胸腺嘧啶的合成工艺

以甲酸乙酯和丙酸乙酯为原料,在金属钠存在下缩合得到胸腺嘧啶中间体α-甲酰基丙酸乙酯;α-甲酰基丙酸乙酯在酸催化下与尿素缩合,最后在甲醇钠作用下环合得到胸腺嘧啶。合成α-甲酰基丙酸乙酯的正交实验结果表明,最佳反应溶剂为异丙醚,金属钠、甲酸乙酯和丙酸乙酯的质量比是1:1.5:2.0;在该优化条件下,α-甲酰基丙酸乙酯的收率达到41.8%。合成胸腺嘧啶的正交实验结果表明,随反应温度的升高,胸腺嘧啶的收率逐渐增大,表明反应温度越高越好,最好在溶液回流温度(68℃)下进行反应;在反应温度为64℃、α-甲酰基丙酸乙酯、尿素和甲醇钠的摩尔比为1:4.7:1.4的条件下,胸腺嘧啶的收率达到78.8%。

Synthesis of Thymine

Ethyl α formylpropionate(EFP), an important intermediate for synthesis of thymine was first prepared by condensation from ethyl formate and ethyl propionate in presence of metal sodium and in N_2 atmosphere. From the obtained EFP, the end product thymine was prepared by acid catalyzed condensation with urea, followed by cyclization with sodium methylate. Orthogonal experimental results of EFP synthesis showed that using isopropyl ether as solvent was most preferable. When the mass ratio of metal sodium, ethyl formate and ethyl propionate was 1:1.5:2.0,the reaction gave the best yield of EFP 41.8%. Orthogonal experimental results of thymine synthesis showed that the yield increased with rise of reaction temperature. High reaction temperature was preferable for high yield. Refluxing of system mixture was also helpful. The optimal conditions for thymine synthesis were: reaction temperature 64 ℃, mole ratio of EFP, urea and sodium methylate 1:4.7:1.4,refluxing temperature 68 ℃, the yield of thymine was up to 78.8%.