Correlation of the von Braun, Ritter, Bischler-Napieralski, Beckmann and Schmidt reactions via nitrilium salt intermediates

Abstract

The Bischler-Napieralski dihydroisoquinoline synthesis from N-arylethyl-amides a formerly “one-pot” process was proven to occur via the imidoyl chlorides and the corresponding nitrilium salt. This led to the recognition of using other leaving groups better than chloride (e.g. trifluoroacetate, trifluoromethanesulfonate) and electrophiles better than phosphoryl chloride-POCl 4 − being an unfavorable counterion for the nitrilium ion. Previous facts about better yields with phosphorus pentoxide than phosphorus oxychloride were interpreted in the same light. The two-step process requires much milder conditions, 20–70° vs 110–205°. The “anomaly”, that is, the failure of 1,2-diaryl-ethylbenzamides to undergo cyclization as reported in literature was now rationalized in terms of fragmentation of the nitrilium salts into stilbenes, with formation of the conjugated π-system being the driving force for this product-controlled reaction. This, in fact, was now recognized as a reversal of the Ritter reaction which itself had been used in the synthesis of isoquinolines. The intermediate carbonium ion, from the nitrilium salt can, alternatively, undergo nucleophilic attack by an ionic halogen yielding products, expected from a von Braun reaction. Thus, correlation of the formerly unrelated Ritter, von Braun, Bischler-Napieralski, Beckmann and the Schmidt reactions has been established (Scheme 18) and a few other aspects of nitrilium salt chemistry such as elaboration of a modified Vilsmeier-Haack aldehyde synthesis via nitrilium salt intermediates and an attempt to synthesize compounds with the nitrilium group in a ring are discussed.