27063-93-0

108-47-4

27063-92-9

29976-20-3

27063-93-0

在搅拌下，将2,4-二甲基吡啶（5.39 mL，46.7 mmol，1当量）溶于含20%游离SO3的溴化物（50 mL）中，保持反应温度为0℃。安装高效回流冷凝器，将反应混合物在油浴中加热至165℃。在5小时内，以0.5 mL的份量缓慢加入溴（4.30 mL，83.4 mmol，0.9当量），并在155-175℃下继续搅拌20小时。反应完成后，将溶液冷却至室温，倒入碎冰（200 g）上，搅拌1小时。通过小心加入固体Na2CO3中和所得橙色溶液，用水稀释后，用EtOAc（2×250 mL）萃取。合并有机层，用Na2SO4干燥，真空浓缩。通过自动快速柱色谱法（Biotage KP-Sil.TM.SNAP 340g柱，0-15% EtOAc/己烷）纯化粗产物，真空干燥，得到三种溴代产物：3,5-二溴-2,4-二甲基吡啶（8）、5-溴-2,4-二甲基吡啶（9）和3-溴-2,4-二甲基吡啶（10）。 3,5-二溴-2,4-二甲基吡啶（8）为白色固体（1.48 g，12%），熔点28-30℃；1H NMR (400 MHz, CDCl3) δ 2.54 (s, 3H, CH3), 2.61 (s, 3H, CH3), 8.41 (s, 1H, pyHortho); 13C NMR (100 MHz, CDCl3) δ 23.8 (CH3), 25.7 (CH3), 120.3 (ArC), 124.4 (ArC), 146.4 (ArC), 148.5 (ArCH), 156.5 (ArC); IR νmax (film)/cm?1 3045, 2998, 2956, 2921, 1558, 1433, 1376, 1349, 1232, 1049, 993, 928, 783; HRMS (ESI+) m/z calcd for C7H8Br2N [M+H]+ 263.9018, found 263.9027. 5-溴-2,4-二甲基吡啶（9）为无色油状物（1.89 g，22%）；1H NMR (400 MHz, CDCl3) δ 2.32 (s, 3H, CH3), 2.44 (s, 3H, CH3), 7.00 (s, 1H, pyHortho), 8.47 (s, 1H, pyHmeta); 13C NMR (100 MHz, CDCl3) δ 22.1 (CH3), 23.6 (CH3), 120.4 (ArC), 125.5 (ArCH), 146.7 (ArC), 150.5 (ArCH), 157.0 (ArC); IR νmax (film)/cm?1 2985, 2957, 2924, 2854, 1592, 1461, 1377, 1353, 1289, 1177, 1032; HRMS (ESI+) m/z calcd for C7H9BrN [M+H]+ 185.9913, found 185.9918. 3-溴-2,4-二甲基吡啶（10）为无色油状物（3.04 g，35%）；1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H, CH3), 2.61 (s, 3H, CH3), 6.91 (d, J = 5.0 Hz, 1H, pyHmeta), 8.18 (d, J = 5.0 Hz, 1H, pyHortho); 13C NMR (100 MHz, CDCl3) δ 23.2 (CH3), 25.7 (CH3), 123.4 (ArCH), 124.3 (ArC), 146.7 (ArCH), 147.3 (ArC), 157.4 (ArC); IR νmax (film)/cm?1 3050, 2995, 2958, 2922, 1585, 1437, 1389, 1123, 1024, 916, 825; HRMS (ESI+) m/z calcd for C7H9BrN [M+H]+ 185.9913, found 185.9917.

参考文献：

[1] Zeitschrift fuer Chemie (Stuttgart, Germany), 1988, vol. 28, # 2, p. 59 - 60

[2] Zeitschrift fuer Chemie (Stuttgart, Germany), 1988, vol. 28, # 2, p. 59 - 60

[3] Patent: WO2010/43866, 2010, A2. Location in patent: Page/Page column 48; 87-88

[4] Organic and Biomolecular Chemistry, 2011, vol. 9, # 1, p. 127 - 135

3-溴-2,4-二甲基哌啶为杂环有机物，可用作医药中间体。