Synthesis, Purification And Property Research Of Advantame Intermediate?3-hydroxy-4-methoxy Benzene Acrolein

Advantame is a kind of high-potency,low-caloric functional sweetener.Its sweetness is20000 times as sucrose,the highest sweetness substance used by mankind,therefore,it has broad application prospects and promotion of value.Synthesis of advantame intermediate is the most important and difficult part for producing the advantame.This paper aims at discussing and studying on the synthesis technique of advantame intermediate 3-hydroxy-4-methoxy benzene acrolein,and to pave the way for the synthesis research and large-scale industrialized production of advantame.Preparing intermediate reference substances by separation and purification of crude products,and to establish a high-performance liquid chromatography analysis method,exploring the crystallization conditions and antioxidant activities of intermediates.The main results and conclusions are as follows:?1?3-hydroxy-4-methoxy benzal acrolein,the key intermediate of advantame was prepared via the reaction of isovanillin and acetaldehyde under strong alkaline condition.The processes were optimized with the yield of intermediate as index through single factor test and response surface test,the optimal reaction condition were determined to be-5?,2h,12%and2:1 for reaction temperature,aldehyde dropwise time,NaOH concentration and the solid-liquid ratio of isovanillin to aldehyde,the yield of the intermediate was 64.28%under this condition.?2?The processes were optimized with the yield and purity of intermediate as index,the optimum conditions for the separation and purification of intermediate by medium pressure column chromatograph were determined as follows:the flow rate was 6 mg/mL,the injection volume was 10 mg,and the mobile phase proportion was methanol/water?v/v,6:4?,its purity was 98.56%determined by HPLC area normalized method.Characterization of the modified fiber was respectively done through the ultraviolet visible absorption spectrum?UV-Vis?,Fourier transform infrared spectroscopy?FTIR?,high resolution mass spectra technique?ESI-MS?and nuclear magnetic resonance hydrogen spectrum?NMR?.The results show that the structure of synthetic product coincides with the expected structure.The established HPLC method for detecting the content of intermediate was accurate,simple and fast.It can be used for qualitative and quantitative analysis of intermediate.?3?Methanol was selected as the solvent,The processes were optimized with the crystallization yield and purity of the intermediate as index,the optimum reaction condition were determined to be 45 mL,2:1,12h,5?of dosage of solvent,methanol:water,crystallization time and crystallization temperature.The peak of the crystal diffraction peak in the X-ray diffraction pattern of the intermediate was sharp,indicating that the crystal state was good,the solubility in water was 13.8 g/L,and the pH of the aqueous solution was 7.32.?4?Antioxidant test results showed that the intermediates had DPPH·,·OH and O₂^-·scavenging activity after 3-hydroxy-4-methoxy-phenylpropenal was synthesized by the condensation of isovanillin with acetaldehyde aldol.And the reducing power was significantly higher than that of isovanillin.The results of antioxidant test show:the DPPH·radical,·OH radical,O₂^-·radical scavenging activities and reducing power of intermediate increased very significantly compared with the isovanillin.And it indicated that the intermediate and isovanillin both has strong ability to scavenge ABTS⁺·,and there is no significant difference in their scavenging ability of ABTS⁺·free radicals.