Process and apparatus for the continuous synthesis of 4-methyl-5-thiazole ethanol based on flow chemistry

Abstract

The present application relates to the technical fields of chemical synthesis, and particularly relates to a 4-methyl-5-thiazole ethanol continuous synthesis device based on flow chemistry, comprising: a liquid feeding module, used for containing and respectively pumping reaction liquid and oxidizing liquid; a micro-reaction module, arranged at the rear end of the liquid feeding module, used for receiving the reaction liquid and the oxidizing liquid delivered by the liquid feeding module, comprising a mixing plate and a reaction plate group, the mixing plate is communicated with the liquid feeding module through a reaction liquid pipe and an oxidizing liquid pipe, the mixing plate has a mixing main cavity and a lateral ring cavity, the two ends of the mixing main cavity have a first liquid inlet and a liquid outlet, and the lateral ring cavity is arranged at intervals around the mixing main cavity; and a collection module, arranged at the rear end of the micro-reaction module, used for receiving the product output by the micro-reaction module. The 4-methyl-5-thiazole ethanol continuous synthesis device based on flow chemistry provided by the present application organically integrates key processes such as liquid feeding, micro-reaction and collection through special equipment, realizes continuous production from feeding to discharging, and has good application value.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, and in particular to a continuous synthesis method and apparatus for 4-methyl-5-thiazolylethanol based on flow chemistry. Background Technology

[0002] 4-Methyl-5-thiazolylethanol (CAS No.: 137-00-8) is an extremely important thiazole flavor compound. It exhibits a strong meaty and nutty aroma and is widely used in the synthesis of meat flavorings, seasonings, instant noodle seasonings, pet food additives, and pharmaceutical intermediates (such as vitamin B1 and thiamine). The market demand is huge and continues to grow.

[0003] Currently, most publicly reported synthetic routes for 4-methyl-5-thiazolylethanol in industry and academia use 2-mercapto-4-methyl-5-thiazolylethanol (hereinafter referred to as "mercapto precursor") as a key intermediate. The final synthetic steps all involve the oxidative desulfurization of this mercapto group to generate the target thiazole ring. In this oxidation step, hydrogen peroxide is considered the most ideal and commonly used oxidant due to its low cost, lack of salt residue after reaction, and relatively environmentally friendly properties.

[0004] However, almost all existing and publicly disclosed technologies using hydrogen peroxide oxidation are based on traditional batch reactors. Through in-depth analysis and industrial practice, this traditional process suffers from the following inherent defects and major technical problems that are difficult to overcome: 1. Intense exothermic effect and serious safety hazards The oxidation of thiol groups by hydrogen peroxide is a violently exothermic reaction. In batch reactors, a high-concentration hydrogen peroxide solution needs to be slowly added dropwise to the reaction solution containing the thiol precursor. This dropwise addition process is highly susceptible to localized overheating. The instantaneous high concentration of hydrogen peroxide in localized areas leads to accelerated decomposition, further exacerbating the exothermic reaction and creating a vicious cycle of "exothermic-decomposition-re-exothermic," resulting in the so-called "runaway temperature phenomenon." Runaway temperature causes a rapid spike in the temperature and pressure of the reaction system, making it difficult to control. This not only causes the decomposition of the target product and a decrease in yield but can also trigger material overflow or even explosions, leading to serious safety accidents. This makes the production process extremely dangerous, placing extremely stringent requirements on the reactor's cooling system, safety pressure relief system, and the explosion-proof rating of the plant, significantly increasing equipment investment and operating costs.

[0005] 2. Low mass and heat transfer efficiency leads to unsatisfactory product selectivity and yield. Traditional reactors rely on mechanical stirring for mixing, but their mixing efficiency is limited by factors such as the type of impeller, rotation speed, and reactor size, resulting in macroscopic mixing. For reagents like hydrogen peroxide that require instantaneous uniform dispersion, the macroscopic mixing rate is much slower than the chemical reaction rate, leading to severe uneven concentration distribution within the reactor. Excess hydrogen peroxide in localized areas can cause side reactions such as over-oxidation, including ring-opening of thiazole rings and oxidation of ethanol side chains into aldehydes or carboxylic acids, generating various structurally complex byproducts. Excess thiol precursors in other localized areas may lead to dimerization and disulfide bond formation. These side reactions directly result in a significant reduction in reaction selectivity.

[0006] 3. Poor process controllability, resulting in large batch-to-batch variations in product quality. Batch processes are highly dependent on operator experience. Even minute fluctuations in parameters such as dripping rate, cooling water temperature, and stirring efficiency can directly affect the reaction process and the final result. This dependence leads to poor reproducibility of product quality (purity, color, aroma intensity) between different production batches, making it difficult to achieve standardized and stable high-quality production and meet the stringent requirements of the high-end fragrance market for product consistency.

[0007] Existing hydrogen peroxide oxidation technology, based on batch reactors, suffers from inherent fatal flaws such as high safety risks, poor selectivity, low efficiency, and poor controllability, severely hindering the high-quality, large-scale, and safe production of 4-methyl-5-thiazolylethanol, an important fragrance. Therefore, there is an urgent need in this field for a novel synthetic system capable of addressing these problems. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide a continuous synthesis method and apparatus for 4-methyl-5-thiazolidineethanol based on flow chemistry, which solves the problems of high risk, poor selectivity, low efficiency and poor controllability in the existing synthesis process of 2-mercapto-4-methyl-5-thiazolidineethanol.

[0009] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is: a continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry, comprising: The infusion module is used to contain and pump the reaction solution and oxidation solution separately. The micro-reaction module, located at the rear end of the infusion module, receives the reaction solution and oxidizing solution delivered by the infusion module. It includes a mixing plate and a reaction plate assembly. The mixing plate is connected to the infusion module through reaction solution pipes and oxidizing solution pipes. The mixing plate has a main mixing chamber and a lateral annular chamber. The two ends of the main mixing chamber have a first inlet and an outlet. The lateral annular chambers are spaced around the main mixing chamber and are connected to a second inlet located on the side wall of the main mixing chamber. The reaction solution pipe is connected to the first inlet, the oxidizing solution pipe is connected to the second inlet, and the reaction plate assembly is connected to the outlet. The oxidizing solution enters the main mixing chamber in segments through the lateral annular chambers. The collection module, located at the rear end of the microreaction module, is used to receive the products output by the microreaction module.

[0010] In one embodiment, the mixing plate also has a cooling chamber, which is disposed between the main mixing chamber and the lateral annular chamber. The lateral annular chamber is connected to the second liquid inlet through an inclined channel.

[0011] In one embodiment, a partition wall is provided inside the cooling chamber, and the partition wall is located between the lateral annular cavities. The partition wall divides the cooling chamber into multiple independent sealed cavities, and each cooling cavity is provided with a cooling medium inlet and outlet pipe.

[0012] In one embodiment, a shrinkage ring wall is provided in the mixing main chamber. The shrinkage ring wall extends towards the side near the liquid outlet while the diameter of the shrinkage ring wall gradually shrinks. The shrinkage ring wall is located at the rear end of the second liquid inlet.

[0013] In one embodiment, the reaction plate assembly includes a first reaction plate and a second reaction plate. The first reaction plate is provided with a serpentine reaction channel and pressure regulating components spaced at the corners of the serpentine reaction channel. The pressure regulating components are used to buffer and regulate the pressure of the mixed liquid in the serpentine reaction channel. One end of the serpentine reaction channel is connected to the liquid outlet, and the other end of the serpentine reaction channel is connected to the collection module.

[0014] In one embodiment, the pressure regulating assembly includes a pressure regulating chamber, a first regulating diaphragm, a second regulating diaphragm, and a gas supply pipe. The pressure regulating chamber extends from the first reaction plate to the second reaction plate and is embedded at the corner of the serpentine reaction channel. The mixed liquid in the serpentine reaction channel enters through an inflow arc located at the bottom of the pressure regulating chamber and flows out through an outflow arc located in the middle of the pressure regulating chamber. The first regulating diaphragm is disposed in the pressure regulating chamber located within the first reaction plate and is disposed above the outflow arc. The second regulating diaphragm is disposed in the pressure regulating chamber located within the second reaction plate. A buffer gas chamber is formed between the first regulating diaphragm and the second regulating diaphragm. The gas supply pipe enters from the side wall of the second reaction plate and communicates with the buffer gas chamber. The gas supply pipe is connected to an external gas supply device.

[0015] In one embodiment, the pressure regulating assembly further includes a liquid supply pipe, the second regulating diaphragm and the top of the pressure regulating chamber form a liquid regulating chamber, the liquid supply pipe enters from the top of the second reaction plate and communicates with the liquid regulating chamber, and the liquid supply pipe is connected to an external liquid supply device.

[0016] In one embodiment, a heat exchange platform is provided in the pressure regulating cavity, extending upward from the bottom of the pressure regulating cavity, and there is a gap between the heat exchange platform and the first regulating diaphragm; a heat exchange channel is provided in the first reaction plate, the heat exchange channel is arranged corresponding to the serpentine reaction channel, and the part of the heat exchange channel corresponding to the heat exchange platform forms a heat exchange spiral from top to bottom in the heat exchange platform.

[0017] A continuous synthesis method employing any of the above-described flow chemistry-based continuous synthesis apparatuses for 4-methyl-5-thiazolyl ethanol comprises the following steps: S1. The 2-mercapto-4-methyl-5-thiazol ethanol reaction solution with pH adjusted to 2.0-4.0 and the 20%-35% (w / w) hydrogen peroxide oxidizing solution are respectively introduced into the infusion module; S2. The infusion module pumps the reaction solution into the mixing main chamber through the first inlet, and pumps the oxidizing solution into the lateral annular chamber. The oxidizing solution is then input into the mixing main chamber in sections through the second inlet. The oxidizing solution and the reaction solution are fully mixed in the mixing main chamber to form a mixed solution before entering the reaction plate assembly. S3. The mixture is reacted fully in the reaction plate assembly at 20℃~40℃ and 0.2~1.0MPa to obtain a product solution. The obtained product solution is collected through the collection module, and then extracted, dried, filtered and rotary evaporated to obtain 4-methyl-5-thiazolylethanol.

[0018] In one embodiment, in step S3, the mixture undergoes a three-stage reaction in the reaction plate assembly, with the temperature of the first stage being 20°C to 25°C, and the temperatures of the second and third stages being 25°C to 40°C.

[0019] The beneficial effects of this invention are as follows: 1. The continuous synthesis device for 4-methyl-5-thiazolidineethanol based on flow chemistry provided by this invention organically integrates key processes such as liquid delivery, micro-reaction and collection through special equipment, realizing continuous production from feeding to discharging, and effectively solving the problems of dispersed equipment, low operating efficiency and safety hazards such as overheating in traditional batch reactor processes.

[0020] 2. The micro-reaction module used in the continuous synthesis device of 4-methyl-5-thiazolidineethanol based on flow chemistry provided by the present invention has a mixing main chamber and a side ring chamber. Combined with the double-layer membrane pressure regulating component set at the corner, the oxidation liquid is injected in stages and the pressure is precisely controlled continuously in the same device, which ensures that the reaction liquid is fully mixed and the pressure fluctuation is minimal, which greatly improves the reaction selectivity and system stability.

[0021] 3. The continuous synthesis method provided by this invention can efficiently convert thiol precursors into 4-methyl-5-thiazolethanol products. The reaction process is highly controllable through precise control of reaction parameters. At the same time, the generation of side reactions and the online inventory of hazardous materials are reduced through segmented temperature control and pressure buffering. It has both economic and safety benefits and has good application value.

[0022] 4. The 4-methyl-5-thiazol ethanol product prepared by this invention has high purity and good batch-to-batch quality consistency, which can meet the application needs of high-end fragrance and pharmaceutical intermediate fields. It solves the problem of large product quality fluctuations in traditional processes. At the same time, the production process is stable and reliable, and has good prospects for industrial promotion.

[0023] Other features and beneficial effects of the invention will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the invention. The objects of the invention and other beneficial effects may be realized and obtained by means of the structures and / or components pointed out in the description and claims. Attached Figure Description

[0024] Figure 1 This is an overall structural diagram of an embodiment of the present invention; Figure 2 A three-dimensional schematic diagram of a micro-reaction module in one embodiment of the invention; Figure 3 A top view of a micro-reaction module in one embodiment of the invention; Figure 4 for Figure 3 Cross-sectional view at point AA; Figure 5 for Figure 4 A magnified view of a section at point I; Figure 6 for Figure 3 Cross-sectional view at point BB; Figure 7 for Figure 6 Enlarged view of a section at point II; Figure 8 A front view of a micro-reaction module in one embodiment of the invention; Figure 9 for Figure 8 Cross-sectional view at point C; Figure 10 for Figure 8 Cross-sectional view at point DD.

[0025] Label Explanation: 1. Infusion module; 11. Reaction liquid pipe; 12. Oxidation liquid pipe; 2. Micro-reaction module; 21. Mixing plate; 211. Main mixing chamber; 212. Lateral annular chamber; 213. Cooling chamber; 214. First inlet; 215. Second inlet; 216. Outlet; 217. Partition wall; 218. Contraction annular wall; 22. Reaction plate assembly; 221. First reaction plate; 2211. Serpentine reaction channel; 2212. Heat exchange channel; 222. Second reaction plate; 223. Pressure regulating assembly; 2231. Pressure regulating chamber; 2232. First regulating diaphragm; 2233. Second regulating diaphragm; 2234. Gas supply pipe; 2235. Liquid supply pipe; 2236. Heat exchange guide platform; 2237. Heat exchange spiral; 3. Collection module. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments. The technical features designed in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] In the description of this invention, it should be noted that all terms used in this invention (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains, and should not be construed as limiting the invention; it should be further understood that the terms used in this invention should be understood to have the same meaning as those in the context of this specification and in the relevant field, and should not be understood in an idealized or overly formal sense, except as expressly defined in this invention.

[0028] like Figures 1 to 10 As shown, a continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry includes: Infusion module 1 is used to contain and pump the reaction solution and oxidation solution separately; The micro-reaction module 2, located at the rear end of the infusion module 1, is used to receive the reaction liquid and oxidizing liquid delivered by the infusion module 1. It includes a mixing plate 21 and a reaction plate assembly 22. The mixing plate 21 is connected to the infusion module 1 through the reaction liquid pipe 11 and the oxidizing liquid pipe 12. The mixing plate 21 has a main mixing chamber 211 and a lateral annular chamber 212. The two ends of the main mixing chamber 211 have a first inlet 214 and an outlet 216. The lateral annular chamber 212 is arranged around the main mixing chamber 211 at intervals and is connected to a second inlet 215 opened on the side wall of the main mixing chamber 211. The reaction liquid pipe 11 is connected to the first inlet 214, the oxidizing liquid pipe 12 is connected to the second inlet 215, and the reaction plate assembly 22 is connected to the outlet 216. The oxidizing liquid enters the main mixing chamber 211 in segments through the lateral annular chamber 212. Collection module 3 is located at the rear end of micro-reaction module 2 and is used to receive the products output by micro-reaction module 2.

[0029] Specifically, three lateral annular cavities 212 are provided, and the flow ratio of the lateral annular cavities 212 from front to back along the flow direction of the lateral annular cavities 212 is 0.2~0.3:0.4~0.6:0.1~0.4.

[0030] Specifically, a distribution valve is provided between the oxidizing liquid pipe 12 and the side annular cavity 212. The distribution valve distributes the oxidizing liquid into liquid streams according to a preset ratio, so that liquid streams of different flow rates enter the corresponding side annular cavity 212.

[0031] Since the oxidation of the thiol precursor by hydrogen peroxide is a violently exothermic reaction, local hot spots are easily generated during mixing. Furthermore, the oxidizing solution needs to be injected in stages through the lateral annular cavity 212 to control the reaction rate, requiring extremely high temperature control in the mixing area. Therefore, in this embodiment, the mixing plate 21 also includes a cooling chamber 213, located between the main mixing chamber 211 and the lateral annular cavity 212. The lateral annular cavity 212 is connected to the second inlet 215 via an inclined channel. This arrangement allows the cooling chamber 213 to be located close to both the main mixing chamber 211 and the lateral annular cavity 212, thereby removing the heat of reaction immediately and effectively preventing runaway thermal decomposition of hydrogen peroxide due to localized overheating during the mixing stage. Simultaneously, the cooling chamber 213 physically isolates the main mixing chamber 211 and the lateral annular cavity 212, preventing the exothermic heat from being conducted to the lateral annular cavity 212, avoiding heat accumulation, preventing premature heating of the hydrogen peroxide, and ensuring temperature stability during the mixing process. Furthermore, the inclined channel reduces the resistance of fluid entering the mixing main chamber 211 and optimizes the injection jet angle, promoting rapid turbulent mixing of the oxidant and the reaction liquid, thereby significantly improving mixing efficiency, reaction selectivity, and inherent process safety. Since the oxidizing solution needs to be injected in stages through the lateral annular cavity 212, each stage requires a lower temperature in the initial stage of the mixing reaction to suppress side reactions. However, a single cooling circuit cannot achieve differentiated and precise temperature control to match the staged injection. Therefore, in this embodiment, a partition wall 217 is provided inside the cooling cavity 213. The partition wall 217 is located between the lateral annular cavities 212, dividing the cooling cavity 213 into multiple independent sealed cavities. Each cooling cavity 213 is equipped with a cooling medium inlet and outlet pipe. This arrangement allows each cooling cavity 213 to independently adjust the temperature or flow rate of the cooling medium, achieving staged precise temperature control. This ensures that each stage receives sufficient heat exchange after injection, effectively preventing uncontrolled hydrogen peroxide decomposition and side reaction formation caused by local overheating, and significantly improving the safety of the reaction and the purity of the product.

[0032] In this embodiment, a contraction ring wall 218 is provided inside the mixing main cavity 211. The contraction ring wall 218 extends towards the side near the liquid outlet 216, and its diameter gradually narrows. The contraction ring wall 218 is located at the rear end of the second liquid inlet 215. After setting the contraction ring wall 218, the cross-sectional area of ​​the channel is reduced and the flow velocity is significantly increased when the mixed solution flows through the contraction ring wall 218. The resulting high shear force further enhances the turbulent mixing effect of the liquid and liquid phases, ensuring that the oxidizing liquid and the reaction liquid are uniformly dispersed before entering the reaction plate group 22. This effectively suppresses the side reactions caused by local overheating, and the local resistance barrier formed by the contraction structure blocks the backflow path of the reaction liquid, improving the stability and inherent safety of the feeding system.

[0033] During the reaction, the vaporization of low-boiling-point solvents under localized temperature conditions can cause system pressure fluctuations, affecting reaction stability. Traditional flow chemistry systems typically use external back pressure valves for pressure control; however, the connecting pipeline between the reactor and the back pressure valve has dead volume, which can easily lead to "post-reactions" at the outlet, affecting product purity. Therefore, in this embodiment, the reaction plate assembly 22 includes a first reaction plate 221 and a second reaction plate 222. The first reaction plate 221 contains a serpentine reaction channel 2211 and pressure regulating components 223 spaced at the corners of the serpentine reaction channel 2211. The pressure regulating components 223 buffer and regulate the pressure of the mixed liquid within the serpentine reaction channel 2211. One end of the serpentine reaction channel 2211 is connected to the outlet 216, and the other end is connected to the collection module 3. This configuration integrates the pressure control function directly into the reaction plate assembly 22, eliminating dead volume, preventing secondary reactions of the product, and ensuring the stability of product purity. At the same time, the pressure regulating component 223 can effectively absorb pumping pulsations and trace gas volume changes, significantly reducing system pressure fluctuations and improving the controllability and safety of the reaction process.

[0034] Specifically, the pressure regulating component 223 is located on one side of the serpentine reaction channel 2211.

[0035] In this embodiment, the pressure regulating assembly 223 includes a pressure regulating chamber 2231, a first regulating diaphragm 2232, a second regulating diaphragm 2233, and a gas supply pipe 2234. The pressure regulating chamber 2231 extends from the first reaction plate 221 to the second reaction plate 222 and is embedded at the corner of the serpentine reaction channel 2211. The mixed liquid in the serpentine reaction channel 2211 enters through the inflow arc located at the bottom of the pressure regulating chamber 2231 and exits through the outflow arc located in the middle of the pressure regulating chamber 2231. The flow path is as follows: A first regulating diaphragm 2232 is disposed in the pressure regulating chamber 2231 located within the first reaction plate 221 and positioned above the outflow arc; a second regulating diaphragm 2233 is disposed in the pressure regulating chamber 2231 located within the second reaction plate 222; a buffer gas chamber is formed between the first regulating diaphragm 2232 and the second regulating diaphragm 2233; a gas supply pipe 2234 enters from the side wall of the second reaction plate 222 and communicates with the buffer gas chamber; the gas supply pipe 2234 is connected to an external gas supply device. This configuration allows the pressure regulating component 223 to precisely adjust the pressure within the buffer gas chamber via an external gas supply device, thereby transmitting the pressure to the reaction liquid through the double-layer diaphragm to achieve precise back pressure control. Simultaneously, the buffer gas chamber effectively absorbs flow pulsations generated by the metering pump and volume changes of trace amounts of gas generated in the reaction, thus providing a buffering and damping effect.

[0036] Preferably, an inert gas is filled into the buffer gas chamber, thereby forming a gas seal while regulating the pressure. When the first regulating diaphragm 2232 ruptures, it can isolate the pressure regulating chamber 2231 and prevent leakage of the reaction liquid.

[0037] Because the gas medium is compressible, there may be response lag or pressure fluctuations during pressure regulation, making it difficult to meet the requirements of high-precision back pressure control. Therefore, in this embodiment, the pressure regulation component 223 also includes a liquid supply pipe 2235. The second regulating diaphragm 2233 and the top of the pressure regulation chamber 2231 form a liquid regulation chamber. The liquid supply pipe 2235 enters from the top of the second reaction plate 222 and communicates with the liquid regulation chamber. The liquid supply pipe 2235 is connected to an external liquid supply device. This configuration allows the external liquid supply device to apply pressure to the second regulating diaphragm 2233 through an incompressible liquid medium. After coupling through the buffer gas chamber, the pressure is transmitted to the first regulating diaphragm 2232 and the reaction liquid, achieving precise regulation and stable maintenance of back pressure. Furthermore, the liquid regulation chamber and the buffer gas chamber below work together to form a dual regulation of "hydraulic drive and pneumatic buffering," which combines pressure control speed and appropriate buffering capacity, further controlling the overall pressure fluctuation of the micro-reaction module 2 to an extremely low range, effectively improving the controllability, repeatability, and safety of the process.

[0038] In this embodiment, a heat exchange platform 2236 is provided in the pressure regulating cavity 2231. The heat exchange platform 2236 extends upward from the bottom of the pressure regulating cavity 2231, and there is a gap between the heat exchange platform 2236 and the first regulating diaphragm 2232. A heat exchange channel 2212 is provided in the first reaction plate 221. The heat exchange channel 2212 is arranged corresponding to the serpentine reaction channel 2211. The part of the heat exchange channel 2212 corresponding to the heat exchange platform 2236 forms a heat exchange spiral 2237 that goes from top to bottom in the heat exchange platform 2236. This design allows the heat exchange medium to fully exchange heat with the mixed solution in the pressure regulating chamber 2231 through the heat exchange spiral 2237, ensuring the temperature stability of the mixed solution. At the same time, the gap between the heat exchange platform 2236 and the first regulating diaphragm 2232 provides space for the elastic change of the first regulating diaphragm 2232. When the first regulating diaphragm 2232 expands excessively, it can limit the first regulating diaphragm 2232, thereby preventing the first regulating diaphragm 2232 from rupturing, ensuring the sealing of the pressure regulating chamber 2231, and preventing leakage of the mixed solution.

[0039] Preferably, the heat exchange channel 2212 is configured with multiple independent sections, which enables sufficient heat exchange and temperature control of the mixed solution at different reaction stages, ensuring accurate reaction temperature. Specifically, the heat exchange channel 2212 is configured with three independent sections, with the heat exchange channel 2212 being the input or output at the corner of the serpentine reaction channel 2211 without the pressure regulating component 223.

[0040] A continuous synthesis method employing any of the above-described flow chemistry-based continuous synthesis apparatuses for 4-methyl-5-thiazolyl ethanol comprises the following steps: S1. The 2-mercapto-4-methyl-5-thiazol ethanol reaction solution with pH adjusted to 2.0-4.0 and the 20%-35% (w / w) hydrogen peroxide oxidizing solution are respectively fed into the infusion module 1; S2. The infusion module 1 pumps the reaction solution into the mixing main chamber 211 through the first inlet 214, and pumps the oxidizing solution into the lateral annular chamber 212. The oxidizing solution is then input into the mixing main chamber 211 in stages through the second inlet 215. The oxidizing solution and the reaction solution are fully mixed in the mixing main chamber 211 to form a mixed solution, which then enters the reaction plate group 22. S3. The mixture is reacted fully in reaction plate group 22 at 20℃~40℃ and 0.2~1.0MPa to obtain a product solution. The obtained product solution is collected through collection module 3, and then extracted, dried, filtered and rotary evaporated to obtain 4-methyl-5-thiazolylethanol.

[0041] In one embodiment, in step S3, the mixture undergoes a three-stage reaction in the reaction plate assembly 22. The temperature of the first stage is 20°C to 25°C, and the temperatures of the second and third stages are 25°C to 40°C. The length ratio of the serpentine reaction channels 2211 in the first, second, and third stages is 1:3:3.

[0042] Example 1 S1. Accurately weigh 32.6 g (0.20 mol) of 2-mercapto-4-methyl-5-thiazolylethanol and dissolve it in ethanol. Slowly add concentrated hydrochloric acid dropwise while stirring to adjust the pH of the solution to 2.5 ± 0.1, then bring the volume to 100 mL to obtain a reaction solution with a concentration of 2.0 mol / L. Prepare a 30% hydrogen peroxide aqueous solution with a molar concentration of 9.8 mol / L. Input the reaction solution and oxidizing solution into infusion module 1.

[0043] S2. The infusion module 1 pumps the reaction solution into the mixing main chamber 211 via the first inlet 214, and pumps the oxidizing solution into the side annular chamber 212. The oxidizing solution is then input into the mixing main chamber 211 in stages via the second inlet 215. The oxidizing solution and reaction solution are thoroughly mixed in the mixing main chamber 211 to form a mixed solution before entering the reaction plate assembly 22. The reaction solution flow rate is set to 3 mL / min. The oxidizing solution flow rate is set to 0.7 mL / min. The molar ratio of the oxidizing solution to the reaction solution is 1.05:1. The flow rate ratio input into the side annular chamber 212 is 0.2:0.5:0.3.

[0044] S3. The mixture underwent a three-stage reaction in reaction plate group 22 at 0.5 MPa. The temperature of the first stage was 22℃±1℃, and the temperature of the second and third stages was 25±1℃. After the reaction was completed, a product solution was obtained. The product solution was collected through collection module 3 and then extracted multiple times with dichloromethane (3×20mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation under reduced pressure to obtain a pale yellow oily liquid product, which is 4-methyl-5-thiazolylethanol.

[0045] Yield and purity analysis of the obtained product was performed: Yield calculation: 27.6 g of the product 4-methyl-5-thiazolylethanol was obtained by weighing. Based on the input precursor, the yield was calculated to be 92.6%.

[0046] Purity analysis: Analysis was performed using gas chromatography (GC). The results showed that the GC purity of the product was greater than 98%.

[0047] It should be noted that the specific parameters or some commonly used reagents in the above embodiments are specific or preferred embodiments under the concept of the present invention, and not limitations thereof; those skilled in the art can make adaptive adjustments within the concept and protection scope of the present invention.

[0048] In addition, unless otherwise specified, the raw materials used may be commercially available products in the field, or prepared by conventional methods in the field.

[0049] Furthermore, those skilled in the art should understand that although many problems exist in the prior art, each embodiment or technical solution of the present invention can be improved in only one or a few aspects, without necessarily solving all the technical problems listed in the prior art or background art simultaneously. Those skilled in the art should understand that any content not mentioned in a claim should not be construed as a limitation on that claim.

[0050] Although this document uses terms such as infusion module and reaction fluid tubing frequently, the possibility of using other terms is not excluded. These terms are used merely for the convenience of describing and explaining the essence of the invention; interpreting them as any kind of additional limitation would contradict the spirit of the invention. The terms "first," "second," etc. (if present), in the description and claims of the embodiments of the invention are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence.

[0051] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A continuous synthesis apparatus for 4-methyl-5-thiazolylethanol based on flow chemistry, characterized in that, include: Infusion module (1) is used to contain and pump the reaction solution and oxidation solution separately; The micro-reaction module (2) is located at the rear end of the infusion module (1) and is used to receive the reaction liquid and the oxidation liquid delivered by the infusion module (1). It includes a mixing plate (21) and a reaction plate group (22). The mixing plate (21) is connected to the infusion module (1) through the reaction liquid pipe (11) and the oxidation liquid pipe (12). The mixing plate (21) has a mixing main chamber (211) and a lateral annular chamber (212). The two ends of the mixing main chamber (211) have a first inlet (214) and an outlet (216). The lateral annular cavity (212) is arranged at intervals around the mixing main cavity (211), and the lateral annular cavity (212) is connected to the second liquid inlet (215) opened on the side wall of the mixing main cavity (211); the reaction liquid pipe (11) is connected to the first liquid inlet (214), the oxidation liquid pipe (12) is connected to the second liquid inlet (215), the reaction plate group (22) is connected to the liquid outlet (216), and the oxidation liquid enters the mixing main cavity (211) in sections through the lateral annular cavity (212); The collection module (3) is located at the rear end of the micro-reaction module (2) and is used to receive the products output by the micro-reaction module (2).

2. The continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry according to claim 1, characterized in that: The mixing plate (21) also has a cooling chamber (213), which is located between the mixing main chamber (211) and the lateral annular chamber (212). The lateral annular chamber (212) is connected to the second liquid inlet (215) through an inclined channel.

3. The continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry according to claim 2, characterized in that: The cooling chamber (213) is provided with a partition wall (217), which is located between the lateral annular cavities (212). The partition wall (217) divides the cooling chamber (213) into multiple independent sealed cavities, and each section of the cooling chamber (213) is provided with a cooling medium inlet and outlet pipe.

4. The continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry according to claim 2, characterized in that: The mixing chamber (211) is provided with a shrinkage ring wall (218). The shrinkage ring wall (218) extends towards the side near the liquid outlet (216) while the diameter of the shrinkage ring wall (218) gradually shrinks. The shrinkage ring wall (218) is located at the rear end of the second liquid inlet (215).

5. The continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry according to claim 1, characterized in that: The reaction plate assembly (22) includes a first reaction plate (221) and a second reaction plate (222). The first reaction plate (221) is provided with a serpentine reaction channel (2211) and a pressure regulating component (223) spaced at the corners of the serpentine reaction channel (2211). The pressure regulating component (223) is used to buffer and regulate the pressure of the mixed liquid in the serpentine reaction channel (2211). One end of the serpentine reaction channel (2211) is connected to the liquid outlet (216), and the other end of the serpentine reaction channel (2211) is connected to the collection module (3).

6. The continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry according to claim 5, characterized in that: The pressure regulating assembly (223) includes a pressure regulating chamber (2231), a first regulating diaphragm (2232), a second regulating diaphragm (2233), and a gas supply pipe (2234). The pressure regulating chamber (2231) extends from the first reaction plate (221) to the second reaction plate (222) and is embedded at the corner of the serpentine reaction channel (2211). The mixed liquid in the serpentine reaction channel (2211) enters through the inflow arc channel located at the bottom of the pressure regulating chamber (2231) and flows out through the outflow arc channel located in the middle of the pressure regulating chamber (2231). A regulating diaphragm (2232) is disposed in the pressure regulating chamber (2231) located within the first reaction plate (221) and above the outflow arc. A second regulating diaphragm (2233) is disposed in the pressure regulating chamber (2231) located within the second reaction plate (222). A buffer gas chamber is formed between the first regulating diaphragm (2232) and the second regulating diaphragm (2233). The gas supply pipe (2234) enters from the side wall of the second reaction plate (222) and communicates with the buffer gas chamber. The gas supply pipe (2234) is connected to an external gas supply device.

7. The continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry according to claim 6, characterized in that: The pressure regulating assembly (223) further includes a liquid supply pipe (2235). The second regulating diaphragm (2233) and the top of the pressure regulating chamber (2231) form a liquid regulating chamber. The liquid supply pipe (2235) enters from the top of the second reaction plate (222) and communicates with the liquid regulating chamber. The liquid supply pipe (2235) is connected to an external liquid supply device.

8. The continuous synthesis apparatus for 4-methyl-5-thiazolyl ethanol based on flow chemistry according to claim 5, characterized in that: The pressure regulating chamber (2231) is provided with a heat exchange platform (2236), which extends upward from the bottom of the pressure regulating chamber (2231). There is a gap between the heat exchange platform (2236) and the first regulating diaphragm (2232). The first reaction plate (221) is provided with a heat exchange channel (2212), which is arranged corresponding to the serpentine reaction channel (2211). The part of the heat exchange channel (2212) corresponding to the heat exchange platform (2236) forms a heat exchange spiral (2237) that goes from top to bottom in the heat exchange platform (2236).

9. A continuous synthesis method employing the flow chemistry-based 4-methyl-5-thiazolylethanol continuous synthesis apparatus as described in any one of claims 1 to 8, characterized in that, The steps are as follows: S1. 2-Mercapto-4-methyl-5-thiazol ethanol reaction solution with pH adjusted to 2.0-4.0 and 20%-35% (w / w) hydrogen peroxide oxidizing solution are respectively input into the infusion module (1); S2. The infusion module (1) pumps the reaction solution into the mixing main chamber (211) through the first inlet (214), and pumps the oxidizing solution into the lateral annular chamber (212), and inputs it into the mixing main chamber (211) in segments through the second inlet (215); the oxidizing solution and the reaction solution are fully mixed in the mixing main chamber (211) to form a mixed solution and then enter the reaction plate group (22); S3. The mixture is fully reacted in the reaction plate group (22) at 20℃~40℃ and 0.2~1.0MPa to obtain a product solution. The obtained product solution is collected through the collection module (3), and then extracted, dried, filtered and rotary evaporated to obtain 4-methyl-5-thiazolylethanol.

10. The continuous synthesis method according to claim 9, characterized in that: In step S3, the mixture undergoes a three-stage reaction in the reaction plate group (22), with the temperature of the first stage being 20℃~25℃ and the temperatures of the second and third stages being 25℃~40℃.

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