阅读说明：本技术 一种改进的三氯蔗糖-6-乙酸酯的制备方法 (Improved preparation method of sucralose-6-acetate ) 是由 刘瑞祥 王林波 石剑 于 2020-05-22 设计创作，主要内容包括：本发明公开了一种改进的三氯蔗糖-6-乙酸酯的制备方法,包括以下步骤：1)向容器中加入三氯乙烷和氯化亚砜,三氯乙烷与氯化亚砜摩尔比为3.2~4.2：1；2)加入蔗糖-6-乙酸酯的DMF定溶液,3)反应液加热至68℃～71℃,然后进行梯度升温：升温至90℃,98℃～101℃,109℃～112℃,每段升温时间＞1h,温度到达后保温1-2 h,制得的三氯蔗糖-6-乙酸酯O-烷基氯盐反应液；4)制得的反应液经氨水调节至pH为10.0,再经酸中和后可得到三氯蔗糖-6-乙酸酯。本发明的有益效果：本发明功地提高了产率,三氯蔗糖-6-乙酸酯收率可达到44%—77%,同时减轻了中和液抽滤难度,降低了生产成本,减少了三废。(The invention discloses an improved preparation method of sucralose-6-acetate, which comprises the following steps: 1) adding trichloro ethane and thionyl chloride into a container, wherein the molar ratio of the trichloro ethane to the thionyl chloride is 3.2-4.2: 1; 2) adding DMF solution of sucrose-6-acetate, 3) heating the reaction solution to 68-71 ℃, and then carrying out gradient temperature rise: heating to 90 ℃, 98-101 ℃, 109-112 ℃, wherein the heating time of each section is more than 1h, and keeping the temperature for 1-2 h after the temperature is reached to prepare the sucralose-6-acetate O-alkyl chloride reaction solution; 4) the pH of the prepared reaction solution is adjusted to 10.0 by ammonia water, and the sucralose-6-acetate can be obtained after acid neutralization. The invention has the beneficial effects that: the invention successfully improves the yield, the yield of the sucralose-6-acetate can reach 44-77 percent, simultaneously lightens the suction filtration difficulty of the neutralization solution, reduces the production cost and reduces the three wastes.)

1. An improved method for preparing sucralose-6-acetate is characterized by comprising the following steps:

1) adding trichloromethane into a container, stirring and cooling to below 0 ℃, dropwise adding thionyl chloride into the container, wherein the temperature is not more than 5 ℃, stirring uniformly, and stirring for 20 min after dropwise adding, wherein the molar ratio of the trichloromethane to the thionyl chloride is 3.2-4.2: 1;

2) dropwise adding DMF solution of sucrose-6-acetate into the mixed solution of trichloroethane and thionyl chloride at the temperature of 0-10 ℃, uniformly stirring, naturally returning to the room temperature after dropwise adding, and stirring for 30 min at the room temperature, wherein the molar ratio of sucrose-6-acetate to thionyl chloride is 1: 9;

3) heating and stirring the reaction solution obtained in the step 2) to 68-71 ℃, and then carrying out gradient temperature rise: heating to 90 deg.C for more than 1h, and keeping the temperature for 30 min;

heating to 98-101 ℃, wherein the heating time is more than 1h, and keeping the temperature for 1.5 h after the temperature is reached;

heating to 109-112 ℃, keeping the temperature for more than 1h after the temperature is reached, and keeping the temperature for 2 h to prepare sucralose-6-acetate O-alkyl chloride reaction solution;

4) adjusting the pH of the sucralose-6-acetate O-alkyl chloride reaction solution prepared in the step 3) to 10.0 by ammonia water, and neutralizing by acid to obtain the sucralose-6-acetate.

2. The process of claim 1 for the preparation of improved sucralose-6-acetate wherein: the concentration of sucrose-6-acetate in DMF was determined as one of the following: 280g/L, 290g/L, 300g/L, 310g/L, 320g/L, 330g/L, 340g/L, 350g/L and 360 g/L.

3. The process of claim 1 or 2 for the preparation of improved sucralose-6-acetate, wherein: the concentration of sucrose-6-acetate in DMF is preferably 340 g/L.

Technical Field

The invention relates to an improved preparation method of sucralose-6-acetate.

Background

Sucralose-6-acetate (4, 1 ', 6' -trichloro sucrose-6-acetate), chemical name: 4,1 ', 6' -trichloro-4, 1 ', 6' -trideoxygalactosucrose-6-acetate having the following structure:

sucralose was first developed by Tate & Lyle in the united kingdom in 1976 and was marketed in 1988 as an intense sweetener having about 600 times the sweetness of sucrose. The sucralose has zero caloric value, can be eaten by fat patients, cardiovascular disease patients, the elderly and the like, and has a very wide application range. At present, a plurality of manufacturers produce the product in China, but the yield is not too high.

The synthesis of the sucralose-6-acetate is complex, is also a key step for producing the sucralose, and has the problems of low reaction concentration, long period and low conversion rate, the yield of the sucralose-6-acetate product is 20-40%, more impurities and difficult purification. Therefore, how to increase the yield of sucralose-6-acetate is the key to reduce the production cost of sucralose. Currently, the mainstream production process for obtaining sucralose-6-acetate is to use sucrose-6-acetate as a starting material at 115^oAnd C, obtaining sucralose-6-acetate by using a chlorinating reagent. The route is as follows:

the reaction route has the advantages of easily obtained raw materials, low price, low yield, more tar-like carbide generated in the reaction process, bad smell of pyridine, unfavorable operation and the like.

Disclosure of Invention

The invention aims to solve the problem of low yield of the existing sucralose production process, and provides an improved preparation method of sucralose-6-acetate.

In order to achieve the purpose, the technical scheme for solving the problems comprises the following steps:

an improved method for preparing trichlorosucrose-6-acetate uses DMF solution of sucrose-6-acetate and chlorinating agent as initial raw materials, and adjusts reaction temperature and reaction time length by changing the concentration of sucrose-6-acetate, thus obtaining trichlorosucrose-6-acetate with higher yield.

The preparation method of the invention comprises the following steps:

1) adding trichloromethane into a container, stirring and cooling to below 0 ℃, dropwise adding thionyl chloride into the container, wherein the temperature is not more than 5 ℃, stirring uniformly, and stirring for 20 min after dropwise adding, wherein the molar ratio of the trichloromethane to the thionyl chloride is 3.2-4.2: 1.

2) dropwise adding DMF solution of sucrose-6-acetate into the mixed solution of trichloroethane and thionyl chloride at the temperature of 0-10 ℃, uniformly stirring, naturally returning to the room temperature after dropwise adding, and stirring for 30 min at the room temperature, wherein the molar ratio of sucrose-6-acetate to thionyl chloride is 1: 9;

3) heating and stirring the reaction solution obtained in the step 2) to 68-71 ℃, and then carrying out gradient temperature rise: heating to 90 deg.C for more than 1h, and keeping the temperature for 30 min;

heating to 98-101 ℃, wherein the heating time is more than 1h, and keeping the temperature for 1.5 h after the temperature is reached;

heating to 109-112 ℃, keeping the temperature for more than 1h after the temperature is reached, and keeping the temperature for 2 h to prepare sucralose-6-acetate O-alkyl chloride reaction solution;

4) adjusting the pH of the sucralose-6-acetate O-alkyl chloride reaction solution prepared in the step 3) to 10.0 by ammonia water, and neutralizing by acid to obtain the sucralose-6-acetate.

The further technical scheme is as follows: the concentration of sucrose-6-acetate in DMF was determined as one of the following: 280g/L, 290g/L, 300g/L, 310g/L, 320g/L, 330g/L, 340g/L, 350g/L and 360 g/L.

The further technical scheme is as follows: the concentration of sucrose-6-acetate in DMF is preferably 340 g/L.

The invention has the beneficial effects that:

the invention successfully improves the reaction yield, the yield of the sucralose-6-acetate can reach 44-77 percent, simultaneously lightens the suction filtration difficulty of the neutralization solution, reduces the production cost and reduces the three wastes.

Detailed Description