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 POCl(3) caused an unprecedented carbon insertion reaction into a benzene ring, producing 7-5 ring (azaazulene) systems as valence isomers of isoquinoline skeletons. Precise examination of this abnormal Bischler-Napieralski reaction (BNR) using various substrates led to the following scope and limitations: (i) the 7-5 ring systems were constructed when either 2-alkoxy-4, 5-methylenedioxyphenyl- or 4,5-dialkoxy-2-hydroxyphenyl-substituted formamides were used as a starting 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 cyclization competed with an abnormal carbon insertion reaction; (iii) the presence of a hydroxy group at the 2'-position as in the latter cases caused exclusive carbon insertion, in which alternative C(1)-C(2) insertion products were quantitatively formed; (iv) 3, 6-dimethoxy-2-hydroxyphenyl-substituted formanilide electronically equivalent to 4,5-dialkoxy-2-hydroxy derivatives produced an indole-pyrone as an abnormal BNR product. Theoretical approaches using 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 followed by recyclization was proposed for the 2'-hydroxy-directed abnormal BNRs leading to the C(1)-C(2) insertion product or the indole-pyrone derivative.