Houben-Hoesch synthesis intramolecular

The intramolecular acylation of 2-aryloxybenzonitriles allowed the synthesis of molecules with dixanthone skeleton.363 The procedure, in fact, is an intramolecular Houben-Hoesch reaction364 to afford the intermediate bisiminium salts [Eq. (5.144)] which, after hydrolysis, gave the final diketo products. 

In the laboratory of D.W. Cameron the total synthesis of the azaanthraquinone natural product bosttycoidin was undertaken using the Minisci reaction and the intramolecular Houben-Hoesch reaction as the key steps. It is worth noting that the synthesis of specific di- and trihydroxyazaanthraquinones by the Friedel-Crafts acylation is very limited due to the lack of orientational specificity and the lack of reactivity of pyridine derivatives in acylation reactions. 

For a complete description of the synthetic utility of the Houben-Hoesch reaction as it applies to other aromatic systems, as well as some mechanistic discussions, the reader is directed to two reviews on the subject. Due to the diminished electrophilic reactivity of nitriles compared to other carboxylic acid derivatives as well as the broad number of Friedel-Crafts substrates, most Houben-Hoesch pyrrole acylation reactions are conducted intramolecularly. However, an impressive intermolecular example was delineated by Chang and co-workers in efforts directed toward the synthesis of novel 2-[5-aroylpyrrolo]alkanoic acids, for evaluation of their potential analgesic and anti-inflammatory activities. Treatment of substituted pyrrole 4 and 3-cyanopyridine (5) with acid in dry chloroform resulted in the preparation of 6 in good yield. 

The intramolecular Houben-Hoesch acylation of pyrroles has been used for the synthesis of a number of compounds with interesting properties. An intramolecular acylation was reported by the Meinwald group to synthesize the hairpencil secretion of the butterfly Lycorea ceres... 

The intramolecular attack of a nitrilium ion is a key step in the Meerwein quinazoline synthesis. A recent example of this reaction can be seen in the synthesis of 4-(A -dimethylamino)-2-arylquinazolines, as demonstrated below. Treatment of imidoyl chloride 39 with NJ -dimethylcyanamide (40) followed by TiCU results in the formation of intermediate 41. Mechanistically, after the production of the likely intermediate nitrilium ion 41, the Houben-Hoesch reaction occurs to give quinazoline 42. A related procedure has been utilized for the synthesis of... 

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