2-苯基-1-丁醇与2-二甲氨基-2-苯基丁腈的合成

Syntheses of 2-phenyl-1-butanol and 2-dimethylamino-2-phenylbutanenitrile

目的为马来酸曲美布汀的重要中间体2-二甲氨基-2-苯基-1-丁醇的合成奠定基础。方法苯乙腈与溴乙烷进行烃化反应得2-苯基-1-丁腈,所得产物经水解得2-苯基-1-丁酸,然后通过硼氢化钠-碘体系还原得2-苯基-1-丁醇;苯乙腈与N-溴代丁二酰亚胺进行卤代反应得溴代苯乙腈,所得产物与二甲胺进行烃化反应得2-二甲氨基苯乙腈,然后与溴乙烷进行烃化反应得2-二甲氨基-2-苯基丁腈。结果合成了2-苯基-1-丁醇和2-二甲氨基-2-苯基丁腈,总收率为分别为51%和59.4%。目标产物的结构经核磁共振氢谱、质谱确证。结论本合成方法原料易得,操作简单,收率较高,适合于工业化生产。

Objective To synthesize 2-Phenyl-1-butanol and 2-dimethylarnino-2-phenylbutanenitrile, the key intermediates for the synthesis of trimebutine. Methods 2-Phenylacetonitrile was alkylated with bromoethane to prepare 2-phenylbutanenitrile, which was hydrolyzed to give 2-phenylbutanoic acid, and then the intermediate was reduced with NaBH4-I2 system to give 2-phenyl-1-butanol. The 2-bromo-2-phenylacetonitrile was obtained by bromination of 2-phenylacetonitrile with NBS, followed by amination with dimethylamine to afford 2-dimethylamino-2-phenylacetonitrile,finally, the intermediate was alkylated with bromoethane to give 2-dimethylamino-2-phenylbutanenitrile. Results 2-Phenyl-1-butanol and 2-dimethylamino-2-phenylbutanenitrile were synthesized with total yields of 51% and 59.4% respectively,and the structures of the target compounds were identified by ^1H-NMR and ESI-MS. Conclusions Two efficient synthetic routes are developed for the syntheses of 2-phenyl-1-butanol and 2-dimethylamino-2-phenylbutanenitrile separately.