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7‐Benz[ c ] acridinemethanols as tetracyclic analogs of the 2‐phenyl‐4‐quinolinemethanol antimalarials
Author(s) -
Rosowsky Andre,
Chaykovsky Michael,
Yeager Sandra A.,
St. Amand Richard A.,
Lin May,
Modest Edward J.
Publication year - 1971
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.5570080524
Subject(s) - chemistry , morpholine , piperidine , dehydrogenation , steric effects , ring (chemistry) , stereochemistry , hydrogen bond , performic acid , medicinal chemistry , organic chemistry , molecule , catalysis
A series of new 7‐benz[ c ]acridinemethanols and 5,6‐dihydro‐7‐benz[ c ]acridinemethanols was prepared as rigid, tetracyclic analogs of the antimalarial 2‐phenyl‐4‐quinolinemethanols. Condensation of 5,7‐dichloroisatin with 6‐chloro‐, 7‐chloro‐, and 6,7‐dichloro‐1‐tetralone furnished halogenated 5,6‐dihydro‐7‐benz[ c ]acridinecarboxylic acids, which were transformed into the corresponding acid chlorides, acyl malonates, α‐bromomethyl ketones, and epoxides. Fully aromatic members of the series obtained via dehydrogenation of the 5,6‐dihydro acids were likewise converted into epoxides via the acylmalonate route. Although all the epoxides studied proved to be exceptionally resistant to ring‐opening by di‐ n ‐butylamine, probably on account of steric effects, they could be cleaved readily with piperidine or morpholine. Nmr spectra of the resulting amino alcohols suggest that these compounds exist in a single preferred conformation stabilized by internal O‐H····N hydrogen bonding, and that free rotation about the side chain C‐C bond does not occur at room temperature.