Metal-free oxidative coupling of quinoxalin-2(1: H)-ones with arylaldehydes leading to 3-acylated quinoxalin-2(1 H)-ones

Article abstract of DOI:10.1039/c8ob00206a

A facile TBHP-mediated direct oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes has been developed under metal-free conditions. This method provided a convenient and efficient approach to various 3-acylated quinoxalin-2(1H)-ones from readily available starting materials with excellent regioselectivity. This reaction proceeded efficiently under mild conditions over a broad range of substrates and with functional group tolerance.

Full text of DOI:10.1039/c8ob00206a

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Metal-free oxidative coupling of quinoxalin-2(1H)-ones with
arylaldehydes leading to 3-acylated quinoxalin-2(1H)-ones
Jin-Wei Yuan,*a Jun-Hao Fu,a Shuai-Nan Liu,a Yong-Mei Xiao,a Pu Maoa and Ling-Bo Qu*b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A facile TBHP-mediated direct oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes has been developed under
metal-free conditions. This method provided a convenient and efficient approach to various 3-acylated quinoxalin-2(1H)-
ones from readily available starting materials with excellent regioselectivity. This reaction proceeded efficiently under mild
conditions, over a broad range of substrates and functional group tolerance.
www.rsc.org/
benzoylquinoxaline-2(1H)-ones through an unprecedented metal-
free oxidative ring contraction of 1,5-benzodiazepin-2-ones
Introduction
16]
(Scheme
1b).[11a,
Recently,
transition-metal-catalyzed
The nitrogen-containing heterocycle quinoxalin-2(1H)-one has
undoubtedly become a privileged skeleton within the quinoxaline
family.[1] Quinoxalin-2(1H)-one derivatives exhibit an amazingly
wide spectrum of biological properties including anticancer,[2]
antimicrobial,[3] antithrombotic,[4] protein kinase inhibitory,[5] or
benzodiazepine receptor agonist activity.[6] Importantly, they have
been extensively investigated in organic synthesis, materials
chemistry and pharmaceuticals.[7] In particular, 3-acylquinoxalin-
2(1H)-one as an important pharmacophore has appeared numerous
novel biological properties, including pteridine reductase
inhibitors,[8] and antitumor agents.[9] Furthermore, electronic
properties of them have been leveraged in free radical
photoinitiated polymerization processes[10] and fluorescence
applications.[11]
decarboxylative coupling[17] is an attractive synthetic method for C-
C bond formation since it does not require the use of stoichiometric
organometallic coupling reagents and produces CO2 as the sole
waste. In 2017, Hu and co-workers achieved a silver-catalyzed
decarboxylative acylation of quinoxaline-2(1H)-ones with α-oxo-
carboxylic acids[18] (Scheme 1c), which was only found to provide
C3-acylated products of quinoxaline-2(1H)-ones. Although these
methods represent important advances, they suffered often some
drawbacks, such as: (1) a multi-step synthesis was required; (2) high
temperatures are not energy efficient; (3) the complicated
substrate was not commercially available or was expensive; (4)
metal catalyst was toxic as well as being commonly undesired
residual impurities in pharmaceutical products. Therefore, the
search for a more mild and simple method for synthesizing 3-
acylquinoxalin-2(1H)-ones is still highly desirable.
Recently, a number of methods have been developed for the
synthesis of 3-substituted quinoxalin-2-ones, such as arylation,[12]
amination,[13] phosphonation.[14] In contrast, only a few examples
have been reported for the selective C-3 acyl quinoxalin-2-ones.
Conventional methods involve construction of 3-acylquinoxalin-
2(1H)-ones based on the condensation of ethyl 3-aryl-3-bromo-2-
oxopropanoates with o-phenylenediamine in acetic acid to give 3-
(α-bromobenzyl)quinoxalin-2(1H)-ones which were converted into
the corresponding 3-aroylquinoxalin-2(1H)-ones via oxidative
dehydrobromination in dimethyl sulfoxide according to Kornblum
oxidation reaction (Scheme 1a).[15] In more elaborate approach,
In recent years, metal-free oxidative functionalizations of
aldehydes have emerged as one of the most powerful methods for
the construction of C-C bonds.[19] Aldehydes are known to be easily
accessible as well as relatively safe and stable, and are hence
common
synthons
in
metal-
or
non-metal-catalyzed
transformations.[20] Aldehydes as acylating agents have attracted
significant attention owing to their functional group tolerance, mild
reaction conditions, and cost-effectiveness.[21] In 2015, our groups
has developed an efficient protocol for iron-catalyzed cross-
coupling of coumarins with aromatic aldehydes.[22] To the best of
our knowledge, direct C-3 acylation of quinoxalin-2(1H)-ones using
aldehydes as acylating agents without transition-metal catalyst has
not been reported. Herein, we describe an effective and metal-free
oxidative cross-dehydrogenative coupling of quinoxalin-2(1H)-ones
with diverse aldehydes in the presence of tert-butyl hydroperoxide
(TBHP) (Scheme 1d).
Sabot and co-workers reported
a
practical access to
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Previous works:
entries 9, 18-21), perhaps because high temperature could make
the intermediate benzoyl radical react with itself to produce other
side-products. Subsequently, the effect of reaction time was also
investigated, and 5.0 h was proved be optimal time (Table 1, entries
9, 22-24). In addition, the ratio of 1a and 2a was investigated. When
the ratio of 1a and 2a was 1:2, the best yield (80%) could be
obtained (Supporting Information, Table S1, entries 1-4). Finally,
when the reaction was protected by nitrogen, the desired product
3aa was obtained in 78% yield (Table 1, entry 25), which indicated
that the oxygen molecule from air was tolerated. After screening
the reaction conditions, the optimal conditions were identified as
follows: the molar ratio of 1a and 2a for 1:2, 4.0 equiv. TBHP as the
oxidant in DCE at 70 oC under air atmosphere for 5.0 h.
Table 1 Optimization of reaction conditionsa
This work:
Scheme 1. Synthesis of 3-aroylquinoxalin-2(1H)-ones
Oxidant
(equiv.)
Temp
(oC)
Time
(h)
Yieldb
(%)
Entry
Solvent
1c
2
TBHPd (3.0)
−
DCE
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
50
60
80
90
70
70
70
70
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
3.0
4.0
6.0
5.0
72
DCE
0
3
TBHP (3.0)
DTBP (3.0)
K2S2O8 (3.0)
(NH4)2S2O8 (3.0)
TBPB (3.0)
TBHP (2.0)
TBHP (4.0)
TBHP (5.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
TBHP (4.0)
DCE
75
Results and discussion
4
DCE
trace
trace
trace
35
5
DCE
Our initial study focused on the cross-coupling reaction of
quinoxalin-2(1H)-one (1a) with benzaldehyde (2a) as a model
reaction for a screening of the various reaction parameters (Table
1). The benzoylated product 3aa was produced in 72% yield using
10 mol% Cu(OAc)2 as a catalyst and 3.0 equiv. of 70 % tert-butyl
hydroperoxide (TBHP) in H2O as an oxidant (Table 1, entry 1). The
structure of 3aa was confirmed by NMR spectra. It was noticeable
that 75% of 3aa could be obtained in the absence of copper, while
3aa was not observed in the absence of TBHP, indicating that the
reaction was mainly mediated by TBHP (Table 1, entries 2-3).
However, the use of tert-butyl peroxybenzoate (TBPB) as an oxidant
did not improve the yield of 3aa (Table 1, entry 7). Other oxidants,
such as di-tert-butyl peroxide (DTBP), K2S2O8, and (NH4)2S2O8 were
found to be ineffective in the reaction (Table 1, entries 4-6).
Screening of the loading of the oxidant revealed that 4.0 equiv. of
TBHP was optimal, and the yield of 3aa was 80% (Table 1, entries 3,
8-10). Then, the effect of various solvents, such as 1,2-
dichloroethane (DCE), CH3CN, DMSO, H2O, acetone, CH3OH,
dioxane, and ethyl acetate, were tested, and DCE was found to be
the best choice (Table 1, entries 9, 11-17). The result clearly
indicated that the solvent was essential for the coupling reaction.
The effect of temperature was also screened. Raising the
6
DCE
7
DCE
8
DCE
50
9
DCE
80
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25e
DCE
36
CH3CN
DMSO
H2O
30
10
30
Acetone
CH3OH
Dioxane
Ethyl acetate
DCE
10
50
<5
30
10
DCE
20
DCE
72
DCE
65
DCE
50
DCE
65
DCE
80
DCE
78
a
Reaction conditions: 1-methylquinoxalin-2(1H)-one 1a (0.2 mmol, 32.0 mg),
o
o
b
temperature from 50 C to 70 C increased the yield from 10 to
benzaldehyde 2a (0.4 mmol, 42.4 mg), oxidant, and solvent (2.0 mL). Isolated
yield. c10 mmol% Cu(OAc)2 was used. d70% tert-butyl hydroperoxide (TBHP) in
H2O. eUnder nitrogen condition.
o
80%, however, the yield decreased obviously at 90 C (Table 1,
2 | J. Name., 2012, 00, 1-3
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Table 2 Substrate scope with aryl aldehydes[a,b]
ARTICLE
electron-poor substituents reacted smoothly affording the
corresponding products in moderate to good yields (45-85%).
Generally, benzaldehydes with electron-donating groups (3aa-3ai)
gave higher yields than electron-withdrawing groups (3aj-3ar). In
particular, halogen-substituted benzaldehydes could work well to
give the desired products in moderate yields, which make this
reaction particularly attractive for further transformation by
transition-metal-catalyzed coupling reactions. Furthermore, when
the strong electron-withdrawing group, such as 4-
cyanobenzaldehyde (2r), was present, the corresponding product
3ar was generated in 56% yield. Unfortunately, 4-
nitrobenzaldehyde (2s) failed to give the desired product 3as. In
addition, 2-naphthaldehyde (2i) gave a slightly higher yield relative
to 1-naphthaldehyde (2h). When 2-methoxyl benzaldehyde (2d), 2-
chlorobenzaldehyde (2l), and 2-borobenzaldehyde (2n) were
employed, the yields of products were lower slightly than that of
the corresponding 4-substituted aldehydes. Remarkably, the steric
hindrance effect of aromatic aldehydes has some influence on the
coupling reaction. It was noteworthy that heterocyclic aromatic
aldehydes, 2-thenaldehyde (2t) and 2-furaldehyde (2u), were well
tolerated to provide the products 3at (65%) and 3au (70%).
O
O
O
O
O
O
N
N
N
N
N
N
O
3aa (80%)
3ab (82%)
3ac (85%)
(1 g scale: 78%)
O
O
O
N
O
N
N
N
O
N
O
S
N
O
N
3ad (45%)
3ae (75%)
3af (65%)
O
N
O
N
O
N
O
O
N
O
N
O
N
O
3ag (82%)
3ah (75%)
3ai (70%)
Table 3 Substrate scope with substituted quinoxalin-2(1H)-onesa,b
O
N
O
N
O
N
Cl
N
O
F
Br
I
N
O
Cl
N
O
3aj (70%)
3ak (67%)
3al (45%)
O
O
N
O
N
Br
N
Br
N
O
N
O
N
O
3am (65%)
3an (48%)
3ao (57%)
O
O
O
O
O
O
O
O
N
O
N
N
F
N
N
Cl
N
N
N
N
O
N
O
CN
N
O
N
O
O
3ba (85%)
3ca (73%)
3da (75%)
3ap (75%)
3aq (70%)
3ar (56%)
O
N
O
N
O
N
O
N
O
O
N
O2N
N
O
S
Cl
N
O
Br
N
O
N
O
N
O
NO2
N
O
N
O
3ea (78%)
3fa (80%)
3ga (0 %)
3as (0 %)
3at (65%)
3au (70%)
O
N
O
N
O
N
O
N
O
N
N
O
N
O
N
O
N
O
N
O
3av (40%)
3aw (35%)
O
3ha (73%)
3ia (75%)
3ja (84%)
O
a
Reaction conditions: 1-methylquinoxalin-2(1H)-ones 1a (0.2 mmol, 32 mg),
N
arylaldehyde 2 (0.4 mmol), TBHP (0.8 mmol, 104 mg) in 2.0 mL DCE solvent at 70
oC for 5.0 h. b Isolated yield.
N
O
O
O
3ka (75%)
a
Reaction conditions: quinoxalin-2(1H)-ones 1 (0.2 mmol), benzaldehyde 2a (0.4
With the optimal reaction conditions in hand, we turned our
attention to embarking on the generality and scope of
arylaldehydes for this transformation. The results are summarized
in Table 2. A variety of benzaldehydes bearing electron-rich and
mmol, 42.4 mg), TBHP (0.8 mmol, 104 mg) in 2.0 mL DCE solvent at 70 oC for 5.0
h. b Isolated yield.
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Gratifyingly, aliphatic aldehydes, n-butanal (3v) and iso-butanal under mild conditions. To further demonstrate the synthetic utility
(3w), could also react smoothly to deliver the desired products (3av of this protocol, we applied it to the synthesis of 3-benzoyl-1-
and 3aw) with the current catalytic system. The coupling of 1a with methylquinoxalin-2(1H)-one 3aa using benzylalcohol as an acylated
2a on a 1.0 g scale proceeded smoothly, affording 3aa in a reagent (Table 5). Gratifyingly, substituted benzyl alcohols 4 could
comparable yield to the smaller scale reaction, demonstrating the react smoothly with quinoxalin-2(1H)-one 1a to provide the product
capacity to apply the protocol to scale up reactions.
3 though lower yields (28-46%) were obtained. The related
references have described that benzylic alcohols could be oxidated
into aldehydes in the presence of oxidants using copper as a
catalyst.[23] When 0.05 eq Cu2O was employed as a catalyst for this
transformation, the corresponding products were provided with
good yields (68-88%). The fact showed that benzyl alcohol could
also be used as an aroylated source for this oxidative coupling
reaction.
To further explore the substrate scope and limitations of this
process, a broad range of quinoxalin-2-ones (1b-k) were screened,
as shown in Table 3. Both electron-donating and electron-
withdrawing groups (Me, F, Cl, Br) on the phenyl of quinoxalin-2-
ones could also proceed smoothly to deliver the corresponding
products with moderate to good yields. Notably, quinoxalin-2-ones
containing halogen moieties were tolerated well, and it hardly
affected the reaction. Unfortunately, when 6-nitro-1-
methylquinoxalin-2-one was employed, the coupling reaction failed
to provide the product (3ga), which may be resulted from the fact
that the electron density on C3-position of 1g was reduced
significantly by the substitution of the strong electron-withdrawing
nitro group. To our delight, other N-substituted quinoxalin-2-ones
were also well compatible with the reaction. We observed that the
presence of N-hexy, N-benzyl, N-2-oxo-2-phenylethyl, and N-esteryl
groups did not restrict formation of the desired products (3ha, 3ia,
3ja, and 3ka). To investigate the versatility of the coupling reaction
beyond N-protected quinoxalin-2(1H)-one derivatives, we carried
out the reaction of unprotected quinoxalin-2(1H)-one with
substituted aromatic aldehydes (Table 4). It was interesting to
observe that N-unsubstituted quinoxalin-2(1H)-one was well
compatible with this reaction condition. Furthermore, N-
unsubstituted substrate (1l) could provide the higher yields than
that of N-substituted substrates (1a, and 1h-k).
Table 5 Synthesis of 3-benzoylated quinoxalin-2(1H)-ones 3 using
substituted benzylalcoholsa,b
a Reaction conditions: quinoxalin-2(1H)-ones 1a (0.2 mmol, 32 mg), substituted
benzylalcohols 4 (0.4 mmol), TBHP (0.8 mmol, 104 mg) in 2.0 mL DCE solvent at
70 oC for 5.0 h. b Isolated yield. c No metal catalyst was added. d Cu2O (0.01 mmol,
1.4 mg) was added as a catalyst.
Table 4 The reaction of unprotected quinoxalin-2(1H)-ones with
arylaldehydesa,b
a Reaction conditions: quinoxalin-2(1H)-ones 1l (0.2 mmol, 29.2 mg), arylaldehyde
2 (0.4 mmol), TBHP (0.8 mmol, 104 mg) in 2.0 mL DCE solvent at 70 oC for 5.0 h. b
Isolated yield.
Scheme 2 Control experiments
To unambiguously clarify this transformation, we conducted a
preliminary mechanism study by control experiments (Scheme 2).
Firstly, a radical scavenger, TEMPO, was introduced into the
reaction of 1-methylquinoxalin-2(1H)-one (1a) with benzaldehyde
(2a) under standard reaction conditions: 1.0 equiv of TEMPO results
As summarized in Table 2, 3 and 4, the tolerance of various
functionalities highlights the potential for downstream modification
of the acylated products via metal-free cross-coupling reaction
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in the product (3aa) in 20% yield, and only less than 5% desired performed using 300-400 mesh silica with the indicated solvent
product was found in the presence of 2.0 equiv of TEMPO. The system according to standard techniques. Nuclear magnetic
adduct of TEMPO and benzoyl radical could be detected m/z = resonance spectra were recorded on Bruker Avance 400 MHz
1
262.1807 by HR MS (ESI)(Supporting Information)(Scheme 2, a). spectrometer. Chemical shifts for H NMR spectra are recorded in
These results indicate that a radical intermediate was involved parts per million from tetramethylsilane. Data were reported as
during this transformation. When benzoic acid was employed as an follows: chemical shift, multiplicity (s = singlet, d = doublet, t =
aroylated reagent under standard conditions, no conversion 3aa triplet, m = multiplet and br = broad), coupling constant in Hz and
was observed (Scheme 2, b). Therefore, the intermediate of benzoic integration. Chemical shifts for 13C NMR spectra were recorded in
acid can be ruled out.
parts per million from tetramethylsilane. 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.
General experimental procedure for the synthesis of 3-
aroylquinoxalin-2(1H)-ones (3)
Quinoxalin-2(1H)-ones
1 (0.2 mmol), arylaldehydes 2 (0.4
mmol), TBHP (0.8 mmol, 104 mg) in DCE (2.0 mL) were added
o
to a 25 mL Schlenk tube. The mixture was stirred at 70 C for
5.0 h (monitored by TLC). After completion of the reaction, the
solvent was distilled under vacuum. 10 mL ethyl acetate was
added to the residuum, and 20 mL saturated sodium chloride
solution washed two times. The organic phase was dried over
anhydrous NaSO4 and concentrated under vacuum. The
residue was purified by silica gel column chromatography to
Scheme 3 Proposed reaction mechanism
give
3-aroylquinoxalin-2(1H)-ones
3
using
ethyl
On the basis of the experimental results obtained above and
previously reported literatures,[17k,20-22] the reaction mechanism was
proposed and is shown in Scheme 3. tert-Butyl hydroperoxide
(TBHP) generates a tert-butoxyl radical along with a hydroxide
radical by the heat. The tert-butoxyl radical then abstracts the H-
atom from the aldehyde to give acyl radical A which attacks
selectively C3-position of quinoxalin-2(1H)-one 1a to give the
nitrogen radical B stabilized by the phenyl group. Subsequently, a
acetate/petroleum ether (1:2 to 5:1) as eluant.
3-Benzoyl-1-methylquinoxalin-2(1H)-one (3aa). Yellow solid
(42.2 mg, 80% yield); mp 157-158 oC (lit.16 155-157 oC); IR (KBr)
1
ν
(cm-1): 2934, 1643, 1575, 1466, 1311, 1184. H NMR (400
MHz, CDCl3)
1H), 7.68-7.59 (m, 2H), 7.46 (t, JH-H = 7.8 Hz, 1H), 7.40-7.36 (m,
2H), 3.72 (s, 3H); 13C NMR (100 MHz, CDCl3)
: 191.8 (C=O),
δ: 7.97 (d, JH-H = 7.3 Hz, 2H), 7.89 (d, JH-H = 8.2 Hz,
δ
single-electron transfer (SET) from
B
would release the
154.6 (C=O), 153.3, 134.8, 134.2 (CH), 133.8, 132.1 (CH), 130.9
(CH), 129.9 (CH), 128.7 (CH), 124.2 (CH), 114.0 (CH), 29.0 (CH3);
HR MS (ESI) m/z: calcd for C16H13N2O2 [M + H]+ 265.0972,
found 265.0973.
intermediate nitrogen cation C, simultaneously the hydroxide
radical would release the intermediate hydroxide anion. Finally, the
expected oxidative coupling product 3aa is obtained by the
deprotonation of C.
1-Methyl-3-(4-methylbenzoyl)quinoxalin-2(1H)-one (3ab). Yellow
solid (45.6 mg, 82% yield); mp 184-185 oC (lib18 190-192 oC); IR (KBr)
1
ν(cm-1): 2934, 1676, 1635, 1554, 1323, 1163, 1075; H NMR (400
Conclusions
MHz, CDCl3) δ: 7.92-7.86 (m, 3H), 7.66 (t, JH-H = 8.2 Hz, 1H), 7.41-
7.37 (m, 2H), 7.27 (d, JH-H = 8.0 Hz, 2H), 3.73 (s, 3H), 2.41 (s, 3H); 13
C
In conclusion, we have developed an efficient TBHP-mediated direct
acylation of quinoxalin-2(1H)-ones with an excellent regioselectivity
at the C3 position using arylaldehydes as the acylated source under
metal-free conditions. This reaction has a broad scope of substrates
and provides a convenient process with respect to the preparation
of 3-aroyl quinoxalin-2(1H)-ones. Moreover, mechanistic studies
revealed that the aroylation occurs through a radical mechanism.
NMR (100 MHz, CDCl3) δ: 191.4 (C=O), 154.9 (C=O), 153.3, 145.3,
133.8, 132.4, 132.2, 131.9 (CH), 130.9 (CH), 130.1 (CH), 129.4 (CH),
124.1 (CH), 114.0 (CH), 29.0 (CH3), 21.8 (CH3); HR MS (ESI) m/z:
calcd for C17H15N2O2 [M + H]+ 279.1128, found 279.1128.
3-(4-Methoxybenzoyl)-1-methylquinoxalin-2(1H)-one (3ac). Yellow
solid (49.9 mg, 85% yield); mp 204-205 oC (lib18 191-193 oC); IR (KBr)
ν(cm-1): 2924, 2850, 1670, 1647, 1599, 1425, 1321, 1269, 1167,
1
Experimental section
1030; H NMR (400 MHz, CDCl3) δ: 7.97 (dd, JH-H = 6.9 Hz, JH-H = 2.2
Hz, 2H), 7.92 (dd, JH-H = 8.4 Hz, JH-H = 1.5 Hz, 1H), 7.67 (td, JH-H = 8.5
General information
Hz, JH-H = 1.4 Hz, 1H), 7.42-7.39 (m, 2H), 6.95 (dd, JH-H = 7.1 Hz, JH-H
2.0 Hz, 2H), 3.87 (s, 3H), 3.75 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
=
All substrates purchased from J & K Scientific Ltd. were used
without further purification. Column chromatography was
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190.2 (C=O), 164.5 (C=O), 155.0, 153.3, 133.8, 132.5 (CH), 131.8
(CH), 130.9 (CH), 127.9, 124.1 (CH), 114.0 (CH), 113.9 (CH), 55.6
(CH3), 29.0 (CH3); HR MS (ESI) m/z: calcd for C17H15N2O3 [M + H]+
295.1077, found 295.1076.
MHz, CDCl3) δ: 8.40 (d, JH-H = 1.2 Hz, 1H), 8.12 (dd, JH-H = 8.6 Hz, JH-H
= 1.7 Hz, 1H), 7.96-7.92 (m, 2H), 7.87 (d, JH-H = 9.0 Hz, 2H), 7.72-7.66
(m, 1H), 7.62-7.58 (m, 1H), 7.53-7.51 (m, 1H), 7.44-7.40 (m, 2H),
3.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 191.8 (C=O), 154.8 (C=O),
153.4, 136.2, 133.9, 133.0 (CH), 132.4, 132.3, 132.2, 132.1 (CH),
131.0 (CH), 129.8 (CH), 129.0 (CH), 128.8 (CH), 127.9 (CH), 126.8
(CH), 124.4 (CH), 124.2 (CH), 114.0 (CH), 29.1 (CH3); HR MS (ESI)
m/z: calcd for C20H15N2O2 [M + H]+ 315.1128, found 315.1126.
3-(2-Methoxybenzoyl)-1-methylquinoxalin-2(1H)-one
(3ad).
o
Orange solid (26.5 mg, 45% yield); mp 160-161 C; IR (KBr) ν(cm-1):
2945, 1662, 1593, 1468, 1284, 1248, 1171, 1090; 1H NMR (400 MHz,
CDCl3) δ: 8.05 (dd, JH-H = 7.8 Hz, JH-H = 1.7 Hz, 1H), 7.87 (dd, JH-H = 7.9
Hz, JH-H = 1.1 Hz, 1H), 7.61 (td, JH-H = 7.9 Hz, JH-H = 1.4 Hz, 1H), 7.53 3-(1-Naphthoyl)-1-methylquinoxalin-2(1H)-one (3ai). Yellow solid
o
(43.9 mg, 70% yield); mp 176-177 C; IR (KBr) ν(cm-1): 2925, 1643,
(td, JH-H = 7.8 Hz, JH-H = 1.7 Hz, 1H), 7.38-7.33 (m, 2H), 7.08 (t, JH-H
7.3 Hz, 1H), 6.90 (d, JH-H = 8.4 Hz, 1H), 3.71 (s, 3H), 3.55 (s, 3H); 13
=
C
1
1597, 1469, 1234, 1150, 1065; H NMR (400 MHz, CDCl3) δ: 8.05 (d,
NMR (100 MHz, CDCl3) δ: 191.2 (C=O), 160.1 (C=O), 157.3, 153.4,
135.7 (CH), 133.6, 132.5, 131.2 (CH), 130.9 (CH), 130.6 (CH), 125.4,
123.9 (CH), 121.3 (CH), 113.8 (CH), 112.2 (CH), 56.1 (CH3), 28.7
(CH3); HR MS (ESI) m/z: calcd for C17H15N2O3 [M + H]+ 295.1077,
found 295.1074.
JH-H = 8.2 Hz, 1H), 7.89 (d, JH-H = 8.0 Hz, 2H), 7.85 (dd, JH-H = 7.2 Hz,
JH-H = 1.0 Hz, 1H), 7.69-7.61 (m, 2H), 7.59-7.55 (m, 1H), 7.43 (t, JH-H
=
7.6 Hz, 1H), 7.39-7.35 (m, 2H), 3.70 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ: 194.0 (C=O), 155.7 (C=O), 153.4, 134.8 (CH), 134.0, 133.8,
132.9 (CH), 132.2, 131.9 (CH), 131.5, 131.0, 130.9 (CH), 128.8 (CH),
128.5 (CH), 126.8 (CH), 126.1 (CH), 124.3 (CH), 124.2 (CH), 114.0
(CH), 29.0 (CH3); HR MS (ESI) m/z: calcd for C20H15N2O2 [M + H]+
315.1128, found 315.1126.
1-Methyl-3-(4-(methylthio)benzoyl)quinoxalin-2(1H)-one
(3ae).
Light yellow solid (46.5 mg, 75% yield); mp 151-152 oC; IR (KBr)
1
ν(cm-1): 2920, 1674, 1651, 1583, 1468, 1317, 1246, 1171, 1086; H
NMR (400 MHz, CDCl3) δ: 7.92-7.87 (m, 3H), 7.66 (td, JH-H = 7.9 Hz, 3-(4-Fluorobenzoyl)-1-methylquinoxalin-2(1H)-one (3aj). Yellow
o
solid (39.5 mg, 70% yield); mp 163-164 C; IR (KBr) ν(cm-1): 3074,
JH-H = 1.5 Hz, 1H), 7.42-7.38 (m, 2H), 7.26 (d, JH-H = 8.5 Hz, 2H), 3.73
(s, 3H), 2.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 190.7 (C=O), 154.6 2920, 1696, 1643, 1601, 1545, 1466, 1408, 1325, 1234, 1153, 1007,
1
(C=O), 153.3, 147.8, 133.8, 132.1, 132.0 (CH), 131.0, 130.9 (CH),
130.3 (CH), 124.8 (CH), 124.2 (CH), 114.0 (CH), 29.0 (CH3), 14.6
(CH3); HR MS (ESI) m/z: calcd for C17H15N2O2S [M + H]+ 311.0849,
found 311.0846.
748; H NMR (400 MHz, CDCl3) δ: 8.04-8.01 (m, 2H), 7.92 (dd, JH-H
=
8.4 Hz, JH-H = 1.6 Hz, 1H), 7.71-7.66 (m, 1H), 7.44-7.40 (m, 2H), 7.18-
7.13 (m, 2H), 3.75 (s, 3H; 13C NMR (100 MHz, CDCl3) δ: 190.1 (C=O),
166.4 (d, JF-C = 255.5 Hz), 165.1 (C=O), 154.2, 153.3, 133.9, 132.7 (d,
JF-C = 9.6 Hz), 132.3, 132.1, 131.3 (d, JF-C = 2.8 Hz), 131.0, 124.3,
115.9 (d, JF-C = 21.9 Hz), 114.0 (CH), 29.1 (CH3); 19F NMR (376 MHz,
CDCl3) δ: -102.8; HR MS (ESI) m/z: calcd for C16H12FN2O2 [M + H]+
283.0877, found 283.0874.
3-(4-(Dimethylamino)benzoyl)-1-methylquinoxalin-2(1H)-one
o
(3af). Orange solid (39.9 mg, 65% yield); mp 235-236 C; IR (KBr)
1
ν(cm-1): 2920, 1655, 1587, 1379, 1327, 1161, 1092; H NMR (400
MHz, CDCl3) δ: 7.91 (d, JH-H = 8.0 Hz, 1H), 7.86 (d, JH-H = 8.9 Hz, 2H),
7.64 (t, JH-H = 7.6 Hz, 1H), 7.40-7.36 (m, 2H), 6.64 (d, JH-H = 8.9 Hz,
2H), 3.73 (s, 3H), 3.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 189.5 solid (39.9 mg, 67% yield); mp 181-182 C (lit18 180-182 oC); IR (KBr)
3-(4-Chlorobenzoyl)-1-methylquinoxalin-2(1H)-one (3ak). Yellow
o
ν(cm-1): 3074, 1693, 1648, 1580, 1545, 1480, 1325, 1171, 1005, 750;
(C=O), 155.9 (C=O), 154.2, 153.5, 133.8, 132.4 (CH), 132.3, 131.5
1H NMR (400 MHz, CDCl3) δ: 7.93-7.88 (m, 3H), 7.67 (td, JH-H = 7.9
(CH), 130.8 (CH), 123.9 (CH), 122.7, 113.8 (CH), 110.8 (CH), 40.0
(CH3), 29.0 (CH3); HR MS (ESI) m/z: calcd for C18H18N3O2 [M + H]+
Hz, JH-H = 1.3 Hz, 1H), 7.45-7.38 (m, 4H), 3.73 (s, 3H); 13C NMR (100
MHz, CDCl3) δ: 190.5 (C=O), 153.9 (C=O), 153.2, 140.7, 133.9, 133.2,
132.3 (CH), 132.1, 131.3 (CH), 131.0 (CH), 129.0 (CH), 124.3 (CH),
114.0 (CH), 29.1 (CH3); HR MS (ESI) m/z: calcd for C16H12ClN2O2 [M +
H]+ 299.0582, found 299.0580.
308.1394, found 308.1391.
3-(3,4-Dimethoxybenzoyl)-1-methylquinoxalin-2(1H)-one
(3ag).
o
Yellow solid (53.1 mg, 82% yield); mp 89-90 C; IR (KBr) ν(cm-1):
2981, 2839, 1736, 1645, 1589, 1415, 1275, 1020; 1H NMR (400 MHz,
CDCl3) δ: 7.89 (dd, JH-H = 8.6 Hz, JH-H = 1.6 Hz, 1H), 7.67-7.63 (m, 2H),
7.45 (dd, JH-H = 8.4 Hz, JH-H = 2.0 Hz, 1H), 7.40-7.36 (m, 2H), 6.86 (d,
JH-H = 8.4 Hz, 1H), 3.93 (s, 3H), 3.92 (s, 3H), 3.72 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 190.4 (C=O), 154.7 (C=O), 154.4, 153.3, 149.3,
133.7, 132.0, 131.9 (CH), 130.7 (CH), 127.9, 126.3 (CH), 124.1 (CH),
114.0 (CH), 110.6 (CH), 110.0 (CH), 56.1 (CH3), 56.0 (CH3), 29.0
(CH3); HR MS (ESI) m/z: calcd for C18H17N2O4 [M + H]+325.1183,
found 325.1181.
3-(2-Chlorobenzoyl)-1-methylquinoxalin-2(1H)-one (3al). Yellow
o
solid (26.8 mg, 45% yield); mp 131-132 C; IR (KBr) ν(cm-1): 2927,
1693, 1644, 1464, 1328, 1165, 1023, 752; 1H NMR (400 MHz, CDCl3)
δ: 7.91-7.88 (m, 2H), 7.66 (td, JH-H = 7.9 Hz, JH-H = 1.3 Hz, 1H), 7.49
(td, JH-H = 7.6 Hz, JH-H = 1.7 Hz, 1H), 7.44-7.36 (m, 4H), 3.73 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 191.5 (C=O), 153.9 (C=O), 153.2, 136.1,
134.1, 133.5 (CH), 133.3, 132.4 (CH), 131.6 (CH), 131.3 (CH), 130.4
(CH), 127.2 (CH), 124.1 (CH), 114.0 (CH), 29.0 (CH3); HR MS (ESI)
m/z: calcd for C16H12ClN2O2 [M + H]+ 299.0582, found 299.0579.
3-(2-Naphthoyl)-1-methylquinoxalin-2(1H)-one (3ah). Orange solid
(47.1 mg, 75% yield); mp 184-185 oC (lit18 178-180oC); IR (KBr) ν(cm-
3-(4-Bromobenzoyl)-1-methylquinoxalin-2(1H)-one (3am). Yellow
1
1): 3043, 1666, 1647, 1603, 1466, 1308, 1176, 1120; H NMR (400
o
solid (44.5 mg, 65% yield); mp 195-196 C (lit18 195-197 oC); IR (KBr)
6 | J. Name., 2012, 00, 1-3
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1
ν(cm-1): 2976, 1691, 1648, 1585, 1468, 1325, 1168, 1003, 760; H
4-(4-Methyl-3-oxo-3,4-dihydroquinoxaline-2-carbonyl)benzonitrile
o
(3ar). Yellow solid (32.4 mg, 56% yield); mp 211-212 C; IR (KBr)
NMR (400 MHz, CDCl3) δ: 7.90 (dd, JH-H = 8.3 Hz, JH-H = 1.5 Hz, 1H),
ν(cm-1): 2924, 1695, 1643, 1603, 1541, 1454, 1336, 1161, 1005, 766;
7.84 (dd, JH-H = 6.8 Hz, JH-H = 1.7 Hz, 2H), 7.67 (td, JH-H = 7.2 Hz, JH-H
=
1.4 Hz, 1H), 7.61 (dd, JH-H = 6.8 Hz, JH-H = 1.7 Hz, 2H), 7.42-7.39 (m, 1H NMR (400 MHz, CDCl3) δ: 8.08 (d, JH-H = 8.4 Hz, 2H), 7.92 (dd, JH-H
2H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 190.6 (C=O), 153.8
= 8.4 Hz, JH-H = 1.5 Hz, 1H), 7.78 (d, JH-H = 8.4 Hz, 2H), 7.72 (td, JH-H
=
7.9 Hz, JH-H = 1.5 Hz, 1H), 7.46-7.42 (m, 2H), 3.76 (s, 3H); 13C NMR
(C=O), 153.2, 133.9, 133.7, 132.3 (CH), 132.1, 132.0 (CH), 131.3
(CH), 131.0 (CH), 129.6, 124.3 (CH), 114.0 (CH), 29.1 (CH3); HR MS (100 MHz, CDCl3) δ: 190.1 (C=O), 153.2 (C=O), 152.9, 138.0, 134.0,
(ESI) m/z: calcd for C16H12BrN2O2 [M + H]+ 343.0077, found 132.7 (CH), 132.4 (CH), 132.1, 131.2 (CH), 130.2 (CH), 124.4 (CH),
343.0076.
117.8, 117.0, 114.1 (CH), 29.1 (CH3); HR MS (ESI) m/z: calcd for
C17H12N3O2 [M + H]+ 290.0924, found 290.0925.
3-(2-Bromobenzoyl)-1-methylquinoxalin-2(1H)-one (3an). Yellow
o
solid (32.8 mg, 48% yield); mp 119-120 C (lit18 111-113 oC); IR (KBr) 1-Methyl-3-(thiophene-2-carbonyl)quinoxalin-2(1H)-one
(3at).
o
Yellow solid (35.1 mg, 65% yield); mp 142-143 C (lit18 142-144oC);
ν(cm-1): 3012, 1665, 1653, 1535, 1420, 1310, 1285, 764; H NMR
(400 MHz, CDCl3) δ: 7.90 (dd, JH-H = 8.4 Hz, JH-H = 1.6 Hz, 1H), 7.84
1
IR (KBr) ν(cm-1): 3072, 2924, 1657, 1587, 1468, 1412, 1356, 1265,
(dd, JH-H = 7.6 Hz, JH-H = 1.8 Hz, 1H), 7.65 (td, JH-H = 8.3 Hz, JH-H = 1.1 1165, 1061, 769, 725; 1H NMR (400 MHz, CDCl3) δ: 7.92 (d, JH-H = 8.2
Hz, 1H), 7.60 (dd, JH-H = 7.9 Hz, JH-H = 1.1 Hz, 1H), 7.48 (td, JH-H = 7.5 Hz, 1H), 7.79-7.77 (m, 2H), 7.68 (t, JH-H = 8.2 Hz, 1H), 7.42-7.39 (m,
Hz, JH-H = 1.2 Hz, 1H), 7.43-7.37 (m, 2H), 3.73 (s, 3H); 13C NMR (100 2H), 7.15 (t, JH-H = 4.5 Hz, 1H), 3.74 (s, 3H); 13C NMR (100 MHz,
MHz, CDCl3) δ: 192.2 (C=O), 153.3 (C=O), 153.2, 138.4, 134.2, 133.5, CDCl3) δ: 183.1 (C=O), 152.9 (C=O), 152.7, 141.5, 136.2 (CH), 136.1
133.3, 132.5, 132.4, 131.8, 131.5, 127.6, 124.1, 121.3, 113.9, 29.0 (CH), 134.1, 132.5 (CH), 131.8, 131.0 (CH), 128.4 (CH), 124.2 (CH),
(CH3); HR MS (ESI) m/z: calcd for C16H12BrN2O2 [M + H]+ 343.0077, 114.1 (CH), 29.2 (CH3); HR MS (ESI) m/z: calcd for C14H11N2O2S [M +
found 343.0078.
H]+ 271.0536, found 271.0538.
3-(3-Bromobenzoyl)-1-methylquinoxalin-2(1H)-one (3ao). Yellow 3-(Furan-2-carbonyl)-1-methylquinoxalin-2(1H)-one (3au). Yellow
o
o
solid (38.9 mg, 57% yield); mp 138-139 C; IR (KBr) ν(cm-1): 3010, solid (35.6 mg, 70% yield); mp 148-149 C; IR (KBr) ν(cm-1): 3115,
1662, 1650, 1537, 1418, 1308, 1195, 768; 1H NMR (400 MHz, CDCl3) 3087, 2925, 1682, 1635, 1464, 1392, 1315, 1269, 1159, 1038, 1009,
1
δ: 8.10 (t, JH-H = 1.7 Hz, 1H), 7.93-7.88 (m, 2H), 7.75-7.67 (m, 2H), 987, 754; H NMR (400 MHz, CDCl3) δ: 7.92 (dd, JH-H = 8.4 Hz, JH-H
=
7.44-7.38 (m, 2H), 7.34 (t, JH-H = 7.9 Hz, 1H), 3.74 (s, 3H); 13C NMR 1.5 Hz, 1H), 7.71-7.66 (m, 2H), 7.43-7.39 (m, 2H), 7.35 (d, JH-H = 3.6
Hz, 1H), 6.61 (d, JH-H = 3.6 Hz, JH-H = 1.6 Hz, 1H), 3.74 (s, 3H); 13C
(100 MHz, CDCl3) δ: 190.3 (C=O), 153.7 (C=O), 153.2, 136.9 (CH),
136.6, 133.9, 132.6 (CH), 132.4 (CH), 132.1, 131.0 (CH), 130.2 (CH), NMR (100 MHz, CDCl3) δ: 178.6 (C=O), 153.0 (C=O), 152.7, 151.1,
128.5 (CH), 124.3 (CH), 122.9, 114.1 (CH), 29.1 (CH3); HR MS (ESI) 148.3 (CH), 134.1, 132.4, 132.0 (CH), 131.1 (CH), 124.2 (CH), 121.9
m/z: calcd for C16H12BrN2O2 [M + H]+343.0077, found 343.0076.
(CH), 114.0 (CH), 112.7 (CH), 29.1 (CH3); HR MS (ESI) m/z: calcd for
C14H11N2O3 [M + H]+ 255.0764, found 255.0765.
3-(4-Iodobenzoyl)-1-methylquinoxalin-2(1H)-one (3ap). Yellow
o
solid (58.3 mg, 75% yield); mp 207-208 C; IR (KBr) ν(cm-1): 2920,
3-Butyryl-1-methylquinoxalin-2(1H)-one (3av). Yellow solid (18.4
1693, 1645, 1581, 1539, 1323, 1169, 1003, 758; H NMR (400 MHz, mg, 40% yield); mp 95-96 C; IR (KBr) ν(cm-1): 2956, 2896, 1709,
CDCl3) δ: 7.92 (dd, JH-H = 8.6 Hz, JH-H = 1.5 Hz, 1H), 7.87-7.83 (m, 2H), 1653, 1577, 1453, 1033, 760; 1H NMR (400 MHz, CDCl3) δ: 7.92 (dd,
7.71-7.67 (m, 3H), 7.44-7.40 (m, 2H), 3.75 (s, 3H); 13C NMR (100 JH-H = 8.0 Hz, JH-H = 1.4 Hz, 1H), 7.68-7.64 (m, 1H), 7.41-7.35 (m, 2H),
1
o
3.71 (s, 3H), 3.05 (t, JH-H = 7.3 Hz, 2H), 1.83-1.74 (m, 2H), 1.02 (t, JH-H
133.9, 132.3 (CH), 132.1, 131.2 (CH), 131.1 (CH), 124.3 (CH), 114.3 = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 201.0 (C=O), 152.9
MHz, CDCl3) δ: 191.0 (C=O), 153.8 (C=O), 153.2, 138.0 (CH), 134.2,
(CH), 102.7, 29.1 (CH3); HR MS (ESI) m/z: calcd for C16H12IN2O2 [M + (C=O), 152.8, 134.2, 132.4 (CH), 131.9, 131.2 (CH), 124.1 (CH), 113.9
H]+ 390.9938, found 390.9939.
(CH), 42.6 (CH2), 29.0 (CH3), 16.9 (CH2), 13.7 (CH3); HR MS (ESI) m/z:
calcd for C13H15N2O2 [M + H]+ 231.1128, found 231.1125.
Methyl
4-(4-methyl-3-oxo-3,4-dihydroquinoxaline-2-
carbonyl)benzoate (3aq). Yellow solid (45.1 mg, 70% yield); mp 3-isoButyryl-1-methylquinoxalin-2(1H)-one (3aw). Yellow solid
o
o
152-153 C; IR (KBr) ν(cm-1): 2924, 2854, 1722, 1689, 1647, 1601, (16.1 mg, 35% yield); mp 88-89 C; IR (KBr) ν(cm-1): 2966, 2932,
1
1
1539, 1435, 1290, 1255, 1169, 1099, 1005, 752; H NMR (400 MHz, 1705, 1647, 1583, 1541, 1466, 1375, 1311, 1161, 1032; H NMR
CDCl3) δ: 8.14 (d, JH-H = 8.4 Hz, 2H), 8.04 (d, JH-H = 8.4 Hz, 2H), 7.93 (400 MHz, CDCl3) δ: 7.90 (dd, JH-H = 7.9 Hz, JH-H = 1.2 Hz, 1H), 7.68-
(dd, JH-H = 8.4 Hz, JH-H = 1.5 Hz, 1H), 7.72-7.68 (m, 1H), 7.45-7.41 (m, 7.64 (m, 1H), 7.41-7.36 (m, 2H), 3.71 (s, 3H), 3.64-3.54 (m, 1H), 1.25
2H), 3.95 (s, 3H), 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 191.1 (d, JH-H = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 204.5 (C=O),
(C=O), 166.1 (C=O), 153.8 (C=O), 153.2, 138.1, 134.6, 133.9, 132.4 153.7 (C=O), 152.9, 134.0, 132.2, 131.9, 131.0, 124.0, 113.9 (CH),
(CH), 132.1, 131.1 (CH), 129.9 (CH), 129.8 (CH), 124.3 (CH), 114.0 38.2 (CH), 28.9 (CH3), 17.5 (CH3); HR MS (ESI) m/z: calcd for
(CH), 52.5 (CH3), 29.1 (CH3); HR MS (ESI) m/z: calcd for C18H15N2O4 C13H15N2O2 [M + H]+ 231.1128, found 231.1125.
[M + H]+ 323.1026, found 323.1025.
3-Benzoyl-1,6,7-trimethylquinoxalin-2(1H)-one (3ba). Yellow solid
o
(49.6 mg, 85% yield); mp 161-162 oC (lib18 152-154 C); IR (KBr)
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ν(cm-1): 3082, 2934, 1645, 1565, 1468, 1317, 1178; H NMR (400
3-Benzoyl-1-hexylquinoxalin-2(1H)-one (3ha). Sticky liquid (48.7
mg, 73% yield); IR (KBr) ν(cm-1): 3056, 2850, 1678, 1566, 1346; H
1
MHz, CDCl3) δ: 7.97 (d, JH-H = 7.1 Hz, 2H), 7.67 (s, 1H), 7.60 (t, JH-H
=
7.4 Hz, 1H), 7.47 (t, JH-H = 7.8 Hz, 2H), 7.16 (s, 1H), 3.72 (s, 3H), 2.46 NMR (400 MHz, CDCl3) δ: 7.98-7.96 (m, 2H), 7.93 (dd, JH-H = 7.8 Hz,
(s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 192.0 (C=O), 153.4
(C=O), 153.2, 142.4, 135.1, 134.0 (CH), 133.3, 132.0, 130.9 (CH),
130.6, 130.0 (CH), 128.6 (CH), 114.4 (CH), 28.9 (CH3), 20.8 (CH3),
J
H-H = 1.3 Hz, 1H), 7.68-7.59 (m, 2H), 7.47 (t, JH-H = 7.8 Hz, 2H), 7.41-
7.37 (m, 2H), 4.27 (t, JH-H = 7.8 Hz, 2H), 1.83-1.75 (m, 2H), 1.48-1.43
(m, 2H), 1.37-1.30 (m, 4H), 0.89 (t, JH-H = 7.1 Hz, 3H); 13C NMR (100
19.1 (CH3); HR MS (ESI) m/z: calcd for C18H17N2O2 [M + H]+ 293.1285, MHz, CDCl3) δ: 191.9 (C=O), 154.7 (C=O), 153.0, 134.9, 134.1 (CH),
found 293.1287.
133.1, 132.5, 131.9 (CH), 131.2 (CH), 129.9 (CH), 128.6 (CH), 123.9
(CH), 113.9 (CH), 42.4 (CH2), 31.3 (CH2), 27.2 (CH2), 26.6 (CH2), 22.5
(CH2), 13.9 (CH3); HR MS (ESI) m/z: calcd for C21H23N2O2 [M + H]+
335.175, found 335.1749.
3-Benzoyl-6-fluoro-1-methylquinoxalin-2(1H)-one (3ca). Yellow
solid (41.2 mg, 73% yield); mp 160-161 C; IR (KBr) ν(cm-1): 3080,
o
2924, 1699, 1647, 1598, 1547, 1498, 1446, 1323, 1263, 1169, 1126,
1
3-Benzoyl-1-benzylquinoxalin-2(1H)-one (3ia). Yellow solid (51.0
1007, 823, 609; H NMR (400 MHz, CDCl3) δ: 7.96 (d, JH-H = 8.0 Hz,
mg, 75% yield); mp 128-129 C (lit.18 123-125 oC); IR (KBr) ν(cm-1):
o
2H), 7.65-7.59 (m, 2H), 7.48 (t, JH-H = 7.4 Hz, 2H), 7.43-7.36 (m, 2H),
3.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 191.4 (C=O), 160.0 (C=O),
1
3059, 1687, 1845, 1599, 1448, 1325, 1171, 893, 762; H NMR (400
MHz, CDCl3) δ: 8.01 (dd, JH-H = 8.0 Hz, JH-H = 1.4 Hz, 2H), 7.92 (dd, JH-H
= 8.4 Hz, JH-H = 1.4 Hz, 1H), 7.67-7.61 (m, 1H), 7.56-7.47 (m, 3H),
7.36 (d, JH-H = 7.7 Hz, 2H), 7.33-7.27 (m, 5H), 5.52 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ: 191.7 (C=O), 154.7 (C=O), 153.4, 134.9, 134.8,
134.3, 133.2, 132.4, 132.0, 131.1, 130.0, 129.0, 128.7, 127.9, 127.1,
124.2, 114.8, 45.9 (CH2); HR MS (ESI) m/z: calcd for C22H17N2O2 [M +
H]+ 341.1285, found 341.1287.
157.6, 154.5 (d, JF-C = 310.0 Hz), 134.5, 134.4 (CH), 132.7 (d, JF-C
=
11.3 Hz), 130.6, 129.9 (CH), 128.7 (CH), 120.0 (d, JF-C = 24.0 Hz, CH),
116.2 (d, JF-C = 22.5 Hz, CH), 115.3 (d, JF-C = 8.6 Hz, CH), 29.3 (CH3);
19F NMR (376 MHz, CDCl3) δ: -117.6; HR MS (ESI) m/z: calcd for
C16H12FN2O2 [M + H]+ 283.0877, found 283.0874.
3-Benzoyl-6-chloro-1-methylquinoxalin-2(1H)-one (3da). Colorless
o
solid (44.7 mg, 75% yield); mp 189-190 C; IR (KBr) ν(cm-1): 3080,
1
3-Benzoyl-1-(2-oxo-2-phenylethyl)quinoxalin-2(1H)-one
(3ja).
1685, 1655, 1597, 1431, 1344, 1171, 987, 719; H NMR (400 MHz,
Colorless solid (61.8 mg, 84% yield); mp 139-140 oC; IR (KBr) ν(cm-1):
2939, 1684, 1658, 1577, 1448, 1227, 752; 1H NMR (400 MHz, CDCl3)
δ: 8.05 (dd, JH-H = 8.5 Hz, JH-H = 1.2 Hz, 2H), 7.99 (dd, JH-H = 8.4 Hz, JH-
CDCl3) δ: 7.97-7.95 (m, 2H), 7.84 (d, JH-H = 8.5 Hz, 1H), 7.65-7.60 (m,
1H), 7.48 (t, JH-H = 7.6 Hz, 2H), 7.40 (d, JH-H = 2.0 Hz, 1H), 7.36 (d, JH-H
= 8.5 Hz, JH-H = 2.0 Hz, 1H), 3.71 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
191.3 (C=O), 154.5 (C=O), 153.0, 138.2, 134.7, 134.6, 134.3 (CH),
132.0 (CH), 130.6, 130.0 (CH), 128.7 (CH), 124.7 (CH), 114.1 (CH),
29.2 (CH3); HR MS (ESI) m/z: calcd for C16H12ClN2O2 [M + H]+
299.0582, found 299.0579.
= 1.4 Hz, 2H), 7.93 (dd, JH-H = 8.0 Hz, JH-H = 1.3 Hz, 1H), 7.66-7.59
H
(m, 2H), 7.55-7.45 (m, 5H), 7.36 (td, JH-H = 7.6 Hz, JH-H = 0.7 Hz, 2H),
7.05 (d, JH-H = 8.4 Hz, 1H), 5.76 (s, 2H); 13C NMR (100 MHz, CDCl3) δ:
191.5 (C=O), 190.7 (C=O), 154.2 (C=O), 153.1, 134.8, 134.4 (CH),
134.3, 134.2 (CH), 133.3, 132.3, 132.1 (CH), 131.2 (CH), 130.0 (CH),
129.1 (CH), 128.7 (CH), 128.2 (CH), 124.3 (CH), 114.0 (CH), 48.2
(CH2); HR MS (ESI) m/z: calcd for C23H17N2O3 [M + H]+ 369.1234,
found 369.1232.
3-Benzoyl-7-chloro-1-methylquinoxalin-2(1H)-one (3ea). Colorless
o
solid (46.5 mg, 78% yield); mp 213-214 C; IR (KBr) ν(cm-1): 3076,
1
1653, 1581, 1450, 1173, 1099, 810, 575; H NMR (400 MHz, CDCl3)
δ: 7.96-7.94 (m, 2H), 7.89 (d, JH-H = 2.4 Hz, 1H), 7.65-7.59 (m, 2H),
7.48 (t, JH-H = 7.6 Hz, 2H), 7.35 (d, JH-H = 9.0 Hz, 1H), 3.72 (s, 3H); 13
C
Ethyl 2-(3-benzoyl-2-oxoquinoxalin-1(2H)-yl)acetate (3ka). Sticky
liquid (50.5 mg, 75% yield); IR (KBr) ν(cm-1): 2956, 1735, 1665, 1651,
NMR (100 MHz, CDCl3) δ: 191.3 (C=O), 155.8 (C=O), 152.9, 134.5,
134.4 (CH), 132.6, 132.5, 132.0 (CH), 130.1 (CH), 129.9 (CH), 129.6,
128.7 (CH), 115.2 (CH), 29.2 (CH3); HR MS (ESI) m/z: calcd for
C16H12ClN2O2 [M + H]+ 299.0582, found 299.0580.
1575, 1348, 1235, 1190; 1H NMR (400 MHz, CDCl3) δ: 7.96 (dd, JH-H
=
7.3 Hz, JH-H = 1.1 Hz, 2H), 7.90 (d, JH-H = 8.0 Hz, 1H), 7.62-7.58 (m,
2H), 7.45 (t, JH-H = 7.8 Hz, 2H), 7.37 (t, JH-H = 7.4 Hz, 1H), 7.18 (d, JH-H
= 8.0 Hz, 1H), 7.36 (td, JH-H = 7.6 Hz, JH-H = 0.7 Hz, 2H), 7.05 (d, JH-H
=
3-Benzoyl-7-bromo-1-methylquinoxalin-2(1H)-one (3fa). Yellow
solid (54.7 mg, 80% yield); mp 199-200 C; IR (KBr) ν(cm-1): 3039,
8.4 Hz, 1H), 5.05 (s, 2H), 4.23 (q, JH-H = 7.1 Hz, 2H), 1.25 (t, JH-H = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 191.4 (C=O), 166.7 (C=O),
154.2 (C=O), 152.9, 134.7, 134.3 (CH), 133.0, 132.3 (CH), 132.2,
131.1 (CH), 129.9 (CH), 128.7 (CH), 124.5 (CH), 113.6 (CH), 62.2
(CH2), 43.3 (CH2), 14.1 (CH3); HR MS (ESI) m/z: calcd for C19H17N2O4
[M + H]+ 337.1183, found 337.1181.
o
1682, 1651, 1595, 1554, 1448, 1327, 1173, 1097, 1007, 808; 1H
NMR (400 MHz, CDCl3) δ: 8.07 (d, JH-H = 2.2 Hz, 1H), 7.97-7.95 (m,
2H), 7.75 (dd, JH-H = 8.9 Hz, JH-H = 2.2 Hz, 1H), 7.65-7.61 (m, 1H), 7.48
(t, JH-H = 7.6 Hz, 2H), 7.29 (d, JH-H = 8.9 Hz, 1H), 3.72 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 191.2 (C=O), 155.7 (C=O), 152.9, 134.7 (CH),
134.5, 134.4 (CH), 133.2 (CH), 133.0, 132.9, 130.0 (CH), 128.7 (CH),
116.8, 115.5 (CH), 29.2 (CH3); HR MS (ESI) m/z: calcd for
C16H12BrN2O2 [M + H]+ 343.0077, found 343.0079.
3-Benzoylquinoxalin-2(1H)-one (3la). Colorless solid (42.5 mg, 85%
yield); mp 251-252 oC (lit18 256-258 oC); IR (KBr) ν(cm-1): 1697, 1664,
1
1576, 1530, 1434, 1326, 1275; H NMR (400 MHz, DMSO) δ: 12.88
(s, 1H), 7.98 (d, JH-H = 7.0 Hz, 2H), 7.83 (dd, JH-H = 8.1 Hz, JH-H = 1.1
Hz, 1H), 7.74 (t, JH-H = 7.4 Hz, 1H), 7.68-7.64 (m, 1H), 7.58 (t, JH-H
=
8 | J. Name., 2012, 00, 1-3
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7.6 Hz, 2H), 7.42-7.36 (m, 2H); 13C NMR (100 MHz, DMSO) δ: 192.9 ν(cm-1): 1686, 1645, 1603, 1448, 1263, 1034, 760; 1H NMR (400
(C=O), 156.7 (C=O), 153.8, 135.1 (CH), 135.0, 133.1, 132.2 (CH),
131.6, 130.1 (CH), 129.5 (CH), 129.4 (CH), 124.3 (CH), 116.3 (CH); HR
MS (ESI) m/z: calcd for C15H11N2O2 [M + H]+ 251.0815, found
251.0816.
MHz, CDCl3) δ: 7.93 (d, JH-H = 1.6 Hz, 1H), 7.91-7.65 (m, 1H), 7.51-
7.49 (m, 2H), 7.43-7.39 (m, 2H), 6.84 (dd, JH-H = 7.6 Hz, JH-H = 1.1 Hz,
1H), 6.06 (s, 2H), 3.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 189.9
(C=O), 154.8 (C=O), 153.8, 152.9, 148.3, 133.8, 132.1, 131.9 (CH),
130.9 (CH), 129.6, 127.6 (CH), 124.2 (CH), 113.9 (CH), 108.9 (CH),
108.1 (CH), 102.0 (CH2), 29.0 (CH3); HR MS (ESI) m/z: calcd for
C17H13N2O4 [M + H]+ 309.0870, found 309.0872.
3-(4-Methylbenzoyl)quinoxalin-2(1H)-one (3lb). Light yellow solid
(46.5 mg, 88% yield); mp 247-248 oC (lit18 248-250oC); IR (KBr) ν(cm-
1
1): 2962, 1693, 1650, 1582, 1378, 1290, 1164; H NMR (400 MHz,
DMSO) δ: 12.88 (s, 1H), 7.88 (d, JH-H = 8.1 Hz, 2H), 7.84 (d, JH-H = 7.5
Hz, 1H), 7.65 (td, JH-H = 7.7 Hz, JH-H = 1.0 Hz, 1H), 7.42 (d, JH-H = 8.1
Hz, 1H), 7.39-7.36 (m, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, DMSO)
δ: 192.4 (C=O), 156.9 (C=O), 153.8, 145.8, 133.1, 132.6, 132.1 (CH),
131.6, 130.2 (CH), 130.0 (CH), 129.5 (CH), 124.2 (CH), 116.3 (CH),
21.8 (CH3); HR MS (ESI) m/z: calcd for C16H13N2O2 [M + H]+ 265.0972,
found 265.0970.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work was supported by the Project of Youth Backbone
Teachers of Henan University of Technology (2016003).
3-(4-Bromobenzoyl)quinoxalin-2(1H)-one (3lm). Yellow solid (54.3
mg, 83% yield); mp 208-209 C; IR (KBr) ν(cm-1): 1691, 1653, 1565,
o
1
1345, 1270, 1051, 752; H NMR (400 MHz, DMSO) δ: 12.89 (s, 1H),
Notes and references
7.94-7.92 (m, 2H), 7.84 (dd, JH-H = 8.0 Hz, JH-H = 1.0 Hz, 1H), 7.79 (dd,
JH-H = 6.8 Hz, JH-H = 1.8 Hz, 1H), 7.66 (td, JH-H = 7.7 Hz, JH-H = 1.3 Hz,
1H), 7.42-7.36 (m, 2H); 13C NMR (100 MHz, DMSO) δ: 192.0 (C=O),
156.0 (C=O), 153.8, 134.0, 133.2, 132.6 (CH), 132.3 (CH), 132.0 (CH),
131.7, 129.6 (CH), 129.4, 124.3 (CH), 116.3 (CH); HR MS (ESI) m/z:
calcd for C15H10BrN2O2 [M + H]+ 328.9920, found 328.9924.
1
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General experimental procedure for the synthesis of 3-
aroylquinoxalin-2(1H)-ones (3) using substituted benzylalcohols
Quinoxalin-2(1H)-ones 1a (0.2 mmol, 32 mg), substituted benzyl
alcohols 4 (0.4 mmol), TBHP (0.8 mmol, 104 mg) and Cu2O (0.01
mmol, 1.4 mg) in DCE (2.0 mL) were added to a 25 mL Schlenk tube.
The mixture was stirred at 70 oC for 5.0 h (monitored by TLC). After
completion of the reaction, the solvent was distilled under vacuum.
10 mL ethyl acetate was added to the residuum, and 20 mL
saturated sodium chloride solution washed two times. The organic
phase was dried over anhydrous NaSO4 and concentrated under
vacuum. The residue was purified by silica gel column
chromatography to give 3-aroylquinoxalin-2(1H)-ones 3 using ethyl
acetate/petroleum ether (1:2 to 1:4) as eluant.
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3-([1,1'-Biphenyl]-4-carbonyl)-1-methylquinoxalin-2(1H)-one (3ax).
o
Yellow solid (59.8 mg, 88% yield); mp 195-196 C; IR (KBr) ν(cm-1):
1
1687, 1638, 1611, 1452, 1254, 1032; H NMR (400 MHz, CDCl3) δ:
8.06 (d, JH-H = 8.4 Hz, 2H), 7.94 (dd, JH-H = 8.3 Hz, JH-H = 1.5 Hz, 1H),
7.71-7.65 (m, 3H), 7.63-7.61 (m, 2H), 7.48-7.39 (m, 5H), 3.75 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 191.3 (C=O), 154.7 (C=O), 153.3, 146.9,
139.8, 133.9, 133.6, 132.1 (CH), 131.0 (CH), 130.6 (CH), 128.9 (CH),
128.4 (CH), 127.4 (CH), 127.3 (CH), 124.2 (CH), 114.0 (CH), 29.1
(CH3); HR MS (ESI) m/z: calcd for C22H17N2O2 [M + H]+ 341.1285,
found 341.1286.
8
9
A. Cavazzuti, G. Paglietti, W. N. Hunter, F. Gamarro, S. Piras,
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3-(Benzo[d][1,3]dioxole-5-carbonyl)-1-methylquinoxalin-2(1H)-
one (3ay). Yellow solid (52.4 mg, 85% yield); mp 205-206 oC; IR (KBr)
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This journal is © The Royal Society of Chemistry 20xx
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Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB00206A
Metal-free oxidative coupling of quinoxalin-2(1H)-ones with aryl
aldehydes leading to 3-acylated quinoxalin-2(1H)-ones
Jin-Wei Yuan,*a Jun-Hao Fu,a Shuai-Nan Liu,a Yong-Mei Xiao,a Pu Maoa and Ling-Bo Qu*b
a School of Chemistry and Chemical Engineering, Henan University of Technology; Academician
Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, PR China
b College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR
China
An efficient protocol for the synthesis of 3-aroylquinoxalin-2(1H)-ones has been developed via
metal-free oxidative cross-coupling reaction of quinoxalin-2(1H)-ones with aryl aldehydes in mild
conditions with good yields.
O
N
N
H
O
O
Ar
TBHP
DCE, 70oC
36 examples
R2
R2
ArCH
+
N
R1
O
N
R1
up to 88% yield
Transition-metal-free
Broad substrate scope
Mild reaction conditions
Highly regioselective
Good yields
Operationaly simple