Oxidation of alkynes using PdCl2/CuCl2 in PEG as a recyclable catalytic system: One-pot synthesis of quinoxalines

Article abstract of DOI:10.1016/j.tetlet.2010.05.006

Alkynes were oxidized efficiently using the catalytic amount of PdCl ₂ and CuCl₂ in PEG-400 in the presence of water, providing excellent yields of the corresponding 1,2-diketones. A variety of alkynes were well-suited substrates for the oxidation under the described conditions. Further, the optimized conditions were successfully utilized for the one-pot synthesis of 2,3-disubstituted quinoxaline derivatives.

Full text of DOI:10.1016/j.tetlet.2010.05.006

Tetrahedron Letters 51 (2010) 3623–3625
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Oxidation of alkynes using PdCl2/CuCl2 in PEG as a recyclable catalytic
system: one-pot synthesis of quinoxalines
*
S. Chandrasekhar , N. Kesava Reddy, V. Praveen Kumar
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 February 2010
Revised 3 May 2010
Accepted 6 May 2010
Available online 10 May 2010
Alkynes were oxidized efficiently using the catalytic amount of PdCl2 and CuCl2 in PEG-400 in the pres-
ence of water, providing excellent yields of the corresponding 1,2-diketones. A variety of alkynes were
well-suited substrates for the oxidation under the described conditions. Further, the optimized condi-
tions were successfully utilized for the one-pot synthesis of 2,3-disubstituted quinoxaline derivatives.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Poly(ethylene glycol)
Alkynes
Quinoxaline
Palladium chloride
Copper chloride
Poly (ethylene glycol) (PEG) has been emerging as a promising
green solvent and receiving more attention for both combinatorial
as well as for heterogeneous catalysts.1 The viscosity of PEG at
ambient and higher temperatures gives them significant advantage
to use for all general operations. PEG offers advantages such as un-
ique solubility properties, low vapor pressure, ready availability,
and low cost, which renders it a good solvent for various organic
transformations, such as coupling,2 oxidation,3 addition,4 reduction
reactions.5 We have also successfully demonstrated the use of PEG
as a reusable solvent for asymmetric dihydroxylation,6a Pd(OAc)2-
catalyzed Heck reaction,6b DABCO-catalyzed Baylis–Hillman reac-
tion,6c Pd/CaCO3-catalyzed partial reduction of alkynes to cis-ole-
reagent system, PdCl2/CuCl2 in PEG/H2O (8:2), for the oxidation
of alkynes to 1,2-diketones as a recyclable system (Scheme 1).
Our studies started with the reaction of diphenylacetylene (1a)
with catalytic amount (5 mol %) of PdCl2/CuCl2 in polyethylene gly-
col in the presence of water (8:2), which provided the correspond-
ing ketone 2a in 80% yield (Table 1, entry 1). The reaction
proceeded at room temperature in 10 h for completion. We then
explored the generality of the reaction by varying the substituent
on the acetylene and the results are summarized in Table 1. All
the substrates studied, diaryl acetylenes (1b–g), have been oxi-
dized to the corresponding 1,2-diketones in good yields (Table 1,
entries 2–7). Moreover, the reactions also proceeded with aryl al-
kyl acetylenes 1h and 1i (Table 1, entries 8 and 9), though slightly
lower yields were obtained.13
The recycling performance of the present reagent system,
PdCl2/CuCl2 in PEG, was investigated in the oxidation of 4-(phen-
ylethynyl)benzonitrile (1c). The data presented in Table 2 show
that the described reagent system could be recycled and reused
five times without the loss of reactivity. Further, the reusability
of the recycled reagent system was also tested for the different
substrates. As the first experiment, the oxidation of 1e gave dike-
tone 2e in 78% yield. The recycled reagent system from this reac-
fins,6d -proline-catalyzed asymmetric Aldol reactions,6e one-pot
L
conversion of amines to homologated esters.6f Further applications
of PEG in organic transformations are still welcome.
Oxidation of substituted internal alkynes is one of the most use-
ful methods among the reported methods for the synthesis of 1,2-
diketones. The known oxidation methods include the use of
KMnO4,7 transition metal catalysts,8 DMSO,9 Wacker-type oxida-
tion using molecular oxygen,10 oxone in trifluoroacetic acid,11 or
acid-promoted reactions.12 However, most of these oxidation reac-
tions suffer from a variety of disadvantages such as the use of toxic
or expensive reagents, higher temperatures, or cryogenic reaction
conditions. In continuation of our interest on the development of
PEG-mediated reactions, we now report a mild oxidizing catalytic
O
PdCl2/CuCl2 (5 mol%)
R
Ph
R
Ph
PEG/H2O (8:2), rt,
8 - 14h
O
R= alkyl, aryl
63- 87 %
* Corresponding author. Tel.: +91 4027193210; fax: +91 4027160512.
E-mail address: srivaric@iict.res.in (S. Chandrasekhar).
Scheme 1. Oxidation of alkynes to 1,2-diketones.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.006

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S. Chandrasekhar et al. / Tetrahedron Letters 51 (2010) 3623–3625
Table 1
Oxidation of alkyne with PdCl2/CuCl2 in PEG/H2Oa
S.No.
Alkyne
Time (h)
10
1,2-Diketoneb
Yieldc (%)
O
1
80
1a
OH
2a
O
O
12
10
85
87
OH
2b
CN
2
3
1b
O
O
CN
1c
2c
O
O
F
4
5
9
83
78
F
1d
O
O
2d
CH3
CH3
1e
14
2e
But
O
O
But
6
7
14
8
80
82
1f
2f
O
O
OMe
OMe
O
O
2g
2h
1g
1h
8
9
12
12
63
68
O
O
OBn
1i
OBn
2i
O
a
b
c
Reaction conditions: Internal alkyne (1 mmol), PdCl2 (5 mol %), CuCl2 (5 mol %), PEG/H2O (8:2), rt.
Products were characterized by 1H, 13C NMR, and mass spectroscopy.
Isolated yields.
Table 3
Table 2
Recyclability for different substrates
Recyclability for same substrate
Alkyne
Yielda (%)
Alkyne
Yielda (%)
1st
1st Run
2nd Run
1e
1g
78
80
2nd
87
3rd
80
4th
80
5th
75
1c
87
a
Isolated yield after column chromatography.
a
Isolated yield after column chromatography.
synthesis of quinoxaline derivatives under the described condi-
tions (Scheme 2).15
tion was used for the oxidation of 1g, which also furnished the
corresponding diketone 2g in 80% yield and no contaminants
were observed (Table 3).
The obtained products in the above-described transformation,
1,2-diketones, are the useful compounds for the preparation of
quinoxaline derivatives,14 by reacting with 1,2-diaminobenzene.
By taking this advantage, further, we have explored the one-pot
Accordingly, the oxidation of 1b was carried out using 5 mol %
of PdCl2/CuCl2 in PEG/H2O (8:2) followed by the addition of 1,2-
diaminobenzene. Interestingly, the expected quinoxaline 3a was
obtained in 80% yield at room temperature (Table 4, entry 1). To
prove the generality of the reagent system for this one-pot trans-
formation, a few more substrates 1c, 1e, and 1g were studied

S. Chandrasekhar et al. / Tetrahedron Letters 51 (2010) 3623–3625
3625
4. (a) Kumar, D.; Patel, G.; Mishra, B. G.; Varma, R. S. Tetrahedron Lett. 2008, 49,
6974; (b) Kouznetsov, V. V.; Arenas, D. R. M.; Bohorqez, A. R. R. Tetrahedron Lett.
2008, 49, 3097.
5. Zhou, H.-F.; Fan, Q.-H.; Tang, W.-J.; Xu, L. J.; He, Y.-M.; Deng, G.-J.; Zhao, L.-W.;
Gu, L.-Q.; Chan, A. S. C. Adv. Synth. Catal. 2006, 348, 2172.
i) PdCl2/CuCl2 (5 mol%),
PEG/H2O (8:2)
N
N
R
R
R1
ii). 1,2-diaminobenzene
rt, 14 - 20h
R1
6. (a) Chandrasekhar, S.; Narsihmulu, Ch.; Sultana, S. S.; Reddy, N. R. Chem.
Commun. 2003, 1716; (b) Chandrasekhar, S.; Narsihmulu, Ch.; Sultana, S. S.;
Reddy, N. R. Org. Lett. 2002, 4, 4399; (c) Chandrasekhar, S.; Narsihmulu, Ch.;
Saritha, B.; Sultana, S. S. Tetrahedron Lett. 2004, 45, 5865; (d) Chandrasekhar, S.;
Narsihmulu, Ch.; Chandrasekhar, G. Tetrahedron Lett. 2004, 45, 2421; (e)
Chandrasekhar, S.; Narsihmulu, Ch.; Reddy, N. R. Tetrahedron Lett. 2004, 45,
4581; (f) Chandrasekhar, S.; Reddy, G. P. K.; Nagesh, Ch.; Reddy, Ch. R.
Tetrahedron Lett. 2007, 48, 1269.
Scheme 2. Oxidation of alkynes to 1,2-diketones.
Table 4
One-pot synthesis of quinoxaline derivatives
S.No
Alkyne
Time (h)
Quinoxalinea
Yieldb (%)
7. (a) Deng, X.; Mani, N. S. Org. Lett. 2006, 8, 269; (b) Lee, D.; Chang, V. S. Synthesis
1978, 462.
8. (a) Li, P.; Cheong, F. H.; Chao, L. C. F.; Lin, Y. H.; Williams, I. D. J. Mol. Catal. A
1999, 145, 111; (b) Sheu, C.; Richert, S. A.; Cofre, P.; Ross, B., Jr.; Sobkowiak, A.;
Sawyer, D. T.; Kanofsky, J. R. J. Am. Chem. Soc. 1990, 112, 1936; (c) Giraud, A.;
Provot, O.; Peyrat, J. F.; Alami, M.; Brion, J. D. Tetrahedron 2006, 62, 7667.
9. (a) Wan, Z.; Jones, C. D.; Mitchell, D.; Pu, J. Y.; Zhang, T. Y. J. Org. Chem. 2006, 71,
826; (b) Yusubov, M. S.; Zholobova, G. A.; Vasilevsky, S. F.; Tretyakov, E. V.;
Knight, D. W. Tetrahedron 2002, 58, 1607; (c) Rogatchov, V. O.; Filimonov, V. D.;
Yusubov, M. S. Synthesis 2001, 1001.
N
N
3a
1
lb
16
80
OH
10. Ren, W.; Xia, Y.; Jun Ji, S.; Zhang, Y.; Wan, X. Org. Lett. 2009, 11, 1841.
11. Chu, J.; Chen, Y.; wu, M. Synthesis 2009, 2155.
12. Gebeyehu, G.; McNelis, E. J. Org. Chem. 1980, 45, 4280.
N
N
13. General procedure for 1,2-diketones: To a stirred solution of alkyne (1 mmol) in
10 mL PEG/H2O (8:2) were added PdCl2 (5 mol %) and CuCl2 (5 mol %). The
solution was stirred at room temperature for the completion of the reaction
(see Table 1). The solution was diluted with ether (2 Â 20 mL) and cooled in ice
bath. The ether layer was separated, dried over anhydrous Na2SO4, and
concentrated under vacuum. The residue was purified by column
chromatography to give the corresponding 1,2-diketone in good yield.
Spectral data of representative new products (2b): 1H NMR (300 MHz, CDCl3): d
7.95 (d, J = 7.3 Hz, 2H), 7.70–7.62 (t, J = 7.3 Hz, 1H), 7.55–7.45 (m, 4H), 7.40–
7.32 (d, J = 7.9, 8.1 Hz, 1H), 7.17–7.12 (m, 1H), 5.89 (s, 1H); 13C NMR (75 MHz,
CDCl3): d 194.8, 194.6, 156.4, 135.1, 134.1, 132.7, 130.4, 129.9, 129.0, 122.8,
2
3
lc
le
14
20
81
75
3b
CN
N
N
3c
122.6, 115.5; IR (KBr):
m 3421, 3060, 2924, 1660, 1618, 1477, 1176, 861,
710 cmÀ1; MS-ESI: m/z 249 (M+Na)+.
CH3
Compound (2d): 1H NMR (300 MHz, CDCl3): d 7.97 (d, J = 8.3 Hz, 2H), 7.77–7.64
(m, 3H), 7.58–7.45 (m, 3H), 7.41–7.32 (m, 1H); 13C NMR (75 MHz, CDCl3): d
193.6, 193.0, 164.4, 135.0, 132.6, 130.8, 130.7, 129.9, 129.0, 125.9, 122.1, 121.8,
N
N
116.1, 115.8; IR (KBr):
m 3325, 3070, 2923, 1670, 1587, 1446, 1241, 837,
717 cmÀ1; MS-ESI: m/z 251 (M+Na)+.
4
lg
15
78
Compound (2f): 1H NMR (300 MHz, CDCl3): d 7.98–7.93 (m, 2H), 7.91–7.86 (m,
2H), 7.66–7.59 (m, 1H), 7.53–7.46 (m, 4H), 1.35 (s, 9H); 13C NMR (75 MHz,
CDCl3): d 194.7, 194.2, 159.0, 134.7, 133.1, 130.4, 129.8, 128.9, 126.0, 35.3,
3d
30.9, 29.6; IR (KBr):
ESI: m/z 289 (M+Na)+.
m
3464, 2963, 1670, 1598, 1217, 1177, 882, 661 cmÀ1; MS-
OMe
Compound (2g): 1H NMR (300 MHz, CDCl3): d 7.98–7.93 (m, 2H), 7.91–7.86 (m,
2H), 7.66–7.59 (m, 1H), 7.53–7.46 (m, 4H), 1.35 (s, 9H); 13C NMR (75 MHz,
CDCl3): d 194.7, 194.2, 160.4, 138.1, 134.6, 133.1, 133.0, 131.3, 129.8, 128.8,
Products were characterized by 1H, 13C NMR, and mass spectroscopy.
Isolated yields.
a
b
128.1, 127.6, 127.4, 124.3, 119.9, 105.8, 55.3; IR (KBr):
m 3431, 3060, 2925,
2841, 1662, 1617, 1478, 1263, 860, 710 cmÀ1; MS-ESI: m/z 313 (M+Na)+.
14. (a) Nair, V.; Dhanya, R.; Rajesh, C.; Bhadbhade, M. M.; Manoj, K. Org. Lett. 2004,
6, 4743; (b) Aqad, E.; Lakshmikantham, M. V.; Cava, M. P. Org. Lett. 2003, 5,
4089; (c) Heravi, M. M.; Baghaernejad, B.; Oskooie, H. A. Tetrahedron Lett. 2009,
50, 767; (d) Madhav, B.; Murthy, S. N.; Reddy, V. P.; Rao, K. R.; Nageswar, Y. V.
D. Tetrahedron Lett. 2009, 50, 6025.
and the results are summarized in Table 4. The reaction of alkynes
1c, 1e, and 1g under the present reaction conditions in the pres-
ence of 1,2-diaminobenzene provided the 2,3-disubstituted quin-
oxaline derivatives in good yields (Table 4, entries 2–4).
In summary, an efficient recyclable catalytic system for the oxi-
dation of internal alkynes to 1,2-diketones has been demonstrated.
5 mol % of PdCl2/CuCl2 in PEG/H2O was used for the described
transformation, and the recyclability has also been proved. Further,
the efficiency of this reagent system in one-pot synthesis of 2,3-
disubstituted quinoxaline derivatives was successfully explored.
15. General procedure for quinoxalines: To a stirred solution of alkyne (1 mmol) in
10 mL PEG/H2O (8:2) were added PdCl2 (5 mol %) and CuCl2 (5 mol %) and the
solution was stirred at room temperature. After the completion of alkyne
(monitored by TLC), 1,2-diaminobenzene (1 mmol) was added and stirring was
continued at room temperature (see Table 4). The solution was diluted with
ether (2 Â 20 mL) and cooled in ice bath. The ether layer was separated, dried
over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified
by column chromatography to give the corresponding 2,3-disubstituted
quinoxaline in good yield.
Spectral data of representative new products (3a): 1H NMR (300 MHz, CDCl3): d
8.21–8.12 (m, 2H), 7.81–7.71 (m, 2H), 7.53–7.42 (m, 2H), 7.30–7.20 (m, 3H),
7.10–6.96 (m, 2H), 6.91–6.83 (d, J = 7.5 Hz, 1H), 6.76–6.69 (m, 1H); 13C NMR
(75 MHz, CDCl3): d 156.1, 153.4, 153.1, 141.1, 140.7, 139.7, 138.5, 130.1, 129.6,
Acknowledgments
N.K.R. thanks UGC and V.P.K. thanks CSIR, New Delhi, for the
financial assistance.
129.3, 129.0, 128.8, 128.6, 128.1, 121.8, 116.8, 116.3; IR (KBr):
m 3053, 2924,
2853, 1581, 1347, 1273, 762, 695 cmÀ1; MS-ESI: m/z 321 (M+Na)+.
Compound (3d): 1H NMR (300 MHz, CDCl3): d 8.24–8.15 (m, 2H), 8.07 (s, 1H),
7.81–7.73 (m, 2H), 7.70 (d, J = 8.8 Hz, 1H), 7.63 (d, J = 8.7 Hz, 2H), 7.59–7.53 (m,
2H), 7.51–7.45 (dd, J = 1.7, 8.5 Hz, 1H), 7.38–7.26 (m, 3H), 7.17–7.08 (m, 2H),
3.92 (s, 3H); 13C NMR (75 MHz, CDCl3): d 158.3, 153.5, 153.3, 141.3, 141.1,
139.2, 134.5, 134.2, 130.1, 129.9, 129.7, 129.6, 129.1, 129.1, 128.7, 128.5, 128.3,
References and notes
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Zhang, Z.-h.; Wang, Y.-M. Tetrahedron 2006, 62, 9359; (c) Li, J.-H.; Liu, W.-J.; Xie,
Y.-X. J. Org. Chem. 2005, 70, 5409.
127.6, 126.4, 119.1, 105.5, 55.3; IR (KBr):
m 3446, 3053, 2921, 2853, 1342, 756,
696 cmÀ1; MS-ESI: m/z 385 (M+Na)+.
3. Alper, H. Pure Appl. Chem. 1988, 60, 35.