化学合成；材料科学。3-溴咔唑是芳基烃类受体激动剂，是环境测试和研究的标准，可用于生物活性研究、单链到四卤代咔唑的表征；作为医药中间体，亦是合成光电材料的重要中间体。
化学合成；材料科学；医药中间体；光电材料合成；芳基烃受体激动剂（环境测试和生物活性研究）
合成路线 1（N-溴代琥珀酰亚胺溴代法）
- 步骤：在室温（约25℃）下搅拌咔唑、NBS和THF，反应完成后得到中间体F，产率95％。
- 条件：With N-Bromosuccinimide In tetrahydrofuran at 25℃
- 收率：95%
- 参考文献：[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, #1, p. 363-366；[2] Organic and Biomolecular Chemistry, 2016, vol. 14, #39, p. 9406-9415；[3] Journal of Materials Chemistry C, 2016, vol. 4, #24, p. 5795-5805；[4] Patent: US8558007, 2013, B2；[5] Patent: CN104650153, 2017, B；[6] Journal of the Brazilian Chemical Society, 2010, vol. 21, #3, p. 496-501；[7] Journal of Materials Chemistry C, 2016, vol. 4, #38, p. 8973-8979；[8] Patent: CN105601621, 2016, A；[9] RSC Advances, 2016, vol. 6, #116, p. 115298-115302；[10] Journal of Chemical Research, 2014, vol. 38, #10, p. 593-596；[11] Journal of Polymer Science, Part A: Polymer Chemistry, 2010, vol. 48, #7, p. 1607-1616；[12] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, #19, p. 4304-4307；[13] Journal of Molecular Structure, 2014, vol. 1058, #1, p. 14-21；[14] Dyes and Pigments, 2016, vol. 124, p. 268-276；[15] Journal of the American Chemical Society, 2013, vol. 135, #12, p. 4805-4814；[16] MedChemComm, 2017, vol. 8, #1, p. 202-210；[17] Chemical Communications, 2010, vol. 46, #12, p. 2091-2093；[18] European Journal of Inorganic Chemistry, 2018, vol. 2018, #3, p. 531-543；[19] RSC Advances, 2013, vol. 3, #30, p. 12091-12095；[20] Patent: WO2016/112027, 2016, A1；[21] Patent: WO2006/82245, 2006, A1；[22] Organic Letters, 2002, vol. 4, #14, p. 2321-2323；[23] Chemistry of Materials, 2015, vol. 27, #19, p. 6535-6542；[24] Patent: US2017/352818, 2017, A1；[25] Patent: EP1972619, 2008, A1；[26] Patent: CN105566199, 2016, A；[27] Journal of Fluorescence, 2011, vol. 21, #2, p. 497-506；[28] Patent: WO2010/43693, 2010, A1；[29] Patent: WO2013/162284, 2013, A1；[30] Patent: WO2014/3440, 2014, A1；[31] Chemical Communications, 2017, vol. 53, #97, p. 13039-13042；[32] Patent: WO2016/8010, 2016, A1；[33] Patent: WO2011/137072, 2011, A1；[34] Patent: CN106046054, 2016, A；[35] Advanced Synthesis and Catalysis, 2002, vol. 344, #2, p. 192-199；[36] Synthesis, 2005, #10, p. 1619-1624；[37] Z. Ang., 1901, vol. 14, p. 784；[38] Helvetica Chimica Acta, 1946, vol. 29, p. 573,580；[39] European Journal of Pharmacology, Molecular Pharmacology Section, 1995, vol. 288, #3, p. 285-294；[40] Organic and Biomolecular Chemistry, 2011, vol. 9, #20, p. 6913-6916；[41] Journal of Materials Chemistry, 2011, vol. 21, #14, p. 5422-5429；[42] Journal of Materials Chemistry, 2011, vol. 21, #21, p. 7811-7819；[43] Chemistry - A European Journal, 2012, vol. 18, #48, p. 15512-15522；[44] Dyes and Pigments, 2013, vol. 99, #1, p. 41-51；[45] Arkivoc, 2014, vol. 2014, #5, p. 123-131；[46] Dyes and Pigments, 2017, vol. 141, p. 148-160；[47] Dyes and Pigments, 2015, vol. 114, #C, p. 239-252；[48] Patent: CN103159745, 2016, B；[49] Patent: KR2016/51210, 2016, A；[50] Physical Chemistry Chemical Physics, 2016, vol. 18, #43, p. 30105-30116；[51] ChemCatChem, 2018, vol. 10, #18, p. 3960-3963
合成路线 2（三苯基膦参与的邻二氯苯回流法）
- 步骤：在氮气氛下，将中间体F溶于邻二氯苯中，加入三苯基膦并回流；反应完成后，加入MC和H₂O，萃取MC层，浓缩并用柱色谱分离，用Hex：EA = 5：1，无水MgSO₄干燥，得到中间体G，产率79％。
- 条件：With triphenylphosphine In 1,2-dichloro-benzene Inert atmosphere; Reflux
- 收率：79%
- 参考文献：[1] Patent: KR2015/102733, 2015, A；[2] Patent: KR2015/102734, 2015, A；[3] Patent: KR2015/112880, 2015, A；[4] Patent: US2017/125677, 2017, A1；[5] Patent: US2017/125678, 2017, A1；[6] Patent: KR101565039, 2015, B1；[7] Patent: KR2015/98062, 2015, A；[8] Patent: KR101535606, 2015, B1
合成路线 3（CuCl₂·2H₂O催化的DMSO法）
- 步骤：将起始化合物和CuCl₂·2H₂O在DMSO中混合，100℃搅拌7小时；通过薄层色谱监测反应进程（PMA用于染色溶液）；反应混合物倒入冰冷的水中，柱色谱纯化（乙酸乙酯和石油醚为洗脱剂），得到咔唑。
- 条件：With copper(II) choride dihydrate In dimethyl sulfoxide at 100℃; for 7 h
- 收率：91%
- 参考文献：[1] Tetrahedron Letters, 2018, vol. 59, #22, p. 2145-2149；[2] Organic and Biomolecular Chemistry, 2014, vol. 12, #27, p. 4832-4836；[3] Journal of the Chemical Society, 1945, p. 530,532
通用合成步骤（N,N-二甲基甲酰胺溴代法）
- 步骤：向DMF中加入咔唑，室温搅拌15分钟；0℃下缓慢滴加NBS的DMF溶液；滴加完毕后，升温至室温继续搅拌2小时；反应完成后倒入水中，析出白色沉淀，过滤收集沉淀，溶解于二氯甲烷，水洗有机层，无水硫酸钠干燥，减压浓缩，乙醇重结晶，得到3-溴咔唑，收率72%。
- 条件：With N-Bromosuccinimide In N,N-dimethylformamide at 0℃ to room temperature
- 收率：72%
- 参考文献：[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, #1, p. 363-366；[2] Organic and Biomolecular Chemistry, 2016, vol. 14, #39, p. 9406-9415；[3] Journal of Materials Chemistry C, 2016, vol. 4, #24, p. 5795-5805
