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Ring closure reaction of 4‐(2‐hydroxyanilino)‐2‐phenyl‐5‐pyrimidinecarboxylic acid with acetic anhydride. Synthesis of pyrimido[5,4‐ c ] [1,5]benzoxazepin‐5(11 H )ones
Author(s) -
Kim Dong Han,
Santilli Arthur A.,
Fieber Richard A.
Publication year - 1972
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.5570090627
Subject(s) - chemistry , acetic anhydride , acetic acid , hydrolysis , ring (chemistry) , derivative (finance) , catalysis , medicinal chemistry , acid anhydride , carboxylic acid , ethyl ester , pyrimidine , organic chemistry , stereochemistry , financial economics , epoxy , economics
Syntheses of 11‐acety1‐2‐phenylpyrimido[5,4‐ c ][1,5]benzoxazepin‐5(11 H )one ( 16a ) and analogs ( 16b,c, 22 ) were described. The reaction of 4‐chloro‐2‐phenyl‐5‐pyrimidinecarboxylic acid ethyl ester ( 7 ) with 2‐aminophenol afforded 4‐(2‐hydroxyanilino)‐2‐phenyl‐5‐pyrimidine‐carboxylic acid ethyl ester ( 8a ). The latter was also prepared by catalytic reduction of 4‐(2‐nitrophenoxy)‐2‐phenyl‐5‐pyrimidinecarboxylic acid ethyl ester ( 9 ), which was obtained from 7 and 2‐nitrophenol. Involvement of 4‐(2‐aminophenoxy)‐2‐phenyl‐5‐pyrimidinecarboxylic acid ethyl ester ( 12a ) in this reduction as an intermediate was demonstrated by an independent synthesis of 12a and its subsequent rearrangement to 8a. Hydrolysis of 8a or 12a gave 4‐(2‐hydroxyanilino)‐2‐phenyl‐5‐pyrimidinecarboxylic acid ( 15a ). Reaction of 15a with acetic anhydride afforded 16a , the first member of a novel ring system, the pyrimido[5,4‐ c ][1,5]‐benzoxazepin. Additional examples ( 16b,c ) were prepared similarly. The corresponding 11‐ethyl derivative ( 22 ) was prepared in similar fashion, starting with 7 and 2‐ethylaminophenol. A possible reaction mechanism for the formation of 16a‐c from 15a‐c and acetic anhydride was discussed.