4-(2-氯苯基)-6-甲基-2-硫代-1,2,3,4-四氢嘧啶-5-羧酸乙酯作为一种含硫杂环化合物，在医药和农药领域具有潜在应用价值，可作为相关药物或农药的中间体或活性成分。
医药; 农药
合成路线 1（1. 合成：301359-45-5）
产率：86%
合成条件：With nanometasilica disulfuric acid In neat (no solvent) at 80℃; for 0.25 h; Green chemistry
实验步骤：一般步骤：将纳米二氧化硅二硫酸（NMSDSA）（10mol％; 0.024g）或纳米二氧化硅一硫酸钠盐（NMSMSA）（10mol％; 0.018g）作为绿色温和催化剂加入到芳香醛（1mmol）的混合物中 在圆底烧瓶中加入乙酰乙酸乙酯（1mmol; 0.132g）和尿素（1.5mmol; 0.090）或硫脲（1.5mmol; 0.114），然后在80℃下首先在无溶剂的无磁条件下搅拌随后的混合物。 反应完成后，通过TLC正己烷/乙酸乙酯（5：2）检查，将乙酸乙酯（10mL）加入到反应混合物中，搅拌并回流5分钟，然后用水（10mL）洗涤。 倾析以从反应混合物中分离催化剂（反应混合物可溶于热乙酸乙酯，NMSDSA或NMSMSA催化剂可溶于水）。 蒸发有机层溶剂，通过乙醇/水（10：1）重结晶纯化粗产物。
参考文献：
- [1] Synthetic Communications, 2013, vol. 43, # 11, p. 1477 - 1483 [2] Chinese Journal of Chemistry, 2011, vol. 29, # 9, p. 1863 - 1868 [3] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2007, vol. 46, # 12, p. 2045 - 2048 [4] Synthetic Communications, 2009, vol. 39, # 5, p. 880 - 886 [5] Tetrahedron Letters, 2009, vol. 50, # 24, p. 2889 - 2892 [6] New Journal of Chemistry, 2016, vol. 40, # 12, p. 10412 - 10417 [7] Journal of Chemical Research - Part S, 2003, # 9, p. 601 - 602 [8] Chinese Chemical Letters, 2011, vol. 22, # 3, p. 318 - 321 [9] Catalysis Letters, 2012, vol. 142, # 12, p. 1505 - 1511 [10] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 5, p. 879 - 883 [11] Journal of the Iranian Chemical Society, 2017, vol. 14, # 1, p. 121 - 134 [12] Tetrahedron, 2015, vol. 71, # 29, p. 4830 - 4834 [13] Research on Chemical Intermediates, 2017, vol. 43, # 5, p. 3325 - 3347 [14] Research on Chemical Intermediates, 2018, vol. 44, # 7, p. 4083 - 4101 [15] Journal of Molecular Catalysis A: Chemical, 2013, vol. 370, p. 197 - 204 [16] Catalysis Communications, 2013, vol. 42, p. 104 - 108 [17] New Journal of Chemistry, 2017, vol. 41, # 14, p. 6893 - 6901 [18] Bulletin of the Korean Chemical Society, 2010, vol. 31, # 6, p. 1715 - 1718 [19] Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 2011, vol. 41, # 9, p. 1135 - 1140 [20] Applied Organometallic Chemistry, 2017, vol. 31, # 4, [21] Synthetic Communications, 2006, vol. 36, # 4, p. 451 - 456 [22] Chemical Papers, 2011, vol. 65, # 6, p. 829 - 834 [23] Bioorganic Chemistry, 2016, vol. 68, p. 265 - 274 [24] Synthetic Communications, 2006, vol. 36, # 1, p. 129 - 136 [25] Phosphorus, Sulfur and Silicon and the Related Elements, 2014, vol. 189, # 6, p. 791 - 795 [26] Tetrahedron Letters, 2007, vol. 48, # 33, p. 5777 - 5780 [27] Croatica Chemica Acta, 2017, vol. 90, # 1, [28] Catalysis Science and Technology, 2014, vol. 4, # 1, p. 71 - 80 [29] Indian Journal of Heterocyclic Chemistry, 2010, vol. 19, # 3, p. 273 - 276 [30] Tetrahedron Letters, 2013, vol. 54, # 14, p. 1862 - 1865 [31] Chemical Communications, 2014, vol. 50, # 88, p. 13555 - 13558 [32] Chinese Chemical Letters, 2017, vol. 28, # 5, p. 1074 - 1078 [33] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 140 - 151 [34] Letters in Organic Chemistry, 2018, vol. 15, # 4, p. 241 - 245
合成路线 2（2. 合成：301359-45-5）
产率：90%
合成条件：at 110℃; for 1 h;
实验步骤：通用方法：将醛（4mmol），β-酮酯（4mmol）和硫氰酸铵（4.8mmol）的混合物在110℃下加热。 通过薄层色谱监测反应。 反应完成后，将混合物冷却至室温并用水（5mL）淬灭; 将固体沉淀物在真空泵中过滤，用水（3×5mL）洗涤，在真空下干燥并从甲醇和丙酮（8：2）中重结晶，得到纯产物。
参考文献：
- [1] Tetrahedron Letters, 2017, vol. 58, # 18, p. 1778 - 1780
