General synthetic route to benz[g]isoquinolines (2-azaanthracenes)

✍ Scribed by A. Paul Krapcho; Timothy P. Gilmor

• Publisher: Journal of Heterocyclic Chemistry
• Year: 1998
• Tongue: English
• Weight: 465 KB
• Volume: 35
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570350328

✦ Synopsis

Abstract

Benzylic zinc reagents add with high regioselectivity to 1‐(phenoxycarbonyl) salts derived from pyridine‐3‐carboxaldehyde (1a) or 3‐acetylpyridine (1b) to yield 1‐(phenoxylcarbonyl)‐4‐benzyl‐1,4‐dihydropyridine‐3‐carboxaldehydes 5a, 5c or ketones 5b, 5d. Aromatizations of these dihydro analogues with sulfur led to the corresponding aldehydes 6a, 6c or ketones 6b, 6d. An alternate synthesis to the aldehydic precursors involved additions of benzylic zinc reagents to 1‐(phenoxycarbonyl) salts formed from methyl nicotinates which led to the corresponding methyl 1‐(phenoxycarbonyl)‐4‐benzyl‐1,4‐dihydronicotinates 7a, 7b. Aromatizations of 7a, 7b led to the corresponding pyridine esters 8a, 8b which on reduction with lithium aluminum hydride yielded the corresponding carbinols 9a, 9b. Oxidation of 9a, 9b by manganese dioxide afforded aldehydes 6e, 6f. Aldehydes 6a‐f were readily converted into the benz[g]isoquinolines 10a‐f on heating in polyphosphoric acid.