阅读说明：本技术 一种硒代蛋氨酸的合成方法及装置 (Synthetic method and device of selenomethionine ) 是由 周华 戴扬晓 廖津 郑洁 欧仕益 傅亮 于 2021-08-13 设计创作，主要内容包括：本发明属于化学转化领域,具体公开了一种硒代蛋氨酸的合成方法及装置。所述方法具体为将高丝氨酸、二氯亚砜、乙酸、盐酸(或氢溴酸)混合后在一定温度下搅拌反应,然后过滤收集滤渣为氯代高丝氨酸盐酸盐；将滤渣加入由硒粉、强碱性物质、吊白块混合后反应生成的溶液中,反应一定时间后过滤后获得中间产物二硒代高丝氨酸；将中间产物溶于强碱溶液中,加入三乙酰氧基硼氢化钠、碘甲烷反应,再加入无水乙醇,析出固体即为硒代蛋氨酸。本发明反应温和,安全可靠,且操作简单易行,具有良好的应用前景。(The invention belongs to the field of chemical conversion, and particularly discloses a method and a device for synthesizing selenomethionine. The method specifically comprises the steps of mixing homoserine, thionyl chloride, acetic acid and hydrochloric acid (or hydrobromic acid), stirring and reacting at a certain temperature, and then filtering and collecting filter residues to obtain chloro-homoserine hydrochloride; adding filter residues into a solution generated by reacting after mixing selenium powder, strong alkaline substances and sodium formaldehyde sulfoxylate, reacting for a certain time, and filtering to obtain an intermediate product diseleno homoserine; dissolving the intermediate product in strong alkali solution, adding sodium triacetoxyborohydride and methyl iodide for reaction, and then adding absolute ethyl alcohol to separate out solid, namely selenomethionine. The method has the advantages of mild reaction, safety, reliability, simple and easy operation and good application prospect.)

1. A preparation method of selenomethionine is characterized by comprising the following steps:

mixing homoserine, thionyl chloride, acetic acid, hydrochloric acid or hydrobromic acid, stirring for reaction, filtering after the reaction is finished, and collecting filter residue as chlorohomoserine hydrochloride;

secondly, mixing selenium powder, strong alkaline substances, water and rongalite, stirring for reaction, cooling after the reaction is finished, adding chlorohomoserine hydrochloride, stirring at normal temperature, adding acid, filtering to remove redundant selenium powder, adding alkali into the obtained filtrate, adjusting the filtrate to weak acidity, standing, and filtering to obtain filter residue which is diseleno-homoserine;

thirdly, diseleno homoserine is mixed with strong base substance, dissolved in water, added with triacetoxy sodium borohydride and methyl iodide, added with acid to adjust to subacidity after the reaction at normal temperature is finished, and added with organic solvent to separate out solid selenomethionine.

2. The method of claim 1, wherein: in the third step, the mass ratio of diseleno homoserine to sodium acetoxy borohydride is 1: (0.5-2).

3. The method of claim 1, wherein: in the third step, the mass ratio of sodium acetoxyborohydride to methyl iodide is 1: (0.3-3).

4. The method of claim 1, wherein: in the first step, the mass ratio of homoserine, thionyl chloride, acetic acid, hydrochloric acid or hydrobromic acid is 2: (1-6): (2-10): (1-3).

5. The method of claim 1, wherein: in the second step, the molar equivalent ratio of the selenium powder, the strong alkaline substance and the rongalite is 1: (0.5-3): (0.1-1).

6. The method of claim 1, wherein: in the second step, the molar equivalent ratio of the selenium powder to the chlorohomoserine hydrochloride is (1-5): 1.

7. the method of claim 1, wherein: in the first step, the temperature of the stirring reaction is 70-100 ℃, and the time of the stirring reaction is 20-50 hours; in the second step, the stirring reaction temperature is 40-70 ℃; the reaction time is 1-3 hours under stirring.

8. The method of claim 1, wherein: in the second step, the stirring temperature at normal temperature is 8-16 hours; in the third step, the reaction time at normal temperature is 10-60 minutes.

9. The method of claim 1, wherein: in the second and third steps, the strong alkaline substance comprises sodium hydroxide and potassium hydroxide solid or solution;

in the third step, the molar equivalent ratio of diseleno homoserine to strong base is 3 (5-50);

in the second step and the third step, the weak acidity is pH 5-7;

in the third step, the organic solvent is at least one of absolute ethyl alcohol, acetone and methanol.

10. A reaction apparatus for carrying out the production process according to any one of claims 1 to 9,

comprises a reactor, a filter, a chemical pump, a raw material tank, a hydrochloric acid tank, an alkali liquor tank, a product tank and a waste liquor tank;

the first reactor comprises a stirring paddle, a sand core filtering device, a material inlet and a material outlet, wherein the bottom of the first reactor is attached with the sand core filtering device; the material inlets are respectively used for feeding raw materials of homoserine, thionyl chloride, acetic acid, hydrochloric acid or hydrobromic acid and inputting a preparation solution of a source reactor II; the liquid discharge port is used for discharging reaction waste liquid and discharging an intermediate product; the second reactor comprises a stirring paddle, a material inlet and a material outlet; the material inlets are respectively used for feeding the raw materials of selenium powder, sodium formaldehyde sulfoxylate and solid alkali or alkali solution; the discharge hole is used for discharging the reacted mixture; the reactor III comprises a stirring paddle, a sand core filtering device, a material inlet and a material outlet, wherein the bottom of the stirring paddle is attached with the sand core filtering device; the material inlet is respectively used for feeding raw materials of sodium triacetyl borohydride, methyl iodide and ethanol and inputting an intermediate product alkali solution; the discharge port is respectively connected with the finished product tank and the waste liquid tank.

Technical Field

The invention belongs to the field of chemical conversion, and particularly relates to a method and a device for synthesizing selenomethionine.

Background

Selenium is an indispensable micronutrient for humans. The organic selenium substances are the most effective selenium supplementing forms, have weaker toxicity than inorganic selenium and are more suitable for being absorbed by human bodies. Selenomethionine is the main bioactive form of selenium in the body, and selenomethionine is usually non-specifically doped into protein to replace methionine in the body, so that the selenomethionine has a very prominent selenium supplementing effect. China and the european union have approved its use as a feed additive. Although selenomethionine is widely distributed in plants, the content is low, and the selenomethionine is not practical to be extracted from natural plants. Currently, selenomethionine is mainly prepared by chemical synthesis, but remains basically in the laboratory stage, including the following ways: (1) methionine is used as a raw material, and is reacted with dimethyl sulfate, hydrolyzed, cyclized under the catalysis of hydrochloric acid, and finally added with sodium methylselenolate for ring opening and acidification to generate selenomethionine. (2) Firstly, reducing alpha-amino protected aspartic acid beta-alkyl ester to generate alpha-amino protected homoserine, and then catalyzing and cyclizing under an acidic condition to obtain homoserine lactone; reacting a lactone with M₂Se₂Reacting to obtain diseleno homoserine; reacting diseleno homoserine with a reducing agent, and then reacting with a methylating agent to obtain alpha-amino protected selenomethionine; and (4) obtaining selenomethionine after deprotection. (3) Homoserine is firstly subjected to N-acylation and cyclization reaction, then is subjected to reaction with methyl mercaptan, and finally is hydrolyzed to form selenomethionine. (4) Using diethyl sulfate or halogenated alkyl acid or derivative ester thereof to alkylate methionine to generate sulfonium salt, performing desulfurization and ring closure, performing addition ring opening with methyl selenol salt MeSeM, and acidifying to obtain selenomethionine. (5) Selenium and a reducing agent are mixed to carry out reduction reaction, homoserine lactone protected by alpha-amino is added to obtain diseleno homocystine protected by alpha-amino, methylation is carried out after reduction, and finally, selenomethionine is obtained by deprotection. (6) Performing nucleophilic substitution reaction on sodium methylselenolate and 3, 6-di- (2-chloroethyl) -2, 5-diketopiperazine, and hydrolyzing in a hydrochloric acid solution to obtain the L-selenomethionine. (7) Adding hydrogen bromide in acetic acid to homoserine to obtainbromo-L- (+) -homoserine hydrobromide, then reacting with sodium methylselenolate to obtain L- (+) -selenomethionine. The method can obtain the final product, but has the defects of complex preparation process, harsh reaction conditions, low yield, most of the methods use the sodium methylselenolate, the sodium methylselenolate needs to be prepared at present, the smell is large, and the pollution is strong. (8) Homoserine reacts in acetic acid hydrogen bromide solution, filtering is carried out to obtain bromohomoserine solid, then bromohomoserine solid is added into ethanol solution obtained by reacting sodium borohydride with selenium, reaction is continuously carried out for a certain time at about 80 ℃, filtering is carried out to obtain intermediate product diseleno homoserine, finally sodium borohydride is used for reduction, and methyl iodide is added dropwise for reaction to obtain product selenomethionine (shown in figure 1). The method has the advantages of less volatile gas generation, easy product purification and industrial potential.

However, the method also has problems to be overcome, and three problems are mainly faced: firstly, preparing bromohomoserine requires the use of saturated hydrogen bromide acetic acid solution, and has the disadvantages of expensive reagent, high cost, strong volatility and inconvenient use: secondly, reducing selenium powder by using sodium borohydride, performing the reduction in ethanol, heating to 80 ℃ for backflow, wherein the backflow is close to the boiling point of ethanol, and the sodium borohydride is a flammable and explosive reagent, so that the operation risk coefficient is extremely high; in addition, when sodium borohydride is used for reducing diseleno homoserine, the problem that the solution is large in use and high in solution recovery cost due to the dilemma that the pH value of the solution is adjustable within a very small range is faced. The reason is that the alkalinity of the solution is strong, the reaction of reducing diseleno-homoserine by sodium borohydride cannot be started, and if the alkalinity is too weak, the solubility of diseleno-homoserine is too low, and the usage amount of the solvent is too large.

Disclosure of Invention

In order to solve the problems, a novel preparation process is provided: homoserine is used as an initial raw material, and is subjected to chlorination reaction, then the reaction with sodium diselenide solution obtained by reducing selenium powder by a sodium formaldehyde sulfoxylate is carried out, diseleno-homoserine is obtained by filtering, and finally the diseleno-homoserine is reduced by sodium triacetoxyborohydride and is reacted with methyl iodide to prepare selenomethionine. The method has the advantages of simple operation, mild reaction and high comprehensive yield.

Another object of the present invention is to provide a novel apparatus for preparing selenomethionine.

In order to achieve the purpose, the invention adopts the following technical scheme:

a method for preparing selenomethionine comprises the following steps:

mixing homoserine, thionyl chloride, acetic acid, hydrochloric acid or hydrobromic acid, stirring for reaction, filtering after the reaction is finished, and collecting filter residue as chlorohomoserine hydrochloride;

secondly, mixing selenium powder, strong alkaline substances, water and rongalite, stirring for reaction, cooling after the reaction is finished, adding chlorohomoserine hydrochloride, stirring at normal temperature, adding acid, filtering to remove redundant selenium powder, adding alkali into the obtained filtrate, adjusting the filtrate to weak acidity, standing, and filtering to obtain filter residue which is diseleno-homoserine;

thirdly, diseleno homoserine is mixed with strong base substance, dissolved in water, added with triacetoxy sodium borohydride and methyl iodide, added with acid to adjust to subacidity after the reaction at normal temperature is finished, and added with organic solvent to separate out solid selenomethionine.

Preferably, in the first step, the mass ratio of homoserine, thionyl chloride, acetic acid, hydrochloric acid or hydrobromic acid is 2: (1-6): (2-10):(1-3).

Preferably, in the first step, the temperature of the stirring reaction is 70-100 ℃, and the time of the stirring reaction is 20-50 hours.

Preferably, in the second step, the molar equivalent ratio of the selenium powder, the strong alkaline substance and the sodium formaldehyde sulfoxylate is 1: (0.5-3): (0.1-1).

Preferably, in the second step, the stirring reaction temperature is 40-70 ℃; the reaction time is 1-3 hours under stirring.

Preferably, in the second step, the molar equivalent ratio of the selenium powder to the chlorohomoserine hydrochloride is (1-5): 1.

preferably, in the second step, the stirring temperature at normal temperature is 8-16 hours.

Preferably, in the third step, the molar equivalent ratio of the diseleno homoserine to the strong base is 3 (5-50).

Preferably, in the third step, the mass ratio of sodium acetoxyborohydride to methyl iodide is 1: (0.3-3).

Preferably, in the third step, the mass ratio of diseleno homoserine to sodium acetoxy borohydride is 1: (0.5-2).

Preferably, in the third step, the reaction time at normal temperature is 10-60 minutes.

Preferably, in the second and third steps, the strongly alkaline substance comprises solid or solution of sodium hydroxide and potassium hydroxide.

Preferably, in the second and third steps, the weak acidity is pH 5 to 7.

Preferably, in the third step, the organic solvent is at least one of absolute ethyl alcohol, acetone and methanol.

The room temperature, the normal temperature and the unspecified temperature in the invention mean 20-35 ℃.

A reaction device for preparing selenomethionine by taking homoserine as a raw material comprises a reactor, a filter, a chemical pump, a raw material tank, a hydrochloric acid tank, an alkali liquor tank, a finished product tank and a waste liquor tank;

the first reactor comprises a stirring paddle, a sand core filtering device, a material inlet and a material outlet, wherein the bottom of the first reactor is attached with the sand core filtering device; the material inlets are respectively used for feeding raw materials of homoserine, thionyl chloride, acetic acid and hydrochloric acid (or hydrobromic acid) and inputting a preparation solution of a source reactor II; the liquid discharge port is used for discharging reaction waste liquid and discharging an intermediate product; the second reactor comprises a stirring paddle, a material inlet and a material outlet; the material inlets are respectively used for feeding the raw materials of selenium powder, sodium formaldehyde sulfoxylate and solid alkali or alkali solution; the discharge hole is used for discharging the reacted mixture; the reactor III comprises a stirring paddle, a sand core filtering device, a material inlet and a material outlet, wherein the bottom of the stirring paddle is attached with the sand core filtering device; the material inlet is respectively used for feeding raw materials of sodium triacetyl borohydride, methyl iodide and ethanol and inputting an intermediate product alkali solution; the discharge port is respectively connected with the finished product tank and the waste liquid tank.

Compared with the prior art, the invention has the following advantages and beneficial effects:

the invention has the advantages that the homoserine is chlorinated, and the cost is lower than that of document bromination. The solvent prepared by using thionyl chloride, acetic acid and hydrochloric acid (or hydrobromic acid) is easy to prepare at present, is more convenient to use than a hydrogen bromide/acetic acid solution, and is easier to control the emission of waste gas (because the saturated hydrogen bromide acetic acid solution has high volatility). And secondly, reacting the homoserine chloride product with a sodium diselenide solution obtained by reducing selenium powder by a sodium formaldehyde sulfoxylate, wherein the reaction pH is wider in application range (the homoserine bromide product is reacted with the sodium diselenide solution obtained by reducing selenium powder by sodium borohydride in the document, the pH reaction range is about 8-9, bromine atoms in the bromide product are easier to be attacked by strong alkali to reversely generate homoserine), the pH reaction range can be 8-14, and great convenience is brought to actual production. And thirdly, the chlorine content on the earth is far greater than the bromine content, and the chlorine is used for replacing the bromine, so that the conventional resources are used for replacing rare resources, and the utilization efficiency of the resources is improved. And fourthly, reducing the intermediate product diseleno homoserine by using sodium triacetyl borohydride, and compared with the sodium borohydride (the pH value is 9-10 during use) used in the literature, the method can greatly improve the alkalinity of the solution (the pH value can be above 14), promote the dissolution of the raw materials, reduce the usage amount of the solution and reduce the treatment cost.

Drawings

FIG. 1 shows the synthesis process of selenomethionine reported in the literature.

FIG. 2 is a new process for synthesizing selenomethionine according to the invention.

FIG. 3 is a mass spectrum of diseleno-homoserine in example 1.

FIG. 4 is a hydrogen spectrum of diseleno-homoserine in example 1.

FIG. 5 is a carbon spectrum of diseleno-homoserine in example 1.

FIG. 6 is a mass spectrum of selenomethionine in example 1.

FIG. 7 is a hydrogen spectrum of selenomethionine in example 1.

FIG. 8 is a carbon spectrum of selenomethionine in example 1.

FIG. 9 is a diagram of a reaction apparatus for preparing selenomethionine according to the invention

The device comprises a 01-homoserine tank, a 02-acetic acid tank, a 03-thionyl chloride tank, a 04-hydrochloric acid (or hydrobromic acid) tank, a 05-selenium powder tank, a 06-rongalite tank, a 07-lye tank, a 08-sodium triacetoxyborohydride tank, a 09-iodomethane tank, a 10-ethanol tank, an 11-reactor, a 12-reactor, a 13-reactor, a 14-waste liquid tank, a 15-middle tank, a 16-filter, a 17-filter, an 18-dryer, a 19-waste liquid tank, a 20-chemical pump, a 21-chemical pump and 001-021-pipelines.

Detailed Description

The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto. The reagents used in the examples are commercially available without specific reference.

FIG. 9 shows a reaction apparatus for preparing selenomethionine. The reactor 11, it has stirring rake and filters the sand core (bottom), and five feed inlets, connect homoserine tank 01, acetic acid tank 02, thionyl chloride tank 03, hydrochloric acid (or hydrobromic acid) tank 04, chemical pump 20 through pipeline 001, 002, 003, 004, 013 separately, in addition, have two discharge ports, connect waste liquid tank 14 and filter 16 through pipeline 011 and 012 separately. The reactor 12 is provided with a stirring paddle and three feed inlets which are respectively connected with a selenium powder tank 05, a rongalite tank 06 and an alkali liquor tank 07 through pipelines 005, 006 and 007, and is also provided with a discharge outlet which is connected with a middle tank 15 through a pipeline 015, and the middle tank is connected with a chemical pump 20 through the pipeline 015. The filter 17 is provided with two feed inlets which are respectively connected with the filter 16 and the lye tank 07 through pipelines 016 and 007, and is provided with a discharge outlet which is connected with the chemical pump 21 through a pipeline 017. The reactor 13 is provided with a stirring paddle, a filtering sand core (bottom) and four feed inlets which are respectively connected with a chemical pump 21, a sodium triacetoxyborohydride tank 08, a methyl iodide tank 09 and an ethanol tank 10 through pipelines 018, 008, 009 and 010, and is also provided with two discharge outlets which are respectively connected with a finished product tank 18 and a waste liquid tank 19 through pipelines 019 and 020.

A method for preparing selenomethionine by taking homoserine as a raw material. Homoserine, acetic acid, thionyl chloride and hydrochloric acid (or hydrobromic acid) are respectively added into the reactor 11 from a homoserine tank 01, an acetic acid tank 02, a thionyl chloride tank 03 and a hydrochloric acid (or hydrobromic acid) tank 04 through feeding pipes 001, 002, 003, 004 and 013, stirring is started to fully and uniformly mix the materials, the materials are heated and reacted for a certain time at a certain temperature and then cooled to room temperature, waste liquid enters a waste liquid tank 14 through a discharging pipe 011, and solid is reserved in the reactor 11 (solid products are separated out after cooling). Meanwhile, selenium powder, rongalite and sodium hydroxide solution respectively enter the reactor 12 from a selenium powder tank 05, a rongalite tank 06 and an alkali liquor tank 07 through pipelines 005, 006 and 007, are heated and reacted for a certain time at a certain temperature, are cooled to room temperature, are then input into the intermediate tank 15 through a pipeline 015, are kept stand for a certain time, are started up with a chemical pump 20, inject the reaction liquid in the intermediate tank 15 into the reactor 11, and are reacted for a certain time at normal temperature, and then all the solution is discharged into the filter 16 through a pipeline 012. Hydrochloric acid (or hydrobromic acid) is added into the filter 16 from a hydrochloric acid (or hydrobromic acid) tank 04 through a pipeline 004, the pH is adjusted to about 1-2, after standing for a certain time, the filtrate enters the filter 17 through a pipeline 016. The alkali liquor enters the filter 17 from the alkali liquor tank 07 through the pipeline 007, the pH is adjusted to about 5-7, after standing for a certain time, the filtrate is discharged into the waste liquor tank 14 through the pipeline 021, the filter residue is further added with the alkali, the pH is adjusted to about 10-12 until the alkali liquor is completely dissolved, and then the alkali liquor is added into the reactor 13 through the pipeline 018 by the chemical pump 21. Then sodium triacetoxyborohydride (added from a sodium triacetoxyborohydride tank 08 through a pipeline 008) and methyl iodide (added from a methyl iodide tank 09 through a pipeline 009) are sequentially added, the mixture is stirred at normal temperature for 20 minutes, ethanol (added from an ethanol tank 10 through a pipeline 010) is added, the product selenomethionine is separated out from the solution, the waste liquid is transferred to a waste liquid tank 19 through a pipeline 020, and the product is transferred to a dryer 18 through a pipeline 009.

Example 1

1mL of thionyl chloride (1.64 g), 3mL of acetic acid (3.15 g), and 0.5mL of concentrated hydrochloric acid (0.59 g) were mixed, and then 1 g of homoserine was added and stirring was continued at 90 ℃ for 48 hours, cooled to room temperature, and filtered to obtain 1.26 g of chlorohomoserine hydrochloride (yield 85%). Dissolving 2 g of selenium powder and 1.2 g of sodium formaldehyde sulfoxylate in 8ml of 5.0mol/L aqueous solution of sodium hydroxide, stirring for 2 hours at 60 ℃, cooling to room temperature, adding chlorohomoserine hydrochloride (1.26 g), stirring for 10 hours at room temperature, adding hydrochloric acid, standing for 24 hours, filtering to remove excessive selenium powder, adjusting the pH of the filtrate to 5-7 by using sodium hydroxide, standing for 2 days, filtering to obtain 0.47 g of solid (yield 36%), and identifying the solid to be diseleno-homoserine by mass spectrometry and nuclear magnetism. Dissolving the filter residue diseleno homoserine obtained in the previous step into 10 mL of 1.0mol/L sodium hydroxide aqueous solution, adding 1.0 g of triacetoxyborohydride sodium and 0.8mL of methyl iodide, reacting for 20 minutes, adding hydrochloric acid to adjust the pH value to 5-7, adding absolute ethyl alcohol, and separating out 0.43 g of solid (yield 86%), wherein the solid is identified as selenomethionine through mass spectrometry and nuclear magnetism.

Example 2

1.5mL of thionyl chloride, 3mL of acetic acid, and 0.5mL of concentrated hydrochloric acid were mixed, and then 1 g of homoserine was added and stirring was continued at 80 ℃ for 48 hours, cooled to room temperature, and filtered to obtain 1.46 g of chlorohomoserine hydrochloride (yield 99%). Dissolving 2 g of selenium powder and 1.2 g of sodium formaldehyde sulfoxylate in 8ml of 5.0mol/L aqueous sodium hydroxide solution, stirring at 40 ℃ for 3 hours, cooling to room temperature, adding chlorohomoserine hydrochloride (1.46 g), stirring at room temperature for 10 hours, adding hydrochloric acid, standing for 36 hours, filtering to remove excessive selenium powder, adjusting the pH of the filtrate to 5-7 with sodium hydroxide, standing for 3 days, and filtering to obtain 0.39 g of a solid (yield 26%). The diseleno homoserine residue obtained in the previous step is dissolved in 10 mL of 1.0mol/L sodium hydroxide aqueous solution, 0.6 g of triacetoxyborohydride sodium and 0.5mL of methyl iodide (1.14 g) are added, after the reaction is carried out for 30 minutes, hydrochloric acid is added to adjust the pH value to 5-7, and absolute ethyl alcohol is added, so that 0.30 g of solid is precipitated (yield is 70%).

Example 3

1.0mL of thionyl chloride, 3mL of acetic acid, and 1.5mL of concentrated hydrochloric acid were mixed, and then 1 g of homoserine was added and stirring was continued at 70 ℃ for 20 hours, cooled to room temperature, and filtered to obtain 1.26 g of chlorohomoserine hydrochloride (yield 85%). Dissolving 2 g of selenium powder and 1.4 g of sodium formaldehyde sulfoxylate into 8ml of 5.0mol/L aqueous solution of sodium hydroxide, stirring for 3 hours at 50 ℃, cooling to room temperature, adding chlorohomoserine hydrochloride (1.26 g), stirring for 15 hours at normal temperature, adding hydrochloric acid, standing for 36 hours, filtering to remove excessive selenium powder, adjusting the pH of the filtrate to 5-7 by 10 ml of 1.0mol/L sodium hydroxide, standing for 3 days, and filtering to obtain 0.43 g of solid (yield 30%). The diseleno-homoserine residue obtained in the previous step is dissolved in 10 mL of 1.0mol/L sodium hydroxide aqueous solution, 0.8 g of triacetoxyborohydride sodium and 0.5mL of methyl iodide (1.14 g) are added, after 10 minutes of reaction, hydrochloric acid is added to adjust the pH value to 5-7, and absolute ethyl alcohol is added to precipitate 0.35 g of solid (yield is 75%).

Example 4

1.5mL of thionyl chloride, 3mL of acetic acid, and 0.5mL of concentrated hydrochloric acid were mixed, and then 1 g of homoserine was added and stirring was continued at 90 ℃ for 20 hours, cooled to room temperature, and filtered to obtain 1.48 g of chlorohomoserine hydrochloride (yield 100%). Dissolving 2 g of selenium powder and 1.2 g of sodium formaldehyde sulfoxylate in 8ml of 5.0mol/L aqueous sodium hydroxide solution, stirring at 60 ℃ for 2 hours, cooling to room temperature, adding chlorohomoserine hydrochloride (1.48 g), stirring at room temperature for 15 hours, adding hydrochloric acid, standing for 48 hours, filtering to remove excessive selenium powder, adjusting the pH of the filtrate to 5-7 with sodium hydroxide, standing for 3 days, and filtering to obtain 0.53 g of solid (yield 35%). The diseleno-homoserine residue obtained in the previous step is dissolved in 10 mL of 1.0mol/L sodium hydroxide aqueous solution, 1.0 g of triacetoxyborohydride sodium and 0.5mL of methyl iodide (1.14 g) are added, after 10 minutes of reaction, hydrochloric acid is added to adjust the pH value to 5-7, and absolute ethyl alcohol is added to precipitate 0.45 g of solid (yield 79%).

Example 5

1.5mL of thionyl chloride, 3mL of acetic acid, and 0.5mL of hydrobromic acid were mixed, and then 1 g of homoserine was added and stirring was continued at 90 ℃ for 20 hours, cooled to room temperature and filtered to obtain 1.51 g of chlorohomoserine hydrochloride (yield 100%). Dissolving 2 g of selenium powder and 1.2 g of sodium formaldehyde sulfoxylate in 8ml of 5.0mol/L aqueous sodium hydroxide solution, stirring at 60 ℃ for 2 hours, cooling to room temperature, adding chlorohomoserine hydrochloride (1.51 g), stirring at room temperature for 15 hours, adding hydrochloric acid, standing for 48 hours, filtering to remove excessive selenium powder, adjusting the pH of the filtrate to 5-7 with sodium hydroxide, standing for 3 days, and filtering to obtain 0.55 g of solid (yield: 35%). Dissolving the filter residue diseleno homoserine obtained in the previous step into 10 mL of 1.0mol/L sodium hydroxide aqueous solution, adding 1.0 g of sodium triacetoxyborohydride and 0.2mL of methyl iodide, reacting for 10 minutes, adding hydrochloric acid to adjust the pH value to 5-7, adding absolute ethyl alcohol, and precipitating solid 0.51 g (yield 86%).

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.