7
4
Y. Jiao, H. Yu et al.
LETTER
(5) Herrmann, W. A.; Fisher, R. W.; Correia, J. D. G. J. Mol.
The oxidation of 6-chloro- and 6-bromopurine10 was
problematic. The use of more catalyst (5 mol%), longer
reaction time (up to 5 days), and elevated reaction temper-
ature (40 ºC) did not produce the desired product with a
reasonable yield. The poor yield may be due to the elec-
tron withdrawing effect by chlorine and bromine. Also,
the oxidation products seemed unstable because new sig-
nals appeared in their NMR spectra after they were left in
the NMR tube for several days.
Catalysis 1994, 94, 213.
(
6) Zhu, Z.; Espenson, J. H. J. Org. Chem. 1995, 60, 1326.
Murray, R. W.; Iyanar, K.; Chen, J.; Wearing, J. T.
Tetrahedron Lett. 1996, 37, 805.
(7) Coperet, C.; Adolfsson, H.; Khuong, T.-A. V.; Yudin, A. K.;
Sharpless, K. B. J. Org. Chem. 1998, 63, 1740.
(8) General procedure: A mixture of MeReO (5 mg, 0.02 mmol)
3
and 30% aqueous H
was stirred at room temperature for 10 min. Then 119 mg
1 mmol) of 1H-imidazo[4,5-c]pyridine in 4 mL methanol was
O (0.4 mL, 4 mmol) in 6 mL methanol
2
2
(
The oxidation of 1H-pyrrolo[2,3-b]pyridine (7-azaindole)
afforded 1H-pyrrolo[2,3-b]pyridine-N-oxide. However, it
added dropwise while stirring. The stirring was continued at
room temperature (20 ºC) until the starting material vanished
as was shown by TLC. The solution was then evaporated to
dryness and the residue was crystallized from water to give
needed a much longer reaction time (7 days). The oxida-
tion of 1-methyl-pyrrolo[2,3-b]pyridine11 (1-methyl-7-
9
8 mg (73%) of 1H-imidazo[4,5-c]pyridine-N-oxide.
9) 1H-imidazo[4,5-c]pyridine was prepared by the reaction of
,4-diaminopyridine with formic acid. All other purine related
azaindole) also did not proceed as expected. Only traces
of products were identified through GC-MS. This is pos-
sibly because the neighboring methyl group hinders the
interaction of the substrate with the catalyst.
(
3
compounds were purchased from Aldrich Chemical
Company.
1
(
10) The oxidation product for 6-chloropurine: H NMR (DMSO-
d6): one singlet each at 7.75 ppm and 7.68 ppm. MS for
C H ClN O: 169 and 171(intensity ratio is about 3:1). For
In conclusion, purine, 6-methylpurine, 1H-imidazo[4,5-
c]pyridine, and 1H-imidazo[4,5-b]pyridine were selec-
tively oxidized to their respective N-oxides with good
yields under mild conditions. The isolation of the N-oxi-
dation products was simple and the reaction time was rel-
atively short. Although the oxidation of purine and related
compounds to their corresponding N-oxides can be
achieved by peracetic acid, aqueous H O , or m-chlo-
roperbenzoic acid,
even at high temperatures up to 80 ºC. Therefore, this
method for the oxidation of purines proves to be more ef-
5
3
4
6
-bromopurine: a mixture of the N1- and the N3-oxide was
1
isolated with about 3:1 ratio (NMR, TLC). H NMR (DMSO-
d6): one singlet each at 8.43 ppm and 8.32 ppm for one set and
at 8.49 ppm and 8.50 ppm for another set. MS for C
14 and 216 (intensity ratio is about 1:1).
(11) 1-Methyl-pyrrolo[2,3-b]pyridine was prepared by the
H BrN O:
5
3 4
2
1
2
13
2
2
methylation of 1H-pyrrolo[2,3-b]pyridine: Chen, Y.; Rich, R.
L.; Cai, F.; Petrich, J. W. J. Phys. Chem. 1993, 97, 1770.
12) Stevens, M. A.; Magrath, D. I.; Smith, H. W.; Brown, G. B. J.
Am. Chem. Soc. 1958, 80, 2755.
1
5,16
the reaction time is usually long
(
ficient than the previous methods. The N-oxides of pu- (13) Stevens, M. A.; Giner-Sorolla, A.; Smith, H. W; Brown G. B.
rines are also important intermediates for structural
modification of purines or purine nucleosides.
J. Org. Chem. 1962, 27, 567.
(14) Mizuno, Y.; Itoh, T.; Saito, K. Chem. Pharm. Bull. 1964, 12,
1
6, 17
8
66.
15) Vaughan, J. R.; Krapcho, J.; English, J. P. J. Am. Chem. Soc.
949, 71, 1885.
(
(
1
Acknowledgement
16) Antonini, I.; Claudi, F.; Cristalli, G.; Franchetti, P.; Grifantini,
M.; Martelli, S. J. Med. Chem. 1982, 25, 1258. Schneller, S.
W.; Luo, J.-K. J. Org. Chem. 1980, 45, 4045.
This research is supported by a generous grant NIH-MBRS
S06GM08047 (to JSU) from the National Institutes of Health.
#
(
17) Deghati, P. Y. F.; Bieraugel, H.; Wanner, M. J.; Koomen, G.-
J. Tetrahedron 2000, 41, 569. Brown, G. B. 4th International
Congress of Biochemistry, Vienna, Vol. XIII-Colloquia,
Pergamon Press: London 1958, p111. Clarke, D. A.; Phillips,
F. S.; Sternberg, S. S.; Stock, C. C. Ann. N. Y. Acad. Sci. 1954,
References and Notes
(
1) Herrmann, W. A; Fisher, R. W.; Marz, D. W. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 1638.
60, 235.
(
(
2) Zhu, Z.; Espenson, J. H. J. Org. Chem. 1995, 60, 7728.
3) Adam, W.; Herrmann, W. A.; Lin, J.; Saha-Moller, C. R.;
Fisher, R. W.; Correia, J. D. G. Angew. Chem., Int. Ed. Engl.
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1
994, 33, 2475.
1
(
4) Adam, W.; Herrmann, W. A.; Lin, J.; Saha-Moller, C. R. J.
Org. Chem. 1994, 59, 8281.
Synlett 2001, No. 1, 73–74 ISSN 0936-5214 © Thieme Stuttgart · New York