Transition-metal free C3-amidation of quinoxalin-2(1: H)-ones using Selectfluor as a mild oxidant

Article abstract of DOI:10.1039/c9ob02157d

A practical and efficient synthetic route to construct a variety of 3-amidated quinoxalin-2(1H)-ones was developed via transition-metal free direct oxidative amidation of quinoxalin-2(1H)-ones with amidates using Selectfluor reagent as a mild oxidant. This protocol features mild reaction conditions, operational simplicity, broad substrate scope, and good to excellent yields.

Full text of DOI:10.1039/c9ob02157d

Organic &
Biomolecular Chemistry
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PAPER
Transition-metal free C3-amidation of quinoxalin-
2(1H)-ones using Selectfluor as a mild oxidant†
Cite this: Org. Biomol. Chem., 2019,
17, 10178
Jin-Wei Yuan, *a Jun-Liang Zhu,a Bing Li,a Liang-Yu Yang, a Pu Mao,a
Shou-Ren Zhang, *b Yan-Chun Lib and Ling-Bo Quc
Received 7th October 2019,
Accepted 19th November 2019
A practical and efficient synthetic route to construct a variety of 3-amidated quinoxalin-2(1H)-ones was
developed via transition-metal free direct oxidative amidation of quinoxalin-2(1H)-ones with amidates
using Selectfluor reagent as a mild oxidant. This protocol features mild reaction conditions, operational
simplicity, broad substrate scope, and good to excellent yields.
DOI: 10.1039/c9ob02157d
rsc.li/obc
ling (CDC) methods have received much attention in organic
synthesis.7 From the view point of step- and atom-economy,
Introduction
Quinoxalin-2(1H)-ones are important N-heterocyclic moieties direct C–H/N–H cross-coupling of C–H bonds and non-acti-
found in natural products and pharmaceuticals,1 and exhibit vated amines and amides may prove to be a remarkably practi-
an amazingly wide spectrum of biological activities including cal and sustainable approach for the synthesis of nitrogen-con-
protein kinase inhibitory, antimicrobial, anticancer, antith- taining compounds.8 Recently, the syntheses of 3-amino qui-
rombotic, and benzodiazepine receptor agonist activities.2 noxalin-2(1H)-ones have been realized via C–H/N–H cross-
Recently, the synthesis of C3-functionalized quinoxalin-2(1H)- coupling reactions with primary and secondary alkyl amines as
one analogues has attracted considerable attention. Various the coupling partners (Scheme 1a),9 but this transformation
3-substituted quinoxalin-2(1H)-one derivatives have been syn- was only used for alkyl amines. In 2019, a convenient palla-
thesized.3 Amide bond construction is one of the most funda- dium-catalyzed direct oxidative amidation of quinoxalin-2(1H)-
mental reactions in organic chemistry, given the occurrence of ones with acetonitrile was developed by our group to syn-
this functional group in a vast array of natural and synthetic thesize 3-amidated quinoxalin-2(1H)-ones (Scheme 1b),10
compounds.4 Amide bonds attached to quinoxalin-2(1H)-ones which was conducted by using stoichiometric amounts of the
have attracted interest due to the presence of 3-acylamino qui- strong oxidant K2S2O8, and transition-metal Pd(OAc)2 as a cata-
noxalin-2(1H)-ones in numerous biologically active molecules lyst under harsh reaction conditions. Very recently, our group
and functional materials.5 Accordingly, the development of
efficient methods for the construction of highly functionalized
3-acylamino quinoxalin-2(1H)-ones is highly desirable.
Traditionally, prefunctionalized substrates such as 3-amino
quinoxalin-2(1H)-ones are employed for coupling with acyla-
tion reagents, or the addition of amide to 3-chloro quinoxalin-
2(1H)-ones.6 However, the classic coupling reactions suffer
from drawbacks such as multi-step procedures, low tolerance
for functional groups, high reaction temperatures, and moder-
ate to low yields. In recent years, cross-dehydrogenation coup-
aSchool of Chemistry & Chemical Engineering, Henan University of Technology;
Academician Workstation for Natural Medicinal Chemistry of Henan Province,
Zhengzhou 450001, China. E-mail: yuanjinweigs@126.com
bHenan Key Laboratory of Nanocomposites and Applications; Institute of
Nanostructured Functional Materials, Huanghe Science and Technology College,
Zhengzhou 450006, China
cCollege of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou
450001, China
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c9ob02157d
Scheme 1 Synthesis of 3-amidated quinoxalin-2(1H)-one derivatives.
10178 | Org. Biomol. Chem., 2019, 17, 10178–10187
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Table 1 Optimization of the reaction conditionsa
described a copper-catalyzed direct oxidative amidation of qui-
noxalin-2(1H)-ones with a variety of aromatic and aliphatic
amides under microwave irradiation (Scheme 1c).11 This well-
developed approach may suffer from some disadvantages such
as the requirement of transition-metal CuBr as a catalyst and
the inevitable use of
a strong oxidant and microwave
irradiation, which could thereby limit its large scale appli-
cations. Although much progress has been made on the ami-
dation of quinoxalin-2(1H)-ones, transition-metal free C3-ami-
dation of quinoxalin-2(1H)-ones with amides as the coupling
partners via C–H/N–H cross-coupling reactions has proved to
be very challenging due to the low nucleophilicity of amides
(electron-withdrawing carbonyl groups).
Temp.
(°C)
Time
(h)
Yieldb
(%)
Entry
Oxidant (equiv.)
Solvent
1
K2S2O8 (1.0)
TBHP (3.0)
TBPB (3.0)
Selectfluor (1.0)
NFSI (1.0)
Selectfluor (0.5)
Selectfluor (1.3)
Selectfluor (1.5)
Selectfluor (2.0)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMSO
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
Trace
0
0
75
0
55
80
85
85
0
Trace
0
45
0
15
25
Trace
2c
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1-Chloromethyl-4-fluoro-1,4-diazoniabi
cyclo[2.2.2]octane
bis(tetrafluoroborate) (Selectfluor) is commercially available,
exceptionally stable, and useful as a powerful fluorination
regent and oxidant.12 Synthesis of several functionalized
heterocyclic molecules has been realized successfully using
Selectfluor as a mild oxidant.13 Recently, Lei’s group described
an oxidative α sp3 C–H arylation of alcohols, ethers, and
cyclanes with heterocycles promoted by Selectfluor under
visible light irradiation.14 Very recently, our group has also
developed a practical synthetic route through a fluorination-
triggered tandem cyclization of styrene-type carboxylic acids to
construct a variety of 4-fluoro-3-aryl-3,4-dihydroisocoumarins
and 3-arylisocoumarins using Selectfluor as an electrophilic
reagent and oxidant.15 Expanding the application of
Selectfluor reagent for the cross-coupling reaction is still a
challenging work. To the best of our knowledge, transition-
metal free direct cross-dehydrogenative amidation of the unac-
tivated quinoxalin-2(1H)-ones is still rarely investigated using
amides as the coupling partners in the presence of Selectfluor
reagent. Herein, we reported a practical and efficient tran-
sition-metal free approach for the direct amidation of quinoxa-
lin-2(1H)-ones with easily available amides using Selectfluor as
H2O
Acetone
CH3OH
DCE
Dioxane
DMF
CH3CN : H2O
= 1 : 1
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
18
19
20
21
22
23
24
25d
26e
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
Selectfluor (1.5)
—
20
40
70
60
60
60
60
60
60
6.0
6.0
6.0
1.0
2.0
3.0
4.0
4.0
4.0
60
70
85
65
75
80
85
0
Selectfluor (1.5)
84
a Reaction conditions: 1-methylquinoxalin-2(1H)-one 1a (0.2 mmol,
32.0 mg), benzamide 2a (0.4 mmol, 48.4 mg), oxidant, and solvent
(2.0 mL) at 60 °C. b Isolated yield. c TBHP (70% in water). d No
Selectfluor was added. e Under a N2 atmosphere.
a mild oxidant (Scheme 1d). This protocol features good to (NFSI) was employed, this transformation also could not
excellent yields and does not require toxic metals, ligands, and proceed (entry 5, Table 1). These facts showed that Selectfluor
bases, and could serve as an efficient approach for the reagent played a paramount role in this transformation. The
functionalization of quinoxalin-2(1H)-ones under mild effect of Selectfluor loading was also investigated. As a result,
conditions.
1.5 equiv. was found to be the best choice and the yield could
reach 85% (entries 4 and 6–9, Table 1). Subsequently, the
effect of various solvents, such as CH3CN, DMSO, H2O,
acetone, CH3OH, DCE, dioxane, and DMF, and the co-solvent
CH3CN–H2O (1 : 1, v : v) was studied, and CH3CN was found to
Results and discussion
We initiated our investigation with 1-methylquinoxalin-2(1H)- be best choice (entries 8 and 10–17, Table 1). The effect of
one (1a) and benzamide (2a) as the model substrates to ident- temperature was also tested. On increasing the temperature
ify suitable reaction conditions (Table 1). Firstly, when from 20 °C to 60 °C, the yield increased from 60 to 85%. But
different oxidants, including K2S2O8, tert-butyl hydroperoxide upon increasing it further to 70 °C, the yield did not increase
(TBHP), tert-butyl peroxybenzoate (TBPB), and Selectfluor, (entries 8 and 18–20, Table 1). Then, the molar ratio of 1a and
were used for this coupling reaction in CH3CN at 60 °C for 2a was investigated. When the ratio of 1a and 2a was 1 : 1.5,
6.0 h, the results showed that direct C-3 amidation took place the best yield (85%) could be obtained (ESI, entries 1–5,
in the presence of Selectfluor (1.0 equiv.), affording product Table S1†). The effect of reaction time was also tested. 4.0 h
3aa in 75% yield in the absence of any metals (entry 4, proved be the optimal time, and could provide a yield of 85%
Table 1), and the desired product was not observed in the pres- (entries 8 and 21–24, Table 1). When the reaction proceeded in
ence of other oxidants such as K2S2O8 and TBHP (entries 1–3, the absence of Selectfluor reagent, no desired product 3aa was
Table 1). Moreover, when N-fluorobenzenesulphonimide detected (entry 25, Table 1), thus indicating that Selectfluor is
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Table 2 Scope of amides in the amidation of 1-methylquinoxalin-2
(1H)-onesa,b
crucial for the reaction to occur. Furthermore, when the reac-
tion was protected under nitrogen, the desired product 3aa
was obtained with a slight decrease in yield (entry 26, Table 1),
which indicated that the oxygen molecule from air was toler-
ated in this transformation. After surveying the reaction con-
ditions, the optimal conditions were identified as follows: the
molar ratio of 1a and 2a being 1 : 1.5, 1.5 equiv. Selectfluor as
the oxidant, and 2.0 mL CH3CN at 60 °C for 4.0 h. This
approach provides a practical and facile functionalization of
quinoxalin-2(1H)-ones with amides without any need for toxic
metals, and additives, and could find numerous applications
in pharmaceutics and industry.
With the optimized reaction conditions in hand, we
assessed the scope and generality of the approach by using a
variety of quinoxalin-2(1H)-one derivatives (Table 2). First, the
variation in the amides part of the reaction was examined. A
variety of aryl primary amides bearing electron-rich and elec-
tron-poor substituents reacted smoothly affording the corres-
ponding products (3aa–3ai) in good to excellent yields
(74–90%). Generally, aryl amides with electron-donating
groups (–OMe, –OEt) gave higher yields in comparison with
those with electron-withdrawing groups (–F, –Cl, –Br, –I).
Moreover, good yields could be obtained for halogen-bearing
substrates (3ad–3ah). The survival of a halogen substituent
offered a great opportunity to further functionalize the pro-
ducts. To our delight, when an aryl amide with a strong elec-
tron-withdrawing –CF3 group 2i was employed, the coupling
reaction tolerated the reaction conditions and provided 3ai in
74% yield. Fortunately, heterocyclic amides, pyridine-2-carbox-
amide and thiophene-2-carboxamide, were suitable substrates,
and the corresponding products 3aj and 3ak were obtained in
good yields. It is disappointing that N-methylbenzamide could
not undergo this reaction. Gratifyingly, when aliphatic primary
and secondary amides were employed, the coupling reactions
proceeded smoothly to afford the corresponding desired pro-
ducts (3al–3ar) in excellent yields (80–93%). Compared with
aliphatic secondary amides, aliphatic primary amides could
afford higher yields. It is noteworthy that formamides were
well tolerated to provide the formylated products 3ap and 3ar
a Reaction conditions: 1-methylquinoxalin-2(1H)-one 1a (0.2 mmol,
32.0 mg), amides 2 (0.3 mmol), Selectfluor agent (0.3 mmol, 106.2 mg)
in CH3CN (2.0 mL) at 60 °C for 4.0 h. b Isolated yield.
in excellent yields under our present conditions. Because were well tolerated to provide the desired products (3ee, 3fe,
N-arylated lactams and oxazolidinones show important bio- and 3ge) in excellent yields (80–82%). Fortunately, when we
logical activities, various lactams and oxazolidinones were carried out the reaction of N-unprotected quinoxalin-2(1H)-one
employed for this reaction. Fortunately, the corresponding with 4-chlorobenzamide, the corresponding desired product
desired products (3as–3au) were obtained in excellent yields 3ke was obtained in 45% yield. The result indicated that the
(82–90%). When 2-ethoxybenzamide (2c), 2-bromobenzamide oxidant Selectfluor had a weak effect on the reactive hydrogen
(2g), 2-iodobenzamide (2h), and second aliphatic amides (2p– of quinoxalin-2(1H)-one. Notably, quinoxalin-2(1H)-ones con-
2t) were employed, the reactions provided good yields taining halogen moieties were tolerated well, and it hardly
(79–90%), which indicated that the steric factor did not affected this reaction (3ie and 3je). Unfortunately, quinoxalin-2
obstruct the progress of this reaction.
(1H)-one bearing a strong electron-withdrawing –NO2 group
After studying the scope of amides, we turned our attention could not undergo this reaction to yield the desired product
toward substituted quinoxalin-2(1H)-ones (Table 3). Generally, under the present conditions. To our delight, the amidation
N-substituted quinoxalin-2(1H)-ones were well compatible with reaction of 1-methylquinolin-2(1H)-one with 4-chlorobenza-
the reaction. It was observed that the presence of N-alkyl and mide was also successful, albeit in low yield (3le, 20%).
N-benzyl groups did not restrict the formation of the desired
Additionally, to verify the utility and robustness of this pro-
products (3be–3de, 3he). It is noteworthy that quinoxalin-2 tocol, gram-scale reactions were conducted using substrate 1a
(1H)-ones bearing N-allyl, N-propargyl, and N-esteryl groups (7 mmol, 1.12 g) with benzamide in a 100 mL round-bottom
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Table 3 Scope of quinoxalin-2(1H)-ones for the amidationa,b
Scheme 3 Control experiments.
a Reaction conditions: quinoxalin-2(1H)-one 1a (0.2 mmol), 4-chloro-
benzamides 2e (0.3 mmol, 46.5 mg), Selectfluor agent (0.3 mmol,
106.2 mg) in CH3CN (2.0 mL) at 60 °C for 4.0 h. b Isolated yield.
Scheme 4 Proposed reaction mechanism.
On the basis of the above-mentioned results and literature
reports,14,15 a plausible catalytic cycle was proposed and is
depicted in Scheme 4. Initially, the reaction between benz-
amide 2a and Selectfluor by single electron transfer (SET) gives
intermediate I together with a Selectfluor radical anion.12m,13g
Next, the generated N radical cation I produces the corres-
flask under the standard conditions. As expected, the reaction
proceeded well to produce N-(4-methyl-3-oxo-3,4-dihydroqui-
noxalin-2-yl)benzamide 3aa in 78% yield (Scheme 2), which
has promising applications in preparative syntheses.
To further understand the mechanism of this reaction,
some control experiments were carried out. While 2.0 equiv. of
2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) as the radical-
trapping reagent were subjected to the standard reaction con-
ditions, the yield of 3aa decreased obviously and only 28% 3aa
was obtained. When 3.0 equiv. of TEMPO were added to the
reaction system, this transformation was completely sup-
pressed (Scheme 3a). The amidation reaction was totally shut
off when 3.0 equiv. of 2,6-di-tert-butyl-4-methylphenol (BHT)
were added. In contrast, a coupling product of benzamide with
BHT, N-(2,6-di-tert-butyl-4-hydroxybenzyl)benzamide (4) was
obtained in 56% yield (Scheme 3b). These results reveal that
the transformation may proceed via a radical course.
ponding benzamido radical II by losing
a
proton.
Subsequently, the electron-deficient heteroarene, 1-methyl-
quinoxalin-2(1H)-one 1a, can capture the nucleophilic radical
II and generate the radical adduct III. Intermediate III would
furnish the corresponding nitrogen cation IV via single-elec-
tron transfer (SET). Finally, the expected coupling product 3aa
is obtained by the deprotonation of IV.
Conclusions
In conclusion, we have developed an intriguing and efficient
approach for oxidative C(sp2)–H amidation of quinoxalin-2
(1H)-ones with various amides, which was mediated by
Selectfluor under relatively mild conditions. This reaction has
a broad scope of substrates and provides a convenient method
for the preparation of 3-amidated quinoxalin-2(1H)-ones.
Control experiments reveal that the transformation proceeds
via a radical pathway. Not having to use a transition-metal
catalyst and the direct coupling of the quinoxalin-2(1H)-one
without further activation procedures make this protocol
Scheme 2 Gram-scale synthesis experiment.
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greener and practical for the synthesis of substituted quinoxa- 1276, 1204; 1H NMR (400 MHz, DMSO-d6) δ: 10.24 (s, 1H), 7.69
lin-2(1H)-ones.
(d, JH–H = 7.9 Hz, 1H), 7.56–7.51 (m, 3H), 7.50–7.46 (m, 2H),
7.41–7.38 (m, 1H), 7.23–7.20 (m, 1H), 3.84 (s, 3H), 3.69 (s, 3H);
13C NMR (100 MHz, DMSO-d6) δ: 164.5 (CvO), 159.8, 151.4,
145.7, 135.6, 132.1, 131.7, 130.4 (CH), 129.1 (CH), 128.4 (CH),
124.5 (CH), 120.1 (CH), 118.8 (CH), 115.3 (CH), 113.3 (CH),
55.8 (CH3), 30.1 (CH3); HR MS (ESI) m/z: calcd for C17H16N3O3
[M + H]+ 310.1186, found 310.1187.
Experimental
General information
All chemicals were commercially available and used as received
without further purification. Column chromatography was per-
formed using 300–400 mesh silica. Nuclear magnetic reso-
nance spectra were recorded on a Bruker Avance 400 MHz
spectrometer. Chemical shifts for 1H NMR spectra are
recorded in parts per million using tetramethylsilane. Data
were reported as follows: chemical shift, multiplicity (s =
singlet, d = doublet, t = triplet, m = multiplet and br = broad),
coupling constant in Hz and integration. Chemical shifts for
13C NMR spectra were recorded in parts per million using
tetramethylsilane. Chemical shifts for 19F NMR spectra were
recorded in parts per million with fluorobenzene as the exter-
nal standard. High resolution mass spectra (HR MS) were
obtained on a Thermo Scientific LTQ Orbitrap XL instrument
using the ESI technique. IR spectra were recorded on a
Shimadazu IR-408 Fourier transform infrared spectrophoto-
meter using a thin film supported on KBr pellets. Melting
points were measured on XT4A microscopic apparatus and are
uncorrected.
2-Ethoxy-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
benzamide (3ac)
Colorless solid, mp 189–190 °C (lit.11 188–189 °C); IR (KBr)
ν(cm−1): 3249, 2927, 1656, 1598, 1501, 1485, 1448, 1354, 1287,
1242, 1140; 1H NMR (400 MHz, CDCl3) δ: 11.69 (s, 1H), 8.34
(dd, JH–H = 7.8 Hz, JH–H = 1.8 Hz, 1H), 7.94 (dd, JH–H = 8.0 Hz,
JH–H = 1.4 Hz, 1H), 7.49 (td, JH–H = 7.8 Hz, JH–H = 1.8 Hz, 1H),
7.44 (td, JH–H = 7.8 Hz, JH–H = 1.4 Hz, 1H), 7.34 (td, JH–H = 7.6
Hz, JH–H = 1.2 Hz, 1H), 7.27 (dd, JH–H = 8.2 Hz, JH–H = 0.8 Hz,
1H), 7.10 (td, JH–H = 7.6 Hz, JH–H = 0.6 Hz, 1H), 7.03 (d, JH–H
=
8.3 Hz, 1H), 4.34 (q, JH–H = 7.0 Hz, 2H), 3.76 (s, 3H), 1.69 (t,
JH–H = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 162.9, 157.0,
151.4, 145.2, 133.9 (CH), 133.1 (CH), 132.2, 130.9, 129.3 (CH),
127.9 (CH), 124.3 (CH), 121.4, 121.2 (CH), 113.4 (CH), 112.3
(CH), 65.3 (CH2), 29.7 (CH3), 14.7 (CH3); HR MS (ESI) m/z:
calcd for C18H18N3O3 [M + H]+ 324.1343, found 324.1345.
4-Fluoro-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
benzamide (3ad)
General experimental procedure for the synthesis of
3-amidated quinoxalin-2(1H)-one derivatives (3)
Colorless crystal, mp 209–210 °C (lit.11 212–214 °C); IR (KBr)
ν(cm−1): 3360, 2922, 1650, 1594, 1514, 1488, 1474, 1413, 1360,
1234, 1200; 1H NMR (400 MHz, DMSO-d6) δ: 10.33 (s, 1H),
8.05–8.02 (m, 2H), 7.68 (d, JH–H = 7.8 Hz, 1H), 7.56 (d, JH–H = 3.9
Hz, 2H), 7.41–7.37 (m, 3H), 3.69 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ: 165.5 (d, JF–C = 252.5 Hz), 163.1, 151.4, 144.2,
132.1, 130.8, 130.1 (d, JF–C = 9.5 Hz, CH), 129.5 (CH), 128.5
(CH), 124.7 (CH), 116.0 (d, JF–C = 21.2 Hz, CH), 113.6 (CH), 29.9
(CH3); 19F NMR (376 MHz, DMSO-d6) δ: −107.3; HR MS (ESI) m/
z: calcd for C16H13FN3O2 [M + H]+ 298.0986, found 298.0988.
Quinoxalin-2(1H)-ones 1 (0.2 mmol), amides 2 (0.3 mmol),
Selectfluor agent (0.3 mmol, 106.2 mg), and acetonitrile
(2.0 mL) were added to a 10 mL reaction tube. The mixture was
stirred at 60 °C for 4.0 h. After completion of the reaction, the
solvent was distilled under vacuum. Then, the resulting
mixture was dissolved with ethyl acetate (10 mL) and washed
with saturated sodium chloride solution (10 mL × 2). The
organic phase was dried over anhydrous Na2SO4 and concen-
trated under vacuum. The residue was purified by silica gel
column chromatography to give 3-amidated quinoxalin-2(1H)-
ones 3 using ethyl acetate/dichloromethane as the eluant.
4-Chloro-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
benzamide (3ae)
N-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)benzamide (3aa)
Light yellow crystal, mp 203–205 °C (lit.11 201–202 °C); IR (KBr)
ν(cm−1): 3368, 2930, 1698, 1649, 1586, 1491, 1467, 1411, 1357,
1274, 1201; 1H NMR (400 MHz, CDCl3) δ: 9.87 (s, 1H), 7.94–7.92
(m, 3H), 7.52–7.48 (m, 3H), 7.39 (td, JH–H = 7.6 Hz, JH–H = 1.2
Hz, 1H), 7.33 (dd, JH–H = 8.3 Hz, JH–H = 0.9 Hz, 1H), 3.79 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 163.1 (CvO), 151.3, 144.1 (CH),
139.1, 132.2, 132.0, 130.8, 129.5 (CH), 129.2 (CH), 129.0 (CH),
128.5 (CH), 124.7 (CH), 113.7 (CH), 29.9 (CH3); HR MS (ESI) m/
z: calcd for C16H13ClN3O2 [M + H]+ 314.0691, found 314.0692.
Colorless crystal, mp 176–177 °C (lit.11 175–176 °C); IR (KBr)
ν(cm−1): 3372, 2924, 1698, 1647, 1597, 1502, 1481, 1354, 1271,
1
1201; H NMR (400 MHz, CDCl3) δ: 10.25 (s, 1H), 7.96 (d, JH–H
= 7.2 Hz, 2H), 7.69–7.63 (m, 2H), 7.59–7.55 (m, 4H), 7.41–7.37
(m, 1H), 3.69 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 164.7
(CvO), 151.4, 145.7, 134.1, 133.0 (CH), 132.0, 131.7, 129.3
(CH), 129.0 (CH), 128.4 (CH), 128.1 (CH), 124.5 (CH), 115.3
(CH), 30.1 (CH3); HR MS (ESI) m/z: calcd for C16H14N3O2 [M +
H]+ 280.1081, found 280.1082.
4-Bromo-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
3-Methoxy-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
benzamide (3af)
benzamide (3ab)
Colorless solid, mp 180–181 °C (lit.11 176–178 °C); IR (KBr)
Colorless crystal, mp 109–110 °C (lit.11 108–109 °C); IR (KBr) ν(cm−1): 3322, 1691, 1636, 1605, 1590, 1507, 1479, 1273, 1216; 1H
ν(cm−1): 3368, 2919, 1703, 1641, 1595, 1503, 1482, 1469, 1354, NMR (400 MHz, CDCl3) δ: 9.87 (s, 1H), 7.94 (dd, JH–H = 8.0 Hz,
10182 | Org. Biomol. Chem., 2019, 17, 10178–10187
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JH–H = 1.0 Hz, 1H), 7.86 (d, JH–H = 8.5 Hz, 2H), 7.66 (d, JH–H
=
1H), 8.21 (d, JH–H = 7.8 Hz, 1H), 8.13 (td, JH–H = 7.6 Hz, JH–H =
8.5 Hz, 2H), 7.50 (td, JH–H = 7.8 Hz, JH–H = 1.3 Hz, 1H), 7.39 (td, 1.4 Hz, 1H), 7.77–7.74 (m, 1H), 7.70 (d, JH–H = 8.0 Hz, 1H),
JH–H = 7.6 Hz, JH–H = 0.9 Hz, 1H), 7.33 (d, JH–H = 8.3 Hz, 1H), 3.80 7.57–7.51 (m, 2H), 7.39 (td, JH–H = 7.3 Hz, JH–H = 1.9 Hz, 1H),
(s, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.3, 151.3, 144.1, 132.7, 3.71 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 160.8 (CvO),
132.2 (CH), 130.8, 129.5 (CH), 129.1 (CH), 128.6 (CH), 127.7, 151.3, 149.3 (CH), 149.0, 144.4, 139.1 (CH), 131.9, 131.7, 128.6
124.8 (CH), 113.7 (CH), 29.9 (CH3); HR MS (ESI) m/z: calcd for (CH), 128.3 (CH), 124.6 (CH), 122.9 (CH), 115.3 (CH), 30.2
C16H13BrN3O2 [M + H]+ 358.0186, found 358.0188.
(CH3); HR MS (ESI) m/z: calcd for C15H13N4O2 [M + H]+
281.1033, found 281.1031.
2-Bromo-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
benzamide (3ag)
N-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)thiophene-2-
Light yellow crystal, mp 162–163 °C (lit.11 168–169 °C); IR
(KBr) ν(cm−1): 3342, 1721, 1647, 1612, 1584, 1498, 1465, 1427,
1355, 1267, 1199; 1H NMR (400 MHz, CDCl3) δ: 9.71 (s, 1H),
7.64 (dd, JH–H = 7.6 Hz, JH–H = 1.6 Hz, 1H), 7.60 (dd, JH–H = 8.0
Hz, JH–H = 0.8 Hz, 1H), 7.46 (td, JH–H = 8.6 Hz, JH–H = 1.4 Hz,
1H), 7.39 (td, JH–H = 7.6 Hz, JH–H = 1.1 Hz, 1H), 7.35–7.27 (m,
3H), 3.71 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 165.0 (CvO),
151.0, 143.8 (CH), 137.2, 133.4 (CH), 131.8, 131.7 (CH), 130.9,
129.8 (CH), 129.2 (CH), 128.6 (CH), 127.6 (CH), 124.5 (CH),
119.2, 113.7 (CH), 29.8 (CH3); HR MS (ESI) m/z: calcd for
C16H13BrN3O2 [M + H]+ 358.0186, found 358.0189.
carboxamide (3ak)
Colorless solid, mp 178–180 °C (lit.11 184–185 °C); IR (KBr)
ν(cm−1): 3484, 3096, 2920, 1688, 1651, 1622, 1592, 1505, 1490,
1472, 1414, 1274, 1204; H NMR (400 MHz, DMSO-d6) δ: 10.32
(s, 1H), 8.02 (dd, JH–H = 3.7 Hz, JH–H = 0.9 Hz, 1H), 7.96 (dd,
JH–H = 5.0 Hz, JH–H = 1.0 Hz, 1H), 7.69 (d, JH–H = 7.9 Hz, 1H),
1
7.57 (d, JH–H = 3.7 Hz, 1H), 7.41–7.37 (m, 1H), 7.25 (dd, JH–H
=
4.9 Hz, JH–H = 3.8 Hz, 1H), 3.70 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ: 159.4 (CvO), 151.3, 145.6, 139.1, 133.8, 132.2,
131.6, 131.0, 129.1, 128.9, 128.4, 124.5, 115.3, 30.1 (CH3); HR
MS (ESI) m/z: calcd for C14H12N3O2S [M + H]+ 286.0645, found
286.0647.
2-Iodo-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
benzamide (3ah)
N-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)acetamide (3al)
Light yellow crystal, mp 197–198 °C (lit.11 195–196 °C); IR
(KBr) ν(cm−1): 3343, 2919, 2850, 1716, 1641, 1498, 1476, 1418,
1319, 1265; 1H NMR (400 MHz, CDCl3) δ: 9.46 (s, 1H), 7.92 (dd,
JH–H = 7.9 Hz, JH–H = 0.8 Hz, 1H), 7.81 (d, JH–H = 7.8 Hz, 1H),
7.54 (dd, JH–H = 7.6 Hz, JH–H = 1.6 Hz, 1H), 7.51–7.47 (m, 1H),
7.44 (td, JH–H = 7.6 Hz, JH–H = 1.0 Hz, 1H), 7.36 (td, JH–H = 7.6
Hz, JH–H = 1.2 Hz, 1H), 7.31 (dd, JH–H = 8.3 Hz, JH–H = 0.9 Hz,
Colorless crystal, mp 192–194 °C (lit.11 209–210 °C); IR (KBr)
ν(cm−1): 3246, 2931, 1686, 1655, 1603, 1506, 1470, 1366, 1285,
1203; 1H NMR (400 MHz, DMSO-d6) δ: 9.73 (s, 1H), 7.61 (d,
JH–H = 7.9 Hz, 1H), 7.51–7.33 (m, 2H), 7.37–7.33 (m, 1H), 3.66
(s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 169.7,
151.0, 145.0, 131.7, 131.6, 128.4 (CH), 128.0 (CH), 124.4 (CH),
115.0 (CH), 30.1 (CH3), 25.4 (CH3); HR MS (ESI) m/z: calcd for
C11H12N3O2 [M + H]+ 218.0924, found 218.0924.
1H), 7.18 (td, JH–H = 7.8 Hz, JH–H = 1.7 Hz, 1H), 3.77 (s, 3H); 13
C
NMR (100 MHz, CDCl3) δ: 166.6 (CvO), 151.1, 143.8, 141.3,
140.0, 131.8, 131.7, 129.5, 128.7, 128.6, 128.3, 124.6, 113.6,
92.1, 29.9 (CH3); HR MS (ESI) m/z: calcd for C16H13IN3O2 [M +
H]+ 406.0047, found 406.0049.
N-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)propionamide
(3am)
Colorless solid, mp 161–162 °C (lit.11 161–162 °C); IR (KBr)
ν(cm−1): 3256, 2922, 1682, 1659, 1608, 1507, 1472, 1370, 1216;
N-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)-4-
(trifluoromethyl)benzamide (3ai)
1H NMR (400 MHz, DMSO-d6) δ: 9.71 (s, 1H), 7.61 (d, JH–H
8.0 Hz, 1H), 7.53–7.47 (m, 2H), 7.35 (td, JH–H = 7.0 Hz, JH–H
=
=
Colorless crystal, mp 152–153 °C; IR (KBr) ν(cm−1): 3365, 1700,
1
2.1 Hz, 1H), 3.66 (s, 3H), 2.71 (q, JH–H = 7.4 Hz, 2H), 1.07 (t,
JH–H = 7.4 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 173.1,
151.0, 145.0, 131.7, 131.6, 128.3 (CH), 128.0 (CH), 124.4 (CH),
115.1 (CH), 30.4 (CH3), 30.1 (CH2), 9.39 (CH3); HR MS (ESI) m/z:
calcd for C12H14N3O2 [M + H]+ 232.1081, found 232.1083.
1647, 1612, 1515, 1504, 1489, 1473, 1324, 1276, 1111; H NMR
(400 MHz, CDCl3) δ: 9.90 (s, 1H), 8.08 (d, JH–H = 8.1 Hz, 2H),
7.87 (dd, JH–H = 8.0 Hz, JH–H = 1.3 Hz, 1H), 7.76 (d, JH–H = 8.2
Hz, 2H), 7.48–7.43 (m, 1H), 7.35 (td, JH–H = 7.6 Hz, JH–H = 1.2
Hz, 1H), 7.29 (d, JH–H = 0.9 Hz, 1H), 3.74 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 162.9 (CvO), 151.1, 144.0 (CH), 137.0,
134.0 (q, JH–H = 32.7 Hz), 131.8, 130.8, 129.3 (CH), 128.6 (CH),
N-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)isobutyramide (3an)
128.0 (CH), 125.9 (q, JH–H = 3.6 Hz, CH), 124.7 (CH), 123.5 (q, Colorless solid, mp 126–128 °C (lit.11 116–117 °C); IR (KBr)
JH–H = 271.1 Hz), 113.7 (CH), 29.9 (CH3); 19F NMR (376 MHz, ν(cm−1): 3254, 2966, 2931, 2873, 1675, 1652, 1606, 1500, 1484,
1
CDCl3) δ: −63.0; HR MS (ESI) m/z: calcd for C17H13F3N3O2 1468, 1382, 1358, 1223, 1158; H NMR (400 MHz, DMSO-d6) δ:
[M + H]+ 348.0954, found 348.0954.
9.77 (s, 1H), 7.59 (d, JH–H = 7.9 Hz, 1H), 7.48 (d, JH–H = 3.8 Hz,
2H), 7.35–7.31 (m, 1H), 3.64 (s, 3H), 3.17–3.10 (m, 1H), 1.11 (d,
JH–H = 6.8 Hz, 6H); 13C NMR (100 MHz, DMSO-d6) δ: 175.8,
N-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)picolinamide (3aj)
Colorless solid, mp 232–233 °C; IR (KBr) ν(cm−1): 3302, 2921, 151.0, 145.0, 131.7, 131.6, 128.3 (CH), 128.0 (CH), 124.3 (CH),
1715, 1647, 1588, 1502, 1491, 1466, 1434, 1353; 1H NMR 115.0 (CH), 35.0 (CH3), 30.0 (CH2), 19.6 (CH3); HR MS (ESI) m/
(400 MHz, DMSO-d6) δ: 11.60 (s, 1H), 8.78 (d, JH–H = 4.6 Hz, z: calcd for C13H16N3O2 [M + H]+ 246.1237, found 246.1235.
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3-Methoxy-N-(3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydroquinoxalin-2-
yl)benzamide (3ao)
2H), 2.29–2.21 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 175.1,
151.6, 147.7, 133.1, 131.4, 130.1 (CH), 129.5 (CH), 123.9 (CH),
113.6 (CH), 48.3 (CH2), 31.8 (CH2), 29.7 (CH3), 19.1 (CH2); HR
MS (ESI) m/z: calcd for C13H14N3O2 [M + H]+ 244.1081, found
244.1082.
Colorless crystal, mp 138–140 °C; IR (KBr) ν(cm−1): 3246, 2960,
1
2871, 1657, 1606, 1504, 1471, 1376, 1208; H NMR (400 MHz,
DMSO-d6) δ: 9.72 (s, 1H), 7.61 (d, JH–H = 8.4 Hz, 1H), 7.53–7.48
(m, 2H), 7.37–7.33 (m, 1H), 3.67 (s, 3H), 2.66 (t, JH–H = 7.3 Hz,
2H), 1.66–1.57 (m, 2H), 0.93 (t, JH–H = 7.3 Hz, 3H); 13C NMR
(100 MHz, DMSO-d6) δ: 172.2, 151.0, 144.9, 131.7, 131.6, 128.3
(CH), 128.0 (CH), 124.4 (CH), 115.1 (CH), 38.9 (CH2), 30.1
(CH3), 18.4 (CH2), 14.0 (CH3); HR MS (ESI) m/z: calcd for
C13H16N3O2 [M + H]+ 246.1237, found 246.1236.
1-Methyl-3-(2-methyl-5-oxopyrrolidin-1-yl)quinoxalin-2(1H)-one
(3at)
Light yellow crystal, mp 149–151 °C (lit.11 153–154 °C); IR
(KBr) ν(cm−1): 2955, 2922, 2852, 1710, 1646, 1595, 1583, 1467,
1
1374, 1291, 1245, 1209; H NMR (400 MHz, CDCl3) δ: 7.83 (dd,
JH–H = 8.0 Hz, JH–H = 1.4 Hz, 1H), 7.57 (td, JH–H = 7.8 Hz, JH–H
=
1.5 Hz, 1H), 7.38–7.31 (m, 2H), 4.68–4.60 (m, 1H), 3.74 (s, 3H),
2.72–2.53 (m, 2H), 2.46–2.39 (m, 1H), 1.90–1.81 (m, 1H), 1.28
(d, JH–H = 6.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 175.3,
152.0, 147.4, 133.2, 131.6, 130.4 (CH), 129.8 (CH), 123.9 (CH),
113.7 (CH), 55.6 (CH3), 31.2 (CH2), 29.7 (CH3), 27.8 (CH2), 20.3
(CH3); HR MS (ESI) m/z: calcd for C14H16N3O2 [M + H]+
258.1237, found 258.1235.
N-Methyl-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
formamide (3ap)
Light yellow crystal, mp 149–150 °C (lit.11 154–155 °C); IR
(KBr) ν(cm−1): 3379, 2930, 1649, 1597, 1584, 1548, 1474, 1413,
1331, 1300, 1246; 1H NMR (400 MHz, DMSO-d6) δ: 9.43 (s, 1H),
7.66 (d, JH–H = 7.6 Hz, 1H), 7.55–7.50 (m, 2H), 7.37–7.34 (m,
1H), 3.62 (s, 3H), 3.28 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ:
164.3 (CvO), 152.0, 147.9, 132.1, 131.1, 129.4 (CH), 128.4
(CH), 124.3 (CH), 115.0 (CH), 30.2 (CH3), 29.7 (CH3); HR MS
(ESI) m/z: calcd for C11H12N3O2 [M + H]+ 218.0924, found
218.0924.
3-(4-Methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)oxazolidin-2-one
(3au)
Light yellow crystal, mp 181–182 °C (lit.11 181–182 °C); IR
(KBr) ν(cm−1): 3337, 2921, 2849, 1765, 1663, 1532, 1511, 1371,
1246; 1H NMR (400 MHz, CDCl3) δ: 7.76 (dd, JH–H = 8.0 Hz,
JH–H = 1.1 Hz, 1H), 7.54 (td, JH–H = 7.8 Hz, JH–H = 1.1 Hz, 1H),
7.36–7.28 (m, 2H), 4.53 (t, JH–H = 7.8 Hz, 2H), 4.30 (t, JH–H = 7.8
Hz, 2H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 154.6,
151.3, 145.9, 132.9, 131.2, 130.0 (CH), 129.3 (CH), 124.0 (CH),
113.7 (CH), 63.0 (CH3), 45.8 (CH2), 29.7 (CH3); HR MS (ESI) m/
z: calcd for C13H13N2O3 [M + H]+ 246.0873, found 246.0875.
N-Methyl-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
acetamide (3aq)
Colorless crystal, mp 183–184 °C (lit.11 193–195 °C); IR (KBr)
ν(cm−1): 3052, 2945, 1671, 1644, 1599, 1584, 1465, 1363, 1340,
1
1310, 1257; H NMR (400 MHz, CDCl3) δ: 7.80 (dd, JH–H = 8.0
Hz, JH–H = 1.2 Hz, 1H), 7.62 (td, JH–H = 7.8 Hz, JH–H = 1.4 Hz,
1H), 7.42–7.36 (m, 2H), 3.77 (s, 3H), 3.35 (s, 3H), 2.15 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 171.2, 152.4, 151.0, 133.3, 131.2, 4-Chloro-N-(4-ethyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
130.7, 129.8, 124.3, 113.8 (CH), 34.3 (CH3), 29.9 (CH3), 23.0 benzamide (3be)
(CH3); HR MS (ESI) m/z: calcd for C12H14N3O2 [M + H]+
Colorless solid, mp 162–163 °C; IR (KBr) ν(cm−1): 3357, 3053,
232.1081, found 232.1082.
1
2978, 1702, 1633, 1606, 1591, 1505, 1481, 1379, 1204; H NMR
(400 MHz, DMSO-d6) δ: 10.39 (s, 1H), 7.98 (dd, JH–H = 6.7 Hz,
JH–H = 1.9 Hz, 2H), 7.70 (dd, JH–H = 8.0 Hz, JH–H = 1.3 Hz, 1H),
7.65–7.62 (m, 3H), 7.57 (td, JH–H = 7.8 Hz, JH–H = 1.4 Hz, 1H),
7.39 (td, JH–H = 7.6 Hz, JH–H = 1.0 Hz, 1H), 4.33 (q, JH–H = 7.0
Hz, 2H), 1.27 (t, JH–H = 7.1 Hz, 3H); 13C NMR (100 MHz,
DMSO-d6) δ: 164.1, 150.9, 145.8, 137.7, 132.9, 131.9, 130.9,
130.2 (CH), 129.3 (CH), 129.2 (CH), 128.8 (CH), 124.4 (CH),
115.0 (CH), 38.0 (CH2), 12.7 (CH3); HR MS (ESI) m/z: calcd for
C17H15ClN3O2 [M + H]+ 328.0847, found 328.0846.
N-Benzyl-N-(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
formamide (3ar)
Colorless crystal, mp 133–135 °C; IR (KBr) ν(cm−1): 2922, 1675,
1
1655, 1583, 1549, 1468, 1353, 1304, 1184; H NMR (400 MHz,
CDCl3) δ: 9.76 (s, 1H), 7.71 (dd, JH–H = 8.0 Hz, JH–H = 1.4 Hz,
1H), 7.48–7.44 (m, 1H), 7.38 (d, JH–H = 7.4 Hz, 2H), 7.31 (td,
JH–H = 7.6 Hz, JH–H = 1.2 Hz, 1H), 7.25–7.20 (m, 3H), 7.17–7.14
(m, 1H), 5.38 (s, 2H), 3.66 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ: 163.8 (CvO), 151.9, 146.2, 137.3, 131.7, 131.3, 129.4 (CH),
129.0 (CH), 128.4 (CH), 128.3 (CH), 127.2 (CH), 124.3 (CH),
113.6 (CH), 45.0 (CH2), 29.9 (CH3); HR MS (ESI) m/z: calcd for
C17H16N3O2 [M + H]+ 294.1237, found 294.1236.
4-Chloro-N-(3-oxo-4-propyl-3,4-dihydroquinoxalin-2-yl)
benzamide (3ce)
Colorless crystal, mp 145–146 °C; IR (KBr) ν(cm−1): 3371, 2962,
1
1702, 1645, 1614, 1585, 1503, 1469, 1371, 1272, 1196; H NMR
1-Methyl-3-(2-oxopyrrolidin-1-yl)quinoxalin-2(1H)-one (3as)
(400 MHz, DMSO-d6) δ: 10.35 (s, 1H), 7.97–7.95 (m, 2H), 7.68
Light yellow crystal, mp 141–142 °C (lit.11 145–146 °C); IR (dd, JH–H = 7.9 Hz, JH–H = 1.2 Hz, 1H), 7.61 (d, JH–H = 8.5 Hz,
(KBr) ν(cm−1): 2955, 2915, 2850, 1704, 1653, 1596, 1460, 1383, 3H), 7.56 (td, JH–H = 7.8 Hz, JH–H = 1.2 Hz, 1H), 7.36 (td, JH–H
=
1303, 1253, 1221; 1H NMR (400 MHz, CDCl3) δ: 7.79 (dd, JH–H
=
7.5 Hz, JH–H = 0.8 Hz, 1H), 4.23 (t, JH–H = 7.7 Hz, 2H), 1.74–1.64
8.0 Hz, JH–H = 1.4 Hz, 1H), 7.55 (m, 1H), 7.37–7.30 (m, 2H), (m, 2H), 0.95 (t, JH–H = 7.4 Hz, 3H); 13C NMR (100 MHz,
4.04 (t, JH–H = 7.0 Hz, 2H), 3.74 (s, 3H), 2.64 (d, JH–H = 7.8 Hz, DMSO-d6) δ: 164.0, 151.1, 145.7, 137.7, 132.9, 131.9, 131.1,
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130.2 (CH), 129.2 (CH), 128.8 (CH), 124.4 (CH), 115.1 (CH), (CH), 124.8 (CH), 115.1 (CH), 61.9 (CH2), 44.7 (CH2), 14.4
44.2 (CH2), 20.7 (CH2), 11.5 (CH3); HR MS (ESI) m/z: calcd for (CH3); HR MS (ESI) m/z: calcd for C19H17ClN3O4 [M + H]+
C18H17ClN3O2 [M + H]+ 342.1004, found 342.1002.
386.0902, found 386.0903.
4-Chloro-N-(4-hexyl-3-oxo-3,4-dihydroquinoxalin-2-yl)
benzamide (3de)
Colorless solid, mp 117–118 °C; IR (KBr) ν(cm−1): 3388, 2957,
2930, 2854, 1707, 1641, 1609, 1589, 1503, 1466, 1276, 1201; H
NMR (400 MHz, CDCl3) δ: 9.89 (s, 1H), 7.94–7.92 (m, 3H),
7.50–7.46 (m, 3H), 7.37 (td, JH–H = 7.6 Hz, JH–H = 1.0 Hz, 1H),
7.32 (d, JH–H = 8.3 Hz, 1H), 4.30 (t, JH–H = 7.9 Hz, 2H),
1.83–1.75 (m, 2H), 1.50–1.43 (m, 2H), 1.38–1.31 (m, 4H), 0.90
(t, JH–H = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 163.1,
151.0, 144.1, 139.0, 132.3, 132.2, 129.9, 129.7 (CH), 129.2 (CH),
129.0 (CH), 128.4 (CH), 124.5 (CH), 113.6 (CH), 43.2 (CH2),
31.4 (CH2), 27.2 (CH2), 26.6 (CH2), 22.5 (CH2), 14.0 (CH3); HR
MS (ESI) m/z: calcd for C21H23ClN3O2 [M + H]+ 384.1473, found
384.1472.
N-(4-Benzyl-3-oxo-3,4-dihydroquinoxalin-2-yl)-4-
chlorobenzamide (3he)
Colorless crystal, mp 118–119 °C; IR (KBr) ν(cm−1): 3345, 2922,
1703, 1640, 1594, 1517, 1505, 1477, 1453, 1342, 1271, 1206; H
NMR (400 MHz, DMSO-d6) δ: 10.48 (s, 1H), 8.00 (d, JH–H = 8.6
Hz, 2H), 7.71 (d, JH–H = 7.8 Hz, 1H), 7.63 (d, JH–H = 8.6 Hz, 2H),
7.45 (d, JH–H = 3.9 Hz, 2H), 7.37–7.24 (m, 6H), 5.57 (s, 2H); 13C
NMR (100 MHz, DMSO-d6) δ: 164.2 (CvO), 151.7, 146.1, 137.8,
136.0, 132.9, 132.0, 131.3, 130.3 (CH), 129.3 (CH), 129.1 (CH),
128.7 (CH), 127.9 (CH), 127.3 (CH), 124.6 (CH), 115.6 (CH),
46.0 (CH2); HR MS (ESI) m/z: calcd for C22H17ClN3O2 [M + H]+
390.1004, found 390.1005.
1
1
4-Chloro-N-(6-chloro-4-methyl-3-oxo-3,4-dihydroquinoxalin-2-
yl)benzamide (3ie)
N-(4-Allyl-3-oxo-3,4-dihydroquinoxalin-2-yl)-4-chlorobenzamide
(3ee)
Colorless crystal, mp 240–241 °C; IR (KBr) ν(cm−1): 3369, 3073,
Colorless solid, mp 147–148 °C; IR (KBr) ν(cm−1): 3388, 2918,
1
1703, 1656, 1586, 1505, 1481, 1463, 1353, 1277, 1251, 1205; H
1
2850, 1705, 1650, 1593, 1515, 1480, 1358, 1276, 1198; H NMR
NMR (400 MHz, CDCl3) δ: 9.83 (s, 1H), 7.90 (d, JH–H = 8.5 Hz,
2H), 7.86 (d, JH–H = 2.2 Hz, 1H), 7.48 (d, JH–H = 8.5 Hz, 2H),
7.40 (dd, JH–H = 8.8 Hz, JH–H = 2.2 Hz, 1H), 7.21 (d, JH–H = 8.9
Hz, 1H), 3.75 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 162.9
(CvO), 151.0, 144.9, 139.3, 132.7, 131.9, 130.0, 129.5, 129.2
(CH), 129.0 (CH), 128.6 (CH), 128.3 (CH), 114.8 (CH), 30.1
(CH3); HR MS (ESI) m/z: calcd for C16H12Cl2N3O2 [M + H]+
348.0301, found 348.0301.
(400 MHz, CDCl3) δ: 10.42 (s, 1H), 7.98 (dd, JH–H = 6.7 Hz, JH–H
= 1.9 Hz, 2H), 7.70 (dd, JH–H = 8.9 Hz, JH–H = 1.1 Hz, 1H), 7.63
(dd, JH–H = 6.7 Hz, JH–H = 1.8 Hz, 2H), 7.54–7.49 (m, 2H), 7.38
(td, JH–H = 7.3 Hz, JH–H = 1.6 Hz, 1H), 6.01–5.93 (m, 1H), 5.20
(dd, JH–H = 10.5 Hz, JH–H = 1.1 Hz, 1H), 5.11 (dd, JH–H = 8.6 Hz,
JH–H = 1.1 Hz, 1H), 4.95 (d, JH–H = 4.7 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ: 164.2, 151.1, 145.9, 137.7, 132.9, 131.8,
131.7 (CH), 131.2, 130.2 (CH), 129.2 (CH), 129.1, 128.6 (CH),
124.5 (CH), 117.8 (CH), 115.6 (CH), 44.9 (CH2); HR MS (ESI) m/
z: calcd for C18H15ClN3O2 [M + H]+ 340.0847, found 340.0846.
N-(6-Bromo-4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)-4-
chlorobenzamide (3je)
Colorless crystal, mp 236–237 °C; IR (KBr) ν(cm−1): 3369, 2921,
4-Chloro-N-(3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydroquinoxalin-2-
yl)benzamide (3fe)
1
1703, 1657, 1587, 1504, 1479, 1463, 1351, 1288, 1249; H NMR
Colorless solid, mp 195–196 °C; IR (KBr) ν(cm−1): 3388, 3251,
(400 MHz, CDCl3) δ: 9.86 (s, 1H), 8.10 (d, JH–H = 2.2 Hz, 1H),
7.93 (d, JH–H = 8.6 Hz, 2H), 7.59 (dd, JH–H = 8.9 Hz, JH–H = 2.2
Hz, 1H), 7.51 (dd, JH–H = 6.7 Hz, JH–H = 1.8 Hz, 2H), 7.20 (d,
JH–H = 8.9 Hz, 1H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
163.0 (CvO), 151.1, 144.9, 139.3, 133.0, 132.0, 131.8 (CH),
131.2 (CH), 130.0, 129.3 (CH), 129.0 (CH), 117.5, 115.0 (CH),
30.1 (CH3); HR MS (ESI) m/z: calcd for C16H12BrClN3O2 [M +
H]+ 391.9796, found 391.9795.
1
2982, 2922, 1704, 1651, 1593, 1516, 1480, 1358, 1275, 1198; H
NMR (400 MHz, DMSO-d6) δ: 10.49 (s, 1H), 8.00–7.97 (m, 2H),
7.72 (d, JH–H = 7.6 Hz, 1H), 7.64–7.61 (m, 4H), 7.44–7.40 (m,
1H), 5.15 (d, JH–H = 2.3 Hz, 2H), 3.40 (t, JH–H = 2.4 Hz, 1H); 13C
NMR (100 MHz, DMSO-d6) δ: 164.4, 150.6, 145.9, 137.8, 132.8,
131.8, 130.6, 130.3 (CH), 129.4 (CH), 129.2 (CH), 128.7 (CH),
124.9 (CH), 115.5 (CH), 78.1, 76.0, 32.4 (CH2); HR MS (ESI) m/
z: calcd for C18H13ClN3O2 [M + H]+ 338.0691, found 338.0690.
Ethyl 2-(3-(4-chlorobenzamido)-2-oxoquinoxalin-1(2H)-yl)
acetate (3ge)
4-Chloro-N-(3-oxo-3,4-dihydroquinoxalin-2-yl)benzamide (3ke)
Light yellow crystal, mp 281–282 °C (lit.16 281 °C); IR (KBr)
Colorless crystal, mp 158–159 °C; IR (KBr) ν(cm−1): 3363, 3988, ν(cm−1): 3382, 3055, 2916, 1670, 1588, 1505, 1470, 1389, 1254;
3954, 1730, 1712, 1666, 1595, 1518, 1483, 1471, 1357, 1271, 1H NMR (400 MHz, DMSO-d6) δ: 12.76 (s, 1H), 10.34 (s, 1H),
1
1199; H NMR (400 MHz, CDCl3) δ: 10.52 (s, 1H), 7.98 (d, JH–H 8.00–7.97 (m, 2H), 7.66–7.63 (m, 3H), 7.46 (td, JH–H = 7.6 Hz,
= 8.6 Hz, 2H), 7.73 (d, JH–H = 7.6 Hz, 1H), 7.63 (dd, JH–H = 6.8 JH–H = 1.2 Hz, 1H), 7.33–7.29 (m, 2H); 13C NMR (100 MHz,
Hz, JH–H = 1.8 Hz, 2H), 7.56–7.54 (m, 2H), 7.43–7.40 (m, 1H), DMSO-d6) δ: 164.0 (CvO), 151.7, 146.9, 137.7, 132.9, 131.4,
5.18 (s, 2H), 4.18 (q, JH–H = 7.1 Hz, 2H), 1.22 (t, JH–H = 7.1 Hz, 130.9, 130.2 (CH), 129.2 (CH), 128.9 (CH), 127.7 (CH), 124.2
3H); 13C NMR (100 MHz, CDCl3) δ: 167.7, 164.5, 151.3, 145.8, (CH), 115.8 (CH); HR MS (ESI) m/z: calcd for C15H11ClN3O2
137.8, 132.8, 131.6, 130.4 (CH), 129.5 (CH), 129.2 (CH), 128.8 [M + H]+ 300.0534, found 300.0533.
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Organic & Biomolecular Chemistry
4-Chloro-N-(quinolin-2-yl)benzamide (3le)
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MedChemComm, 2015, 6, 202–211.
Colorless crystal, mp 139–140 °C (lit.17 138–139 °C); IR (KBr)
ν(cm−1): 3330, 1665, 1598, 1574, 1524, 1498, 1455, 1425, 1319,
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1263; 1H NMR (400 MHz, CDCl3) δ: 8.85 (s, 1H), 8.53 (d, JH–H
=
8.4 Hz, 1H), 8.22 (d, JH–H = 9.0 Hz, 1H), 7.92 (d, JH–H = 8.4 Hz,
1H), 7.83–7.79 (m, 2H), 7.69–7.65 (m, 1H), 7.49–7.45 (m, 3H);
13C NMR (100 MHz, CDCl3) δ: 164.9 (CvO), 150.9, 146.5,
138.8, 132.5, 130.1, 129.1, 128.7, 127.6, 127.2, 126.4,
125.3, 114.3, 99.9 (CH); HR MS (ESI) m/z: calcd for
C16H12ClN2O [M + H]+ 283.0633, found 283.0632.
N-(2,6-Di-tert-butyl-4-hydroxybenzyl)benzamide (4)
Colorless solid, mp 201–203 °C (lit.11 196–197 °C); IR (KBr)
ν(cm−1): 3627, 3338, 2960, 1634, 1538, 1431, 1297, 1210, 1144;
1H NMR (400 MHz, CDCl3) δ: 7.78 (d, JH–H = 7.2 Hz, 2H),
7.49–7.45 (m, 1H), 7.40 (t, JH–H = 7.1 Hz, 2H), 7.16 (s, 2H), 5.23
(s, 1H), 4.54 (d, JH–H = 5.3 Hz, 2H), 1.43 (s, 18H); 13C NMR
(100 MHz, CDCl3) δ: 167.2 (CvO), 153.4, 136.3, 134.7,
131.4 (CH), 128.6, 128.5 (CH), 126.9 (CH), 125.1 (CH), 44.6
(CH2), 34.3, 30.2 (CH3); HR MS (ESI) m/z: calcd for C22H30NO2
[M + H]+ 340.2271, found 340.2273.
Conflicts of interest
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There are no conflicts to declare.
Acknowledgements
We gratefully acknowledge the Natural Science Foundation in
the Henan Province Department of Education (No.
18A150004), the Training Program of Youth Backbone Teacher
of Henan Province (No. 2018GGJS178), the Program for
Innovative
Research
Team
from
Zhengzhou
(No.
131PCXTD605), and the Project of Youth Backbone Teachers of
Henan University of Technology (No. 2016003).
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Org. Biomol. Chem., 2019, 17, 10178–10187 | 10187