本章我们将对硫脲的合成方法做个简短的小结，在总结之前先介绍一下单伯硫脲的合成。

单伯硫脲的合成

除了上述合成硫脲的方法以外，还有些特殊的方法合成伯硫脲，这其中最常用的方法是硫氰酸钾与胺直接反应，当这种方法无法获得相应得伯硫脲或不能得到满意的收率时，我们也会采用苯异氰酸酯的方法合成伯硫脲。

实例一：硫氰酸盐和胺反应生成硫脲

To a magnetically stirred solution of p-toluidine hydrochloride (10.0 g, 69.6 mmol) in THF (150 mL) was added KSCN (10.1 g, 104 mmol). The mixture was heated at reflux for 24 h at which point TLC analysis (1/1, EtOAc/hexane) indicated the complete consumption of the starting material. The mixture was diluted with H2O (100 mL) and extracted with EtOAc (2×100 mL). The interfacial solids and EtOAc extracts were combined and washed with 1 N HCl (100 mL) and brine (50 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford title product as a yellow solid (8.6 g, 74% yield). [1]

实例二：通过苯异硫氰酸酯合成伯硫脲

To a solution of 2-aminobiphenyl (5 g, 29.55 mmol) in acetone (100 mL) was added benzoylisothiocyanate (5.30 g, 32.50 mmol) and the resulting reaction mixture was stirred at room temperature for 30 min. The solvent was evaporated and the residue was repeatedly washed with hexane to obtain N-([1,1'-biphenyl]-2-ylcarbamothioyl)benzamide(9.67 g, 98% yield). To a solution of intermediate(9.60 g, 28.91 mmol) in THF (125 mL) was added a solution of NaOH (5.80 g, 145mmol) in H2O (50 mL). The resulting reaction mixture was heated to 85 ºC for 16 h. THF was evaporated, water was added and the mixture extracted with EtOAc (3 × 250 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to obtain 1-([1,1'-biphenyl]-2-yl)thiourea (5.30 g, 80% yield). [2]

实例三：通过硫氰酸铵合成伯硫脲

NH4SCN(3.8 g, 50 mmol) was added to a stirred solution of m-toluidine (5.35 g, 50mmol) in 1M HCl (50 mL) at 100 oC and the solution stirred at 100 oC for 16 h. The solution was diluted with water (60 mL) and stood at 5 oC for 2 h. The precipitate was filtered, washed with water (5 mL),washed with ether (5 mL), and dried. The precipitate was purified by column chromatography, eluting with an appropriate blend (30-100%) of EtOAc/petroleumether, to give the thiourea (7.1 g, 86%yield). [3]

【参考文献】

[1] R. Jason Herr etcSynthesis, 2000,1569

[2] David J. Haydon etc Journal of Medicinal Chemistry, 2010, 53(10),3927-3936