Heterocycle synthesis Bischler-Napieralski isoquinoline

An alternate approach to the fused heterocyclic compounds is the intramolecular cyclisation at an aromatic position. The Bischler-Napieralski reaction for the synthesis of the isoquinoline ring system illustrates this approach. 

The isoquinoline syntheses, which utilize intramolecular S Ar reactions for building the heterocycle, are of greater preparative importance [116]. For instance, on treatment with strong protic acids (H2SO4, polyphosphoric acid), Lewis acid or POCI3, A-(2-arylethyl)amides 46 cyclize giving 1-substituted 3,4-dihydroisoquinolines 47 Bischler-Napieralski synthesis) ... 

The Bischler-Napieralski cyclization is a classic reaction for the synthesis of heterocycles such as quinolines and isoquinolines. Thus, early efforts were devoted to the application of this transformation within this series of compounds (via activation of a carbamate or an analogue), along with known variants (using Vilsmeier-like intermediates, isocyanates, or activated ami-dines). These types of cyclization would produce the desired 6-azaindole at the correct oxidation state. To our dismay, none of these approaches provided the desired target. Instead, they resulted in either no reaction, decomposition, or unproductive reaction. 

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