Pictet-Hubert Reaction

The Pictet-Hubert reaction describes the construction of the phenanthridine nucleus (2) by dehydration of acyl-o-xenylamines (1). The application of zinc chloride at high temperature facilitates the dehydration/ This reaction is also referred as the Morgan-Walls Reaction. 

There have also been reports of adding zinc chloride or tin chloride to the Morgan-Walls conditions to catalyze the reaction (see experimental section).  

A heteroatom (in ring A) will control the electron density at the position of ring closure by its inductive and resonance effects. If the substituent increases the electron density of the ring, then ring closure will be facilitated by the heteroatom. If the heteroatom decreases electron density, then the ring closure will be hindered. 

The acyl residue controls the formation and stability of the carbonium ion. If the carbonium ion is destabilized (by electron withdrawing groups), then cyclization to the phenanthridine nucleus will be sluggish. The slower the rate of cyclization, the greater the chance of side reactions with the cyclization reagent. Therefore, the yield of the phenanthridine will depend on the relative rates of cyclization and side reactions, which is controlled by the stability of the carbonium ion. 

The synthetic utility of the Pictet-Hubert reaction is limited. This is due to the requirement of having a substituent in the para position of the A ring (10) or no substituent on the A ring. Substituents present in the meta position of the A ring (12) 

The Pictet-Hubert reaction is a variant of the Morgan-Walls reaction where the phenanthridine cychzation was accomphshed by dehydrative ring closure of acyl-o-aminobiphenyls on heating with zinc chloride at 250-300 °C. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 181, Springer International Publishing Switzerland 2014 

Holsworth, D. D. Pictet-Hubert Reaction. In Name Reactions in Heterocyclic Chemistry, Li, J. J., Ed. Wiley Hoboken, NJ, 2005,465-468. (Review). 

Sivasubramanian, S. Muthusubramanian, S. Ramasamy, S. Arumugam, N. Indian J. Chem., Sect. B 1981,20B, 552. 

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The Pictet-Hubert reaction has found utility in the production of phenanthridine molecules that act as DNA-intercalator antitumor and antiviral agents (17). 

Pictet-Hubert Reaction / Morgan-Walls Reaction... 

Homer-Wadsworth-Emmons Reaction Hosomi-Sakurai Reaction Houben-Fischer Synthesis Houben-Hoesch Reaction Houdry Cracking Process Huang-Minlon Modification Hubert (see Pictet-Hubert Reaction)... 

Cf. Bradsher Reaction Pechmann Condensation Pictet-Gams Isoquinoline Synthesis Pictet-Hubert Reaction Skraup Reaction. 

Morgan-Walls reaction (Pictet-Hubert reaction)... 

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