CN119977905A

CN119977905A - A green synthesis method of saccharin and its derivatives

Info

Publication number: CN119977905A
Application number: CN202510006876.5A
Authority: CN
Inventors: 刘欢; 赵云辉
Original assignee: Hunan University of Science and Technology
Current assignee: Hunan University of Science and Technology
Priority date: 2025-01-03
Filing date: 2025-01-03
Publication date: 2025-05-13

Abstract

The invention discloses a green synthesis method of saccharin and a saccharin derivative. The method comprises the steps of taking substituted toluene as a raw material, reacting with chlorosulfonic acid in methylene dichloride under the catalysis of ferric trichloride to prepare substituted sulfonyl chloride, then reacting with ammonia water to form sulfonamide, and oxidizing with hydrogen peroxide to obtain the target compound. The saccharin has the advantages of simple synthetic route, mild condition, green, high efficiency and environmental protection.

Description

Green synthesis method of saccharin and saccharin derivative

Technical Field

The invention relates to the field of synthesis of fine chemicals, in particular to a preparation method of saccharin

Background

Phthalimides are synthetic sweeteners commonly used in the food industry and last for the longest period of time. The total production amount in China is over ten thousand tons at present. The sweetness of phthalimide is 300-500 times that of sucrose, which is the oldest synthetic sweetener. The phthalylsulfonyl imide is a chemical synthetic food additive with the lowest application cost and the most extensive application range in all high-power sweeteners so far, is mainly used for processing foods and beverages together with meals, and is widely applied to the fields of medicines, daily chemical industry, electroplating, feeds, pesticides and the like. The current processes for producing phthalylsulfonyl imide in the market are mainly divided into toluene method and phthalic anhydride method according to the main raw materials.

Toluene is subjected to chlorosulfonation at the ortho position in chlorosulfonic acid and then reacts with ammonia to obtain o-toluenesulfonamide, then methyl is oxidized into carboxyl by potassium permanganate or chromium trioxide and the like, and one molecule of water is removed for cyclization to obtain saccharin, and the reaction generates byproducts of para-sulfonation of toluene in the first step, but can be separated after the second step is finished. 1950. Over the years, maumee developed a Maumee process from methyl anthranilate, which was first diazotized to give the corresponding diazonium salt, then treated with sulfur dioxide and chlorine gas, the diazonium salt was converted to sulfonyl chloride, and then treated with ammonia to give saccharin. In both methods, heavy metals or hazardous gases harmful to the environment are used, which is not beneficial to industrial production.

Disclosure of Invention

Aiming at the technical problems, the invention provides a green and efficient saccharin synthesizing method.

The technical scheme of the invention is as follows:

a preparation method of saccharin and derivatives thereof comprises the following steps:

(1) Dissolving a compound 1 and a proper amount of chlorosulfonic acid in dichloromethane, adding a certain amount of catalyst, wherein the amount ratio of the compound 1 to chlorosulfonic acid is 1:1-1:2, the catalyst is 20% -100% of the compound 1, stirring for 6-12 hours at 0-room temperature, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain a crude product 2;

(2) Dissolving an intermediate compound 2 in 1, 4-dioxane, adding ammonia water, reacting for 4 hours at room temperature, extracting and drying after the reaction is finished, and removing a solvent under reduced pressure to obtain a crude product 3;

(3) Dissolving the intermediate compound 3 in acetonitrile, adding an oxidant, heating for reaction for 6-10 hours, extracting and drying after the reaction is finished, and performing column chromatography to obtain the target compound 4.

The above compounds are identified by the following numbers for each compound in the reaction scheme.

Further, in the synthesis step (1), the ratio of the amounts of the substances of the compound 1 and chlorosulfonic acid is preferably 1:2.

Further, in the synthesis step (1), the catalyst is ferric trichloride.

Further, in the synthesizing step (3), the oxidant is one of hydrogen peroxide and chlorosuccinimide (NCS) or hydrogen peroxide and bromosuccinimide (NBS) or hydrogen peroxide and iodosuccinimide (NIS).

The invention has the beneficial effects that:

the invention provides a green and efficient synthesis method of saccharin and derivatives thereof, which avoids the use of excessive chlorosulfonic acid and avoids the use of transitional heavy metal oxidizing reagents.

Detailed Description

The present invention will be described in further detail by way of specific examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples. All techniques implemented based on the above description of the invention are within the scope of the invention.

The invention uses the instrument and the reagent:

The reagents used were all commercially available chemically pure or analytically pure.

Example 1

The saccharin and the derivatives thereof are prepared by the following steps:

(1) Dissolving 1mmol of toluene and 2mmol of chlorosulfonic acid in 5 ml dichloromethane, adding 0.5mmol of ferric trichloride, stirring at 0 ℃ to room temperature for 12 hours, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain a crude product o-toluenesulfonyl chloride, wherein the yield is about 90%;

(2) Dissolving 1mmol of intermediate o-toluenesulfonyl chloride in 1, 4-dioxane, adding 1mL of ammonia water, reacting for 4 hours at room temperature, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain the intermediate o-toluenesulfonamide, wherein the yield is about 80%;

(3) Dissolving an intermediate compound o-toluenesulfonamide in acetonitrile, adding hydrogen peroxide and NBS, heating for reaction for 5 hours, extracting and drying after the reaction is finished, and performing column chromatography to obtain the saccharin target compound, wherein the yield is about 70%.

Example 2

(1) Dissolving 2mmol of m-chlorotoluene and 5mmol of chlorosulfonic acid in 10 ml dichloromethane, adding 1mmol of ferric trichloride, stirring at 0 ℃ to room temperature for 12 hours, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain a crude product of 4-chloro-2-methylbenzenesulfonyl chloride, wherein the yield is about 90%;

(2) Dissolving 1mmol of intermediate 4-chloro-2-methylbenzenesulfonyl chloride in 1, 4-dioxane, adding 1mL of ammonia water, reacting for 4 hours at room temperature, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain intermediate 4-chloro-2-methylbenzenesulfonamide, wherein the yield is about 70%;

(3) Dissolving 1mmol of intermediate compound 4-chloro-2-methylbenzenesulfonamide in acetonitrile, adding hydrogen peroxide and NIS, heating for reaction for 5 hours, extracting and drying after the reaction is finished, and performing column chromatography to obtain the target compound saccharin with the yield of about 60%.

Example 3

(1) Dissolving 2mmol of m-fluorotoluene and 5mmol of chlorosulfonic acid in 10 ml dichloromethane, adding 1mmol of ferric trichloride, stirring at 0 ℃ to room temperature for 12 hours, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain a crude product of 4-fluoro-2-methylbenzenesulfonyl chloride, wherein the yield is about 80%;

(2) Dissolving 1mmol of intermediate 4-chloro-2-methylbenzenesulfonyl chloride in 1, 4-dioxane, adding 1mL of ammonia water, reacting for 4 hours at room temperature, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain intermediate 4-fluoro-2-methylbenzenesulfonamide, wherein the yield is about 70%;

(3) Dissolving 1mmol of intermediate compound 4-fluoro-2-methylbenzenesulfonamide in acetonitrile, adding hydrogen peroxide and NCS, heating for reaction for 5 hours, extracting and drying after the reaction is finished, and performing column chromatography to obtain the target compound saccharin with the yield of about 50%.

Example 4

(1) Dissolving 2mmol of m-bromotoluene and 5mmol of chlorosulfonic acid in 10 ml dichloromethane, adding 1mmol of ferric trichloride, stirring at 0 ℃ to room temperature for 12 hours, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain a crude product of 4-bromo-2-methylbenzenesulfonyl chloride, wherein the yield is about 80%;

(2) Dissolving 1mmol of intermediate 4-bromo-2-methylbenzenesulfonyl chloride in 1, 4-dioxane, adding 1mL of ammonia water, reacting for 4 hours at room temperature, extracting and drying after the reaction is finished, and removing the solvent under reduced pressure to obtain intermediate 4-bromo-2-methylbenzenesulfonamide, wherein the yield is about 70%;

(3) Dissolving 1mmol of intermediate compound 4-bromo-2-methylbenzenesulfonamide in acetonitrile, adding hydrogen peroxide and NBS, heating for reaction, extracting and drying after the reaction is finished, and performing column chromatography to obtain the target compound saccharin with the yield of about 55%.

Claims

1. A method for preparing saccharin and its derivatives, characterized in that it comprises the following steps:

(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.