling to 50 ° C, capture the ionic liquid through an electrostatic adsorption column (packed with cationic resin), the crude product is dissolved in a mixed solvent of ethanol and water (7:3), cooled to 25 ° C, and centrifuged (3000g, 10min), the moisture content of the wet product is <5%.

[0071] By adopting a dynamic switching mode and matching the stirring type with the rheological properties of the material, the energy waste problem of turbine stirring at high viscosity is solved, and the defect of insufficient mixing of anchor stirring at low viscosity is overcome.

[0072] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. 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), and 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 a low viscosity, the clutch unit causes the lower rotating sleeve (5) to transmit the power to the rotating shaft (3); when the reaction liquid has a high viscosity, the clutch unit causes the upper rotating sleeve (4) to transmit the power to the rotating shaft (3); 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 in the 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 cavity of the upper rotating sleeve (4) and the lower rotating sleeve (5), and a group of clutch plate groups (13) respectively abutting against each other at both ends of the inner rotating sleeve (12), 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), 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) is connected to 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) squeezes 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.

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 plate group (13) includes 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 on the upper side are spline-connected to the inner wall of the upper rotating sleeve (4), the friction plates (17) located on the lower side 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).

4. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 1, 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).

5. The esterification reaction device for synthesizing aromatic pharmaceutical intermediates according to claim 1, 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).

6. 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).

7. 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 feed port (24), and the bottom surface of the tank body (1) is provided with a discharge port (25).

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