Copper-Catalyzed Direct C-3 Benzylation of Quinoxalin-2(1H)-ones with Methylarenes under Microwave Irradiation

Article abstract of DOI:10.1002/ejoc.201800697

A novel and efficient approach to the C(sp²)–H/C(sp³)–H oxidative coupling of quinoxalin-2(1H)-ones with methylarenes by using Cu^I as catalyst is reported. Various substrates were well tolerated in this methodology and the desired products were given in moderate-to-good yields. This reaction features good functional group compatibility and broad substrate scope.

Full text of DOI:10.1002/ejoc.201800697

A Journal of
Accepted Article
Title: Copper-catalyzed Direct C-3 Benzylation of Quinoxalin-2(1H)-
ones with Methylarenes under Microwave Irradiation
Authors: Leqian Hu, Jinwei Yuan, Junhao Fu, Taotao Zhang, Lele Gao,
Yongmei Xiao, Pu Mao, and Lingbo Qu
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800697
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800697
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10.1002/ejoc.201800697
European Journal of Organic Chemistry
FULL PAPER
Copper-catalyzed Direct C-3 Benzylation of Quinoxalin-2(1H)-
ones with Methylarenes under Microwave Irradiation
Leqian Hu,[a] Jinwei Yuan,*[a] Junhao Fu,[a] Taotao Zhang,[a] Lele Gao,[a] Yongmei Xiao,[a] Pu Mao,[a] and
Lingbo Qu*[a],[b]
Abstract: A novel and efficient approach for the C(sp2)-H/C(sp3)-H
oxidative coupling of quinoxalin-2(1H)-ones with methylarenes was
N
reported by using the Cu(I) as a catalyst. Various substrates were
N
well tolerated in this methodology and the desired products were
F
N
O
O
Br
given in moderate to good yields. This reaction features good
functional group compatibility, and broad substrate scope.
N
O
OH
aldose reductase inhibitor
MDR antagonist
N
Introduction
N
N
N
O
O
Quinoxalin-2(1H)-ones have attracted considerable attention
since they are endowed with significant biological activities and
outstanding chemical properties. They have been extensively
investigated in organic synthesis, materials chemistry and
pharmaceuticals.[1] In particular, 3-benzylquinoxalin-2(1H)-one
as an important pharmacophore has appeared in numerous
biological molecules, examples include MDR antagonist,[2]
aldose reductase inhibitor,[3] MAO-A inhibitor,[4] caroverine,[5]
(Figure 1). Therefore, the construction and functionalization of
quinoxalin-2(1H)-one skeletons have attracted consideration
attention.[6]
N
O
OMe
NH
N
Et
Et
OH
MAO-A inhibitor
caroverine
Figure 1. Representative biologically active 3-benzylquinoxalin-2(1H)-ones.
toluene and its derivatives have been used in cross-
dehydrogenative coupling (CDC) reactions as ArCOO- and
ArCO- surrogates.[14] To the best of our knowledge, there are
only a few examples in which toluene has been used as a
benzyl source and remains intact under the reaction conditions
without further oxidation.[15] Yang and Liu’s group reported a
practical iodine-catalyzed and Y(OTf)3-catalyzed oxidative
Over the past decades, transition-metal or transition-metal-free
catalyzed direct C-H bond functionalization has proven to be a
versatile technique for a step- and atom-economic method in
modern organic synthesis.[7] In this field, catalytic direct C3-H
functionalization of quinoxalin-2(1H)-ones has emerged as an
attractive approach to 3-substituted quinoxalin-2(1H)-ones,
which usually exhibit significant pharmaceutical properties.[8]
Recently, several important advances have been reported,
functionalization
of
isoquinolines
with
methylarenes,
respectively.[16] In 2015, Guo’s group developed an iron-
catalyzed radical cyclization of olefinic dicarbonyl compounds
with benzyl hydrocarbons with moderate to good yields.[17] In
2016, a novel CDC of heterocyclic N-oxides with toluene
derivatives was disclosed by Guo’s group.[18] A copper-catalyzed
regioselective cross-dehydrogenative coupling of coumarins with
benzylic C(sp3)-H bonds has also been developed.[19] Inspired
by these fascinating works of CDC, we dedicated to investigate
a novel method for the construction of C-C bond between
quinoxalin-2(1H)-ones and methylarene. Over the past few
years, the radical-mediated cross-dehydrogenative coupling
reaction has become a useful tool to construct the C-C bond via
an atom economic and environmentally friendly procedure.[20]
Very recently, a transition-metal-free direct C3 arylation of
quinoxalin-2(1H)-ones with arylamines has been disclosed
through a radical-mediated CDC reaction under mild conditions
by our group.[9f] Herein, we present a practical and efficient
copper-catalyzed approach for the direct benzylation of
including
radical
C3-H
arylation,[9]
phosphonation,[10]
amination,[11] acylation,[12] and cyanoalkylation[13] of quinoxalin-
2(1H)-ones (Scheme 1a). However, C-H benzylation of
quinoxalin-2(1H)-ones is still rare. Because of their importance,
it is desirable and in demand to introduce benzyl substituent at
3-position of quinoxalin-2(1H)-ones, which would probably
promote their applications in new drug discovery.
Toluene and its derivatives are the simplest and most highly
valuable starting materials in nature. Hence, developing novel
and efficient methodology toward their efficient utilization
continues to be a research focus in organic synthesis. Recently
[a]
Prof. L. Hu, Prof. J.Yuan, J. Fu, T. Zhang, L. Gao, Prof. Y. Xiao,
Prof. P. Mao, Prof. L. Qu
School of Chemistry and Chemical Engineering, Henan University of
Technology; Academicain Workstation for Natural Medicinal
Chemistry of Henan Province, Zhengzhou 450001, PR China
E-mail: yuanjinweigs@126.com, qulingbo@zzu.edu.cn
Prof. L. Qu,
[b]
quinoxalin-2(1H)-ones
using
nonprefunctionalized
and
College of Chemistry and Molecular Engineering, Zhengzhou
University, Zhengzhou 450001, PR China
inexpensive methylarenes as the benzyl source under
microwave irradiation (Scheme 1b).
Supporting information and the ORCID identification number for the
author of this article can be found under
https://doi.org/10.1002/ejoc.201800697.
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10.1002/ejoc.201800697
European Journal of Organic Chemistry
FULL PAPER
Table 1. Optimization of reaction conditions.[a]
Entry
1
Catalyst (equiv)
-
Oxidant (equiv)
TBPB(2.0)
TBHP (2.0)[c]
DTBP (2.0)
K2S2O8 (2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(1.0)
TBPB(3.0)
TBPB(4.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0)
TBPB(2.0) [d]
TBPB(2.0)
Time (h)
1.0
Yield (%)[ b]
28
15
Trace
0
Scheme 1. Synthesis of 3-substituted quinoxalin-2(1H)-one derivatives
2
-
1.0
3
-
1.0
Results and Discussion
4
-
1.0
Initially, the oxidative coupling reaction of 1-methylquinoxalin-
2(1H)-one (1a) with toluene (2a) was selected as the model
reaction under microwave irradiation (Table 1). When 2.0 equiv
tert-butyl peroxybenzoate (TBPB) was employed as the oxidant,
only 28% of the desired product 3aa was given at 100 oC for 1.0
5
Cu(OAc)2 (0.2)
CuSO4 (0.2)
CuO (0.2)
Cu2O (0.2)
CuI (0.2)
CuBr (0.2)
CuCl (0.2)
FeCl3 (0.2)
FeCl2 (0.2)
TBAI (0.2)
CuCl (0.05)
CuCl (0.1)
CuCl (0.15)
CuCl (0.2)
CuCl (0.2)
CuCl (0.2)
CuCl (0.2)
CuCl (0.2)
CuCl (0.2)
CuCl (0.2)
CuCl (0.2)
1.0
50
0
6
1.0
7
1.0
45
48
0
h
(Table 1, entry 1). Other oxidants including tert-butyl
8
1.0
hydroperoxide (TBHP), di-tert-butyl peroxide (DTBP), and
K2S2O8 were also tested, but TBPB exhibited the best efficiency
(Table 1, entries 1-4). According to our previous observation in
the C-H benzylation,[16,17,19] we envisioned that a transition-metal
catalyst might be beneficial for enhancing the reaction efficiency.
To our delight, a transition-metal catalyst proved to be crucial to
this coupling reaction. When 0.2 equiv Cu(OAc)2 as the catalyst
was used, the yield of 3aa increased to 50% (Table 1, entry 5).
To improve the reaction efficiency, different copper and iron
catalysts were screened, and CuCl was found to possess the
highest catalytic activity compared to other catalysts (Table 1,
entries 6-13). Unfortunately, no reaction was observed when
9
1.0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25[e]
1.0
55
65
30
45
Trace
50
52
55
45
50
15
30
70
45
68
18
1.0
1.0
1.0
1.0
1.0
tetra-n-butylammonium iodide (TBAI) was employed as
a
1.0
nonmetal catalyst (Table 1, entry 14). Subsequently, the amount
of CuCl was investigated, and 0.2 equiv could provide the best
yield (Table 1, entries 11, 15-17). The effect of the TBPB loading
was also screened. As a result, 2.0 equiv was found to be the
best choice and the yield could reach 65% (Table 1, entries 11,
18-20). Moreover, the effect of temperature was also tested.
Decreasing the temperature from 100 oC to 90 oC, the yield
reduced from 65% to 20%. In addition, raising the temperature
from 100 oC to 110 oC, the yield also decreased obviously (Table
S1, Supporting Information), perhaps because high temperature
could make the intermediate benzyl radical react with itself to
produce other side-products. The result clearly indicated that the
reaction temperature was essential for the coupling reaction. In
addition, the effect of reaction time was also investigated. 0.75 h
was proved be optimal time, and could provide the yield of 70%
(Table 1, entries 11, 21-23). Furthermore, the reaction was
proceeded under nitrogen atmosphere, the desired product 3aa
was obtained in 68% yield (Table 1, entry 24), which indicated
that the oxygen molecule from air was tolerated. When the
reaction proceeded using the conventional heating method, the
only 18% yield was obtained to prolong the reaction time to 16h
(Table 1, entry 25). Compared with the conventional heating, the
1.0
1.0
1.0
1.0
0.5
0.75
1.5
0.75
16.0
[a] Reaction conditions: 1-methylquinoxalin-2(1H)-one 1a (0.2 mmol, 32.0
mg), toluene 2a (1.0 mL), oxidant, and catalyst at 100 oC under microwave
irradiation. [b] Isolated yield. [c] 70% tert-butyl hydroperoxide (TBHP) in H2O.
[d] Under nitrogen atmosphere. [e] Conventional heating method with
magnetic stirring.
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10.1002/ejoc.201800697
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for strong electron-withdrawing substituted toluenes (-CN, -NO2),
the transformation wasn’t realized (3ak and 3al). It is noteworthy
that halo-substituted toluenes were tolerated well with moderate
to good yields (3af-3aj), opening the door for further
functionalization. Pleasingly, mono- and di- methyl substituted
toluenes were well compatible with the reaction system and the
other methyl groups maintaining intact. The reaction efficiency
was not sensitive to the substituent pattern of methylarenes
(3ab-3ae), whereas 1,3,5-trimethylbenzene seemed to favour
the formation of the desired product 3ae. More importantly, for
sterically hindered substrates such as -substituted-toluenes (2c,
2h and 2i) and -methylnaphthalene (2n) also proceeded well
under the optimized conditions, albeit with a slightly lower yield
(3ac, 3ah, 3ai and 3an). Fortunately, besides toluene
derivatives, ethylbenzene could also react smoothly with 1a to
provide the desired product 3am in 67% yield. Furthermore, the
reaction of 1-methylquinoxalin-2(1H)-one 1a with 2-
methylthiophene 2o could proceeded smoothly to provide the
desired product 3ao with moderate yield (58%).
use of microwave irradiation leads to faster reaction and higher
yield. Finally, the best yield was achieved using 0.2 equiv CuCl
as a catalyst, 2.0 equiv TBPB as an oxidant at 100 C for 45
o
min under microwave irradiation.
N
N
N
N
Cl
N
N
O
F
O
O
3ba (78%)
3ca (65%)
3da (70%)
N
N
Br
N
Br
N
O
Cl
N
O
N
O
3ea (72%)
3fa (68%)
3ga (75%)
N
Cl
Cl
N
O2N
N
N
N
O
N
O
O
3ha (68%)
3ia (0%)
3ja (68%)
N
N
N
N
O
N
O
O
N
O
Scheme 2. Substrate scope of substituted toluenes [Reaction conditions: 1-
methylquinoxalin-2(1H)-one 1a (0.2 mmol, 32.0 mg), substituted toluene 2 (1.0
mL), CuCl (0.04 mmol, 3.9 mg), and TBPB (0.4 mmol, 77.6 mg) at 100 oC
under microwave irradiation for 45 min; isolated yield of the product].
O
O
3ka (78%)
3la (64%)
3ma (65%)
N
N
H
O
With the optimized conditions in hand, we first examined the
generality and scope of methylarenes 2 for this transformation.
The results are summarized in Scheme 2. Under the standard
conditions, 1-methylquinoxalin-2(1H)-one 1a was smooth
benzylated with a set of toluene derivatives bearing both
electron-donating and electron-withdrawing groups. The
corresponding products were afforded in moderate yields (45-
78%). In general, it was found that toluenes with electron-rich
groups (-CH3) exhibited higher reactivity than those with
electron-poor (-F, -Cl, -Br, and -I), perhaps because the
corresponding benzylic carbon radical is more nucleophilic and
easier reacting with 1-methylquinoxalin-2(1H)-one. Unfortunately,
3na (0%)
Scheme 3. Substrate scope of substituted quinoxalin-2(1H)-ones [Reaction
conditions: quinoxalin-2(1H)-one 1 (0.2 mmol), toluene 2a (1.0 mL), CuCl
(0.04 mmol, 3.9 mg), and TBPB (0.4 mmol, 77.6 mg) at 100 oC under
microwave irradiation for 45 min; isolated yield of the product].
Next, we explored the coupling reaction of different quinoxalin-
2(1H)-ones (1) with toluene (2a) (Scheme 3). In general, both
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10.1002/ejoc.201800697
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electron-donating and electron-withdrawing groups on the
phenyl of quinoxalin-2(1H)-ones could also proceed smoothly to
deliver the corresponding products with moderate to good yields
(3ba-3ha). Notably, quinoxalin-2(1H)-ones containing halogen
moieties were tolerated well, and it hardly affected the reaction.
Unfortunately, when 6-nitro 1-methylquinoxalin-2(1H)-one was
employed, the corresponding product (3ia) could not be
provided. It is noteworthy that the presence of N-butyl, N-benzyl,
N-esteryl, and N-2-oxo-2-phenylethyl groups did not restrict
formation of the desired products (3ja, 3ka, 3la, and 3ma).
Regretfully, when we carried out the reaction of N-unprotected
quinoxalin-2(1H)-one with toluene, the desired product (3na)
was not provided, possibly quinoxalin-2(1H)-one including
reactive hydrogen was oxidized into other complexes.
oxidant TBPB was increased, and the reaction time was also
prolonged to 1.0 h. Interestingly, the result showed that the
corresponding bisbenzylated quinoxalin-2(1H)-one derivatives 3
could be provided with moderate yields (39-49%), their
structures were elucidated by HR MS, IR, and NMR.
To further demonstrate the synthetic utility of this protocol, we
applied it to the synthesis of an aldose reductase inhibitor 6
(Scheme 5). 7-Fluorouinoxalin-2(1H)-ones reacted with ethyl 2-
bromoacetate in the presence of K2CO3 to provide the ethyl 2-(7-
fluoro-2-oxoquinoxalin-1(2H)-yl)acetate 4.[21] Subsequently, the
substrate 4 was coupled with 4-bromotoluene to give ethyl 2-(3-
(4-bromobenzyl)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetate
5
under the optimized standard conditions. Finally, the desired
product 6 was afforded by the hydrolysis and the acidification.
To gain insight into the mechanism, some mechanistic studies
were designed and performed (Scheme 6). First, 2.0 equiv of
radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO)
was added into the reaction of 1-methylquinoxalin-2(1H)-one
(1a) with toluene (2a) under standard conditions, and it was
found that this transformation was completely inhibited. Adducts
of TEMPO and benzyl radical could be detected by HR MS (m/z
= 248.2010). Thus, these results suggested that the present
reactions should involve a free radical process (Scheme 6a).
Then, we studied the intermolecular competing kinetic isotope
effect (KIE) (Scheme 6b). An additional competitive experiment
involving a 1:1 mixture of 2a/D8-2a was carried out under the
standard conditions, and an intermolecular kinetic isotope effect
(KIE, kH/kD = 1.5) was obtained. However, the kinetic isotope
effect (kH/kD = 0.7) determined by the comparision of rates of two
independent reactions with 2a or D8-2a as the substrate
indicated that the cleavage of the benzyl C(sp3)-H bond is not a
rate-determining step of this transformation.[22]
Scheme 4. Synthesis of bisbenzyl quinoxalin-2(1H)-ones [Reaction conditions:
1-methylquinoxalin-2(1H)-one 1a (0.3 mmol, 48.0 mg), methylarene 2 (2.5 mL),
CuCl (0.06 mmol, 5.9 mg), and TBPB (1.5 mmol, 291 mg) at 100 oC under
microwave irradiation for 1.0 h; isolated yield of the product].
Scheme 5. Application of the coupling strategy to the synthesis of an aldose
reductase inhibitor 6.
Moreover, the synthesis of bisbenzylated quinoxalin-2(1H)-one
derivatives was also investigated. Herein, we further examined
the reaction of 1-methylquinoxalin-2(1H)-one (1a) and
methylarene (2) using copper-catalyzed this transformation
(Scheme 4). The loading amount of substrate methylarene and
Scheme 6. Control experiments.
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Based on the above results and previously reported studies,[15-19]
a plausible catalytic cycle was proposed and depicted in
Scheme 7. Initially, a tert-butoxyl radical A could be generated
by homolysis of TBPB or the Cu(I)-mediated single-electron
transfer (SET) to TBPB. The tert-butoxyl radical then abstracts a
hydrogen atom from toluene 2a to afford the benzyl radical B,
which selectively attacks the C=C double bond of 1a to afford
more stable nitrogen radical C. Subsequently, C would furnish
the corresponding nitrogen cation D via single-electron oxidation
by Cu(II). Finally, the expected coupling product 3aa is provided
by the deprotonation of D.
General procedure for the synthesis of 3-benzyl quinoxalin-2(1H)-ones (3)
Quinoxalin-2(1H)-ones 1 (0.2 mmol), methylarenes 2 (1.0 mL), CuCl (0.04 mmol, 3.9 mg),
and TBPB (0.4 mmol, 77.6 mg) were added to a 5 mL microwave reaction tube. The
mixture was stirred at 100 oC for 45 min under microwave irradiation. After completion of
the reaction, the solvent was distilled under vacuum. The residue was dissolved in ethyl
acetate (10 mL), then washed with saturated brine (10 mL  2). The organic phase was
dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by
silica gel column chromatography to give 3-benzyl quinoxalin-2(1H)-ones 3 using ethyl
acetate/dichloromethane/petroleum ether (1 : 5 : 15) as eluant.
3-Benzyl-1-methylquinoxalin-2(1H)-one (3aa). White solid (35.0 mg, 70% yield), m.p. 90-
91 oC (lit.23 72-74 oC). IR (KBr) (cm-1): 2978, 2875, 1647, 1600, 1469, 750, 699. 1H NMR
(400 MHz, CDCl3) : 7.83 (dd, JH-H = 8.0 Hz, JH-H = 1.4 Hz, 1H), 7.47-7.43 (m, 3H), 7.30-
7.26 (m, 3H), 7.20-7.16 (m, 2H), 4.25 (s, 2H), 3.60 (s, 3H). 13C NMR (100 MHz, CDCl3) :
159.2 (C=O), 154.7, 137.0, 133.3, 132.7, 129.9 (CH), 129.8 (CH), 129.5 (CH), 128.4 (CH),
126.6 (CH), 123.6 (CH), 113.5 (CH), 40.7 (CH2), 29.0 (CH3). HR MS (ESI) ([M + H]+) calcd.
for C16H15N2O: 251.1179, found: 251.1181.
1-Methyl-3-(4-methylbenzyl)quinoxalin-2(1H)-one (3ab). White solid (38.5 mg, 73%
yield), m.p. 105-106 oC. IR (KBr) (cm-1): 2935, 2897, 1647, 1591, 1488, 795, 748. 1H NMR
(400 MHz, CDCl3) : 7.85 (dd, JH-H = 8.0 Hz, JH-H = 1.2 Hz, 1H), 7.53-7.49 (m, 1H), 7.36-
7.30 (m, 3H), 7.26-7.25 (m, 2H), 7.09 (d, JH-H = 7.8 Hz, 2H), 4.22 (s, 2H), 3.65 (s, 3H), 2.29
(s, 3H). 13C NMR (100 MHz, CDCl3) : 159.5 (C=O), 154.7, 136.1, 133.9, 133.3, 132.7,
129.9, 129.8, 129.4, 129.1, 123.5, 113.5, 40.4 (CH2), 29.0 (CH3), 21.0 (CH3). HR MS (ESI)
([M + H]+) calcd. for C17H17N2O: 265.1335, found: 265.1338.
1-Methyl-3-(2-methylbenzyl)quinoxalin-2(1H)-one (3ac). White solid (34.3 mg, 65% yield),
m.p. 97-98 oC. IR (KBr) (cm-1): 2941, 2885, 1634, 1595, 1463, 792, 754, 743. 1H NMR
(400 MHz, CDCl3) : 7.78 (dd, JH-H = 8.0 Hz, JH-H = 1.4 Hz, 1H), 7.47 (td, JH-H = 7.8 Hz, JH-H
= 1.4 Hz, 1H), 7.34-7.32 (m, 1H), 7.28 (td, JH-H = 8.1 Hz, JH-H = 1.2 Hz, 1H), 7.22 (d, JH-H
=
Scheme 7. Proposed reaction mechanism.
8.3 Hz, 1H), 7.17-7.13 (m, 1H), 7.12-7.10 (m, 2H), 4.27 (s, 2H), 3.63 (s, 3H), 2.45 (s, 3H).
13C NMR (100 MHz, CDCl3) : 159.1 (C=O), 154.7, 137.3, 135.5, 133.2, 132.7, 130.3 (CH),
130.1 (CH), 129.9 (CH), 129.8 (CH), 126.7 (CH), 125.8 (CH), 123.5 (CH), 113.5 (CH), 37.9
(CH2), 29.1 (CH3), 20.0 (CH3). HR MS (ESI) ([M + H]+) calcd. for C17H17N2O: 265.1335,
found: 265.1338.
Conclusions
In conclusion, we have developed an efficient copper-catalyzed
direct benzylation of quinoxalin-2(1H)-ones at the C3 position
using methylarenes as the benzylated reagent under microwave
irradiation condition. This reaction has a broad scope of
substrates and provides a convenient process with respect to
the preparation of 3-benzyl quinoxalin-2(1H)-ones. Moreover,
mechanistic studies revealed that the benzylation occurs
through a radical mechanism.
1-Methyl-3-(3-methylbenzyl)quinoxalin-2(1H)-one (3ad). White solid (34.3 mg, 65%
yield), m.p. 52-53 oC. IR (KBr) (cm-1): 2954, 2887, 1650, 1590, 1469, 1094, 751, 698. 1H
NMR (400 MHz, CDCl3) : 7.84 (dd, JH-H = 8.0 Hz, JH-H = 1.4 Hz, 1H), 7.48 (td, JH-H = 7.8 Hz,
JH-H = 1.4 Hz, 1H), 7.31 (td, JH-H = 7.6 Hz, JH-H = 1.0 Hz, 1H), 7.27-7.24 (m, 2H), 7.22 (d, JH-
H = 8.3 Hz, 1H), 7.17 (t, JH-H = 7.9 Hz, 1H), 7.00 (d, JH-H = 7.5 Hz, 1H), 4.22 (s, 2H), 3.63 (s,
3H), 2.30 (s, 3H). 13C NMR (100 MHz, CDCl3) : 159.4 (C=O), 154.7, 137.9, 136.9, 133.3,
132.7, 130.2 (CH), 129.9 (CH), 129.8 (CH), 128.3 (CH), 127.3 (CH), 126.5 (CH), 123.5
(CH), 113.5 (CH), 40.7 (CH2), 29.1 (CH3), 21.4 (CH3). HR MS (ESI) ([M + H]+) calcd. for
C17H17N2O: 265.1335, found: 265.1338.
3-(3,5-Dimethylbenzyl)-1-methylquinoxalin-2(1H)-one (3ae). White solid (43.3 mg, 78%
Experimental Section
yield), m.p. 117-119 oC. IR (KBr) (cm-1): 2957, 2896, 1644, 1601, 1589, 1467, 753, 709. 1
H
NMR (400 MHz, CDCl3) : 7.87 (dd, JH-H = 8.0 Hz, JH-H = 1.3 Hz, 1H), 7.51 (td, JH-H = 7.8 Hz,
JH-H = 1.4 Hz, 1H), 7.33 (td, JH-H = 7.6 Hz, JH-H = 1.0 Hz, 1H), 7.26 (d, JH-H = 7.6 Hz, 1H),
7.06 (s, 2H), 6.84 (s, 1H), 4.19 (s, 2H), 3.65 (s, 3H), 2.27 (s, 3H). 13C NMR (100 MHz,
CDCl3) : 159.5 (C=O), 154.7, 137.8, 136.8, 133.4, 132.7, 129.9 (CH), 129.8 (CH), 128.3
(CH), 127.2 (CH), 123.5 (CH), 113.5 (CH), 40.6 (CH2), 29.1 (CH3), 21.2 (CH3). HR MS (ESI)
([M + H]+) calcd. for C18H19N2O: 279.1492, found: 279.1496.
General information
All substrates purchased from J & K Scientific Ltd. were used without further purification.
Column chromatography was performed using 300-400 mesh silica with the indicated
solvent system according to standard techniques. A CEM Discover microwave reactor with
infrared pyrometer and pressure control system was used. Nuclear magnetic resonance
spectra were recorded on Bruker Avance 400 MHz spectrometer. Chemical shifts for 1H
NMR spectra are recorded in parts per million from tetramethylsilane. Data were reported
as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet),
coupling constant in Hz and integration. Chemical shifts for 13C NMR spectra were recorded
in parts per million from tetramethylsilane. Chemical shifts for 19F NMR spectra were
recorded in parts per million with fluorobenzene ( = -113.15 ppm) as external standard.
High resolution mass spectra (HR MS) were obtained on Thermo Scientific LTQ Orbitrap
XL instrument using the ESI technique. IR spectra were recorded on Shimadazu IR-408
Fourier transform infrared spectrophotometer using a thin film supported on KBr pellets.
Melting points were measured on an XT4A microscopic apparatus uncorrected.
3-(4-Fluorobenzyl)-1-methylquinoxalin-2(1H)-one (3af). White solid (32.2 mg, 60% yield),
m.p. 99-100 oC. IR (KBr) (cm-1): 2989, 2886, 1652, 1601, 1504, 1219, 804, 753. 1H NMR
(400 MHz, CDCl3) : 7.84 (dd, JH-H = 8.0 Hz, JH-H = 1.3 Hz, 1H), 7.51 (td, JH-H = 7.8 Hz, JH-H
= 1.7 Hz, 1H), 7.44-7.40 (m, 2H), 7.32 (td, JH-H = 7.6 Hz, JH-H = 1.1 Hz, 1H), 7.26 (d, JH-H
=
8.3 Hz, 1H), 6.96 (t, JF-H = 8.7 Hz, 2H), 4.22 (s, 2H), 3.65 (s, 3H). 13C NMR (100 MHz,
CDCl3) : 161.7 (d, JF-C = 242.9 Hz), 159.0 (C=O), 154.6, 133.3, 132.7, 132.6 (d, JF-C = 3.4
Hz), 131.0 (d, JF-C = 7.9 Hz, CH), 129.9 (d, JF-C = 3.6 Hz, CH), 123.6 (CH), 115.1 (d, JF-C
=
21.1 Hz, CH), 113.6 (CH), 39.9 (CH2), 29.1 (CH3). 19F NMR (376 MHz, CDCl3) : -116.6.
HR MS (ESI) ([M + H]+) calcd. for C16H14FN2O: 269.1085, found: 269.1087.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800697
European Journal of Organic Chemistry
FULL PAPER
3-(4-Bromobenzyl)-1-methylquinoxalin-2(1H)-one (3ag). White solid (41.9 mg, 64%
yield), m.p. 126-128 oC. IR (KBr) (cm-1): 2943, 1650, 1599, 1483, 1468, 804, 753. 1H NMR
(400 MHz, CDCl3) : 7.83 (dd, JH-H = 8.0 Hz, JH-H = 1.4 Hz, 1H), 7.52 (td, JH-H = 7.8 Hz, JH-H
= 1.4 Hz, 1H), 7.40-7.38 (m, 2H), 7.35-7.31 (m, 3H), 7.26 (d, JH-H = 8.0 Hz, 1H), 4.20 (s, 2H),
3.65 (s, 3H). 13C NMR (100 MHz, CDCl3) : 158.6 (C=O), 154.6, 136.0, 133.3, 132.7, 131.4
(CH), 131.3 (CH), 130.0 (CH), 129.9 (CH), 123.6 (CH), 120.6, 113.6 (CH), 40.2 (CH2), 29.1
(CH3), 21.0 (CH3). HR MS (ESI) ([M + H]+) calcd. for C16H14BrN2O: 329.0284, found:
329.0282.
MHz, CDCl3) : 7.60 (s, 1H), 7.45 (d, JH-H = 7.4 Hz, 2H), 7.28 (d, JH-H = 7.3 Hz, 2H), 7.19 (t,
JH-H = 7.4 Hz, 1H), 7.02 (s, 1H), 4.23 (s, 2H), 3.63 (s, 3H), 2.39 (s, 3H), 2.33 (s, 3H). 13C
NMR (100 MHz, CDCl3) : 158.0 (C=O), 154.8, 139.6, 137.3, 132.4, 131.3, 131.1, 130.0
(CH), 129.5 (CH), 128.3 (CH), 126.4 (CH), 114.1 (CH), 40.7 (CH2), 29.0 (CH3), 20.5 (CH3),
19.1 (CH3). HR MS (ESI) ([M + H]+) calcd. for C18H19N2O: 279.1492, found: 279.1494.
3-Benzyl-7-fluoro-1-methylquinoxalin-2(1H)-one (3ca). White solid (34.8 mg, 65% yield),
m.p. 112-113 oC. IR (KBr) (cm-1): 2986, 2878, 1660, 1645, 1478, 1435, 1251, 1045, 811,
749. 1H NMR (400 MHz, CDCl3) : 7.54 (dd, JF-H = 8.8 Hz, JH-H = 2.8 Hz, 1H), 7.45 (d, JH-H
=
3-(2-Chlorobenzyl)-1-methylquinoxalin-2(1H)-one (3ah). White solid (25.6 mg, 45%
yield), m.p. 139-140 oC. IR (KBr) (cm-1): 2945, 1636, 1597, 1466, 1034, 749, 736. 1H NMR
(400 MHz, CDCl3) : 7.76 (dd, JH-H = 8.0 Hz, JH-H = 1.2 Hz, 1H), 7.50 (td, JH-H = 7.8 Hz, JH-H
= 1.3 Hz, 1H), 7.39-7.37 (m, 1H), 7.33-7.26 (m, 3H), 7.20-7.17 (m, 2H), 4.42 (s, 2H), 3.68 (s,
3H). 13C NMR (100 MHz, CDCl3) : 158.1 (C=O), 154.6, 135.2, 134.7, 133.2, 132.7, 131.3
(CH), 130.1 (CH), 129.9 (CH), 129.4 (CH), 127.9 (CH), 126.6 (CH), 123.5 (CH), 113.5 (CH),
38.0 (CH2), 29.1 (CH3). HR MS (ESI) ([M + H]+) calcd. for C16H14ClN2O: 285.0789, found:
285.0787.
8.0 Hz, 2H), 7.31-7.18 (m, 5H), 4.25 (s, 2H), 3.65 (s, 3H). 13C NMR (100 MHz, CDCl3) :
160.8, 159.8 (C=O), 157.4, 154.3, 136.7, 133.3 (d, JF-C = 11.0 Hz), 129.9, 129.5 (CH),
128.4 (CH), 126.7 (CH), 117.5 (d, JF-C = 23.8 Hz, CH), 115.4 (d, JF-C = 22.3 Hz, CH), 114.6
(d, JF-C = 8.7 Hz, CH), 40.7 (CH2), 29.3 (CH3). 19F NMR (376 MHz, CDCl3) : -119.0. HR MS
(ESI) ([M + H]+) calcd. for C16H14FN2O: 269.1085, found: 269.1087.
3-Benzyl-6-chloro-1-methylquinoxalin-2(1H)-one (3da). White solid (39.8 mg, 70% yield),
m.p. 162-163 oC. IR (KBr) (cm-1): 2964, 1652, 1598, 1467, 1454, 1054, 745, 697. 1H NMR
(400 MHz, CDCl3) : 7.75 (d, JH-H = 8.5 Hz, 1H), 7.44 (d, JH-H = 7.4 Hz, 2H), 7.30-7.19 (m,
5H), 4.23 (s, 2H), 3.61 (s, 3H). 13C NMR (100 MHz, CDCl3) : 159.4 (C=O), 154.4, 136.7,
135.7, 134.2, 131.2, 131.0 (CH), 129.5 (CH), 128.4 (CH), 126.7 (CH), 123.9 (CH), 113.6
(CH), 40.7 (CH2), 29.2 (CH3). HR MS (ESI) ([M + H]+) calcd. for C16H14ClN2O: 285.0789,
found: 285.0792.
3-(2-Bromobenzyl)-1-methylquinoxalin-2(1H)-one (3ai). White solid (31.5 mg, 48% yield),
m.p. 141-142 oC. IR (KBr) (cm-1): 2965, 1636, 1613, 1435, 1023, 749, 729. 1H NMR (400
MHz, CDCl3) : 7.75 (dd, JH-H = 8.0 Hz, JH-H = 1.3 Hz, 1H), 7.57 (dd, JH-H = 8.0 Hz, JH-H
1.0 Hz, 1H), 7.50 (td, JH-H = 7.8 Hz, JH-H = 1.4 Hz, 1H), 7.31-7.21 (m, 4H), 7.10 (td, JH-H
=
=
7.8 Hz, JH-H = 1.7 Hz, 1H), 4.42 (s, 2H), 3.68 (s, 3H). 13C NMR (100 MHz, CDCl3) : 158.1
(C=O), 154.6, 137.1, 133.1, 132.8 (CH), 132.7, 131.3 (CH), 130.1 (CH), 129.9 (CH), 128.2
(CH), 127.2 (CH), 125.3, 123.5 (CH), 113.5 (CH), 40.5 (CH2), 29.1 (CH3). HR MS (ESI) ([M
+ H]+) calcd. for C16H14BrN2O: 329.0284, found: 329.0287.
3-Benzyl-7-chloro-1-methylquinoxalin-2(1H)-one (3ea). White solid (40.9 mg, 72% yield),
m.p. 105-106 oC. IR (KBr) (cm-1): 2956, 1650, 1606, 1468, 1435, 1043, 808, 699. 1H NMR
(400 MHz, CDCl3) : 7.83 (d, JH-H = 2.4 Hz, 1H), 7.46-7.43 (m, 3H), 7.29 (t, JH-H = 7.7 Hz,
2H), 7.20 (t, JH-H = 7.3 Hz, 1H), 7.17 (d, JH-H = 8.9 Hz, 1H), 4.24 (s, 2H), 3.62 (s, 3H). 13C
NMR (100 MHz, CDCl3) : 160.7 (C=O), 154.3, 136.6, 13.2, 132.0, 129.8 (CH), 129.5 (CH),
129.3 (CH), 128.8, 128.4 (CH), 126.7 (CH), 114.6 (CH), 40.7 (CH2), 29.2 (CH3). HR MS
(ESI) ([M + H]+) calcd. for C16H14ClN2O: 285.0789, 285.0792.
3-(4-Iodobenzyl)-1-methylquinoxalin-2(1H)-one (3aj). Light yellow solid (48.9 mg, 65%
yield), m.p. 135-137 oC. IR (KBr) (cm-1): 2987, 2922, 1651, 1600, 1481, 1469, 1320, 1058,
1005, 752. 1H NMR (400 MHz, CDCl3) : 7.84 (dd, JH-H = 8.0 Hz, JH-H = 1.3 Hz, 1H), 7.60 (d,
JH-H = 8.3 Hz, 2H), 7.53 (td, JH-H = 7.8 Hz, JH-H = 1.4 Hz, 1H), 7.34 (td, JH-H = 7.7 Hz, JH-H
=
1.0 Hz, 1H), 7.28 (d, JH-H = 8.4 Hz, 1H), 7.21 (d, JH-H = 8.3 Hz, 2H), 4.19 (s, 2H), 3.66 (s,
3H). 13C NMR (100 MHz, CDCl3) : 158.6 (C=O), 154.6, 137.4 (CH), 136.7, 133.3, 132.7,
131.6 (CH), 130.1 (CH), 129.9 (CH), 123.7 (CH), 113.6 (CH), 92.1, 40.2 (CH2), 29.1 (CH3),
21.0 (CH3). HR MS (ESI) ([M + H]+) calcd. for C16H14IN2O: 377.0145, found: 377.0148.
3-Benzyl-6-bromo-1-methylquinoxalin-2(1H)-one (3fa). White solid (44.6 mg, 68% yield),
m.p. 142-143 oC. IR (KBr) (cm-1): 3025, 2987, 1651, 1591, 1584, 1465, 1073, 828, 736. 1
H
NMR (400 MHz, CDCl3) : 7.68 (d, JH-H = 8.4 Hz, 1H), 7.45-7.40 (m, 4H), 7.29 (t, JH-H = 7.6
Hz, 2H), 7.21 (t, JH-H = 7.3 Hz, 1H), 4.22 (s, 2H), 3.61 (s, 3H). 13C NMR (100 MHz, CDCl3)
: 159.6 (C=O), 154.3, 136.6, 134.3, 131.5, 131.1 (CH), 129.5 (CH), 128.4 (CH), 126.8 (CH),
126.7 (CH), 123.8, 116.6 (CH), 40.7 (CH2), 29.2 (CH3). HR MS (ESI) ([M + H]+) calcd. for
1-Methyl-3-(1-phenylethyl)quinoxalin-2(1H)-one (3am). White solid (35.4 mg, 67% yield),
m.p. 125-127 oC. IR (KBr) (cm-1): 2978, 2897, 1648, 1592, 1649, 750, 707. 1H NMR (400
MHz, CDCl3) : 7.90 (dd, JH-H = 7.9 Hz, JH-H = 1.0 Hz, 1H), 7.47-7.42 (m, 3H), 7.32-7.23 (m,
3H), 7.19-7.13 (m, 2H), 4.82 (q, JH-H = 7.1 Hz, 1H), 3.57 (s, 3H), 1.68 (d, JH-H = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3) : 161.8 (C=O), 154.4, 143.1, 133.0, 132.7, 130.1 (CH), 129.7
(CH), 128.4 (CH), 128.1 (CH), 126.5 (CH), 123.4 (CH), 113.5 (CH), 41.8 (CH), 29.1 (CH3),
19.7 (CH3). HR MS (ESI) ([M + H]+) calcd. for C17H17N2O: 265.1335, found: 265.1337.
C16H14BrN2O: 329.0284, found: 329.0287.
3-Benzyl-7-bromo-1-methylquinoxalin-2(1H)-one (3ga). White solid (49.2 mg, 75% yield),
m.p. 134-135 oC. IR (KBr) (cm-1): 2991, 2987, 1648, 1590, 1582, 1462, 1290, 1075, 806,
760. 1H NMR (400 MHz, CDCl3) : 7.99 (d, JH-H = 2.2 Hz, 1H), 7.59 (dd, JH-H = 8.9 Hz, JH-H
=
2.3 Hz, 1H), 7.44 (d, JH-H = 7.8 Hz, 2H), 7.31-7.27 (m, 2H), 7.23-7.19 (m, 1H), 7.12 (d, JH-H
= 8.9 Hz, 1H), 4.24 (s, 2H), 3.62 (s, 3H). 13C NMR (100 MHz, CDCl3) : 160.6 (C=O), 154.3,
136.6, 133.5, 132.5 (CH), 132.4, 132.3 (CH), 129.5 (CH), 128.4 (CH), 126.7 (CH), 116.1,
115.0 (CH), 40.7 (CH2), 29.2 (CH3). HR MS (ESI) ([M + H]+) calcd. for C16H14BrN2O:
329.0284, found: 329.0288.
1-Methyl-3-(naphthalen-1-ylmethyl)quinoxalin-2(1H)-one (3an). Light yellow solid (37.8
mg, 63% yield), m.p. 114-116 oC. IR (KBr) (cm-1): 2974, 1634, 1592, 1467, 1094, 770, 753.
1H NMR (400 MHz, CDCl3) : 8.39 (d, JH-H = 8.4 Hz, 1H), 7.80 (d, JH-H = 8.0 Hz, 1H), 7.73 (t,
JH-H = 7.4 Hz, 2H), 7.62 (d, JH-H = 7.0 Hz, 1H), 7.49 (t, JH-H = 7.2 Hz, 1H), 7.44-7.39 (m, 3H),
7.23 (t, JH-H = 7.4 Hz, 1H), 7.15 (d, JH-H = 8.3 Hz, 1H), 4.72 (s, 2H), 3.60 (s, 3H). 13C NMR
(100 MHz, CDCl3) : 158.9 (C=O), 154.7, 133.9, 133.3, 133.1, 132.6, 132.5, 130.0 (CH),
129.8 (CH), 128.5 (CH), 128.3 (CH), 127.4 (CH), 125.9 (CH), 125.5 (CH), 125.4 (CH),
124.8 (CH), 123.4 (CH), 113.4 (CH), 37.7 (CH3), 29.1 (CH2). HR MS (ESI) ([M + H]+) calcd.
for C20H17N2O: 301.1335, found: 301.1335.
3-Benzyl-6,7-dichloro-1-methylquinoxalin-2(1H)-one (3ha). White solid (43.2 mg, 68%
yield), m.p. 189-190 oC. IR (KBr) (cm-1): 2954, 2876, 1660, 1610, 1468, 1438, 1284, 1036,
887, 755. 1H NMR (400 MHz, CDCl3) : 7.92 (s, 1H), 7.42 (d, JH-H = 7.3 Hz, 2H), 7.34 (s,
1H), 7.29 (t, JH-H = 7.7 Hz, 2H), 7.21 (t, JH-H = 7.3 Hz, 1H), 4.23 (s, 2H), 3.60 (s, 3H). 13C
NMR (100 MHz, CDCl3) : 160.8 (C=O), 154.1, 136.3, 133.9, 132.7, 131.8, 130.7 (CH),
129.5 (CH), 128.5 (CH), 127.3, 126.8 (CH), 115.0 (CH), 40.6 (CH2), 29.3 (CH3). HR MS
(ESI) ([M + H]+) calcd. for C16H13Cl2N2O: 319.0399, found: 319.0395.
1-Methyl-3-(thiophen-2-ylmethyl)quinoxalin-2(1H)-one (3ao). White solid (29.7 mg, 58%
yield), m.p. 117-119 oC. IR (KBr) (cm-1): 2981, 1643, 1592, 1470, 1375, 753, 702. 1H NMR
(400 MHz, CDCl3) : 7.84 (dd, JH-H = 7.9 Hz, JH-H = 1.2 Hz, 1H), 7.51 (td, JH-H = 7.8 Hz, JH-H
= 1.4 Hz, 1H), 7.32 (t, JH-H = 7.5 Hz, 1H), 7.25 (d, JH-H = 8.4 Hz, 1H), 7.15 (dd, JH-H = 5.1 Hz,
JH-H = 1.0 Hz, 1H), 7.05 (d, JH-H = 3.2 Hz, 1H), 6.94-6.91 (m, 1H), 4.46 (s, 2H), 3.67 (s, 3H).
13C NMR (100 MHz, CDCl3) : 157.9 (C=O), 154.5, 138.5, 133.3, 132.6, 130.1 (CH), 129.9
(CH), 126.7 (CH), 126.6 (CH), 124.6 (CH), 123.6 (CH), 113.6 (CH), 34.8 (CH2), 29.1 (CH3).
HR MS (ESI) ([M + H]+) calcd. for C14H13N2OS: 257.0743, found: 257.0747.
3-Benzyl-1-butylquinoxalin-2(1H)-one (3ja). Viscous liquid (39.7 mg, 68% yield). IR (KBr)
(cm-1): 2989, 2978, 1650, 1601, 1487, 1454, 753, 738. 1H NMR (400 MHz, CDCl3) : 7.85
(dd, JH-H = 8.0 Hz, JH-H = 1.4 Hz, 1H), 7.51-7.45 (m, 3H), 7.32-7.25 (m, 4H), 7.20 (td, JH-H
=
4.7 Hz, JH-H = 1.1 Hz, 1H), 4.26 (s, 2H), 4.19 (t, JH-H = 7.9 Hz, 2H), 1.73-1.66 (m, 2H), 1.49-
1.40 (m, 2H), 0.97 (t, JH-H = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) : 159.3 (C=O), 154.4,
137.1, 133.0, 132.5, 130.1 (CH), 129.8 (CH), 129.5 (CH), 128.4 (CH), 126.5 (CH), 123.3
(CH), 113.5 (CH), 42.2 (CH2), 40.7 (CH2), 29.2 (CH2), 20.3 (CH2), 13.8 (CH3). HR MS (ESI)
([M + H]+) calcd. for C19H21N2O: 293.1648, found: 293.1650.
3-benzyl-1,6,7-trimethylquinoxalin-2(1H)-one (3ba). White solid (43.4 mg, 78% yield),
m.p. 157-158 oC. IR (KBr) (cm-1): 2923, 1642, 1618, 1579, 1450, 764, 698. 1H NMR (400
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800697
European Journal of Organic Chemistry
FULL PAPER
1,3-Dibenzylquinoxalin-2(1H)-one (3ka). Light yellow solid (50.8 mg, 78% yield), m.p.
132-133 oC (lit.24 136 oC). IR (KBr) (cm-1): 2989, 2876, 1650, 1601, 1453, 750, 736. 1H
NMR (400 MHz, CDCl3) : 7.84 (d, JH-H = 1.5 Hz, 1H), 7.49 (d, JH-H = 7.3 Hz, 2H), 7.39 (td,
JH-H = 7.8 Hz, JH-H = 1.5 Hz, 1H), 7.33-7.27 (m, 5H), 7.24-7.18 (m, 5H), 5.46 (s, 2H), 4.33 (s,
2H). 13C NMR (100 MHz, CDCl3) : 159.4 (C=O), 154.8, 137.0, 135.2, 133.0, 132.6, 130.0
(CH), 129.9 (CH), 129.5 (CH), 128.9 (CH), 128.4 (CH), 127.6 (CH), 126.8 (CH), 126.6 (CH),
123.6 (CH), 114.3 (CH), 45.9 (CH2), 40.7 (CH2). HR MS (ESI) ([M + H]+) calcd. for
C22H19N2O: 327.1492, found: 327.1494.
7.00 (m, 2H), 6.90-6.88 (m, 1H), 6.82-6.79 (m, 2H), 5.36 (dd, JH-H = 8.6 Hz, JH-H = 6.9 Hz,
1H), 3.96 (q, JH-H = 8.6 Hz, 1H), 3.63 (s, 3H), 3.58 (q, JH-H = 8.6 Hz, 1H). 13C NMR (100
MHz, CDCl3) : 159.2 (C=O), 154.3, 143.5, 142.2, 133.1, 132.5, 130.2 (CH), 130.1 (CH),
126.6 (CH), 126.4 (CH), 125.8 (CH), 125.7 (CH), 124.5 (CH), 123.6 (CH), 113.5 (CH), 44.5
(CH3), 35.1 (CH2), 29.2 (CH3). HR MS (ESI) ([M + H]+) calcd. for C19H17N2OS2: 353.0777,
found: 353.0776.
Acknowledgements
Ethyl 2-(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetate (3la). White solid (41.2 mg, 64%
yield), m.p. 108-109 oC. IR (KBr) (cm-1): 2988, 1739, 1650, 1573, 1221, 1189, 756, 699. 1
H
We gratefully acknowledge the Department of Henan Province
NMR (400 MHz, CDCl3) : 7.85 (dd, JH-H = 8.0 Hz, JH-H = 1.4 Hz, 1H), 7.47-7.43 (m, 3H),
7.32-7.24 (m, 3H), 7.21-7.17 (m, 1H), 7.01 (dd, JH-H = 8.3 Hz, JH-H = 0.6 Hz, 1H), 4.95 (s,
2H), 4.26 (s, 2H), 4.20 (q, JH-H = 7.1 Hz, 2H), 1.22 (t, JH-H = 7.1 Hz, 3H). 13C NMR (100 MHz,
CDCl3) : 167.0 (C=O), 159.1, 154.3, 136.8, 132.8, 130.3 (CH), 130.0 (CH), 129.5 (CH),
128.4 (CH), 126.6 (CH), 123.8 (CH), 113.0 (CH), 62.0 (CH2), 43.5 (CH2), 40.6 (CH2), 14.1
(CH3). HR MS (ESI) ([M + H]+) calcd. for C19H19N2O3: 323.1390, found: 323.1394.
Natural
Science
and
Technology
Foundation
(No.
172102210225, 172102210222), Natural Science Foundation in
Henan Province Department of Education (No. 17A150005,
17A150007), the Program for Innovative Research Team from
Zhengzhou (No. 131PCXTD605), and Project of Youth
Backbone Teachers of Henan University of Technology (No.
2016003).
3-benzyl-1-(2-oxo-2-phenylethyl)quinoxalin-2(1H)-one (3ma). White solid (46.0 mg, 65%
yield), m.p. 143-144 oC. IR (KBr) (cm-1): 2956, 1710, 1645, 1599, 1226, 749, 686. 1H NMR
(400 MHz, CDCl3) : 8.03 (dd, JH-H = 7.2 Hz, JH-H = 1.3 Hz, 2H), 7.88 (dd, JH-H = 8.0 Hz, JH-H
= 1.4 Hz, 1H), 7.65 (t, JH-H = 6.4 Hz, 1H), 7.51 (t, JH-H = 7.9 Hz, 2H), 7.45 (d, JH-H = 7.2 Hz,
2H), 7.40 (dd, JH-H = 8.1 Hz, JH-H = 1.5 Hz, 1H), 7.32-7.27 (m, 3H), 7.21 (t, JH-H = 7.3 Hz,
1H), 6.90 (d, JH-H = 8.3 Hz, 1H), 5.67 (s, 2H), 4.28 (s, 2H). 13C NMR (100 MHz, CDCl3) :
191.1 (C=O), 158.9 (C=O), 154.5, 136.9, 134.4, 134.3, 132.9, 132.7, 130.2, 129.9, 129.5,
129.0, 128.4, 128.1, 126.6, 123.7, 113.5 (CH), 48.5 (CH2), 40.7 (CH2). HR MS (ESI) ([M +
H]+) calcd. for C23H19N2O2: 355.1441, found: 355.1443.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: quinoxalin-2(1H)-one • methylarene • benzylation •
General procedure for the synthesis of bisbenzyl quinoxalin-2(1H)-ones (3)
transition-metal-catalyzed • radical reaction
1-Methylquinoxalin-2(1H)-one 1a (0.3 mmol, 48.0 mg), methylarenes 2 (2.5 mL), CuCl (0.06
mmol, 5.9 mg), and TBPB (1.5 mmol, 291 mg) were added to a 5 mL microwave reaction
tube. The mixture was stirred at 100 oC for 1.0 h under microwave irradiation. After
completion of the reaction, the solvent was distilled under vacuum. The residue was
dissolved in ethyl acetate (10 mL), then washed with saturated brine (10 mL  2). The
organic phase was dried over anhydrous Na2SO4 and concentrated under vacuum. The
residue was purified by silica gel column chromatography to give bisbenzyl quinoxalin-
2(1H)-ones 3 using ethyl acetate/ dichloromethane/petroleum ether (1 : 5 : 15) as eluant.
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Direct C-3 Benzylation of Quinoxalin-
2(1H)-ones
Leqian Hu, Jinwei Yuan,* Junhao Fu,
Taotao Zhang, Lele Gao, Yongmei Xiao,
Pu Mao, Lingbo Qu*
Page No. – Page No.
Text for Table of Contents
Copper-catalyzed Direct C-3
Benzylation of Quinoxalin-2(1H)-ones
with Methylarenes under Microwave
Irradiation
A simple and efficient protocol for the C3 benzylation of quinoxalin-
2(1H)-ones with methylarenes was developed.
This article is protected by copyright. All rights reserved.