A kind of preparation method of N-acetyl-L-cysteine

Abstract

The invention discloses a method for preparing N-acetyl-L-cysteine, and relates to the technical field of amino acid preparation. The preparation method comprises the following steps: S1. adding hydrochloric acid to L-cysteine ​​to prepare an L-cysteine ​​hydrochloric acid solution, feeding the solution into the cathode chamber of an electrolytic cell, feeding sulfuric acid into the anode chamber of the electrolytic cell, performing electrolysis, obtaining a cathode liquid, performing reduced pressure concentration, cooling and crystallizing, and centrifugal filtration to obtain L-cysteine ​​hydrochloride; S2. adding acetic anhydride to L-cysteine ​​hydrochloride in an ice bath to perform an acylation reaction, adding a hydrochloric acid solution to adjust the pH value after the acylation reaction is completed, performing reduced pressure concentration, adding deionized water to dissolve the solution, filtering, cooling and crystallizing the solution, centrifugal filtration, and vacuum drying to obtain a crude N-acetyl-L-cysteine ​​product; and S3. adding deionized water to the crude N-acetyl-L-cysteine ​​product to dissolve the solution, cooling and crystallizing the solution, filtering, washing a filter cake, and drying the solution to obtain the N-acetyl-L-cysteine.

Description

Technical Field

[0001] The invention relates to the technical field of amino acid preparation, and in particular to a method for preparing N-acetyl-L-cysteine. Background Art

[0002] N-acetyl-L-cysteine ​​has a strong mucolytic effect. It breaks the disulfide bonds (-SS) in the mucin polypeptide chain through the sulfhydryl group (-SH) in the chemical structure that can react with the electrophilic oxidizing group, decomposes the mucin complex, reduces sputum viscosity, and makes sticky sputum easier to cough up. N-acetyl-L-cysteine ​​can also break the DNA fibers in purulent sputum, so it can not only dissolve white sticky sputum, but also purulent sputum.

[0003] The existing production method of N-acetyl-L-cysteine ​​has high requirements for production equipment and high energy consumption. In addition, excessive acetic anhydride will also lead to a large increase in impurity D, thereby reducing the reaction yield. Summary of the invention

[0004] In view of the defects in the prior art, the present invention provides a method for preparing N-acetyl-L-cysteine. The preparation method provided by the present invention has low equipment requirements, low energy consumption, reasonable material ratio and reaction conditions, high reaction conversion rate, greatly reduces the generation of impurities, and post-treatment operations can further remove impurities. The obtained N-acetyl-L-cysteine ​​has high purity and high reaction yield.

[0005] The object of the present invention is to protect a method for preparing N-acetyl-L-cysteine, the steps are as follows:

[0006] S1. L-cystine is added with hydrochloric acid to prepare L-cystine hydrochloric acid solution, which is fed into the cathode chamber of the electrolytic cell, and sulfuric acid is fed into the anode chamber of the electrolytic cell for electrolysis to obtain a cathode solution, which is concentrated under reduced pressure, cooled for crystallization, and centrifuged to obtain L-cysteine ​​hydrochloride;

[0007] S2. In an ice bath, acetic anhydride is added to L-cysteine ​​hydrochloride to carry out an acylation reaction. After the acylation reaction is completed, a hydrochloric acid solution is added to adjust the pH value, the reaction is concentrated under reduced pressure, deionized water is added to dissolve, the reaction is filtered, the reaction is cooled and crystallized, the reaction is centrifuged and filtered, and the reaction is dried in vacuo to obtain a crude N-acetyl-L-cysteine ​​product;

[0008] S3. Add deionized water to the crude N-acetyl-L-cysteine ​​to dissolve it, cool it for crystallization, filter it, wash the filter cake, and dry it to obtain the N-acetyl-L-cysteine.

[0009] Preferably, in step S1, the concentration of the hydrochloric acid is 3M, and the solid-liquid ratio of L-cystine to hydrochloric acid is 70-80g:500-550ml; the concentration of the sulfuric acid is 3M, and the amount of sulfuric acid is 500-600ml.

[0010] Preferably, in step S1, the electrolysis is performed until the optical rotation of the cathode chamber solution is stable, the voltage of the electrolysis is 60-100V, and the current is 500-300A.

[0011] Preferably, in step S1, the reduced pressure concentration is concentrated to 30-31 degrees Baume.

[0012] Preferably, in step S2, after the acylation reaction is completed, a hydrochloric acid solution is added to adjust the pH value to 2.

[0013] Preferably, in step S2, while carrying out the acylation reaction, sodium hydroxide solution is added to adjust the pH of the acylation reaction process to 9-10.

[0014] Preferably, in step S2, the cooling crystallization is cooling to 4-5°C for crystallization for 5-10 hours; the temperature of the reduced pressure concentration is 65-75°C, and the temperature of the vacuum drying is 50-60°C.

[0015] Preferably, in step S3, the solid-to-liquid ratio of the crude N-acetyl-L-cysteine ​​and deionized water is 1 g:1 ml.

[0016] Preferably, in step S3, the cooling crystallization is performed by cooling to 4-5°C for crystallization for 3 hours, and then cooling to -4-0°C for crystallization for 3 hours.

[0017] Preferably, in step S3, the drying is performed at 60-70° C. for 4 hours and then naturally cooled.

[0018] The beneficial effects of the present invention are embodied in:

[0019] (1) The preparation method provided by the present invention has low equipment requirements, low energy consumption, reasonable material ratio and reaction conditions, high reaction conversion rate, greatly reduces the generation of impurities, and the post-treatment operation can further remove impurities. The obtained N-acetyl-L-cysteine ​​has high purity and high reaction yield.

[0020] (2) The preparation method provided by the present invention is simple to operate, has stable technology, and the obtained product has excellent effect and great promotion value. DETAILED DESCRIPTION

[0021] The following embodiments of the technical solution of the present invention are described in detail. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and are therefore only used as examples, and cannot be used to limit the protection scope of the present invention.

[0022] It should be noted that, unless otherwise specified, the technical terms or scientific terms used in this application should have the common meanings understood by those skilled in the art to which the present invention belongs.

[0023] Example 1

[0024] This embodiment provides a method for preparing N-acetyl-L-cysteine, the steps are as follows:

[0025] S1. L-cystine is added with hydrochloric acid to prepare L-cystine hydrochloric acid solution, which is fed into the cathode chamber of the electrolytic cell, and sulfuric acid is fed into the anode chamber of the electrolytic cell for electrolysis to obtain a cathode solution, which is concentrated under reduced pressure, cooled for crystallization, and centrifuged to obtain L-cysteine ​​hydrochloride;

[0026] S2. In an ice bath, acetic anhydride is added to L-cysteine ​​hydrochloride to carry out an acylation reaction. After the acylation reaction is completed, a hydrochloric acid solution is added to adjust the pH value, the reaction is concentrated under reduced pressure, deionized water is added to dissolve, the reaction is filtered, the reaction is cooled and crystallized, the reaction is centrifuged and filtered, and the reaction is dried in vacuo to obtain a crude N-acetyl-L-cysteine ​​product;

[0027] S3. Add deionized water to the crude N-acetyl-L-cysteine ​​to dissolve it, cool it for crystallization, filter it, wash the filter cake, and dry it to obtain the N-acetyl-L-cysteine.

[0028] In step S1, the concentration of the hydrochloric acid is 3M, and the solid-liquid ratio of L-cystine to hydrochloric acid is 75g:525ml; the concentration of the sulfuric acid is 3M, and the amount of sulfuric acid is 550ml.

[0029] In step S1, the electrolysis is performed until the optical rotation of the cathode chamber solution is stable, and the voltage of the electrolysis is 80V and the current is 400A.

[0030] In step S1, the reduced pressure concentration is concentrated to 30 degrees Baume.

[0031] In step S2, after the acylation reaction is completed, hydrochloric acid solution is added to adjust the pH value to 2.

[0032] In step S2, while the acylation reaction is being carried out, a sodium hydroxide solution is added to adjust the pH of the acylation reaction process to 9.

[0033] In step S2, the cooling crystallization is performed by cooling to 4°C for 8 hours; the temperature of the reduced pressure concentration is 70°C, and the temperature of the vacuum drying is 55°C.

[0034] In step S3, the solid-to-liquid ratio of the crude N-acetyl-L-cysteine ​​to deionized water is 1 g:1 ml.

[0035] In step S3, the cooling crystallization is performed by cooling to 4°C for crystallization for 3 hours, and then cooling to -4°C for crystallization for 3 hours.

[0036] In step S3, the drying is performed at 65° C. for 4 hours and then naturally cooled.

[0037] Example 2

[0038] This embodiment provides a method for preparing N-acetyl-L-cysteine, the steps are as follows:

[0039] S1. L-cystine is added with hydrochloric acid to prepare L-cystine hydrochloric acid solution, which is fed into the cathode chamber of the electrolytic cell, and sulfuric acid is fed into the anode chamber of the electrolytic cell for electrolysis to obtain a cathode solution, which is concentrated under reduced pressure, cooled for crystallization, and centrifuged to obtain L-cysteine ​​hydrochloride;

[0040] S2. In an ice bath, acetic anhydride is added to L-cysteine ​​hydrochloride to carry out an acylation reaction. After the acylation reaction is completed, a hydrochloric acid solution is added to adjust the pH value, the reaction is concentrated under reduced pressure, deionized water is added to dissolve, the reaction is filtered, the reaction is cooled and crystallized, the reaction is centrifuged and filtered, and the reaction is dried in vacuo to obtain a crude N-acetyl-L-cysteine ​​product;

[0041] S3. Add deionized water to the crude N-acetyl-L-cysteine ​​to dissolve it, cool it for crystallization, filter it, wash the filter cake, and dry it to obtain the N-acetyl-L-cysteine.

[0042] In step S1, the concentration of the hydrochloric acid is 3M, and the solid-liquid ratio of L-cystine to hydrochloric acid is 80g:550ml; the concentration of the sulfuric acid is 3M, and the amount of sulfuric acid is 600ml.

[0043] In step S1, the electrolysis is performed until the optical rotation of the solution in the cathode chamber is stable, and the voltage of the electrolysis is 100V and the current is 500A.

[0044] In step S1, the reduced pressure concentration is concentrated to 30 degrees Baume.

[0045] In step S2, after the acylation reaction is completed, hydrochloric acid solution is added to adjust the pH value to 2.

[0046] In step S2, while performing the acylation reaction, sodium hydroxide solution is added to adjust the pH of the acylation reaction process to 10, and the sodium hydroxide solution is.

[0047] In step S2, the cooling crystallization is cooling to 5°C for crystallization for 10 hours; the temperature of the reduced pressure concentration is 75°C, and the temperature of the vacuum drying is 60°C.

[0048] In step S3, the solid-to-liquid ratio of the crude N-acetyl-L-cysteine ​​to deionized water is 1 g:1 ml.

[0049] In step S3, the cooling crystallization is performed by cooling to 4°C for crystallization for 3 hours, and then cooling to -4°C for crystallization for 3 hours.

[0050] In step S3, the drying is performed at 70° C. for 4 hours and then naturally cooled.

[0051] Example 3

[0052] This embodiment provides a method for preparing N-acetyl-L-cysteine, the steps are as follows:

[0053] S1. L-cystine is added with hydrochloric acid to prepare L-cystine hydrochloric acid solution, which is fed into the cathode chamber of the electrolytic cell, and sulfuric acid is fed into the anode chamber of the electrolytic cell for electrolysis to obtain a cathode solution, which is concentrated under reduced pressure, cooled for crystallization, and centrifuged to obtain L-cysteine ​​hydrochloride;

[0054] S2. In an ice bath, acetic anhydride is added to L-cysteine ​​hydrochloride to carry out an acylation reaction. After the acylation reaction is completed, a hydrochloric acid solution is added to adjust the pH value, the reaction is concentrated under reduced pressure, deionized water is added to dissolve, the reaction is filtered, the reaction is cooled and crystallized, the reaction is centrifuged and filtered, and the reaction is dried in vacuo to obtain a crude N-acetyl-L-cysteine ​​product;

[0055] S3. Add deionized water to the crude N-acetyl-L-cysteine ​​to dissolve it, cool it for crystallization, filter it, wash the filter cake, and dry it to obtain the N-acetyl-L-cysteine.

[0056] In step S1, the concentration of the hydrochloric acid is 3M, and the solid-liquid ratio of L-cystine to hydrochloric acid is 70g:500ml; the concentration of the sulfuric acid is 3M, and the amount of sulfuric acid is 500ml.

[0057] In step S1, the electrolysis is performed until the optical rotation of the cathode chamber solution is stable, and the voltage of the electrolysis is 60V and the current is 300A.

[0058] In step S1, the reduced pressure concentration is concentrated to 30 degrees Baume.

[0059] In step S2, after the acylation reaction is completed, hydrochloric acid solution is added to adjust the pH value to 2.

[0060] In step S2, while the acylation reaction is being carried out, a sodium hydroxide solution is added to adjust the pH of the acylation reaction process to 9.

[0061] In step S2, the cooling crystallization is cooling to 4°C for crystallization for 5 hours; the temperature of the reduced pressure concentration is 65°C, and the temperature of the vacuum drying is 50-60°C.

[0062] In step S3, the solid-to-liquid ratio of the crude N-acetyl-L-cysteine ​​to deionized water is 1 g:1 ml.

[0063] In step S3, the cooling crystallization is performed by cooling to 4°C for crystallization for 3 hours, and then cooling to -4°C for crystallization for 3 hours.

[0064] In step S3, the drying is performed at 60° C. for 4 hours and then naturally cooled.

[0065] Test example

[0066] The purity and product quality yield of N-acetyl-L-cysteine ​​prepared by the preparation method of test examples 1-3 were tested.

[0067] Test results: See Table 1.

[0068] Table 1

[0069] purity(%) Product quality yield (%) Example 1 99.9 109.3 Example 2 99.8 108.8 Example 3 99.6 109.0

[0070] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein by equivalents. These modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be included in the scope of the claims and specification of the present invention.

Claims

1. A method for preparing N-acetyl-L-cysteine, characterized in that: The preparation method comprises the following steps: S1. L-cystine is added with hydrochloric acid to prepare L-cystine hydrochloric acid solution, which is fed into the cathode chamber of the electrolytic cell, and sulfuric acid is fed into the anode chamber of the electrolytic cell for electrolysis to obtain a cathode solution, which is concentrated under reduced pressure, cooled for crystallization, and centrifuged to obtain L-cysteine ​​hydrochloride; S2. In an ice bath, acetic anhydride is added to L-cysteine ​​hydrochloride to carry out an acylation reaction. After the acylation reaction is completed, a hydrochloric acid solution is added to adjust the pH value, the reaction is concentrated under reduced pressure, deionized water is added to dissolve, the reaction is filtered, the reaction is cooled and crystallized, the reaction is centrifuged and filtered, and the reaction is dried in vacuo to obtain a crude N-acetyl-L-cysteine ​​product; S3. Add deionized water to the crude N-acetyl-L-cysteine ​​to dissolve it, cool it for crystallization, filter it, wash the filter cake, and dry it to obtain the N-acetyl-L-cysteine; In step S1, the concentration of the hydrochloric acid is 3M, and the solid-liquid ratio of L-cystine and hydrochloric acid is 70-80g:500-550ml; the concentration of the sulfuric acid is 3M, and the amount of sulfuric acid is 500-600ml; the electrolysis is performed until the optical rotation of the cathode chamber solution is stable, the voltage of the electrolysis is 60-100V, and the current is 500-300A.

2. The method for preparing N-acetyl-L-cysteine ​​according to claim 1, wherein: In step S1, the reduced pressure concentration is concentrated to 30-31 degrees Baume.

3. The method for preparing N-acetyl-L-cysteine ​​according to claim 1, wherein: In step S2, after the acylation reaction is completed, hydrochloric acid solution is added to adjust the pH value to 2.

4. The method for preparing N-acetyl-L-cysteine ​​according to claim 1, wherein: In step S2, while the acylation reaction is being carried out, a sodium hydroxide solution is added to adjust the pH of the acylation reaction process to 9-10.

5. The method for preparing N-acetyl-L-cysteine ​​according to claim 1, wherein: In step S2, the cooling crystallization is cooling to 4-5°C for crystallization for 5-10 hours; the temperature of the reduced pressure concentration is 65-75°C, and the temperature of the vacuum drying is 50-60°C.

6. The method for preparing N-acetyl-L-cysteine ​​according to claim 1, wherein: In step S3, the solid-to-liquid ratio of the crude N-acetyl-L-cysteine ​​to deionized water is 1 g:1 ml.

7. The method for preparing N-acetyl-L-cysteine ​​according to claim 1, wherein: In step S3, the cooling crystallization is performed by cooling to 4-5°C for crystallization for 3 hours, and then cooling to -4-0°C for crystallization for 3 hours.

8. The method for preparing N-acetyl-L-cysteine ​​according to claim 1, wherein: In step S3, the drying is performed at 60-70° C. for 4 hours and then naturally cooled.