2510
F. Pan et al. / Tetrahedron Letters 53 (2012) 2508–2510
In summary, a new Ga(ClO4)3-catalyzed reaction of diamines
with -hydroxyketones to afford 2-substituted quinoxalines is
developed. Compared to the literature methods, this reaction has
the advantages of simple manipulation, mild reaction conditions,
and high product yields.
NH2
NH2
R1
a
O
H
N
H
N
O
R2
R1
OH
R1
1
R2
N
R2
NH2
Ga(ClO4)3
2
5
4
Acknowledgment
air
NH2
NH2
air
Ga(ClO4)3
R1
J.-P.Z. thanks the financial support from The National Natural
Science Foundation of China (Nos. 20772088 & 21172163).
O
N
R1
O
1
R2
N
R2
3
Supplementary data
6
Scheme 2. Proposed reaction mechanism.
Supplementary data associated with this article can be found, in the
DMSO, and H2O gave the product in much lower yields (Table 1,
entries 3–6). Reactions with other gallium salts or with lanthanum
and ytterbium salts in EtOH were also conducted. It was found that
Ga(OTf)3 gave 55% yield of 3a (Table 1, entry 7), whereas, La(OTf)3
and Yb(OTf)3 gave 3a in 72% and 75%, respectively. Thus, using
equal molar substrates of 1a and 2a with 10 mol % of Ga(ClO4)3
in EtOH was selected as the optimized condition for the synthesis
of 2-substituted quinoxalines 3.
References and notes
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tions of various o-phenylenediamines 1 and
a-hydroxyketones 2
(Table 2). It was found that -hydroxyketones 2 containing elec-
a
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tron-donating and weak electron-withdrawing substitution groups
such as Me, MeO, Br, and Cl afforded products in good yields (84–
95%) (Table 2, entries 2–5). However, strong electron-withdrawing
substitution groups such as NO2 reduced the yield to 71% yield (Ta-
ble 2, entry 6). The reactivity and regioselectivity of the substitu-
ents on o-phenylenediamines 1 were also investigated. It was
found that o-phenylenediamines 1b and 1d, each has a group at
the 4-position, afforded corresponding quinoxalines as two iso-
mers (Table 2, entries 7, 8, 10). Interestingly, reactions of 1e and
1f yielded the corresponding quinoxalines 3k and 3l as single iso-
mers, respectively (Table 2, entries 11 and 12). The reaction of 2-
hydroxy-1,2-diphenylethanone 2g with 1a was also proceeded
smoothly to give 2,3-diphenylquinoxaline 3m in 70% yield (Table 2,
entry 13).
Two possible routes for Ga(ClO4)3-catalyzed reaction of dia-
mines and
a-hydroxyketones are proposed in Scheme 2. The first
route involving intermediates 4 and 5 is proceeded through the
substitution/cyclization/aromatization steps to form quinoxaline
3. The reaction is also possible to go through an alternative path-
way in which diaryl-1,2-diketone 2 is oxidized to 1,2-diketone 4
and then undergoes cycloaddition with 1,2-aryldiamine 1 to afford
product 3.
13. Venkateswara Rao, K. T.; Sai Prasad, P. S.; Lingaiah, N. J. Mol. Catal. A: Chem.
2009, 312, 65–69.
14. Pan, X. Q.; Zou, J. P.; Huang, Z. H.; Zhang, W. Tetrahedron Lett. 2008, 49, 5302–
5308.
15. Cai, J. J.; Zou, J. P.; Pan, X. Q.; Zhang, W. Tetrahedron Lett. 2008, 49, 7386–7390.