Visible-light induced decarboxylative alkylation of quinoxalin-2(1H)-ones at the C3-position

Article abstract of DOI:10.1039/c9ob01169b

A simple and efficient method for the visible light induced direct carbon alkylation of quinoxalin-2(1H)-ones at the C3 position is described. This protocol employs cheap and readily available phenyliodine(iii) dicarboxylates as the alkylation reagents to conduct decarboxylative radical coupling reaction with quinoxalin-2(1H)-ones. The process exhibits excellent compatibility to functional groups and provides a convenient and selective access to various 3-alkylquinoxalin-2(1H)-ones in good yields.

Full text of DOI:10.1039/c9ob01169b

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DOI: 10.1039/C9OB01169B
ARTICLE
Visible-Light Induced Decarboxylative Alkylation of Quinoxalin-
2(1H)-ones at C3-position
Received 00th January 20xx,
Accepted 00th January 20xx
Wenxuan Xue,a Yingpeng Su,a Ke-Hu Wang,a Rong Zhang,a Yawei Feng,a Lindan Cao,a Dangfeng
Huang,a Yulai Hu*a,b
DOI: 10.1039/x0xx00000x
A simple and efficient method for the visible light induced direct carbon alkylation of quinoxalin-2(1H)-ones at C3 position
is described. This protocol employs cheap and readily available phenyliodine(III) dicarboxylates as the alkylation reagents
to conduct decarboxylative radical coupling reaction with quinoxalin-2(1H)-ones. The process exhibits excellent
compatibility of functional groups and provides a convenient and selective access to various 3-alkylquinoxalin-2(1H)-ones
in good yields.
ones in recent years.4 For instance, arylation,4b,4h-j,4n
acylation,4a,4g phosphonation,4m amination4k,4l as well as
trifluoromethylation4c of quinoxalin-2(1H)-ones at C3 position
Introduction
Quinoxalin-2(1H)-ones are a privileged class of structural
motifs found in various bioactive natural products and
pharmaceutical compounds because of their significant
biological activities and outstanding chemical properties.1
Especially, 3-alkylquinoxalin-2(1H)-one has appeared in
numerous bioactive molecules (Figure 1).2
have been realized. However, the method of the direct
alkylation at C3 position of quinoxalin-2(1H)-ones to access 3-
alkylquinoxalin-2(1H)-ones is very scarce until now. Only a few
reports were found in literature (Scheme 1, a–c).5 For instance,
Guo and co-workers demonstrated a Fe(acac)2-catalyzed direct
C3-alkylation of quinoxalin-2(1H)-ones by using cyclobutanone
oxime esters as alkylation reagents (Scheme 1, a).5b Qu and co-
workers reported the direct introduction of cyclic ethers at C3-
N
N
O
N
O
position of quinoxalin-2(1H)-ones in the presence of
a
N
O
O
N
HOOC
H
stoichiometric amount of TBHP (Scheme 1, b).5a More recently,
Wei and co-workers developed a photocatalytic strategy for
the synthesis of 3-oxyalkylated quinoxalin-2(1H)-ones (Scheme
1, c).5c Despite these alkylation methods at C3-position of
quinoxalin-2(1H)-ones, more convenient direct alkylation at
C3-position of quinoxalin-2(1H)-ones to access 3-
alkylquinoxalin-2(1H)-ones is still necessary.
O
N
N
Angintens in II receptor antagonist
Multiple-Drug-Resistance (MDR) antagonist
Br
N
N
O
O
N
Br
O
F
N
H
F3
C
N
H
O
N
H2
N
N
H
O
O
On the other hand, the visible-light induced reactions have
been widely applied in organic synthesis with excellent
features such as environmentally benign operation, mild
reaction conditions and excellent functional group tolerance.6
Furthermore, the phenyliodine(III) dicarboxylates have proved
to be effective reagents to introduce their alkyl group into
organic molecular through radical decarboxylation process.7 In
view of the stability, commercial availability and low cost of
aliphatic acids, we are wondered if the aliphatic acids could be
used to introduce alkyl group at C3-position of quinoxalin-2(1H)-
ones through visible-light photoredox catalysis in the presence
of PhI(OAc)2. Herein we would like to report a visible-light
induced radical alkylation at C3-position of quinoxalin-2(1H)-
ones to obtain 3-alkylquinoxalin-2(1H)-ones by using
phenyliodine(III) dicarboxylate and aliphatic acids as alkylation
reagents. (Scheme 1, d).
c-Met kinase inhibitor
GW420867X
Antiviral
Anticancer activity
in vitro against cell lines
Figure 1. Biologically active 3-alkylquinoxalin-2(1H)-ones
Traditionally, quinoxalin-2(1H)-ones are synthesized by
condensation of 1,2-diaminobenzene derivatives with various
two-carbon unit donors such as α-keto acids, α-aldehyde acids
and their esters.3 In particular, direct functionalization of
quinoxalin-2(1H)-ones at C3 position provides a convenient
way to increase their structural diversity, and emerges as an
attractive approach to access 3-substituted quinoxalin-2(1H)-
a. College of Chemistry and Chemical Engineering, Northwest Normal University,
Lanzhou, 730070, P. R. China. Email: huyl@nwnu.edu.cn.
b. State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou
730000, P. R. China.
†
Electronic supplementary information (ESI) available: General experimental
details and copies of 1H and 13C NMR spectra. For ESI see DOI: 10.1039/x0xx00000x
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Journal Name
3b). However, when the amide nitrogen of quinoxalin-2(1H)-
Previous work: 5
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one were protected by alkyl or aryl grouDpOs,I:t1h0e.10p3r9o/Cd9uOctB0y1i1e6l9dBs
greatly improved (Table 2, 3a–3m). Especially, when the aryl
protecting groups were electron-deficient ones, the yields of
corresponding products were higher than those with electron-
rich ones. Afterwards, the quinoxalin-2(1H)-ones with different
substituents on their phenyl rings were studied. Among all of
the examined quinoxalin-2(1H)-ones, the reaction occurred
smoothly to afford the corresponding products in good yields
(Table 2, 3n–3u).
N
OCOC6F5
N
N
Fe(acac)2
MeCN, 100 oC, N2
R2
CN
+
+
R2
(a)
(b)
N
R1
O
O
N
R1
O
O
N
TBHP
N
O
R2
R2
100 o
C
N
R1
H
N
R1
O
X
Photocatalyst
3 W blue LEDs
N
N
X
(c)
R2
R2
+
DABCO
TBHP
N
R1
O
H
N
R1
O
This work:
Table 1. Optimization of Reaction Conditionsa
R4COOH
PhI(OAc)2
+
Ligand exchange
Photocatalyst
visible-light
N
N
CH3
O
N
N
R2
R3
N
R4
O
R2
R3
N
Ru(bpy3)Cl2·6H2O
24w white LED
PhI(OAc)2
+
PhI(OOCR4)2
(d)
+
solvent, rt
N
R1
O
N
O
DMSO, rt, air
R1
R=alkyl
1a
2
3a
Scheme 1. Synthesis of 3-Alkylquinoxalin-2(1H)-ones
Entry
Molar ratio of 1a/2
Photocatalyst
(1 mol%)
Solvent
Yield of 3a
(%)b
65
79
90
88
56
78
75
82
0
1
2
3
4
5
1/1.5
1/2
1/2.5
1/3
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Eosin B
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CH3CN
DMF
Results and discussion
As an initial study, the methylation of quinoxalin-2(1H)-ones at
C3-position by using PhI(OAc)2 as methylation reagent was
investigated. A mixture of 1-methylquinoxalin-2(1H)-one (1a,
0.2 mmol), PhI(OAc)2 (2a, 0.3 mmol) and Ru(bpy)3Cl2·6H2O
(0.01 mmol) in DMSO was irradiated with a 24 W white LED
bulb and stirred at room temperature for 8 h. The desired
product 1,3-dimethylquinoxalin-2(1H)-one 3a was obtained in
65% yield (Table 1, entry 1). In order to improve the product
yield, the amount of PhI(OAc)2 was increased, and the 90%
yield of the product 3a was obtained when the amount of
PhI(OAc)2 went up to 2.5 equiv. (Table 1, entries 2–4). The
other photocatalysts such as Eosin B and Eosin Y were
examined, but the yield of 3a decreased (Table 1, entries 5 and
6). The different light source such as 24 W blue and green LED
were tested in the reaction, but the yield of the product 3a
was not improved (Table 1, entries 7 and 8). Especially, no
product 3a was formed when the reaction was conducted in
the dark (Table 1, entry 9). If the photocatalysts were taken off
from the reaction mixture, no reaction occurred (Table 1, entry
10). The examination of solvent effects on the reaction
revealed that the reaction in other solvents such as CH3CN,
DMF, DCM and toluene did not improve the yield of product
3a (Table 1, entries 11–14). Finally, the reaction was
conducted under argon atmosphere, and the desired product
3a was obtained in 89% yield (Table 1, entry 15). Thus, the
optimal reaction condition was to conduct the reaction at
room temperature in DMSO in the presence of 1 mol%
Ru(bpy)3Cl2·6H2O by irradiation with a 24 W white LED with
the 1/2.5 molar ratio of 1a/2.
1/2.5
1/2.5
1/2.5
1/2.5
1/2.5
1/2.5
1/2.5
1/2.5
1/2.5
1/2.5
1/2.5
6
Eosin Y
7c
8d
9e
10
11
12
13
14
15f
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
—
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
0
64
81
31
26
89
DCM
toluene
DMSO
aReaction conditions: 1 (0.20 mmol), 2 (0.30–0.60 mmol), photocatalyst (1.0
mol%), solvent (3 mL), room temperature, 8 h, air atmosphere. bIsolated yield.
cUsing 24 W blue LED. dUsing 24 W green LED. eIn the dark. fArgon atmosphere.
Table 2. Scope of Quinoxalin-2(1H)-onesa
R2
R3
N
R2
R3
N
CH3
O
Ru(bpy)3Cl2•6H2O
PhI(OAc)2
+
N
R1
O
N
R1
24 W white LED
DMSO, rt
1
2
3
N
CH3 3a, R1 = Methyl, 90%, 8 h
R2
R3
N
N
CH3
, R1 = H, 60%, 12 h
3b
, R1 = Ethyl, 82%, 8.5 h
3c
N
R1
O
O
1
3d
, R
=
nC4H9, 81%, 9 h
, R1 = Benyl, 84%, 11 h
3e
3a-3m
3n-3u
, R1 = CH2COOCH3, 72%, 9 h
, R1 = CH2COOCH2C6H5, 79%, 8 h
, R1 = Phenyl, 81%, 7 h
, R2 = Cl, R3 = H, 81%, 9.5 h
, R2 = H, R3 = Cl, 83%, 8 h
, R2 = Br, R3 = H, 86%, 7 h
, R2 = H, R3 = Br, 89%, 8 h
3f
3n
3o
3p
3q
3r
3g
3h
3i
With the optimal conditions in hand, we next examined the
scope of various quinoxalin-2(1H)-ones. First of all, the effects
of the protecting groups on amide nitrogen atom of
quinoxalin-2(1H)-one were examined. The results indicated
that the protecting groups were favorable for the reaction. For
instance, the product 3b was obtained in only 60% yield if
there was no protect group on amide nitrogen atom (Table 2,
, R1 = 4-Methylphenyl, 78%, 8 h
, R1 = 4-Chlorophenyl, 85%, 6.5 h
, R2 = NO2, R3 = H, 86%, 6 h
3j
, R1 = 3,5-Bis(trifluoromethyl)phenyl, 91%, 6 h
, R2 = R3 = F, 83%, 9 h
, R2 = R3 = Cl, 88%, 8 h
3k
3l
3s
3t
3u
, R1 = Allyl, 55%, 10 h
,R1 = Propargyl, 65%, 9 h
, R2 = R3 = Methyl, 67%, 11 h
3m
aReaction conditions: 1 (0.2 mmol), 2 (0.5 mmol), Ru(bpy)3Cl2·6H2O (1 mol%),
DMSO (3 mL), room temperature, 6–12 h, air atmosphere.
2 | J. Name., 2012, 00, 1-3
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As we knew, the phenyliodine(III) dicarboxylate reagents obtained in 79% yield under the optimized reaction conditions.
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could be easily prepared from ligand exchange between This demonstrated that the protocol wasDsOcIa:l1a0b.1l0e3a9n/Cd9OprBa0c11t6ic9aBl
PhI(OAc)2 and carboxylic acids, and then used directly without (Scheme 2).
further purification.8 Thus, we tried to combine aliphatic acids
N
N
N
N
CH3
O
with PhI(OAc)2 to introduce alkyl group at C3-position of
quinoxalin-2(1H)-ones. Initially, propionic acid 4a and
Ru(bpy)3Cl2•6H2O
PhI(OAc)2
+
24 W white LED
DMSO, rt
O
o
PhI(OAc)2 was stirred in CHCl3 at 50 C for 30 min, and the
1a: 7 mmol, 1.12g
2
3a: 79%, 0.96g
mixture was then evaporated off under reduced pressure to
remove the volatile compounds such as CHCl3 and in-situ
formed HOAc to afford PhI(OOCEt)2, which was reacted with
1a without further purification under the standard reaction
conditions, and the product 3-ethylquinoxalin-2(1H)-one 5a
was produced in 73% yield (Table 3, 5a). To expand the scope
of carboxylic acids, the other aliphatic acids were applied in
the reaction. As showed in Table 3, different aliphatic
carboxylic acids were reacted with various quinoxalin-2(1H)-
one derivatives. The corresponding products 5 obtained in
good yields (Table 3, 5a–5m). It was worth noting that the
sterically hindered carboxylic acids such as pivalic acid and
cyclohexanecarboxylic acid also gave the products in
reasonable yields (Table 3, 5g and 5i). However, the aromatic
acid such as benzoic acid did not produce the product, and the
1a was recovered in 95% yield (Table 3, 5n).
Scheme 2. Gram-scale Reaction
In order to find application in drug synthesis, the potential
bioactive nonpeptide angiotensin II receptor antagonist had
been prepared by this method. The compound 6 was reacted
with PIDA or combination of PIDA and pentanoic acid under
the optimized reaction to give the corresponding product 7a
and 7b, which were hydrolyzed to give target compounds
(Scheme 3).2c
N
N
N
N
R
O
PhI(OOCR)2
Ru(bp
O
y3)Cl
2·6H
2O
MeOOC
O
MeOOC
O
DMSO,
rt
24 W
white
LED
N
N
N
N
ysis
2c
7a
7b
, R = Methyl, 88%
, R = Buthyl, 76%
6
Hydrol
ref.
Table 3. Scope of Phenyliodine(III) Dicarboxylatesa
N
N
R
O
2
1. PhI(OAc)2 ( )
N
N
R4
O
2. Ru(bpy)3Cl2•6H2O
HOOC
+
R4COOH
O
N
R1
O
N
R1
24 W white LED
DMSO, rt
N
N
Angintensin II receptor antagonist
5
1
4
Scheme 3. Synthetic Application in Physiological Active Compounds
N
N
N
N
N
To investigate the mechanism, control experiments were
performed (Scheme 4). Deuterated DMSO-d6 was used as the
solvent instead of DMSO to make sure where the methyl group
came from in the methylated products. The result indicated
that only 3-methylquinoxalin-2(1H)-ones 3a was obtained in
86% yield without deuterated product 8 (Scheme 4, a). This
meant that the methyl group came from the PhI(OAc)2 instead
of the DMSO (Scheme 4, a). Next, 2,2,6,6-
tetramethylpiperidine oxide (TEMPO) was added into the
reaction, the 3-methylquinoxalin-2(1H)-ones 3a was not
formed while the compound 9 was detected by HRMS (Scheme
4, b). This result implied that the reaction was a radical process.
O
N
O
O
5a
5b
5c
73% yield, 8 h
78% yield, 8 h
74% yield, 9 h
N
N
C11H23
N
N
O
N
O
N
O
5d
5e
5f
73% yield, 9 h
71% yield, 9 h
70% yield, 8.5 h
N
N
N
N
N
N
O
N
O
O
N
O
COOEt
5g
5h
5i
5j
63% yield, 10 h
69% yield, 9 h
57% yield, 12 h
68% yield, 9 h
N
N
N
N
N
N
CH3
O
N
N
CD3
O
N
N
O
N
O
N
O
Ru(bpy)3Cl2•6H2O
(a)
+
PhI(OAc)2
+
24 W white LED
DMSO-d6, rt
N
O
O
N
F3
C
CF3
3a
8
1a
, 86% yield
5m
5k
5l
5n
detected by 1H NMR
0% yield
81% yield, 8 h
68% yield, 8 h
62% yield, 10 h
0% yield, 8 h
N
N
N
CH3
PhI(OAc)2
a
Ru(bpy)3Cl2•6H2O
(b)
Reaction conditions: (1) aliphatic carboxylic acid 4 (2.0 equiv.), PhI(OAc)2 2 (1.0
+
TEMPO
+
N
O
24 W white LED
DMSO, rt
equiv.), CHCl3 (4 mL) 50 oC, 30 min; (2) 1 (0.2 mmol), phenyliodine(III)
dicarboxylate (0.5 mmol), photocatalyst (1 mol%), DMSO (3 mL), room
temperature, 8–12 h, air atmosphere.
O
N
O
CH3
1a
3a,
9
0% yield
detected by HRMS
HRMS (ESI): calcd for C10H22NO [M + H]+ 172.1701;
found 172.1696.
To explore the practical utility of this method, a gram-scale
experiment was performed by using quinoxalin-2(1H)-ones 1a
(1.12g, 7 mmol) as substrates. The desired product 3a could be
Scheme 4. Control Experiments for Mechanism
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J. Name., 2013, 00, 1-3 | 3
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In the light of cyclic votlammertric study, emission 19F NMR spectra were recorded at 376 MHz spectrometers.
View Article Online
DOI: 10.1039/C9OB01169B
quenching experiment (see supporting information) and Chemical shifts are reported as δ values relative to internal
1
1
literature information,7c,9 a radical mechanism was tentatively TMS (δ 0.00 for H NMR), chloroform (δ 7.26 for H NMR),
proposed in Scheme 5. The catalyst Ru(II) was irradiated by dimethyl sulfoxide (δ 2.50 for H NMR), chloroform (δ 77.00
1
visible light to its excited state *Ru(II). A single electron transfer for 13C{1H} NMR) and dimethyl sulfoxide (δ 39.50 for 13C{1H}
(SET) from *Ru(II) to PhI(OOCR)2 generateed Ru(III) (E1/2 NMR) in parts per million (ppm). The following abbreviations
(RuIII/Ru*II) = -0.81V vs. SCE) and alkyl radical 10, which added are used for the multiplicities: s: singlet, d: doublet, dd:
to the C=N double bond of substrate 1 to produce radical 11. doublet of doublet, t: triplet, q: quartet, m: multiplet, br:
The oxidation of radical 11 by Ru(III) produced nitrogen cation broad signal for proton spectra. Coupling constants (J) are
12, and Ru(III) was reduced to the catalyst Ru(II) at the same reported in Hertz (Hz). Melting points were uncorrected. All
time (E1/2 (RuIII/RuII) = +1.29V vs. SCE). The deprotonation of starting materials were prepared according to the literature:
cation 12 by carboxylate to furnish the final product 5.
1a−r,4n 1s−u,10 611.
Methyl
2-(5-(4-((2-oxoquinoxalin-1(2H)-yl)methyl)phenyl)-
R2
R3
N
1,3,4-oxadiazol-2-yl)benzoate (6).10 White solid; mp: 150–153
oC; 1H NMR (600 MHz, CHCl3) δ 8.42 (s, 1H), 8.04 (d, J = 7.8 Hz,
2H), 7.92–7.90 (m, 3H), 7.66–7.61 (m, 2H), 7.49 (t, J = 7.8 Hz,
1H), 7.39 (d, J = 8.4 Hz, 2H), 7.34 (t, J = 7.8 Hz, 1H), 7.23 (d, J =
8.4 Hz, 1H), 5.56 (s , 2H), 3.81 (s, 3H); 13C NMR (150 MHz, CHCl3)
δ 167.1, 164.5, 164.0, 155.0, 150.2, 139.0, 133.6, 132.3, 131.7,
131.6, 131.4, 131.2, 130.8, 130.4, 130.0, 127.6, 127.5, 124.1,
123.6, 123.4, 114.3, 52.7, 45.3; HRMS (ESI): calcd for
C25H18N4O4Na [M + Na]+ 461.1220; found 461.1222.
N
R1
O
1
PhI + -OOCR + CO2
PhI(OOCR)2
R
10
*Ru(II)
Ru(III)
R2
R3
N
R
O
N
R1
General Procedure for the Synthesis of 3-Methylquinoxalin-2(1H)-
ones.
11
R2
R3
N
R
O
R2
R3
N
R
Ru(II)
In a dried Schlenk tube, quinoxalin-2(1H)-ones (0.2 mmol),
PhI(OAc)2 (2.5 equiv) and Ru(bpy)3Cl2·6H2O (1.5 mg, 1.0 mol%)
were mixed in DMSO (3.0 mL) at room temperature. The tube
was placed at a distance (app. 5 cm) from 24 W white LED, and
the solution was stirred under visible-light irradiation. After
the reaction was completed (monitored by TLC), the reaction
mixture was quenched by saturated aqueous Na2CO3 solution
(5 mL), and then the mixture was extracted with ethyl acetate
(3 × 5 mL). The combined organic phase was dried over
anhydrous MgSO4 and evaporated under vacuum. The crude
product was purified by column chromatography over silica gel
(230−400 mesh) using EtOAc/petroleum ether as eluent to
afford the desired products 3 or 7a.
1,3-Dimethylquinoxalin-2(1H)-one (3a). 31 mg, 90% yield,
yellow solid, mp 87–88 oC; 1H NMR (600 MHz, CDCl3) δ 7.81 (d,
J = 7.8 Hz, 1H), 7.53 (t, J = 8.4 Hz, 1H), 7.34 (t, J = 8.4 Hz, 1H),
7.30 (d, J = 8.4 Hz, 1H), 3.71 (s, 3H), 2.60 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 158.4, 155.2, 133.2, 132.7, 129.6, 129.4, 123.6,
113.6, 29.0, 21.6; HRMS (ESI): calcd for C10H10N2ONa [M + Na]+
197.0691; found 197.0694.
3-Methylquinoxalin-2(1H)-one (3b). 19 mg, 60% yield, yellow
solid, mp 194–196 oC; 1H NMR (600 MHz, DMSO-d6) δ 12.29 (s,
1H), 7.69 (d, J = 8.4 Hz, 1H), 7.46 (t, J = 8.4 Hz, 1H), 7.30–7.25
(m, 2H), 2.40 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 159.6,
155.3, 132.4, 132.1, 129.7, 128.3, 123.4, 115.6, 21.0; HRMS
(ESI): calcd for C9H8N2ONa [M + Na]+ 183.0529; found
183.0524.
1-Ethyl-3-methylquinoxalin-2(1H)-one (3c). 31 mg, 82% yield,
brown solid, mp 79–81 oC; 1H NMR (600 MHz, CDCl3) δ 7.81 (d,
J = 8.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.33–7.30 (m, 2H), 4.31
(q, J = 7.2 Hz, 2H), 2.59 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 158.4, 154.6, 132.9, 132.1, 129.7, 129.5,
N
R1
N
R1
O
-OOCR
HOOCR
12
5
Scheme 5. Proposed mechanism.
Conclusions
In summary, we have developed an efficient protocol for direct
decarboxylative alkylation of quinoxalin-2(1H)-one derivatives
at C3 position under visible light irradiation by using readily
available and sustainable aliphatic carboxylic acids as
alkylation reagents. The advantages of this process are wide
substrate scope, good regioselectivity, mild reaction conditions
and ease of operation. It provides a convenient and efficient
method for synthesis of 3-alkylquinoxalin-2(1H)-ones from
quinoxalin-2(1H)-ones.
Experimental section
General Methods
The solvents were distilled by standard methods. Reagents
were obtained from commercial suppliers and used without
further purification unless otherwise noted. Silica gel column
chromatography was carried out using silica gel 60 (230−400
mesh). Analytical thin layer chromatography (TLC) was done
using silica Gel (silica gel 60 F254). TLC plates were analyzed by
an exposure to ultraviolet (UV) light and/or submersion in
KMnO4 solution or in I2. High-resolution mass spectra were
recorded on Fourier transform ion cyclotron resonance mass
spectrometer. NMR experiments were carried out in CDCl3 and
(CD3)2SO. H NMR, 13C{1H} NMR spectra were recorded at 400
or 600 MHz and 100 or 150 MHz spectrometers, respectively.
1
4 | J. Name., 2012, 00, 1-3
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123.4, 113.4, 37.2, 21.5, 12.4; HRMS (ESI): calcd for 1-(3,5-Bis(trifluoromethyl)phenyl)-3-methylquinoxalin-2(1H)-
View Article Online
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1
C11H12N2ONa [M + Na]+ 211.0842; found 211.0843.
one (3k). 67 mg, 91% yield, yellow solid, mp 159–161 C; H
DOI: 10.1039/C9OB01169B
1-Butyl-3-methylquinoxalin-2(1H)-one (3d). 35 mg, 81% yield, NMR (600 MHz, CDCl3) δ 8.09 (s, 1H), 7.89–7.87 (m, 1H), 7.83
yellow solid, mp 79–81 oC; 1H NMR (600 MHz, CDCl3) δ 7.80 (d, (s, 2H), 7.39–7.35 (m, 2H), 6.57–6.54 (m, 1H), 2.64 (s, 3H); 13C
J = 7.8 Hz, 1H), 7.50 (t, J = 8.4 Hz, 1H), 7.32–7.28 (m, 2H), 4.24 NMR (150 MHz, CDCl3) δ 158.9, 154.4, 137.3, 134.0 (q, J = 34.5
(t, J = 7.8 Hz, 2H), 2.59 (s, 3H), 1.76–1.71 (m, 2H), 1.51–1.45 Hz), 133.1, 132.5, 129.8, 129.7, 129.4 (q, J = 3.0 Hz), 124.6,
(m, 2H), 1.00 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 123.6 (hept, J = 3.0 Hz), 122.6 (q, J = 271.5 Hz), 114.4, 21.3; 19
F
158.4, 154.9, 132.9, 132.4, 129.7, 129.4, 123.3, 113.6, 42.1, NMR (376 MHz, CDCl3) δ –63.25 (s); HRMS (ESI): calcd for
29.3, 21.5, 20.3, 13.8; HRMS (ESI): calcd for C13H16N2ONa [M + C17H10F6N2ONa [M + Na]+ 395.0595; found 395.0589.
Na]+ 239.1160; found 239.1158.
1-Allyl-3-methylquinoxalin-2(1H)-one (3l). 22 mg, 55% yield,
1-Benzyl-3-methylquinoxalin-2(1H)-one (3e). 42 mg, 84% yellow solid, mp 53–55 oC; 1H NMR (600 MHz, CDCl3) δ 7.81 (d,
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1
yield, yellow solid, mp 93–94 C; H NMR (600 MHz, CDCl3) δ J = 7.8 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.32 (t, J = 7.8 Hz, 1H),
7.81 (d, J = 7.8 Hz, 1H), 7.39 (t, J = 8.4 Hz, 1H), 7.32–7.28 (m, 7.27 (d, J = 8.4 Hz, 1H), 5.97–5.90 (m, 1H), 5.27 (d, J = 10.2 Hz,
3H), 7.28–7.23 (m, 4H), 5.50 (s, 2H), 2.66 (s, 3H); 13C NMR (150 1H), 5.16 (d, J = 16.8 Hz, 1H), 4.91 (d, J = 5.4 Hz, 2H), 2.61 (s,
MHz, CDCl3) δ 158.5, 155.3, 135.2, 132.9, 132.6, 129.5, 128.9, 3H); 13C NMR (150 MHz, CDCl3) δ 158.4, 154.8, 132.8, 132.4,
127.7, 126.8, 123.6, 114.4, 45.9, 21.7; HRMS (ESI): calcd for 130.6, 129.5, 129.4, 123.6, 118.1, 114.2, 44.5, 21.6; HRMS
C16H14N2ONa [M + Na]+ 273.0998; found 273.1000.
(ESI): calcd for C12H12N2ONa [M + Na]+ 223.0847; found
Methyl 2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetate (3f). 33 223.0850.
mg, 72% yield, yellow solid, mp 131–133 oC; 1H NMR (600 3-Methyl-1-(prop-2-yn-1-yl)quinoxalin-2(1H)-one (3m). 26 mg,
o
1
MHz, CDCl3) δ 7.82 (d, J = 7.8 Hz, 1H), 7.48 (t, J = 8.4 Hz, 1H), 65% yield, yellow solid, mp 138–141 C; H NMR (600 MHz,
7.34 (t, J = 7.8 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 5.03 (s, 2H), 3.77 CDCl3) δ 7.81 (d, J = 7.8 Hz, 1H), 7.55 (t, J = 7.8 Hz, 1H), 7.44 (d,
(s, 3H), 2.60 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 167.6, 158.2, J = 8.4 Hz, 1H), 7.36 (t, J = 7.8 Hz, 1H), 5.05 (d, J = 2.4 Hz, 2H),
154.7, 132.7, 132.3, 129.8, 129.7, 123.9, 113.0, 52.8, 43.4, 2.60 (s, 3H), 2.28 (t, J = 2.4 Hz, 1H). 13C NMR (150 MHz, CDCl3)
21.5; HRMS (ESI): calcd for C12H12N2O3Na [M + Na]+ 255.0740; δ 158.2, 154.1, 132.8, 131.7, 129.7, 129.6, 124.0, 114.1, 76.8,
found 255.0734.
73.2, 31.4, 21.5; HRMS (ESI): calcd for C12H10N2ONa [M + Na]+
Benzyl 2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetate (3g). 48 221.0691; found 221.0691.
mg, 78% yield, yellow solid, mp 123–125 oC; 1H NMR (600 6-Chloro-1,3-dimethylquinoxalin-2(1H)-one (3n). 33 mg, 81%
MHz, CDCl3) δ 7.82 (d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), yield, yellow solid, mp 185–187 oC; 1H NMR (600 MHz, CDCl3) δ
7.37–7.32 (m, 4H), 7.30–7.28 (m, 2H), 7.00 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 2.4 Hz, 1H), 7.47 (dd, J = 8.4, 1.8 Hz, 1H), 7.22 (d, J =
5.22 (s, 2H), 5.07 (s, 2H), 2.61 (s, 3H); 13C NMR (150 MHz, 9.0 Hz, 1H), 3.68 (s, 3H), 2.59 (s, 3H); 13C NMR (150 MHz, CDCl3)
CDCl3) δ 167.0, 158.1, 154.7, 134.9, 132.7, 132.3, 129.8, 129.7, δ 159.9, 154.8, 133.2, 131.9, 129.5, 128.9, 128.8, 114.7, 29.2,
128.6, 128.5, 128.3, 123.9, 113.0, 67.6, 43.5, 21.5; HRMS (ESI): 21.7; HRMS (ESI): calcd for C10H9ClN2ONa [M + Na]+ 231.0296;
calcd for C18H16N2O3Na [M + Na]+ 331.1059; found 331.1054.
found 231.0299.
3-Methyl-1-phenylquinoxalin-2(1H)-one (3h). 38 mg, 81% 7-Chloro-1,3-dimethylquinoxalin-2(1H)-one (3o). 34 mg, 83%
yield, yellow solid, mp 166–169 oC; 1H NMR (600 MHz, CDCl3) δ yield, yellow solid, mp 175–177 oC; 1H NMR (600 MHz, CDCl3) δ
7.86–7.83 (m, 1H), 7.61 (t, J = 7.2 Hz, 2H), 7.55 (t, J = 7.2 Hz, 7.70 (d, J = 9.0 Hz, 1H), 7.28–7.27 (m, 2H), 3.65 (s, 3H), 2.56 (s,
1H), 7.31–7.27 (m, 4H), 6.67–6.64 (m, 1H), 2.64 (s, 3H); 13C 3H); 13C NMR (150 MHz, CDCl3) δ 158.5, 154.9, 135.4, 134.1,
NMR (150 MHz, CDCl3) δ 159.2, 154.9, 135.8, 134.1, 132.5, 131.1, 130.5, 123.9, 113.6, 29.2, 21.6; HRMS (ESI): calcd for
130.2, 129.4, 129.2, 129.0, 128.2, 123.7, 115.4, 21.4; HRMS C10H10ClN2O [M + H]+ 209.0476; found 209.0475.
(ESI): calcd for C15H12N2ONa [M + Na]+ 259.0842; found 6-Bromo-1,3-dimethylquinoxalin-2(1H)-one (3p). 43 mg, 86%
259.0837.
yield, yellow solid, mp 173–175 oC; 1H NMR (600 MHz, CDCl3) δ
3-Methyl-1-(p-tolyl)quinoxalin-2(1H)-one (3i). 39 mg, 78% 7.94–7.92 (m, 1H), 7.61–7.57 (m, 1H), 7.16–7.12 (m, 1H), 3.66
yield, yellow solid, mp 169–171 oC; 1H NMR (600 MHz, CDCl3) δ (s, 3H), 2.57 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 159.8, 154.8,
7.84–7.82 (m, 1H), 7.40 (d, J = 7.8 Hz, 2H), 7.31–7.28 (m, 2H), 133.5, 132.4, 132.3, 131.9, 116.1, 115.0, 29.2, 21.7; HRMS
7.16 (d, J = 8.4 Hz, 2H), 6.71–6.68 (m, 1H), 2.63 (s, 3H), 2.47 (s, (ESI): calcd for C10H9BrN2ONa [M + Na]+ 274.9790; found
3H); 13C NMR (150 MHz, CDCl3) δ 159.2, 155.0, 139.4, 134.3, 274.9789.
133.1, 132.5, 130.9, 129.1, 129.0, 127.9, 123.6, 115.5, 21.5, 7-Bromo-1,3-dimethylquinoxalin-2(1H)-one (3q). 44 mg, 89%
21.3; HRMS (ESI): calcd for C16H14N2ONa [M + Na]+ 273.1004; yield, yellow solid, mp 198–200 oC; 1H NMR (600 MHz, CDCl3) δ
found 273.1004.
7.63 (d, J = 8.4 Hz, 1H), 7.43–7.40 (m, 2H), 3.65 (s, 3H), 2.56 (s,
1-(4-Chlorophenyl)-3-methylquinoxalin-2(1H)-one (3j). 46 mg, 3H); 13C NMR (150 MHz, CDCl3) δ 158.8, 154.8, 134.3, 131.5,
o
1
85% yield, yellow solid, mp 192–193 C; H NMR (600 MHz, 130.6, 126.8, 123.5, 116.6, 29.2, 21.6; HRMS (ESI): calcd for
CDCl3) δ 7.85–7.83 (m, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.34–7.29 C10H9BrN2ONa [M + Na]+ 274.9790; found 274.9795.
(m, 2H), 7.24 (d, J = 8.4 Hz, 2H), 6.68–6.65 (m, 1H), 2.63 (s, 3H); 1,3-Dimethyl-6-nitroquinoxalin-2(1H)-one (3r). 27 mg, 67%
13C NMR (150 MHz, CDCl3) δ 159.1, 154.8, 135.5, 134.2, 133.8, yield, yellow solid, mp 169–171 oC;1H NMR (600 MHz, CDCl3) δ
132.5, 130.6, 129.7, 129.3, 129.2, 124.0, 115.1, 21.4; HRMS 8.69 (d, J = 2.4 Hz, 1H), 8.38 (dd, J = 9.6, 3.0 Hz, 1H), 7.39 (d, J =
(ESI): calcd for C15H11ClN2ONa [M + Na]+ 293.0458; found 9.0 Hz, 1H), 3.75 (s, 3H), 2.63 (s, 3H); 13C NMR (150 MHz, CDCl3)
293.0448.
δ 161.2, 154.8, 143.4, 137.9, 131.9, 125.3, 124.2, 114.2, 29.7,
This journal is © The Royal Society of Chemistry 20xx
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21.8; HRMS (ESI): calcd for C10H10N3O3 [M + H]+ 220.0717; over silica gel (230−400 mesh) using EtOAc/petrolVeiuewmAretictlhe eOrnlianes
DOI: 10.1039/C9OB01169B
eluent to afford the desired products 5 or 7b.
found 220.0713.
6,7-Difluoro-1,3-dimethylquinoxalin-2(1H)-one (3s). 35 mg, 3-Ethyl-1-methylquinoxalin-2(1H)-one (5a). 27 mg, 73% yield,
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83% yield, yellow solid, mp 109–111 C; H NMR (600 MHz, yellow solid, mp 95–97 oC; 1H NMR (600 MHz, CDCl3) δ 7.83 (d,
CDCl3) δ 7.59 (dd, J = 10.2, 8.4 Hz, 1H), 7.08 (dd, J = 11.4, 7.2 J = 7.8 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.8 Hz, 1H),
Hz, 1H), 3.64 (s, 3H), 2.55 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 7.29 (d, J = 8.4 Hz, 1H), 3.69 (s, 3H), 2.97 (q, J = 7.2 Hz, 2H),
158.9 (d, J = 3.0 Hz), 154.7, 150.9 (dd, J = 250.5, 15.0 Hz), 146.5 1.33 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 161.9,
(dd, J = 246.0, 13.5 Hz), 130.3 (dd, J = 9.0, 1.5 Hz), 128.9 (dd, J = 154.8, 133.1, 132.7, 129.6, 129.4, 123.5, 113.5, 29.0, 27.5,
9.0, 3.0 Hz), 117.1 (dd, J = 18.0, 1.5 Hz), 102.2 (d, J = 22.5 Hz), 10.8; HRMS (ESI): calcd for C11H13N2O [M + H]+ 211.0842; found
29.5, 21.49; 19F NMR (376 MHz, CDCl3) δ –132.21 (m), –142.62 211.0843.
(m); HRMS (ESI): calcd for C10H8F2N2ONa [M + Na]+ 233.0497; 3-Butyl-1-methylquinoxalin-2(1H)-one (5b). 42 mg, 78% yield,
found 233.0504.
6,7-Dichloro-1,3-dimethylquinoxalin-2(1H)-one (3t). 42 mg, J = 7.8 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.8 Hz, 1H),
yellow solid, mp 56–58 oC; 1H NMR (600 MHz, CDCl3) δ 7.83 (d,
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88% yield, yellow solid, mp 176–178 C; H NMR (600 MHz, 7.29 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 2.95 (t, J = 7.8 Hz, 2H),
CDCl3) δ 7.87 (s, 1H), 7.37 (s, 1H), 3.65 (s, 3H), 2.57 (s, 3H); 13
C
1.80–1.74 (m, 2H), 1.50–1.44 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H);
NMR (150 MHz, CDCl3) δ 160.0, 154.6, 133.6, 132.6, 131.7, 13C NMR (150 MHz, CDCl3) δ 161.3, 154.9, 133.1, 132.7, 129.6,
130.3, 127.3, 115.1, 29.3, 21.7 ； HRMS (ESI): calcd for 129.4, 123.4, 113.5, 34.1, 29.0, 28.9, 22.7, 13.9; HRMS (ESI):
C10H9Cl2N2O [M + H]+ 243.0086; found 243.0092.
calcd for C13H16N2ONa [M + Na]+ 239.1160; found 239.1158.
1,3,6,7-Tetramethylquinoxalin-2(1H)-one (3u). 27 mg, 67% 1-Methyl-3-pentylquinoxalin-2(1H)-one (5c). 34 mg, 74%
o
1
yield, yellow solid, mp 169–171 oC; 1H NMR (600 MHz, CDCl3) δ yield, yellow solid, mp 58–60 C; H NMR (600 MHz, CDCl3) δ
7.53 (s, 1H), 7.03 (s, 1H), 3.66 (s, 3H), 2.55 (s, 3H), 2.39 (s, 3H), 7.82 (d, J = 8.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.8
2.33 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 156.9, 155.2, 139.2, Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 2.93 (t, J = 7.8 Hz,
132.4, 131.2, 131.0, 129.5, 114.1, 28.9, 21.5, 20.4, 19.1; HRMS 2H), 1.82–1.76 (m, 2H), 1.49–1.35 (m, 4H), 0.91 (t, J = 7.2 Hz,
(ESI): calcd for C12H14N2ONa [M + Na]+ 225.0998; found 3H); 13C NMR (150 MHz, CDCl3) δ 161.4, 154.9, 133.1, 132.7,
225.1003.
Methyl
129.6, 129.4, 123.5, 113.5, 34.3, 31.8, 29.0, 26.5, 22.5, 14.0;
2-(5-(4-((3-methyl-2-oxoquinoxalin-1(2H)- HRMS (ESI): calcd for C14H19N2O [M + H]+ 231.1497; found
yl)methyl)phenyl)-1,3,4-oxadiazol-2-yl)benzoate (7a). 79 mg, 231.1487.
o
1
88% yield, yellow solid, mp 189–191 C; H NMR (600 MHz, 3-Hexyl-1-methylquinoxalin-2(1H)-one (5d). 35 mg, 73% yield,
CDCl3) δ 8.02 (d, J = 8.4 Hz, 2H), 7.91–7.89 (m, 2H), 7.83 (dd, J = yellow solid, mp 37–39 oC; 1H NMR (600 MHz, CDCl3) δ 7.82 (d,
7.8, 1.2 Hz, 1H), 7.66–7.60 (m, 2H), 7.42–7.37 (m, 3H), 7.32– J = 8.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.2 Hz, 1H),
7.29 (m, 1H), 7.18 (d, J = 8.4 Hz, 1H), 5.55 (s, 2H), 3.80 (s, 3H), 7.29 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 2.94 (t, J = 7.8 Hz, 2H),
2.66 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 167.1, 164.5, 163.9, 1.80–1.75 (m, 2H), 1.47–1.42 (m, 2H), 1.37–1.29 (m, 4H), 0.89
158.4, 155.2, 139.3, 132.9, 132.3, 131.7, 131.6, 131.4, 130.4, (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 161.4, 154.9,
130.0, 129.8, 129.7, 127.6, 127.5, 123.9, 123.6, 123.3, 114.1, 133.1, 132.7, 129.6, 129.4, 123.5, 113.5, 34.4, 31.7, 29.3, 29.0,
52.7, 45.7, 21.6; HRMS (ESI): calcd for C26H20N4O4Na [M + Na]+ 26.8, 22.6, 14.1; HRMS (ESI): calcd for C15H21N2O [M + H]+
475.1377; found 475.1365.
245.1654; found 245.1651.
General Procedure for the Synthesis of 3-Alkylquinoxalin- 1-Methyl-3-undecylquinoxalin-2(1H)-one (5e). 45 mg, 71%
o
1
2(1H)-ones.
yield, yellow solid, mp 56–58 C; H NMR (600 MHz, CDCl3) δ
Aliphatic carboxylic acid (2.0 equiv) and PhI(OAc)2 (1.0 equiv) 7.82 (d, J = 7.8 Hz, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.32 (t, J = 7.2
was dissolved in CHCl3 (10 mL). The mixture was stirred at Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 3.69 (s, 3H), 2.93 (t, J = 7.8 Hz,
room temperature for 30 minutes. The solvent was 2H), 1.80–1.75 (m, 2H), 1.45–1.40 (m, 2H), 1.37–1.32 (m, 2H),
evaporated off at 30–40 oC under reduced pressure to remove 1.29–1.25 (m, 12H), 0.87 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
the CHCl3 and in situ formed HOAc, The phenyliodine(III) CDCl3) δ 161.4, 154.9, 133.1, 132.7, 129.6, 129.4, 123.5, 113.5,
dicarboxylate was obtained as a white solid or a viscous oil, 34.4, 31.9, 29.6, 29.6, 29.6, 29.6, 29.5, 29.3, 29.0, 26.9, 22.7,
which was directly used without further purification. 14.1; HRMS (ESI): calcd for C20H31N2O [M + H]+ 315.2436; found
Subsequently, in a dried Schlenk tube, quinoxalin-2(1H)-ones 315.2440.
(0.2 mmol), phenyliodine(III) dicarboxylate (2.5 equiv) and 3-Isobutyl-1-methylquinoxalin-2(1H)-one (5f). 30 mg, 70%
o
1
Ru(bpy)3Cl2·6H2O (1.5 mg, 1 mol%) were mixed in DMSO (3.0 yield, yellow solid, mp 42–44 C; H NMR (600 MHz, CDCl3) δ
mL) at room temperature. The tube was placed at a distance 7.83 (d, J = 7.8 Hz, 1H), 7.52 (t, J = 7.2 Hz, 1H), 7.33 (t, J = 7.2
(app. 5 cm) from 24 W white LED, and the solution was stirred Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 2.83 (d, J = 7.2 Hz,
under visible-light irradiation. After the reaction was 2H), 2.37–2.28 (m, 1H), 1.01 (d, J = 6.6 Hz, 6H); 13C NMR (150
completed (monitored by TLC), the reaction mixture was MHz, CDCl3) δ 160.7, 155.1, 133.1, 132.7, 129.7, 129.5, 123.5,
quenched by saturated aqueous Na2CO3 solution (5 mL) and 113.5, 42.9, 29.0, 26.8, 22.7; HRMS (ESI): calcd for
stirred for 10 min, and then the mixture was extracted with C13H16N2ONa [M + Na]+ 239.1160; found 239.1161.
ethyl acetate (3 × 5 mL). The combined organic phase was 3-(Tert-butyl)-1-methylquinoxalin-2(1H)-one (5g). 32 mg, 63%
o
1
dried over anhydrous MgSO4 and evaporated under vacuum. yield, yellow solid, mp 96–99 C; H NMR (600 MHz, CDCl3) δ
The crude product was purified by column chromatography 7.83 (d, J = 8.4 Hz, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.31 (t, J = 7.2
6 | J. Name., 2012, 00, 1-3
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Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 3.67 (s, 3H), 1.49 (s, 9H); 13
NMR (150 MHz, CDCl3) δ 165.3, 153.7, 133.3, 132.2, 130.1, 124.5, 123.5 (hept, J = 3.0 Hz), 122.62 (q, J = 271.5 Hz), 114.4,
129.5, 123.1, 113.2, 39.5, 28.7, 27.9; HRMS (ESI): calcd for 33.8, 28.8, 22.7, 13.9; 19F NMR (376 MHz, CDCl3) δ –63.25 (s);
C13H16N2ONa [M + Na]+ 239.1160; found 239.1165.
ARTICLE
C
(q, J = 34.5 Hz), 132.9, 132.6, 129.9, 129.7, 129.5 (Vqie,wJ A=rti3cl.e0OHnlzin)e,
DOI: 10.1039/C9OB01169B
HRMS (ESI): calcd for C20H16F6N2ONa [M + Na]+ 437.1065;
1-Methyl-3-(2,4,4-trimethylpentyl)quinoxalin-2(1H)-one (5h). found 437.1069.
o
1
35 mg, 69% yield, yellow solid, mp 45–46 C; H NMR (600 Methyl
2-(5-(4-((3-butyl-2-oxoquinoxalin-1(2H)-
MHz, CDCl3) δ 7.84 (d, J = 7.8 Hz, 1H), 7.51 (t, J = 8.4 Hz, 1H), yl)methyl)phenyl)-1,3,4-oxadiazol-2-yl)benzoate (7b). 75 mg,
o
1
7.33 (t, J = 8.4 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 2.96 76% yield, yellow solid, mp 123–125 C; H NMR (600 MHz,
(dd, J = 13.8, 6.6 Hz, 1H), 2.72 (dd, J = 13.8, 7.8 Hz, 1H), 2.33– CDCl3) δ 8.04 (d, J = 8.4 Hz, 2H), 7.90–7.90 (m, 2H), 7.86 (d, J =
2.28 (m, 1H), 1.40 (dd, J = 13.8, 3.6 Hz, 1H), 1.19 (dd, J = 13.8, 7.8 Hz, 1H), 7.67–7.62 (m, 3H), 7.42–7.37 (m, 2H), 7.32 (t, J =
6.0 Hz, 1H), 1.00 (d, J = 6.6 Hz, 3H), 0.89 (s, 9H); 13C NMR (150 7.8 Hz, 1H), 7.18 (d, J = 8.4 Hz, 1H), 5.56 (s, 2H), 3.81 (s, 3H),
MHz, CDCl3) δ 160.7, 155.1, 133.1, 132.7, 129.7, 129.5, 123.5, 3.01 (t, J = 7.8 Hz, 2H), 1.85–1.80 (m, 2H), 1.53–1.47 (m, 2H),
113.5, 50.9, 43.7, 31.2, 30.0, 29.0, 27.8, 22.9; HRMS (ESI): calcd 1.00 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 167.1,
for C17H24N2ONa [M + Na]+ 295.1786; found 295.1781.
164.6, 163.9, 161.5, 154.9, 139.4, 133.0, 132.2, 131.7, 131.6,
3-Cyclohexyl-1-methylquinoxalin-2(1H)-one (5i). 34 mg, 57% 131.4, 130.4, 130.0, 129.9, 129.6, 127.6, 127.5, 123.8, 123.7,
yield, yellow solid, mp 102–104 oC; 1H NMR (600 MHz, CDCl3) δ 123.3, 114.0, 52.7, 45.7, 34.1, 28.9, 22.7, 14.0; HRMS (ESI):
7.83 (d, J = 8.4 Hz, 1H), 7.50 (t, J = 8.4 Hz, 1H), 7.32 (t, J = 8.4 calcd for C29H26N4O4Na [M + Na]+ 517.1846; found 517.1840.
Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 3.69 (s, 3H), 3.36–3.14 (m, 1H),
1.96 (d, J = 15.0 Hz, 2H), 1.87 (d, J = 13.2 Hz, 2H), 1.76 (d, J =
12.6 Hz, 1H), 1.60–1.54 (m, 2H), 1.50–1.42 (m, 2H), 1.34–1.27
(m, 1H); 13C NMR (150 MHz, CDCl3) δ 164.2, 154.5, 132.9,
Conflicts of interest
There are no conflicts to declare
132.8, 129.7, 129.3, 123.3, 113.4, 40.7, 30.5, 29.0, 26.3, 26.1;
HRMS (ESI): calcd for C15H18N2ONa [M + Na]+ 265.1317; found
265.1311.
Acknowledgements
We are thankful for financial support from the National
Ethyl 2-(3-butyl-2-oxoquinoxalin-1(2H)-yl)acetate (5j). 39 mg,
o
1
68% yield, yellow solid, mp 102–104 C; H NMR (600 MHz,
CDCl3) δ 7.84 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 7.8 Hz, 1H), 7.33 (t,
J = 7.8 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 5.02 (s, 2H), 4.24 (q, J =
7.2 Hz, 2H), 2.95 (t, J = 7.8 Hz, 2H), 1.80–1.75 (m, 2H), 1.50–
Natural Science Foundation of China (Grant No. 21662030,
21861033); Key Laboratory Polymer Materials of Gansu
Province (Northwest Normal University); Key Laboratory of
Polymer Materials of Ministry of Education of Ecological
Environment; and State Key Laboratory of Applied Organic
Chemistry (Lanzhou University).
1.44 (m, 2H), 1.27 (t, J = 7.2 Hz, 3H), 0.97 (t, J = 7.8 Hz, 3H); 13
C
NMR (150 MHz, CDCl3) δ 167.2, 161.1, 154.5, 132.8, 132.2,
129.9, 129.6, 123.8, 112.9, 62.0, 43.5, 33.9, 28.8, 22.7, 14.1,
13.9; HRMS (ESI): calcd for C16H20N2O3Na [M + Na]+ 311.1372;
found 311.1383.
3-Butyl-1-phenylquinoxalin-2(1H)-one (5k). 52 mg, 68% yield,
yellow solid, mp 107–109 oC; 1H NMR (600 MHz, CDCl3) δ 7.88–
7.85 (m, 1H), 7.61 (t, J = 7.8 Hz, 2H), 7.55 (t, J = 7.8 Hz, 1H),
7.31–7.27 (m, 4H), 6.67–6.64 (m, 1H), 2.98 (t, J = 7.8 Hz, 2H),
1.85–1.80 (m, 2H), 1.52–1.46 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H);
13C NMR (150 MHz, CDCl3) δ 162.2, 154.6, 135.9, 133.9, 132.6,
130.2, 129.3, 129.2, 129.1, 128.3, 123.6, 115.3, 33.9, 29.0,
22.8, 13.9; HRMS (ESI): calcd for C18H18N2O Na [M + Na]+
301.1317; found 301.1324.
Notes and references
1
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3-Isobutyl-1-phenylquinoxalin-2(1H)-one (5l). 47 mg, 62%
o
1
yield, yellow solid, mp 91–94 C; H NMR (600 MHz, CDCl3) δ
7.89–7.86 (m, 1H), 7.61 (t, J = 7.2 Hz, 2H), 7.54 (t, J = 7.8 Hz,
1H), 7.31–7.28 (m, 4H), 6.67–6.64 (m, 1H), 2.87 (d, J = 7.2 Hz,
2H), 2.41–2.34 (m, 1H), 1.04 (d, J = 6.6 Hz, 6H); 13C NMR (150
MHz, CDCl3) δ 161.5, 154.8, 136.0, 133.9, 132.6, 130.2, 130.1,
129.3, 129.1, 128.3, 123.6, 115.3, 42.8, 26.9, 22.8; HRMS (ESI):
calcd for C18H19N2O [M + H]+ 279.1497; found 279.1502.
2
3
a) H. A. Abbas, A. R. Al-Marhabi, S. I. Eissa, Y. A. Ammar,
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o
1
one (5m). 67 mg, 82% yield, yellow solid, mp 159–162 C; H
NMR (600 MHz, CDCl3) δ 8.08 (s, 1H), 7.92–7.89 (m, 1H), 7.83
(s, 2H), 7.38–7.35 (m, 2H), 6.56–6.53 (m, 1H), 2.98 (t, J = 7.8
Hz, 2H), 1.85–1.79 (m, 2H), 1.53–1.47 (m, 2H), 0.99 (t, J = 7.2
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 161.9, 154.1, 137.5, 133.9
This journal is © The Royal Society of Chemistry 20xx
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
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Farmaco 1999, 54, 169.
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8 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C9OB01169B
Journal Name
ARTICLE
Visible-Light Induced Decarboxylative Alkylation of Quinoxalin-2(1H)-ones at C3-
position
Wenxuan Xue, Yingpeng Su, Ke-Hu Wang, Rong Zhang, Yawei Feng, Lindan Cao, Dangfeng Huang, Yulai Hu*
R4COOH
PhI(OAc)2
3-Alkylquinoxalin-2(1H)-ones are
synthesized via direct alkylation of
quinoxalin-2(1H)-one at C3 position under
visible light irradiation.
+
Ligand exchange
Ru(bpy3)Cl2·6H2O
R2
R3
N
N
R4
O
R2
R3
N
PhI(OOCR4)2
DMSO, rt, air
+
N
R1
O
24 W white LED
R1
36 Examples;
Up to 91% Yield;
 readily available alkyl radical sources
 mild conditions and visiable light induced
 high efficiency
 excellent functional group tolerance
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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