Synthesis of quinoxalines catalysed by cetyltrimethyl ammonium bromide (CTAB) in aqueous media

Article abstract of DOI:10.3184/030823409X12591655855261

A facile and simple method has been developed for the condensation of 1,2-diaminobenzenes with α-bromoketones to form quinoxalines with good yields using cetyltrimethyl ammonium bromide (CTAB) in aqueous media. The efficiency of this reaction was demonstrated by the compatibility with nitro, methyl, methoxy, fluoro chloro bromo and furanyl groups. The important features of the methodology are broad substrate scope, simple workup, and no requirement for metal catalysts.

Full text of DOI:10.3184/030823409X12591655855261

JOURNAL OF CHEMICAL RESEARCH 2009
DECEMBER, 761–765
RESEARCH PAPER 761
Synthesis of quinoxalines catalysed by cetyltrimethyl ammonium
bromide (CTAB) in aqueous media
Tieqiang Huanga, Qaing Zhanga, Jiuxi Chena*, Wenxia Gaoa, Jinchang Dinga,b and Huayue Wua
aCollege of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, P.R. China
bWenzhou Vocational and Technical College, Wenzhou, 325035, P.R. China
A facile and simple method has been developed for the condensation of 1,2-diaminobenzenes with a-bromoketones
to form quinoxalines with good yields using cetyltrimethyl ammonium bromide (CTAB) in aqueous media. The
efficiency of this reaction was demonstrated by the compatibility with nitro, methyl, methoxy, fluoro chloro bromo
and furanyl groups. The important features of the methodology are broad substrate scope, simple workup, and no
requirement for metal catalysts.
Keywords: quinoxaline, cetyltrimethyl ammonium bromide (CTAB), aqueous media
Quinoxaline derivatives have shown a broad spectrum
of biological activities such as anticancer, anthelmintic,
antifungal and insecticidal agents.1 The quinoxaline ring
is present in a number of antibiotics such as echinomycin,
levomycin, and actinomycin, which are known to inhibit the
growth of gram-positive bacteria and are also active against
various transplantable tumours.2,3 They have also found
applications as dyes,4 efficient electroluminescent materials,5
organic semiconductors,6 dehydroannulenes,7 cavitands8
and chemically controllable switches.9 Thus, a large number
of procedures have been developed for the construction
of quinoxaline derivatives involving condensation of
1,2-diamines with 1,2-diketones,10,11 oxidation-trapping
of a-hydroxyketones with 1,2-diamines,12-14 1,4-addition
of 1,2-diamines to diazenylbutenes,15 POCl3-mediated
heteroannulation of a-nitroketene N,S-anilinoacetals,16
oxidative coupling of epoxides with ene-1,2-diamines,17
Table 1 Synthesis of 2-phenylquinoxaline under different
reaction conditionsa
NH2
NH2
O
N
Catalyst
Br
+
Ph
Ph
N
1a
2a
3a
Entry
Catalyst
Solvent
Yield/%b
1
2
none
SDS
TBAF
TBAI
TMAB
CTAB
CTAB
CTAB
CTAB
CTAB
CTAB
CTAB
H2O
H2O
29
52
50
51
64
81
53c
70d
60
59
61
70
3
H2O
4
H2O
5
H2O
6
H2O
7
H2O
8
H2O
9
EtOH
CH3CN
1,4-dioxane
DMSO
10
11
12
cyclisation–oxidation
of
phenacyl
bromides
and
o-phenylenediamines through solid-phase synthesis18,19
or high temperature and pressure20,21 (150°C and 20 psi)
aAll the reactions were run with a-bromoketone 1a (1.0 mmol),
1,2-diaminobenzene 2a (1.2 mmol) and catalyst (25 mol%) in
22
by microwave irradiation or using HClO4·SiO2 as hetero-
geneous catalyst. Nevertheless, most of these methods suffer
from drawbacks such as unsatisfactory yields, difficult
experimental procedures, expensive and harmful reagents
and harsh reaction conditions. Therefore, the development of
environmentally benign, efficient and high-yielding methods
for the synthesis of quinoxalines remains a highly desirable
goal in organic synthesis.
water (5 mL) at reflux for 8 h.
bIsolated yield.
c5 mol%.
d10 mol%.
were examined to explore the scope and generality of this
protocol for the synthesis of various quinoxalines and the
results are summarised in Table 2.
In continuation of our efforts to develop green synthetic routes
for the formation of C–C and carbon–heteroatom bond,23-32
we report here a green, simple and practical method for the
synthesis of quinoxaline derivatives from a-bromoketones and
1,2-diaminobenzenes catalysed by CTAB in aqueous media.
At the onset of the research, the efficacy of various
catalysts was investigated in the model reaction between
a-bromoketone 1a and 1,2-diaminobenzene 2a under different
reaction conditions (Table 1). The results showed that CTAB
was superior with respect to product yields. Entry 1 shows the
control reaction without addition of any catalyst, in this case
2-phenylquinoxaline 3a was obtained in low yield. We next
planned to determine the influence of solvent on the rate and
yield of the model reaction. As shown in Table 1, the presence
of organic solvents lowers the reaction rate (Table 1, entries
9–12). So we chose to perform this reaction in aqueous media.
The structure of 3a was characterised by 1H NMR, 13C NMR,
IR and by comparison with authentic samples prepared by a
literature procedure.
As shown in Table 2, the substitutent groups on the
aromatic ring of the a-bromoketone had no obvious effect on
the yields. It was observed that the a-bromoacetophenones
with electron-donating functionality as well as electron-
withdrawing functionality undergo condensation reactions
with 1,2-diaminobenzenes equally well to afford the
corresponding products in good to excellent yields. When
employing the more hindered a-methylphenacyl bromide
and 1,2-diaminobenzenes, moderate to good yields were
also obtained (Table 2, entries 8, 17 and 22). Compared with
the unsubstitued diamine, the reaction of most aromatic
diamines bearing two substituents with a-bromoketones
gave slightly lower product yields (Table 2, entries 11–22).
The results showed that the scope of the reaction is quite broad
and the conditions are tolerant of various functional groups
such as nitro, methyl, methoxy, fluoro, chloro, bromo and
furan groups.
In conclusion, we have developed an eco-friendly synthesis
of quinoxalines catalysed by CTAB in water. Compared to
previous reported methodologies, the present protocol features
broad substrate scope, good yields, simple workup and has no
requirement for metal catalysts. Further investigations on the
With the optimised conditions in place, the reactions of
various a-bromoketones with different 1,2-diaminobenzenes
* Correspondent. E-mail: jiuxichen@wzu.edu.cn
PAPER: JC090785
JCR_12_2009 Book.indb 761
11/12/2009 15:37

762 JOURNAL OF CHEMICAL RESEARCH 2009
Table 2 Synthesis of quinoxalines using CTAB in watera
R1
N
N
R2
R2
O
H2N
R2
R2
CTAB
water
Br
+
Ar
R1
Ar
H2N
1
2
3
Entry
a-Bromoketone
R2
H
Products
Yield/%b
81c
Ar
R1
N
1
2
C6H5
H
Ph
N
3a
N
p-ClC6H4
p-BrC6H4
H
H
92
N
Cl
Br
3b
3c
N
N
3
4
H
H
H
H
95
N
N
p-MeOC6H4
96c
MeO
3d
N
N
5
6
p-MeC6H4
p-NO2C6H4
H
H
H
H
87c
81
3e
N
N
O2N
3f
N
N
7
8
o-ClC6H4
H
H
H
90
71
Cl
3g
N
N
C6H5
Me
3h
N
N
9
2-furyl
H
H
H
H
80
88
O
3i
N
N
10
p-FC6H4
F
3j
N
11
12
C6H5
H
H
Me
Me
89c
81
Ph
Cl
N
3k
N
p-ClC6H4
N
3l
N
N
13
14
p-BrC6H4
H
H
Me
Me
85
80
Br
3m
N
N
p-MeOC6H4
MeO
PAPER: JC090785
JCR_12_2009 Book.indb 762
11/12/2009 15:37

JOURNAL OF CHEMICAL RESEARCH 2009 763
Table 2 Continued
Entry
a-Bromoketone
R2
Products
Yield/%b
Ar
R1
H
N
N
15
16
p-NO2C6H4
Me
Me
71
85
O2N
N
N
o-ClC6H4
H
Cl
3p
3q
N
N
17
18
C6H5
C6H5
Me
H
Me
Cl
52
81
N
N
Cl
Cl
Ph
3r
N
N
Cl
Cl
19
20
p-MeOC6H4
p-NO2C6H4
H
H
Cl
Cl
75
70
MeO
3s
3t
N
Cl
Cl
N
O2N
N
Cl
21
22
o-ClC6H4
H
Cl
Cl
60
85
N
Cl
Cl
3u
3v
N
N
Cl
Cl
C6H5
Me
aAll reactions were run with a-bromoketone 1 (1.0 mmol), 1,2-diaminobenzene 2 (1.2 mmol), CTAB (25 mol%, 0.25 mmol) and
water (5 mL) at reflux for 24 h.
bIsolated yield.
cThe reaction was carried out for 8 h.
the organic layer washed with brine (3 × 10 mL), and then dried over
anhydrous Na2SO4 and concentrated. The product was separated and
purified by column chromatography on silica gel (300–400 mesh)
using an ethyl acetate/petrol mixture as the eluent to afford a pure
product. When necessary, the products are purified by recrystallising
with an ethyl acetate/petrol mixture.
reaction mechanism, scope and limitations of these reactions
and a biological evaluation of the new class of compounds are
under way.
Experimental
2-Phenylquinoxaline (3a): Solid, m.p. 74–76°C (lit.33 75–76°C);
1H NMR (300 MHz, CDCl3): d 7.56–7.59 (m, 3H), 7.77–7.81 (m,
2H), 8.13–8.23 (m, 4H), 9.35 (s, 1H); 13C NMR (75 MHz, CDCl3)
d 127.4, 127.7, 129.0, 129.3, 129.5, 130.0, 130.1, 136.5, 141.4,
142.1, 143.2, 151.5.
Chemicals were purchased and used without further purification.
Melting points were recorded on Digital Melting Point Apparatus
WRS-1B and are uncorrected. IR spectra were recorded on a Bruker-
EQUINOX55 spectrometer. Mass spectra (EI, 70 ev) were measured
with SHIMADZU GCMS-QP2010 Plus instrument. 1H NMR and
13C NMR spectra were recorded on a Brucker AC 300 instrument
using CDCl3 or DMSO-d6 or acetone-d6 as the solvent with
tetramethylsilane (TMS) as an internal standard at room temperature.
Chemical shifts were given in d relative to TMS, the coupling
constants J are given in Hz. Elemental analysis was determined on a
Carlo-Erba 1108 instrument. Column chromatography was performed
using EM Silica gel 60 (300–400 mesh). All known products were
identified by comparison with authentic samples.
2-(4-Chlorophenyl)quinoxaline (3b): Solid, m.p. 12–128°C (not
reported);22 1H NMR (300 MHz, CDCl3): d 7.53–7.56 (m, 2H), 7.56–
7.81 (m, 2H), 8.11–8.18 (m, 2H), 9.31 (s, 1H); 13C NMR (75 MHz,
CDCl3) d 128.7, 129.1, 129.4, 129. 6, 129.7, 130.4, 135.1, 136.6,
141.6, 142.2, 142.8, 150.5.
2-(4-Bromophenyl)quinoxaline (3c): Solid, m.p. 136–139°C (not
reported);13 1H NMR (300 MHz, CDCl3): d 7.63–7.66 (m, 2H), 7.74–
7.76 (m, 2H), 8.02–8.11 (m, 2H), 9.24 (s, 1H); 13C NMR (75 MHz,
CDCl3) d 124.91, 128.89, 129.09, 129.51, 129.73, 130.40, 132.25,
135.47, 141.57, 142.10, 142.70, 150.48.
2-(4-Methoxyphenyl)quinoxaline (3d): Solid, m.p. 100–101°C
(lit.33 99–100°C); 1H NMR (300 MHz, CDCl3): d 3.88 (s, 3H),
7.05–7.08 (m, 2H), 7.71–7.75 (m, 2H), 8.07–8.18 (m, 4H), 9.28 (s,
1H); 13C NMR (75 MHz, CDCl3) d 55.4, 114.5, 128.9, 129.0, 129.0,
129.2, 129.3, 130.1, 141.2, 142.3, 143.0, 151.3,161.4.
General synthetic procedure for synthesis of 2-substituted
quinoxalines of 3a–o
To a mixture of a-bromoketone 1 (1 mmol) and 1,2-diaminobenzene
2 (1.2 mmol), CTAB (25 mol%) was added in water (5 mL) under
reflux. The reaction was monitored by TLC. After completion of the
reaction, the product was extracted with ethyl acetate (3 × 10 mL),
PAPER: JC090785
JCR_12_2009 Book.indb 763
11/12/2009 15:37

764 JOURNAL OF CHEMICAL RESEARCH 2009
2-(4-Methylphenyl)quinoxaline (3e): Solid, m.p. 93–94°C (lit.33
90–91°C); 1H NMR (300 MHz, CDCl3): d 2.44 (s, 3H), 7.36 (d,
J = 8.0 Hz, 2H), 7.71–7.77 (m, 2H), 8.09–8.16 (m, 4H), 9.30 (s,
1H); 13C NMR (75 MHz, CDCl3) d 21.3, 127.3, 129.0, 129.2, 129.4,
129.8, 130.1,133.8, 140.4, 141.3, 142.2, 143.2, 151.7.
6,7-Dichloro-2-phenylquinoxaline (3r): Solid, m.p. 153–156°C
(not reported);40 1H NMR (300 MHz, CDCl3): d 7.58–7.61 (m, 3H),
8.19–8.22 (m, 2H), 8.26 (s, 1H), 8.30 (s, 1H), 9.34 (s, 1H); 13C NMR
(75 MHz, CDCl3): d 127.6, 129.3, 129.8, 130.2, 130.8, 134.1, 136.1,
140.3, 141.1, 144.3, 152. 7.
2-(4-Nitrophenyl)quinoxaline (3f): Solid, m.p. 188–191°C (not
reported);34 1H NMR (300 MHz, DMSO-d6): d 7.90–7.93 (m, 2H),
8.13–8.16 (m, 2H), 8.39–8.42 (m, 2H), 8.56–8.59 (m, 2H), 9.67 (s,
1H); 13C NMR (75 MHz, DMSO-d6) d 124.6, 129.2, 129.36, 129.9,
131.4, 131.5, 141.8, 142.0, 142.4, 144.4, 148. 9, 149.4.
6,7-Dichloro-2-(4-methoxyphenyl) quinoxaline (3s): Solid, m.p.
199–201°C; IR (KBr) nmax/cm-1: 2920, 2417, 1460, 1260, 1180, 1114,
837; 1H NMR (300 MHz, CDCl3): d 3.92 (s, 3H), 7.1 (d, J = 8.8 Hz,
2H), 8.16 (d, J = 8.8 Hz, 2H), 8.19 (s, 1H), 8.22 (s, 1H), 9.27 (s,
1H); 13C NMR (75 MHz, CDCl3): d 55.5, 114.7, 128.4, 129.1, 129.7,
129.9, 133.3, 134.7, 139.9, 141.1, 144.0, 152.2. 161.9; MS (EI,
70 eV) m/z (%): 308 (M+ + 4, 11), 306 (M+ + 2, 63), 304 (M+, 100),
289 (21), 133 (19). Anal. Calcd for C15H10Cl2N2O: C, 59.04; H, 3.30;
N, 9.18. Found: C, 59.16; H, 3.43; N, 9.27%.
2-(2-Chlorophenyl)quinoxaline (3g): Solid, m.p. 86–88°C (not
reported);35 1H NMR (300 MHz, CDCl3): d 7.45–7.48 (m, 2H), 7.55–
7.74 (m, 2H),7.81–7.84 (m, 2H), 8.16–8.19 (m, 2H), 9.22 (s, 1H);
13C NMR (75 MHz, CDCl3): d 127.4, 129.1, 129.5, 130.1, 130.2,
130.2,1 30.7, 131.8, 132.5, 136.4, 141.2, 142.2, 146.1, 152.3.
2-Methyl-3-phenyl-quinoxaline (3h): Solid, m.p. 54–56°C (lit.11
6,7-Dichloro-2-(4-nitrophenyl) quinoxaline (3t): Solid, m.p.
223–225°C; IR (KBr) nmax/cm-1: 2921, 2398, 1733, 1458, 1348,
1
56°C); H NMR (300 MHz, CDCl3): d 2.77 (s, 3H), 7.48–7.52 (m,
1
1110, 859; H NMR (300 MHz, acetone-d6): d 8.39 (d, J = 8.7 Hz,
3H), 7.63–7.66 (m, 4H), 7.69–7.73 (m, 2H); 13C NMR (75 MHz,
CDCl3): 24.3, 128.2, 128.5, 128.8, 128.9, 129.1, 129.2, 129.7, 138.9,
140.9, 141.1, 152.4, 154.8.
2H), 8.43 (s, 2H), 8.53 (d, J = 8.7 Hz, 2H), 9.68 (s, 1H); 13C NMR
(75 MHz, acetone-d6): d 124.10, 128.86 (× 2), 130.02, 130.41,
134.08, 134.39, 140.92, 141.77, 145.04, 205.22, 205.48; MS (EI,
70 eV) m/z (%): 323 (M+ + 4, 11), 321 (M+ + 2, 62), 319 (M+, 100),
289 (26), 144 (22), 77 (32). Anal. Calcd for C14H7Cl2N3O2: C, 52.53;
H, 2.20; N, 13.13. Found: C, 52.41; H, 2.29; N, 13.22%.
2-(2-Furanyl)quinoxaline(3i):Solid,m.p.98–99°C(lit.3397–98°C);
1H NMR (300 MHz, CDCl3): d 6.61–6.62 (m, 1H), 7.30–7.31 (m,
1H), 7.67–7.75 (m, 3H), 8.04–8.10 (m, 2H), 9.23 (s, 1H); 13C NMR
(75 MHz, CDCl3): d 111.8, 112.5, 129.2, 129.2, 129.3, 130.5, 141.2,
142.0, 142.1, 143.8, 145.1, 151.5.
6,7-Dichloro-2-(2-chlorophenyl)quinoxaline (3u): Solid, m.p.
113–115°C; IR (KBr) nmax/cm-1: 3048, 2918, 1453, 1316, 1112, 939,
2-(4-Fluorophenyl)quinoxaline (3j): Solid, m.p. 120–122°C
(lit.33 120–121°C); 1H NMR (300 MHz, CDCl3): d 7.21–7.27 (m,
2H), 7.75–7.78 (m, 2H), 8.09–8.21 (m, 4H), 9.27 (s, 1H); 13C NMR
1
752; H NMR (300 MHz, CDCl3): d 7.46–7.57 (m, 3H), 7.70–7.72
(m, 1H), 8.28 (s, 1H), 8.29 (s, 1H), 9.22 (s, 1H); 13C NMR (75 MHz,
CDCl3): d 127.6, 129.9, 130.2, 130.4, 131.2, 131.9, 132.5, 134.7,
134.9, 135.8, 140.0, 141.0, 147.1, 153.3; MS (EI, 70 eV) m/z (%):
314 (M+ + 6, 3), (312 (M+ + 4, 24), 310 (M+ + 2, 68), 308 (M+, 77),
275 (52), 273 (100), 109 (35). Anal. Calcd for C14H7Cl3N2: C, 54.32;
H, 2.28; N, 9.05. Found: C, 54.49; H, 2.17; N, 8.96%.
2
(75 MHz, CDCl3): d 116.16 (d, JCF = 21.3 Hz), 129.07, 129.43 (d,
3JCF = 8.25 Hz), 129.46, 129.54, 130.36, 132.84 (d, 3JCF = 3.45 Hz),
141.4, 142.1, 142.9, 150.7, 164.2 (d, 1JCF = 248.93 Hz).
6,7-Dimethyl-2-phenylquinoxaline (3k): Solid, m.p. 127–129°C
(lit.33 128–129°C); 1H NMR (300 MHz, CDCl3): d 2.49 (s, 6H),
7.49–7.55 (m, 3H), 7.84 (s, 1H), 7.89 (s, 1H), 8.14–8.18 (m, 2H),
9.21 (s, 1H); 13C NMR (75 MHz, CDCl3): d 20.3, 20.3, 127.3, 128.1,
128.6, 129.0, 129.8, 137.0, 140.1, 140.5, 140.7, 141.1, 142.3, 150.9.
6,7-Dimethyl-2-(4-chlorophenyl)quinoxalin (3l): Solid, m.p. 160–
163°C (not reported);36,37 1H NMR (300 MHz, CDCl3): d 2.49 (s,
6H), 7.49 (d, J = 8.57 Hz, 2H), 7.82 (s, 1H), 7.85 (s, 1H), 8.09 (d,
J = 8.57 Hz, 2H), 9.15 (s, 1H); 13C NMR (75 MHz, CDCl3): d 20.3,
20.4, 128.1, 128.5, 128.5, 129.2, 135.4, 136.1, 140.4, 140.5, 141.0,
141.0, 141.8, 149.6.
2-Methyl-6,7-dichloro-3-phenylquinoxaline (3v): Solid, m.p. 151–
153°C (not reported);39 1H NMR (300 MHz, CDCl3): d 2.78 (s, 3H),
7.54–7.56 (m, 3H), 7.64–7.65 (m, 2H), 8.17 (s, 1H), 8.23 (s, 1H); 13
C
NMR (75 MHz, CDCl3): d 24.5, 128.6, 128.96, 129.1, 129.4, 129.8,
133.6, 134.1, 138.2, 139.7, 139.9, 154.0, 155.9.
We are grateful to the Natural Science Foundation of Zhejiang
Province (Y4080107) for financial support.
6,7-Dimethyl-2-(4-bromophenyl)quinoxalin (3m): Solid, m.p. 140–
142°C (lit.38 141–142°C); 1H NMR (300 MHz, CDCl3): d 2.50
(s, 6H), 7.66 (d, J = 8.7 Hz, 2H); 7.83 (s, 1H), 7.86 (s, 1H), 8.03 (d,
J = 8.7 Hz, 2H), 9.16 (s, 1H); 13C NMR (75 MHz, CDCl3): d 20.3,
20.4, 124.5, 128.1, 128.5, 128.8, 132.2, 135.9, 140.4, 140.6, 141.0,
141.1, 141.8, 149.7.
Received 14 September 2009; accepted 20 November 2009
Paper 09/0785 doi:10.3184/030823409X12591655855261
Published online: 8 December 2009
References
6,7-Dimethyl-2-(4-methoxyphenyl)quinoxaline (3n): Solid, m.p.
126–129°C; 1H NMR (300 MHz, CDCl3): d 2.48 (s, 6H), 3.89 (s,
3H), 7.06 (d, J = 8.57 Hz, 2H), 7.82 (s, 1H), 7.85 (s, 1H), 8.13 (d,
J = 8.57 Hz,2H), 9.17 (s, 1 H); 13C NMR (75 MHz, CDCl3): d 20.2,
20.3, 55.3, 114.4, 128.0, 128.4, 128.7, 129.5, 139.5, 140.0, 140.58,
141.1, 142.0, 150.5, 161.1. MS (EI, 70 eV) m/z (%): 266 (M+ + 2, 2),
265 (M+ + 1, 19), 264 (M+, 100), 249 (32). Anal. Calcd for C17H16N2O:
C, 77.25; H, 6.10; N, 10.60. Found: C, 77.29; H, 6.07; N, 10.65%.
6,7-Dimethyl-2-(4-nitrophenyl)quinoxaline (3o): Solid, m.p. 197–
1
2
G. Sakata, K. Makino and Y. Kuraswa, Heterocycles, 1988, 27, 2481.
A. Dell, D.H. William, H.R. Morris, G.A. Smith, J. Feeney and
G.C.K. Roberts, J. Am. Chem. Soc., 1975, 97, 2497.
C. Bailly, S. Echepare, F. Gago and M. Waring, Anti-Cancer Drug Des.,
1999, 15, 291.
3
4
5
A. Katoh, T. Yoshida and J. Ohkanda, Heterocycles, 2000, 52, 911.
K.R.J Thomas, M. Velusamy, J.T. Lin, C.H. Chuen and Y.T. Tao, Chem.
Mater., 2005, 17, 1860.
6
S. Dailey, W.J. Feast, R.J. Peace, I.C. Sage, S. Till and E.L. Wood,
J. Mater. Chem., 2001, 11, 2238.
1
200°C; H NMR (300 MHz, CDCl3): d 2.54 (s, 6H), 7.88 (s, 1H),
7.91 (s, 1H), 8.33 (d, J = 9.11 Hz,2H), 8.38 (d, J = 9.11 Hz, 2H),
9.26 (s, 1H); 13C NMR (75 MHz, CDCl3): d 20.4, 20.4, 124.2, 128.0,
128.2, 128.7, 141.1, 141.1, 141.5, 141.6, 141.8, 142.9, 148.2, 148.5.
MS (EI, 70 eV) m/z (%): 281 (M+ + 3, 2), 280 (M+ + 1, 19), 279 (M+,
100), 103 (42). Anal. Calcd for C16H13N3O2: C, 68.81; H, 4.69; N,
15.05. Found: C, 68.87; H, 4.72; N, 15.09%.
7
8
O. Sascha and F. Rüdiger, Synlett, 2004, 150.
J.L. Sessler, H. Maeda, T. Mizuno, V.M. Lynch and H. Furuta, J. Am.
Chem. Soc., 2002, 124, 13474.
9
M.J. Crossley and L.A. Johnston, Chem. Commun., 2002, 1122.
10 R.S. Bhosale, S.R. Sarda, S.S. Andhapure, W.N. Jadhav, S.R. Bhusare and
R.P. Pawar, Tetrahedron Lett., 2005, 46, 7183.
6,7-Dimethyl-2-(2-Chlorophenyl)quinoxaline (3p): Solid, m.p. 96–
98°C; IR (KBr) nmax/cm-1: 3044, 2917, 1736, 1482, 1439, 1035, 755;
1H NMR (300 MHz, CDCl3): 2.50–2.51 (m, 6H), 7.40–7.44 (m, 2H),
7.51–7.52 (m, 1H), 7.69–7.72 (m, 1H), 7.89–7.91 (m, 2H), 9.10 (s,
1H); 13C NMR (75 MHz, CDCl3): d 20.3, 20.4, 127.1, 127.3, 128.1,
128.5, 130.1, 130.5, 131.8, 132.5, 136.7, 140.2, 140.8, 141.1, 145.1,
151.3; MS (EI, 70 eV) m/z (%): 270 (M+ + 2, 26), 268 (M+, 72), 233
(100), 134 (15), 103 (28). Anal. Calcd for C16H13ClN2: C, 71.51; H,
4.88; N, 10.42. Found: C, 71.64; H, 4.96; N, 10.27%.
2,6,7-Trimethyl-3-phenylquinoxaline (3q): Solid, m.p. 92–95°C
(not reported);39 1H NMR (300 MHz, CDCl3): d 2.48 (s, 3H), 2.49
(s, 3H), 2.75 (s, 3H), 7.48–7.52 (m, 3H), 7.63–7.66 (m, 2H), 7.80 (s,
1H), 7.86 (s, 1H); 13C NMR (75 MHz, CDCl3): d 20.3, 20.4, 24.2,
127.3, 128.2, 128.4, 128.7, 128.9, 139.3, 139.5, 139.9, 140.1, 140.1,
151.3, 153.8.
11 S.V. More, M.N.V. Sastry and C.-F. Yao, Green Chem., 2006, 8, 91.
12 S.A. Raw, C.D.Wilfred and R.J.K. Taylor, Org. Biomol. Chem., 2004,
2, 788.
13 S.Y. Kim, K.H. Park and Y.K. Chung, Chem. Commun., 2005, 1321.
14 R.S. Robinson and R.J.K. Taylor, Synlett, 2005, 1003.
15 D. Aparicio, O.A. Attanasi, P. Filippone, R. Ignacio, S. Lillini,
F. Mantellini, F. Palacios and J.M. de los Santos, J. Org. Chem., 2006,
71, 5897.
16 C. Venkatesh, B. Singh, P.K. Mahata, H. Ila and H. Junjappa, Org. Lett.,
2005, 7, 2169.
17 S. Antoniotti and E. Duñach, Tetrahedron Lett., 2002, 43, 3971.
18 Z. Wu and N.J. Ede, Tetrahedron Lett., 2001, 42, 8115.
19 S.K. Singh, P. Gupta, S. Duggineni and B. Kundu, Synlett, 2003, 2147.
20 J.F. Zhou; G.X. Gong, L.T. An and Y. Liu, Synlett, 2008, 3163.
21 Y. Vara, E. Aldaba, A. Arrieta, J.L. Pizarro and M.I. Arriortua, Org.
Biomol. Chem., 2008, 6, 1763.
PAPER: JC090785
JCR_12_2009 Book.indb 764
11/12/2009 15:37

JOURNAL OF CHEMICAL RESEARCH 2009 765
22 B. Das, K. Venkateswarlu, K. Suneel and A. Majhi, Tetrahedron Lett.,
2007, 48, 5371.
23 D.J. Zhu, J.X. Chen, M.C. Liu, D.C. Ding and H.Y. Wu, J. Braz. Chem.
Soc., 2009, 20, 482.
24 J.X. Chen, H.Y. Wu, C. Jin, X.X. Zhang, Y.Y. Xie and W.K. Su, Green
Chem., 2006, 8, 330.
25 J.X. Chen, H.Y. Wu, Z.G. Zheng, C. Jin, X.X. Zhang and W.K. Su,
Tetrahedron Lett., 2006, 47, 5383.
32 H.L. Xiao, J.X. Chen, M.C. Liu, D.J. Zhu, J.C. Ding and H.Y. Wu, Chem.
Lett., 2009, 38, 170.
33 C.S. Choa and S.G. Oh, J. Mol. Catal. A: Chem., 2007, 276, 205.
34 M.H. Rao, A.P.R. Reddy and V. Veeranagaiah, Indian J. Chem., Sect. B:
Org. Chem. Incl. Med. Chem., 1992, 31B, 88.
35 H. Inoue, M. Takeda, K. Higaki and H.Kugita, Yakugaku Zasshi, 1965,
85, 95.
36 C.S. Cho, W.X. Ren and S.C. Shim, Tetrahedron Lett., 2007, 48, 4665.
37 B. Insuasty, F. Fernandez, J. Quiroga, R. Moreno and R. Abonia,
Heterocycl. Commun., 2002, 8, 259.
38 A.I. Zbruyev, F.G. Yaremenko, V.A. Chebanov, S.M. Desenko,
O.V. Shishkin, E.V. Lukinova and I.V. Knyazeva, Russ. Chem. Bull.,
2006, 55, 362.
39 C.S. Mahajanshetti and M.N. Balse, Indian J. Chem., Sect. B: Org. Chem.
Incl. Med. Chem., 1978, 16B, 830.
40 A. Gazit, H. App, G. McMahon, J. Chen, A. Levitzki and F.D. Bohmer,
J. Med. Chem., 1996, 39, 2170.
26 W.K. Su, J.X. Chen, H.Y. Wu and C. Jin, J. Org. Chem., 2007, 72, 4524.
27 X.A. Chen, C.F. Zhang, H.Y. Wu, X.C. Yu, W.K. Su and J. Cheng,
Synthesis, 2007, 3233.
28 J.X. Chen, W.K. Su, H.Y. Wu, M.C. Liu and C. Jin, Green Chem., 2007,
9, 972.
29 J.X. Chen, D.Z. Wu, F. He, M.C. Liu, H.Y. Wu, J.C. Ding and W.K. Su,
Tetrahedron Lett., 2008, 49, 3814.
30 W.X. Guo, J.X. Chen, D.Z. Wu, J.C. Ding, F. Chen and H.Y. Wu,
Tetrahedron, 2009, 65, 5240.
31 H.M. Zheng, Q. Zhang, J.X. Chen, M.C. Liu, S.H. Cheng, J.C. Ding,
H.Y. Wu and W.K. Su, J. Org. Chem., 2009, 74, 943.
PAPER: JC090785
JCR_12_2009 Book.indb 765
11/12/2009 15:37

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.