Synthesis of Strong Sweetener Sucralose

The sucralose is TGS for short, its chemical name is 1 ', 6 ' dichloro 1 ', 6 ' -didesoxy β-D fructofuranose 4chloro 4desoxy α-D fructofuranose, is one derivative of the halogeno sucrose. It’s mild and mellow, with aromatic flavor and stable property, it’s low in calories and good for consumers’ health; it can be used together with the traditional sweetener, and used independently. it’s good in sweet taste and mouth feel (Kang, 2001, pp. 12). However, the sucralose can’t rot teeth away, and not cause many diseases as the fructose and maltose, besides its low sugar price is not so high as other nutritional sweeteners(Huang, 2000, pp. 22),moreover, the toxicology and the safety test indicated: sucralose does not have teratogenicity, discontinuity, reproduction toxicity, cancerous as well as nerve toxicity, also does not have any effects on animal's blood sugar level and the insulin secretion (Gao, 2004, pp. 5).Therefore, it could be edible for obese patients, patients with cardiovascular disease and diabetes. It is a strong sweetener prepared by British Professor Hough L in the late 1970s (Yan, 2004, pp 165), it’s also artificially developed, and the most competitive, non-nutrition, perfect high-intensity sweetener until now (Tian, 2006, pp. 3).

The sucralose is TGS for short, its chemical name is 1 ', 6 ' -dichloro -1 ', 6 ' -didesoxy -β-D -fructofuranose -4chloro -4-desoxy -α-D -fructofuranose, is one derivative of the halogeno sucrose.It's mild and mellow, with aromatic flavor and stable property, it's low in calories and good for consumers' health; it can be used together with the traditional sweetener, and used independently.it's good in sweet taste and mouth feel (Kang, 2001, pp. 12).However, the sucralose can't rot teeth away, and not cause many diseases as the fructose and maltose, besides its low sugar price is not so high as other nutritional sweeteners (Huang, 2000, pp. 22),moreover, the toxicology and the safety test indicated: sucralose does not have teratogenicity, discontinuity, reproduction toxicity, cancerous as well as nerve toxicity, also does not have any effects on animal's blood sugar level and the insulin secretion (Gao, 2004, pp. 5).Therefore, it could be edible for obese patients, patients with cardiovascular disease and diabetes.It is a strong sweetener prepared by British Professor Hough L in the late 1970s (Yan, 2004, pp 165), it's also artificially developed, and the most competitive, non-nutrition, perfect high-intensity sweetener until now (Tian, 2006, pp. 3).
The demand for sucralose in China is about 50 tons annually, the majority depends on imports, and is only used in some relatively high-grade food at present, it hasn't been widely used in China yet (Shen, 2007,pp. 137).Therefore, if the basic research on the sucralose production technology can be strengthened, that will further improve the technique of production, reduce the cost of product, and extend its application range greatly, and thus give an impetus to the development of food additive industry in China.Nowadays, people have explored many methods of the development about sucralose, such as the tritylation method, the monoesterification, biosynthesis, the hydrolyzing raffinose and the chlorination of sucrose derivative .etc(Chen, 2007, pp. 90).The chemical synthesis method above always take too many steps and the technical process is complex.The fermentation of chemically enzymatic synthesis is complex, and it's difficult to purify the intermediary product, with high cost.The monoesterification only needs three steps in the reaction of synthesis, with high yield and low cost, the intermediary product is easy to separate, so it's an ideal technical process for the synthesis of sucralose (Kang, 2006, pp. 59).
We synthesize sucralose from sucrose as a starting material by following steps: first synthesis sucrose-6-acetate, and then by chlorination, at last deacetylation (just as the following figure shows), and make research on technological process, reaction conditions, etc.

The chlorination of sucrose -6-acetate
Take sucrose -6-acetate (10g) to dissolve in anhydrous DMF (100ml), under the ice-bath condition, add dropwize the mixed solvent of thionyl chloride (23ml) and 1,1,2-trichlorethane (43ml) slowly, when it's finished, maintain the low temperature in 30 minutes; heat up to 115 slowly wit ℃ hin 2 hours, reflux in 1.5 hours; and then cool off the reaction liquid until the temperature is below 15 , add weak aqua ammonia (6mol/L,20ml ) dropwise slowly, and keep ℃ temperature below 30 , it is neutralized with the alkaline solution, The organic pha ℃ se is separated from the aqueous phase, extract the aqueous phase with 1,1,2 trichlorethane(20ml×3),the organic phase is combined, and the solvent was evaporated under the diminished pressure, thick product(5.9g,59%.) is obtained.

Discussion
When it comes to the catalytic reaction with p-TsOH, if the quantity of the acid is insufficient, the solution PH value would be high, and the reaction won't be complete, plenty of sucrose have not participated in the reaction, it would affect the yield of sucrose-6-acetate directly.If p-TsOH is excessive, it would make the product break down.if the quantity of tert-Butylamine is insufficient, the PH value of solution is low, the reaction would not be complete.
Since DMF is also used for solvent during the chlorination of sucrose -6-acetate, after obtaining the sucrose -6acetate in the reaction, the solid intermediate may not be obtained directly, it only need provide sucrose -6-acetate in DMF solution for the chlorination In the process of sucralose's preparation, the chloride reaction is the key to the entire synthesis process.when thionyl chloride is added, the reaction temperature needs to be controlled, because a quantity of heat will be emitted at this time, the product is prone to charring.In order to control the temperature, this ice-bath was used, it could keep the reaction temperature low, be beneficial for the reaction to carry on smoothfully.The mixture of thionyl chloride and 1,1,2-trichloroethane is added dropwise with the dropping funnel, otherwise heat would be emitted too quickly in reaction mixture, the temperature can't be diminished in time, it would have negative effect on the experiment.
We used the method of group protected in our experiment, carried on improvement to the existing preparation method, the product is obtained only through three-step reaction, each step is easy to operate, the raw material is easily obtained, increasing the yield of the product, reducing the production costs greatly and being more helpful for the industrial production.