Direct C-H arylation of quinoxalinones with aryl acylperoxides under catalyst-free condition

Article abstract of DOI:10.1016/j.tetlet.2020.152681

A simple and novel method for the direct C-H arylation of quinoxalinones with aryl acylperoxides has been developed. This reaction proceeded smoothly through a radical process under catalyst-free condition, giving the target products in moderate good yields. Such strategy provides a simple and green alternative for the synthesis of 3-arylquinoxalinones.

Full text of DOI:10.1016/j.tetlet.2020.152681

Journal Pre-proofs
Direct C-H arylation of quinoxalinones with aryl acylperoxides under cata‐
lyst-free condition
Bajin Chen, Shengpeng Wang, Jinxing Song, Xiaojun Wang, Bencheng Yu,
Xiaobo Yang
PII:
S0040-4039(20)31192-8
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.152681
TETL 152681
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
14 September 2020
12 November 2020
16 November 2020
Please cite this article as: Chen, B., Wang, S., Song, J., Wang, X., Yu, B., Yang, X., Direct C-H arylation of
quinoxalinones with aryl acylperoxides under catalyst-free condition, Tetrahedron Letters (2020), doi: https://
doi.org/10.1016/j.tetlet.2020.152681
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover
page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version
will undergo additional copyediting, typesetting and review before it is published in its final form, but we are
providing this version to give early visibility of the article. Please note that, during the production process, errors
may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2020 Published by Elsevier Ltd.

Tetrahedron Letters
Direct C-H arylation of quinoxalinones with aryl acylperoxides under catalyst-
free condition
Bajin Chen, Shengpeng Wang, Jinxing Song, Xiaojun Wang, Bencheng Yu, and Xiaobo Yang
Transfar Zhilian Co.,Ltd., Hangzhou, 311215, China. E-mail: 4437@etransfar.com
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple and novel method for the direct C-H arylation of quinoxalinones with aryl
acylperoxides has been developed. This reaction proceeded smoothly through a radical process
under catalyst-free condition, giving the target products in moderate good yields. Such strategy
provides a simple and green alternative for the synthesis of 3-arylquinoxalinones.
Available online
Keywords:
2020 Elsevier Ltd. All rights reserved.
Quinoxalinones
Aryl Acylperoxides
C-H Arylation
Green Chemistry
Introduction
arylhydrazines arylating reagents in the presence of strong
oxidant PhIO (Scheme 1b) [14]. The same year, Zhang reported
Quinoxalinone derivatives are widely distributed in natural
products, pharmaceuticals, bioactive compounds and function
materials [1]. In particular, 3-functional quinoxalinones are well
known for their superior biological and pharmacological effects
and outstanding chemical properties, such as aldose reductase
inhibitors [2], antitumor agents [3], stearoyl coenzyme A
desaturases [4] and semiconductors [5]. Therefore, the synthesis
of 3-functional quinoxalinones has received more extensive
attention. The traditional method to access 3-substituted
quinoxalinones is the cyclization of 1, 2-diaminobenzene with 1,
2-dicarbonyls and its derivatives [6]. However, such
transformations often require high temperature and harsh
reaction conditions. Direct C3-H functionalization of
quinoxalinones has subsequently emerged as a useful tool for
the construction of such compounds. So far, a series of cross-
coupling reactions including C-C coupling [7], C-O coupling [8], C-
N coupling [9], C-CF3 coupling [10], C-S coupling [11], C-P
coupling [12] have been realized using quinoxalinones and the
corresponding partners as starting materials. Among them, the
construction of C3-C bond of quinoxalinones with arylating
reagents is particularly important due to their widely application
in new drug research and discovery. In 2013, Alami and co-
workers realized C3-arylation of quinoxalinones using
arylboronic acids as arylating reagent (Scheme 1a) [13]. Despite
the wide range of substrates and good yields, notable palladium
catalyst was inevitably used, increasing synthetic cost. Besides,
Lee successfully synthesized 3-arylquinoxalinones using
direct C-H arylation of quinoxalinones with diaryliodonium salts
in the presence of Cs2CO3 under N2 atmosphere (Scheme 1c) [15].
Although various arylating reagents have been created in these
reactions for the construction of the construction of C3-C bond
of quinoxalinones, complicated preparation process still limited
their application.
Very recently, He and co-works reported a green and
environmentally friendly decarboxylative acylation of
quinoxalinones without any metal, photocatalyst or oxidant
[16]. Such transformation encouraged us to consider using aryl
carboxylic acid derivatives as starting materials to achieve C-H
Scheme 1. The C3-H functionalization of quinoxalinones.
 Corresponding author. E-mail: 4437@etransfar.com

2
Tetrahedron
Table 3. Substrate scope of acyl peroxide substrate. [a,b]
Table 1. Optimization of reaction conditions. [a,b]
Entry
Temp. ( oC )
Solvent
2a (x)
Yield (%)[b]
1
2
80
80
80
80
80
80
80
100
60
80
80
80
80
80
80
DCE
CH3CH2OH
MeCN
2
2
60
18
3
2
23
4
Acetone
THF
2
72
[a] Reaction conditions: 1 (0.2 mmol), 2a (1.5 equiv), acetone
5
2
32
(2.0 mL), 80 oC, 12 h. [b] Isolated yields.
6
H2O
2
trace
66
Herein, we demonstrated a strategy for the direct C-H arylation
of quinoxalinones using aryl acylperoxides as arylating reagent
under catalyst-free condition, providing a simple and green
alternative for the synthesis of 3-arylquinoxalinones. To the best
of our knowledge, such methodology has never been reported
yet.
7
Acetone/H2O = 1:1
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
2
8
2
71
9
2
55
10
11
12[c]
13[d]
14[e]
1.5
1
73
51
Results and discussion
1.5
1.5
1.5
1.5
42
In the beginning, we chose quinoxalinone (1a) and dibenzoyl
peroxide (BPO) (2a) as starting substrates to screen the reaction
condition. Target product (3a) was obtained in 60% yield when
the reaction was performed in DCE at 80 oC for 12 hours (Table 1,
entry 1). Subsequently, various solvents including CH3CH2OH,
MeCN, acetone, THF, H2O and mixture of acetone and H2O were
studied (Table 1, entries 2-7), and the product yield was
increased to 72% when acetone was used as solvent (Table 1,
entry 4). The influence of temperature on the reaction yield was
then investigated. The reaction yield was lowered no matter
that the temperature was increased (100 oC) or decreased (60 oC,
Table 1, entries 8-9). The amount of BPO was also affected the
reaction yield, and the highest yield can be obtiand when 1.5
equivalents of BPO was added into the reaction system (Table 1,
entries 10-11). Further studies on reaction time and atmosphere
could not enhance the product yield (Table 1, entries 12-15).
67
72
15[f]
70
[a]
Reaction conditions: 1a (0.2 mmol), 2a (x equiv.), solvent
[b]
[c]
(2.0 mL), 12 h.
Isolated yields.
The reaction was
performed for 6 h. [d] The reaction was performed for 24 h.[e]
[f]
The reaction was performed under N2 atmosphere. The
reaction was performed under O2 atmosphere.
arylation of quinoxalinones. Aryl acylperoxides are commonly
used as radical initiators in polymerization based on their
decomposition to aryl radical under the condition of heat or
visible light [17]. Besides, aryl acylperoxides could be easily
synthesized from the readily available aryl carboxylic acids [18].
Table 2. Substrate scope of quinoxalinones. [a,b]
Under the optimized conditions, the transformations were
further carried out to investigate the substrate scope of
quinoxalinones with BPO (Table 2). The quinoxalinones with N-
substituted alkyl groups such as methyl, ethyl, isopropyl,
cyclopropylmethyl gave the corresponding products (3a-d) in
63%-73% yields. It was worth mentioning that the alkenyl,
alkynyl and ester groups, which can be further modified, were
also compatible, providing the corresponding products (3e-h) in
59%-65% yields. The benzyl group with electron-donating or
electron-withdrawing groups can undergo the reaction smoothly,
[a] Reaction conditions: 1 (0.2 mmol), 2a (1.5 equiv), acetone
(2.0 mL), 80 °C, 12 h. [b] Isolated yields.
Scheme 2. Method application.

catalyst-free condition. This reaction realized a new approach of
synthesizing 3-arylquinoxalinones under simple and green
conditions, which improved the possibility of practical
application in the later stage.
Declaration of Competing Interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
Scheme 3. Control experiments.
Appendix A. Supplementary data
yielding the products (3i-l) in 58-66% yields. In addition, the
quinoxalinones bearing methyl, chloro and bromo on benzene
ring could also be transformed into the corresponding products
in moderate yields (3m-3p). From the above experimental
results, it can be seen that the reaction has good functional
group tolerance for quinoxalinones. Subsequently, the substrate
scope of aryl acyl peroxide derivatives was studied (Table 3). The
product yields were acceptable by employing aryl acyl peroxides
with electron-donating or electron-withdrawing groups (3q-w).
However, probably because of steric hindrance effect, the
corresponding product (3x) is not obtained when using
naphthalene containing acyl peroxides as arylating reagent.
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.catcom.xxx.
References
[1] (a) R. E. TenBrink, W. B. Im, V. H. Sethy, A. H. Tang, D. B. Carter, J. Med.
Chem., 37 (1994), 758-768;
(b) A. Carta, S. Piras, G. Loriga, G. Paglietti, Mini-Rev. Med. Chem., 6
(2006), 1179-1200;
(c) X. Li, K. Yang, W. Li, W. Xu, Drugs Future, 31 (2006), 979−989;
(d) L. Shi, J. Zhou, J. Wu, J. Cao, Y. Shen, H. Zhou, X. Li, Bioorg. Med.
Chem., 24 (2016), 1840-1852.
In order to prove the application value of such method, the
gram-scale synthesis of 3-arylquinoxalinones was carried out,
the target product was obtained in 58% yield (Scheme 2a). Then,
the antitumor drug 3y can be successfully synthesized in good
yield by the reaction of 1y with peroxide 2a [19], which implied
that such method has a great potential in the preparation of
some quinoxalone drug skeletons (Scheme 2b).
[2] X. Qin, X. Hao, H. Han, S. Zhu, Y. Yang, B. Wu, S. Hussain, S. Parveen, C.
Jing, B. Ma, C. Zhu, J. Med. Chem., 58 (2015), 1254-1267.
[3] S. A. M. El-Hawash, N. S. Habib, M. A. Kassem, Arch. Pharm., 339 (2006),
564-571.
[4] D. O. Koltun, E. Q. Parkhill, N. I. Vasilevich, A. I. Glushkov, T. M.
Zilbershtein, A. V. Ivanov, A. G. Cole, I. Henderson, N. A. Zautke, S. A.
Brunn, N. Mollova, K. Leung, J. W. Chisholm, J. Zablocki, Bioorg. Med.
Chem. Lett., 2009, 19, 2048-2052.
To find out the reasonable mechanism of this transformation,
the control experiments were carried out (Scheme 3). First of all,
we added 2.0 equivalents of 2,2,6,6-tetramethyl-1-
piperidinyloxy (TEMPO) to the reaction system, the target
product was not generated, which indicated that a free radical
mechanism was involved in the reaction. For further verify this
[5] J. Quinn, C. Guo, L. Ko, B. Sun, Y. He, Y. Li, RSC Adv., 6 (2016), 22043-22051.
[6] Z. Xu, A. Y. Shaw, J. Dietrich, A. P. Cappelli, G. Nichol, C. Hulme, Mol.
Diversity, 16 (2012), 73-79.
[7] (a) A. Carrër, J.-D. Brion, M. Alami, S. Messaoudi, Adv. Synth. Catal., 356
(2014), 3821;
(b) B. Ramesh, C. R. Reddy, G. R. Kumar, B. V. S. Reddy, Tetrahedron Lett.,
59 (2018), 628-631;
(c) L. Yang, P. Gao, X.-H. Duan, Y.-R. Gu, L.-N. Guo, Org. Lett., 20 (2018),
1034-1037;
(d) H. Zhang, J. Xu, M. Zhou, J. Zhao, P. Zhang, W. Li, Org. Biomol. Chem.,
17 (2019), 10201-10208;
(e) Z. Wei, S. Qi, Y. Xu, H. Liu, J. Wu, H. Li, C. Xia, G. Duan, Adv. Synth.
Catal., 361 (2019), 5490-5498.
Scheme 4. Plausible mechanism.
assumption, the DPE trapping reagent was used to capture free
radicals, and the corresponding product 4 was successfully
detected by HRMS.
[8] (a) J. Zhou, P. Zhou, T. Zhao, Q. Ren and J. Li, Adv. Synth. Catal., 361 (2019),
5371;
(b) J. Xu, H. Yang, H. Cai, H. Bao, W. Li, P. Zhang, Org. Lett., 21 (2019) ,
4698-4702.
Based on the above results and literatures [20], the plausible
mechanism of this reaction was stated in Scheme 4. Initially,
BPO (2a) was thermally decomposed to benzoyloxyl radicals (A).
Among them, a part of the benzoyloxyl radicals (A) were
converted into phenyl radicals (B) by releasing CO2. Then, the
phenyl radicals (B) attack the C3-position of quinoxalinones to
produce intermediates C. After a 1,2-H shift and benzoyloxyl
radical capture single electron and proton to produce the
product 3a with the generation of benzoic acid.
[9] (a) G. Abhishek, S. D. Mahesh, J. Nidhi, J. Org. Chem., 82 (2017), 4784-
4792;
(b) W. Wei, L. Wang, P. Bao, Y. Shao, H. Yue, D. Yang, X. Yang, X. Zhao, H.
Wang, Org. Lett., 20 (2018), 7125-7130.
[10] (a) G. Hong, J. Yuan, J. Fu, G. Pan, Z. Wang, L. Yang, Y. Xiao, P. Mao, X.
Zhang, Org. Chem. Front., 6 (2019), 1173-1182;
(b) L. Wang, Y. Zhang, F. Li, X. Hao, H.-Y. Zhang, J. Zhao, Adv. Synth. Catal.,
360 (2018), 3969-3977.
[11] (a) L.-Y. Xie, Y.-L. Chen, L. Qin, Y. Wen, J.-W. Xie, J.-X. Tan, Y. Huang, Z. Cao,
W.-M. He, Org. Chem. Front., 6 (2019), 3950-3955;
(b) Q.-H. Teng, Y. Yao, W.-X. Wei, H.-T. Tang, J.-R. Li, Y.-M. Pan, Green
Chem., 21 (2019), 6241-6245.
Conclusion
In conclusion, we have established a method for the direct C-H
arylation of quinoxalinones with aryl acylperoxides under

4
Tetrahedron
[12] (a) W.-P. Mai, J.-W. Yuan, J.-L. Zhu, Q.-Q. Li, L.-R. Yang, Y.-M. Xiao, P. Mao,
1001-1009.
L.-B. Qu, ChemistrySelect, 4 (2019), 11066-11070;
(b) K.-J. Li, Y.-Y. Jiang, K. Xu, C.-C. Zeng, B.-G. Sun, Green Chem., 21
(2019), 4412-4421.
[18] (a) N. Zhu, J. Zhao, H. Bao, Chem. Sci., 8 (2017), 2081-2085;
(b) X. Yao, X. Weng, K. Wang, H. Xiang, X. Zhou, Green Chem., 20 (2018),
2472-2476;
[13] A. Carrër, J.-D. Brion, S. Messaoudi, M. Alami, Org. Lett., 15 (2013), 5606-
5609.
(c) V. Botla, N. Pillia, C. Malapaka, Green Chem., 21 (2019), 1735-1742.
[19] J. Yuan, S. Liu, L. Qu, Adv. Synth. Catal., 359 (2017), 4197-4207.
[20] (a) X.-H. Yao, X. Weng, K.-X. Wang, H-F. Xiang, X.-G. Zhou, Green Chem.,
20 (2018), 2472-2476;
[14] S. Paul, J. H. Ha, G. E. Park, Y. R. Lee, Adv. Synth. Catal., 359 (2017), 1515-
1521.
[15] K. Yin, R.-H. Zhang, Org. Lett., 19 (2017), 1530-1533.
[16] L.-Y. Xie, Y.-S. Bai, X.-Q. Xu, X. Peng, H.-S. Tang, Y. Huang, Y.-W. Lin, Z. Cao,
W.-M. He, Green Chem., 22 (2020), 1720-1725.
(b) C. Jin, X. Zhang, B. Sun, Z.-Y. Yan, T.-W. Xu, Synlett, 30 (2019), 1585-
1591.
[17] A. R. H. Ali, N. Sébastien, M. Vincent, R. Jean, Polym. Chem., 11 (2020),
2. Characterization
of
the
products
4
3. References
10
4. Copies
11
of
NMR
Direct C-H arylation of quinoxalinones
with aryl acylperoxides under catalyst
-free condition
Bajin Chen* Shengpeng Wang, Jinxing Song,
Xiaojun Wang,
Bencheng Yu, and Xiaobo Yang
Transfar Zhilian Co., Ltd., Hangzhou, 311215,
China.
1. Experimental section
E-mail: 4437@etransfar.com
General Information
All the chemicals were obtained commercially and
used without any prior purification. All products
were isolated by short chromatography on a silica
gel (200-300 mesh) column using petroleum ether
(60-90°C) and ethyl acetate. 1H and 13C NMR
spectra were recorded on a Bruker Advance 500
spectrometer at ambient temperature with CDCl3 or
DMSO as solvent and tetramethylsilane (TMS) as
the internal standard. Melting points were
Supporting Information
Table of contents
determined on an X-5 Data microscopic melting
point apparatus. Analytical thin layer
chromatography (TLC) was performed on Merk
precoated TLC (silica gel 60 F254) plates.
Compounds for HRMS were analyzed by positive
mode electrospray ionization (ESI) using Agilent
6530 QTOF mass spectrometer.
1. Experimental section
2

General procedure for the synthesis of 3-
arylquinoxalinones 3
1 (0.2 mmol), 2 (0.3 mmol) and acetone (2 mL)
were added to a 15 mL pressure tube. The reaction
mixture was heated at 80 °C for 12 h. Then, the
mixture was cooled down to room temperature, and
quenched with ethyl acetate-sodium hydrogen
carbonate solution. The organic layer was dried
with anhydrous MgSO4 and distilled under reduced
pressure. The crude product was further purified by
silica gel column chromatography (PE/EA = 10:1)
to afford product 3.
(a): 1a (0.2 mmol), 5 (0.3 mmol) and acetone (2
mL) were added to a 15 mL pressure tube. The
reaction mixture was heated at 80 °C for 12 h.
Product 6 was barely generated.
(b): 7 (0.2 mmol), 2a (0.3 mmol) and acetone (2
mL) were added to a 15 mL pressure tube. The
reaction mixture was heated at 80 °C for 12 h.
Product 8 was barely generated.
General procedure for gram-scale
synthesis of product 3a
1a (10 mmol), 2a (15 mmol) and acetone (50 mL)
were added to a 200 mL round bottom flask. The
reaction mixture was heated at 80 °C for 12 h.
Then, the mixture was cooled down to room
temperature, and quenched with ethyl acetate-
sodium hydrogen carbonate solution. The organic
layer was dried with anhydrous MgSO4 and
distilled under reduced pressure. The crude product
was further purified by silica gel column
chromatography (PE/EA = 10:1) to afford product
3a.
The experimental results prove that the reaction
does not apply to alkyl acyl peroxides or is carried
out with N-unsubstituted quinoxalinones.
General procedure for control
experiments
(a): 1a (0.2 mmol), 2a (0.3 mmol), TEMPO (0.4
mmol) and acetone (2 mL) were added to a 15 mL
pressure tube. The reaction mixture was heated at
80 °C for 12 h. Then, the mixture was cooled down
to room temperature, and product 3aa was barely
detectable.
(b): 2a (0.2 mmol), DPE (0.4 mmol) and acetone (2
mL) were added to a 15 mL pressure tube. The
reaction mixture was heated at 80 °C for 12 h.
Then, the corresponding product 4 was successfully
detected by HRMS.
2. Characterization of the products
1-Methyl-3-phenylquinoxalin-2(1H)-one (3a)1
Reaction with alkyl acyl peroxides or N-
unsubstituted quinoxalinones
The product was obtained as yellow solid in 73%
yield. 1H NMR (500 MHz, CDCl3) δ 8.30 (dd, J =
6.6, 3.0 Hz, 2H), 7.94 (dd, J = 8.0, 1.0 Hz, 1H),
7.59 – 7.55 (m, 1H), 7.50 – 7.47 (m, 3H), 7.37 (t, J
= 7.6 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 3.77 (s,
3H).
1-Ethyl-3-phenylquinoxalin-2(1H)-one (3b)1

6
Tetrahedron
The product was obtained as yellow solid in 65%
yield. 1H NMR (500 MHz, CDCl3) δ 8.33 (m, 2H),
7.96 (d, J = 8.0 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H),
7.48 (d, J = 3.0 Hz, 3H), 7.36 (t, J = 7.6 Hz, 1H),
7.31 (d, J = 8.4 Hz, 1H), 5.99 (m, 1H), 5.29 (m,
1H), 5.22 (m, 1H), 4.98 (d, J = 3.9 Hz, 2H).
3-Phenyl-1-(prop-2-yn-1-yl)quinoxalin-2(1H)-
one (3f)1
The product was obtained as yellow solid in 71%
yield. 1H NMR (500 MHz, CDCl3) δ 8.34 – 8.29
(m, 2H), 7.97 (d, J = 7.8 Hz, 1H), 7.57 (t, J = 7.7
Hz, 1H), 7.49 (d, J = 3.2 Hz, 3H), 7.39 – 7.34 (m,
2H), 4.40 (q, J = 7.1 Hz, 2H), 1.43 (t, J = 7.1 Hz,
3H).
1-Isopropyl-3-phenylquinoxalin-2(1H)-one (3c)
The product was obtained as yellow solid in 64%
yield. 1H NMR (500 MHz, CDCl3) δ 8.36 – 8.30
(m, 2H), 7.96 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 7.8
Hz, 1H), 7.51 – 7.46 (m, 4H), 7.40 (t, J = 7.6 Hz,
1H), 5.12 (d, J = 1.3 Hz, 2H), 2.31 (d, J = 4.8 Hz,
1H).
The product was obtained as yellow liquid in 68%
yield. 1H NMR (500 MHz, CDCl3) δ 8.14 (d, J =
7.9 Hz, 2H), 8.07 (d, J = 8.2 Hz, 1H), 7.83 (d, J =
7.4 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.55 (t, J =
7.6 Hz, 1H), 7.53 – 7.47 (m, 3H), 5.70 – 5.63 (m,
1H), 1.48 (d, J = 6.2 Hz, 6H). 13C NMR (126 MHz,
CDCl3) δ 155.06 (s), 146.77 (s), 140.08 (s), 138.65
(s), 136.35 (s), 130.54 (s), 129.79 (s), 129.53 (s),
128.94 (s), 128.11 (s), 126.63 (s), 126.45 (s), 69.59
(s), 21.90 (s). HRMS (ESI+): Calculated for:
Ethyl 2-(2-oxo-3-phenylquinoxalin-1(2H)-
yl)acetate (3g)3
C17H16N2O [M+H]+ 265.1336, Found 265.1328.
The product was obtained as yellow solid in 59%
yield. 1H NMR (500 MHz, CDCl3) δ 8.36 – 8.30
(m, 2H), 7.96 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 7.1
Hz, 1H), 7.49 (dd, J = 8.5, 5.9 Hz, 3H), 7.36 (t, J =
7.6 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 5.08 (s, 2H),
4.26 (q, J = 7.1 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H).
1-(Cyclopropylmethyl)-3-phenylquinoxalin-
2(1H)-one (3d)2
Tert-butyl 2-(2-oxo-3-phenylquinoxalin-1(2H)-
yl)acetate (3h)4
The product was obtained as yellow solid in 63%
yield. 1H NMR (500 MHz, CDCl3) δ 8.33 – 8.27 (m,
2H), 7.97 (d, J = 7.9 Hz, 1H), 7.57 (t, J = 7.8 Hz,
1H), 7.48 (m, 4H), 7.36 (t, J = 7.6 Hz, 1H), 4.29 (d,
J = 7.0 Hz, 2H), 1.37 – 1.30 (m, 1H), 0.61 (t, J =
4.4 Hz, 2H), 0.57 (m, 2H).
1-Allyl-3-phenylquinoxalin-2(1H)-one (3e)1
The product was obtained as yellow solid in 61%
yield. 1H NMR (500 MHz, CDCl3) δ 8.33 – 8.28
(m, 2H), 7.95 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 7.8
Hz, 1H), 7.47 (d, J = 6.6 Hz, 3H), 7.35 (t, J = 7.6
Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 4.99 (s, 2H), 1.47
(s, 9H).

1-Benzyl-3-phenylquinoxalin-2(1H)-one (3i)2
CDCl3) δ 8.41 – 8.32 (m, 2H), 7.96 (d, J = 8.0 Hz,
1H), 7.49 (m, 3H), 7.45 (d, J = 7.2 Hz, 1H), 7.33 (t,
J = 7.6 Hz, 1H), 7.31 – 7.24 (m, 3H), 7.00 (t, J =
8.6 Hz, 2H), 5.51 (s, 2H). 13C NMR (126 MHz,
CDCl3) δ 162.25 (d, J = 246.4 Hz), 154.75 (s),
154.23 (s), 135.93 (s), 133.41 (s), 132.60 (s),
131.14 (d, J = 3.2 Hz), 130.73 (s), 130.52 (s),
130.37 (s), 129.65 (s), 128.89 (d, J = 8.2 Hz),
128.15 (s), 123.93 (s), 115.90 (d, J = 21.7 Hz),
114.12 (s), 45.49 (s). 19F NMR (471 MHz, CDCl3)
δ -114.34 (s). HRMS (ESI+): Calculated for:
C21H15FN2O [M+H]+ 331.1241, Found 331.1239.
The product was obtained as yellow solid in 66%
yield. 1H NMR (500 MHz, CDCl3) δ 8.40 – 8.36
(m, 2H), 7.96 (d, J = 8.0 Hz, 1H), 7.52 – 7.49 (m,
3H), 7.45 (t, J = 7.1 Hz, 1H), 7.35 – 7.27 (m, 7H),
5.58 (s, 2H).
1-(2,6-Dichlorobenzyl)-3-phenylquinoxalin-
2(1H)-one (3l)
1-(2-Fluorobenzyl)-3-phenylquinoxalin-2(1H)-
one (3j)
The product was obtained as yellow solid in 58%
yield. M. P. 167–168 oC. 1H NMR (500 MHz,
CDCl3) δ 8.32 (d, J = 4.3 Hz, 2H), 7.93 (m, 1H),
7.50 (d, J = 7.7 Hz, 3H), 7.43 – 7.37 (m, 1H), 7.31
(m, 3H), 7.19 (m, 2H), 5.91 (m, 2H). 13C NMR
(126 MHz, CDCl3) δ 155.38 (s), 153.98 (s), 136.12
(s), 135.51 (s), 133.54 (s), 132.47 (s), 131.08 (s),
130.66 (s), 130.38 (s), 130.03 (s), 129.53 (s),
129.48 (s), 129.36 (s), 128.14 (s), 123.66 (s),
114.25 (s), 42.26 (s). HRMS (ESI+): Calculated
for: C21H14Cl2N2O [M+H]+ 381.0556, Found
381.0550.
The product was obtained as yellow solid in 65%
yield. M. P. 140–141 oC. 1H NMR (500 MHz,
CDCl3) δ 8.37 (m, 2H), 7.96 (d, J = 8.0 Hz, 1H),
7.48 (m, 4H), 7.33 (t, J = 7.6 Hz, 1H), 7.27 (d, J =
8.5 Hz, 1H), 7.24 (m, 1H), 7.15 – 7.06 (m, 2H),
7.01 (t, J = 7.5 Hz, 1H), 5.62 (s, 2H). 13C NMR
(126 MHz, CDCl3) δ 160.40 (d, J = 245.8 Hz),
154.95 (s), 154.11 (s), 135.95 (s), 133.37 (s),
132.47 (s), 130.65 (s), 130.54 (s), 130.52 (s),
129.67 (s), 129.47 (d, J = 8.2 Hz), 128.60 (d, J =
3.5 Hz), 128.16 (s), 124.73 (d, J = 3.5 Hz), 123.99
(s), 122.45 (d, J = 13.9 Hz), 115.56 (d, J = 21.4
Hz), 113.99 (s), 39.58 (d, J = 5.3 Hz). 19F NMR
(471 MHz, CDCl3) δ -118.25 (s). HRMS (ESI+):
Calculated for: C21H15FN2O [M+H]+ 331.1241,
Found 331.1244.
1,6,7-Trimethyl-3-phenylquinoxalin-2(1H)-one
(3m)3
1-(4-Fluorobenzyl)-3-phenylquinoxalin-2(1H)-
one (3k)
The product was obtained as yellow solid in 60%
yield. H NMR (500 MHz, CDCl3) δ 8.29 (d, J =
1
7.7 Hz, 2H), 7.71 (s, 1H), 7.49 – 7.44 (m, 3H), 7.09
(s, 1H), 3.74 (s, 3H), 2.43 (s, 3H), 2.36 (s, 3H).
6,7-Dichloro-1-methyl-3-phenylquinoxalin-
2(1H)-one (3n)3
The product was obtained as yellow solid in 64%
yield. M. P. 109–110 oC. 1H NMR (500 MHz,

8
Tetrahedron
The product was obtained as yellow solid in 59%
yield. 1H NMR (500 MHz, CDCl3) δ 8.29 (d, J =
8.3 Hz, 2H), 7.99 (s, 1H), 7.48 (t, J = 7.9 Hz, 3H),
7.39 (s, 1H), 3.69 (s, 3H).
The product was obtained as yellow solid in 68%
yield. 1H NMR (500 MHz, CDCl3) δ 8.25 (d, J =
7.7 Hz, 2H), 7.93 (d, J = 7.8 Hz, 1H), 7.54 (t, J =
7.6 Hz, 1H), 7.37 – 7.33 (m, 1H), 7.30 (t, J = 7.9
Hz, 3H), 3.75 (s, 3H), 2.42 (s, 3H).
6-Bromo-1-methyl-3-phenylquinoxalin-2(1H)-
one (3o)3
3-(4-Fluorophenyl)-1-methylquinoxalin-2(1H)-
one (3s)3
The product was obtained as yellow solid in 51%
yield. 1H NMR (500 MHz, CDCl3) δ 8.33 – 8.27 (m,
2H), 7.77 (d, J = 8.4 Hz, 1H), 7.50 – 7.44 (m, 5H),
3.72 (s, 3H).
The product was obtained as yellow solid in 71%
yield. 1H NMR (500 MHz, CDCl3) δ 8.42 – 8.36
(m, 2H), 7.92 (d, J = 7.0 Hz, 1H), 7.57 (t, J = 7.8
Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.33 (d, J = 8.4
Hz, 1H), 7.15 (t, J = 8.7 Hz, 2H), 3.76 (s, 3H). 19F
NMR (471 MHz, CDCl3) δ -109.98 (s).
7-Bromo-1-methyl-3-phenylquinoxalin-2(1H)-
one (3p)3
3-(4-Chlorophenyl)-1-methylquinoxalin-2(1H)-
one (3t)3
The product was obtained as yellow solid in 55%
yield. 1H NMR (500 MHz, CDCl3) δ 8.31 (dd, J =
7.6, 2.1 Hz, 2H), 8.09 (d, J = 2.2 Hz, 1H), 7.64 (dd,
J = 8.9, 2.3 Hz, 1H), 7.49 (dd, J = 6.0, 4.7 Hz, 3H),
7.20 (d, J = 8.9 Hz, 1H), 3.74 (s, 3H).
The product was obtained as yellow solid in 70%
yield. 1H NMR (500 MHz, CDCl3) δ 8.34 (d, J =
8.6 Hz, 2H), 7.93 (m, 1H), 7.59 (t, J = 7.1 Hz, 1H),
7.45 (d, J = 8.6 Hz, 2H), 7.38 (t, J = 7.2 Hz, 1H),
7.34 (d, J = 8.4 Hz, 1H), 3.77 (s, 3H).
3-(3-Bromophenyl)-1-methylquinoxalin-2(1H)-
one (3q)3
3-(4-Bromophenyl)-1-methylquinoxalin-2(1H)-
one (3u)3
The product was obtained as yellow solid in 67%
yield. 1H NMR (500 MHz, CDCl3) δ 8.51 (t, J = 1.6
Hz, 1H), 8.33 (d, J = 7.9 Hz, 1H), 7.94 (d, J = 8.0
Hz, 1H), 7.59 (t, J = 8.2 Hz, 2H), 7.37 (m, 3H),
3.77 (s, 3H).
The product was obtained as yellow solid in 70%
yield. 1H NMR (500 MHz, CDCl3) δ 8.26 (d, J =
8.7 Hz, 2H), 7.92 (d, J = 8.0 Hz, 1H), 7.58 (m, 3H),
7.37 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H),
3.75 (s, 3H).
1-Methyl-3-(p-tolyl)quinoxalin-2(1H)-one (3r)3

[2] Y. S. Arthur, R. D. Christine, H. Christopher,
Synthesis, 45 (2013), 459–462.
[3] K. Yin, R. Zhang, Org. Lett., 19 (2017),
1530−1533.
1-Methyl-3-(4-
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(3v)3
[4] L. Wang, P. Bao, W. Liu, S. Liu, C. Hu, H.
Yue, D. Yang, W. Wei, J. Org. Chem., 38
(2018), 3189-3196.
[5] B. Ramesh, C. R. Reddy, G. R. Kumar, B. V. S.
Reddy, Tetrahedron Lett., 59 (2018), 628.
[6] J. Yuan, S. Liu, L. Qu, Adv. Synth. Catal., 359
(2017), 4197–4207.
The product was obtained as yellow solid in 68%
yield. 1H NMR (500 MHz, CDCl3) δ 8.46 (d, J =
8.2 Hz, 2H), 7.95 (d, J = 8.0 Hz, 1H), 7.72 (d, J =
8.2 Hz, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.39 (t, J =
7.6 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 3.77 (s, 3H).
19F NMR (471 MHz, CDCl3) δ -62.80 (s).
1-Methyl-3-(4-phenoxyphenyl)quinoxalin-2(1H)-
one (3w)5
4. Copies of NMR
The product was obtained as yellow solid in 62%
1
yield. H NMR (500 MHz, CDCl3) δ 8.38 (d, J =
8.8 Hz, 2H), 7.93 (d, J = 8.0 Hz, 1H), 7.55 (t, J =
7.8 Hz, 1H), 7.37 (m, 3H), 7.32 (d, J = 8.3 Hz, 1H),
7.15 (t, J = 7.4 Hz, 1H), 7.09 (d, J = 8.7 Hz, 4H),
3.76 (s, 3H).
N-(4-chlorophenyl)-2-(2-oxo-3-
phenylquinoxalin-1(2H)-yl)acetamide (3y)6
The product was obtained as yellow solid in 65%
yield. 1H NMR (500 MHz, DMSO) δ 10.65 (s, 1H),
8.29 – 8.26 (m, 2H), 7.94 (d, J = 7.9 Hz, 1H), 7.63
(dd, J = 8.0, 3.8 Hz, 3H), 7.58 (d, J = 7.8 Hz, 1H),
7.52 (dd, J = 7.1, 4.6 Hz, 3H), 7.43 (t, J = 7.5 Hz,
1H), 7.38 (d, J = 8.9 Hz, 2H), 5.22 (s, 2H).
3. References
[1] B. D. Nibedita, B. Mayurakhi, B. Gakul, RSC
Adv., 10 (2020), 3615–3624.

10
Tetrahedron

12
Tetrahedron

14
Tetrahedron

16
Tetrahedron

1. Catalyst-free arylation
2. Cheap and available arylating reagent
3. 24 examples with moderate-to-good yields
The authors declare that they have no known
competing financial interests or personal
relationships that could have appeared to influence
the work reported in this paper.