Metal-Free C3 Hydroxylation of Quinoxalin-2(1H)-ones in Water

Article abstract of DOI:10.1002/adsc.201901163

A practical protocol for the preparation of quinoxaline-2,3(1H,4H)-diones through direct C(sp²)?H hydroxylation of quinoxalin-2(1H)-ones in recyclable DL-α-Tocopherol methoxypolyethylene glycol succinate solution (2 wt% in water) (TPGS-750-M/H<

Full text of DOI:10.1002/adsc.201901163

Title: Metal-Free C3 Hydroxylation of Quinoxalin-2(1H)-ones in Water
Authors: Sha Peng, Die Hu , Jia-Li Hu, Ying-Wu Lin, Shan-Shan Tang,
Hai-Shan Tang, Jun-Yi He, Zhong Cao, and Wei-Min He
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901163
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10.1002/adsc.201901163
Advanced Synthesis & Catalysis
UPDATES
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Metal-Free C3 Hydroxylation of Quinoxalin-2(1H)-ones in
Water
Sha Penga, Die Hua, Jia-Li Hua, Ying-Wu Linc, Shan-Shan Tanga, Hai-Shan Tanga, Jun-
Yi Heb, Zhong Caob and Wei-Min Hea,b*
a
Department of Chemistry, Hunan University of Science and Engineering, Yongzhou 425100, China
Fax: (+86)-746-6381166; phone: (+86)-018175151053; e-mail: weiminhe@huse.edu.cn
Hunan Provincial Key Laboratory of Materials Protection for Electric Power and Transportation, Changsha University
b
of Science and Technology, Changsha, 410114, China
School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China
c
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A practical protocol for the preparation of developed. The target products were exclusively generated
quinoxaline-2,3(1H,4H)-diones through direct C(sp2)-H and could be collected through extraction and
hydroxylation of quinoxalin-2(1H)-ones in recyclable DL-α- recrystallization.
Tocopherol methoxypolyethylene glycol succinate solution
Keywords: hydroxylation; quinoxalin-2(1H)-one; in water;
(2 wt% in water) (TPGS-750-M/H2O) was
TPGS-750-M; green chemistry
volatile organic solvent, and harsh reaction conditions.
Introduction
Given the readily available quinoxalin-2(1H)-ones,
significant progress has been achieved on the C-H
bond functionalization of quinoxalin-2(1H)-ones,
The direct hydroxylation of C(sp2)-H bond in
heterocycles is a powerful tool for the construction of
C-OH bonds, for which the establishment of efficient
and practical protocols is still a field of interest owing
to the widespread presence of hydroxylated
heterocyclic compounds in natural products, synthetic
pharmaceuticals, agrochemicals and functional
materials. In addition, the hydroxylated heterocycles
also serve as useful and versatile building blocks and
synthetic intermediates in organic synthesis. Over the
past decades, plenty of efforts and remarkable
progress have been made in the development of novel
hydroxylation reaction.[1] However, for a majority of
hydroxylation reactions, transition-metal catalysts and
harmful organic solvent are demanded to promote the
chemical process, which not only greatly restricts
their application in pharmaceutical industry but also
cause environmental problem.
including
the
regioselective
alkylation,[3]
alkoxylation,[4] arylation,[5] acylation,[6] amination,[7]
trifluoromethylation[8] and phosphonation reaction[9] .
During the past decade, water has received much
attention as the expected reaction medium for organic
reactions due to safety, cost and environmental
concerns.[10] However, to the best of our knowledge,
the aqueous construction of C-3 hydroxylated
quinoxalin-2(1H)-ones through hydroxylation of
quinoxalin-2(1H)-ones has not been reported.
Quinoxaline-2,3-dione and their derivatives play
an important role in organic synthesis, pharmaceutical
chemistry and materials science.[2] Traditionally, N-
functionalized quinoxaline-2,3-diones are prepared
through base-promoted condensation reaction
between mono N-substituted 1,2-diaminobenzenes
and oxalyl chloride (or ethyl chloroglyoxalate)
(Scheme 1a).[2a, 2b] However, from a practical and
eco-friendly point of view, those procedures still
suffer from some drawbacks, such as the difficulties
of preparation and isolation of mono N-substituted
substrates, the usage of toxic oxalyl chloride and
Scheme 1. Synthesis of N-substituted quinoxaline-
2,3(1H,4H)-diones
As
a
part of our ongoing interest in
functionalization of quinoxalin-2(1H)-ones,[11] herein
we reported a sustainable method for the clean
preparation of various mono N-functionalized
1
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10.1002/adsc.201901163
Advanced Synthesis & Catalysis
quinoxaline-2,3(1H,4H)-diones
through
direct however, decreasing to 2 equiv. led to a lower yield of
hydroxylation of N-functionalized quinoxalin-2(1H)- 2a (entry 13). Further efforts in varying the reaction
ones in water (Scheme 1b). In the present reaction, temperature did not give improved yield of the target
the desired product can be obtained through simple product (entries 14 - 15). No hydroxylation reaction
extraction and recrystallization without tedious was observed in the absence of (NH4)2S2O8, and the
column chromatography.
raw material 1a was wholly recovered (entry 16).
Table 2. Reaction Scopea
Results and Discussion
Table 1. Optimization of reaction conditionsa
Entry
Oxidant(equiv.)
Solvent
Yieldb
(NH4)2S2O8 (2.5)
(NH4)2S2O8 (2.5)
(NH4)2S2O8 (2.5)
(NH4)2S2O8 (2.5)
(NH4)2S2O8 (2.5)
(NH4)2S2O8 (2.5)
(NH4)2S2O8 (2.5)
K2S2O8 (2.5)
H2O
38%
61%
52%
81%
83%
78%
94%
13%
18%
N.R.
N.R.
94%
86%
63%
92%
N.R.
1
2
2 wt% SDS/H2O
2 wt% TEBAC/H2O
3
2 wt% NP-40/H2O
4
2 wt% Span-60/H2O
5
2 wt% Triton-X100/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
2 wt% TPGS-750-M/H2O
6
7
8
Na2S2O8 (2.5)
TBHP (2.5)
9
10
11
12
13
14c
15d
H2O2 (2.5)
(NH4)2S2O8 (3)
(NH4)2S2O8 (2)
(NH4)2S2O8 (2.5)
(NH4)2S2O8 (2.5)
--
16
[a]
Conditions: 1a (0.1 mmol), oxidant, H2O (0.4 mL), surfactant,
12 h.
[b]
Estimated by 1H NMR using diethyl phthalate as internal
reference.
[c] at 40 ℃.
[d] at 80 ℃. TEBAC: benzyltriethylammonium chloride; NP-40:
substitute octylphenoxypolyethoxyethanol.
[a] Reaction conditions: 1 (0.5 mmol), (NH4)2S2O8 (1.25 mmol), 2
wt% TPGS750M/H2O (2 mL), 60 ℃, 12 h.
Our preliminary study began with N-
methylquinoxalin-2(1H)-one (1a) as
a
model
With the optimal reaction conditions in hand (Table
1, entry 7), we then explored the scope of this
substrate to optimize the reaction conditions (Table 1).
Treatment of 1a with (NH4)2S2O8 (2.5 equiv.) at
60 °C in water for 12 hours resulted in 38% yield of aqueous hydroxylation reaction. As shown in Table 2,
the desired product N-methylquinoxaline-2,3(1H,4H)-
dione (2a) and 40% conversion of 1a (Table 1, entry
1). The low yield of the transformation was probably
due to the poor solubility of 1a in water. To address
this issue, we introduced the 2 wt% sodium
dodecylsulfate (SDS) as a surfactant[1k, 12] to improve
the solubility of 1a. To our delight, the yield of 2a
was improved to 61% (entry 2). Next, a series of
surfactants[13] (entries 3 - 7) were surveyed and DL-α-
Tocopherol methoxypolyethylene glycol succinate
solution (2 wt% in water) (TPGS-750-M) was found
to be the most efficient surfactant for this
hydroxylation reaction (entry 7). Various oxidants
were also investigated, revealing that (NH4)2S2O8 is
more suitable for the transformation (entries 8 - 11).
Increasing the loading of (NH4)2S2O8 to 3 equiv. did
not provide an improved yield of 2a (entry 12),
a series of N-substituted quinoxalin-2(1H)-ones were
allowed, and all the yields of desired products were ≥
82%. The N-1 position of quinoxalin-2(1H)-ones with
varying length chains, and various isomeric structures
of alkyl and functionalized phenyl substituents
underwent the present reaction smoothly to deliver
the expected products in good to excellent yields (2a -
2w). The developed reaction was tolerant of a series
of important functional-groups, including alkenyl (2f
and 2g), alkynyl (2h), and ester (2i - 2k) groups,
which could allow an opportunity for further
functionalization. When N-free quinoxalin-2(1H)-one
was used as substrate, only a trace amount of the
desired product was detected. Quinoxalin-2(1H)-ones
bearing electron-withdrawing, -neutral, and -donating
substituents at phenyl ring could stereo-selectively
2
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10.1002/adsc.201901163
Advanced Synthesis & Catalysis
furnish the expected products (2o - 2t) in excellent
yields. A wide range of functional-groups are well
tolerated including fluoro (2o), chloro (2p), bromo (2j
and 2q), trifluoromethyl (2r), ester (2s) and nitro (2t)
at the different positions of substrates. Di-substituted
quinoxalin-2(1H)-ones (1u
-
1w) and 3,4-
dihydrobenzo[g]quinoxalin-2(1H)-one (1x) provided
the desired products (2u - 2x) in excellent yields.
Remarkably, all the targeted products were easily
collected
recrystallization without using tedious silica gel
column chromatograph No
purification.[14]
through
simple
extraction
and
hydroxylation reaction occurred when quinolin-
2(1H)-one was used as reaction substrate.
Figure 1 Recyclability of TPGS-750-M/H2O
Conditions: 1a (0.3 mmol), (NH4)2S2O8 (0.75 mmol), 2 wt%
TPGS-750-M/H2O (1.2 mL), to the recycled water, only 0.3 mmol
of 1a, 0.75 mmol of (NH4)2S2O8 were added, and the next cycle
1
was carried out under the same conditions, H NMR yields were
reported
The sustainability of the reaction media was also
examined in the template reaction. After completion
of the hydroxylation reaction, the target product 2a
was extracted with ethyl acetate and only fresh
reagents (1a and (NH4)2S2O8) was added to the
TPGS-750-M/H2O solution for the next hydroxylation
reaction cycle. As illustrated in Figure 1, the chemical
process could be repeated 5 times without an obvious
loss in reaction efficiency.
Scheme 2. Gram-scale reaction and synthetic application
Next,
a
large-scale
synthesis
of
N-
methylquinoxaline-2,3(1H,4H)-dione 2a was carried
out under the optimized conditions (Scheme 2a). To
our delight, the hydroxylation reaction provided the
target product 2a in 89% yield (1.56 g), showing a
high potential application for industry scale-up. The
absence of organic side-products when employing
(NH4)2S2O8 offered a great opportunity to us for
investigations on sequential synthesis. Performing the
reaction in 1 wt% TPGS-750-M/H2O leading to the
target product 2a in 75% yield. Increasing the
concentration of 1a to 0.5 mmol/mL resulted in a
drop in the yield of 2a (81%). Coupled with a
subsequent chlorination reaction upon simple workup,
this reaction led to 3y, which is a key precursor for
the synthesis of commercial available drug, namely
Glycogen phosphorylase inhibitor (Scheme 2b).[2b]
Scheme 3. Control Experiments
To understand the reaction mechanism, a series of
control experiments were carried out as shown in
Scheme 3. The hydroxylation reaction of 1a under the
standard conditions in the presence of 2 equiv. of
radical scavenger (BTH or TEMPO) gave no desired
product, suggesting that the present reaction might
proceed through a free-radical pathway (Scheme 3a-
b). When p-phthalic acid, a well-known hydroxyl
radical inhibitor, was added to the reaction mixture
3
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10.1002/adsc.201901163
Advanced Synthesis & Catalysis
To a solution of quinoxalin-2(1H)-ones (0.5 mmol) in
water (2 mL, containing 2 wt% TPGS-750-M) was
added (NH4)2S2O8 (1.25 mmol). The reaction mixture
under the standard conditions, an 86% NMR yield of
product 2a was detected (Scheme 3c), indicating that
hydroxyl free-radical might not be involved in the
transformation. When the reaction of 1a was
o
was stirred at 60 C for about 12 h. After completion
18
of the reaction, the resulting mixture was extracted
with EtOAc (3 X 6 mL) and the organic layer was
dried over anhydrous Na2SO4, filtered and
concentrated to about 3 mL under vacuum, then 5 mL
of petroleum ether was added. After 30 min, filtered
to obtain the desired quinoxaline-2,3(1H,4H)-diones 2.
conducted in 2 wt% TPGS-750-M/H2 O under
nitrogen atmosphere, no 18O-labeled product 2a was
detected by GC-MS analysis. Taken together, the
incorporated oxygen atom of 2a originated from
(NH4)2S2O8.
Acknowledgements
We are grateful for financial support from the
Hunan Provincial Natural Science Foundation of
China (No. 2019JJ20008).
Scheme 4. Proposed Reaction Mechanism
Based on these above-mentioned experiment
results and previous literature reports,[1k,
a
15]
plausible mechanism is depicted in Scheme 4. At first,
the substrate 1 reacts with the in situ generated sulfate
radical anion to form a nitrogen-centred radical A.
Then, the radical A is attacked by water to generate
free-radical B, which coupled with sulfate radical
anion to afford 3-hydroxy-1-methylquinoxalin-2(1H)-
one (C) with the release of bisulfate anion. Finally,
compound C rapidly tautomerized to form the more
stable product 2.
References
[1] a) J. Dong, P. Liu, P. Sun, J. Org. Chem. 2015, 80,
2925; b) Y.-H. Sun, T.-Y. Sun, Y.-D. Wu, X. Zhang, Y.
Rao, Chem. Sci. 2016, 7, 2229; c) H.-T. Song, W. Ding,
Q.-Q. Zhou, J. Liu, L.-Q. Lu, W.-J. Xiao, J. Org. Chem.
2016, 81, 7250; d) S. Duan, Y. Xu, X. Zhang, X. Fan,
Chem. Commun. 2016, 52, 10529; e) X. Chen, W. Hao,
Y. Liu, Org. Biomol. Chem. 2017, 15, 3423; f) L.-Y. Xie,
Y. Duan, L.-H. Lu, Y.-J. Li, S. Peng, C. Wu, K.-J. Liu, Z.
Wang, W.-M. He, ACS Sustainable Chem. Eng. 2017, 5,
10407; g) Q. Wu, L. Pan, G. Du, C. Zhang, D. Wang,
Org. Chem. Front. 2018, 5, 2668; h) S. Mondal, A. Hajra,
J. Org. Chem. 2018, 83, 11392; i) N. Viswanadh, G. S.
Ghotekar, M. B. Thoke, R. Velayudham, A. C. Shaikh,
M. Karthikeyan, M. Muthukrishnan, Chem. Commun.
2018, 54, 2252; j) L. Yang, Z. Huang, G. Li, W. Zhang,
R. Cao, C. Wang, J. Xiao, D. Xue, Angew. Chem. Int. Ed.
2018, 57, 1968; k) W.-T. Wei, W.-M. Zhu, Q. Shao, W.-
H. Bao, W.-T. Chen, G.-P. Chen, Y.-J. Luo, H. Liang,
ACS Sustainable Chem. Eng. 2018, 6, 8029; l) Z. Zhang,
S. Wang, C. Hu, N. Ma, G. Zhang, Q. Liu, Tetrahedron
2018, 74, 7472; m) C. Hu, G. Hong, P. D. Nahide, Y. He,
C. Zhou, M. C. Kozlowski, L. Wang, Org. Chem. Front.
2019, 6, 3167; n) L.-H. Gao, X.-X. Meng, Y.-N. Wang,
S.-Z. Song, G.-P. Ge, Y. Dong, W.-T. Wei, Y.-Y. Liu, Q.
Li, Asian J. Org. Chem. 2019, 8, 348.
[2] a) B. Loev, J. H. Musser, R. E. Brown, H. Jones, R.
Kahen, F. C. Huang, A. Khandwala, P. Sonnino-
Goldman, M. J. Leibowitz, J. Med. Chem. 1985, 28, 363;
b) J. Dudash, Y. Zhang, J. B. Moore, R. Look, Y. Liang,
M. P. Beavers, B. R. Conway, P. J. Rybczynski, K. T.
Demarest, Bioorg. Med. Chem. Lett. 2005, 15, 4790; c)
D. Xie, Y. Wang, J. Xie, J. Lu, J. Cui, M. Zhang, L. Fu,
Y. Wang, Med. Chem. Res. 2014, 23, 4977; d) Q.-H. Xia,
W. Hu, C. Li, J.-F. Wu, L. Yang, X.-M. Han, Y.-M. Shen,
Z.-Y. Li, X. Li, Eur. J. Med. Chem. 2016, 124, 311; e) W.
Xie, Y. Wu, J. Zhang, Q. Mei, Y. Zhang, N. Zhu, R. Liu,
H. Zhang, Eur. J. Med. Chem. 2018, 145, 35; f) D.
Dewangan, K. Nakhate, A. Mishra, A. S. Thakur, H.
Rajak, J. Dwivedi, S. Sharma, S. Paliwal, J. Heterocycl.
Chem. 2019, 56, 566.
Conclusions
In summary, we have developed a simple and
efficient method for the clean preparation of
various N-functionalized quinoxaline-2,3(1H,4H)-
diones (25 examples, 82 - 94%) through direct
C(sp2)-H hydroxylation of quinoxalin-2(1H)-ones
in recyclable 2 wt% TPGS-750-M/H2O. The
(NH4)2S2O8 has a dual function (acts as oxidant
and oxygen source) in this transformation, thus
simplifying the reaction conditions and operation.
The TPGS-750-M/H2O solution can be easily
recycled up to 5 times by simple extraction
without the significant loss of its reaction
efficiency. Importantly, the target products were
exclusively produced and could be easily
collected through extraction and recrystallization.
In comparison with the traditional synthetic
protocols, the developed methodology has the
following advantages such as operational
simplicity and high scalability, mild condition,
readily availability of starting material, eco-
friendly and sustainable reaction medium,
chemical waste minimization which make this
present protocol highly attractive in organic
synthesis and pharmaceutical chemistry.
Experimental Section
General Procedure for the Synthesis of
Quinoxaline-2,3(1H,4H)-diones 2
[3] a) W. Wei, L. Wang, H. Yue, P. Bao, W. Liu, C. Hu, D.
Yang, H. Wang, ACS Sustainable Chem. Eng. 2018, 6,
17252; b) J. Yuan, J. Fu, J. Yin, Z. Dong, Y. Xiao, P.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901163
Advanced Synthesis & Catalysis
Mao, L. Qu, Org. Chem. Front. 2018, 5, 2820; c) J. Fu, J.
Abdukader, D. Lu, H. Zhang, C. Liu, Green Chem. 2017,
19, 1255; c) D.-Q. Dong, S.-H. Hao, H. Zhang, Z.-L.
Wang, Chin. Chem. Lett. 2017, 28, 1597; d) W. Wei, H.
Cui, D. Yang, H. Yue, C. He, Y. Zhang, H. Wang, Green
Chem. 2017, 19, 5608; e) B. Wang, L. Tang, L. Liu, Y.
Li, Y. Yang, Z. Wang, Green Chem. 2017, 19, 5794; f) G.
Yang, H. Du, J. Liu, Z. Zhou, X. Hu, Z. Zhang, Green
Chem. 2017, 19, 675; g) J. Yang, F. Mei, S. Fu, Y. Gu,
Green Chem. 2018, 20, 1367; h) L. Liu, Q. Sun, Z. Yan,
X. Liang, Z. Zha, Y. Yang, Z. Wang, Green Chem. 2018,
20, 3927; i) P. Bao, L. Wang, Q. Liu, D. Yang, H. Wang,
X. Zhao, H. Yue, W. Wei, Tetrahedron Lett. 2019, 60,
214; j) K. Sun, S.-J. Li, X.-L. Chen, Y. Liu, X.-Q. Huang,
D.-H. Wei, L.-B. Qu, Y.-F. Zhao, B. Yu, Chem. Commun.
2019, 55, 2861; k) Y. Zheng, M. Liu, G. Qiu, W. Xie, J.
Wu, Tetrahedron 2019, 75, 1663; l) D.-Q. Dong, W.-J.
Chen, Y. Yang, X. Gao, Z.-L. Wang, ChemistrySelect
2019, 4, 2480; m) J. Li, W. Tang, D. Ren, J. Xu, Z. Yang,
Green Chem. 2019, 21, 2088; n) Q. Sun, L. Liu, Y. Yang,
Z. Zha, Z. Wang, Chin. Chem. Lett. 2019, 30, 1379.
Yuan, Y. Zhang, Y. Xiao, P. Mao, X. Diao, L. Qu, Org.
Chem. Front. 2018, 5, 3382; d) L. Yang, P. Gao, X.-H.
Duan, Y.-R. Gu, L. N. Guo, Org. Lett. 2018, 20, 1034; e)
L. Hu, J. Yuan, J. Fu, T. Zhang, L. Gao, Y. Xiao, P. Mao,
L. Qu, Eur. J. Org. Chem. 2018, 2018, 4113; f) W. Xue,
Y. Su, K.-H. Wang, R. Zhang, Y. Feng, L. Cao, D.
Huang, Y. Hu, Org. Biomol. Chem. 2019, 17, 6654; g) W.
Zhang, Y.-L. Pan, C. Yang, L. Chen, X. Li, J.-P. Cheng,
J. Org. Chem. 2019, 84, 7786; h) W. Zhang, Y.-L. Pan,
C. Yang, X. Li, B. Wang, Org. Chem. Front. 2019, 6,
2765.
[4] a) J. Xu, H. Yang, H. Cai, H. Bao, W. Li, P. Zhang, Org.
Lett. 2019, 21, 4698; b) Q. Yang, X. Han, J. Zhao, H.-Y.
Zhang, Y. Zhang, J. Org. Chem. 2019, 84, 11417; c) X.-
F. Tang, J.-N. Zhao, Y.-F. Wu, S.-H. Feng, F. Yang, Z.-
Y. Yu, Q.-W. Meng, Adv. Synth. Catal. 2019,
10.1002/adsc.201900777.
[5] a) A. Carrër, J.-D. Brion, M. Alami, S. Messaoudi, Adv.
Synth. Catal. 2014, 356, 3821; b) X. Zhang, B. Xu, M.-H.
Xu, Org. Chem. Front. 2016, 3, 944; c) J.-W. Yuan, L.-R. [11] a) L.-Y. Xie, L.-L. Jiang, J.-X. Tan, Y. Wang, X.-Q.
Yang, Q.-Y. Yin, P. Mao, L.-B. Qu, RSC Adv. 2016, 6,
35936; d) J. Yuan, S. Liu, L. Qu, Adv. Synth. Catal. 2017,
359, 4197; e) K. Yin, R. Zhang, Org. Lett. 2017, 19,
1530; f) S. Paul, J. H. Ha, G. E. Park, Y. R. Lee, Adv.
Xu, B. Zhang, Z. Cao, W.-M. He, ACS Sustainable Chem.
Eng. 2019, 7, 14153; b) L.-Y. Xie, S. Peng, T.-G. Fan,
Y.-F. Liu, M. Sun, L.-L. Jiang, X.-X. Wang, Z. Cao, W.-
M. He, Sci. China Chem. 2019, 62, 460.
Synth. Catal. 2017, 359, 1515; g) K. Yin, R. Zhang, [12] D.-l. Kong, G.-p. Lu, M.-s. Wu, Z.-f. Shi, Q. Lin, ACS
Synlett 2018, 14, 597; h) S. Paul, H. D. Khanal, C. D. Sustainable Chem. Eng. 2017, 5, 3465.
Clinton, S. H. Kim, Y. R. Lee, Org. Chem. Front. 2019, [13] a) M.-j. Bu, G.-p. Lu, J. Jiang, C. Cai, Catal. Sci.
6, 231.
Technol. 2018, 8, 3728; b) Y. Yang, X. Meng, B. Zhu, Y.
Jia, X. Cao, S. Huang, Eur. J. Org. Chem. 2019, 2019,
1166; c) Q. Feng, D. Chen, M. Hong, F. Wang, S. Huang,
J. Org. Chem. 2018, 83, 7553; d) D. Chen, Q. Feng, Y.
Yang, X.-M. Cai, F. Wang, S. Huang, Chem. Sci. 2017, 8,
1601; e) D. Chen, Y. Zhang, X. Pan, F. Wang, S. Huang,
Adv. Synth. Catal. 2018, 360, 3607; f) C. M. Gabriel, N.
R. Lee, F. Bigorne, P. Klumphu, M. Parmentier, F.
Gallou, B. H. Lipshutz, Org. Lett. 2017, 19, 194; g) S.
Handa, E. D. Slack, B. H. Lipshutz, Angew. Chem. Int.
Ed. 2015, 54, 11994.
[6] a) X. Zeng, C. Liu, X. Wang, J. Zhang, X. Wang, Y. Hu,
Org. Biomol. Chem. 2017, 15, 8929; b) J.-W. Yuan, J.-H.
Fu, S.-N. Liu, Y.-M. Xiao, P. Mao, L.-B. Qu, Org.
Biomol. Chem. 2018, 16, 3203.
[7] a) Y. Li, M. Gao, L. Wang, X. Cui, Org. Biomol. Chem.
2016, 14, 8428; b) A. Gupta, M. S. Deshmukh, N. Jain, J.
Org. Chem. 2017, 82, 4784; c) W. Wei, L. Wang, P. Bao,
Y. Shao, H. Yue, D. Yang, X. Yang, X. Zhao, H. Wang,
Org. Lett. 2018, 20, 7125; d) Q. Yang, Y. Zhang, Q. Sun,
K. Shang, H.-Y. Zhang, J. Zhao, Adv. Synth. Catal. 2018,
360, 4509; e) Q. Yang, Z. Yang, Y. Tan, J. Zhao, Q. Sun, [14] a) P. Xie, J. Wang, Y. Liu, J. Fan, X. Wo, W. Fu, Z.
H.-Y. Zhang, Y. Zhang, Adv. Synth. Catal. 2019, 361,
1662; f) T. Guo, C.-C. Wang, X.-H. Fu, Y. Liu, P.-K.
Zhang, Org. Biomol. Chem. 2019, 17, 3333; g) K.-J. Li,
Sun, T.-P. Loh, Nat. Commun. 2018, 9, 1321; b) H.-K.
Sha, F. Liu, J. Lu, Z.-Q. Liu, W.-J. Hao, J.-L. Tang, S.-J.
Tu, B. Jiang, Green Chem. 2018, 20, 3476.
K. Xu, Y.-G. Liu, C.-C. Zeng, B.-G. Sun, Adv. Synth. [15] C. Chen, Y. Pan, H. Zhao, X. Xu, Z. Luo, L. Cao, S.
Catal. 2019, 361, 1033; h) J. Yuan, S. Liu, Y. Xiao, P.
Mao, L. Yang, L. Qu, Org. Biomol. Chem. 2019, 17,
876; i) J. Yuan, J. Zhu, J. Fu, L. Yang, Y. Xiao, P. Mao,
X. Du, L. Qu, Org. Chem. Front. 2019, 6, 925.
Xi, H. Li, L. Xu, Org. Lett. 2018, 20, 6799.
[8] a) L. Wang, Y. Zhang, F. Li, X. Hao, H.-Y. Zhang, J.
Zhao, Adv. Synth. Catal. 2018, 360, 3969; b) C. Jin, X.
Zhuang, B. Sun, D. Li, R. Zhu, Asian J. Org. Chem.
2019, 8, 1490; c) G. Hong, J. Yuan, J. Fu, G. Pan, Z.
Wang, L. Yang, Y. Xiao, P. Mao, X. Zhang, Org. Chem.
Front. 2019, 6, 1173; d) G.-Y. Dou, Y.-Y. Jiang, K. Xu,
C.-C. Zeng, Org. Chem. Front. 2019, 6, 2392; e) L.
Wang, H. Liu, F. Li, J. Zhao, H.-Y. Zhang, Y. Zhang,
Adv. Synth. Catal. 2019, 361, 2354.
[9] a) M. Gao, Y. Li, L. Xie, R. Chauvin, X. Cui, Chem.
Commun. 2016, 52, 2846; b) K.-J. Li, Y.-Y. Jiang, K. Xu,
C.-C. Zeng, B.-G. Sun, Green Chem. 2019, 21, 4412.
[10] a) G.-p. Lu, C. Cai, F. Chen, R.-l. Ye, B.-j. Zhou, ACS
Sustainable Chem. Eng. 2016, 4, 1804; b) Y. Sun, A.
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10.1002/adsc.201901163
Advanced Synthesis & Catalysis
UPDATES
Metal-Free C3 Hydroxylation of Quinoxalin-
2(1H)-ones in Water
Adv. Synth. Catal. Year, Volume, Page – Page
A clean protocol for the preparation of N-
functionalized
quinoxaline-2,3(1H,4H)-diones
through hydroxylation reaction in recyclable
TPGS-750-M/H2O was established.
6
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