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The chemistry of 5 H ‐benzoxazolo[3,2‐ a ]quinolin‐5‐ones. 5 H ‐Benzoxazolo[3,2‐ a ]quinolin‐5‐ones as synthons for the preparation of novel quinoline derivatives
Author(s) -
Kim Dong Han
Publication year - 1981
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.5570180723
Subject(s) - chemistry , synthon , potassium hydroxide , alkoxy group , formylation , oxazole , medicinal chemistry , acetic anhydride , hexamethylphosphoramide , nucleophile , reagent , isopropylamine , stereochemistry , organic chemistry , catalysis , alkyl
The usefulness of 5 H ‐benzoxazolo[3,2‐ a ]quinolin‐5‐ones (I) as synthons for the preparation of otherwise difficulty obtainable quinolin‐5‐ones is demonstrated. Nucleophilic reagents cleaved the oxazole ring of I at the 7‐position, resulting in 1‐(2‐hydroxyphenyl)‐2‐substituted 4‐(1 H )quinolinones. Treatment of 5 H ‐benzoxazolo‐[3,2‐ a ]quinolin‐5‐one (Ia) with ethanoiic potassium hydroxide gave 1‐(2‐hydroxyphenyl)‐2‐ethoxy‐4‐(1 H )quinolinone (IIIa), and attempted formylation of Ia with the Vilsmeier‐Haak reagent instead gave 2‐chloro‐1‐(2‐hydroxyphenyl)‐4‐(1 H )quinolinone (II). Likewise, 10‐chloro‐5 H ‐benzoxazolo[3,2‐ a ]quinolin‐5‐ones (Ib) afforded 2‐ethoxy‐ and 2‐methoxy‐1‐(5‐chloro‐2‐hydroxyphenyl)‐4‐(1 H )quinolinone (IIIb and IIId) upon treatment with ethanol and methanol, respectively. Reaction of Ib with 1‐phenylpiperazine yielded 1‐(5‐chloro‐2‐hydroxyphenyl)‐2‐(4‐phenyl‐1‐piperazinyl)‐4‐(1 H )quinolinone (IV). Alkaline hydrolysis of IIIb gave 1‐(2‐hydroxy‐5‐chlorophenyl)‐2‐(1 H )quinolinone (V). Treatment of IIId with epichlorohvdrin gave 1‐[5‐chloro‐2‐(2‐oxiranylmethoxy)phenyl]‐2‐methoxy‐4‐(1H)quinolinone (VIa) which in turn upon treatment with isopropylamine gave 1‐[5‐chloro‐2‐[2‐hydroxy‐3‐(1‐methylethylamino)propoxy]phenyl]‐2‐methoxy‐4‐(1 H )quinolinone (VIIa). Similarly, the ethoxy analog (VIIb) was prepared. Reaction of Ib with sodium cyanide in dimethylsulfoxide produced 1‐(5‐chloro‐2‐hydroxyphenyl)‐1,4‐dihydro‐4‐oxo‐2‐quinolinecarbonitrile (X) which was hydrolized to give the corresponding carboxamide (XIV) and carboxylic acid (XI) depending on the reaction conditions. The latter yielded 2‐chloroquino[2,1‐ c ][1,4]benzoxazine‐6,8‐dione (XII) when heated with an excess of acetic anhydride. Treatment of XII with methoxyethylamine gave 1‐(5‐chloro‐2‐hydroyphenyl)‐1,4‐dihydro‐ N ‐2(methoxyethyl)‐4‐oxo‐2‐quinolinecarboxamide (XV). 1‐(5‐chloro‐2‐hydroxyphenyl)‐2‐(1H‐tetrazoyl‐5‐y1)‐4‐(1 H )qutnolinone (XIII) was prepared from X. When Ib was allowed to react with sodium diethylmalonate, there was obtained [1‐(5‐chloro‐2‐hydroxyphenyl)‐1,4‐dihydro‐4‐oxo‐2‐quinolinyl]‐propanedioic acid diethyl ester (XVI) which was transformed to 1‐(5‐chloro‐2‐hydroxyphenyl)‐1,4‐dihydro‐4‐oxo‐2‐quinolinacetic acid ethyl ester (XVII) upon heating in hexamethylphosphoramide.