Vilsmeier ring closure with

Ring closure with Vilsmeier salts Pyrazolo[4,3-b][l,4]benzoxazines... 

Ring closure y to a heteroatom is also a rather uncommon [5 + 1] procedure although there are some important exceptions. The most widely investigated is the Bernthsen acridine synthesis in which a diarylamine is condensed with a carboxylic acid in the presence of a Lewis acid (equation 73). More recently, it has been shown that acylanilines react with the Vilsmeier-Haack reagent to give quinolines in good yield (e.g. equation 74) and the mechanism of the reaction has been elucidated. A final example of [5 +1] ring closure y to a heteroatom which is of occasional use is the pyrazine synthesis outlined in equation (75). 

The resulting enamine 25 then reacts with the Vilsmeier reagent 27, which results from DMF and phosphoryl chloride by way of intermediate 26 Elimination of hydrogen chloride leads to compound 28. Ring closure presumably occurs via intermediate 29. Rearomati/.ation with elimination of dimethylamine produces the desired quinoline 9. 

Acylation of 3-substituted indoles is more difficult, however 2-acetylation can be effected with the aid of boron trifluoride catalysis." " Indoles, with a carboxyl-containing side-chain acid at C-3, undergo intramolecular acylation forming cyclic 2-acylindoles." Intramolecular Vilsmeier processes, using tryptamine amides, have been used extensively for the synthesis of 3,4-dihydro-p-carbolines, a sub-structure found in many indole alkaloids (P-carboline is the widely used, trivial name for pyrido[3,4-fc]indole). Note that it is the imine, rather than a ketone, that is the final product the cyclic nature of the imine favours its retention rather than hydrolysis to amine plus ketone as in the standard Vilsmeier sequence " this ring closure is analogous to the Bischler-Napieralski synthesis of 3,4-dihydro-isoquinolines (9.15.1.7). 

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