固体超强酸SO_4~(2-)/TiO_2催化合成利巴韦林缩合物研究

以1,2,4-三氮唑-3-羧酸甲酯和1,2,3,5-四-O-乙酰基-β-D-呋喃核糖为原料,在催化剂固体超强酸SO42-/TiO2的作用下得到了1-(2,3,5-三-O-乙酰基-β-D-呋喃核糖基)-1H-1,2,4-三唑-3-羧酸甲酯,简称利巴韦林缩合物。它是广谱抗病毒药物利巴韦林的重要中间体。通过对影响反应的多种因素进行研究以及反应条件的优化,结果表明:当催化剂为固体超强酸SO42-/TiO2、催化剂用量为12%、1,2,4-三氮唑-3-羧酸甲酯和1,2,3,5-四-O-乙酰基-β-D-呋喃核糖投料摩尔比为1.05:1、反应温度控制在100℃～110℃、反应时间为2h、甲醇重结晶,所得产物收率为87.0%,纯度99.5%(HPLC)。该反应方法催化剂易制备,催化效率较高,容易循环使用,不污染环境,有一定的再生能力,易从产品中除去,操作过程简便,产品色泽好、纯度高。

Synthesis of Derivative of Ribavirin Catalyzed by Solid Superacid SO_4~(2-)/TiO_2

1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester, which is called "derivative of Ribavirin" for short, is an important intermediate of Ribavirin which is a broad-spectrum antiviral drug. In this study, the derivative of Ribavirin was synthesized with the reaction of using 1,2,4-triazole-3-carboxylic acid methyl ester and 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose as raw materials and solid superacid SO_4~(2-)/TiO_2 as catalyst. Various factors affecting the synthesis reaction were investigated, and the reaction conditions were optimized. The results show that the suitable synthesis conditions are as follows: the amount of catalyst SO_4~(2-)/TiO_2 used is 12%(mass) of the tetra-acetyl-D-ribofuranose used, the mole ratio of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose to 1,2,4-triazole-3-carboxylic acid methyl ester is 1:1.05, the reaction temperature is 100～110℃ and the reaction time is 2 h. Using the above optimized conditions, the yield of the product is 87.0% and its purity is 99.5%. The proposed synthetic route for synthesizing derivative of Ribavirin has following advantages: the preparation of the catalyst SO_4~(2-)/TiO_2 is simple, the catalyst has higher catalytic efficiency and can easily be removed from the product and be regenerated and reused cyclically, the synthesis process is environmentally benign and its operation is simple, both the color and purity of the product are good.