Chemistry Letters Vol.36, No.9 (2007)
1119
In conclusion, we have developed this new method which
is simple, mild, efficient and inexpensive for the synthesis of
xanthopterin, 6-formylpterin, 2(1H)-quinoxalinone, pyrido[2,3-
b]pyrazinone derivatives, 3-hydroxymethyl-2(1H)-quinoxali-
none, 2-hydroxy-1-quinoxalin-2-ylethanone, and quinoxaline
aldehyde from the corresponding methyl or sugar derivatives
under microwave oxidative degradation.
O
OH
O
CH3
N
N
H
O
N
N
SeO2
O
O
Se
Se
N
H
O
N
H
O
O
2
II
I
NaIO4 / H2O
H2O
OH
+
OH
H
N
N
N
H
O
N
O
O
OH
Se
O
O
N
H
O
I
O
N
O
OH
H
We thank DST [SR/S1/OC-13/2005], Govt. of India for
financial support. ACM thanks UGC, Govt. of India for a
research fellowship. We appreciate Professor Thomas Schrader
of Philipps-Universitat, Marburg, Germany and Dr. Avijit Kr.
Adak for mass spectral help.
H2O
IV
12
III
Scheme 1. Plausible mechanism for the formation of 12 from 2
by SeO2 or NaIO4.
pyrido[2,3-b]pyrazinone derivatives 3 and 4 respectively were
made by condensing corresponding diaminopyridine with pyr-
uvic acid.8 2-Acetylamino-7-methyl-4,6(3H,5H)-pteridinedione
(1), 3-methyl-2(1H)-quinoxalinone9 (2) and 3-substituted sugar
of 2(1H)-quinoxalinone10 5 were subjected to selenium dioxide
and sodium periodate oxidations respectively affording 11 from
1 and 12 from 2 and 5, respectively. However, selenium dioxide
could not produce compound 12 from the staring material 5
which remained almost unreacted. The yield was better with
selenium dioxide compared to sodium periodate oxidation in
case of 3-methyl-2(1H)-quioxalinone as the starting substrate.
Interestingly, manganese dioxide produced only the new 3-hy-
droxymethyl-2(1H)-quinoxalinone (15) from 5 under micro-
wave condition. All the compounds made here were well charac-
terized by spectroscopic studies as well as by comparison
with authentic samples. The reaction conditions and yields are
summarized in Table 1.
A plausible mechanism for the formation of compound 12
from 2 by sodium periodate as well as by selenium dioxide
oxidation is shown in Scheme 1. The presence of lactam moiety
in the compounds (Entry 1–6) seems to play a key role in the
above such oxidative total carbon chain loss with simple substi-
tution by hydrogen. In the cases of compounds (Entry 7–10)
where lactam carbonyl moiety is absent, only the corresponding
aldehydes were obtained with sodium periodate oxidation.
Thus, we have succeeded in achieving a facile oxidative and
degradative one-step synthesis of 2-acetylamino-6-formylpterin
(16) (Entry 7 and 8) and quinoxaline aldehyde 17 (Entry 9 and
10) by using simple sodium periodate as an oxidant. However,
selenium dioxide oxidation failed to give the desired aldehydes.
6-Formylpterin is a precursor of the pteridine substrate of dihy-
dropteroate biosynthesis.11 We are interested in synthetic stud-
ies12 on compound Z of molybdenum cofactor13 which has a
C-6-substituted pterin ring system. N-Acetylaminotetrol 7 when
oxidized by sodium periodate gave the acetyl protected 6-
formylpterin14 16 in 30–35% yield which thus constitutes a
new synthesis of 6-formylpterin.
References and Notes
1
For a recent book on microwave-assisted reaction, see:
Hayes, B.L., in Microwave Synthesis: Chemistry at the
Speed of Light., CEM Publishing, Matthews, 2002,
NC28105.
2
For recent discussion on microwave-assisted organic
b) A. Loupy, A. Pettit, J. Hamelin, F. Texier-Boult, P.
Jacquault, D. Mathe, Synthesis 1998, 1213. c) For recent
review on reactions under microwave irradiation with out
solvent: R. S. Verma, Green Chem. 1999, 43. d) M. Larhed,
3
4
5
See the Supporting Information which is available electroni-
journals/chem-lett/.
6
a) A. J. Fatiadi, Synthesis 1976, 65, 133. b) J. S. Pizey, in
Synth. Reagents, John Wiley and Sons, Inc. New York,
1974, Vol. 2, p. 143.
7
8
a) G. B. Elion, G. H. Hitchings, J. Am. Chem. Soc. 1947, 69,
a) D. G. Bekerman, M. I. Abasolo, B. M. Fernandez, J.
Heterocycl. Chem. 1992, 29, 129. b) Y. Blache, A. Gueiffier,
O. Chavignon, J. C. Teulade, J. C. Milhavet, H. Viols, J. P.
Chapat, G. Dauphin, J. Heterocycl. Chem. 1994, 31, 161.
9
10 a) H. Ohle, Ber. 1934, 67, 155. b) W. S. Chilton, R. C. Krahn,
12 a) R. S. Pilato, K. A. Erickson, M. A. E. Greaney, I. Stiefel,
S. P. Goswami, L. Kilpatric, T. C. Spiro, E. C. Taylor,
S. P. Goswami, Heterocycles 1993, 35, 1552.
H. E. Hainline, B. H. Arison, K. V. Rajagopalan, J. Biol.
Chem. 1984, 259, 5414.
14 E. C. Taylor, P. S. Roy, Synth. Commun. 1987, 1865.
12, 401. b) E. Alder, H. D. Becker, Acta. Chem. Scand. 1961,
15, 849.
Further, quinoxaline tetrols7 9 and 10 provide a convenient
route to the synthesis of quinoxaline aldehyde 17 in 50–60%
yield by simple periodate oxidation from inexpensive starting
materials. The partial oxidative degradation of quinoxaline
tetrols 9 and 10 by manganese dioxide presumably occured by
the facile oxidative benzylic bond cleavage15 and gave the major
product quinoxaline aldehyde 17 (56%) and also 2-hydroxy-1-
quinoxalin-2-ylethanone (18) in a low yield (14%).