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New 2‐methyl‐6‐alkylamino‐5,8‐quinolinequinones and 1,2,3,4‐tetrahydro derivatives
Author(s) -
Wan YiehPing,
Porter Thomas H.,
Folkers Karl
Publication year - 1974
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.5570110414
Subject(s) - chemistry , raney nickel , crotonaldehyde , yield (engineering) , medicinal chemistry , quinoline , hydrogen peroxide , thermal decomposition , organic chemistry , catalysis , nuclear chemistry , materials science , metallurgy
The syntheses of six new 2‐methyl‐6‐alkylamino‐5,8‐quinolinequinones, three 1,2,3,4‐tetrahydro‐5,8‐quinolinequinones, and 7‐(2′,6′,10′‐trimethylundecyl)‐6‐hydroxy‐5,8‐quinolinequinone are described as potential antimetabolites of coenzyme Q and as potential antimalarial agents. The six 2‐methyl‐6‐alkylamino‐5,8‐quinolinequinones were prepared by a six‐step synthesis. 2‐Methyl‐6‐methoxy‐8‐nitroquinoline was prepared from 2‐nitro‐4‐methoxyaniline and crotonaldehyde by a Skraup reaction. Raney nickel reduction gave 2‐methyl‐6‐metboxy‐8‐aminoquinoline, which upon diazotization followed by dithionite reduction yielded 2‐methyl‐6‐methoxy‐5,8‐diaminoquinoline. Subsequent dichromate oxidation gave 2‐methyl‐6‐methoxy‐5,8‐quinolinequinone, which yielded the corresponding 2‐methyl‐6‐alkylamino‐5,8‐quinolinequinone in good yield when treated with the appropriate alkylamine. The telrahydro‐5,8‐quinolinequinones were prepared by catalytic hydrogenation of the appropriate 5,8‐quinolinequinones at elevated H 2 pressure followed by air oxidation of the reduction product. 7‐(2′,6′,10′‐Trimethylundecyl)‐6‐hydroxy‐5,8‐quinolinequinone was synthesized by radical alkylation of 6‐hydroxy‐5,8‐quinolinequinone by thermal decomposition of di‐3,7,11‐trimethyldodecanoyl peroxide, which was prepared by a multistep procedure from farnesol. Of the five new 2‐methyl‐6‐alkylamino‐5,8‐quinoline‐quinones tested against P. berghei in mice (blood schizonticidal test), only 2‐methyl‐6‐cycloheptylamino‐5,8‐quinolinequinone was active (T‐C = 6.1 at 320 mg./kg.). Both 7‐(2′,6′,10′‐trimelhytundecyl)‐6‐hydroxy‐5,8‐quinolinequinone and the tetrahydro derivatives were inactive in this same test system.