Claisen重排反应合成5-烯丙基-4-羟基异吲哚啉-2-羧酸叔丁酯

Synthesis of tert-butyl 5-allyl-4-hydroxyisoindoline-2-carboxylate by Claisen rearrangement reaction

以2,3-二甲基苯酚(2)和烯丙基溴为原料,经过醚化、溴代、关环及Claisen重排等四步反应,合成得到5-烯丙基-4-羟基异吲哚啉-2-羧酸叔丁酯(1),4步反应总收率为17.8%。中间体及产物结构经1H NMR和ESI-MS表征,产物结构进一步经过FT-IR、^(13)C NMR及X-射线单晶衍射进行确认。同时,重点考察了溴代反应及Claisen重排反应的主要影响因素。确定最佳溴代反应条件为:n(NBS)∶n(1-(烯丙氧基)-2,3-二甲基苯3)=2.2∶1,反应温度77℃,反应时间为2.5 h;确定Claisen重排反应条件为:n(BBr 3)∶n(4-(烯丙氧基)异吲哚啉-2-羧酸叔丁酯5)=2.5∶1,反应温度25℃,反应时间2 h。

Tert-butyl 5-allyl-4-hydroxyisoindoline-2-carboxylate(1)was synthesized from 2,3-dimethylphenol(2)and allyl bromide as starting materials via etherification,bromination,cyclization and Claisen rearrangement reaction in a total yield of 17.8%.The structure of the intermediates and the product was characterized by 1H NMR and ESI-MS.The structure of the product was further confirmed by FT-IR,^(13)C NMR and X-ray single crystal diffraction.At the same time,the main influencing factors of bromination reaction and Claisen rearrangement reaction were also investigated respectively.The optimum bromination reaction conditions were determined as follows:n(NBS)∶n(1-(allyloxy)-2,3-dimethylbenzene 3)=2.2∶1,reaction temperature was 77℃,reaction time was 2.5 h.And the optimum Claisen rearrangement reaction conditions were determined as follows:n(BBr_(3))∶n(tert-butyl 4-(allyloxy)isoindoline-2-carboxylate 5)=2.5∶1,reaction temperature was 25°C,reaction time was 2 h.