Pictet-Hubert reaction

What is Pictet-Hubert reaction?

The Pictet-Hubert reaction is a chemical process, discovered in 1896, for creating phenanthridine by cyclizing and dehydrating N-acyl ortho-aminobiphenyls through heating with zinc chloride (ZnCl2) at temperatures ranging from 250-300 ºC. If phosphorus oxychloride POClis used instead and the reaction is conducted in boiling nitrobenzene, it is referred to as the Morgan-Walls reaction or Morgan-Walls cyclization.

Morgan-Walls cyclization - general reaction scheme - ZnCl2 Pictet-Hubert reaction - POCl3 Morgan-Walls reaction
Morgan-Walls cyclization (ZnCl2 Pictet-Hubert reaction or POCl3 Morgan-Walls reaction)

R = H, alkyl, aryl (see list of acronyms)

However, due to the low yield and lengthy reaction time associated with the original protocol, the Morgan-Walls condition using POCl3 as a dehydrating agent is more commonly used to prepare phenanthridine. This condition is also referred to as the Morgan-Walls cyclization. Although this condition was not successful in transforming ortho-formamidobiphenyl to the parent phenanthridine scaffold, it is still used.

To achieve optimal results, high-boiling solvents like nitrobenzene should be used. Additionally, the use of HBF4 as a catalyst has been shown to facilitate this cyclization.