叶酸合成工艺优化

Optimization of folic acid synthesis process

摘要:

叶酸合成工艺中反应物2,4,5-三氨基-6-羟基嘧啶硫酸盐水溶性差是导致反应过程中用水量大、副反应多等问题的主要原因。将2,4,5-三氨基-6-羟基嘧啶硫酸盐与等量的碳酸钾反应进行预处理后，再用于叶酸的合成工艺中，可有效改善其水溶性，并进一步对碱的种类、反应温度、反应时间、反应物用量、相转移催化剂、酸的种类以及碱精制溶液pH等条件进行考察。结果表明，当n(N-对氨基苯甲酰-L-谷氨酸) : n(2,4,5-三氨基-6-羟基嘧啶硫酸盐) : n(碳酸钾) : n(三氯丙酮) =1.0 : 1.2 : 1.2 : 2.6，且在四丁基溴化铵的作用下，反应温度为40 ℃，在pH为2.5-2.8下反应3 h，随后在pH为3.2-3.5下反应3 h可得到收率为82.22%，纯度为72.81%的叶酸粗品。用盐酸对其进行酸精制，再在pH为8.5的条件下进行碱精制，最终得到收率为66.35%，纯度为97.69%的叶酸产品。相较于原工艺收率提升了5.59%，用水量减少了33%。且合成工艺母液可循环利用两次，减少了原料的用量及水的消耗，具有潜在的实际应用价值。

Abstract:

The poor water solubility of the reactant 2,4,5-triamino-6-hydroxypyrimidine sulfate in the folic acid synthesis process is the main reason for the large water consumption and many side reactions during the reaction.The reaction of 2,4,5-triamino-6-hydroxypyrimidine sulfate with the same amount of potassium carbonate was pretreated and then used in the synthesis process of folic acid, which could effectively improve its water solubility.And further investigate the conditions such as the type of alkali, the reaction temperature, the reaction time, the proportion of reactants, the phase transfer catalyst, the type of acid, and the pH of the alkali refining solution.The results show that when n(N-p-aminobenzoyl-L-glutamic acid):n(2,4,5-Triamino-6-hydroxypyrimidine sulfate):n(potassium carbonate):n(trichloroacetone) =1.0:1.2:1.2:2.6.Under the action of tetrabutylammonium bromide, the reaction temperature is 40 ℃, the reaction time is 2.5-2.8 for 3 h, and then the reaction time is 3 h at pH 3.2-3.5. The yield of folic acid is 82.22%, and the purity is 72.81%.After acid purification with hydrochloric acid and alkali purification at pH 8.5, folic acid product with yield of 66.35% and purity of 97.69% was finally obtained. Compared with the original process, the yield increased by 5.59%, and the water consumption decreased by 33%.Moreover, the mother liquor of the synthesis process can be recycled twice, which reduces the amount of raw materials and water consumption, and has potential practical application value.