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摘要：氨基噻唑化合物是重要的N-杂环化合物，近年来被广泛应用于药物研发等多个领域，特别是在作为抗癌药物中间体方面有着突出的贡献。因此氨基噻唑类化合物的合成受到了越来越多的关注。本文研究的是以氯乙腈为原料，通过四步反应，得到我们所需要的产物4-三氟乙酰基-氨基噻唑。第一步，是以氯乙腈和硫氰化钾为原料，以甲醇为溶剂，通过控制两种原料配比和反应温度，确定了硫氰化钾与氯乙腈的配比为1.25:1，温度为45℃，得到硫氰基乙腈；第二步，得到的硫氰基乙腈在0℃温度条件下，通入干燥的溴化氢气体，使硫氰基乙腈发生环化；第三步，环化产物与三氟乙酸酐发生反应得到2-溴-4-三氟乙酰基-氨基噻唑，4位上不稳定的氨基被保护；第四步，在Pd/C催化条件下通入氢气，控制反应体系的压力和温度，确定最优反应条件为常压下80℃，脱去环上的溴原子，得到最终产物4-三氟乙酰基-氨基噻唑。19507
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关键词：抗癌药物；氨基噻唑；合成
The synthesis of 4 - trifluoroacetyl - aminothiazole
Abstract: Aminothiazoles, as important N-heterocyclic compounds, have been used in drug discovery, especially in as an anticancer drug intermediates. The synthesis of aminothiazoles has attracted more and more attention. This paper is based on chloroacetonitrile as a raw material, through a four-step reaction, we need to give the product of 4-trifluoroacetyl-aminthiazole. In the first step, it was started with chloroacetonitrile and potassium thiocyanate as a raw, using methanol as a solvent, by controlling the ratio of the two materials and the reaction temperature to determine the chloroacetonitrile and potassium thiocyanate ratio of 1.25:1, the temperature is 45℃, getting thiocyanate acetonitrile ; In the second step, the product in the first step at 0℃, through a dry hydrogen bromide gas, making the cyanomethyl thiocyanate cyclization; In the third step, the cyclization product is reacted with trifluoroacetic anhydride to give 2-bromo-4-trifluoroacetyl-aminothiazole, the unstable amino on the 4 position was protected; In the fourth step, under the Pd/C catalytic conditions, controlling the pressure and reaction temperature, we determine the optimal reaction conditions for the atmospheric pressure and 80℃, removal of a bromide atom on the ring to give the final product 4-trifluroacetyl-aminothiazole.
Key words: Anti-cancer drugs; Aminothiazole; synthesis
目录
1 绪论 1
1.1 本课题研究背景概述 1
1.2 课题研究意义与目的 5
2 由氯乙腈合成4-三氟乙酰基-氨基噻唑 7
2.1 合成路线设计思路 7
2.1.1 拟采用的总合成路线 7
2.1.2 拟定的合成步骤 8
2.2 使用的材料试剂、仪器设备 9
2.2.1 主要化学原料与试剂 9
2.2.2 仪器设备 9
2.3 硫氰基乙腈的制备 10
2.3.1 反应方程式 10
2.3.2 实验步骤 11
2.3.3 实验注意事项 11
2.4 硫氰基乙腈的环化与提纯 11
2.4.1 反应方程式 11
2.4.2 实验步骤 11
2.4.3 实验注意事项 11
2.5 2-溴-4-三氟乙酰基-氨基噻唑的制备 12
2.5.1 反应方程式 12
2.5.2 实验步骤 12
2.5.3 实验注意事项 12
2.6 4-三氟乙酰基-氨基噻唑的制备 12
2.6.1 反应方程式 12
2.6.2 实验步骤 12
2.6.3 实验注意事项 13
2.6.4 谱图数据 13