Ceric ammonium nitrate mediated oxidations for the synthesis of xanthones and related products
Date
2011-06-06
Authors
Johnson, Myron Mario
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Abstract
Xanthones are a class of secondary metabolites widely found in many natural
organisms. Their diverse pharmacological activities have elicited much interest,
particularly in their synthesis. This class of compound contains the basic dibenzo-γ-
pyrone ring system. The dissertation involves the use of a ceric ammonium nitrate
(CAN) mediated oxidation reaction as a key step to form a range of xanthone and
dione compounds, which include 2,3-dimethoxy-9H-xanthen-9-one, 12a-methoxy-
5H-benzo[c]xanthenes-5,7(12aH)-dione and the unexpected spiro compound 5-
chloro-2',5'-dimethoxy-3H-spiro(benzofuran-2,1'-cyclohexa[2,5]diene)-3,4'-dione.
The synthesis of 2,3-dimethoxy-9H-xanthen-9-one started with the preparation of (2-
(benzyloxy)-5-chlorophenyl)(2,4,5-trimethoxyphenyl)methanone from benzyl-2-
(benzyloxy)benzoate and 1-bromo-2,4,5-trimethoxybenzene. This was followed by
deprotection to afford hydroxyphenyl(2,4,5-trimethoxyphenyl)methanone. CAN was
then utilized to execute the ring closure thus forming the xanthone nucleus in 91%
yield. Using similar methodology 12a-methoxy-5H-benzo[c]xanthenes-5,7(12aH)-
dione was afforded from CAN mediated oxidation reaction of (1,4-
dimethoxynaphthalene-2-yl)2-hydroxyphenyl methanone in 72% yield. Having
successfully produced xanthones and diones using simple systems, we then decided
to determine how generalized the synthetic route is. The addition of halogens is
believed to be important as they add to the biological activity by increasing the
binding capacity, especially against malaria. For example in one transformation we
prepared (5-chloro-2-hydroxyphenyl)(2,4,5-trimethoxyphenyl)methanone by similar
methodology used for the preparation of hydroxyphenyl(2,4,5-
trimethoxyphenyl)methanone. CAN oxidation of this precursor lead to the isolation of
three products. The first two were the expected 7-chloro-2,3-dimethoxy-9Hxanthene-
9-one and 7-chloro-3,4a-dimethoxy-2H-xanthene-2,9(4aH)-dione products
while the third unexpected product was the spiro compound 5-chloro-2’,5’-
dimethoxy-3H-spiro(benzofuran-2,1'-cyclohexa[2,5]diene])-3,4-dione, the structure of which was confirmed using x-ray crystallography.