Synthesis method of cysteamine hydrochloride

Abstract

The invention discloses a synthesis method of cysteamine hydrochloride, and relates to the technical field of pharmaceutical manufacturing intermediates, the synthesis method comprises the following steps: S1, synthesis of 2-aminoethyl sulfate; s2, synthesizing alpha-mercaptothiazoline by taking the 2-aminoethyl sulfate as a raw material; s3, synthesizing S, S '-bis (2-aminoethyl ester) dithioformic acid by taking the alpha-mercaptothiazoline as a raw material; and S4, synthesizing cysteamine hydrochloride by taking the S, S '-bis (2-aminoethyl ester) dithioformic acid as a raw material. According to the invention, alpha-mercaptothiazoline and 2-aminoethyl sulfate react to generate an intermediate dithioformic acid S, S '-bis (2-aminoethyl ester), and then hydrolysis is carried out, so that the purposes of reducing serious hydrogen sulfide pollution, improving the atom utilization rate, improving the yield and being environmentally friendly are achieved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical manufacturing intermediates, and more specifically to a method for synthesizing cysteine ​​hydrochloride. Background Technology

[0002] Cysteine ​​hydrochloride is a white crystalline powder at room temperature and is readily soluble in water. It is also an important chemical raw material and pharmaceutical intermediate with a wide range of applications. It can be used not only in the production of cosmetics, animal additives, and heavy metal ion chelating agents, but also as a raw material for the preparation of anti-ulcer drugs such as ranitidine and cimetidine.

[0003] There are currently three main methods for preparing cysteine ​​hydrochloride: (1) The ethanolamine-sulfuric acid-thiazoline method involves the following steps: ethanolamine reacts with concentrated sulfuric acid to produce 2-aminoethyl sulfate, which then reacts with carbon disulfide to obtain α-mercaptothiazoline. Finally, α-mercaptothiazoline is hydrolyzed in the presence of hydrochloric acid to obtain cysteine ​​hydrochloride. This method has a long hydrolysis cycle, typically exceeding 15 days. Furthermore, a large amount of hydrogen sulfide gas is released during hydrolysis. Hydrogen sulfide is highly toxic and has a strong irritating odor, causing significant environmental pollution. It cannot be directly discharged, and complete recovery requires multiple processing steps, significantly increasing the consumption of personnel, equipment, and raw materials. Costs cannot be effectively controlled.

[0004] (2) 2 Ethanolamine-sulfuric acid-cycloethylamine method, the steps are as follows: ethanolamine reacts with sulfuric acid to obtain 2-aminoethyl sulfate, which is then heated and distilled with sodium hydroxide to obtain cycloethylamine. Cycloethylamine is passed through dry hydrogen sulfide gas in anhydrous ethanol environment and undergoes an addition reaction to generate cysteine ​​hydrochloride. This method is complicated to operate, and the reaction conditions are extremely demanding when adding hydrogen sulfide, and the yield is low.

[0005] In view of the above, this application is hereby submitted. Summary of the Invention

[0006] The purpose of this invention is to provide a method for synthesizing cysteine ​​hydrochloride, which involves reacting α-mercaptothiazoline with 2-aminoethyl sulfate to generate the intermediate dithiocarboxylic acid S,S'-bis(2-aminoethyl ester), followed by hydrolysis. This method addresses the technical problems of severe hydrogen sulfide pollution, low atom utilization, limited yield, and environmental unfriendliness associated with the direct hydrolysis process in the prior art.

[0007] This invention is achieved through the following technical solution: An embodiment of this invention provides a method for synthesizing cysteine ​​hydrochloride, comprising the following steps: S1: Synthesis of 2-aminoethyl sulfate; S2: Using the 2-aminoethyl sulfate as a raw material, α-mercaptothiazoline is synthesized; S3: Using the α-mercaptothiazoline as a raw material, S,S'-bis(2-aminoethyl ester) of dithiocarbamate is synthesized; S4: Cysteine ​​hydrochloride is synthesized using the dithiocarboxylic acid S,S'-bis(2-aminoethyl ester) as a raw material.

[0008] As an optional implementation, the synthesis route of S1 is as follows: .

[0009] As an optional implementation, the synthesis of aminoethyl sulfate in S1 includes adding ethanolamine and water to a reaction flask, cooling the water to 10-15°C, adding a 40-60% sulfuric acid aqueous solution dropwise, heating to 25-35°C, and reacting for 1.5-2.5 hours. After the reaction is complete, the water in the reaction system is concentrated, ethanol is added, and the mixture is stirred for 1-3 hours before filtration. The filter cake is then washed with ethanol to obtain an off-white solid powder. The molar ratio of sulfuric acid to ethanolamine is 1~2:1.

[0010] As an alternative implementation method, the synthesis route of S2 is as follows: .

[0011] As an optional implementation method, the synthesis of α-mercaptothiazoline in S2 includes adding 15-25% sodium hydroxide aqueous solution and 2-aminoethyl sulfate to a reaction flask, heating to 30-50°C, adding carbon disulfide dropwise, and maintaining the temperature at 30-50°C for 5-7 hours. Then, an alkaline solution is added, and the reaction continues for 12-18 hours. After the reaction is complete, the alkaline solution is neutralized with an acidic solution to make the pH of the system 7-8. Dichloromethane is then added, and the mixture is stirred for 0.5-2 hours. The liquid is then separated, and the organic phase is concentrated to obtain a white solid. The alkaline solution includes at least one of sodium hydroxide solution, sodium carbonate solution, triethylamine solution, sodium methoxide solution, and sodium ethoxide solution.

[0012] As an optional embodiment, the alkaline solution is a 15-25% sodium hydroxide aqueous solution, and the acidic solution is a hydrochloric acid solution.

[0013] As an optional implementation, the synthesis route in S3 is as follows: .

[0014] As an optional implementation, the synthesis of S,S'-bis(2-aminoethyl ester) dithiocarboxylic acid in S3 includes adding 2-aminoethyl sulfate and / or chloroethylamine, α-mercaptothiazoline, and hydrochloric acid solution to a reaction flask, heating to 90-130°C and refluxing for 45-55 hours. After the α-mercaptothiazoline reaction is complete, the water in the system is concentrated to obtain a yellow oily substance. The molar ratio of 2-aminoethyl sulfate to α-mercaptothiazoline is 1.0~2.5:1, preferably 1.2:1.

[0015] As an optional implementation, the synthesis route in S4 is characterized by the following: .

[0016] As an optional implementation, the synthesis of cysteine ​​hydrochloride in S4 includes adding the hydrolysate of dithiocarboxylic acid S,S'-bis(2-aminoethyl ester) to a high-pressure vessel, heating to 150-220°C and reacting for 40-55 hours, adding concentrated hydrochloric acid and continuing the reaction for another 40-55 hours, detecting that the reaction of the raw materials is complete, concentrating to obtain a crude product, and recrystallizing with ethanol to obtain a qualified product; The hydrolysis includes at least one of the following: hydrochloric acid solution, sulfuric acid solution, sodium hydroxide solution, potassium hydroxide solution, sodium methoxide solution, and sodium tert-butoxide solution.

[0017] Compared with the prior art, the embodiments of the present invention have the following advantages and beneficial effects: This invention provides a method for synthesizing cysteamine hydrochloride. The synthetic route is simple, the raw materials are readily available and the cost is low, and the reaction conditions are mild. The main method involves first reacting α-mercaptothiazoline and 2-aminoethyl sulfate to generate the intermediate S,S'-bis(2-aminoethyl ester) dithiocarboxylic acid, followed by hydrolysis of the intermediate S,S'-bis(2-aminoethyl ester). This replaces the traditional process of directly hydrolyzing α-mercaptothiazoline. Direct hydrolysis of α-mercaptothiazoline yields only one molecule of cysteamine hydrochloride from one molecule of α-mercaptothiazoline, and also produces one molecule of hydrogen sulfide as a byproduct. In contrast, this process yields two molecules of cysteamine hydrochloride from one molecule of α-mercaptothiazoline, without generating hydrogen sulfide. This not only improves atom utilization and reduces raw material costs but is also more environmentally friendly, making it well-suited for industrial production. Detailed Implementation

[0018] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments.

[0019] Therefore, the detailed description of the embodiments of the present invention provided below is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0020] This invention provides a method for synthesizing cysteamine hydrochloride, the synthetic route of which is as follows: .

[0021] Specifically, it includes the following steps: (1) Synthesis of 2-aminoethyl sulfate Ethanolamine and water were added to a reaction flask, and the mixture was cooled to 10-15°C with ice water. A 40-60% sulfuric acid aqueous solution was added dropwise, and the mixture was heated to 25-35°C and reacted for 1.5-2.5 hours. After the reaction was completed, the water in the reaction system was concentrated, ethanol was added, and the mixture was refluxed and stirred for 1-3 hours. The mixture was then filtered, and the filter cake was washed with ethanol to obtain an off-white solid powder. The molar ratio of sulfuric acid to ethanolamine is 1~2:1.

[0022] (2) Synthesis of α-mercaptothiazoline Add 15-25% sodium hydroxide aqueous solution and 2-aminoethyl sulfate to a reaction flask, heat to 30-50℃, add carbon disulfide dropwise, and maintain the temperature at 30-50℃ for 5-7 hours. Then add an alkaline solution and continue the reaction for 12-18 hours. After the reaction is complete, neutralize the alkaline solution with an acidic solution to make the pH of the system 7-8, then add dichloromethane and stir for 0.5-2 hours. After separation, concentrate the organic phase to obtain a white solid. The alkaline solution includes at least one selected from sodium hydroxide solution, sodium carbonate solution, triethylamine solution, sodium methoxide solution, and sodium ethoxide solution. The alkaline solution is preferably a 15-25% aqueous sodium hydroxide solution, and the acidic solution is preferably a hydrochloric acid solution.

[0023] (3) Synthesis of S,S'-bis(2-aminoethyl ester) dithiocarboxylic acid Add 2-aminoethyl sulfate and / or chloroethylamine, α-mercaptothiazoline, and hydrochloric acid solution to a reaction flask, heat to 90~130℃ and reflux for 45~55h. After the α-mercaptothiazoline reaction is complete, concentrate the water in the system to obtain a yellow oily substance. The molar ratio of 2-aminoethyl sulfate to α-mercaptothiazoline is 1.0~2.5:1, preferably 1.2:1.

[0024] (4) Synthesis of cysteine ​​hydrochloride The hydrolysate of S,S'-bis(2-aminoethyl ester) dithiocarboxylic acid was added to a high-pressure vessel and heated to 150-220℃ for 40-55 hours. Concentrated hydrochloric acid was added to continue the reaction for another 40-55 hours. After the reaction was confirmed to be complete, the product was concentrated to obtain a crude product. The qualified product was then obtained by recrystallization with ethanol. The hydrolysis includes at least one of hydrochloric acid containing solution, sulfuric acid solution, sodium hydroxide solution, potassium hydroxide solution, sodium methoxide solution, and sodium tert-butoxide solution, preferably hydrochloric acid containing solution.

[0025] Example 1: This embodiment of the invention provides a method for synthesizing cysteine ​​hydrochloride, specifically including the following steps: (1) Synthesis of 2-aminoethyl sulfate Ethanolamine (305.4 g, 5.0 mol, 1.0 eq) and 305.4 g of water were added to a reaction flask, cooled to 12 °C with ice water, and 50% sulfuric acid aqueous solution (990 g, 5.05 mol, 1.01 eq) was added dropwise. The mixture was then heated to 30 °C and reacted for 2 h. After the reaction was complete, the water in the reaction system was concentrated, 200 ml of ethanol was added, and the mixture was refluxed and stirred for 2 h. The mixture was then filtered, and the filter cake was washed with ethanol to obtain 674.89 g of off-white solid powder. 1 ¹H NMR (400MHz, CD₃OD) δ (ppm) 3.35–3.38 (t, 2H), 4.30–4.32 (t, 2H), yield 95.63%. It can be directly used in the next step.

[0026] (2) Synthesis of α-mercaptothiazoline A 20% sodium hydroxide aqueous solution (200 g, 1 mol, 2.0 eq) and 2-aminoethyl sulfate (70.63 g, 0.5 mol, 1.0 eq) were added to a reaction flask. The mixture was heated to 40 °C in an oil bath, and carbon disulfide (76.14 g, 1 mol, 2.0 eq) was added dropwise. The reaction was maintained at 40 °C for 6 h. Then, another 20% sodium hydroxide aqueous solution (200 g, 1 mol, 2.0 eq) was added, and the reaction continued for 15 h. After the reaction was complete, the sodium hydroxide was neutralized with concentrated hydrochloric acid to bring the pH of the system to 7.5. Dichloromethane was then added and stirred for 1 h. The mixture was then separated (extracted twice with 500 mL of dichloromethane twice). The organic phase was concentrated to obtain 54.16 g of white solid with a purity of 98% and a yield of 90.86%. Mp: 106-107 °C; 1 NMR (400 MHz, DMSO-d6, TMS): δ (ppm) 10.08 (brs, 1H), 3.88(t, 2H, J = 8.0 Hz), 3.51 (t, 2H, J = 8.0 Hz). 13 C NMR (400 MHz, DMSO-d6, TMS): δ (ppm) 199.4, 51.9, 33.3. This can be directly used for the next step.

[0027] (3) Synthesis of S,S'-bis(2-aminoethyl ester) dithiocarboxylic acid 2-Aminoethyl sulfate (59.2 g, 0.45 mol, 1.07 eq), α-mercaptothiazoline (50 g, 0.42 mol, 1 eq), and concentrated hydrochloric acid (192 g, 1.88 mol, 4.5 eq) were added to a reaction flask and refluxed at 110 °C for 48 h. After the α-mercaptothiazoline had reacted completely, the water in the system was concentrated to obtain 72 g of a yellow oily substance, with a yield of 95.1%, which was directly used in the next step. ¹H-NMR (D₂O, 40 MHz): δ 3.32 (t, 2H), 3.13 (t, 2H).

[0028] (4) Synthesis of cysteine ​​hydrochloride S,S'-bis(2-aminoethyl) dithiocarboxylic acid (180.28 g, 1 mol, 1 eq) and 500 ml concentrated hydrochloric acid (6 mol, 6 eq) were added to a high-pressure vessel, and the mixture was heated to 200 °C and reacted for 48 h. Then, 500 ml concentrated hydrochloric acid (6 mol, 6 eq) was added, and the reaction was continued for another 48 h. After confirming the completion of the reaction, the mixture was concentrated to obtain a crude product. Recrystallization with 100 ml ethanol yielded 180.8 g of qualified product with a purity of 99.2% and a yield of 80%. ¹H-NMR (D₂O, 40 MHz): δ 3.18 (t, 2H), 2.83 (t, 2H).

[0029] Example 2: This embodiment of the invention provides a method for synthesizing cysteine ​​hydrochloride, specifically including the following steps: (1) Synthesis of 2-aminoethyl sulfate Ethanolamine (610.8 g, 10 mol, 1.0 eq) and 610.8 g of water were added to a reaction flask, cooled to 10°C with ice water, and 40% sulfuric acid aqueous solution (2475 g, 10.1 mol, 1.01 eq) was added dropwise. The mixture was then heated to 25°C and reacted for 2.5 h. After the reaction was complete, the water in the reaction system was concentrated, ethanol was added, and the mixture was refluxed and stirred for 1 h. The mixture was then filtered, and the filter cake was washed with ethanol to obtain 1370 g of off-white solid powder, with a yield of 97.1%. This powder can be used directly in the next step.

[0030] (2) Synthesis of α-mercaptothiazoline 800 g (3 mol, 2.0 eq) of 15% sodium hydroxide aqueous solution and 2-aminoethyl sulfate (211.9 g, 1.5 mol, 1.0 eq) were added to a reaction flask. The mixture was heated to 30°C in an oil bath, and carbon disulfide (229.23 g, 3 mol, 2.0 eq) was added dropwise. The mixture was kept at 30°C for 7 h. Then, 800 g (3 mol, 2.0 eq) of 15% sodium hydroxide aqueous solution was added again, and the reaction was continued for 12 h. After the reaction was complete, the sodium hydroxide was neutralized with concentrated hydrochloric acid to make the pH of the system 7. Dichloromethane was then added and stirred for 0.5 h. The mixture was then separated (extracted twice with 1500 mL of dichloromethane twice). The organic phase was concentrated to obtain 168 g of white solid with a purity of 98.5% and a yield of 93.96%. This solid can be used directly in the next step.

[0031] (3) Synthesis of S,S'-bis(2-aminoethyl ester) dithiocarboxylic acid 2-Aminoethyl sulfate and / or chloroethylamine (592 g, 4.5 mol, 1.07 eq), α-mercaptothiazoline (500 g, 4.2 mol, 1 eq), and 1920 g (18.8 mol, 4.5 eq) of concentrated hydrochloric acid were added to a reaction flask, and the mixture was heated to 90 °C and refluxed for 55 h. After the α-mercaptothiazoline reaction was complete, the water in the system was concentrated to obtain 732 g of a yellow oily substance with a yield of 96.6%, which was directly used in the next step.

[0032] (4) Synthesis of cysteine ​​hydrochloride S,S'-bis(2-aminoethyl) dithiocarboxylic acid (1800.3 g, 10 mol, 1 eq) and 5000 ml concentrated hydrochloric acid (60 mol, 6 eq) were added to a high-pressure vessel. The mixture was heated to 150 °C and reacted for 40–55 h. Then, another 5000 ml of concentrated hydrochloric acid (60 mol, 6 eq) was added, and the reaction continued for another 40 h. Once the reaction was complete, the mixture was concentrated to obtain the crude product. Recrystallization with 100 ml of ethanol yielded 1820.8 g of qualified product with a purity of 99.4% and a yield of 80.57%.

[0033] Example 3: This embodiment of the invention provides a method for synthesizing cysteine ​​hydrochloride, specifically including the following steps: (1) Synthesis of 2-aminoethyl sulfate Ethanolamine (305.4 g, 5.0 mol, 1.0 eq) and 305.4 g of water were added to a reaction flask, and the mixture was cooled to 15°C with ice water. A 60% sulfuric acid aqueous solution (825 g, 5.05 mol, 1.01 eq) was added dropwise, and the mixture was heated to 35°C and reacted for 1 h. After the reaction was complete, the water in the reaction system was concentrated, and 200 ml of ethanol was added. The mixture was refluxed and stirred for 3 h, then filtered. The filter cake was washed with ethanol to obtain 674.89 g of off-white solid powder, with a yield of 95.63%. This powder can be used directly in the next step.

[0034] (2) Synthesis of α-mercaptothiazoline A 25% sodium hydroxide aqueous solution (160 g, 1 mol, 2.0 eq) and 2-aminoethyl sulfate (70.63 g, 0.5 mol, 1.0 eq) were added to a reaction flask. The mixture was heated to 50°C in an oil bath, and carbon disulfide (76.14 g, 1 mol, 2.0 eq) was added dropwise. The reaction was maintained at 50°C for 5 hours. Then, another 25% sodium hydroxide aqueous solution (160 g, 1 mol, 2.0 eq) was added, and the reaction continued for 18 hours. After the reaction was complete, the sodium hydroxide was neutralized with concentrated hydrochloric acid to bring the pH of the system to 8. Dichloromethane was then added and stirred for 2 hours. The mixture was then separated (extracted twice with 500 mL of dichloromethane). The organic phase was concentrated to obtain 54.16 g of a white solid with a purity of 98% and a yield of 90.86%. This solid can be used directly in the next step.

[0035] (3) Synthesis of S,S'-bis(2-aminoethyl ester) dithiocarboxylic acid 2-Aminoethyl sulfate (88.9 g, 0.63 mol, 1.5 eq), α-mercaptothiazoline (50 g, 0.42 mol, 1 eq), and concentrated hydrochloric acid (192 g, 1.88 mol, 4.5 eq) were added to a reaction flask and the mixture was heated to 130 °C and refluxed for 45 h. After the α-mercaptothiazoline reaction was complete, the water in the system was concentrated to obtain 71 g of a yellow oily substance with a yield of 93.8%, which was directly used in the next step.

[0036] (4) Synthesis of cysteine ​​hydrochloride: S,S'-bis(2-aminoethyl) dithiocarboxylic acid (180.28 g, 1 mol, 1 eq) and 500 ml concentrated hydrochloric acid (6 mol, 6 eq) were added to a high-pressure vessel, and the mixture was heated to 220 °C and reacted for 40 h. Then, 500 ml concentrated hydrochloric acid (6 mol, 6 eq) was added, and the reaction was continued for another 40 h. After confirming the completion of the reaction, the mixture was concentrated to obtain the crude product. Recrystallization from ethanol yielded 165.6 g of the qualified product with a purity of 99.2% and a yield of 73.3%. NMR: 1H-NMR (D₂O, 300 MHz): δ 3.18 (t, 2H), 2.83 (t, 2H).

[0037] Comparative Example 1: Preparation of cysteine ​​hydrochloride using the 1-ethanolamine-sulfuric acid-thiazoline method, including the following steps: The method for preparing thiazoline is the same as in Example 1. After obtaining thiazoline, 20g of thiazoline was added to 120g of concentrated hydrochloric acid and refluxed in a high-pressure reactor at 150℃ for 15 days. After concentrating the reaction solution, 16g of crude product was obtained. Ethanol was added and the mixture was cooled to crystallize, yielding 12g of product with a purity of 98.9% and a yield of 63.2%. NMR: H-NMR (D2O, 300 MHz): δ3.18 (t, 2H), 2.83 (t, 2H).

[0038] Comparative Example 2: Preparation of cysteine ​​hydrochloride using the 2-ethanolamine-sulfuric acid-cycloethylamine method, including the following steps: The preparation method for 2-aminoethyl sulfate was the same as in Example 1. Then, 50 g of 2-aminoethyl sulfate was added to 100 g of 40% sodium hydroxide solution and refluxed under sealed conditions. After 12 h, the reaction system was cooled to 50-60 °C and distilled at atmospheric pressure to obtain 10.2 g of cycloethylamine. The 10.2 g of cycloethylamine was added to 50 ml of ethanol, and hydrogen sulfide was introduced to react. After the reaction was complete, the ethanol was concentrated, and crystallization was performed to obtain 10.4 g of cysteine ​​hydrochloride. The purity was 99%, and the yield was 26%.

[0039] In summary, the preparation method of cysteamine hydrochloride (N-vinylcarbamate benzyl ester) provided in this invention has a simple synthetic route, readily available and low-cost raw materials, and mild reaction conditions. It primarily involves first reacting α-mercaptothiazoline and 2-aminoethyl sulfate to generate the intermediate dithiocarbamate S,S'-bis(2-aminoethyl ester), followed by hydrolysis of the intermediate S,S'-bis(2-aminoethyl ester). This replaces the traditional process of directly hydrolyzing α-mercaptothiazoline. Direct hydrolysis of α-mercaptothiazoline yields only one molecule of cysteamine hydrochloride from one molecule of α-mercaptothiazoline, along with one molecule of hydrogen sulfide as a byproduct. In contrast, this process yields two molecules of cysteamine hydrochloride from one molecule of α-mercaptothiazoline without generating hydrogen sulfide. This not only improves atom utilization and reduces raw material costs but is also more environmentally friendly, making it well-suited for industrial production.

[0040] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for synthesizing cysteamine hydrochloride, characterized in that, Includes the following steps: Synthesis of S1: 2-aminoethyl sulfate; S2: Using the 2-aminoethyl sulfate as a raw material, α-mercaptothiazoline is synthesized; S3: Using the α-mercaptothiazoline as a raw material, S,S'-bis(2-aminoethyl ester) of dithiocarbamate is synthesized; S4: Cysteine ​​hydrochloride is synthesized using the dithiocarboxylic acid S,S'-bis(2-aminoethyl ester) as a raw material.

2. The method for synthesizing cysteine ​​hydrochloride according to claim 1, characterized in that, The synthetic route of S1 is as follows: 。 3. The method for synthesizing cysteamine hydrochloride according to claim 1 or 2, characterized in that, The synthesis of aminoethyl sulfate described in S1 includes adding ethanolamine and water to a reaction flask, cooling the water to 10-15°C, adding a 40-60% sulfuric acid aqueous solution dropwise, heating to 25-35°C, and reacting for 1.5-2.5 hours. After the reaction is complete, the water in the reaction system is concentrated, ethanol is added, and the mixture is stirred for 1-3 hours before filtration. The filter cake is then washed with ethanol to obtain an off-white solid powder. The molar ratio of sulfuric acid to ethanolamine is 1~2:

1.

4. The method for synthesizing cysteine ​​hydrochloride according to claim 1, characterized in that, The synthesis route for S2 is as follows: 。 5. The method for synthesizing cysteine ​​hydrochloride according to claim 4, characterized in that, The synthesis of α-mercaptothiazoline described in S2 involves adding 15-25% sodium hydroxide aqueous solution and 2-aminoethyl sulfate to a reaction flask, heating to 30-50°C, adding carbon disulfide dropwise, and maintaining the temperature at 30-50°C for 5-7 hours. Then, an alkaline solution is added, and the reaction continues for 12-18 hours. After the reaction is complete, the alkaline solution is neutralized with an acidic solution to bring the pH of the system to 7-8. Dichloromethane is then added, and the mixture is stirred for 0.5-2 hours. The liquid is separated, and the organic phase is concentrated to obtain a white solid. The alkaline solution includes at least one of sodium hydroxide solution, sodium carbonate solution, triethylamine solution, sodium methoxide solution, and sodium ethoxide solution.

6. The method for synthesizing cysteine ​​hydrochloride according to claim 5, characterized in that, The alkaline solution is a 15-25% sodium hydroxide aqueous solution, and the acidic solution is a hydrochloric acid solution.

7. The method for synthesizing cysteine ​​hydrochloride according to claim 1, characterized in that, The synthesis route in S3 is as follows: 。 8. The method for synthesizing cysteine ​​hydrochloride according to claim 7, characterized in that, The synthesis of dithiocarboxylic acid S,S'-bis(2-aminoethyl ester) described in S3 includes adding 2-aminoethyl sulfate and / or chloroethylamine, α-mercaptothiazoline, and hydrochloric acid solution to a reaction flask, heating to 90~130℃ and refluxing for 45~55h, and after the α-mercaptothiazoline reaction is complete, concentrating the water in the system to obtain a yellow oily substance. The molar ratio of 2-aminoethyl sulfate to α-mercaptothiazoline is 1.0~2.5:

1.

9. The method for synthesizing cysteine ​​hydrochloride according to claim 1, characterized in that, The synthesis route in S4 is as follows: 。 10. The method for synthesizing cysteine ​​hydrochloride according to claim 9, characterized in that, The synthesis of cysteine ​​hydrochloride described in S4 involves adding the hydrolysate of dithiocarboxylic acid S,S'-bis(2-aminoethyl ester) to a high-pressure vessel, heating to 150-220℃ and reacting for 40-55 hours, then adding concentrated hydrochloric acid and continuing the reaction for another 40-55 hours. After confirming the completion of the reaction, the product is concentrated to obtain a crude product. Recrystallization with ethanol yields a qualified product. The hydrolysis includes at least one of the following: hydrochloric acid solution, sulfuric acid solution, sodium hydroxide solution, potassium hydroxide solution, sodium methoxide solution, and sodium tert-butoxide solution.

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