| The synthetic and purification process of d-a-tocopherol nicotinate was studied. The synthetic process was a "one pot" process consisted of p-toluene sulfonyl chloride, nicotinic acid, and d-a-tocopherol as raw material, pyridine as catalyst and toluene as solvent. The side reaction was also studied. A method was proposed to determine the d-a-tocopherol nicotinate and d-a-tocopherol toluene-p-sulfonate.The main work was to optimize the synthetic process of d-a-tocopherol nicotinate by Uniform Design, which was followed by washing with alkli and water, drying and filtrating. Then, the crude product was purified by silica gel column chromatography.Uniform Design is a method to optimize the reaction conditions. The main discoveries were that two reaction conditions could be considered in one Uniform Design table. The optimum reaction conditions were as follows: the temperature of the first reaction was 50℃ and the time was 83 min, n (nicotinic acid)/n (d-a-tocopherol) was 2.87 (mol/mol),n (nicotinic acid)/n (p-toluene sulfonyl chloride) was 1.05 (mol/mol), n (pyridine)/n (p-toluene sulfonyl chloride) was 3.16 (mol/mol), the total volume of pyridine/d-a-tocopherol was 2.5 (ml/g), the volume of the toluene / d-a-tocopherol was 3.5 (ml/g), the temperature of the second reaction was 98℃and the time was 138 min. The reaction yield of d-a-tocopherol nicotinate was more than 95%. The total yield was more than 90%. The purity of crude d-a-tocopherol nicotinate was more than 80%.The optimum conditions of silica gel column chromatography were as follows: 40 g silica gel (80-120 mesh), filled in a 20 mm (i.d.) X 285 mm column, with V(hexane):V(ethyl acetate)=5:l as the mobile phase, the flow rate 2 ml/min, room temperature, the load of sample 8 g, the concentration in the mobile phase 0.6 g/ml. The purity of the final product was more than 95%. The byproduct d-a-tocopherol toluene-p-sulfonate,nonreacted d-a-tocopherol, and other impurities could all be removed from the crude product.
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