Ligand-free Pd(II)-catalyzed cyclization of α-chloroimino-N-arylamides to synthesis of quinoxalin-2(1H)-ones

Article abstract of DOI:10.1016/j.tetlet.2020.152556

A ligand-free Pd(II)-catalyzed synthesis of quinoxalin-2(1H)-ones has been developed. Pd(TFA)₂ can induce ethyl 2-(N-arylcarbamoyl)-2-chloroiminoacetates to undergo cyclization to afford quinoxalin-2(1H)-one products in high yields in the presence of Na₂CO₃. This catalytic system is also effective to convert α-aryl-α-chloroimino-N-arylamides to the corresponding quinoxalin-2(1H)-one products via tandem N-Cl cleavage and N-arylation in moderate yields. The reaction described herein constitutes simple and effective approach towards quinoxalin-2(1H)-one derivatives.

Full text of DOI:10.1016/j.tetlet.2020.152556

Journal Pre-proofs
Ligand-free Pd(II)-catalyzed Cyclization of α-Chloroimino-N-arylamides to
Synthesis of Quinoxalin-2(1H)-ones
Dianjun Li, Jinhui Yang, Xu Fan
PII:
S0040-4039(20)31049-2
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.152556
TETL 152556
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Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
29 July 2020
26 September 2020
9 October 2020
Please cite this article as: Li, D., Yang, J., Fan, X., Ligand-free Pd(II)-catalyzed Cyclization of α-Chloroimino-N-
arylamides to Synthesis of Quinoxalin-2(1H)-ones, Tetrahedron Letters (2020), doi: https://doi.org/10.1016/
j.tetlet.2020.152556
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Ligand-free Pd(II)-catalyzed Cyclization of
α-Chloroimino-N-arylamides to Synthesis
of Quinoxalin-2(1H)-ones
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Dianjun Li*, Jinhui Yang*, and Xu Fan
N
R3
O
O
R1
R3
N
Pd(TFA)2
Base
R3 = CO2Et, Aryl
R1
N
R2
R2 NCl

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Ligand-free Pd(II)-catalyzed Cyclization of α-Chloroimino-N-arylamides to Synthesis
of Quinoxalin-2(1H)-ones
Dianjun Lia,b  , Jinhui Yanga,b , and Xu Fan b
a,b State Key Laboratory of High-Efficiency Utilization of Coal and Green Chemical Engineering, School of Chemistry and Chemical Engineering, Ningxia
University, Yinchuan 750021, China
b School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021, China
———
ARTICLE INFO
ABSTRACT
 Corresponding author.
e-mail: nxlidj@126.com,
Article history:
A ligand-free Pd(II)-catalyzed synthesis of quinoxalin-2(1H)-ones has been developed.
Pd(TFA)2 can induce ethyl 2-(N-arylcarbamoyl)-2-chloroiminoacetates to undergo Cyclization
to afford quinoxalin-2(1H)-one products in high yields in the presence of Na2CO3. This catalytic
system is also effective to convert α-aryl-α-chloroimino-N-arylamides to the corresponding
quinoxalin-2(1H)-one products via tandem N-Cl cleavage and N-arylation in moderate yields.
The reaction described herein constitutes simple and effective approach towards quinoxalin-
2(1H)-one derivatives.
Received
Received in revised form
e-mail: lyjhmp@163.com
Accepted
 Corresponding author.
Available online
Keywords:
Quinoxalin-2(1H)-ones
Pd(II)-catalyzed
2-(N-arylcarbamoyl)-2-chloroiminoacetate
α-Aryl-α-chloroimino-N-arylamides
Cyclization
2009 Elsevier Ltd. All rights reserved.
Introduction
and Yu et al. [15] developed the cyclization of α-
(aminocarbonyl)iminyl radical which would be useful
As an important pharmacophore and useful heterocyclic
scaffold, quinoxalin-2(1H)-one derivatives have attracted
considerable attention due to their significant bioactive and
medicinal activities in the past decades [1-6]. Quinoxalin-2(1H)-
one derivatives exhibit wide pharmaceutical properties, including
anticancer [2], anti-HIV [3], anti-Toxoplasma [4], antimicrobial
[5] and protein kinase inhibitory [6]. Moreover, quinoxalin-
2(1H)-one derivatives are useful synthetic intermolecules which
could prepare for complex organic compounds [7].
intermediate towards quinoxalin-2(1H)-one derivatives under
AIBN-promoted or visible light-induced conditions, respectively
(Scheme 1e). Although these reactions would provide relatively
simple and straightforward means for the synthesis of quinoxalin-
2(1H)-ones, the reported procedures require hazardous reagents,
harsh conditions and suffer from competition from other
pathways [8,13-15]. Therefore, the development of more
convenient and efficient route towards quinoxalin-2(1H)-one
derivatives is still desirable. Herein, we demonstrate an efficient
ligand-free palladium-catalyzed transformation of α-chloroimino-
N-arylamides to synthesize quinoxalin-2(1H)-ones via
cyclization with expanded scope of substrates at C3 position on
the scaffold (Scheme 1f).
Several versatile methods have been developed for the
construction of quinoxalin-2(1H)-one. The traditional synthetic
route was based on the condensation of o-phenylenediamines
with α-ketone acids or with their related derivatives, such as α-
aldehyde acid, α-ketone acid ester or oxazolones [8] (Scheme
1a). During the past few years, transition metal-catalyzed intra-
and inter-molecular C-N bonds formation have been developed
as fundamental methods for preparation of quinoxalin-2(1H)-
ones [9-11]. One of the transition metal-catalyzed synthesis
approaches to quinoxalin-2(1H)-ones is Ugi multi-component
reaction followed by reductive cyclization [9] (Scheme 1b). More
elaborate approach that involves transition-metal-catalyzed intra-
and inter-molecular N-arylation have received considerable
attention [10] (Scheme 1c). Other strategies such as copper
catalyzed intramolecular oxidative coupling that starts from o-
indolyl-N,N-dimethylarylamines [11] and palladium catalyzed
oxidative carbonylation of C2 C(sp2)-H bond of 2-(1H-indol-1-
yl)anilines [12] have been reported (Scheme 1d). Recently, the
radical cyclization constitutes effective method for the synthesis
of quinoxalin-2(1H)-one. Spagnolo et al. [13] Zhang et al. [14]

2
Tetrahedron Letters
Previous work:
performed in DCE (1,2-dichloroethane) with palladium
N
R2
NH2
O
O
R2
X
trifluoroacetate (Pd(TFA)2, 0.2 equiv.) as catalyst and Cs2CO3
(2.0 equiv.) as base under argon atmosphere (Table 1, entry 1).
Encouraged by this result, we screened a series of inorganic base
(K2CO3, K3PO4, NaHCO3, Na2HPO4, Na2CO3) in DCE at 80 °C
oil bath under argon atmosphere, the desired product 2a was
received in 82% yield in the presence of Na2CO3, but other bases
were not as efficient as Na2CO3 (Table 1, entries 2-6). With TEA
(triethylamine) as base, 2a was produced in 53% yield (Table 1,
entry 7). Then we tried to reduce the amounts of Pd(TFA)2 (0.10
and 0.15 equiv.) and Na2CO3 (1.0 and 1.5 equiv.). However, the
yield was decreased when the amounts were reduced (Table 1,
entries 8-11). The reaction exhibited a large solvent effect: the
model material 1a was decomposed in toluene (Table 1, entry
12), the yield of 2a was significantly decreased in THF (Table 1,
entry 13), and DMF led to a slightly lower yield compared with
DCE (Table 1, entry 14). Air was found to have a small influence
on the reaction (Table 1, entry 15). Afterwards, the reaction was
carried out at different temperatures (Table 1, entries 16 and 17)
and the best yield (85%) was achieved at 100 °C oil bath (Table
1, entry 16). Replacing Pd(TFA)2 with other palladium catalysts,
such as Pd(OAc)2 and PdCl2(PPh3)2, resulted in a decrease in the
yields (Table 1, entries 18 and 19). Finally, the base was
necessary in this transformation and the yield was only 25% in
the absence of the Na2CO3 (Table 1, entry 20). In the condition
control experiment, in the absence of Pd(II) catalyst, only trace of
product was obtained (< 5%, Table 1, entry 21). When the
catalyst and base were removed, no reaction took place (Table 1,
entry 22).
heat
R1
R1
R1
a
+
or microwave
X = OH, OEt
N
H
O
NH2
N
R3
R2CHO
R3CO2H
R4NC
NH2
Cu(I)/ligand
R1
b
c
+
or microwave
N
O
X
X = I, N3
R2 CONHR4
X2 R2
N
R2
NHTs
CuI/1,10-phen
+
R1
X1
R1
N
R
O
O
NHR
R1
CO, Pd(TFA)2
( R2 = H)
Cu(II)/DTBP
( R2 = Me)
R1
O
N
R2
N
d
e
N
N
N
CO2Et
O
O
AIBN/Bu3SnH
or Ru(phen)32+ or NBS
R1
R1
R3
N
N
R2
R2 NCl
vis-light
R3 = H, allyl, CO2Et
This work:
N
R3
O
O
R1
R1
R3
Pd(TFA)2
f
N
N
R2
R2 NCl
R3 = CO2Et, Aryl
Scheme 1 Synthetic strategies of quinoxalin-2(1H)-ones
Results and Discussion
We chose 2-(N-arylcarbamoyl)-2-chloroiminoacetate 1a as the
model substrate and began to our investigation into the optimal
reaction conditions (Table 1). Initially, the target product 2a was
isolated in 40% yield when the cyclization of compound 1a was
Table 1. Optimization of reaction conditions.
N
CO2Et
O
O
Pd, base
solv., temp., atmosphere
CO2Et
N
N
Bn NCl
1a
Bn
2a[a,b]
Pd catalyst
(equiv)
Base
(equiv)
Temperature
Product
[Yield (%)]
Entry
Solvent
Atmosphere
(℃)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.1)
Pd(TFA)2(0.15)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(TFA)2(0.2)
Pd(OAc)2(0.2)
PdCl2(PPh3)2(0.2)
Pd(TFA)2(0.2)
----
Cs2CO3(2.0)
K2CO3(2.0)
K3PO4(2.0)
NaHCO3(2.0)
Na2HPO4(2.0)
Na2CO3(2.0)
TEA(2.0)
Na2CO3(2.0)
Na2CO3(2.0)
Na2CO3(1.0)
Na2CO3(1.5)
Na2CO3(2.0)
Na2CO3(2.0)
Na2CO3(2.0)
Na2CO3(2.0)
Na2CO3(2.0)
Na2CO3(2.0)
Na2CO3(2.0)
Na2CO3(2.0)
----
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
PhCH3
THF
DMF
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
100
120
100
100
100
100
100
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Air
Ar
Ar
Ar
Ar
Ar
Ar
Ar
40
45
65
80
75
82
53
55
69
72
75
----[c]
55
78
74
85
74
40
----[d]
25
Na2CO3(2.0)
----
trace[e]
N.R.[f]
----
[a] The reaction was performed on a 0.2 mmol sacle.
[b] Isolated yield.
[c] The starting material was decomposed.
[d] 70% starting material recovered after 36 hrs.
[e]
2a was trace and 75% starting material recovered.
No reaction took place.
[f]
Pd(TFA)2: palladium(II) trifluoroacetate; DCE: 1,2-dichloroethane; TEA : triethylamine
With the previous optimized conditions, we then investigated
the substrate scope of the current protocol, and the results were
illustrated in Scheme 2. As shown, substrates bearing a
substituent at the para-position of the N-phenyl ring was first
investigated, N-chloroimines compounds 1 with both electron-
donating groups (Me, 1b; MeO, 1c; and Ph, 1d) and electron-
withdrawing groups (F, 1e; Cl, 1f; Br, 1g; I, 1h; and CF3, 1i)
underwent smooth transformation and delivered the
corresponding products (2b–2i) in good to excellent yields and
showed the potential application in further chemical
transformations (2e–2i). For meta-substitution 1j-1n, irrespective
of its electronic character, could be tolerated in general and

3
exerted a moderate influence to the regioisomers, with a tendency
that the sterically less hindered one was the major product, which
was different from our previous studies [15,16]. Unfortunately,
ortho-substitution 1s was incompetent to be converted to the
expected product 2s under the standard conditions. By changing
the starting material 1o-1r and 1t, the reaction demonstrated
good compatibility and furnished the products 2 in good yields.
N
N
CO2t-Bu
N
N
CO2Et
O
Pd(TFA)2 (0.2 equiv)
Na2CO3 (2.0 equiv)
DCE, Ar, 100oC
O
O
R1
Pd(TFA)2 (0.2 equiv)
Na2CO3 (2.0 equiv)
DCE, Ar, 100oC, 9h
57%
R1
CO2t-Bu
CO2Et
N
O
N
R2 NCl
1
R2
Bn NCl
Bn
2v
2[a,b]
1v
R1
Scheme 4. The reactions of 1v under standard conditions.
R1
N
CO2Et
N
CO2Et
N
CO2Et
O
We next examined the applicability of this Pd(TFA)2-catalyzed
system to the reaction of α-aryl-α-chloroimine-N-arylamides 3,
and the results were summarized in Scheme 5. Unfortunately, our
initial experiment showed trace of desired cyclization compound
4a [17] was obtained and 3a was decomposed under previous
optimal conditions. We assumed that for the reaction of 3 to take
place, the α-position of 3 had to be an electron-withdrawing
group. It was likely that electron-withdrawing groups were more
beneficial for palladium coordinating with the nitrogen atom to
form electrophilic intermediates [16a]. Indeed, compound 3b that
contained CF3 group at the para-position of α-phenyl ring was
converted smoothly to the quinoxalin-2(1H)-one product 4b in
moderate yield (50%), the yield was slightly higher (56%) under
air atmosphere. However, a mixture was obtained and the yield
of 4b was decreased when the reaction was performed under neat
oxygen atmosphere (Scheme 5).
+
N
O
R1
N
O
N
Bn
2a
2b
2c
2d
2e
2f
Bn
Bn
R1 = H
R1 = Me
R1 = OMe
R1 = Ph
R1 = F
%
86
%
99
%
48
%
49
%
74
%
80
%
85
%
65
%
74
R1 = Me
R1 = OMe
R1 = Cl
R1 = Br
R1 = CF3
90% (50:50)
94% (51:49)
87% (57:43)
82% (56:44)
79% (81:19)
2j-1
2k-1
2l-1
2j-2
2k-2
2l-2
2m-1
2n-1
2m-2
2n-2
R1 = Cl
R1 = Br
R1 = I
2g
2h
2i
Me
N
N
CO2Et
O
R1 = CF3
N
CO2Et
O
R1
N
CO2Et
N
R2
N
O
Bn
R2 = Me
R2 = Et
R2 = Ph
86%
85%
96%
2p
R1 = 2-Me
R1 = 3-Me
--[c]
2s
2t
2q
2r
84%
2o
54%
[a] Reaction conditions: A mixture of 1 (0.5 mmol), Pd(TFA)2 (0.1 mmol) and
Na2CO3 (1.0 mmol) in 5 mL of anhydrous DCE was stirred at 100 oC.
[b] Isolated yield.
[c] The substrate was decomposed.
N
O
Pd(TFA)2 (0.2 equiv)
R
Na2CO3 (2.0 equiv)
DCE, 100oC
N
Bn NCl
R
Scheme 2. Pd(TFA)2-catalyzed cyclization of 2-(N-arylcarbamoyl)-2-
chloroiminoacetates 1.
N
O
Bn
3a[a]
3b[a]
4a
4b
R = H,
R= p-CF3,
, trace[b]/trace[c]
, 51%[b]/56%[c]/50%[d]
To further explore the effect of the electronic nature of the
substrate, this method was then applied to compound 1u and the
result was summarized in Scheme 3. As shown, the substrate 1u
could afford two regioisomers with the sterically hindered one
2u-2 being more favored and indicate that Pd(II)-catalyzed
intramediate was electrophilic and favored to attack on the more
electron-rich position of N-aryl ring.
[a] The reactions were carried out in 0.2 mmol scale in DCE.
[b] Isolated yield under Argon atmosphere.
[c] Isolated yield under Air atmosphere.
[d] Isolated yield under oxygen atmosphere
Scheme 5. The reactions of 3a and 3b under standard and
modified conditions.
Bn
N
O
We investigated the substrate scope of the modified conditions,
and the results are illustrated in Table 2. First, 3b–3h were tested
under air atmosphere, the reactions underwent smoothly and gave
corresponding products 4b–4h with moderate yields (Table 2,
entries 2-7). In the case of 3i, except for desired compound 4i,
azaspirocyclohexadienone 5i was obtained in 31% yield (Table 2,
entry 8). The substrates-bearing methyl (3j) and bromine (3k) on
the meta-position of N-phenyl ring also proceeded with moderate
yields and two regioisomers were obtained (4j and 4k), with the
sterically more hindered one 4k being the major product (Table
2, entry 10). Notably, two expected products were isolated in the
reaction of 3l, 4l-1 was favored due to the electronic nature of the
substituent (Table 2, entry 11), which was in accordance with the
1u (Scheme 3).
N
CO2Et
O
O
Pd(TFA)2 (0.2 equiv)
Na2CO3 (2.0 equiv)
DCE, Ar, 100oC
CO2Et
+
N
CO2Et
N
N
Bn NCl
1u
Bn
2u-1
2u-2
(30%)
(13%)
Scheme 3. Reaction showing effect of the electronic nature of 1u.
The optimal conditions with Pd(TFA)2 as catalyst was then
applied to tert-butyl group substituted N-chloroimines compound
1v, the reaction also worked well and provided the cyclization
product 2v in 57% yield (Scheme 4). The –CO2t-Bu group would
be easy to hydrolysis and decarboxylation, and 2v could be
further functionalization at C3 position on the scaffold.
Table 2 Pd(TFA)2-catalyzed cyclization of 3 under air atmosphere.
O
N
N
Pd(TFA)2 (0.2 equiv)
Na2CO3 (2.0 equiv)
DCE, Air, 100oC
R1
R3
R3
R1
N
O
R2 NCl
R2
4[a,b]
3
Entry
1
2
3
4
3
R1
H
H
H
H
H
H
p-F
p-MeO
R2
Bn
Bn
Bn
Bn
Et
Ph
Bn
Bn
R3
p-CF3
p-Cl
p-NO2
m-CF3
p-CF3
p-CF3
p-CF3
p-CF3
Product/Yield (%)
4b/56
3b
3c
3d
3e
3f
3g
3h
3i
4c/48
4d/39
4e/50
4f/56
4g/47
4h/59
4i/31+5i/37
5
6
7
8[c]

4
Tetrahedron Letters
9
10
11
3j
3k
3l
m-Me
m-Br
p-Br
Bn
Bn
Ph
p-CF3
p-CF3
p-CF3
4j-1+4j-2/65[d]
4k-1+4k-2(56:44)/57
4l-1+4l-2(62:38)/50
Br
O
R1
N
N
Ph-p-CF3
Ph-p-CF3
Ph-p-CF3
N
Ph-p-CF3
+
O
N
Br
N
O
N
O
Bn
Bn
Bn
O
R1 = H, R2 = Br,
R1 = Br, R2 = H,
4l-1
4l-2
5i
4k-1
4k-2
R2
[a] The reaction was performed on a 0.2 mmol sacle.
[b] Isolated yield.
[c] Besides 4i, 5i was obtained in 37% yield.
[d] The relative configuration is undetermined.
Based on the previous results, this transformation could be
hypothesized following two routes which were depicted in
Scheme 6: (1) Friedel-Crafts cyclization (Hypothesis 1, Scheme
6) [16, 18]; (2) the oxidative addition and reduction elimination
pathways (Hypothesis 2, Scheme 6) [19]. The formation of 2 and
4 is in accordance with the mechanism of Friedel-Crafts
cyclization [16, 18] (Scheme 6), therefore, the Friedel-Crafts type
mechanism was proposed (Hypothesis 1, Scheme 6). Apart from
this mechanism, it is also possible the transformation proceeded
through oxidative addition and reduction elimination pathways.
At the present stage, we cannot distinguish between these two
mechanisms, but we think that oxidative addition and reduction
elimination mechanism is less likely. For Hypothesis 2 (Scheme
6), the reactions would afford the products via Pd-catalyzed
seven-member-cyclic intermediates which were less stable in
principle and unfavorable to the transformation.
Conclusion
In conclusion, we have developed a novel Pd(II)-promoted N-
Cl cleavage/N-arylation route to synthesis quinoxalin-2(1H)-ones
via cyclization process. The reaction proceeds with good
functional group compatibility and broad substrate scope.
Meanwhile, the present protocol also provides a method to not
only construct C-N bond efficiently but also to synthesize the
quinoxalin-2(1H)-ones in good to excellent yields under oxidant
and ligand-free conditions.
Supplementary Material
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2020.XXXXXX.
Acknowledgments
Hypothesis 1:
Cl
This work was supported by the National Natural Science
Foundation of China (Grant no. 21861031), Key Research and
Development project of Ningxia (2019BDE03002), the Ningxia
Cl
N
Pd(II)
N
R3
O
R3
O
N
R3
O
-Cl-, -Pd(II)
-H+
Pd(II)
R1
R1
R1
N
R2
N
R2
Natural Science Foundation of China (2018AAC03023
，
N
R2
NGY2018005, and NGY2018059), and the National First-rate
Discipline Construction Project of Ningxia (Chemical Engineering
and Technology) (NXYLXK2017A04).
or
R3 = CO2Et, Ar
1
3
2
4
or
Cl
N
R3
O
R1
Hypothesis 2:
References
N
R2
or
2
4
product or
Pd(II)
[1] (a) R. Liu, Z. Huang, M. G. Murray, X. Guo, G. Liu, J. Med. Chem. 2011,
54, 5747–5768; (b) L. Zhang, R. Qiu, X. Xue, Y. Pan, C. Xu, H. Li, L.
Xu, Adv. Synth. Catal. 2015, 357, 3529–3537; (c) M. Imanishi, M.
Sonoda, H. Miyazato, K. Sugimoto, M. Akagawa, S. Tanimori, ACS
Omega 2017, 2, 1875−1885;
[2] (a) S. A. Galal, S. H. M. Khairat, F. A. F. Ragab, A. S. Abdelsamie, M.
M. Ali, S. M. Soliman, J. Mortier, G. Wolber, H. El Diwani, Eur. J. Med.
Chem. 2014, 86, 122–132; (b) A. M. S. E. Newahie, N. S. M. Ismail, D.
A. A. E. Ella, K. A. M. Abouzid, Arch. Pharm. Chem. Life Sci. 2016, 349,
309–326;
1
3
TFA
TFA
Cl
Pd(TFA)2
Pd
N
R3
N
R3
R1
R1
N
R2
O
N
R2
O
1
3
or
1
3
or
HCl
[3] Y.-M. Huang, N. S. Alharbi, B. Sun, C. S. Shantharam, K. P. Rakesh, H.-
L. Qin, Eur. J. Med. Chem. 2019, 181, 111566;
[4] Y. Deng, T. Wu, S.-Q. Zhai, C.-H. Li, Eur. J. Med. Chem. 2019, 183,
111711;
Scheme 6. The plausible mechanisms for the transformation of 1
and 3.
It is interesting to see the reactions of 1j–1n and 3k, the former
gave two regioisomers 2j–2n, of which the sterically less
hindered products 2j-1–2n-1 were the major products due to the
steric effect (Figure 1, structures I and II). However, for the
latter, the sterically hindered 4k-1 was the major product (Table
2, entry 10). This difference was possibly due to the favorable
interaction formed between the substituent bromine and the
palladium at the transition state (Figure 1, structure III and IV).
Moreover, the oxygen (air) had a slightly influence on the
transformation (Table 1, entries 6 and 15; Scheme 5).
[5] D. A. E. Issa, N. S. Habib, A. E. Abdel, A. E. Abdel Wahab,
MedChemComm, 2015, 6, 202–211;
[6] M. Weïwer, J. Spoonamore, J. Wei, B. Guichard, N. T. Ross, K. Masson,
W. Silkworth, S. Dandapani, M. Palmer, C. A. Scherer, A. M. Stern, S. L.
Schreiber, B. Munoz, ACS Med. Chem. Lett. 2012, 3, 1034–1038;
[7] For recent examples, see: (a) W. Wei, L. Wang, P. Bao, Y. Shao, H. Yue,
D. Yang, X. Yang, X. Zhao, H. Wang, Org. Lett. 2018, 20, 7125−7130;
(b) S. Toonchue, L. Sumunnee, K. Phomphrai, S. Yotphan, Org. Chem.
Front. 2018, 5, 1928–1932; (c) L. Wang, Y. Zhang, F. Li, X. Hao, H.-Y.
Zhang, J. Zhao, Adv. Synth. Catal. 2018, 360, 3969–3977; (d) J. Xu, H.
Yang, H. Cai, H. Bao, W. Li, P. Zhang, Org. Lett. 2019, 21, 4698−4702;
(e) F. Lian, K. Xu, W. Meng, H. Zhang, Z. Tana, C. Zeng, Chem.
Commun. 2019, 55, 14685–14688; (f) L. Wang, H. Liu, F. Li, J. Zhao, H.-
Y. Zhang, Y. Zhang, Adv. Synth. Catal. 2019, 361, 2354–2359; (g) Z.
Wei, S. Qi, Y. Xu, H. Liu, J. Wu, H. Li, C. Xia, G. Duan, Adv. Synth.
Catal. 2019, 361, 5490–5498; (h) Q. Ke, G. Yan, J. Yu, X. Wu, Org.
Biomol. Chem. 2019, 17, 5863–5881;
Cl
R1 Pd(II)
N
Cl
Br Pd(II)
N
Cl
Cl
Pd(II)
N
Pd(II)
N
CO2Et
O
PH-p-CF3
Br
Ph-p-CF3
CO2Et
O
R1
N
N
N
O
N
O
Bn
Bn
Bn
Bn
[8] (a) G. A. Eller, B. Datterl, W. Holzer, J. Heterocycl. Chem. 2007, 44,
1139–1143; (b) J. Gris, R. Glisoni, L. Fabian, B. Fernández, A. G.
Moglioni, Tetrahedron Lett. 2008, 49, 1053–1056; (c) S. Gräßle, S.
Vanderheiden, P. Hodapp, B. Bulat, M. Nieger, N. Jung, S. Bräse, Org.
Lett. 2016, 18, 3598–3601;
I
II
III
IV
, favored
, favored
Figure 1. Tentative explanation for the regioselectivity of 2j–2n
and 4k.
[9] (a) S. Balalaie, M. Bararjanian, S. Hosseinzadeh, F. Rominger, H. Reza
Bijanzadeh, E. Wolf, Tetrahedron 2011, 67, 7294–7300; (b) Z. Xu, G.
Martinez-Ariza, A. P. Cappelli, S. A. Roberts, C. Hulme, J. Org. Chem.

5
2015, 80, 9007–9015; (c) Y.-M. Yan, Y. Gao, M.-W. Ding, Tetrahedron
2016, 72, 5548–5557;
M. Okada, R. Tanaka, T. Kimachi, Org. Lett. 2011, 13, 6280–6283; (c)
H. Ma, D. Li, W. Yu, Org. Lett. 2016, 18, 868−871; (d) H. Ma, X.
Zhang, L. Chen, W. Yu, J. Org. Chem. 2017, 82, 11841−11847;
[10] For selective examples, see: (a) D. Chen, W. Bao, Adv. Synth. Catal.
2010, 352, 955–960; (b) X. Luo, E. Chenard, P. Martens, Y.-X. Cheng,
M. J. Tomaszewski, Org. Lett. 2010, 12, 3574–3577; (c) V. A. Vaillard,
R. A. Rossi, S. E. Martín, Org. Biomol. Chem. 2011, 9, 4927–4935; (d)
J. Areephong, B. Huo, I. I. Mbaezue, K. E. O. Ylijoki, Tetrahedron Lett.
2016, 57, 3124–3126;
[11] A. Gogoi, P. Sau, W. Ali, S. Guin, B. K. Patel, Eur. J. Org. Chem. 2016,
1449–1453;
[12] S. Sankararaman, A. Chandrasekhar, Org. Biomol. Chem. 2020, 18,
1612–1622;
[18] (a) M. Bandini, A. Melloni, A. Umani-Ronchi, Angew. Chem. Int. Ed.
2004, 43, 550–556; (b) M. Yokota, D. Fujita, J. Ichikawa, Org. Lett.
2007, 9, 4639–4642; (c) T. Nemoto, Y. Ishige, M. Yoshida, Y. Kohno,
M. Kanematsu, Y. Hamada, Org. Lett. 2010, 12, 5020–5023; (d) D. N.
Mai, B. R. Rosen, J. P. Wolfe, Org. Lett. 2011, 13, 2932–2935; (e) Y.
Suzuki, T. Nemoto, K. Kakugawa, A. Hamajima, Y. Hamada, Org. Lett.
2012, 14, 2350–2353; (d) M. Yoshida, T. Nemoto, Z. Zhao, Y. Ishige, Y.
Hamada, Tetrahedron: Asymmetry 2012, 23, 859–866;
[19] (a) X. Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu, Angew. Chem. Int. Ed.
2009, 48, 5094–5115; (b) H. Jiang, W. Wu, B. Nie, Y. Zhang, J. Zhang,
Org. Chem. Front. 2020, doi: 10.1039/D0QO00510J; (c) Y. Liu, A. M.
Kaiser, B. A. Arndtsen, Chem. Sci. 2020, 11, 8610–8616; (d) K. Yang,
M. Song, H. Liu, H. Ge, Chem. Sci. 2020, doi: 10.1039/D0SC03052J.
[13] G. Bencivenni, T. Lanza, R. Leardini, M. Minozzi, D. Nanni, P.
Spagnolo, G. Zanardi, J. Org. Chem. 2008, 73, 4721–4724;
[14] Z.-S. Li, W.-X. Wang, J.-D. Yang, Y.-W. Wu, W. Zhang, Org. Lett.
2013, 15, 3820–3823;
[15] (a) R.-L. Guo, X.-Q. Zhu, X.-L. Zhang, Y.-Q. Wang, Chem. Commun.
2020, 56, 8976–8979; (b) D. Li, T. Yang, H. Su, W. Yu, Adv. Synth.
Catal. 2015, 357, 2529–2539; (c) D. Li, H. Ma, W. Yu, Adv. Synth.
Catal. 2015, 357, 3696–3702;
[16] (a) D. Li, H. Ma, W. Yu, Tetrahedron 2016, 72, 846–852; (b) D. Li, W.
Yu, Adv. Synth. Catal. 2013, 355, 3708–3714;
[17] (a) X. Luo, E. Chenard, P. Martens, Y.-X. Cheng, M. J. Tomaszewski,
Org. Lett. 2010, 12, 3574–3577; (b) Y. Kobayashi, M. Kuroda, N. Toba,
3-7
7-19
19
Spectroscopic data for the substrates 3
Ligand-free Pd(II)-catalyzed
Cyclization of α-Chloroimino-N-
arylamides to Synthesis of Quinoxalin-
2(1H)-ones
Spectroscopic data for the products 2 and
4
References
Copies of 1H NMR and 13C NMR spectra
of the substrates 3
Dianjun Li a,b  , Jinhui Yang a,b , and Xu
20-29
Fan b
a,b State Key Laboratory of High-Efficiency
Utilization of Coal and Green Chemical
Engineering, School of Chemistry and Chemical
Engineering, Ningxia University, Yinchuan
750021, China
Copies of 1H NMR and 13C NMR spectra
of the products
30-70
b School of Chemistry and Chemical Engineering,
Ningxia University, Yinchuan 750021, China
Email:nxlidj@126.com; lyjhmp@163.com
General methods
The 1H NMR and 13C NMR spectra were recorded
on a Bruker AM-400 MHz spectrometer with
CDCl3. The chemical shifts in 1H NMR and 13C
NMR spectra were determined with Si(CH3)4 as the
internal standard (δ = 0.00, 77.00 ppm). The high
resolution mass spectra (HRMS) were measured on
a Bruker micrOTOF QII by ESI. The EI-MS
spectra were measured on an HP 5988A
Supporting Imformation
Contents
Page
General methods
2
2
3
3
General procedure for the synthesis of 3
General procedure for the reactions of 1
General procedure for the reactions of 3
———
spectrometer by direct inlet at 70 eV. Melting
points were measured on an XT-4 melting point
apparatus and were uncorrected. Flash column
chromatography was carried out on silica gel (200-
 Corresponding author.
e-mail: nxlidj@126.com,
 Corresponding author.
e-mail: lyjhmp@163.com

6
Tetrahedron
N
N
CO2Et
O
300 mesh). Pd(TFA)2 was purchased from
Pd(TFA)2 (0.2 equiv)
Na2CO3 (2.0 equiv)
DCE, Ar, 100oC
O
R1
R1
CO2Et
Aldrich. 1,2-Dichloroethane (DCE) was distilled
over P2O5 under argon atmosphere before use.
N
R2 NCl
R2
2
1
General procedure for the synthesis of 3
To a 35 mL tube equipped with a magnetic stirring
bar were added 1 (0.5 mmol, 1.0 equiv.), palladium
trifluroacatate (Pd(TFA)2, 35 mg, 0.2 equiv.),
Na2CO3 (108 mg, 2.0 equiv.), and 1,2-
The ethyl 3-arylamino-2-chloroimino-3-
oxopropanoate were prepared according to the
previous literature methods.[1]
Preparation of compound 3[1,2]
dichloroethane (DCE, 5 mL). The tube was sealed
O
O
O
R1
t-BuOCl
CH2Cl2, 0 oCrt
R1
R1
K3PO4
R3
N
R2
N
N
DMF, 80oC,4h
R3
R3
and stirred in an oil bath at 100 °C under an argon
R2 NH
R2 N3
N
Cl
3
II
I
atmosphere. After the reaction was completed as
indicated by TLC, the reaction mixture was poured
into a saturated aqueous NH4Cl solution (15 mL),
and was extracted with ethyl acetate (3×10 mL).
The combined organic layers were washed with
brine (30 mL) and dried with anhydrous Na2SO4.
The solvent was removed under reduced pressure,
and the residual was treated with silica gel
chromatography to give product.
To a DMF solution of the starting materials I (8
mmol), which was prepared according to the
previous reported methods [1], was added K3PO4
(5.10 g, 24 mmol) at room temperature. The
mixture was heated at 80 °C for 4hrs. After the
reaction was completed, the reaction mixture was
diluted with water (20 mL), extracted with EtOAc
(20 mL × 4). The combined organic layers were
then washed with brine (30 mL × 6), and then dried
over Na2SO4. The organic solvents were then
removed with a rotary evaporator to afford the
crude 2-Imino-N,2-diarylacetamide II without
further purification for the next step. The product II
was dissolved in freshly distilled CH2Cl2 (2 mL)
and stirred in an ice-water bath for 10 min. t-BuOCl
(0.57 mL, 5.0 mmol) was added dropwise into the
thus prepared solution, and the reaction mixture
was stirred for 30 min at room temperature. Upon
completion, the solvent was removed under reduced
pressure, and the residual was treated with flash
column chromatography on silica gel (using ethyl
acetate/petroleum ether as the eluent) to afford pure
2-chloromino-N,2-diarylacetamides 3.
General procedure for the reactions of 3
O
N
Pd(TFA)2 (0.2 equiv)
Na2CO3 (2.0 equiv)
DCE, Air, 100oC
R1
R3
R3
R1
N
N
O
R2 NCl
R2
3
4
To a 35 mL tube equipped with a magnetic stirring
bar, compounds 3 (0.5 mmol), Pd(TFA)2 (35 mg,
0.2 equiv.) and Na2CO3 (108 mg, 2.0 equiv.) was
added followed by DCE (5 ml). The mixture was
heated in an oil bath at 100 °C under air
atmosphere. After the reaction was completed, the
reaction mixture was poured into a saturated
aqueous NH4Cl solution (15 mL) and extracted
with ethyl acetate (3×10 mL). The combined
organic phases were washed with brine, dried over
Na2SO4, filtered and concentrated. The product 4
was purified using silica chromatography.
General procedure for the reactions of 1

7
Cl
O
Spectroscopic data for the substrate 3
N
O
Bn NCl
N
N-benzyl-2-(chloroimino)-2-(4-chlorophenyl)-N-
phenylacetamide (3c)
Bn NCl
N-benzyl-2-(chloroimino)-N,2-
Yellow oil; Rf = 0.31 (petroleum ether : EtOAc =
10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm): 7.41-
7.38 (m, 1.5H), 7.28-7.13 (m, 9H), 7.09 (t, J = 7.6
Hz, 1.5H), 6.85 (t, J = 7.6 Hz, 1.5H), 6.81-6.79 (m,
0.5H), 5.11 (d, J = 14.0 Hz, 0.7H), 5.00-4.94 (m,
1.3H); 13C NMR (CDCl3, 100 MHz, δ ppm): 173.4,
173.2, 163.4, 163.0, 139.6, 138.2, 137.8, 136.9,
135.8, 131.5, 130.2, 129.4, 129.3, 129.14, 129.12,
129.00, 128.96, 128.9, 128.8, 128.7, 128.6, 128.51,
128.49, 128.43, 128.36, 128.0, 127.9, 127.8, 127.7,
127.3, 53.1, 52.4; HRMS (ESI): calcd. for
diphenylacetamide (3a)
Pale yellow oil; Rf = 0.37 (petroleum ether : EtOAc
= 10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm):
7.48-7.44 (m, 1.5H), 7.41-7.36 (m, 1H), 7.31-7.14
(m, 9H), 7.06 (t, J = 7.6 Hz, 1.5H), 6.85 (t, J = 7.6
Hz, 1.5H), 6.80 (t, J = 7.6 Hz, 0.5H), 5.13 (d, J =
14.0 Hz, 0.7H), 4.99-4.94 (m, 1.2H); 13C NMR
(CDCl3, 100 MHz, δ ppm): 174.5, 174.2, 163.8,
163.4, 139.7, 138.3, 136.0, 133.1, 132.0, 131.6,
130.6, 129.24, 129.19, 129.13, 129.06, 129.01,
128.97, 128.9, 128.6, 128.5, 128.3, 128.2, 128.0,
127.9, 127.8, 127.7, 127.52, 127.46, 127.4, 126.8,
53.1, 52.3; HRMS (ESI): calcd. for C21H17ClN2O +
H = 349.1102, found: 349.1100.
C21H16Cl2N2O + H = 383.0712, found: 383.0710.
NO2
O
N
Bn
N
Cl
CF3
N-benzyl-2-(chloroimino)-2-(4-nitrophenyl)-N-
O
phenylacetamide (3d)
N
Bn NCl
Pale yellow oil; Rf = 0.35 (petroleum ether : EtOAc
= 10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm):
8.18-8.14 (m, 2H), 7.62 (d, J = 8.8 Hz, 1.6H), 7.34-
7.18 (m, 7H), 7.11 (t, J = 8.0 Hz, 1.5H), 6.84 (d, J =
7.6 Hz, 2H), 5.16-4.96 (m, 2H); 13C NMR (CDCl3,
100 MHz, δ ppm): 172.9, 162.7, 162.4, 149.2,
148.5, 139.3, 138.4, 137.8, 137.7, 135.54, 135.51,
129.44, 129.38, 129.2, 129.1, 129.0, 128.8, 128.7,
128.61, 128.56, 128.5, 128.4, 128.1, 127.9, 127.7,
123.9, 123.8, 123.4, 53.2, 52.5; HRMS (ESI):
calcd. for C21H16ClN3O3 + Na = 416.0772, found:
N-benzyl-2-(chloroimino)-N-phenyl-2-(4-
(trifluoromethyl)phenyl)acetamide (3b)
Yellow oil; Rf = 0.26 (petroleum ether : EtOAc =
10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm): 7.60-
7.57 (m, 4H), 7.30-7.23 (m, 5H), 7.21-7.19 (m,
1H), 7.12-7.08 (m, 2H), 6.84 (d, J = 7.6 Hz, 2H),
5.13 (d, J = 14.0 Hz, 0.9H), 5.01-4.95 (m, 1.1H);
13C NMR (CDCl3, 100 MHz, δ ppm): 173.5, 162.8,
138.1, 136.3, 135.8, 135.7, 133.6, 133.2, 132.9,
132.6, 129.3, 129.13, 129.08, 128.7, 128.6, 128.0,
127.8, 127.2, 125.71, 125.68, 125.64, 125.60,
125.20, 125.17, 124.9, 122.2, 53.3, 52.5; HRMS
(ESI): calcd. for C22H16ClF3N2O + H = 417.0976,
found: 417.0975.
416.0769.
O
N
CF3
Bn NCl
N-benzyl-2-(chloroimino)-N-phenyl-2-(3-
(trifluoromethyl)phenyl)acetamide (3e)

8
Tetrahedron
Yellow oil; Rf = 0.31 (petroleum ether : EtOAc =
2-(Chloroimino)-N,N-diphenyl-2-(4-
10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm): 7.66-
7.64 (m, 2.4H), 7.47-7.38 (m, 1.4H), 7.31-7.17 (m,
7H), 7.07 (d, J = 8.0 Hz, 1.4H), 6.83-6.78 (m,
1.9H), 5.07 (d, J = 13.6 Hz, 1.5H), 4.95 (s, 0.5H);
13C NMR (CDCl3, 100 MHz, δ ppm): 173.4, 173.2,
163.2, 162.8, 139.4, 138.1, 135.8, 133.9, 132.8,
131.7, 131.4, 131.0, 130.8, 130.7, 130.5, 130.4,
129.8, 129.6, 129.45, 129.36, 129.28, 129.27,
129.2, 129.1, 129.04, 128.96, 128.8, 128.7, 128.65,
128.62, 128.58, 128.5, 128.4, 128.2, 128.0, 127.9,
127.80, 127.76, 127.4, 127.20, 127.16, 124.7,
124.45, 124.4, 123.9, 123.82, 123.79, 123.75,
122.0, 119.3, 53.3, 53.1, 52.4; HRMS (ESI): calcd.
for C22H16ClF3N2O + H = 417.0976, found:
417.0975.
(trifluoromethyl)phenyl)acetamide (3g)
Yellow oil; Rf = 0.49 (petroleum ether : EtOAc =
10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm): 7.73-
7.69 (m, 1.5H), 7.63 (d, J = 8.4 Hz, 2H), 7.45-7.38
(m, 3.5H), 7.35-7.34 (m, 1H), 7.30-7.18 (m, 4H),
7.13-7.08 (m, 2H); 13C NMR (CDCl3, 100 MHz, δ
ppm): 173.4, 173.2, 162.8, 162.5, 140.4, 139.0,
136.5, 135.3, 133.4, 133.1, 129.7, 129.6, 129.4,
129.3, 129.2, 128.6, 128.3, 128.1, 128.0, 127.3,
125.9, 125.84, 125.80, 125.77, 125.6, 125.3, 125.2,
124.9, 122.2; HRMS (ESI): calcd. for
C21H14ClF3N2O + H = 403.0820, found: 403.0823.
F
CF3
O
N
Bn NCl
N-benzyl-2-(chloroimino)-N-(4-fluorophenyl)-2-
(4-(trifluoromethyl)phenyl)acetamide (3h)
Yellow oil; Rf = 0.40 (petroleum ether : EtOAc =
10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm): 7.63-
7.60 (m, 3.5H), 7.36-7.26 (m, 5H), 7.18-7.16 (m,
0.5H), 6.95-6.91 (m, 0.5H), 6.83-6.76 (m, 3.5H),
5.07 (d, J = 14.4 Hz, 0.8H), 4.98-4.92 (m, 1.2H);
13C NMR (CDCl3, 100 MHz, δ ppm): 173.4, 173.1,
163.9, 163.2, 162.8, 161.4, 160.9, 136.1, 135.52,
135.48, 135.3, 134.00, 133.97, 133.5, 133.2, 132.8,
131.2, 131.1, 129.9, 129.8, 129.2, 128.8, 128.73,
128.69, 128.6, 128.2, 128.0, 127.9, 127.2, 125.9,
125.8, 125.7, 125.4, 125.3, 124.8, 122.1, 116.4,
116.3, 116.2, 116.0, 53.4, 52.6; HRMS (ESI):
calcd. for C22H15ClF4N2O + NH4 = 452.1147,
found: 452.1154.
CF3
O
N
Et
NCl
2-(Chloroimino)-N-ethyl-N-phenyl-2-(4-
(trifluoromethyl)phenyl)acetamide (3f)
Yellow oil; Rf = 0.38 (petroleum ether : EtOAc =
10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm): 7.60-
7.58 (m, 3.2H), 7.38-7.35 (m, 1H), 7.27-7.25 (m,
1.4H), 7.22-7.18 (m, 1.4H), 7.05-7.00 (m, 2H),
4.02-3.81 (m, 2H), 1.25 (td, J = 7.2, 2.8 Hz, 2.1H),
1.16 (td, J = 7.2, 2.8 Hz, 0.9H); 13C NMR (CDCl3,
100 MHz, δ ppm): 173.7, 173.6, 162.7, 162.3,
139.6, 138.3, 136.4, 135.6, 133.2, 132.9, 129.6,
129.4, 129.30, 129.26, 129.1, 128.6, 128.6, 127.8,
127.6, 127.4, 127.2, 125.71, 125.68, 125.64,
125.60, 125.2, 125.1, 124.9, 112.2, 45.6, 44.5, 43.6,
13.8, 12.9, 12.6; HRMS (ESI): calcd. for
MeO
CF3
O
N
Bn NCl
C17H14ClF3N2O + H = 355.0820, found: 355.0825.
CF3
O
N-benzyl-2-(chloroimino)-N-(4-methoxyphenyl)-
N
2-(4-(trifluoromethyl)phenyl)acetamide (3i)
Ph NCl

9
Yellow oil; Rf = 0.32 (petroleum ether : EtOAc =
10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm): 7.61-
7.56 (m, 3.5H), 7.32-7.17 (m, 5.5H), 6.73 (dd, J =
8.0, 3.2 Hz, 2.6H), 6.57 (dd, J = 8.0, 3.2 Hz, 1.4H),
5.06 (d, J = 14.0 Hz, 0.7H), 4.96-4.90 (m, 1.3H),
3.77 (s, 0.9H), 3.68 (s, 2.1H); 13C NMR (CDCl3,
100 MHz, δ ppm): 173.7, 173.6, 163.4, 163.1,
160.0, 159.4, 140.6, 136.3, 135.8, 135.6, 133.2,
132.9, 131.9, 130.5, 130.4, 129.2, 129.1, 128.8,
128.6, 128.5, 128.4, 128.0, 127.8, 127.2, 125.7,
125.65, 125.61, 125.57, 125.2, 125.1, 124.9, 122.2,
114.3, 114.1, 55.4, 55.2, 53.4, 52.6; HRMS (ESI):
calcd. for C23H18ClF3N2O2 + H = 447.1082, found:
447.1079.
Ethyl 4-benzyl-3-oxo-3,4-dihydroquinoxaline-2-
carboxylate[1] (2a)
Yellow solid; mp 94-95 oC; yield: 133 mg (86%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.92 (d, J =
8.0 Hz, 1H), 7.52-7.48 (m, 1H), 7.34-7.24 (m, 7H),
5.48 (s, 2H), 4.52 (q, J = 7.2 Hz, 2H), 1.44 (t, J =
7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz, δ ppm):
163.6, 152.5, 149.0, 134.5, 133.2, 132.2, 131.9,
131.0, 128.7, 127.6, 126.8, 124.0, 114.5, 62.3, 45.8,
13.9; EI-MS m/z (rel. int., %): 308 (M+, 49), 234
(30), 207 (73), 206 (76), 91 (100).
Me
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-7-methyl-3-oxo-3,4-
CF3
dihydroquinoxaline-2-carboxylate[1] (2b)
White solid; mp 117-118 oC; yield: 160 mg (99%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.71 (s, 1H),
7.33-7.18 (m, 7H), 5.46 (s, 2H), 4.51 (q, J = 7.2 Hz,
2H), 2.38 (s, 3H), 1.44 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, δ ppm): 163.7, 152.4,
148.8, 134.6, 134.0, 133.6, 131.9, 131.0, 130.6,
128.7, 127.6, 126.8, 114.3, 62.2, 45.7, 20.3, 14.0;
EI-MS m/z (rel. int., %): 322 (M+, 48), 248 (27),
221 (67), 220 (62), 91 (100).
O
Me
N
Bn NCl
N-benzyl-2-(chloroimino)-N-(m-tolyl)-2-(4-
(trifluoromethyl)phenyl)acetamide(3j)
Yellow oil; Rf = 0.31 (petroleum ether : EtOAc =
10 : 1); 1H NMR (CDCl3, 400 MHz,  ppm): 7.59-
7.53 (m, 3.4H), 7.31-7.18 (m, 5.5H), 7.14-7.08 (m,
0.7H), 7.02-6.95 (m, 1.4H), 6.63-6.59 (m, 2H), 5.10
(d, J = 14.0 Hz, 0.7H), 4.98-4.93 (m, 1.3H), 2.20 (s,
0.9H), 2.06 (s, 2.1H); 13C NMR (CDCl3, 100 MHz,
δ ppm): 173.6, 173.4, 163.2, 162.9, 139.5, 139.4,
139.2, 138.0, 136.6, 135.9, 135.8, 135.6, 133.2,
132.8, 130.0, 129.5, 129.3, 129.0, 128.8, 128.7,
128.6, 128.5, 128.4, 128.0, 127.9, 127.8, 127.2,
126.1, 125.62, 125.59, 125.55, 125.51, 125.14,
125.10, 125.07, 124.9, 124.8, 122.2, 53.2, 52.4,
20.9, 20.8; HRMS (ESI): calcd. for C23H18ClF3N2O
+ H = 431.1133, found: 431.1132.
MeO
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-7-methoxy-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2c)
Pale yellow solid; mp 124-125 oC; yield: 82 mg
(48%); 1H NMR (CDCl3, 400 MHz,  ppm): 7.38
(d, J = 2.8 Hz, 1H), 7.31-7.21 (m, 6H), 7.14 (dd, J
= 9.2, 2.8 Hz, 1H), 5.48 (s, 2H), 4.52 (q, J = 7.2 Hz,
2H), 3.82 (s, 3H), 1.46 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, δ ppm): 163.7, 156.1,
152.2, 149.2, 134.7, 132.8, 128.8, 127.7, 127.6,
126.8, 122.0, 115.5, 111.9, 62.4, 55.6, 45.9, 14.0;
Spectroscopic data for the products 2
and 4
N
CO2Et
O
N
Bn

10
Tetrahedron
EI-MS m/z (rel. int., %): 338 (M+, 36), 237 (46), White solid; mp 154-155 oC; yield: 137 mg (80%);
236 (35), 233 (22), 91 (100).
1H NMR (CDCl3, 400 MHz,  ppm): 7.92 (d, J =
2.4 Hz, 1H), 7.46 (dd, J = 8.8, 2.4 Hz, 1H), 7.34-
7.23 (m, 6H), 5.48 (s, 2H), 4.52 (q, J = 7.2 Hz, 2H),
1.46 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100
MHz, δ ppm): 163.4, 152.3, 150.4, 134.3, 132.6,
132.3, 132.0, 130.3, 129.6, 129.0, 128.0, 126.9,
115.8, 62.6, 46.1, 14.1; EI-MS m/z (rel. int., %):
344 (M+ + 2, 19), 342 (M+, 60), 242 (29), 240 (80),
91 (100).
Ph
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-3-oxo-7-phenyl-3,4-
dihydroquinoxaline-2-carboxylate[1] (2d)
Yellow oil; Rf = 0.56 (petroleum ether : EtOAc = 3
: 1); yield: 93 mg (49%); 1H NMR (CDCl3, 400
MHz,  ppm): 8.16 (s, 1H), 7.75-7.73 (m, 1H),
7.57-7.55 (m, 2H), 7.42 (t, J = 7.2 Hz, 2H), 7.36-
7.25 (m, 7H), 5.50 (s, 2H), 4.53 (q, J = 7.2 Hz, 2H),
1.46 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100
MHz, δ ppm): 163.6, 152.4, 149.3, 138.4, 137.1,
134.6, 132.4, 132.3, 131.1, 128.93, 128.87, 127.80,
127.77, 126.9, 126.6, 115.0, 62.4, 45.9, 14.0; EI-
MS m/z (rel. int., %): 384 (M+, 40), 283 (46), 282
(42), 91 (100).
Br
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-7-bromo-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2g)
White solid; mp 165-166 oC; yield: 164 mg (85%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.04 (d, J =
2.4 Hz, 1H), 7.56 (dd, J = 8.8, 2.4 Hz, 1H), 7.32-
7.18 (m, 6H), 5.46 (s, 2H), 4.51 (q, J = 7.2 Hz, 2H),
1.45 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100
MHz, δ ppm): 163.2, 152.1, 150.2, 134.9, 134.2,
133.2, 132.7, 132.3, 128.9, 127.9, 126.8, 116.6,
116.1, 62.5, 46.0, 14.0; EI-MS m/z (rel. int., %):
388 (M+ + 2, 13), 386 (M+, 13), 287 (17), 286 (22),
285 (20), 284 (21), 91 (100).
F
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-7-fluoro-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2e)
White solid; mp 123-124 oC; yield: 121 mg (74%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.62-7.60 (m,
1H), 7.32-7.23 (m, 7H), 5.49 (s, 2H), 4.52 (q, J =
7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, δ ppm): 163.4, 159.7, 157.3,
152.2, 150.5, 134.3, 132.6, 132.5, 129.93, 129.91,
128.9, 127.9, 126.8, 120.3, 120.1, 116.3, 116.1,
116.0, 115.9, 62.5, 46.1, 14.0; EI-MS m/z (rel. int.,
%): 326 (M+, 33), 252 (16), 225 (48), 224 (52), 91
(100).
I
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-7-iodo-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2h)
White solid; mp 163-164 oC; yield: 140 mg (65%);
1H NMR (CDCl3, 400 MHz, ppm): 8.25 (d, J = 2.0
Hz, 1H), 7.74 (dd, J = 8.8, 2.0 Hz, 1H), 7.32-7.22
(m, 5H), 7.05 (d, J = 9.2 Hz, 1H), 5.45 (s, 2H), 4.51
(q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, δ ppm): 163.2, 152.2,
149.9, 140.6, 139.5, 134.2, 133.02, 132.98, 129.0,
127.9, 126.8, 116.3, 86.7, 62.6, 45.9, 14.0; EI-MS
Cl
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-7-chloro-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2f)

11
m/z (rel. int., %): 434 (M+, 25), 333 (21), 332 (24),
91 (100).
White solid; mp 119-120 oC; yield: 72 mg
(45%); 1H NMR (CDCl3, 400 MHz,  ppm): 7.37
F3C
N
CO2Et
(t, J = 8.0 Hz, 1H), 7.30-7.22 (m, 5H), 7.17 (d, J =
7.2 Hz, 1H), 7.11 (d, J = 8.8 Hz, 1H), 5.48 (s, 2H),
4.51 (q, J = 7.2 Hz, 2H), 2.67 (s, 3H), 1.45 (t, J =
7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz, δ ppm):
164.2, 152.5, 147.5, 140.3, 134.8, 133.5, 132.0,
130.9, 128.8, 127.6, 126.8, 125.3, 112.4, 62.2, 45.9,
17.5, 14.0; EI-MS m/z (rel. int., %): 322 (M+, 44),
248 (40), 221 (61), 220 (53), 91 (100).
N
O
Bn
Ethyl 4-benzyl-3-oxo-7-(trifluoromethyl)-3,4-
dihydroquinoxaline-2-carboxylate (2i)
White solid; mp 120-121 oC; yield: 140 mg (74%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.21 (d, J =
0.8 Hz, 1H), 7.73 (dd, J = 8.8, 2.0 Hz, 1H), 7.44 (d,
J = 9.2 Hz, 1H), 7.33-7.24 (m, 5H), 5.51 (s, 2H),
4.53 (q, J = 7.2 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H);
13C NMR (CDCl3, 100 MHz, δ ppm): 163.0, 152.4,
150.6, 135.6, 134.0, 131.4, 129.0, 128.6, 128.53,
128.49, 128.43, 128.40, 128.36, 128.0, 127.3,
126.9, 126.8, 126.6, 126.2, 125.9, 124.6, 121.9,
119.2, 115.5, 62.6, 46.1, 14.0; EI-MS m/z (rel. int.,
%): 376 (M+, 29), 302 (19), 275 (50), 274 (62), 91
(100).
N
CO2Et
MeO
N
O
Bn
Ethyl 4-benzyl-6-methoxy-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate (2k-1)
White solid; mp 128-129 oC; yield: 82 mg (49%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.84 (t, J =
8.5 Hz, 1H), 7.33-7.24 (m, 5H), 6.90 (dd, J = 9.0,
2.0 Hz, 1H), 6.69 (d, J = 2.4 Hz, 1H), 5.47 (s, 2H),
4.51 (q, J = 7.2 Hz, 2H), 3.78 (s, 3H), 1.45 (t, J =
7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz, δ ppm):
163.8, 162.9, 152.9, 144.6, 135.3, 134.6, 132.7,
128.8, 127.8, 126.9, 112.0, 98.4, 62.2, 55.6, 46.0,
14.0; EI-MS m/z (rel. int., %): 338 (M+, 44), 292
N
CO2Et
Me
N
O
Bn
Ethyl 4-benzyl-6-methyl-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2j-1)
White solid; mp 116-117 oC; yield: 72 mg (45%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.81 (d, J =
8.0 Hz, 1H), 7.33-7.25 (m, 5H), 7.15 (d, J = 8.4 Hz,
1H), 7.10 (s, 1H), 5.48 (s, 2H), 4.52 (q, J = 7.2 Hz,
2H), 2.41 (s, 3H), 1.45 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, δ ppm): 163.8, 152.7,
147.5, 143.7, 134.7, 133.4, 130.9, 130.3, 128.9,
127.7, 126.9, 125.6, 114.5, 62.3, 45.8, 22.2, 14.1;
EI-MS m/z (rel. int., %): 322 (M+, 51), 248 (36),
(32), 249 (33), 237 (53), 91 (100).
OMe
N
CO2Et
O
N
Bn
Ethyl 4-benzyl-8-methoxy-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate (2k-2)
White solid; mp 134-135 oC; yield: 77 mg (46%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.44 (t, J =
8.4 Hz, 1H), 7.32-7.23 (m, 5H), 6.86 (d, J = 8.8 Hz,
1H), 6.78 (d, J = 8.0 Hz, 1H), 5.47 (s, 2H), 4.49 (q,
J = 7.2 Hz, 2H), 4.00 (s, 3H), 1.44 (t, J = 7.2 Hz,
3H); 13C NMR (CDCl3, 100 MHz, δ ppm): 163.6,
157.0, 152.7, 146.5, 134.9, 134.7, 133.4, 128.8,
221 (74), 220 (62), 91 (100).
Me
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-8-methyl-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2j-2)

12
Tetrahedron
127.7, 126.8, 122.8, 106.6, 105.3, 62.2, 56.3,
7.35-7.26 (m, 5H), 5.44 (s, 2H), 4.50 (q, J = 7.2 Hz,
2H), 1.45 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz, δ ppm): 163.3, 152.2, 149.1, 134.3,
134.1, 132.3, 130.8, 129.0, 128.0, 127.5, 126.94,
126.90, 117.6, 62.6, 46.0, 14.0; EI-MS m/z (rel.
int., %): 388 (M+ + 2, 15), 386 (M+, 15), 287 (22),
46.2, 14.0; EI-MS m/z (rel. int., %): 338 (M+, 49),
237 (44), 233 (22), 91 (100).
N
CO2Et
O
Cl
N
Bn
Ethyl 4-benzyl-6-chloro-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2l-1)
White solid; mp 124-125 oC; yield: 86 mg (51%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.86 (d, J =
8.8 Hz, 1H), 7.36-7.26 (m, 7H), 5.45 (s, 2H), 4.52
(q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, δ ppm): 163.4, 152.4,
148.9, 138.6, 134.3, 134.1, 132.3, 130.6, 129.1,
128.1, 127.0, 124.7, 114.6, 62.6, 46.1, 14.1; EI-MS
m/z (rel. int., %): 344 (M+ + 2, 10), 342 (M+, 28),
286 (23), 285 (25), 284 (22), 91 (100).
Br
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-8-bromo-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate (2m-2)
White solid; mp 132-133 oC; yield: 69 mg (36%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.60 (d, J =
7.6 Hz, 1H), 7.35-7.21 (m, 7H), 5.48 (s, 2H), 4.52
(q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, δ ppm): 163.3, 152.3,
149.6, 134.7, 134.3, 132.4, 129.9, 129.0, 128.4,
127.9, 126.9, 126.8, 114.3, 62.5, 46.3, 14.0; EI-MS
m/z (rel. int., %): 388 (M+ + 2, 15), 386 (M+, 15),
287 (21), 286 (23), 285 (24), 284 (21), 91 (100).
241 (47), 240 (39), 91 (100).
Cl
N
CO2Et
N
O
Bn
Ethyl 4-benzyl-8-chloro-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate[1] (2l-2)
White solid; mp 134-135 oC; yield: 63 mg (37%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.42-7.40 (m,
2H), 7.34-7.19 (m, 6H), 5.49 (s, 2H), 4.53 (q, J =
7.2 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz, δ ppm): 163.4, 152.3, 149.5,
136.1, 134.9, 134.3, 132.2, 129.04, 129.02, 128.0,
126.8, 125.1, 113.5, 62.6, 46.4, 14.0; EI-MS m/z
(rel. int., %): 344 (M+ + 2, 10), 342 (M+, 28), 243
(14), 241 (44), 91 (100).
N
CO2Et
F3C
N
O
Bn
Ethyl 4-benzyl-3-oxo-6-(trifluoromethyl)-3,4-
dihydroquinoxaline-2-carboxylate (2n-1)
White solid; mp 114-115 oC; yield: 120 mg (64%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.05 (d, J =
8.4 Hz, 1H), 7.61 (s, 1H), 7.57 (d, J = 8.4 Hz, 1H),
7.36-7.27 (m, 5H), 5.52 (s, 2H), 4.54 (q, J = 7.2 Hz,
2H), 1.46 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz, δ ppm): 163.2, 152.3, 151.6, 134.0,
133.9, 133.7, 133.6, 133.3, 133.2, 132.9, 132.0,
129.1, 128.2, 127.1, 124.4, 121.7, 120.6, 120.5,
120.6, 120.5, 112.13, 112.09, 112.05, 112.01, 62.8,
46.2, 14.0; EI-MS m/z (rel. int., %): 376 (M+, 27),
302 (17), 275 (50), 274 (59), 91 (100).
N
CO2Et
Br
N
O
Bn
Ethyl 4-benzyl-6-bromo-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate (2m-1)
White solid; mp 140-141 oC; yield: 89 mg (46%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.77 (d, J =
8.4 Hz, 1H), 7.48 (s, 1H), 7.43 (d, J = 8.8 Hz, 1H),

13
CF3
Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H), 7.40-7.34 (m,
N
CO2Et
O
2H), 4.51 (q, J = 7.2 Hz, 2H), 3.71 (s, 3H), 1.45 (t,
J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz, δ
ppm): 163.6, 152.3, 148.8, 133.8, 132.7, 131.6,
130.8, 123.9, 113.7, 62.2, 28.9, 13.9; EI-MS m/z
(rel. int., %): 232 (M+, 59), 160 (100), 159 (40),
132 (45), 131 (58).
N
Bn
Ethyl 4-benzyl-3-oxo-8-(trifluoromethyl)-3,4-
dihydroquinoxaline-2-carboxylate (2n-2)
White solid; mp 170-171 oC; yield: 27 mg (14%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.66 (d, J =
7.6 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.51 (d, J =
8.4 Hz, 1H), 7.35-7.23 (m, 5H), 5.52 (s, 2H), 4.52
(q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, δ ppm): 163.3, 152.1,
150.1, 134.2, 131.4, 130.1, 129.8, 129.14, 129.07,
128.1, 126.8, 124.3, 122.13, 122.08, 122.05,
121.97, 121.5, 118.7, 62.6, 46.3, 14.0; EI-MS m/z
(rel. int., %): 376 (M+, 30), 275 (35), 274 (41), 193
(18), 91 (100).
N
CO2Et
N
O
Et
Ethyl 4-ethyl-3-oxo-3,4-dihydroquinoxaline-2-
carboxylate (2q)
White solid; mp 74-75 oC; yield: 104 mg (85%); 1H
NMR (CDCl3, 400 MHz,  ppm): 7.93 (d, J = 8.0
Hz, 1H), 7.69-7.65 (m, 1H), 7.41-7.35 (m, 2H),
4.52 (q, J = 7.2 Hz, 2H), 4.35 (q, J = 7.2 Hz, 2H),
1.46 (t, J = 7.2 Hz, 3H), 1.40 (t, J = 7.2 Hz, 3H);
13C NMR (CDCl3, 100 MHz, δ ppm): 163.6, 151.8,
148.8, 132.8, 132.2, 131.9, 131.1, 123.7, 113.5,
62.1, 37.3, 13.9, 12.1; EI-MS m/z (rel. int., %): 246
(M+, 87), 174 (74), 172 (70), 146 (96), 145 (75),
118 (100).
N
CO2Et
N
O
Ethyl 3-oxo-3,5,6,7-tetrahydropyrido[1,2,3-
de]quinoxaline-2-carboxylate (2o)
White solid; mp 167-168 oC; yield: 70 mg (54%);
1H NMR (CDCl3, 400 MHz, ppm): 7.77 (d, J = 8.0
Hz, 1H), 7.40 (d, J = 7.2 Hz, 1H), 7.30-7.26 (m,
1H), 4.51 (q, J = 7.2 Hz, 2H), 4.16 (t, J = 5.0 Hz,
2H), 3.00 (t, J = 6.0 Hz, 2H), 2.15 (t, J = 6.0 Hz,
2H), 1.44 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz, δ ppm): 163.8, 151.8, 148.4, 131.6,
131.3, 130.5, 128.7, 124.7, 123.6, 62.3, 41.8, 26.3,
20.0, 14.0; EI-MS m/z (rel. int., %): 258 (M+, 57),
186 (100), 185 (32), 158 (67), 157 (74).
N
CO2Et
N
O
Ph
Ethyl 3-oxo-4-phenyl-3,4-dihydroquinoxaline-2-
carboxylate (2r)
White solid; mp 151-152 oC; yield: 142 mg (96%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.97 (d, J =
8.0 Hz, 1H), 7.63-7.53 (m, 3H), 7.44 (t, J = 7.6 Hz,
1H), 7.35 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 7.6 Hz,
2H), 6.73 (d, J = 8.4 Hz, 1H), 4.50 (q, J = 7.2 Hz,
2H), 1.43 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz, δ ppm): 163.5, 152.0, 149.6, 134.8,
134.7, 131.9, 131.6, 130.5, 130.1, 129.5, 127.9,
124.1, 115.5, 62.2, 13.9; EI-MS m/z (rel. int., %):
294 (M+, 32), 222 (34), 194 (28), 193 (100), 192
(20).
N
CO2Et
N
O
Me
Ethyl 4-methyl-3-oxo-3,4-dihydroquinoxaline-2-
carboxylate (2p)
White solid; mp 53-54 oC; yield: 100 mg (86%); 1H
NMR (CDCl3, 400 MHz,  ppm): 7.91 (d, J = 8.0

14
Tetrahedron
Pale yellow solid; mp 129-130 oC; yield: 53 mg
Me
N
CO2Et
O
(30%); 1H NMR (CDCl3, 400 MHz,  ppm): 8.93
(d, J = 8.8 Hz, 1H), 7.90 (d, J = 9.2 Hz, 1H), 7.78
(d, J = 8.0 Hz, 1H), 7.69 (t, J = 7,6 Hz, 1H), 7.55 (t,
J = 7,6 Hz, 1H), 7.37 (d, J = 9.2 Hz, 1H), 7.32-7.24
(m, 5H), 5.60 (s, 2H), 4.57 (q, J = 7.2 Hz, 2H), 1.50
(t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz, δ
ppm): 164.2, 153.1, 146.1, 134.8, 134.1, 132.1,
131.2, 129.7, 129.0, 128.6, 127.8, 127.6, 127.2,
126.9, 126.7, 123.3, 113.8, 62.3, 46.3, 14.2; EI-MS
m/z (rel. int., %): 358 (M+, 28), 284 (32), 257 (32),
256 (23), 91 (100).
Me
N
Bn
Ethyl 4-benzyl-6,8-dimethyl-3-oxo-3,4-
dihydroquinoxaline-2-carboxylate (2t)
White solid; mp 136-137 oC yield: 142 mg (84%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.31-7.23 (m,
5H), 7.00 (s, 1H), 6.91 (s, 1H), 5.46 (s, 2H), 4.50
(q, J = 7.2 Hz, 2H), 2.62 (s, 3H), 2.34 (s, 3H), 1.45
(t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz, δ
ppm): 164.3, 152.7, 146.0, 143.2, 139.9, 134.9,
133.6, 129.2, 128.8, 127.6, 126.8, 112.4, 62.1, 45.8,
22.2, 17.3, 14.0; EI-MS m/z (rel. int., %): 336 (M+,
49), 262 (55), 235 (63), 234 (46), 91 (100).
N
CO2t-Bu
N
O
N
CO2Et
Bn
Tert-butyl 4-benzyl-3-oxo-3,4-
N
O
dihydroquinoxaline-2-carboxylate (2v)
Bn
White solid; mp 106-107 oC; yield: 96 mg (57%);
1H NMR (CDCl3, 400 MHz,  ppm): 7.93 (d, J =
8.0 Hz, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.35-7.25 (m,
7H), 5.50 (s, 2H), 1.68 (s, 9H); 13C NMR (CDCl3,
100 MHz, δ ppm): 163.4, 152.7, 150.4, 134.7,
133.3, 132.2, 131.9, 131.1, 129.0, 127.8, 126.9,
124.0, 114.6, 84.2, 45.9, 28.1; HRMS (ESI): calcd.
Ethyl 4-benzyl-3-oxo-3,4-
dihydrobenzo[g]quinoxaline-2-carboxylate (2u-
1)
Yellow oil; Rf = 0.50 (petroleum ether : EtOAc = 3
: 1); yield: 23 mg (13%); 1H NMR (CDCl3, 400
MHz,  ppm): 8.48 (s, 1H), 7.90 (d, J = 8.4 Hz,
1H), 7.78 (d, J = 8.4 Hz, 1H), 7.60 (s, 1H), 7.55 (t,
J = 7,6 Hz, 1H), 7.47 (d, J = 9.2 Hz, 1H), 7.34-7.26
(m, 5H), 5.57 (s, 2H), 4.55 (q, J = 7.2 Hz, 2H), 1.48
(t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz, δ
ppm): 163.7, 152.6, 149.8, 134.8, 134.6, 131.3,
130.9, 129.7, 129.0, 128.87, 128.76, 127.8, 127.4,
127.0, 125.8, 111.3, 62.6, 46.0, 14.2; HRMS (ESI):
calcd. for C22H18N2O3 + Na = 381.1210, found:
for C20H20N2O3 + Na = 359.1366, found: 359.1361.
CF3
N
N
O
Bn
1-Benzyl-3-(4-
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4b)
Yellow oil; Rf = 0.21 (petroleum ether : EtOAc =
20 : 1); yield: 106 mg (56%); 1H NMR (CDCl3, 400
MHz,  ppm): 8.52 (d, J = 8.4 Hz, 2H), 7.96 (dd, J
= 7.6, 1.2 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.48
(td, J = 8.0, 1.2 Hz, 1H), 7.37-7.26 (m, 7H), 5.57 (s,
2H); 13C NMR (CDCl3, 100 MHz, δ ppm): 154.6,
152.6, 139.2, 135.1, 133.2, 132.9, 132.3, 132.0,
381.1205.
CO2Et
O
N
N
Bn
Ethyl 4-benzyl-3-oxo-3,4-
dihydrobenzo[f]quinoxaline-2-carboxylate (2u-2)

15
131.7, 131.4, 131.0, 130.8, 130.0, 128.1, 127.8,
126.9, 125.4, 124.98, 124.95, 124.91, 124.87,
124.0, 122.7, 120.0, 114.4, 46.2; HRMS (ESI):
calcd. for C22H15F3N2O + H = 381.1209, found:
1-Benzyl-3-(3-
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4e)
White solid; mp 145-146 oC; yield: 95 mg (50%);
381.1210.
1H NMR (CDCl3, 400 MHz,  ppm): 8.78 (s, 1H),
8.65 (d, J = 8.0 Hz, 1H), 7.96 (dd, J = 8.0, 1.2 Hz,
1H), 7.73 (d, J = 8.0 Hz, 1H), 7.59 (t, J = 8.0 Hz,
1H), 7.45 (td, J = 8.4, 1.2 Hz, 1H), 7.34-7.25 (m,
7H); 13C NMR (CDCl3, 100 MHz, δ ppm): 154.6,
152.2, 136.6, 135.1, 133.1, 132.9, 132.8, 130.9,
130.74, 130.67, 130.4, 128.9, 128.5, 127.7, 126.85,
126.79, 126.62, 126.58, 126.54, 125.49, 124.0,
122.8, 114.4, 46.1; HRMS (ESI): calcd. for
Cl
N
N
O
Bn
1-Benzyl-3-(4-chlorophenyl)quinoxalin-2(1H)-
one (4c)
Yellow oil; Rf = 0.30 (petroleum ether : EtOAc =
10 : 1); yield: 82 mg (47%); 1H NMR (CDCl3, 400
MHz,  ppm): 8.40 (d, J = 8.8 Hz, 2H), 7.93 (d, J =
7.6 Hz, 1H), 7.46-7.43 (m, 3H), 7.34-7.25 (m, 7H),
5.55 (s, 2H); 13C NMR (CDCl3, 100 MHz, δ ppm):
154.6, 152.6, 136.6, 135.2, 134.4, 133.2, 132.7,
131.1, 130.6, 130.5, 128.9, 128.3, 127.7, 126.9,
123.9, 114.4, 46.1; HRMS (ESI): calcd. for
C22H15F3N2O + H = 381.1209, found: 381.1212.
CF3
N
N
O
Et
1-Ethyl-3-(4-
C21H15ClN2O + H = 347.0946, found: 347.0945.
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
NO2
(4f)
N
Yellow solid; mp 93-94 oC; yield: 88 mg (56%); 1H
NMR (CDCl3, 400 MHz,  ppm): 8.48 (d, J = 8.0
Hz, 2H), 7.94 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8.4
Hz, 2H), 7.60-7.56 (m, 1H), 7.36 (t, J = 8.0 Hz,
2H), 4.37 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz,
3H); 13C NMR (CDCl3, 100 MHz, δ ppm): 153.9,
152.3, 139.2, 133.2, 132.4, 131.8, 131.4, 130.9,
129.9, 128.1, 125.4, 124.84, 124.81, 124.77,
124.73, 123.7, 122.7, 113.4, 37.6, 12.3; HRMS
(ESI): calcd. for C17H13F3N2O + H = 319.1053,
N
O
Bn
1-Benzyl-3-(4-nitrophenyl)quinoxalin-2(1H)-one
(4d)
Yellow solid; mp 183-184 oC; yield: 71 mg (39%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.64 (d, J =
8.8 Hz, 2H), 8.34 (d, J = 8.4 Hz, 2H), 8.00 (d, J =
8.0 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.51-7.34 (m,
7H), 5.60 (s, 2H); 13C NMR (CDCl3, 100 MHz, δ
ppm): 154.6, 151.6, 148.7, 141.8, 135.0, 133.2,
133.0, 131.6, 131.1, 130.7, 129.1, 127.9, 126.9,
124.3, 123.2, 114.6, 46.3; HRMS (ESI): calcd. for
C21H15N3O3 + H = 358.1186, found: 358.1181.
found: 319.1051.
CF3
N
N
N
O
CF3
Ph
N
O
Bn
1-Phenyl-3-(4-
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4g)

16
Tetrahedron
White solid; mp 103-104 oC; yield: 86 mg
2.8 Hz, 1H), 7.32-7.19 (m, 6H), 7.09 (dd, J = 9.2,
2.8 Hz, 1H), 5.53 (s, 2H), 3.86 (s, 3H); 13C NMR
(CDCl3, 100 MHz, δ ppm): 156.2, 154.2, 152.8,
139.3, 135.2, 134.0, 131.9, 131.6, 130.0, 128.9,
128.7, 127.7, 127.1, 126.9, 125.4, 124.9, 124.85,
124.81, 122.7, 120.5, 115.3, 111.8, 55.7, 46.2;
HRMS (ESI): calcd. for C23H17F3N2O2 + H =
411.1315, found: 411.1313.
(47%); 1H NMR (CDCl3, 400 MHz,  ppm): 8.56
(d, J = 8.0 Hz, 2H), 8.00-7.98 (m, 1H), 7.71 (d, J =
8.4 Hz, 2H), 7.66-7.62 (m, 2H), 7.59-7.55 (m, 1H),
7.40-7.33 (m, 4H), 6.72-6.70 (m, 1H); 13C NMR
(CDCl3, 100 MHz, δ ppm): 154.3, 152.8, 139.0,
135.9, 134.3, 132.8, 132.0, 131.7, 130.6, 130.4,
130.3, 130.0, 129.7, 129.5, 129.2, 128.2, 125.6,
125.4, 124.92, 124.88, 124.84, 124.81, 124.1,
122.7, 115.4; HRMS (ESI): calcd. for C21H13F3N2O
CF3
CF3
Me
N
N
+
N
O
Me
N
O
Bn
Bn
+ H = 367.1053, found: 367.1052.
1-Benzyl-5-methyl-3-(4-
CF3
F
N
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4j-1)
N
O
Bn
1-Benzyl-7-methyl-3-(4-
1-Benzyl-6-fluoro-3-(4-
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4j-2)
(4h)
White solid; mp 144-145 oC; yield: 127 mg (64%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.62 (d, J =
8.4 Hz, 1H), 8.51 (d, J = 8.4 Hz, 1H), 7.80 (d, J =
8.0 Hz, 0.5H), 7.70 (d, J = 8.0 Hz, 1H), 7.69 (d, J =
8.0 Hz, 1H), 7.34-7.20 (m, 5.5H), 7.17-7.07 (m,
2H), 5.51-5.50 (m, 2H), 2.73 (s, 1.6H), 2.40 (s,
1.4H); 13C NMR (CDCl3, 100 MHz, δ ppm): 154.6,
154.4, 151.0, 150.0, 142.0, 139.6, 139.3, 135.3,
135.2, 133.0, 132.8, 131.71, 131.66, 131.4, 131.3,
130.8, 130.5, 129.9, 129.8, 128.9, 128.8, 127.7,
127.6, 126.9, 126.8, 125.45, 125.39, 125.1, 124.81,
124.78, 124.7, 122.8, 114.3, 112.3, 46.2, 46.0, 22.1,
17.5; HRMS (ESI): calcd. for C23H17F3N2O + H =
395.1366, found: 395.1367
White solid; mp 138-139 oC; yield: 116 mg (59%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.52 (d, J =
8.4 Hz, 2H), 7.72 (d, J = 8.4 Hz, 2H), 7.63 (dd, J =
8.4, 2.8 Hz, 1H), 7.34-7.20 (m, 7H), 5.53 (s, 2H);
13C NMR (CDCl3, 100 MHz, δ ppm): 160.0, 157.5,
154.2, 153.7, 138.8, 134.8, 133.8, 133.6, 132.3,
132.0, 131.6, 130.1, 129.49, 129.47, 129.0, 128.0,
127.9, 126.8, 125.3, 125.0, 124.93, 124.90, 124.86,
122.6, 118.9, 118.7, 116.0, 115.8, 115.65, 115.56,
46.4; HRMS (ESI): calcd. for C22H14F4N2O + H =
399.1115, found: 399.1120.
CF3
MeO
N
N
O
Bn
CF3
1-Benzyl-6-methoxy-3-(4-
Br
N
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
N
O
(4i)
Bn
Yellow solid; mp 121-122 oC; yield: 64 mg (31%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.52 (d, J =
8.4 Hz, 2H), 7.72 (d, J = 8.4 Hz, 2H), 7.40 (d, J =
1-Benzyl-5-bromo-3-(4-
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4k-1)

17
Yellow solid; mp 163-164 oC; yield: 72 mg (32%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.69 (d, J =
8.0 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.62 (dd, J =
7.6, 1.6 Hz, 1H), 7.34-7.23 (m, 7H), 5.56 (s, 2H);
13C NMR (CDCl3, 100 MHz, δ ppm): 154.3, 152.2,
138.8, 134.8, 134.2, 132.4, 132.1, 131.8, 131.2,
130.7, 130.6, 130.4, 129.6, 129.1, 128.84, 128.76,
128.1, 127.9, 126.81, 126.77, 125.9, 125.4, 125.09,
125.05, 125.02, 124.98, 122.7, 120.0, 114.1, 46.5;
HRMS (ESI): calcd. for C22H14BrF3N2O + H =
(d, J = 8.4 Hz, 2H), 8.01-7.99 (m, 1H), 7.77 (d, J
= 8.8 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.44-7.36
(m, 2H), 7.25-7.22 (m, 2H), 6.72 (dd, J = 8.0, 1.6
Hz, 1H); 13C NMR (CDCl3, 100 MHz, δ ppm):
154.1, 152.8, 138.8, 134.8, 134.0, 133.7, 132.8,
132.3, 132.2, 131.8, 131.5, 130.8, 130.5, 130.1,
130.0, 128.1, 127.0, 125.4, 125.0, 124.91, 124.88,
124.4, 123.7, 122.7, 115.2; HRMS (ESI): calcd. for
C21H12BrF3N2O + H = 445.0158, found: 445.0166.
CF3
Br
N
459.0314, found: 459.0318.
N
O
CF3
Ph
N
6-Bromo-1-phenyl-3-(4-
Br
N
O
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4l-2)
Bn
1-Benzyl-7-bromo-3-(4-
Yellow oil; Rf = 0.34 (petroleum ether : EtOAc =
10 : 1); yield: 41 mg (19%); 1H NMR (CDCl3, 400
MHz,  ppm): 8.55 (d, J = 8.4 Hz, 2H), 8.15 (d, J =
2.0 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.65 (t, J =
7.6 Hz, 2H), 7.59 (t, J = 7.6 Hz, 1H), 7.47 (dd, J =
8.8, 2.0 Hz, 1H), 7.32 (d, J = 7.2 Hz, 2H), 6.59 (d, J
= 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz, δ
ppm): 154.0, 153.9, 138.5, 135.5, 133.6, 133.42,
133.36, 132.6, 132.4, 132.1, 130.5, 130.1, 129.8,
128.1, 125.3, 125.0, 124.94, 124.90, 122.6, 116.9,
116.7; HRMS (ESI): calcd. for C21H12BrF3N2O + H
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4k-2)
Yellow solid; mp 181-182 oC; yield: 56 mg (25%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.51 (d, J =
8.4 Hz, 2H), 7.79 (d, J = 8.8 Hz, 1H), 7.73 (d, J =
8.4 Hz, 2H), 7.47 (d, J = 2.0 Hz, 1H), 7.45 (dd, J =
8.4, 2.0 Hz, 1H), 7.35-7.28 (m, 5H), 5.50 (s, 2H);
13C NMR (CDCl3, 100 MHz, δ ppm): 154.3, 152.6,
138.8, 134.6, 133.8, 132.2, 132.00, 131.95, 130.0,
129.1, 128.0, 127.4, 127.0, 125.4, 125.3. 125.04,
125.00, 124.96, 124.92, 122.6, 117.4, 46.3; HRMS
(ESI): calcd. for C22H14BrF3N2O + H = 459.0314,
= 445.0158, found: 445.0157.
O
N
found: 459.0317.
CF3
CF3
N
Bn
O
N
1-Benzyl-3-(4-(trifluoromethyl)phenyl)-1,4-
diazaspiro[4.5]deca-3,6,9-triene-2,8-dione (5h)
Pale brown solid; mp 182-183; yield: 75 mg (37%);
1H NMR (CDCl3, 400 MHz,  ppm): 8.65 (d, J =
8.4 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.30-7.23 (m,
5H), 6.36 (d, J = 10.0 Hz, 2H), 6.07 (d, J = 9.6 Hz,
2H), 4.61 (s, 2H); 13C NMR (CDCl3, 100 MHz, δ
N
O
Br
1-(4-Bromophenyl)-3-(4-
(trifluoromethyl)phenyl)quinoxalin-2(1H)-one
(4l-1)
Pale yellow solid; mp 174-175 oC; yield: 69 mg
(31%); 1H NMR (CDCl3, 400 MHz,  ppm): 8.53

18
Tetrahedron
ppm): 183.8, 164.7, 163.1, 142.6, 135.7, 134.2,
133.8, 132.9, 132.0, 129.0, 128.8, 128.7, 128.4,
128.3, 127.7, 125.60, 125.56, 125.52, 125.49,
125.0, 122.2, 80.5, 45.1; HRMS (ESI): calcd. for
C22H15F3N2O2 + H = 397.1155, found: 397.1159.
References
[1] D. Li, T. Yang, H. Su, W. Yu, Adv. Synth.
Catal. 2015, 357, 3696–3702;
[2] R. Reck, J. C. Jochims, Chem. Ber. 1982, 115,
14941508.
Copies of 1H NMR and 13C NMR spectra
of the substrates 3
3a
3b

19
3c
3d

20
Tetrahedron
3f
3e

21
3g
3h

22
Tetrahedron
3i
3j

23
Copies of 1H NMR and 13C NMR spectra
2b
of the products
2a

24
Tetrahedron
2c
2d

25
2e
2f

26
Tetrahedron
2g
2h

27
2j-1
2i

28
Tetrahedron
2j-2
2k-1