Green synthesis method of saccharin and derivatives thereof
Through a green and efficient synthesis method, the reaction of compound 1 and chlorosulphonic acid in dichloromethane is used to combine the subsequent reaction in 1,4-dioxane and acetonitrile. The use of heavy metal oxidation reagents was successfully avoided, and the harm of the existing saccharin synthesis process to the environment was solved, and efficient and environmentally friendly saccharin synthesis was achieved.
Patent Information
- Application Number
- CN202510006876.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-03
- Publication Date
- 2025-05-13
AI Technical Summary
The existing saccharin synthesis process uses heavy metals or gases that are harmful to the environment, resulting in industrial production being unfavorable to the environment.
A green and efficient synthesis method is adopted, and the reaction of Compound 1 and chlorosulphonic acid in dichloromethane is carried out by adding a catalyst and stirring, followed by corresponding reaction in 1,4-dioxane and acetonitrile, and finally saccharin is obtained by column chromatography. This method avoids the use of excessive chlorosulfonic acid and transition heavy metal oxidation reagents.
It realizes green and efficient synthesis of saccharin, reduces the harm to the environment, and improves the environmental protection and efficiency of industrial production.
Smart Images
Figure SMS_1 
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Abstract
Description
Technical Field
[0001] The present invention relates to the field of synthesis of fine chemicals, and in particular to a method for preparing saccharin. Background Art
[0002] O-benzoylsulfonyl imide compounds are commonly used synthetic sweeteners in the food industry and have been used for the longest time. The current domestic production volume exceeds 10,000 tons. The sweetness of o-benzoylsulfonyl imide is 300-500 times that of sucrose, and it is the oldest synthetic sweetener. O-benzoylsulfonyl imide is the chemical synthetic food additive with the lowest application cost and the widest application range among all high-intensity sweeteners to date. It is mainly used as a side dish for processed foods and beverages, and is also widely used in the fields of medicine, daily chemicals, electroplating, feed, pesticides, etc. At present, the processes for producing o-benzoylsulfonyl imide on the market are mainly divided into toluene method and phthalic anhydride method according to the main raw materials. Toluene is chlorosulfonated at the ortho position in chlorosulfonic acid and then reacted with ammonia to obtain ortho-toluenesulfonamide. Subsequently, potassium permanganate or chromium trioxide is used to oxidize the methyl group to a carboxyl group and remove a molecule of water for cyclization to obtain saccharin. In the first step of the reaction, toluene para-sulfonation byproducts will be generated, but they can be separated after the second step. In 1950, Maumee Company developed a Maumee process starting from methyl anthranilate. First, methyl anthranilate is diazotized to obtain the corresponding diazonium salt, and then treated with sulfur dioxide and chlorine to convert the diazonium into sulfonyl chloride, which is then treated with ammonia to obtain saccharin. In both of the above methods, heavy metals or harmful gases that are harmful to the environment are used, which is not conducive to industrial production. Summary of the invention
[0003] In view of the above technical problems, the present invention provides a green and efficient method for synthesizing saccharin.
[0004] The technical solution of the present invention is: A method for preparing saccharin and its derivatives comprises the following steps:
[0005] (1) Compound 1 and an appropriate amount of chlorosulfonic acid are dissolved in dichloromethane, and a certain amount of catalyst is added, wherein the molar ratio of compound 1 to chlorosulfonic acid is 1:1-1:2, and the amount of the catalyst is 20%-100% of compound 1, and the mixture is stirred at 0°C to room temperature for 6-12 hours. After the reaction is completed, the mixture is extracted and dried, and the solvent is removed under reduced pressure to obtain a crude product 2; (2) The intermediate compound 2 was dissolved in 1,4-dioxane, and aqueous ammonia was added to react at room temperature for 4 h. After the reaction was completed, the compound was extracted and dried, and the solvent was removed under reduced pressure to obtain a crude product 3; (3) The intermediate compound 3 is dissolved in acetonitrile, an oxidant is added, and the mixture is heated to react for 6-10 hours. After the reaction is completed, the mixture is extracted and dried, and the target compound 4 is obtained by column chromatography.
[0006] The above compounds are distinguished by the serial numbers below each compound in the reaction formula.
[0007] Furthermore, in the synthesis step (1), the molar ratio of compound 1 to chlorosulfonic acid is preferably 1:2.
[0008] Furthermore, in the synthesis step (1), the catalyst is ferric chloride.
[0009] Furthermore, in the synthesis step (3), the oxidant is a combination of hydrogen peroxide and chlorosuccinimide (NCS), a combination of hydrogen peroxide and bromosuccinimide (NBS), or a combination of hydrogen peroxide and iodosuccinimide (NIS).
[0010] The beneficial effects of the present invention are: The invention provides a green and efficient synthesis method of saccharin and its derivatives, which avoids the use of excessive chlorosulfonic acid and eliminates the use of transition heavy metal oxidizing agents. DETAILED DESCRIPTION
[0011] The present invention is further described in detail below through specific examples, but it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples. All technologies realized based on the above content of the present invention belong to the scope of the present invention.
[0012] Instruments and reagents used in the present invention: All reagents used were commercially available chemically pure or analytically pure. Example 1
[0013] The preparation methods of saccharin and its derivatives of the present invention are as follows: (1) Dissolve 1 mmol of toluene and 2 mmol of chlorosulfonic acid in 5 ml of dichloromethane, add 0.5 mmol of ferric chloride, and stir at 0 to room temperature for 12 hours. After the reaction is completed, extract and dry, and remove the solvent under reduced pressure to obtain the crude product o-toluenesulfonyl chloride with a yield of about 90%; (2) Take 1 mmol of the intermediate o-toluenesulfonyl chloride and dissolve it in 1,4-dioxane, add 1 mL of ammonia water and react at room temperature for 4 hours. After the reaction is completed, extract and dry, and remove the solvent under reduced pressure to obtain the intermediate o-toluenesulfonamide with a yield of about 80%; (3) The intermediate compound o-toluenesulfonamide was dissolved in acetonitrile, and hydrogen peroxide and NBS were added. The mixture was heated for 5 hours. After the reaction was completed, the mixture was extracted and dried, and the target compound saccharin was obtained by column chromatography with a yield of about 70%. Example 2
[0014] (1) Take 2 mmol of m-chlorotoluene and 5 mmol of chlorosulfonic acid and dissolve them in 10 ml of dichloromethane, add 1 mmol of ferric chloride, stir at 0 to room temperature for 12 hours, extract and dry after the reaction, remove the solvent under reduced pressure to obtain the crude product 4-chloro-2-methylbenzenesulfonyl chloride, with a yield of about 90%; (2) Take 1 mmol of the intermediate 4-chloro-2-methylbenzenesulfonyl chloride and dissolve it in 1,4-dioxane. Add 1 mL of ammonia water and react at room temperature for 4 hours. After the reaction is completed, extract and dry, and remove the solvent under reduced pressure to obtain the intermediate 4-chloro-2-methylbenzenesulfonamide with a yield of about 70%; (3) Take 1 mmol of the intermediate compound 4-chloro-2-methylbenzenesulfonamide and dissolve it in acetonitrile. Add hydrogen peroxide and NIS and heat to react for 5 hours. After the reaction is completed, extract and dry, and obtain the target compound saccharin by column chromatography with a yield of about 60%. Example 3
[0015] (1) Take 2 mmol of m-fluorotoluene and 5 mmol of chlorosulfonic acid and dissolve them in 10 ml of dichloromethane, add 1 mmol of ferric chloride, stir at 0 to room temperature for 12 hours, extract and dry after the reaction, remove the solvent under reduced pressure to obtain the crude product 4-fluoro-2-methylbenzenesulfonyl chloride, with a yield of about 80%; (2) Take 1 mmol of the intermediate 4-chloro-2-methylbenzenesulfonyl chloride and dissolve it in 1,4-dioxane. Add 1 mL of ammonia water and react at room temperature for 4 hours. After the reaction is completed, extract and dry, and remove the solvent under reduced pressure to obtain the intermediate 4-fluoro-2-methylbenzenesulfonamide with a yield of about 70%; (3) Take 1 mmol of the intermediate compound 4-fluoro-2-methylbenzenesulfonamide and dissolve it in acetonitrile. Add hydrogen peroxide and NCS and heat to react for 5 hours. After the reaction is completed, extract and dry it. Column chromatography is used to obtain the target compound saccharin with a yield of about 50%. Example 4
[0016] (1) Take 2 mmol of m-bromotoluene and 5 mmol of chlorosulfonic acid and dissolve them in 10 ml of dichloromethane, add 1 mmol of ferric chloride, stir at 0 to room temperature for 12 hours, extract and dry after the reaction, remove the solvent under reduced pressure to obtain the crude product 4-bromo-2-methylbenzenesulfonyl chloride, with a yield of about 80%; (2) Take 1 mmol of the intermediate 4-bromo-2-methylbenzenesulfonyl chloride and dissolve it in 1,4-dioxane. Add 1 mL of ammonia water and react at room temperature for 4 h. After the reaction is completed, extract and dry, and remove the solvent under reduced pressure to obtain the intermediate 4-bromo-2-methylbenzenesulfonamide with a yield of about 70%; (3) Take 1 mmol of the intermediate compound 4-bromo-2-methylbenzenesulfonamide and dissolve it in acetonitrile. Add hydrogen peroxide and NBS and heat to react. After the reaction is completed, extract and dry. Column chromatography is used to obtain the target compound saccharin with a yield of about 55%.
Claims
1. A method for preparing saccharin and its derivatives, characterized in that: The steps include: (1) Compound 1 and an appropriate amount of chlorosulfonic acid are dissolved in dichloromethane, and a certain amount of catalyst is added, wherein the molar ratio of compound 1 to chlorosulfonic acid is 1:1-1:2, and the amount of the catalyst is 20%-100% of compound 1, and the mixture is stirred at 0°C to room temperature for 6-12 hours. After the reaction is completed, the mixture is extracted and dried, and the solvent is removed under reduced pressure to obtain a crude product 2; (2) The intermediate compound 2 was dissolved in 1,4-dioxane, and aqueous ammonia was added to react at room temperature for 4 h. After the reaction was completed, the compound was extracted and dried, and the solvent was removed under reduced pressure to obtain a crude product 3; (3) The intermediate compound 3 is dissolved in acetonitrile, an oxidant is added, and the mixture is heated to react for 6-10 hours. After the reaction is completed, the mixture is extracted and dried, and the target compound 4 is obtained by column chromatography.
2. The method for preparing saccharin and its derivatives according to claim 1, characterized in that: In the synthesis step (1), the catalyst is ferric chloride.
3. The method for preparing saccharin and its derivatives according to claim 1, characterized in that: In the synthesis step (3), the oxidant is a combination of hydrogen peroxide and chlorosuccinimide, a combination of hydrogen peroxide and bromosuccinimide, or a combination of hydrogen peroxide and iodosuccinimide.