A continuous turbulent tubular reactor for the preparation of 2,5-dihydroxy-1,4-dithiane

Abstract

The application provides a continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiane, relates to the technical equipment field of organic synthesis, and comprises a cylindrical reaction cavity, a shell coaxially fixed outside the reaction cavity, a closed annular cooling cavity left in the middle, a stirring shaft connected at both ends of the shell, a driving motor connected at one side of the stirring shaft, staggered conical protrusions fixed to the outer wall of the stirring shaft and continuous spiral blades fixed to the conical protrusions, and a temperature sensor arranged in the reaction cavity. The application forms a fluid turbulent reaction field through the composite stirring structure of the spiral blades and the conical protrusions, forms a double-channel cooling mode through the cooling cavity and the cooling channel, and can solve the problems of many impurities, low efficiency and high cost in the process of preparing 2,5-dihydroxy-1,4-dithiane in the prior art.

Description

Technical Field

[0001] This application relates to the field of organic synthesis technology equipment, specifically to a continuous turbulent tubular reactor for the preparation of 2,5-dihydroxy-1,4-dithiane. Background Technology

[0002] 2,5-Dihydroxy-1,4-dithiane is a key intermediate in the active pharmaceutical ingredients lametafenidine and emtricitabine, and is also used in the synthesis of antibiotics, antitumor drugs, and cardiovascular drugs. Due to its strong biological activity and biocompatibility, this compound is widely used in various pharmaceutical and pesticide fields, resulting in a huge market demand.

[0003] Currently, the mainstream production process of 2,5-dihydroxy-1,4-dithiane is to obtain it by condensation of chloroacetaldehyde and sodium hydrosulfide, as shown in the figure below. For example, patents such as CN 109608433 and WO 2010049466 have reported the synthesis process of dithiane. These reports all use the method of mixing haloaldehyde solution and sodium hydrosulfide solution and reacting in a traditional batch reactor.

[0004]

[0005] However, due to the specific nature of the reaction, the traditional batch reactor method has the following drawbacks:

[0006] Uneven mixing: This can easily lead to excessively high local concentrations and an increase in side reactions during the reaction;

[0007] High impurity content: The reaction is highly exothermic, which leads to product decomposition and an increase in side reactions, resulting in impurities.

[0008] Low efficiency: Compared with continuous turbulent tubular reactors, batch production in reactors cannot achieve continuous feeding and discharging. The processing time for feeding and unloading is long, which greatly reduces production efficiency.

[0009] In summary, there is an urgent need for equipment capable of large-scale industrial production of dithiane to address the problems of uneven mixing, numerous impurities, and low efficiency encountered in the preparation of 2,5-dihydroxy-1,4-dithiane using traditional batch reactors. Utility Model Content

[0010] The purpose of this application is to provide a continuous turbulent tubular reactor for the preparation of 2,5-dihydroxy-1,4-dithiane, which can solve the problems of many impurities, low efficiency and high cost in the preparation of 2,5-dihydroxy-1,4-dithiane in the prior art.

[0011] This application provides a continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiane, employing the following technical solution: It includes a cylindrical reaction chamber, characterized in that: a shell is coaxially fixed to the outside of the reaction chamber, with a closed annular cooling chamber in the middle; a stirring shaft is coaxially connected to both ends of the shell via bearings, the stirring shaft penetrating the shell and the reaction chamber, its interior being a hollow cooling channel; a drive motor is connected to one side of the stirring shaft; conical protrusions are alternately fixed to its outer wall, and continuous spiral blades are fixed thereto; the outer edge of the spiral blades is clearance-fitted with the inner wall of the reaction chamber; a first and second sample inlet are provided at the left end of the reaction chamber, the two sample inlets independently penetrating from the outside of the shell and connecting to the inside of the reaction chamber; metering pumps are independently connected to the outside of each sample inlet; a sample outlet is connected to the lower right end of the reaction chamber; a cooling medium inlet and a cooling medium outlet are respectively opened at both ends of the cooling chamber and the cooling channel; a temperature sensor is provided inside the reaction chamber to detect the temperature inside the reaction chamber.

[0012] Furthermore, the first and second injection ports are arranged symmetrically at 180° radially in the reaction chamber.

[0013] Furthermore, the conical protrusions are arranged in multiple rows along the axial direction and staggered in the circumferential direction on the stirring shaft.

[0014] Furthermore, a safety pressure relief valve is installed at the top of the middle section of the reaction chamber.

[0015] Furthermore, the pitch of the helical blade (8) is 1.2 times the diameter of the reaction chamber (1), and the gap between its outer edge and the inner wall of the reaction chamber (1) is ≤1mm.

[0016] Furthermore, the height of the conical protrusion is 12% of the diameter of the reaction chamber.

[0017] Furthermore, the reaction chamber is made of alloy HC-276.

[0018] In summary, this application includes at least one of the following beneficial technical effects:

[0019] This is a continuous turbulent tubular reactor for the preparation of 2,5-dihydroxy-1,4-dithiane. By setting up a composite stirring structure with helical blades and conical protrusions, a turbulent fluid reaction field is formed, resulting in a complete and efficient reaction that can effectively reduce impurities. By setting up a cooling chamber and cooling channels with internal cooling medium, a dual-channel cooling system is formed, and the reaction temperature is precisely controlled by a temperature sensor, which can make the preparation process stable and efficient. Attached Figure Description

[0020] Figure 1 and Figure 2 This is an overall schematic diagram of the present application;

[0021] Figure 3 This is a schematic diagram of the internal structure of this application;

[0022] Figure 4 This is a schematic diagram of the cooling channel and cooling cavity structure of this application;

[0023] In the picture:

[0024] 1-Reaction chamber, 2-Shell, 3-Cooling chamber, 4-Stirring shaft, 5-Cooling channel, 6-Drive motor, 7-Conical protrusion, 8-Helical blade, 9-First sample inlet, 10-Second sample inlet, 11-Metering pump, 12-Sampling outlet, 13-Temperature sensor, 14-Safety pressure relief valve. Detailed Implementation

[0025] The following is in conjunction with the appendix Figure 1 - Appendix Figure 4 This application will be described in further detail below.

[0026] like Figures 1 to 4As shown, a continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiane includes a cylindrical reaction chamber 1 with a diameter of 200 mm and a length of 3000 mm, made of alloy HC-276. A shell 2 with a diameter of 240 mm is coaxially fixed to the outside of the reaction chamber 1, with a closed annular cooling chamber 3 in the middle, 20 mm wide. A stirring shaft 4 is coaxially connected to both ends of the shell 2 via bearings. The stirring shaft 4 passes through the shell 2 and the reaction chamber 1, and its interior is a hollow cooling channel 5. A drive motor 6, which is a variable frequency motor, is connected to one side of the stirring shaft 4. Multiple conical protrusions 7 are staggered and fixed to the outer wall of the stirring shaft 4, and continuous spiral blades 8 are fixed thereon. The outer edge of the spiral blades 8 is clearance-fitted with the inner wall of the reaction chamber 1, with a clearance ≤ 1 mm. The pitch is 1.2 times the diameter of the reaction chamber 1, and the height of the conical protrusions 7 is 12% of the diameter of the reaction chamber 1. The left end of the reaction chamber 1 is provided with a first inlet 9 and a second inlet 10. The two inlets independently penetrate from the outside of the shell 2 and connect to the inside of the reaction chamber 1. A metering pump 11 is independently connected to the outside of each inlet. The lower right end of the reaction chamber 1 is connected to an outlet 12. The first inlet 9 is for chloroacetaldehyde solution, and the second inlet 10 is for sodium hydrosulfide solution. The molar ratio of chloroacetaldehyde to aqueous solution is 1.1:1 to 2.2:1, preferably 1.4:1. The flow rate of sodium hydrosulfide solution is 300 ml / min to 500 ml / min, preferably 400 ml / min. The flow rate of chloroacetaldehyde solution is 1000 ml / min to 1500 ml / min, preferably 1260 ml / min. Cooling medium inlets and outlets are respectively opened at both ends of the cooling chamber 3 and the cooling channel 5. A temperature sensor 13 is provided inside the reaction chamber 1 to detect the temperature inside the reaction chamber. The cooling medium is a -10℃ ethylene glycol aqueous solution. The temperature sensor transmits the temperature inside the reaction chamber to the controller. When the temperature is greater than 30℃ or less than 25℃, the controller sends a command to the cooling medium metering pump to increase or decrease the flow rate of the metering pump, so that the temperature inside the reaction chamber is maintained at 25-30℃.

[0027] Through the above setup, the rotation of the helical blade 8 can form an axial piston flow, and the conical protrusion 7 can generate radial turbulence with localized vortices, enabling the two reaction liquids to mix uniformly. Simultaneously, the cooling medium flowing within the cooling chamber 3 and cooling channel 5 provides precise temperature control of the reaction chamber 1, stabilizing the reaction, reducing side reactions, and thus minimizing impurity formation. In the continuous flow reactor, sodium hydrosulfide solution and chloroacetaldehyde solution are precisely injected continuously. The reactor's unique design allows the materials to flow forward in a piston-like manner. Combined with different blade configurations, the high turbulence overcomes interfacial tension, achieving thorough mixing at the microscale. At this point, the kinetically superior product preferentially precipitates and rapidly separates from the system, while impurities dissolve into the mother liquor, thus inhibiting impurity precipitation from the system. Purification is achieved within the reactor, yielding a high-melting-point, high-purity dithiane product.

[0028] The first injection port 9 and the second injection port 10 are arranged symmetrically at 180° radially in the reaction chamber 1. Figure 1 This creates a counteracting effect between the two liquids, resulting in a uniform mixture. The conical protrusions 7 are arranged in multiple axial rows and staggered circumferentially on the stirring shaft 4. Figure 3 This allows for better generation of turbulence. A safety pressure relief valve 14 is installed at the top of the middle section of reaction chamber 1. Figure 2 This is to prevent pressure buildup from affecting production.

[0029] During production, a 10% chloroacetaldehyde solution is prepared in storage tank 1 and stirred thoroughly. The flow rate of metering pump 11 is adjusted to stabilize the flow rate at 1200 ml / min. A 30% sodium hydrosulfide solution is prepared in storage tank 2 and stirred thoroughly before use. The flow rate of metering pump 11 is adjusted to stabilize the flow rate at 400 ml / min. The tubular reactor is started, and the main shaft speed is adjusted to 400 rpm. Both materials are fed simultaneously, and the chamber temperature is controlled at 25–30°C. After a residence time of 5 minutes in the reactor, continuous discharge begins. The product is collected, filtered to obtain a white solid, washed with a small amount of water, and dried to obtain the final product. Yield: 95% Melting point: 142°C–143°C.

[0030] The embodiments described in this specific implementation are preferred embodiments of this application and are not intended to limit the scope of protection of this application. Identical components are represented by the same reference numerals. Therefore, all equivalent changes made to the structure, shape, and principle of this application should be covered within the scope of protection of this application.

Claims

1. A continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiane, comprising a cylindrical reaction chamber (1), characterized in that: A shell (2) is coaxially fixed to the outside of the reaction chamber (1), with a closed annular cooling chamber (3) in the middle. A stirring shaft (4) is coaxially connected to both ends of the shell (2) through bearings. The stirring shaft (4) passes through the shell (2) and the reaction chamber (1), and its interior is a hollow cooling channel (5). A drive motor (6) is connected to one side of the stirring shaft (4). Its outer wall is fixed with conical protrusions (7) and continuous spiral blades (8). The outer edge of the spiral blades (8) is clearance-fitted with the inner wall of the reaction chamber (1). The left end of the reaction chamber (1) is provided with a first inlet (9) and a second inlet (10). The two inlets penetrate independently from the outside of the shell (2) and connect to the inside of the reaction chamber (1). A metering pump (11) is independently connected to the outside of the inlet. The lower right end of the reaction chamber (1) is connected to an outlet (12). The cooling chamber (3) and the cooling channel (5) are respectively provided with a cooling medium inlet and a cooling medium outlet. A temperature sensor (13) is provided in the reaction chamber (1) to detect the temperature inside the reaction chamber.

2. The continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiane according to claim 1, characterized in that: The first injection port (9) and the second injection port (10) are arranged symmetrically in the radial direction of the reaction chamber (1) at 180°.

3. A continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiane according to claim 2, characterized in that: The conical protrusions (7) are arranged in multiple rows along the axis and staggered around the circumference on the stirring shaft (4).

4. A continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiane according to claim 3, characterized in that: A safety relief valve (14) is provided at the top of the middle section of the reaction chamber (1).

5. A continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiathane according to claim 4, characterized in that: The pitch of the helical blade (8) is 1.2 times the diameter of the reaction chamber (1), and the gap between its outer edge and the inner wall of the reaction chamber (1) is ≤1mm.

6. A continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiathane according to claim 5, characterized in that: The height of the conical protrusion (7) is 12% of the diameter of the reaction chamber (1).

7. A continuous turbulent tubular reactor for preparing 2,5-dihydroxy-1,4-dithiathane according to claim 6, characterized in that: The reaction chamber (1) is made of alloy HC-276.

Images