Wohl–Ziegler反应 ， NBS(N-溴丁二酰亚胺）在自由基引发条件下对烯烃的烯丙位或芳烃的苄位进行取代得到烯丙基溴或苄溴的反应。常见的自由基引发条件有：自由基引发剂（如AIBN, BPO)，加热或光照。四氯化碳是最常用的溶剂。但是实际投反应时，常常发现生成二溴代甚至多溴代副产物，由于这些副产物和和单溴代产物极性相似，分离难度极大。有没有一种方法将此类副产物直接转化为我们想要的单溴代产物？
其实早点2001年，中国科学院成都有机化学研究所邓金根教授团队和兰州大学涂永强教授团队就报道了利用亚磷酸二乙酯和二异丙基乙胺将多溴代苄转化为苄溴的高效制备方法【 Synthesis 2001, 2078】。只需要加入NBS2两倍到八倍当量的亚磷酸二乙酯和二异丙基乙胺在THF中室温下搅拌即可将多溴代产物转化为单溴代产物。
反应机理
此转化机理其实可以参考 Atherton-Todd反应 ， 亚磷酸二酯在温和的碱性条件下与四氯化碳的作用，把P-H键转换成P-Cl键，制备得到氯磷酸二酯的反应。
参考此机理，只是 Atherton-Todd反应 的底物四氯化碳换成了多溴代苄。
反应实例
2-(bromomethyl)-2'-phenyl-1,1'-binaphthalene (2)7,8: To a flame-dried round bottom flask was added SI-16(6.28 g, 18.2 mmol, 1.0 equiv.), NBS (16.2 g, 91 mmol, 5.0 equiv.), AIBN (299 mg, 1.82 mmol, 0.1 equiv.) and cyclohexane (400 mL). The flask was then equipped with a water-cooled condenser and the reaction mixture was refluxed overnight. The reaction was then cooled to 23 ˚C and filtered through Celite with Et2O. The resulting solution was then diluted with H2O and extracted with Et2O (3x). The organic layers were combined and washed with saturated NaHCO3 (aq) , brine, dried with Na2SO4, and concentrated in vacuo. The crude material (12.33 g) containing a mixture of mono-brominated and di-brominated products was added to a round bottom flask and dissolved in THF (40 mL). The resulting solution was cooled to 0 ˚C followed by the addition ofiPr2NEt (31.70 mL, 182 mmol, 10.0 equiv.) and diethyl phosphite (23.44 mL, 182 mmol, 10 equiv.). The reaction mixture was then warmed to 23 ˚C and stirred overnight. The reaction was then cooled to 0 ˚C and quenched with H2O, extracted with Et2O (3x), washed with brine, dried with Na2SO4, and concentrated in vacuo. The resulting reside was filtered through a silica plug using Et2O as the eluent and concentrated. The crude material was then purified via recrystallization from cyclohexane to afford the title compound as an off-white solid (6.29 g, 14.86 mmol, 82% over 2 steps).
【 Org. Lett. 2016, 18, 2883–2885】
2-bromomethyl-4-fluorobenzonitrile (3). N-bromosuccinimide (98.78 g, 0.555 mol) and 2,2'-azobisisobutyronitrile (6.08 g, 0.037 mol) was added to a solution of 4-fluoro-2-methylbenzonitrile (50 g, 0.37 mol) in dichloromethane (250 mL). The slurry was refluxed for 24 h under an atmosphere of nitrogen, filtered and washed with dichloromethane (100 mL). The filtrate was cooled to 0 °C, then diethyl phosphite (25.55 g, 0.185 mol) and diisopropylethylamine (9.56 g, 0.074 mol) was added. The solution was stirred at 0 °C for 1 h and at room temperature for another hour. Potassium carbonate solution (125 mL, 0.2 g/mL) was added, and the organic phase was separated and washed with water (50 mL × 2). Then the solution was concentrated to dryness to give the raw product of 3 as a brown oil (109.5 g), which was used in the next reaction without any purification.
【 Org. Process Res. Dev. 2017, 21, 585–589】
相关反应
Wohl–Ziegler反应
NBS(N-溴丁二酰亚胺）在自由基引发条件下对烯烃的烯丙位或芳烃的苄位进行取代得到烯丙基溴或苄溴的反应。
Atherton-Todd反应
亚磷酸二酯在温和的碱性条件下与四氯化碳的作用，把P-H键转换成P-Cl键，制备得到氯磷酸二酯的反应称为Atherton-Todd反应。 返回搜狐，查看更多
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