碳酸钾80℃将卤代芳烃转化为酚？

经典的Lossen重排反应，碱处理 O-酰基羟肟酸重排得到异氰酸酯的反应。

2016年，Merck公司的Patrick S. Fier和evin M. Maloney利用Lossen重排反应，将缺电子的卤代芳烃或卤代杂芳烃在相对温和条件下转化为相应的酚。利用乙酰氧肟酸通过SNAr进攻活性芳卤代烃，接着通过非经典的Lossen重排得到酚。所用试剂经济易得在空气中稳定，反应无需特殊操作，在相对较弱的碱性体系下进行反应。【Org. Lett. 2016, 18, 9, 2244–2247】

反应机理

应用范围

反应条件温和，酯基不受影响，羧基α位不会发生消旋。

反应操作

Procedure for the conversion of aryl halides to phenols 

To a screw-cap vial or round bottom flask is added acetohydroxamic acid (3.0 equiv), powdered K2CO3 (5.0 equiv), aryl halide substrate (1.0 equiv), and DMSO such that the substrate concentration was 0.3- 0.6 M. In cases where the substrate is an oil, it is added by syringe or pipette after the DMSO is added. The vessel is sealed and heated at 80 o C for 2-18 h, and monitored for conversion by HPLC or TLC. At the end of the reaction, the mixture is cooled to rt and carefully quenched with approximately 9 equiv. of 2M HCl to a final pH of approximately 3-6. The aqueous phase is extracted 2 times with EtOAc and the product is purified by silica gel chromatography. In some cases, the product precipitates directly during the addition of HCl. In these cases, the solid is filtered and washed 3 times with water and dried under vacuum.

这是一种相对温和的将缺电子卤代芳烃转化为相应的酚的方法，在此反应条件下，酯基，酮，腈，磺酸酯等基团都不受影响，非常实用。

参考资料

Org. Lett. 2016, 18, 9, 2244–2247；https://doi.org/10.1021/acs.orglett.6b00876