Study On Raffinose Chlorination Reaction

Sucralose is believed to represent the highest quality level and development direction of high-intensity sweetener at present. Among the traditional synthetic methods from sucrose, omni-group protection method is too complex with multiple steps; mono-group protection method has a lower yield even under more stringent chlorination conditions. This thesis proposed an innovative synthetic process, raffinose method, including chlorination reaction, process optimization, separation, preparation, characterization and quantitative analysis of the chlorinated products. The product mixture was separated into trichloro raffinose, tetrachloro raffinoses 1,2 and 3. Then, the molecular structures were characterized and quantitative analytic methods were established.In this thesis, we obtained standard substances which are not commercially available, and laid a solid foundation for chlorination process optimization.(1) The raw material in this process is raffinose. We used two kinds of chlorinating reagents, thionyl chloride and triphosgene, to form Vilsmeier reagent. The chlorinated products were completely separated by HPLC with a refractive index detector or evaporative light-scattering detector. With thionyl chloride as the chlorinating reagent, the yield of trichloro raffinose, tetrachloro raffinoses 1,2 and 3 was 12.38%,2.43%,4.41% and 4.48%, respectively. Under the same condition with triphosgene as the chlorinating reagent, the yield of trichloro raffinose, tetrachloro raffinoses 1,2 and 3 was similar, as 10.31%,1.93%,5.04% and 4.92%. In this thesis, we used prep-HPLC to separate and prepare chlorinated products, which could be used as the standard substances because of the high purity,99%. Through infrared spectrum, mass spectrum and 2-dimension nuclear magnetic resonance, the molecular structure of the chlorinated products were characterized.(2) This thesis also established quantitative analytic method for trichloro raffinose, tetrachloro raffinoses 1,2 and 3. The quantitative analytic method was validated with regarding to the specificity, linearity, LOD, LOQ, precision and accuracy. The regression equation of trichloro raffinose was y=44753.96 x; tetrachloro raffinose 1 was y=38155.85 x; tetrachloro raffinose 2 was y=46205.48 x, and tetrachloro raffinose 3 was y=43223.10 x. Since r value is more than 0.999, the linearity was proven to be good. The precision and accuracy were also proven to be good because the RSD of them is less than 3%.(3) In the end, the chlorination process was optimized with regarding to reaction temperature, water removal, feed ratio, stirring speed, thionyl chloride:DMF(n/n), ethyl acetate: DMF (n/n), and heating rate. The optimized condition of trichloro raffinose was water removed, temperature at 115℃, raffinose:thionyl chloride(n/n)=1:13, reaction for 3 h, stirring at 600 r/min, ethyl acetate:DMF(n/n)=0, thionyl chloride:DMF(n/n)=1:4. The optimized condition of tetrachloro raffinose 1 was water removed, temperature at 125℃, raffinose:thionyl chloride(n/n)=1:11,reaction for 4 h, speed at 600 r/min, ethyl acetate:DMF(n/n)=0, thionyl chloride:DMF(n/n)=1:4. The optimized condition of tetrachloro raffinoses 2 and 3 was water removed, temperature at 120℃, raffinose:thionyl chloride(n/n)=1:11, reaction for 5 h, speed at 600 r/min, ethyl acetate:DMF(n/n)=1:4, thionyl chloride:DMF (n/n)=1:5.Under the optimized conditions, the average yield of trichloro raffinose (3 batches) is 13.49%. So, the optimized conditions were successfully proven to be reliable.