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Concise Xanthine Synthesis through a Double‐Amidination Reaction of a 6‐Chlorouracil with Amidines using Base‐Metal Catalysis
Author(s) -
Morel Bénédicte,
Franck Philippe,
Bidange Johan,
Sergeyev Sergey,
Smith Dan A.,
Moseley Jonathan D.,
Maes Bert U. W.
Publication year - 2017
Publication title -
chemsuschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.412
H-Index - 157
eISSN - 1864-564X
pISSN - 1864-5631
DOI - 10.1002/cssc.201601483
Subject(s) - catalysis , chemistry , xanthine , base (topology) , metal , combinatorial chemistry , organic chemistry , mathematics , enzyme , mathematical analysis
Abstract A new and concise route towards xanthines through a double‐amidination reaction is described; consecutive intermolecular C−Cl and intramolecular oxidative C−H amidination. N ‐uracil amidines are obtained through S N AE on a 6‐chlorouracil with amidines. Direct Cu‐catalyzed oxidative C−H amidination on these N ‐uracil amidines yields polysubstituted xanthines. Sustainable oxidants, t Bu 2 O 2 or O 2 , can be used in this oxidase‐type reaction. The protocol allows for the introduction of N 1, N 3, N 7, and C 8 substituents during the xanthine‐scaffold construction, thus avoiding post‐functionalization steps. Both 6‐chlorouracils and amidines are readily available commercially or through synthesis.