Sucralose Powder CAS 56038-13-2

6 group protection method This method was developed by Tate-Lyle Company. Firstly, Bacillus strains were used to ferment glucose at 30 °C to generate glucose-6-acetic acid. The highest concentration of glucose-6-acetic acid could reach 15 g/L, and the yield could reach 85% of the theoretical yield. Glucose-6-acetic acid was then purified by a combination of methanol extraction and silica gel column chromatography separation, and the purification yield was 80% to 85%.

Under the action of β-fructosyltransferase produced by Bacillus subtilis, the mixed reaction of glucose-6-acetic acid and Sucralose Powder produces sucrose-6-acetic acid, and the concentration of sucrose-6-acetic acid can reach 120 g/L. The yield of this step is 58%. 70% pure sucrose-6-acetic acid can be obtained by chromatography. 4,1′,6′,-Trichloro-4,1′,6′-trideoxygalactosucrosepentaacetic acid is obtained by reacting Sucralose Powder -6-acetic acid with Vilsmeier’s reagent made of phosphorus pentachloride and DMF , the yield of this step was 39%. Sucralose Powder can be obtained after sucralose pentaacetic acid is removed from the acetate group, and the yield of deacetic acid is 90%. In this method, the fermentation cost of glucose-6-acetic acid is high, and the purification of Sucralose Powder -6-acetic acid is difficult, and the total yield is about 20%. The synthetic route is as follows:

This method is also developed by Tate-Lyle Company to synthesize raffinose as raw material. Raffinose sugar beet, cottonseed and other plants are currently not available in large quantities. They can be synthesized from a saturated solution of galactose and sucrose at 30°C under the action of galactosidase, and the product concentration can reach 7.5g/L.

Raffinose is chlorinated with thionyl chloride in the presence of triphenylphosphine to form 4,1′,6′,6”-tetrachloro-4,1′,6′,6”-tetradeoxygalactose cotton Subsaccharide heptanoic acid. After the latter is deacetic acid, 4,1′,6′,6”-tetrachloro-4,1′,6′,6”-tetradeoxygalactose raffinose (TCR), calculated as raffinose , the yield of TCR was 32.6%. Under the action of α-galactosidase at 30°C, TCR was hydrolyzed for 24 hours to generate Sucralose Powder with a hydrolysis yield of 80% to 90%. The total yield was 26% to 29%. Monoester method The method was proposed by KhanRA and MuytiKS in 1982. Using the reaction principle of alkyd esterification, we try to shield a certain hydroxyl group in the sucrose molecule, and by controlling the conditions, we can obtain as high monoester content as possible. Then it is separated, chlorinated, de-esterified and purified to obtain the product. This method is difficult to control the position and degree of esterification, and the yield is only 5% to 7%.

base transfer method
Using sucrose as raw material, it is obtained by tritylation (shielding three primary hydroxyl groups), acetylation (shielding five secondary hydroxyl groups), detritylation, acetyl transfer, chlorination, deacetylation and other steps. Sucralose.

Tritylation and Acetylation At 50°C, 50 g of sucrose and 60 g of N-methylmorpholine were dissolved in 100 mL of dimethylformamide. After half an hour, 141.8 g of trityl chloride (purity 97%) was added in three times, and the heating was continued for 3.5 h. Then 42.7g of sodium bicarbonate was added, and the temperature was kept at 50°C for 1h. The solution was vacuum-dried, then dissolved in 96.6 mL of acetic anhydride, then 15.6 g of potassium acetate was added, heated to 115° C. and kept at a constant temperature for 3 hours. After cooling, 400 mL of ethanol was added to obtain 183.2 g of crystalline material, which contained 124.6 g of 6,1,6′-trioxy-trityl-pentaacetyl sucrose (TRISPA), with a yield of 68.6%.

Detrityl group 200g TRISPA was dissolved in 800mL toluene, cooled to 0°C, and 1.7g of hydrogen chloride gas was passed through, and a precipitate was formed after 4.5h. It was purged in nitrogen for 1 h to remove residual hydrogen chloride gas, filtered and washed with 65 mL of toluene to form particles, re-dissolved in 120 mL of 1% triethylamine toluene solution, the mixture was filtered again, and washed with 65 mL of toluene, After drying, 81 g of 2,3,3′,4,4′-pentaoxy-acetylsucrose (4-PAS) was obtained, and the yield was 80%.

Acetyl Migration 50 g of 4-PAS was dissolved in 100 mL of water, heated to 60°C, filtered while hot, and cooled to room temperature. 2.5 mL of pyridine was added and stirred at room temperature for 2.5 h. The solution was acidified with 2.5 mL of concentrated hydrochloric acid and extracted with dichloromethane (2 x 125 mL). The extract was concentrated to 50 mL, and heptane (3×50 mL) was added and stirred to precipitate crystals. After 20 min, filter, rinse the crystal with 30 mL of heptane, and dry under vacuum for 16 h to obtain 34 g of 2,3,3′,4′,6-pentaacetylsucrose (6-PAS) with a yield of 58%.

Chlorination 50g 6-PAS and 50.3g triphenylphosphorus oxide (TPPO) were stirred into 150mL toluene solution to make a slurry, 32.8mL thionyl chloride was added at room temperature, the solution was refluxed for 2.5h and then cooled to 40°C. Then 200 mL of water was added to further cool to 0 °C, the mixture was vigorously stirred for 1 h, filtered, and rinsed with 75 mL of toluene: water (1:2) to obtain crude 4,1′,6′-trichloro-4,1′ , 6′-trideoxy-acetyl-galactosucrose (TOSPA). It was dissolved in 200 mL of hot methanol, stirred at 20 °C for 1 h, recrystallized and filtered again to obtain 40 g of pure TOSPA with a yield of 75%.

Deacetylation Dissolve 50 g TOSPA and 0.5 g sodium methoxide in 125 mL methanol, and stir under vacuum for 1.5 h. After adding Amberlite IRC50 (H+) resin, the solution was stirred and neutralized again, filtered, and the filtrate was decolorized with 2 g of activated carbon and 2 g of diatomaceous earth and concentrated. 100 mL of ethyl acetate was added, and the Sucralose Powder was crystallized out. After washing and drying, the product weighed 26 g and had a purity of 92%.