The preparation of Aspartame Powder typically has two sort of chemical synthesis as well as enzymatic synthesis
enzymatic synthesis.
Tao Guoliang, Department of Chemistry, Wuhan University and also others offered the following artificial course:
Preparation of I Add 0.5 mmol benzyloxycarbonyl aspartate, 1.5 mmol phenylalanine methyl ester hydrochloride and also 2.5 mL water into a 25mL Erlenmeyer flask, change the pH worth to 6 with ammonia water, include 7mg thermophilic For protease, mix the response at 40 ° C for 6h. It was filteringed system, washed with pure water, and also dried to acquire 0.29 g of white solid (I), with a yield of 95.6% and a melting point of 116-118 ° C. Elemental analysis results: C62.96%, H6.09%. N6.65%.
( 2) Preparation of II Add 0.5 g of example I and 20 mL of 3 mol/L hydrochloric acid right into a 25 mL Erlenmeyer flask, as well as stir and react at 45 ° C. for 0.5 h. Purification, washing with distilled water, as well as drying provided 0.32 g of item II with a yield of 92% and a melting point of 129-131 ° C. Elemental analysis results: C61.45%, H5.42%, N6.82%.
Preparation of III Include 0.2 g of palladium-carbon (10%) stimulant, 20mL of glacial acetic acid, and also 5mL of water into a 100mL three-necked flask, as well as activate it by hydrogenation for 1.5 h. Add 20mL of antarctic acetic acid liquified in 0.6 g II, as well as mix as well as hydrogenate at 30 ° C for 6h. After the response was completed, filter as well as clean the catalyst three times with glacial acetic acid; focus the filtrate and launderings to dryness under lowered stress, include 15 mL of benzene, and remain to focus under minimized pressure to dry skin to obtain a white solid, which was dried out to obtain 0.38 g of item III, with a return of 92.3%, melting point 245 ° C. Elemental analysis results: C55.63%, H6.23%, N8.96%.
chemical synthesis
Using aspartic acid and phenylalanine as raw materials, it is manufactured with the steps of amino defense, interior anhydride, condensation, hydrolysis, and also neutralization. Different shielding teams and methyl esterification sequences can have various artificial techniques. Such as adopting formyl as the process route of protecting group and also methyl esterification after, its
Put 27mL of 95% methanol and 0.2 g of magnesium oxide into a 250mL flask. After the magnesium oxide is liquified, include 100mL of 98% acetic anhydride. Currently, the temperature progressively rises to 40 ° C. Include 67g of L-aspartic acid, raise the temperature to 50 ° C, mix and also keep it warm for 2.5 h, include 15mL of 98% acetic anhydride, continue to maintain cozy for 2.5 h, add 16mL of isopropanol, remain to respond for 1.5 h, trendy to space temperature after the response.
Add the above-mentioned interior anhydride right into a 1000mL flask, after that add 207mL ethyl acetate as well as 66Gl-phenylalanine, mix at 25 ~ 30 ° C for 1.5 h, then include 126mL of antarctic acetic acid, proceed the reaction for 4.5 h, get rid of the vacuum cleaner after the reaction Solvent, until the temperature level of the response system is 65 ° C. After that 45mL of 35% hydrochloric acid was added, the temperature level was elevated to 60 ° C, as well as the response was refluxed for 2h. After hydrolysis, carry out climatic distillation up until the purification temperature reaches 63 ° C( response system temperature 73 ° C), include 180mL of methanol, and also proceed climatic purification up until the system temperature level is 85 ° C. After cooling down to 25 ° C, the light ends were eliminated in vacuo. Add 54mL of 35% hydrochloric acid, 9mL of methanol and 43mL of water to the above hydrolysis response remedy, and also perform esterification response at 20 ~ 30 ° C for 7 days. Then suction filter and also wash with water to separate α-APM hydrochloride. Liquify it in 600mL of distilled water, as well as neutralize it to Ph= 4.5 with 5% -10% NaOH remedy at 40 ° C. Cool to listed below 5 ° C, suction filter and also wash to acquire the unrefined α-APM, and after that liquify it in a mixture of 500 mL methanol as well as water (volume ratio 1:2). After cooling down and also formation, suction filtering as well as washing, as well as vacuum cleaner drying, the yield is 45% (based upon L-phenylalanine).
Japanese scholars propose an unprotected route:
Dissolve 90g of phenylalanine methyl ester hydrochloride in 450mL of water, neutralize with 24g of sodium carbonate, and then remove with two 350mL dichlorethylene to obtain phenylalanine methyl ester. Add 9g of acetic acid as well as 8mL of methanol to the remove, after that include 15.2 g of aspartic anhydride hydrochloride at -20 ° C, keep mixing for 30min, then add 350mL of warm water at 70 ~ 80 ° C as well as sodium carbonate (5.7 g) solution 300mL. After drawing out the staying phenylalanine methyl ester twice with 150 mL of dichloroethylene, the pH value of the aqueous layer was adjusted to 4.8 with dilute hydrochloric acid. This liquid service was gauged by paper electrophoresis to have 18.2 g (60% molar return) of α-APM and also 6.1 g (20% molar return) of β-APM. This liquid remedy was focused in vacuo to 100mL, as well as added. 30mL of 36% hydrochloric acid, put in the fridge over night. 21.3 g of α-APM · HCl crystals were precipitated (yield 58%), as well as the crystals were filtered off and also dissolved in 200 mL of water. The remedy was mixed at 50 ° C, and the pH worth was adapted to 4.8 with 5% sodium carbonate service, after that placed in the refrigerator overnight, precipitated as well as filtered to obtain 13.0 g of α-APM crystals (return 43%). The crystals were dissolved in 500 mL of water, travelled through a Dowex 1 × 4 (acetate form) column (1 × 20 centimeters) at 45 ° C., as well as washed with 20 mL of water. The effluent was focused in vacuo with the cleaning liquid, as well as 11.2 g of α-APM crystals were sped up. Return 37%, melting point 235 ~ 236 ° C(decomposition), specific rotation αD22 +32.0 ° (C=1, in acetic acid). Elemental evaluation results: C55.30%, H6.19%, N9.36%.
