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General synthetic route to benz[ g ]isoquinolines (2‐azaanthracenes)
Author(s) -
Krapcho A. Paul,
Gilmor Timothy P.
Publication year - 1998
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570350328
Subject(s) - chemistry , reagent , pyridine , zinc , manganese , yield (engineering) , organic chemistry , regioselectivity , lithium (medication) , medicinal chemistry , catalysis , medicine , materials science , metallurgy , endocrinology
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.