A photochemical reaction apparatus for producing dydrogesterone

Abstract

The application discloses a photochemical reaction device for producing dydrogesterone, which comprises a reaction body, an ultraviolet light source, light-transmitting glass, a raw material liquid storage tank and a reaction liquid pump, one side of the light-transmitting glass is sealingly arranged with one side of a reaction cavity, the ultraviolet light source is arranged on the other side of the light-transmitting glass to irradiate ultraviolet light to the reaction cavity; the reaction body is internally provided with the reaction cavity, the reaction body is provided with a liquid inlet and a liquid outlet which are communicated with the reaction cavity, the raw material liquid storage tank is connected with the liquid inlet so that the raw material liquid in the raw material liquid storage tank flows into the liquid inlet by gravity, the raw material liquid storage tank is arranged above the liquid inlet so as to control the pressure in the reaction cavity by controlling the height difference between the liquid level in the raw material liquid storage tank and the liquid inlet, and the liquid outlet is connected with the reaction liquid pump which is used for pumping out the reaction liquid in the reaction cavity. The application realizes industrialization amplification of a photochemical reaction step in a dydrogesterone production process and large-batch production of dydrogesterone.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmacy, in particular to a photochemical reaction device for producing dydrogesterone. BACKGROUND

[0002] Turning the C-10 position methyl of 5,7-diene steroid compound with β-methyl at C-10 position into α configuration generally includes two stages of photochemical reaction (as shown in the following formula): the first stage is ring opening under the irradiation of ultraviolet light in the wavelength range of 270-300 nm, and the second stage is ring closing under the irradiation of ultraviolet light in the wavelength range of 300-350 nm.

[0003]

[0004] In the synthesis process of dydrogesterone (as shown in the following formula), the synthesis of dydrogesterone intermediate needs to apply the photochemical reaction described above.

[0005]

[0006] A typical synthesis route of dydrogesterone is shown as follows, wherein the first step reaction is the photochemical reaction described above.

[0007]

[0008] The ultraviolet light source generally used in such photochemical reaction is LED ultraviolet lamp, high-pressure mercury lamp and the like, and the ultraviolet light is irradiated into the light-transmitting reactor for reaction. There are many problems to be solved in the industrialization of such photochemical reaction, so the photochemical reaction device in the prior art can only be used for small batch synthesis in the laboratory. For example, there is no generic drug of dydrogesterone in China for many years, and the photochemical reaction is one of the difficulties. SUMMARY

[0009] The technical problem to be solved by the present application is to overcome the deficiencies in the prior art, and to provide a photochemical reaction device suitable for industrial production of dydrogesterone.

[0010] In order to solve the above technical problems, the application discloses a photochemical reaction device for producing delmadinone, which comprises a reaction body, an ultraviolet light source, a light-transmitting glass, a raw material liquid storage tank and a reaction liquid pump, one side of the light-transmitting glass is sealingly arranged with one side of the reaction cavity, the ultraviolet light source is arranged on the other side of the light-transmitting glass to irradiate ultraviolet light to the reaction cavity; the reaction body is internally provided with the reaction cavity, the reaction body is provided with a liquid inlet and a liquid outlet which are communicated with the reaction cavity, the raw material liquid storage tank is connected with the liquid inlet so that the raw material liquid in the raw material liquid storage tank flows into the liquid inlet by gravity, the raw material liquid storage tank is arranged above the liquid inlet so as to control the pressure in the reaction cavity by controlling the height difference between the liquid level in the raw material liquid storage tank and the liquid inlet, and the liquid outlet is connected with the reaction liquid pump which is used for pumping out the reaction liquid in the reaction cavity.

[0011] Further, the reaction cavity is internally provided with an S-shaped flow channel for the meandering flow of the reaction liquid.

[0012] Further, the reaction cavity is sequentially provided with a plurality of partitions from the liquid inlet to the liquid outlet, the partitions are provided with liquid flow grooves, and the liquid flow grooves of adjacent two partitions are staggered.

[0013] Further, the two ends of the partition are connected to the two sides of the inner wall of the reaction cavity, and the liquid flow groove is arranged on one side of the partition and close to the inner wall of one side of the reaction cavity.

[0014] Further, the reaction body is provided with a light-transmitting glass mounting hole on one side of the reaction cavity, a sealing ring is mounted between the light-transmitting glass and the bottom of the light-transmitting glass mounting hole, the light-transmitting glass is press-bonded in the light-transmitting glass mounting hole through a detachable pressing plate, and the pressing plate is provided with a light-transmitting hole corresponding to the ultraviolet light source.

[0015] Further, the ultraviolet light source is detachably mounted on the pressing plate, the ultraviolet light source comprises an ultraviolet lamp and an ultraviolet lamp mounting plate, and the ultraviolet lamp is uniformly distributed on one side of the ultraviolet lamp mounting plate.

[0016] Further, the thickness of the reaction cavity is 1.5-3 cm.

[0017] Further, the two sides of the reaction cavity are throughly arranged, and the ultraviolet light source and the light-transmitting glass are arranged on the two sides of the reaction cavity.

[0018] Further, the light-transmitting glass adopts quartz glass, and the thickness of the light-transmitting glass is 5-7 mm.

[0019] Further, the height difference between the liquid level of the raw material liquid storage tank and the liquid inlet is controlled to be 1.5-2.5 m, or the fluid pressure in the reaction cavity 11 is controlled to be below 0.35 atm.

[0020] Compared with the prior art, the present application has the advantages of:

[0021] The present application realizes the process of transporting and photochemical reaction simultaneously by the process that the reaction raw material liquid flows in the reaction cavity and the ultraviolet light irradiates into the transparent reactor for reaction. By adopting the split design of transparent glass + reaction body, and by controlling the height difference between the liquid level of the raw material liquid storage tank and the liquid inlet, the raw material liquid flows into the liquid inlet by gravity, and a reaction liquid pump is arranged at the liquid outlet to control the pressure in the reaction cavity, so that the problem of breakage of the transparent glass during the reaction process which does not occur in the laboratory research stage is solved. By designing the thickness of the transparent glass and the thickness of the reaction cavity, the utilization rate of the light source is improved, and the cost and energy consumption of the LED light source are greatly reduced. Thus, the industrialization and mass production of reactions such as dienogest which need ultraviolet light irradiation are realized, thereby facilitating the industrialization and application. BRIEF DESCRIPTION OF DRAWINGS

[0022] The accompanying drawings, which form a part of this application, are included to provide a further understanding of the application and are incorporated in and constitute a part of this specification. The illustrations are shown to explain the present application and are not intended to be an improper limitation to the present application. In the drawings:

[0023] Figure 1 The front view schematic diagram of the photochemical reaction device for producing dienogest disclosed in the embodiments of the present application (the ultraviolet light source and the transparent glass are hidden);

[0024] Figure 2 The A-A sectional view schematic diagram (after rotating 90 degrees to the left) of Figure 1

[0025] LEGEND KEY:

[0026] 1, reaction body; 11, reaction cavity; 12, partition; 13, liquid flow tank; 14, transparent glass mounting hole; 15, limiting groove; 2, ultraviolet light source; 21, ultraviolet lamp; 22, ultraviolet lamp mounting plate; 3, transparent glass; 4, liquid inlet; 5, liquid outlet; 6, sealing ring; 7, pressing plate; 71, transparent hole; 8, S-shaped conveying path; 9, raw material liquid storage tank; 10, reaction liquid pump. DETAILED DESCRIPTION

[0027] In order to facilitate the understanding of the present application, the present application will be described more fully below with reference to the accompanying drawings and preferred embodiments, but the scope of protection of the present application is not limited to the following specific embodiments.

[0028] As Figures 1-2 ​As shown, the embodiment of the present application discloses a photochemical reaction device for producing dydrogesterone, which comprises a reaction body 1, an ultraviolet light source 2, a light-transmitting glass 3, a raw material liquid storage tank 9 and a reaction liquid pump 10. The reaction body 1 is a square structure made of aluminum. The reaction body 1 is provided with a reaction cavity 11, and the reaction body 1 is provided with a liquid inlet 4 and a liquid outlet 5 which communicate with the reaction cavity 11. The liquid inlet 4 is arranged below one side of the reaction body 1 and is connected with the raw material liquid storage tank 9, and the liquid outlet 5 is arranged above the other side of the reaction body 1 (for example Figure 1 ). One side of the light-transmitting glass 3 is sealingly arranged with one side of the reaction cavity 11, and the ultraviolet light source 2 is arranged on the other side of the light-transmitting glass 3 to irradiate ultraviolet light to the reaction cavity (for example Figure 2 ). Thus, the raw material liquid flows in the reaction cavity 11, and the reaction is carried out in the light-transmitting reactor by irradiation of ultraviolet light, so that the process of photochemical reaction while conveying is realized.

[0029] In order to realize the industrialization amplification of the photochemical reaction step in the dydrogesterone synthesis process and the mass production of dydrogesterone, and facilitate the industrialization popularization and application, a number of problems are faced, such as the problem of breakage in the reaction process caused by the amplification of the light-transmitting glass, and the problem of difficult improvement of the light source efficiency after amplification, etc. Therefore, in the embodiment, the light-transmitting glass 3 is preferably made of quartz glass, which can transmit the required wavelength of ultraviolet light, has high transmittance of ultraviolet light and small light loss. However, the quartz glass is relatively brittle (in the embodiment, the light-transmitting glass 3 is used as the cover plate of the reaction device, especially when the area is large, such as the glass size of 600mm*200mm*6mm, the fluid pressure is greater than 0.5atm, and breakage will occur, and the device can be stably operated under the pressure of 0.3atm). It is found through research that, during the synthesis reaction, the liquid in the reaction cavity 11 is controlled to maintain a low pressure (for example, below 0.35atm), so that the glass breakage can be avoided. The raw material liquid can flow into the liquid inlet 4 from the raw material liquid storage tank 9 on the top by gravity, the reaction liquid pump 10 is arranged at the liquid outlet 5 to extract the reaction liquid, and the height difference between the liquid level of the raw material liquid storage tank 9 and the liquid inlet 4 is controlled to be in the range of 1.5-2.5m, so that the pressure of the raw material liquid at the liquid inlet 4 is maintained at a low level, the device is stably operated, and the flow and sufficient reaction of the raw material liquid are not affected. If the reaction liquid pump 10 is arranged between the liquid inlet 4 and the raw material liquid storage tank 9, the glass breakage is easily caused.

[0030] At the same time, considering the brittleness and light transmittance of the light-transmitting glass 3 (high light transmittance requires thinner glass, but the glass is more brittle), the thickness of the light-transmitting glass 3 is preferably 5-7mm. In this way, the operation stability of the reaction device is ensured, and the utilization rate of the light source is improved.

[0031] Through extensive experimental research, the thickness of the reaction chamber 11 (the distance between the inner wall of the transparent glass 3 and the reaction body 1) is preferably 1.5-2 cm. This ensures that the reaction liquid in the entire reaction chamber 11 is fully irradiated by ultraviolet light, while minimizing heat loss from the conversion of ultraviolet light into heat, thus maximizing the utilization rate of the light source. If the thickness is too large, the internal liquid will not be sufficiently irradiated by light, and the flow rate of the reaction liquid will be slowed down, which is not conducive to a complete reaction. If the thickness is too small, the ultraviolet light will not be fully utilized, and the single-batch yield will be too low.

[0032] In this embodiment, as Figure 1 To maximize the liquid flow path length within the limited length of the reaction chamber 11, thereby ensuring a more complete reaction and increasing yield, an S-shaped flow channel is provided within the reaction chamber 11 for the tortuous flow of the reaction liquid. Specifically, the S-shaped flow channel is formed as follows: multiple baffles 12 are evenly spaced along the direction from the inlet 4 to the outlet 5 of the reaction chamber 11. The baffles 12 divide the reaction chamber into sub-cavities, and liquid flow channels 13 are provided on the baffles 12. The liquid flow channels 13 on adjacent baffles 12 are staggered, thus creating an overall S-shaped liquid transport path 8. Compared to traditional straight flow, the flow path is significantly longer, and it also facilitates the formation of turbulence in the liquid, promoting a more complete reaction.

[0033] In this embodiment, as Figure 1 To accommodate the transparent glass 3, a transparent glass mounting hole 14 is provided on one side of the reaction body 1 located in the reaction chamber 11. The transparent glass mounting hole 14 is a countersunk hole structure, and a sealing ring 6 is installed between the transparent glass 3 and the bottom of the transparent glass mounting hole 14. Figure 2 To securely install the sealing ring 6, a limiting groove 15 is provided at the bottom of the transparent glass mounting hole 14 for limiting the sealing ring 6, thus achieving a sealing effect. The transparent glass 3 is pressed into the transparent glass mounting hole 14 by a detachable pressure plate 7, specifically by bolt connection. The sealing ring 6 also prevents the transparent glass 3 from being cracked by the pressure plate 7. The pressure plate 7 is provided with a light-transmitting hole 71 corresponding to the ultraviolet light source 2, facilitating the transmission of ultraviolet light. The combination of transparent glass 3 + sealing ring 6 + metal reaction body 1 also avoids the fragility problem of using a hollow rectangular glass reactor.

[0034] In this embodiment, the ultraviolet light source 2 is detachably mounted on the pressure plate 7. The ultraviolet light source 2 includes an ultraviolet lamp 21 and an ultraviolet lamp mounting plate 22. The ultraviolet lamp 21 is an evenly distributed row of LED lamps, which are evenly distributed in the countersunk holes on one side of the ultraviolet lamp mounting plate 22.

[0035] For the process of synthesizing dydrogesterone, the photochemical reaction step is divided into two stages, the first stage is carried out under the irradiation of ultraviolet light with a wavelength of 270-300 nm, and the second stage is carried out under the irradiation of ultraviolet light with a wavelength of 300-350 nm. During the reaction process, the ultraviolet light source 2 can be switched to achieve the purpose.

[0036] In this embodiment, in order to improve the reaction efficiency, the reaction cavity 11 is provided with a through hole on both sides (for example, Figure 2 ), and the ultraviolet light source 2 and the light-transmitting glass 3 are arranged on both sides of the reaction cavity 11, so that the liquid in the reaction cavity 11 can be irradiated from both sides at the same time. Compared with single-side irradiation, the light irradiation of the reaction liquid at different positions is more uniform, and the synthesis efficiency is significantly improved. At this time, the thickness of the reaction cavity 11 (the distance between the light-transmitting glass 3 and the inner wall of the reaction body 1) is preferably 2-3 cm.

[0037] In this embodiment, considering that the thickness of the partition plate 12 is relatively thin, in order to facilitate processing and prevent the partition plate 12 from deforming during milling processing, the two ends of the partition plate 12 are connected to the upper and lower sides of the inner wall of the reaction cavity 11 (for example, Figure 2 Figure 2 ), so that both ends are connected with the reaction body 1, and a cantilever-like structure is not formed (which is more serious when the reaction cavity 11 is provided with a through hole on both sides). At this time, the liquid flow groove 13 is arranged on one side of the partition plate 12 and close to the inner wall on one side of the reaction cavity 11.

[0038] In this embodiment, the photochemical reaction device can be enlarged to (500-1000) mm* (150-350) mm (calculated based on the size of the light-transmitting glass 3). And multiple reaction devices can be connected in parallel to realize industrialized scale production.

[0039] Although the present application has been disclosed with reference to the preferred embodiments above, it is not intended to limit the present application. Any person skilled in the art can make many possible changes and modifications to the technical solutions disclosed above, or modify equivalent embodiments with equivalent changes, without departing from the scope of the technical solutions of the present application. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present application, without departing from the content of the technical solutions of the present application, shall fall within the scope of protection of the technical solutions of the present application.

Claims

1. A photochemical reaction apparatus for producing dydrogesterone, characterized by comprising: The application relates to a reaction device for preparing organic compound by ultraviolet irradiation, which comprises a reaction body (1), an ultraviolet light source (2), a light-transmitting glass (3), a raw material liquid storage tank (9) and a reaction liquid pump (10), the reaction body (1) is internally provided with a reaction cavity (11), one side of the light-transmitting glass (3) is sealingly arranged on one side of the reaction cavity (11), the ultraviolet light source (2) is arranged on the other side of the light-transmitting glass (3) to irradiate the reaction cavity (11) with ultraviolet light; the reaction body (1) is provided with a liquid inlet (4) and a liquid outlet (5) which are connected with the reaction cavity (11), the raw material liquid storage tank (9) is connected with the liquid inlet (4) so that the raw material liquid in the raw material liquid storage tank (9) flows into the liquid inlet (4) by gravity, the raw material liquid storage tank (9) is arranged above the liquid inlet (4) to control the pressure in the reaction cavity (11) by controlling the height difference between the liquid level in the raw material liquid storage tank (9) and the liquid inlet (4), the liquid outlet (5) is connected with the reaction liquid pump (10) for pumping out the reaction liquid in the reaction cavity (11), the light-transmitting glass (3) is quartz glass; the thickness of the reaction cavity (11) is 1.5-3 cm; the reaction cavity (11) is provided with through holes on two sides, and the ultraviolet light source (2) and the light-transmitting glass (3) are arranged on the two sides of the reaction cavity (11); the thickness of the light-transmitting glass (3) is 5-7 mm; the height difference between the liquid level in the raw material liquid storage tank (9) and the liquid inlet (4) is controlled to be 1.5-2.5 m, or the fluid pressure in the reaction cavity (11) is controlled to be below 0.35 atm.

2. The photochemical reaction apparatus for producing dydrogesterone according to claim 1, wherein The reaction cavity (11) is provided with an S-shaped flow channel for the meandering flow of the reaction liquid.

3. The photochemical reaction apparatus for producing dydrogesterone according to claim 2, wherein The reaction cavity (11) is sequentially provided with a plurality of baffle plates (12) from the liquid inlet (4) to the liquid outlet (5), the baffle plates (12) are provided with liquid flow grooves (13), and the liquid flow grooves (13) of adjacent two baffle plates (12) are arranged alternately.

4. The photochemical reaction apparatus for producing dydrogesterone according to claim 3, wherein The two ends of the baffle plate (12) are connected to the two sides of the inner wall of the reaction cavity (11), and the liquid flow groove (13) is arranged on one side of the baffle plate (12) and close to the inner wall of one side of the reaction cavity (11).

5. The photochemical reaction apparatus for producing dydrogesterone according to any one of claims 1 to 4, characterized by The reaction body (1) is provided with a light-transmitting glass mounting hole (14) on one side of the reaction cavity (11), a sealing ring (6) is arranged between the light-transmitting glass (3) and the bottom of the light-transmitting glass mounting hole (14), the light-transmitting glass (3) is press-connected in the light-transmitting glass mounting hole (14) through a detachable pressing plate (7), and the pressing plate (7) is provided with a light-transmitting hole (71) corresponding to the ultraviolet light source (2).

6. The photochemical reaction apparatus for producing dydrogesterone according to claim 5, wherein The ultraviolet light source (2) is detachably mounted on the pressing plate (7), and the ultraviolet light source (2) comprises an ultraviolet lamp (21) and an ultraviolet lamp mounting plate (22), and the ultraviolet light source (2) is uniformly arranged on one side of the ultraviolet lamp mounting plate (22).

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