化学合成;具有急性毒性(口服-大鼠LD50: 3100 毫克/公斤);对皮肤有轻度刺激,对眼睛有中度刺激;可燃,燃烧产生有毒氮氧化物烟雾;需库房通风低温干燥储存,可用干粉、泡沫、砂土、二氧化碳、雾状水灭火。
化学合成
合成路线 1(以2454-37-7为原料)
- 步骤:在10mL圆底烧瓶中,将硝基苯(0.123g,1mmol)与水(2mL)混合,加入Ni₂B(0.006g,0.05mmol)搅拌5分钟,再加入NaBH₄(0.095g,2.5mmol),室温搅拌3分钟。TLC监测反应(洗脱液:正己烷/Et₂O=5/3)。反应完成后,加入2% KOH水溶液(5mL)搅拌10分钟,用EtOAc(3×8mL)萃取,无水Na₂SO₄干燥,蒸发溶剂得产物。
- 条件:Stage #1: Ni₂B催化,水介质,0.08h;Stage #2: NaBH₄,水介质,20℃,0.07h;绿色化学工艺。
- 产率:95%(注:原文表2条目1产率为95%,与合成路线1产率94%略有差异)
- 参考文献:[1] Journal of Chemical Research, 2006, #8, p.542-544;[2] Journal of the Iranian Chemical Society, 2015, vol.12, #7, p.1221-1226;[3] Journal of the Iranian Chemical Society, 2016, vol.13, #8, p.1487-1492;[4] Journal of the Iranian Chemical Society, 2017, vol.14, #1, p.101-109;[5] Journal of the Iranian Chemical Society, 2018, vol.15, #12, p.2821-2837;[6] Oriental Journal of Chemistry, 2011, vol.27, #3, p.991-996;[7] Asian Journal of Chemistry, 2010, vol.22, #7, p.5575-5580;[8] Journal of the Iranian Chemical Society, 2017, vol.14, #12, p.2649-2657;[9] Journal of the Chemical Society of Pakistan, 2016, vol.38, #4, p.679-684;[10] Patent: US4021487, 1977, A;[11] Patent: US4021487, 1977, A;[12] Patent: US4024187, 1977, A;[13] Arzneimittel Forschung, 1958, vol.8, p.532,536;[14] Journal of Organic Chemistry, 1946, vol.11, p.405,412;[15] Patent: US4024187, 1977, A;[16] Patent: US4024187, 1977, A;[17] Organic and Biomolecular Chemistry, 2012, vol.10, #36, p.7321-7326;[18] Russian Journal of Physical Chemistry A, 2018, vol.92, #12, p.2374-2378;[19] Zh. Fiz. Khim., 2018, vol.92, #12, p.1846-1850,5
合成路线 2(以2454-37-7为原料)
- 步骤:将3-氨基苯乙酮(2.0g,14.80mmol)溶解于乙醇(25mL),0℃下加入硼氢化钠(1.4g,36.99mmol),搅拌3小时后倒入冰水中,用2N盐酸中和,氯仿萃取,有机层经盐水洗涤、无水硫酸钠干燥、减压浓缩得产物。
- 条件:Stage #1: NaBH₄,乙醇介质,0℃,3h;Stage #2: HCl,乙醇-水混合介质。
- 产率:84%
- 参考文献:[1] Dalton Transactions, 2018, vol.47, #29, p.9889-9896;[2] Patent: EP2364983, 2011, A2;[3] Patent: US2011/218193, 2011, A1;[4] Journal of Organometallic Chemistry, 2018, vol.868, p.95-101;[5] Tetrahedron Letters, 2004, vol.45, #9, p.2003-2007;[6] ChemCatChem, 2015, vol.7, #1, p.107-113;[7] Organic and Biomolecular Chemistry, 2016, vol.14, #13, p.3404-3408;[8] Tetrahedron Letters, 1987, vol.28, #40, p.4725-4728;[9] Journal of the Chemical Society, Dalton Transactions, 2001, #20, p.2989-2995;[10] Organic Letters, 2002, vol.4, #24, p.4297-4300;[11] Organic and Biomolecular Chemistry, 2011, vol.9, #16, p.5863-5870;[12] Organometallics, 2011, vol.30, #17, p.4720-4729;[13] Biocatalysis and Biotransformation, 2012, vol.30, #5-6, p.469-475;[14] Chemistry - A European Journal, 2014, vol.20, #3, p.839-845;[15] Organic and Biomolecular Chemistry, 2017, vol.15, #43, p.9169-9175