Anomalous substituent effects in the Bischler-Napieralski reaction of 2-aryl aromatic formamides

Treatment of some 1-naphthylformamides (or formanilides) possessing a 2,4,5 -trioxygenated phenyl substituent at the 2-position with POCl3 caused an un precedented carbon insertion reaction into a benzene ring, producing 7-5 ri ng (azaazulene) systems as valence isomers of isoquinoline skeletons. Preci se examination of this abnormal Bischler-Napieralski reaction (BNR) using v arious substrates led to the following scope and limitations: (i) the 7-5 r ing systems were constructed when either 2-alkoxy-4,5-methylenedioxyphenyl- or 4,5-dialkoxy-2-hydroxyphenyl-substituted formamides were used as a star ting substrate; (ii) in the former case the formyl carbon was inserted into the C-1-C-6 bond of the 2-phenyl group, and normal isoquinoline cyclizatio n competed with an abnormal carbon insertion reaction; (iii) the presence o f a hydroxy group at,the 2'-position as in the latter cases caused exclusiv e carbon insertion, in which alternative C-1-C-2 insertion;;products were q uantitatively formed; (iv) 3,6-dimethoxy-2-hydroxyphenyl-substituted forman ilide electronically equivalent to 4,5-dialkoxy-2-hydroxy derivatives produ ced an indole-pyrone as an abnormal BNR product. Theoretical approaches usi ng the PM-3 method indicated that these abnormal BNRs could be triggered by ipso attack at the 1'-position yielding spiro intermediates. Ring cleavege of the six-membered ring in the spiro intermediates to a ketene function f ollowed by:recyclization was proposed for the 2'-hydroxy-directed abnormal BNRs leading to the C-1-C-2 insertion product or the indole-pyrone derivati ve.