Synthesis method of tetrachlorosucrose
Through a synthesis method of multiple heating and insulation, the problems of unstable quality and low yield in sucralose synthesis are solved, and the quality and high yield of sucralose are achieved, which is suitable for green and environmentally friendly and industrial applications.
Patent Information
- Application Number
- CN202411416295.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-11
- Publication Date
- 2025-02-25
AI Technical Summary
The existing sucralose synthesis methods have problems of unstable quality and low yields, and require a synthesis method with simple equipment, low cost, green and environmentally friendly to improve the quality stability and yield of sucralose.
A synthetic method including multiple warming and insulating steps is adopted. The specific steps include cooling the trichloroethane and adding sulfoxide chloride and sucrose solution, performing multiple warming and insulating treatments, followed by neutralization and adjustment of pH, and finally removing the solvent by rotary evaporation to obtain sucralose.
The quality of sucralose is stable and yield high, and the method is simple, low in cost, green and environmentally friendly, and is suitable for industrial applications.
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of chemical production, and in particular to a method for synthesizing sucralose. Background Art
[0002] Sucralose is a new type of sweetener. The traditional synthesis method of sucralose is relatively complicated. It needs to go through esterification, chlorination and other processes to synthesize the intermediates sucrose-6-ethyl ester and sucralose-6-ethyl ester, and finally obtain sucralose from sucralose-6-ethyl ester through alcoholysis or alkaline hydrolysis. As an important intermediate in the synthesis of sucralose, the optimization of its synthesis method helps to reduce the cost of sucralose synthesis and improve the yield and quality.
[0003] Prior art, such as patent CN117486950A, discloses a method for obtaining sucralose, comprising the following steps: (1) removing part of the solvent from sucralose waste liquid by rotary evaporation, mixing with water and extracting by graded extraction, obtaining a concentrate and butyl acetate by rotary evaporation, cooling and crystallizing the concentrate to obtain a solid crude product and a mother liquor; (2) performing graded recrystallization on the solid crude product to obtain a crystallization mother liquor and sucralose solid with a purity of 90-99%. The method in the invention can effectively recover sucralose from sucralose waste liquid and realize resource utilization of waste.
[0004] For example, patent CN116368145A discloses a method for preparing sucralose, which includes the following steps: mixing sucrose, N,N-dimethylformamide, trichloroethane and thionyl chloride, and performing a chlorination reaction to obtain a chlorinated product solution; adjusting the pH value of the chlorinated product solution to alkaline, and performing a decomposition reaction to obtain tetrachlorosucrose; and mixing the tetrachlorosucrose, water and an alkaline hydrolysis agent, and performing an alkaline hydrolysis reaction to obtain sucralose. This involves the preparation of the intermediate tetrachlorosucrose in the production of sucralose.
[0005] However, the tetrachlorosucrose in the above invention has the defects of unstable quality and low yield. To address such problems, it is necessary to find a method for synthesizing tetrachlorosucrose with simple equipment, low cost, green and environmental protection, and stable quality and high yield of the obtained tetrachlorosucrose. Summary of the invention
[0006] The present invention aims at the problems existing in the prior art and provides a method for synthesizing sucralose. The method has simple equipment, low cost, and is environmentally friendly. The prepared sucralose has stable quality and high yield.
[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:
[0008] The present invention provides a method for synthesizing sucralose, comprising the following steps:
[0009] (1) After cooling the trichloroethane, thionyl chloride is added, and then a sucrose solution is added, and the mixture is kept warm to obtain material A; (2) heating material A for a first time, keeping warm for a first time, heating it for a second time, keeping warm for a second time, heating it for a third time, keeping warm for a third time, heating it for a fourth time, keeping warm for a fourth time, and cooling the mixture to obtain material B;
[0010] (3) heating up and keeping warm for the fifth time, cooling down and then heating up again;
[0011] Carry out the sixth heating and heat preservation, cooling and then heating again;
[0012] The seventh heating and heat preservation are performed, and the temperature is lowered and then heated again to obtain material C;
[0013] (4) cooling material C, neutralizing it, and adjusting the pH after the reaction;
[0014] (5) Rotary evaporation to remove trichloroethane and DMF to obtain sucralose.
[0015] Furthermore, the cooling temperature in step (1) is 0-20°C.
[0016] Furthermore, in step (1), the volume ratio of trichloroethane, thionyl chloride and sucrose is 45-55:5-10:12-18.
[0017] Preferably, the volume ratio of trichloroethane, thionyl chloride and sucrose in step (1) is 50:8:16.
[0018] Furthermore, in step (2), the first heating refers to heating to 25-35°C, the first insulation refers to insulation for 0.5-1.5h, the second heating refers to heating to 40-50°C, the second insulation refers to insulation for 0.5-1.5h, the third heating refers to heating to 60-75°C, the third insulation refers to insulation for 0.5-1.5h, the fourth heating refers to heating to 80-95°C, and the fourth insulation refers to insulation for 10-20min.
[0019] Preferably, in step (2), the first heating refers to heating to 30°C, the first insulation refers to insulation for 1 hour, the second heating refers to heating to 45°C, the second insulation refers to insulation for 1 hour, the third heating refers to heating to 70°C, the third insulation refers to insulation for 1 hour, the fourth heating refers to heating to 90°C, and the fourth insulation refers to insulation for 15 minutes.
[0020] Furthermore, step (3) specifically includes the following steps:
[0021] ① Raise the temperature to 85-95°C, keep warm for 10-20 minutes, cool down to 60-70°C and then raise the temperature to 85-95°C again, repeat the above steps for more than 4 times (it is worth noting that the above steps here are the "raise the temperature to 85-95°C, keep warm for 10-20 minutes, cool down to 60-70°C and then raise the temperature to 85-95°C again" recorded in step ①);
[0022] ② Raise the temperature to 95-105°C, keep warm for 10-20 minutes, cool to 60-70°C and then raise the temperature to 95-105°C again, repeat the above steps for more than 4 times (it is worth noting that the above steps here are the "raise the temperature to 95-105°C, keep warm for 10-20 minutes, cool to 60-70°C and then raise the temperature to 95-105°C again" recorded in step ②);
[0023] ③ Raise the temperature to 110-120°C, keep warm for 10-20 min, cool to 60-70°C and then heat to 110-120°C again, repeat the above steps for more than 4 times (it is worth noting that the above steps here are the "raise the temperature to 110-120°C, keep warm for 10-20 min, cool to 60-70°C and then heat to 110-120°C again" recorded in step ③) to obtain material C.
[0024] Preferably, step (3) specifically includes the following steps:
[0025] ①Raise the temperature to 90℃, keep it warm for 15 minutes, cool it down to 65℃ and then raise it to 90℃ again, repeat the above steps for more than 4 times;
[0026] ② Raise the temperature to 100℃, keep it warm for 15 minutes, cool it down to 65℃ and then raise it to 100℃ again, repeat the above steps for more than 4 times;
[0027] ③ Raise the temperature to 114°C, keep warm for 15 minutes, cool to 65°C and then raise the temperature to 114°C again, repeat the above steps for more than 4 times to obtain material C.
[0028] Furthermore, the cooling temperature in step (4) is ≤30°C, the neutralization refers to adding ammonia water to neutralize to pH <12, and the pH adjustment is specifically adjusted to 7.
[0029] Preferably, the cooling temperature in step (4) is 0-5°C, the neutralization refers to adding ammonia water to neutralize to pH=9, and the adjustment of pH is specifically adjusted to 7.
[0030] Furthermore, the pH is adjusted by using hydrochloric acid.
[0031] Furthermore, the present invention also provides sucralose obtained by the above-mentioned synthesis method.
[0032] Furthermore, the solvent of the sucrose solution is DMF, and the concentration of the sucrose solution is 330 g / L.
[0033] In some specific embodiments, step (1) specifically includes the following steps: placing trichloroethane in a three-necked flask, cooling it, and adding thionyl chloride dropwise under magnetic stirring; then adding sucrose solution dropwise and keeping the temperature.
[0034] Furthermore, the insulation temperature in step (1) is below 30° C. and the insulation time is ≤5 h.
[0035] Furthermore, the adding of thionyl chloride in step (1) and then adding to the sucrose solution are both done dropwise.
[0036] The technical effects achieved by the present invention are:
[0037] The invention has the advantages of low production cost, high yield, green environmental protection, stable quality, simple equipment, etc., and provides an intermediate for the subsequent further synthesis of sucralose. DETAILED DESCRIPTION
[0038] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.
[0039] Before further describing the specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the examples of the present invention are for describing specific embodiments rather than for limiting the scope of protection of the present invention.
[0040] When the embodiment gives a numerical range, it should be understood that, unless otherwise specified in the present invention, the two endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those of ordinary skill in the art to which the present invention belongs.
[0041] It is worth noting that the raw materials used in the present invention are all common commercially available products, so their sources are not specifically limited.
[0042] Example 1
[0043] Take 500mL of dry trichloroethane and place it in a 1000mL three-necked flask, cool it down to 0-20℃ while stirring, add 80mL of thionyl chloride dropwise, then add 160mL of 330g / L sucrose DMF solution dropwise, then stir the material at room temperature and keep it warm for 1h. Then heat the material to 30℃ and keep it warm for 1h; then heat the material to 45℃ and keep it warm for 1h; then heat the material to 70℃ and keep it warm for 1h; then heat the material to 90℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 90℃ again; then heat the material to 100℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 100℃ again; then heat the material to 114℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 114℃ again. The material was further cooled to 0-5°C, and ammonia water was slowly added to adjust the pH to 9, and then the pH was adjusted to neutral with hydrochloric acid. After removing DMF and trichloroethane on a rotary evaporator, pure water was added to make the volume to 1000 mL to obtain a tetrachlorosucrose solution. The tetrachlorosucrose content was measured to be 52 g / L in liquid chromatography, and the yield was 81%.
[0044] Example 2
[0045] Take 500mL of dry trichloroethane and place it in a 1000mL three-necked flask, cool it down to 0-20℃ while stirring, add 82mL of thionyl chloride dropwise, then add 162mL of 330g / L sucrose DMF solution dropwise, then stir the material at room temperature and keep it warm for 1h. Then heat the material to 30℃ and keep it warm for 1h; then heat the material to 45℃ and keep it warm for 1h; then heat the material to 70℃ and keep it warm for 1h; then heat the material to 90℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 90℃ again; then heat the material to 100℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 100℃ again; then heat the material to 114℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 114℃ again. The material was further cooled to 0-5°C, and ammonia water was slowly added to adjust the pH to 9, and then the pH was adjusted to neutral with hydrochloric acid. After removing DMF and trichloroethane on a rotary evaporator, pure water was added to make the volume to 1000 mL to obtain a tetrachlorosucrose solution. The tetrachlorosucrose content was measured to be 50 g / L in liquid chromatography, and the yield was 79%.
[0046] Example 3
[0047] Take 500mL of dry trichloroethane and place it in a 1000mL three-necked flask, cool it down to 0-20℃ while stirring, add 85mL of thionyl chloride dropwise, then add 165mL of 330g / L sucrose DMF solution dropwise, then stir the material at room temperature and keep it warm for 1h. Then heat the material to 30℃ and keep it warm for 1h; then heat the material to 45℃ and keep it warm for 1h; then heat the material to 70℃ and keep it warm for 1h; then heat the material to 90℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 90℃ again; then heat the material to 100℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 100℃ again; then heat the material to 114℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 114℃ again. The material was further cooled to 0-5°C, and ammonia water was slowly added to adjust the pH to 9, and then the pH was adjusted to neutral with hydrochloric acid. After removing DMF and trichloroethane on a rotary evaporator, pure water was added to make the volume to 1000 mL to obtain a tetrachlorosucrose solution. The tetrachlorosucrose content was measured to be 49 g / L in liquid chromatography, and the yield was 76%.
[0048] Example 4
[0049] Take 500mL of dry trichloroethane and place it in a 1000mL three-necked flask, cool it down to 0-20℃ while stirring, add 88mL of thionyl chloride dropwise, then add 168mL of 330g / L sucrose DMF solution dropwise, then stir the material at room temperature and keep it warm for 1h. Then heat the material to 30℃ and keep it warm for 1h; then heat the material to 45℃ and keep it warm for 1h; then heat the material to 70℃ and keep it warm for 1h; then heat the material to 90℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 90℃ again; then heat the material to 100℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 100℃ again; then heat the material to 114℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 114℃ again. The material was further cooled to 0-5°C, and ammonia water was slowly added to adjust the pH to 9, and then the pH was adjusted to neutral with hydrochloric acid. After removing DMF and trichloroethane on a rotary evaporator, pure water was added to make the volume to 1000 mL to obtain a tetrachlorosucrose solution. The tetrachlorosucrose content was measured to be 48 g / L in liquid chromatography, and the yield was 74%.
[0050] Example 5
[0051] Take 500mL of dry trichloroethane and place it in a 1000mL three-necked flask, cool it down to 0-20℃ while stirring, add 90mL of thionyl chloride dropwise, then add 170mL of 330g / L sucrose DMF solution dropwise, then stir the material at room temperature and keep it warm for 1h. Then heat the material to 30℃ and keep it warm for 1h; then heat the material to 45℃ and keep it warm for 1h; then heat the material to 70℃ and keep it warm for 1h; then heat the material to 90℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 90℃ again; then heat the material to 100℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 100℃ again; then heat the material to 114℃ and keep it warm for 15min; then cool the material to 65℃ and then heat it up to 114℃ again. The material was further cooled to 0-5°C, and ammonia water was slowly added to adjust the pH to 9, and then the pH was adjusted to neutral with hydrochloric acid. After removing DMF and trichloroethane on a rotary evaporator, pure water was added to make the volume to 1000 mL to obtain a tetrachlorosucrose solution. The tetrachlorosucrose content was measured in liquid chromatography to be 49 g / L, and the yield was 80%.
[0052] Comparative Example 1
[0053] Take 500mL of dry trichloroethane and place it in a 1000mL three-necked flask, cool it down to 0-20℃ while stirring, add 80mL of thionyl chloride dropwise, then add 160mL of 330g / L sucrose DMF solution dropwise, then stir the material at room temperature and keep it warm for 1h. Then heat the material to 30℃ and keep it warm for 1h; then heat the material to 45℃ and keep it warm for 1h; then heat the material to 70℃ and keep it warm for 1h; then heat the material to 90℃ and keep it warm for 15min; then heat the material to 100℃ and keep it warm for 15min; then heat the material to 114℃ and keep it warm for 15min. Then cool the material to 0-5℃, slowly add ammonia water dropwise, adjust the pH to 9, and then adjust the pH to neutral with hydrochloric acid. After removing DMF and trichloroethane on a rotary evaporator, add pure water to make the volume to 1000mL to obtain tetrachlorosucrose solution. The sucralose content was measured by liquid chromatography to be 45 g / L, and the yield was 74%.
[0054] Comparative Example 2
[0055] Take 500mL of dry trichloroethane and place it in a 1000mL three-necked flask, cool it down to 0-20℃ while stirring, add 82mL of thionyl chloride dropwise, then add 162mL of 330g / L sucrose DMF solution dropwise, then stir the material at room temperature and keep it warm for 1h. Then heat the material to 30℃ and keep it warm for 1h; then heat the material to 45℃ and keep it warm for 1h; then heat the material to 70℃ and keep it warm for 1h; then heat the material to 90℃ and keep it warm for 15min; then heat the material to 100℃ and keep it warm for 15min; then heat the material to 114℃ and keep it warm for 15min. Then cool the material to 0-5℃, slowly add ammonia water dropwise, adjust the pH to 9, and then adjust the pH to neutral with hydrochloric acid. After removing DMF and trichloroethane on a rotary evaporator, add pure water to make the volume to 1000mL to obtain tetrachlorosucrose solution. The sucralose content was measured in liquid chromatography to be 42 g / L, and the yield was 69%.
[0056] Comparative Example 3
[0057] Take 500mL of dry trichloroethane and place it in a 1000mL three-necked flask, cool it down to 0-20℃ while stirring, add 85mL of thionyl chloride dropwise, then add 165mL of 330g / L sucrose DMF solution dropwise, then stir the material at room temperature and keep it warm for 1h. Then heat the material to 30℃ and keep it warm for 1h; then heat the material to 45℃ and keep it warm for 1h; then heat the material to 70℃ and keep it warm for 1h; then heat the material to 90℃ and keep it warm for 15min; then heat the material to 100℃ and keep it warm for 15min; then heat the material to 114℃ and keep it warm for 15min. Then cool the material to 0-5℃, slowly add ammonia water dropwise, adjust the pH to 9, and then adjust the pH to neutral with hydrochloric acid. After removing DMF and trichloroethane on a rotary evaporator, add pure water to make the volume to 1000mL to obtain tetrachlorosucrose solution. The sucralose content was measured by liquid chromatography to be 43 g / L, and the yield was 70%.
[0058] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.
Claims
1. A method for synthesizing sucralose, characterized in that: The following steps are involved: (1) After cooling the trichloroethane, thionyl chloride is added, and then sucrose solution is added, and the mixture is kept warm to obtain material A; (2) heating material A for the first time, keeping it warm for the first time, heating it for the second time, keeping it warm for the second time, heating it for the third time, keeping it warm for the third time, heating it for the fourth time, keeping it warm for the fourth time, and cooling it to obtain material B; (3) heating up and keeping warm for the fifth time, cooling down and then heating up again; Carry out the sixth heating and heat preservation, cooling and then heating again; The seventh heating and heat preservation are performed, and the temperature is lowered and then heated again to obtain material C; (4) cooling material C, neutralizing it, and adjusting the pH after the reaction; (5) Rotary evaporation to remove trichloroethane and DMF to obtain sucralose.
2. The synthesis method according to claim 1, characterized in that: The cooling temperature in step (1) is 0-20°C.
3. The synthesis method according to claim 1, characterized in that: The volume ratio of trichloroethane, thionyl chloride and sucrose in step (1) is 45-55:5-10:12-18.
4. The synthesis method according to claim 3, characterized in that: The volume ratio of trichloroethane, thionyl chloride and sucrose in step (1) is 50:8:
16.
5. The synthesis method according to claim 1, characterized in that: The first heating in step (2) refers to heating to 25-35°C, the first insulation refers to insulation for 0.5-1.5h, the second heating refers to heating to 40-50°C, the second insulation refers to insulation for 0.5-1.5h, the third heating refers to heating to 60-75°C, the third insulation refers to insulation for 0.5-1.5h, the fourth heating refers to heating to 80-95°C, and the fourth insulation refers to insulation for 10-20min.
6. The synthesis method according to claim 5, characterized in that: The first heating in step (2) refers to heating to 30°C, the first insulation refers to insulation for 1 hour, the second heating refers to heating to 45°C, the second insulation refers to insulation for 1 hour, the third heating refers to heating to 70°C, the third insulation refers to insulation for 1 hour, the fourth heating refers to heating to 90°C, and the fourth insulation refers to insulation for 15 minutes.
7. The synthesis method according to claim 1, characterized in that: Step (3) specifically includes the following steps: ①Raise the temperature to 85-95℃, keep warm for 10-20min, cool down to 60-70℃ and then raise the temperature to 85-95℃ again, repeat the above steps for more than 4 times; ②Raise the temperature to 95-105℃, keep warm for 10-20min, cool down to 60-70℃ and then raise the temperature to 95-105℃ again, repeat the above steps for more than 4 times; ③ Raise the temperature to 110-120°C, keep warm for 10-20 minutes, cool to 60-70°C and then raise the temperature to 110-120°C again, repeat the above steps for more than 4 times to obtain material C.
8. The synthesis method according to claim 7, characterized in that: Step (3) specifically includes the following steps: ①Raise the temperature to 90℃, keep it warm for 15 minutes, cool it down to 65℃ and then raise it to 90℃ again, repeat the above steps for more than 4 times; ② Raise the temperature to 100℃, keep it warm for 15 minutes, cool it down to 65℃ and then raise it to 100℃ again, repeat the above steps for more than 4 times; ③ Raise the temperature to 114°C, keep warm for 15 minutes, cool to 65°C and then raise the temperature to 114°C again, repeat the above steps for more than 4 times to obtain material C.
9. The synthesis method according to claim 1, characterized in that: The cooling temperature in step (4) is ≤30°C, the neutralization refers to adding ammonia water to neutralize to pH <12, and the pH adjustment is specifically adjusted to 7.
10. Sucralose obtained by the synthesis method according to any one of claims 1 to 9.