L-selenium-methyl selenocysteine and continuous production method and system thereof

Abstract

The invention relates to the technical field of organic synthesis, in particular to L-selenium-methyl selenocysteine and a continuous production method and system thereof. The production method comprises the following steps: S1, conveying a reducing agent, selenium powder and an acid solution into a dynamic tubular reactor for reaction to obtain hydrogen selenide gas; s2, the hydrogen selenide gas reacts with a bicarbonate solution to obtain selenium hydride salt, the selenium hydride salt reacts with a methylation reagent to obtain methyl selenol salt, and the methyl selenol salt reacts with a chloro-alanine salt solution to obtain L-selenium-methyl selenocysteine salt; s3, the L-selenium-methyl selenocysteine salt is subjected to acidification, and L-selenium-methyl selenocysteine is obtained; wherein the reaction in the step S2 is carried out in the microchannel reactor. According to the method disclosed by the invention, continuous production of the L-selenium-methyl selenocysteine can be realized, the reaction efficiency is improved, and possibility is provided for mass production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and more specifically, to an L-seleno-methylselenocysteine ​​and its continuous production method and system. Background Technology

[0002] Selenium is an essential trace element for human life and serves as the active site for many enzymes. Selenium deficiency can impair many physiological functions and even lead to serious diseases. Selenium naturally exists in the soil and is accumulated in food through plants. Humans primarily obtain selenium from food; however, approximately 72% of my country's soil is selenium-deficient, with 30% being severely deficient. Long-term living in selenium-deficient areas can damage the immune system and induce various diseases such as cardiovascular disease, diabetes, and cancer. Therefore, supplementing selenium through food can enhance human health. Selenium can be divided into inorganic and organic selenium. Inorganic selenium includes sodium selenite and sodium selenate, while organic selenium is mostly formed through biological transformation into amino acid-bound organic compounds, such as selenomethionine, selenocysteine, and L-methylselenocysteine. Inorganic selenium has low absorption rates and high toxicity; currently, organic selenium is widely used as a dietary supplement. L-selenomethylselenocysteine ​​has been approved as a food additive by the Ministry of Health of China.

[0003] Currently, the synthesis of L-seleno-methylselenocysteine ​​is mostly done in small quantities, typically using serine and selenium powder as raw materials via a nucleophilic substitution reaction. This process often involves the use of toxic and odorous methylselenool and dimethyldiselenoether, and requires large quantities of expensive and hazardous reagents. The reaction procedures are cumbersome, time-consuming, and inefficient, resulting in a high price for L-seleno-methylselenocysteine. Furthermore, existing technologies struggle to achieve continuous production of L-seleno-methylselenocysteine.

[0004] In view of this, the present invention is hereby proposed. Summary of the Invention

[0005] The primary objective of this invention is to provide a continuous production method for L-seleno-methylselenocysteine. This method integrates each reaction step into a dynamic tubular reactor and a microchannel reactor, simplifying the reaction process, avoiding environmental pollution from harmful gases generated during the reaction, improving reaction efficiency, enabling continuous production, and making it possible to mass-produce L-seleno-methylselenocysteine.

[0006] The second objective of this invention is to provide an L-seleno-methylselenocysteine, which is produced by the continuous production method of L-seleno-methylselenocysteine ​​described above.

[0007] A third objective of this invention is to provide a continuous production system for L-seleno-methylselenocysteine, applicable to the continuous production method of L-seleno-methylselenocysteine ​​as described above.

[0008] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted: A continuous production method for L-seleno-methylselenocysteine ​​includes the following steps: S1. The reducing agent, selenium powder and acid solution are fed into a dynamic tubular reactor to react and produce hydrogen selenide gas; S2. The hydrogen selenide gas reacts with bicarbonate solution to obtain selenide salt, the selenide salt reacts with methylating agent to obtain methylselenoolate, and the methylselenoolate reacts with chloroalanine salt solution to obtain L-seleno-methylselenocysteine ​​salt. S3. Acidify the L-seleno-methylselenocysteine ​​salt to obtain the L-seleno-methylselenocysteine; In step S2, all reactions are carried out in a microchannel reactor.

[0009] Preferably, the H in the selenium powder, the reducing agent, and the acid solution is... + The molar ratio is 1:1-1.5:1-1.5.

[0010] Preferably, the reducing agent includes at least one of sodium borohydride, potassium borohydride, and hydrazine hydrate.

[0011] Preferably, the acid solution includes dilute sulfuric acid and / or hydrochloric acid.

[0012] Preferably, the residence time of the selenium powder, the reducing agent, and the acid solution in the dynamic tubular reactor is 3-17 minutes.

[0013] Preferably, the rotational speed of the feed screw of the dynamic tubular reactor is 100-500 r / min.

[0014] Preferably, the molar ratio of the selenium powder to the bicarbonate is 1:2-3.

[0015] Preferably, the bicarbonate includes sodium bicarbonate and / or potassium bicarbonate.

[0016] Preferably, the methylating agent includes dimethyl sulfate and / or dimethyl carbonate.

[0017] Preferably, the molar ratio of the selenium powder to the methylating agent is 1:1.5-2.

[0018] Preferably, the chloroalanine salt comprises sodium chloroalanine and / or potassium chloroalanine.

[0019] Preferably, the molar ratio of the selenium powder to the chloroalanine salt is 1:1-1.2.

[0020] An L-seleno-methylselenocysteine ​​is prepared by the continuous production method of L-seleno-methylselenocysteine ​​described in any of the foregoing embodiments.

[0021] A continuous production system for L-seleno-methylselenocysteine, applicable to the continuous production method of L-seleno-methylselenocysteine ​​as described in any of the foregoing embodiments, comprising a dynamic tubular reactor, a microchannel reactor, a storage tank, and a receiver. The dynamic tubular reactor is provided with a first inlet, a second inlet and a third inlet, and the liquid discharge port on the dynamic tubular reactor is connected to the storage tank. The microchannel reactor includes a first microchannel, a second microchannel, a third microchannel, and a delay tube connected in series. The gas outlet of the dynamic tubular reactor is connected to the inlet of the first microchannel via a vacuum pump. The first microchannel is also provided with a bicarbonate solution inlet, the second microchannel is also provided with a methylation reagent inlet, and the third microchannel is also provided with a chloroalanine salt solution inlet. The outlet of the delay tube is connected to the receiver.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention discloses a method for preparing L-seleno-methylselenocysteine ​​using a dynamic tubular reactor and a microchannel reactor. The method integrates each reaction step into the tubular reactor and the microchannel reactor, which simplifies the reaction process, avoids the environmental pollution caused by harmful gases generated during the reaction, improves the reaction efficiency, and enables continuous production, thus providing the possibility for the mass production of L-seleno-methylselenocysteine. Attached Figure Description

[0023] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0024] Figure 1 This is a schematic diagram of the continuous production system of L-seleno-methylselenocysteine ​​provided in an embodiment of the present invention. Detailed Implementation

[0025] The technical solution of the present invention will be clearly and completely described below with reference to the accompanying drawings and specific embodiments. However, those skilled in the art will understand that the embodiments described below are some embodiments of the present invention, but not all embodiments, and are only used to illustrate the present invention, and should not be regarded as limiting the scope of the present invention. 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. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall be followed. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0026] A first aspect of the present invention provides a continuous production method for L-seleno-methylselenocysteine, comprising the following steps: S1. The reducing agent, selenium powder and acid solution are fed into a dynamic tubular reactor to react and produce hydrogen selenide gas; S2. Hydrogen selenide gas reacts with bicarbonate solution to give selenide salt, selenide salt reacts with methylating agent to give methylselenoolate, and methylselenoolate reacts with chloroalanine salt solution to give L-seleno-methylselenocysteine ​​salt. S3. Acidification of L-seleno-methylselenocysteine ​​salt yields L-seleno-methylselenocysteine; In step S2, all reactions are carried out in a microchannel reactor.

[0027] Existing methods for synthesizing L-seleno-methylselenocysteine ​​are cumbersome, cannot achieve continuous production, are inefficient, and use large quantities of expensive and hazardous reagents, resulting in a high price for the product. To address these issues, this invention discloses a method for preparing L-seleno-methylselenocysteine ​​using a dynamic tubular reactor and microchannel reactor. This method integrates each reaction step into the tubular and microchannel reactors, simplifying the reaction process, avoiding environmental pollution from harmful gases generated during the reaction, improving reaction efficiency, and enabling continuous production. This provides a possibility for the large-scale production of L-seleno-methylselenocysteine.

[0028] In a dynamic tubular reactor, the reducing agent can reduce selenium to hydrogen selenide gas under acidic conditions.

[0029] Hydrogen selenide is introduced into a microchannel reactor and first reacts with a bicarbonate solution to generate selenide hydride. The generated selenide hydride then reacts with a methylating agent to generate methylselenoolate. methylselenoolate reacts with chloroalanine salt to generate L-seleno-methylselenocysteine ​​salt. Finally, acidification yields L-seleno-methylselenocysteine. Using sodium bicarbonate as an example, dimethyl carbonate as an example of the methylating agent, sodium chloroalanine salt as an example of the chloroalanine salt, and hydrochloric acid as an example of the acidification process, the reaction route for obtaining L-seleno-methylselenocysteine ​​from hydrogen selenide is as follows:

[0030] In some specific embodiments of the present invention, in step S1, H in the selenium powder, reducing agent and acid solution + The molar ratio is 1:1-1.5:1-1.5. For example, it can be any one value or a range of any two values ​​from 1:1:1, 1:1:1.2, 1:1:1.5, 1:1.2:1, 1:1.2:1.2, 1:1.2:1.5, 1:1.5:1, 1:1.5:1.2, 1:1.5:1.5.

[0031] In some specific embodiments of the present invention, the reducing agent includes at least one of sodium borohydride, potassium borohydride, and hydrazine hydrate; as an example, the reducing agent is added to a dynamic tubular reactor in the form of an aqueous solution for reaction.

[0032] In some specific embodiments of the present invention, the acid solution includes dilute sulfuric acid and / or hydrochloric acid.

[0033] In some specific embodiments of the present invention, the selenium powder used is a dispersible metal powder with a particle size of 100-200 mesh. For example, it can be any one value or a range of any two values ​​among 100 mesh, 120 mesh, 150 mesh, 180 mesh, and 200 mesh.

[0034] In some specific embodiments of the present invention, the residence time of the selenium powder, reducing agent and acid solution in the dynamic tubular reactor after they are combined is 3-17 min. For example, it can be any one value or a range of any two values ​​among 3 min, 5 min, 10 min, 12 min, 15 min and 17 min.

[0035] In some specific embodiments of the present invention, the feeding rate of the reducing agent is 3.5-17.5 ml / min, the feeding rate of the selenium powder is 1-5 g / min, and the feeding rate of the acid solution is 2.5-12.5 ml / min.

[0036] In some specific embodiments of the present invention, the rotational speed of the feed screw of the dynamic tubular reactor is 100-500 r / min. For example, it can be any one value or a range of any two values ​​among 100 r / min, 200 r / min, 300 r / min, 400 r / min, and 500 r / min.

[0037] In some specific embodiments of the present invention, the molar ratio of selenium powder to bicarbonate is 1:2-3, for example, it can be any one value or a range of any two values ​​among 1:2, 1:2.2, 1:2.4, 1:2.6, 1:2.8, and 1:3.

[0038] In some specific embodiments of the present invention, the feed rate of the bicarbonate solution is 50-250 ml / min.

[0039] In some specific embodiments of the present invention, the bicarbonate salt includes sodium bicarbonate and / or potassium bicarbonate.

[0040] In some specific embodiments of the present invention, the methylating agent includes dimethyl sulfate and / or dimethyl carbonate.

[0041] In some specific embodiments of the present invention, the molar ratio of selenium powder and methylation reagent is 1:1.5-2. For example, it can be any one value or a range of any two values ​​among 1:1.5, 1:1.6, 1:1.8, and 1:2.

[0042] In some specific embodiments of the present invention, the feed rate of the methylating agent is 2-10 ml / min.

[0043] In some specific embodiments of the present invention, the chloroalanine salt includes sodium chloroalanine and / or potassium chloroalanine; wherein the chloroalanine salt solution is obtained by reacting chloroalanine hydrochloride with sodium hydroxide solution or potassium hydroxide solution, and the pH is 9-10.

[0044] In some specific embodiments of the present invention, the molar ratio of selenium powder and chloroalanine salt is 1:1-1.2, for example, it can be any one value or a range of any two values ​​among 1:1, 1:1.05, 1:1.1, 1:1.15, and 1:1.2.

[0045] In some specific embodiments of the present invention, the feed rate of the chloroalanine salt solution is 6.5-32.5 ml / min.

[0046] In some specific embodiments of the present invention, in step S2, the heat exchange medium temperature of the microchannel reactor is 40-50°C. For example, it can be any one value or a range of any two values ​​among 40°C, 42°C, 45°C, 48°C, and 50°C.

[0047] A second aspect of the present invention provides an L-seleno-methylselenocysteine, which is prepared by a continuous production method of L-seleno-methylselenocysteine ​​as described in any of the foregoing embodiments.

[0048] like Figure 1 As shown, a third aspect of the present invention provides a continuous production system for L-seleno-methylselenocysteine, applicable to the continuous production method of L-seleno-methylselenocysteine ​​as described in any of the foregoing embodiments, comprising a dynamic tubular reactor, a microchannel reactor, a storage tank, and a receiver. The dynamic tubular reactor is equipped with a first inlet, a second inlet, and a third inlet, which are used to introduce reducing agent solution, selenium powder, and acid solution into it, respectively. The liquid discharge port on the dynamic tubular reactor is connected to a storage tank, and the remaining liquid phase material after the selenium powder reacts with the reducing agent and acid enters the storage tank. The microchannel reactor comprises a first microchannel, a second microchannel, a third microchannel, and a delay tube connected in series. Each microchannel has two inlets and one outlet. The gas outlet of the dynamic tubular reactor is connected to one inlet of the first microchannel via a vacuum pump. The other inlet of the first microchannel is used to introduce a bicarbonate solution. The outlet of the first microchannel is connected to one inlet of the second microchannel. The other inlet of the second microchannel is used to introduce a methylating agent. The outlet of the second microchannel is connected to one inlet of the third microchannel. The other inlet of the third microchannel is used to introduce a chloroalanine solution. The outlet of the third microchannel is connected to the inlet of the delay tube. The outlet of the delay tube is connected to the receiver.

[0049] In some specific embodiments of the present invention, the continuous production method of L-seleno-methylselenocysteine ​​includes the following steps: S1. The reducing agent is prepared into an aqueous solution and fed into the dynamic tubular reactor via a feed pump. Selenium powder is fed into the dynamic tubular reactor via a solid feed device. Acid solution is fed into the dynamic tubular reactor via a feed pump. The reducing agent solution, selenium powder and acid solution are mixed and reacted in the dynamic tubular reactor to obtain hydrogen selenide gas. The hydrogen selenide gas is pumped into the first microchannel of the microchannel reactor via a vacuum pump. The remaining liquid material enters the storage tank through the liquid discharge port. S2. The bicarbonate solution is fed into the first microchannel of the microchannel reactor via a feed pump, where it reacts with hydrogen selenide gas to obtain hydride. The hydride and methylating agent are then fed into the second microchannel to react and obtain methylselenoolate. The methylselenoolate and chloroalanine solution are fed into the third microchannel and reacted via a delay tube to obtain L-seleno-methylselenocysteine ​​salt, which then enters the receiver. S3. Add an acid solution to acidify L-seleno-methylselenocysteine ​​salt to obtain L-seleno-methylselenocysteine.

[0050] In one specific embodiment of the present invention, a loss-in-weight feed scale is provided at the second feed inlet of the dynamic tubular reactor to accurately control the feed rate of selenium powder.

[0051] The embodiments of the present invention will be described in detail below with reference to specific examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified, specific conditions in the examples are performed under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used without a specified manufacturer are all commercially available conventional products. In the examples, the dynamic tubular reactor has a tube length of 500 mm and a liquid holding capacity of 100 mL. The microchannel reactor's microchannel structure is composed of multiple types of mixed chips arranged in an interlaced and tightly packed manner, with each microchannel holding a liquid holding capacity of 2.8 mL.

[0052] Example 1 A 4 mol / L potassium borohydride aqueous solution is fed into the first inlet of the dynamic tubular reactor via a feed pump at a rate of 3.5 mL / min. Selenium powder is fed into the second inlet of the dynamic tubular reactor via a solid feeder at a rate of 1.0 g / min, with a total amount of 79 g. A 6 mol / L hydrochloric acid solution is fed into the third inlet of the dynamic tubular reactor via a feed pump at a rate of 2.5 mL / min. The jacket water temperature is 90℃. The rotation speed of the feed screw in the dynamic tubular reactor is adjusted to 100 r / min. After the materials converge in the dynamic tubular reactor, the residence time in the reactor is 16.7 min. The hydrogen selenide gas generated by the reaction is pumped to the first microchannel of the microchannel reactor via a vacuum pump. The residue enters the storage tank through the liquid discharge port of the dynamic tubular reactor. The microchannel reactor reaction temperature was adjusted to 45℃. A 5% (0.6 mol / L) sodium bicarbonate aqueous solution was pumped into the first microchannel of the reactor at a feed rate of 50 mL / min. Sodium selenide, obtained from the reaction of sodium bicarbonate aqueous solution and hydrogen selenide gas in the first microchannel, entered the second microchannel. Simultaneously, dimethyl carbonate was introduced into the second microchannel at a feed rate of 2.0 mL / min. Sodium methyl selenool, obtained from the reaction of dimethyl carbonate and sodium selenide gas in the second microchannel, entered the third microchannel. A 2 mol / L sodium 3-chloro-L-alanine solution was introduced into the microchannel at a feed rate of 6.5 mL / min. The length of the delay tube was adjusted to ensure a residence time of 80 min for the material. After the reaction was completed, the material was depressurized through a back pressure valve and then placed into the receiver. When the selenium powder reactant was completely fed, the pH of the reaction solution was adjusted to 3-4 with 6 mol / L hydrochloric acid. The aqueous phase was evaporated using a rotary evaporator until a small amount of solid appeared on the flask wall. 100 mL of ethanol solution was added to obtain a suspension, which was filtered and dried to obtain L-seleno-methylselenocysteine ​​with a yield of 76.9% and a purity >96%.

[0053] Example 2 A 4 mol / L potassium borohydride aqueous solution is fed into the first inlet of the dynamic tubular reactor via a feed pump at a rate of 7.0 mL / min. Selenium powder is fed into the second inlet of the dynamic tubular reactor via a solid feeder at a rate of 2.0 g / min, with a total amount of 79 g. A 6 mol / L hydrochloric acid solution is fed into the third inlet of the dynamic tubular reactor via a feed pump at a rate of 5.0 mL / min. After the materials are combined in the dynamic tubular reactor, the residence time in the reactor is 8.3 min. The hydrogen selenide gas generated by the reaction is pumped into the first microchannel of the microchannel reactor via a vacuum pump, and the residue enters the storage tank through the liquid discharge port of the dynamic tubular reactor. A 5% sodium bicarbonate aqueous solution is fed into the first microchannel of the microchannel reactor via a feed pump at a rate of 100 mL / min. Sodium selenide, obtained from the reaction of the sodium bicarbonate aqueous solution and hydrogen selenide gas in the first microchannel, enters the second microchannel. Simultaneously, dimethyl carbonate is introduced into the second microchannel at a feed rate of 4 mL / min. The sodium methyl selenoside, obtained from the reaction of dimethyl carbonate and sodium selenide in the second microchannel, enters the third microchannel. Simultaneously, 2 mol / L 3-chloro-L- The sodium alanine solution was fed at a rate of 13 mL / min. The length of the delay tube was adjusted so that the material resided in the delay tube for 80 min. After the reaction was completed, the material was depressurized through the back pressure valve and then placed in the receiver. When the selenium powder reactant was completely fed, the pH of the reaction solution was adjusted to 3-4 with 6 mol / L hydrochloric acid. The aqueous phase was evaporated using a rotary evaporator until a small amount of solid appeared on the bottle wall. 100 mL of ethanol solution was added to obtain a suspension. The suspension was filtered and dried to obtain L-seleno-methylselenocysteine ​​with a yield of 80.7% and a purity >96%.

[0054] Example 3 A 4 mol / L potassium borohydride aqueous solution is fed into the first inlet of the dynamic tubular reactor via a feed pump at a rate of 10.5 mL / min. Selenium powder is fed into the second inlet of the dynamic tubular reactor via a solid feeder at a rate of 3.0 g / min, with a total amount of 79 g. A 6 mol / L hydrochloric acid solution is fed into the third inlet of the dynamic tubular reactor via a feed pump at a rate of 7.5 mL / min. The jacket water temperature is 90℃. The rotation speed of the feed screw in the dynamic tubular reactor is adjusted to 100 r / min. After the materials converge in the dynamic tubular reactor, the residence time in the reactor is 5.6 min. The hydrogen selenide gas generated by the reaction is pumped to the first microchannel of the microchannel reactor via a vacuum pump. The residue enters the storage tank through the liquid discharge port of the dynamic tubular reactor. A 5% sodium bicarbonate aqueous solution is fed into the first microchannel of the microchannel reactor via a feed pump at a rate of 150 mL / min. Sodium hydride, formed by the reaction of sodium bicarbonate aqueous solution and hydrogen selenide gas in the first microchannel, enters the second microchannel. Simultaneously, dimethyl carbonate is introduced into the second microchannel at a feed rate of 6.0 mL / min. Sodium methyl selenoside, formed by the reaction of dimethyl carbonate and sodium hydride gas in the second microchannel, enters the third microchannel. Simultaneously, 2 mol / L of 3-chloro- The L-alanine sodium solution was fed at a rate of 19.5 mL / min. The length of the delay tube was adjusted so that the material resided in the delay tube for 80 min. After the reaction was completed, the material was depressurized through the back pressure valve and then placed in the receiver. When the selenium powder reactant was completely fed, the pH of the reaction solution was adjusted to 3-4 with 6 mol / L hydrochloric acid. The aqueous phase was evaporated using a rotary evaporator until a small amount of solid appeared on the flask wall. 100 mL of ethanol solution was added to obtain a suspension, which was filtered and dried to obtain L-seleno-methylselenocysteine ​​with a yield of 82.4% and a purity >96%.

[0055] Example 4 A 4 mol / L potassium borohydride aqueous solution is fed into the first inlet of the dynamic tubular reactor via a feed pump at a rate of 14.0 mL / min. Selenium powder is fed into the second inlet of the dynamic tubular reactor via a solid feeder at a rate of 4.0 g / min, with a total amount of 79 g. A 6 mol / L hydrochloric acid solution is fed into the third inlet of the dynamic tubular reactor via a feed pump at a rate of 10.0 mL / min. The jacket water temperature is 90℃. The rotation speed of the feed screw in the dynamic tubular reactor is adjusted to 100 r / min. After the materials converge in the dynamic tubular reactor, the residence time in the reactor is 4.2 min. The hydrogen selenide gas generated by the reaction is pumped to the first microchannel of the microchannel reactor via a vacuum pump. The residue enters the storage tank through the liquid discharge port of the dynamic tubular reactor. A 5% sodium bicarbonate aqueous solution is fed into the first microchannel of the microchannel reactor via a feed pump at a rate of 200 mL / min. Sodium selenide, formed by the reaction of the sodium bicarbonate aqueous solution and hydrogen selenide gas in the first microchannel, enters the second microchannel. Simultaneously, dimethyl carbonate is introduced into the second microchannel at a feed rate of 8 mL / min. Sodium methylselenoolate, formed by the reaction of dimethyl carbonate and sodium selenide in the second microchannel, enters the third microchannel. Simultaneously, 2 mol / L of 3-chloro- The L-alanine sodium solution was fed at a rate of 26 mL / min. The length of the delay tube was adjusted so that the material resided in the delay tube for 80 min. After the reaction was completed, the material was depressurized through the back pressure valve and then placed in the receiver. When the selenium powder reactant was completely fed, the pH of the reaction solution was adjusted to 3-4 with 6 mol / L hydrochloric acid. The aqueous phase was evaporated using a rotary evaporator until a small amount of solid appeared on the flask wall. 100 mL of ethanol solution was added to obtain a suspension, which was filtered and dried to obtain L-seleno-methylselenocysteine ​​with a yield of 76.9% and a purity >96%.

[0056] Example 5 A 4 mol / L potassium borohydride aqueous solution is fed into the first inlet of the dynamic tubular reactor via a feed pump at a rate of 17.5 mL / min. Selenium powder is fed into the second inlet of the dynamic tubular reactor via a solid feeder at a rate of 5.0 g / min, with a total amount of 79 g. A 6 mol / L hydrochloric acid solution is fed into the third inlet of the dynamic tubular reactor via a feed pump at a rate of 12.5 mL / min. The jacket water temperature is 90℃. The rotation speed of the feed screw in the dynamic tubular reactor is adjusted to 100 r / min. After the materials converge in the dynamic tubular reactor, the residence time in the reactor is 3.3 min. The hydrogen selenide gas generated by the reaction is pumped to the first microchannel of the microchannel reactor via a vacuum pump. The residue enters the storage tank through the liquid discharge port of the dynamic tubular reactor. A 5% sodium bicarbonate aqueous solution is fed into the first microchannel of the microchannel reactor via a feed pump at a rate of 250 mL / min. Sodium selenide, formed by the reaction of the sodium bicarbonate aqueous solution and hydrogen selenide gas in the first microchannel, enters the second microchannel. Simultaneously, dimethyl carbonate is introduced into the second microchannel at a feed rate of 10.0 mL / min. Sodium methyl selenoside, formed by the reaction of dimethyl carbonate and sodium selenide gas in the second microchannel, enters the third microchannel. Simultaneously, 2 mol / L of 3-chloro- The L-alanine sodium solution was fed at a rate of 32.5 mL / min. The length of the delay tube was adjusted so that the material resided in the delay tube for 80 min. After the reaction was completed, the material was depressurized through the back pressure valve and then placed in the receiver. When the selenium powder reactant was completely fed, the pH of the reaction solution was adjusted to 3-4 with 6 mol / L hydrochloric acid. The aqueous phase was evaporated using a rotary evaporator until a small amount of solid appeared on the flask wall. 100 mL of ethanol solution was added to obtain a suspension, which was filtered and dried to obtain L-seleno-methylselenocysteine ​​with a yield of 71.4% and a purity >96%.

[0057] Example 6 Example 6 is similar to Example 3, except that the speed of the feed screw in the dynamic tubular reactor is 150 r / min, and all other conditions are the same as in Example 3. L-seleno-methylselenocysteine ​​was obtained with a yield of 85.2% and a purity of >96%.

[0058] Example 7 Example 7 is similar to Example 3, except that the speed of the feed screw in the dynamic tubular reactor is 200 r / min, and all other conditions are the same as in Example 3. L-seleno-methylselenocysteine ​​was obtained with a yield of 85.7% and a purity of >96%.

[0059] Example 8 Example 8 is similar to Example 3, except that the speed of the feed screw in the dynamic tubular reactor is 250 r / min, and all other conditions are the same as in Example 3. L-seleno-methylselenocysteine ​​was obtained with a yield of 85.8% and a purity of >96%.

[0060] Although the present invention has been illustrated and described with specific embodiments, it should be understood that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; those skilled in the art should understand that modifications can 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 therein, without departing from the spirit and scope of the present invention; 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; therefore, this means that all such substitutions and modifications that fall within the scope of the present invention are included in the appended claims.

Claims

1. A continuous production method for L-seleno-methylselenocysteine, characterized in that, Includes the following steps: S1. The reducing agent, selenium powder and acid solution are fed into a dynamic tubular reactor to react and produce hydrogen selenide gas; S2. The hydrogen selenide gas reacts with bicarbonate solution to obtain selenide salt, the selenide salt reacts with methylating agent to obtain methylselenoolate, and the methylselenoolate reacts with chloroalanine salt solution to obtain L-seleno-methylselenocysteine ​​salt. S3. Acidify the L-seleno-methylselenocysteine ​​salt to obtain the L-seleno-methylselenocysteine; In step S2, all reactions are carried out in a microchannel reactor.

2. The continuous production method of L-seleno-methylselenocysteine ​​according to claim 1, characterized in that, The selenium powder, the reducing agent, and the acid solution contain H. + The molar ratio is 1:1-1.5:1-1.

5.

3. The continuous production method of L-seleno-methylselenocysteine ​​according to claim 1, characterized in that, The reducing agent includes at least one of sodium borohydride, potassium borohydride, and hydrazine hydrate.

4. The continuous production method of L-seleno-methylselenocysteine ​​according to claim 1, characterized in that, The acid solution includes dilute sulfuric acid and / or hydrochloric acid.

5. The continuous production method of L-seleno-methylselenocysteine ​​according to claim 1, characterized in that, The residence time of the selenium powder, the reducing agent and the acid solution in the dynamic tubular reactor is 3-17 minutes. And / or, the rotational speed of the feed screw of the dynamic tubular reactor is 100-500 r / min.

6. The continuous production method of L-seleno-methylselenocysteine ​​according to claim 1, characterized in that, It meets at least one of the following characteristics: (1) The molar ratio of the selenium powder to the bicarbonate is 1:2-3; (2) The bicarbonate includes sodium bicarbonate and / or potassium bicarbonate.

7. The continuous production method of L-seleno-methylselenocysteine ​​according to claim 1, characterized in that, It meets at least one of the following characteristics: (1) The methylating agent includes dimethyl sulfate and / or dimethyl carbonate; (2) The molar ratio of the selenium powder and the methylation reagent is 1:1.5-2.

8. The continuous production method of L-seleno-methylselenocysteine ​​according to claim 1, characterized in that, It meets at least one of the following characteristics: (1) The chloroalanine salt includes sodium chloroalanine and / or potassium chloroalanine; (2) The molar ratio of the selenium powder and the chloroalanine salt is 1:1-1.

2.

9. An L-seleno-methylselenocysteine, characterized in that, L-seleno-methylselenocysteine ​​was prepared using the continuous production method according to any one of claims 1-8.

10. A continuous production system for L-seleno-methylselenocysteine, characterized in that, A continuous production method for L-seleno-methylselenocysteine ​​according to any one of claims 1-8, comprising a dynamic tubular reactor, a microchannel reactor, a storage tank, and a receiver; The dynamic tubular reactor is provided with a first inlet, a second inlet and a third inlet, and the liquid discharge port on the dynamic tubular reactor is connected to the storage tank. The microchannel reactor includes a first microchannel, a second microchannel, a third microchannel, and a delay tube connected in series. The gas outlet of the dynamic tubular reactor is connected to the inlet of the first microchannel via a vacuum pump. The first microchannel is also provided with a bicarbonate solution inlet, the second microchannel is also provided with a methylation reagent inlet, and the third microchannel is also provided with a chloroalanine salt solution inlet. The outlet of the delay tube is connected to the receiver.

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