action of the iodothyronine deiodinases.3,4 In general,
deiodination as well as debromination is achieved by
various reducing agents such as catalytic hydrogenation,5
metal hydrides,6 and acidic conditions such as Pd/C-
HCl,7 Zn8 or SnCl2/CH3CO2H,9 Zn/HCl,10 and CuCN/
FeCl3.11 Nevertheless, these methods are time-consuming
or complicated or use expensive catalysts. Obviously,
these methods also affect the reduction susceptibility of
groups present in the structure.12 Recently, debromina-
tion by HBr has been reported as the first case without
affecting the reductive groups.1
Nonreductive Deiodination of
ortho-Iodo-Hydroxylated Arenes Using
Tertiary Amines
Rahul Subhash Talekar,† Grace Shiahuy Chen,‡
Shin-Yu Lai,† and Ji-Wang Chern*,†
School of Pharmacy, College of Medicine, National Taiwan
University, No. 1, Section 1, Jen-Ai Road, Taipei, Taiwan,
ROC, and Department of Applied Chemistry, Providence
University, 200 Chung-Chi Road, Shalu, Taichung, ROC
Received June 13, 2005
Quinolines and their derivatives have attracted re-
search in areas such as pharmaceuticals and are general
synthetic building blocks due to their chemical and
biological relevance.13 8-Hydroxyquinoline and its halo
derivatives have attracted studies as analytical reagents
and metal-extracting agents because of their ability to
complex with metal ions.14 They are also used as bacte-
ricides,15 fungicides,16 antimalarial agents,17 and anti-
cancer agents.18 Recently, it was reported that antibiotic
clioquinol (1, Table 1 where R ) R′ ) H) was able to
chelate and remove metal ions from the insoluble amyloid
plaque deposited in the brains of patients with Alz-
heimer’s disease.19 In a study related to the derivatives
of 1, we found that the hydrolysis of the pivaloyl ester of
quinolinols 2a-2c in the presence of pyridine was
associated with deiodination to yield quinolinols 4a-4c.
(3) Beck, C.; Jensen, S. B.; Reglinski, J. Bioorg. Med. Chem. Lett.
1994, 4, 1353-1356.
(4) Vasil’ev, A. A.; Engman, L. J. Org. Chem. 1998, 63, 3911-3917.
(5) (a) Pri-Bar, I.; Buchman, O. J. Org. Chem. 1986, 51, 734-736.
(b) Boyer, S. K.; Bach, J.; McKenna, J.; Jagdmann, E., Jr. J. Org. Chem.
1985, 50, 3408-3411. (c) Wiener, H.; Blum, J.; Sasson, Y. J. Org. Chem.
1991, 56, 6145-6148. (d) Marques, C. A.; Selva, M.; Tundo, P. J. Org.
Chem. 1993, 58, 5256-5260.
A convenient and nonreductive deiodination is reported for
the ortho-iodo-hydroxylated arenes including derivatives of
quinolinol, phenol, and naphthol. Tertiary amines pyridine,
triethylamine, and N-methylmorpholine in the presence of
water initiated deiodination of ortho-iodo-hydroxylated are-
nes without affecting para-iodine and other reduction-
susceptible groups. This reported method also works effi-
ciently for polyiodinated systems. Simplicity, short reaction
times, and absence of reducing catalyst are features of this
method.
(6) (a) Johnson, J. E.; Blizzard, R. H.; Carhart, H. W. J. Am. Chem.
Soc. 1948, 70, 3664-3665. (b) Brown, H. C.; Weissman, P. M.; Yoon,
N. M. J. Am. Chem. Soc. 1966, 88, 1458-1463. (c) Yoon, N. M.; Brown,
H. C. J. Am. Chem. Soc. 1968, 90, 2927-2938. (d) Brown, H. C.;
Krishnamurthy, S. J. Org. Chem. 1969, 34, 3918-3923. (e) Corey, E.
J.; Suggs, J. W. J. Org. Chem. 1975, 40, 2554-2555. (f) Lin, S.-T.; Roth,
J. A. J. Org. Chem. 1979, 44, 309-310. (g) Tabaei, S.-M. H.; Pittman,
C. U., Jr.; Mead, K. T. J. Org. Chem. 1992, 57, 6669-6671. (h) Stiles,
M. J. Org. Chem. 1994, 59, 5381-5385.
(7) Nishiyama, S.; Kim, M.-H.; Yamamura, S. Tetrahedron Lett.
1994, 35, 8397-8400.
(8) Zakrzewski, A.; Neckers, D. C. Tetrahedron 1987, 43, 4507-4512.
(9) Scannell, R. T.; Stevenson, R. J. Chem. Soc., Perkin Trans. 1
1983, 12, 2927-2931.
Halogenated arenes are very useful in substitution
reaction. Recently, the bromine on aromatic system was
considered as potential protecting group since the debro-
mination could be achieved selectively and regioselec-
tively by HBr.1 In addition, the iodothyronine deiodinase
enzymes catalyze the interconversion of active and inac-
tive forms of thyroid hormones.2 The enzyme causes
deiodination of thyroxin to an inactive form of hormone.
Some studies have attempted to study the deiodination
by using derivatives of 2,4-diiodophenol to mimic the
(10) Fukata, G.; Kubota, Y.; Mataka, S.; Thiemann, T.; Tashiro, M.
Bull. Chem. Soc. Jpn. 1994, 67, 592-594.
(11) Ellis, G. P.; Hudson, H. V. J. Chem. Res., Miniprint 1985, 12,
3830-3860.
(12) (a) Hutchins, R. O.; Learn, K.; El-Telbany, F.; Stercho, Y. P. J.
Org. Chem. 1984, 49, 2438-2443. (b) Karabatsos, G. J.; Shone, R. L.
J. Org. Chem. 1968, 33, 619-621. (c) Cortese, N. A.; Heck, R. F. J.
Org. Chem. 1977, 42, 3491-3494. (d) Brieger, G.; Nestrick, T. J. Chem.
Rev. 1974, 74, 567-580.
(13) Choi, H. Y.; Kim, D. W.; Chi, D. Y.; Yoon, E. Y.; Kim, D. J. J.
Org. Chem. 2002, 67, 5390-5393.
(14) Phillips, J. P. Chem. Rev. 1956, 56, 271-297.
(15) Takayanagi, T.; Kudoh, T.; Yotsuyanagi, T. Chem. Lett. 1994,
687-690.
* Author to whom correspondence should be addressed. Phone: 886-
2-23939462. Fax: 886-2-23934221.
(16) Gershon, H.; Clarke, D. D.; Gershon, M. Monatsh. Chem. 1994,
125, 51-59.
† National Taiwan University.
‡ Providence University.
(17) Scheibel, L. W.; Adler, A. Mol. Pharmacol. 1980, 18, 320-325.
(18) Swann, E.; Barraja, P.; Oberlander, A. M.; Gardipee, W. T.;
Hudnott, A. R.; Beall, H. D.; Moody, C. J. J. Med. Chem. 2001, 44,
3311-3319.
(1) (a) Choi, H. Y.; Chi, D. Y. J. Am. Chem. Soc. 2001, 123, 9202-
9203. (b) Effenberger, F. Angew. Chem., Int. Ed. 2002, 41, 1699-1700.
(2) Arthur, J. R.; Beckett, G. J. In Selenium in Biology and Human
Health; Burk, R. F., Ed.; Springer-Verlag: New York, 1994; p 93.
(19) Helmuth, L. Science 2000, 290, 1273-1274.
10.1021/jo051191x CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/21/2005
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J. Org. Chem. 2005, 70, 8590-8593