The Synthesis Of Advantame

Advantame is a novel high-intensity sweetener and its sweetness is 20,000 times sweeter than sugar 's.Advantame has no calories and an outstanding flavor profile.Nowadays,Advantame has got approved of the FDA and it's the latest achievement of sweeteners research.The synthetic process of Advantame can be concluded into two reactions including the aldol condensation reaction to synthesize 3-hydroxy-4-methoxycinnamaldehyde and the reduction amination of 3-hydroxy-4-methoxy-cinnamaldehyde.The two-steps synthetic process of Advantame could be inefficient and costly in consideration of the disadvantage of the aldol condensation reaction such as long time,high energy consumption and low yield which could be improved.In this paper,Advantame is synthesized through the aldol condensation of isovanillin and the reductive amination of the 3-hydroxy-4-methoxycinnamaldehyde and identified using IR,NMR.Firstly,the reaction of isovanillin and acetate catalyzed by NaOH is studied to evaluate the influence of the reaction conditions on the yield and obtain the optimum condition.The highest yield of 3-hydroxy-4-methoxy-cinnamaldehyde is 56.7%when the mole ratio of isovanillin and acetate is 1:2.2,the temperature is-10?,the reaction time is 45 h,NaOH concentration is 0.16 g·mL-1,the concentration of acetate solution is 28%.Secondly,substitute acetate with vinyl acetate as the reactant and the influence of the reaction conditions is studied as well.The optimum condition is listed below:the mole ratio of isovanillin and vinyl acetate is 1:2,the temperature is 11 ?,the reaction time is 12 h,the NaOH concentration is 0.18 g·mL-1,.And the highest yield is 79.5%.Finally,phase transfer catalyst is selected to catalyze the aldol condensation of isovanillin and acetate combined with NaOH.The highest yield achieves 64.9%catalyzed by hexadecyl trimethyl ammonium bromide(CTAB)as phase transfer catalyst.And the optimum conditions is listed below:the mole ratio of isovanillin and acetate is 1:2.2,the temperature is 23 ?,the reaction time is 19 h,the NaOH concentration is 0.115 g·mL-1,the concentration of acetate solution is 20%,the dosage of CTAB is 0.1 gCompared with the reaction of isovanillin and acetate,the aldol condensation reaction of vinyl acetate and the aldol condensation reaction of acetate catalyzed by CTAB requires shorter time and more acceptable temperature with a higher yield.Both the two methods have a positive efffct on the yield and can provide the industrialization of Advantame theoretical guidance.