阅读说明：本技术 一种用锌、铁还原制备l-硒-甲基硒代半胱氨酸的方法以及装置 (Method and device for preparing L-selenium-methyl selenocysteine by reducing zinc and iron ) 是由 周华 廖津 戴扬晓 胡长鹰 欧仕益 傅亮 余稳稳 于 2021-08-13 设计创作，主要内容包括：本发明属于化学合成领域,具体公开了一种用锌、铁还原制备L-硒-甲基硒代半胱氨酸的方法以及装置。以硒代胱氨酸为原料,采用锌或铁还原生成硒代半胱氨酸,然后加碘甲烷乙醇溶液甲基化反应,反应完全后,加入无水乙醇,析出L-硒-甲基硒代半胱氨酸固体。该方法简单易行、成本低、产率较高,没有有害物质残留,产品更安全,具有非常显著的经济效益。(The invention belongs to the field of chemical synthesis, and particularly discloses a method and a device for preparing L-selenium-methyl selenocysteine by reducing zinc and iron. The method comprises the steps of using selenocysteine as a raw material, reducing zinc or iron to generate selenocysteine, adding an iodomethane ethanol solution for methylation reaction, and adding absolute ethanol after the reaction is completed to separate out L-selenium-methyl selenocysteine solid. The method is simple and easy to implement, low in cost, high in yield, free of harmful substance residues, safer in product and very remarkable in economic benefit.)

1. A method for preparing L-selenium-methyl selenocysteine by reducing zinc and iron is characterized by comprising the following steps:

dissolving selenocysteine in alkaline or acidic solution, adding reducing agent zinc and/or iron, and stirring for reaction; adjusting the pH of the solution to 4-7, standing, filtering, removing precipitate, and adjusting the pH of the filtrate to 8-10; and dropwise adding methyl iodide and an absolute ethyl alcohol organic solvent, stirring and reacting at room temperature, adding the absolute ethyl alcohol organic solvent after the reaction is finished, separating out a precipitate, filtering, collecting filter residues, and drying to obtain the L-selenium-methyl selenocysteine product.

2. The method of claim 1, wherein: the equivalent molar ratio of selenocysteine to the reducing agent zinc and/or iron is 1: (1-4).

3. The method of claim 1, wherein: the equivalent molar ratio of the selenocysteine to the methyl iodide is 1: (2-4).

4. The method of claim 1, wherein: the pH of the alkaline solution is greater than 8 and the pH of the acidic solution is less than 2.

5. The method of claim 1, wherein: the stirring reaction temperature after the zinc or the iron is added is 30-50 ℃, and the stirring reaction time is 10-180 minutes.

6. The method of claim 1, wherein: the alkaline substance contained in the alkaline solution comprises at least one of sodium hydroxide and potassium hydroxide; the equivalent molar concentration of the alkaline substance is 2.0-10.0 mol/L.

7. The method of claim 1, wherein: the time for adding the iodomethane and stirring for reaction is 10-60 minutes.

8. The method of claim 1, wherein: the organic solvent is at least one of absolute ethyl alcohol, methanol and acetone.

9. A reaction apparatus for carrying out the production method according to any one of claims 1 to 8, characterized in that:

comprises a reactor, a filter, a chemical pump, various raw material tanks, a hydrochloric acid tank, an alkali liquor tank, an adjusting tank, an intermediate tank, a dryer and a waste liquor tank;

the first reactor comprises a stirring paddle, a material inlet and a material outlet; the material inlets are respectively used for feeding raw materials of selenocysteine, zinc or iron, and alkaline solution or acidic solution; the liquid discharge port is used for discharging reaction liquid; the adjusting tank is provided with two material inlets and a material outlet; the material inlet inputs reaction liquid from the first reactor, and the other is connected with a hydrochloric acid tank; the liquid discharge port is used for outputting the solution after acid regulation; the filter is used for removing unreacted reducing agent or a small amount of byproducts and is provided with a material inlet and a material outlet; the second reactor comprises a stirring paddle, a material inlet and a material outlet; the material inlet is respectively used for feeding filtrate, alkali liquor, methyl iodide and absolute ethyl alcohol; the discharge hole is used for discharging reaction liquid; the second filter is provided with two material inlets and two material outlets; the material inlets are respectively used for inputting absolute ethyl alcohol and a crude product in the intermediate tank; and the liquid discharge port is respectively used for outputting waste liquid and finished products.

Technical Field

The invention belongs to the field of chemical synthesis, and particularly relates to a method and a device for preparing L-selenium-methyl selenocysteine by reducing zinc and iron.

Background

Selenium is an indispensable micronutrient for human beings, and the supplement of selenium element in daily diet is advocated by the world health organization and is also applied to the treatment of patients with new coronary pneumonia at present. The organic selenium substance is the most effective selenium supplement form, has weaker toxicity than inorganic selenium, and is more suitable for being absorbed by human bodies. L-selenium-methyl selenocysteine is a methylated derivative of selenocysteine, is widely researched and developed due to the advantages of low toxicity, good selenium supplementing effect, cancer prevention and treatment, oxidation resistance, aging resistance, cardiovascular and cerebrovascular disease treatment, heavy metal poisoning removal and the like, and is approved as a novel nutrition enhancer by the Ministry of health.

The preparation of the L-selenium-methyl selenocysteine comprises an extraction method, an enzymatic synthesis method and a chemical synthesis method, wherein the two methods are caused by the reasons of low content of effective components in raw materials and the like, have high cost and temporarily do not meet the industrialized condition. The chemical synthesis method has relatively low cost and better industrialization prospect. The main synthetic method comprises 1) reacting methyl sodium selenol with chloroalanine and derivatives to obtain the target product. The main problems of this process are the low yield and the emission of volatile gases with a strong odor. 2) The method has the advantages of less volatile gas emission, high yield of target products and stronger application prospect, and has the main problems that a flammable and combustible sodium borohydride reagent is used in the reduction process, and in addition, trace boron element residues possibly exist in the products after separation and purification, thereby bringing safety concerns.

Disclosure of Invention

In order to solve the defects and shortcomings of the prior art, the invention aims at providing a method for preparing L-selenium-methyl selenocysteine by using zinc and iron as reducing agents. The method is simple and easy to implement, low in cost, high in yield, free of harmful substance residues, safer in product and very remarkable in economic benefit.

The invention also aims to provide a preparation device for preparing the L-selenium-methyl selenocysteine by using zinc and iron as reducing agents.

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

a method for preparing L-selenium-methyl selenocysteine by reducing zinc and iron comprises the following steps:

dissolving selenocysteine in alkaline or acidic solution, adding reducing agent zinc and/or iron, and stirring for reaction; adjusting the pH of the solution to 4-7, standing, filtering, removing precipitate, and adjusting the pH of the filtrate to 8-10; and dropwise adding methyl iodide and an organic solvent, stirring and reacting at room temperature, adding the organic solvent after the reaction is finished, separating out a precipitate, filtering, collecting filter residues, and drying to obtain the L-selenium-methyl selenocysteine product.

Preferably, the zinc and iron reducing agent can be in different shapes such as powder, flake, silk and the like.

Preferably, the equivalent molar ratio of the selenocysteine to the reducing agents zinc and iron is 1: (1-4).

Preferably, the pH of the alkaline solution is greater than 8 and the pH of the acidic solution is less than 2;

preferably, the alkaline substance contained in the alkaline solution includes at least one of sodium hydroxide, potassium hydroxide, and the like.

Preferably, the equivalent molar concentration of the alkaline solution is 2.0-10.0 mol/L.

Preferably, the stirring reaction temperature after the zinc or iron is added is 30-50 ℃, and the stirring reaction time is 10-180 minutes.

Preferably, the equivalent molar ratio of selenocysteine to methyl iodide is 1: (2-4).

Preferably, the time for stirring reaction after adding the methyl iodide is 10-60 minutes.

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

The room temperature and unspecified temperatures referred to herein are 20-35 ℃.

A device for preparing L-selenium-methyl selenocysteine by taking zinc and iron as reducing agents comprises a reactor, a filter, a chemical pump, a raw material tank, a hydrochloric acid tank, an alkali liquor tank, a regulating tank, an intermediate tank, a dryer and a waste liquor tank;

the first reactor comprises a stirring paddle, a material inlet and a material outlet; the material inlets are respectively used for feeding raw materials of selenocysteine, zinc or iron, and alkaline solution or acidic solution; the liquid discharge port is used for discharging reaction liquid; the adjusting tank is provided with two material inlets and a material outlet; the material inlet inputs reaction liquid from the first reactor, and the other is connected with a hydrochloric acid tank; the liquid discharge port is used for outputting the solution after acid regulation; the filter is used for removing unreacted reducing agent or a small amount of byproducts and is provided with a material inlet and a material outlet; the second reactor comprises a stirring paddle, a material inlet and a material outlet; the material inlet is respectively used for feeding filtrate, alkali liquor, methyl iodide and absolute ethyl alcohol; the discharge hole is used for discharging reaction liquid; the second filter is provided with two material inlets and two material outlets; the material inlets are respectively used for inputting absolute ethyl alcohol and a crude product (solution after the reaction is finished) in the intermediate tank; and the liquid discharge port is respectively connected with a waste liquid tank and a dryer.

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

the reduction of zinc and iron is different from sodium borohydride, the reaction is mild, the zinc (iron) hydroxide generated by reduction is insoluble in water and very easy to remove, even if trace residues exist, the potential safety hazard can not be caused, and a great amount of zinc supplement products are in great demand in the current market. The invention dissolves the raw materials under acidic or alkaline conditions, then adjusts to the range of weak acidity to precipitate zinc hydroxide/iron, finally adjusts to weak alkalinity to carry out methylation reaction, and successfully obtains the L-selenium-methyl selenocysteine product after a series of pH changes. The cost of both the reagent and the separation and purification is very low.

Drawings

FIG. 1 is a synthetic route of L-selenium-methylselenocysteine;

FIG. 2 is a mass spectrum of L-selenium-methylselenocysteine;

FIG. 3 is a hydrogen spectrum of L-selenium-methylselenocysteine;

FIG. 4 is a carbon spectrum of L-selenium-methylselenocysteine;

FIG. 5 shows a device for preparing L-Se-methylselenocysteine and selenomethionine;

01-selenocysteine ammonia tank, 02-reducing agent (zinc or iron) tank, 03-lye tank, 04-acid solution tank, 05-methyl iodide tank, 06-absolute ethanol tank, 07-reactor, 08-reactor, 09-filter, 10-regulating tank, 11-filter, 12-intermediate tank, 13-waste solution tank, 14-dryer, 15-chemical pump, 16-chemical pump, 001-015) -pipeline.

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.

As shown in fig. 5, the device for preparing L-selenium-methylselenocysteine by using zinc and iron as reducing agents comprises reactors 07, 08, two filters 09 and 11, two chemical pumps 15, 16, an acid liquor tank 04, an alkali liquor tank 05, an adjusting tank 10, a waste liquor tank 13 and a dryer 14. The reactor 07 is provided with feeding pipes 001, 002, 003 and 004 for feeding raw materials of selenocysteine, zinc or iron, an alkali solution and an acid solution; reactor 07 bottom is equipped with material exit tube 007, connects the surge tank 11, and this jar passes through pipeline 004 and connects sour liquid jar 04, and the lye tank 03 is connected to pipeline 003 to and connect filter 11 through pipeline 008. The reactor 08 is provided with feed pipelines 001, 003, 005 and 006 which are respectively connected with a chemical pump 15, an alkali liquor tank 03, a methyl iodide tank 05 and an absolute ethyl alcohol tank 06, and is additionally provided with a discharge port which is connected with an intermediate tank 12 through a pipeline 011. The filter 09 is connected to a chemical pump 16 and an absolute ethanol tank 06 through inlet pipes 013 and 006, and is connected to a waste liquid tank 13 and a dryer 14 through outlet pipes 014 and 015.

A process for preparing L-Se-methylselenocysteine from Zn and Fe as reducer includes such steps as adding selenocysteine and reducer Zn or Fe, alkali solution or acid solution to reactor 07 via feed tubes 001, 002, 003 and 004, stirring at a certain temp for reaction, filling the resultant liquid to regulating tank 10 via pipeline 001, dropping acidic solution or alkaline solution via 004, laying aside for a certain time, adding the solid-liquid mixture to filter 09 via 008, starting chemical pump 15, filling the filtrate to reactor 08 via pipelines 009 and 010, adding alkali solution via pipeline 003, mixing, adding iodomethane and absolute alcohol via pipelines 005 and 006, stirring at ordinary temp for a certain time, discharging the resultant liquid (crude product) to intermediate tank 12 via pipeline 011, starting chemical pump 16, the reaction liquid (crude product) is fed into a filter 11 through a pipe 014, a certain amount of absolute ethanol is supplemented through a pipe 006, the waste liquid recovered through the pipe 014 is filtered to a waste liquid tank 13, and the finished product is discharged to a dryer 14 through a pipe 015.

Example 1

0.49 g of selenocysteine is dissolved in 10 ml of 2mol/L NaOH solution, 0.20 g of zinc powder is added, and the mixture is stirred for 12 minutes at 40 ℃. The solution was adjusted to pH 6.0 with acid at room temperature and white granular material appeared as well as flocculent precipitate and filtered. Adjusting the pH value of the filtrate to 9.0 by 6mol/L NaOH, adding 0.18 ml of methyl iodide and 1 ml of absolute ethyl alcohol, stirring at normal temperature for reaction for 30 minutes, then adding 10 ml of absolute ethyl alcohol, allowing the solution to generate a large amount of white precipitates, filtering, and drying filter residues at 60 ℃ for 30 minutes to obtain the product, wherein the weight of the product is 0.52 g (the yield is 96.3%). The L-selenium-methyl selenocysteine is identified by mass spectrum, hydrogen spectrum and carbon spectrum.

Example 2

0.49 g of selenocysteine is dissolved in 10 ml of 2mol/L NaOH solution, 0.18 g of zinc sheet is added, and the mixture is stirred for 20 minutes at 50 ℃. The solution was adjusted to pH 5.0 with acid at room temperature and white granular material appeared as well as flocculent precipitate and filtered. Adjusting the pH value of the filtrate to 9.0 by using 8mol/L NaOH, adding 0.19 ml of methyl iodide and 1 ml of absolute ethyl alcohol, stirring at normal temperature for reaction for 50 minutes, then adding 10 ml of absolute ethyl alcohol, allowing a large amount of white precipitate to appear in the solution, filtering, and drying filter residues at 60 ℃ for 30 minutes to obtain the product, wherein the weight of the product is 0.40 g (the yield is 74.07%).

Example 3

0.49 g of selenocysteine is dissolved in 10 ml of 4mol/L NaOH solution, 0.18 g of zinc sheet is added, and the mixture is stirred for 30 minutes at the temperature of 30 ℃. The solution was adjusted to pH 6.0 with acid at room temperature and white granular material appeared as well as flocculent precipitate and filtered. Adjusting the pH of the filtrate to 9.0 by using 8mol/L NaOH, adding 0.21 ml of methyl iodide and 1 ml of absolute ethyl alcohol, stirring at normal temperature for reaction for 50 minutes, then adding 6 ml of absolute ethyl alcohol, allowing the solution to generate a large amount of white precipitates, filtering, and drying filter residues at 60 ℃ for 30 minutes to obtain the product, wherein the weight of the product is 0.42 g (the yield is 77.78%).

Example 4

0.49 g of selenocysteine is dissolved in 10 ml of 4mol/L NaOH solution, 0.60 g of iron powder is added, and the mixture is stirred for 120 minutes at the temperature of 60 ℃. The solution was adjusted to pH 6.0 with acid at room temperature and a brown particulate material appeared as well as a flocculent precipitate and filtered. Adjusting the pH value of the filtrate to 9.0 by 6mol/L NaOH, adding 0.25 ml of methyl iodide and 1 ml of absolute ethyl alcohol, stirring at normal temperature for reaction for 50 minutes, then adding 10 ml of absolute ethyl alcohol, precipitating the solution in a large amount, filtering, and drying filter residues at 60 ℃ for 30 minutes to obtain the product, wherein the weight of the product is 0.20 g (the yield is 37.02%).

Example 5

0.50 g of selenocysteine is dissolved in 10 ml of 2mol/L hydrochloric acid solution, 0.18 g of zinc sheet is added, and the mixture is stirred for 30 minutes at the temperature of 30 ℃. The solution was adjusted to pH 6.0 with base at room temperature, white granular material appeared together with a flocculent precipitate, and filtered. Adjusting the pH value of the filtrate to 9.0 by using 8mol/L NaOH, adding 0.21 ml of methyl iodide and 1 ml of absolute ethyl alcohol, stirring at normal temperature for reaction for 50 minutes, then adding 6 ml of absolute ethyl alcohol, allowing a large amount of white precipitate to appear in the solution, filtering, and drying filter residues at 60 ℃ for 30 minutes to obtain the product, wherein the weight of the product is 0.44 g (the yield is 80.01%).

Example 6

0.49 g of selenocysteine is dissolved in 10 ml of 2mol/L hydrochloric acid solution, 0.25 g of iron powder is added, and the mixture is stirred for 120 minutes at room temperature. The solution was adjusted to pH 6.0 with base at room temperature, a brown granular material appeared together with a flocculent precipitate and filtered. Adjusting the pH value of the filtrate to 9.0 by 6mol/L NaOH, adding 0.25 ml of methyl iodide and 1 ml of absolute ethyl alcohol, stirring at normal temperature, reacting for 50 minutes, then adding 10 ml of absolute ethyl alcohol, precipitating the solution, filtering, and drying the filter residue at 60 ℃ for 30 minutes to obtain the product, wherein the weight of the product is 0.14 g (the yield is 25.02%).

Comparative example 1:

0.50 g of selenocysteine is suspended in distilled water, 0.20 g of zinc powder is added, and the mixture is stirred for 20 minutes at 40 ℃. The solution was adjusted to pH 6.0 with acid at room temperature and insoluble material was filtered off. Adjusting the pH value of the filtrate to 9.0 by 6mol/L NaOH, adding 0.18 ml of methyl iodide and 1 ml of absolute ethyl alcohol, stirring at normal temperature for reaction for 30 minutes, then adding 10 ml of absolute ethyl alcohol, allowing a small amount of white precipitate to appear in the solution, filtering, and drying the filter residue at 60 ℃ for 30 minutes to obtain the product, wherein the weight of the product is 0.05 g (the yield is 8%).

Comparative example 2:

0.50 g of selenocysteine is suspended in distilled water, 0.60 g of iron powder is added, and the mixture is stirred for 120 minutes at the temperature of 60 ℃. The solution was adjusted to pH 6.0 with acid at room temperature and insoluble material was filtered off. The filtrate was adjusted to pH 9.0 with 6mol/L NaOH, and 0.18 ml of methyl iodide and 1 ml of absolute ethanol were added and stirred at room temperature for reaction for 30 minutes, and then 10 ml of absolute ethanol was added, and the solution did not precipitate, i.e., the product was not obtained (yield 0%).

Comparative example 3:

dissolving 0.49 g of selenocysteine in 10 ml of 2mol/L NaOH solution, adding 0.20 g of zinc powder, stirring for 12 minutes at 40 ℃, adjusting pH value, adding 0.18 ml of methyl iodide and 1 ml of absolute ethyl alcohol, stirring for reaction for 30 minutes at normal temperature, then adding 10 ml of absolute ethyl alcohol, allowing a large amount of white precipitate to appear in the solution, filtering, and drying filter residues for 30 minutes at 60 ℃ to obtain a white solid with the weight of 1.2 g. The liquid chromatography analysis shows that the yield of L-selenium-methyl selenocysteine is less than 20%, and most of the L-selenium-methyl selenocysteine is a complex of amino acid (including selenocysteine, L-selenium-methyl selenocysteine and the like) and zinc ions.

Comparative example 4:

0.50 g of selenocysteine is dissolved in 10 ml of 2mol/L hydrochloric acid solution, 0.18 g of zinc sheet is added, and the mixture is stirred for 30 minutes at the temperature of 30 ℃. The reaction was carried out at room temperature for 50 minutes by adding 0.21 ml of methyl iodide and 1 ml of anhydrous ethanol without adjusting the pH, and then 6 ml of anhydrous ethanol was added, and the solution was free from white precipitate, i.e., no product could be obtained (no reaction was observed by TLC spotting).

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.