除了上述合成硫脲的方法以外，還有些特殊的方法合成伯硫脲，這其中最常用的方法是硫氰酸鉀與胺直接反應，當這種方法無法獲得相應得伯硫脲或不能得到滿意的收率時，我們也會採用苯異氰酸酯的方法合成伯硫脲。
實例一：硫氰酸鹽和胺反應生成硫脲
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]
實例二：通過苯異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]
實例三：通過硫氰酸銨合成伯硫脲
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]
【參考文獻】
[1] R. Jason Herr etcSynthesis, 2000,1569
[2] David J. Haydon etc Journal of Medicinal Chemistry, 2010, 53(10),3927-3936
[3]Michael P. Hay etc. Journal of Medicinal Chemistry, 2010, 53(2), 787–797
相關連結：
【脲與硫脲】硫脲的合成（中）
【脲與硫脲】硫脲的合成
【脲與硫脲】脲合成方法小結
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