One-step approach for the synthesis of functionalized quinoxalines mediated by T3P-DMSO or T3P: Via a tandem oxidation-condensation or condensation reaction

Article abstract of DOI:10.1039/c6ra03078e

An easy and efficient propylphosphonic anhydride (T3P)-DMSO or T3P mediated oxidation-condensation or condensation reaction for the synthesis of quinoxalines derived from the interaction of different arrays of condensing partners with ortho-phenylene diamines (o-PDs) under simple and mild reaction conditions in one step has been reported for the first time.

Full text of DOI:10.1039/c6ra03078e

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DOI: 10.1039/C6RA03078E
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COMMUNICATION
One-step Approach for Synthesis of Functionalized Quinoxalines
Mediated by T3P® - DMSO or T3P® via Tandem Oxidation –
Condensation or Condensation Reaction
000Received 00th January
20xx,
Kachigere B. Harsha,a# Kanchugarkoppal S. Rangappa.a*
Accepted 00th January
20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
An easy and efficient propyl phosphonic anhydride (T3P®) - DMSO or T3P® mediated oxidation-
condensation or condensation reaction for the synthesis of quinoxalines from the interaction of different
arrays of condensing partners with ortho-phenylene diamines (o-PDs) under simple and mild reaction
conditions in one step has been reported for the first time.
research group, found that T3P® (propane phosphonic anhydride) is
being used in the synthesis of peptides,9 synthesis of
polysubstituted quinolines and naphthyridines,10 β-lactams,11
Introduction
The new synthetic organic transformation for the synthesis of
functionalized N-containing heterocyclic small molecules from
simple starting materials is of great importance in the field of
synthetic organic chemistry. Quinoxalines or benzopyrazines in
particular have been studied as antibacterial, antiviral,
anthelmentic, antiinflamatory, kinase inhibitory and anticancer
activities 1 and quinoxalines have a wide array of other applications.
pyrimidinones in Biginelli reaction,12 1,2,4-oxadiazoles and 1,3,4-
oxadiazoles and 1,3,4-thiadiazoles13 Fischer indole.14 Due to its
significant properties like water scavenger, oxidation-cyclization
recently we have been reported several one pot tandem
approaches for the synthesis of benzimidazoles and
benzothiazoles,15a 4-thiazolidinones15b and imidazo [1, 2-a]
pyridines15c from alcohols, using DMSO-propylphosphonic
anhydride (T3P®) media as an oxidizing as well as cyclodehydrating
agent. In continuation of our research interest in the synthesis of
various heterocycles,16 we report herein a new strategic one-step
method for the synthesis of quinoxalines from α-hydroxy ketone, α-
haloketone and 1,2-diketones with o-PDs by using
DMSO:Propylphosphonic anhydride (T3P®) or propylphosphonic
anhydride (T3P®) in EtOAc as a solvent under room temperature and
reaction underwent via oxidation followed by condensation or by
simple condensation reaction. To optimize the reaction conditions,
Initially we selected the reaction between o-PD 1a and 2-hydroxy
1,2-diphenylethanone 2a (scheme1) in EtOAc:DMSO in the ratio 2:1
as a solvent mixture followed by adding 1 equivalent of T3P®(50%
solution in ethyl acetate) under stirring at O0C-RT for 10 hs which
afforded the desired 2,3-diphenylquinoxaline 3e in 25% yield. The
same reaction we checked different equivalents T3P® could affect
the course of reaction and yield of 3e. Therefore, we carried out the
oxidation-condensation by using various equivalents of T3P®. The
best result was obtained when reaction between 1,2-
diphenylethanone and o-PDs with 2.0 equivalent of T3P® in
presence of DMSO was stirred at RT for 6 h. We also studied by
keeping the equivalent of T3P® (2.0 eq) at constant and by varying
the temperature and time . Finally we were not able to achieve
maximum percentage yield compared to yield obtained in RT
2
In addition, quinoxaline nucleus contains some important
antibiotics such as olaquindox, carbadox, echinomycin, levomycin
and actinoleutin. Owing to their wide range of biological and
technical interest, number of synthetic strategies have been
developed for the synthesis of various substituted quinoxalines. Out
of several methods of synthesis, the oxidation-condensation or
condensation reaction is one of the major synthetic stratergies for
the synthesis of bioactive quinoxaline nucleus from readily available
precursors like o-PDs and α-hydroxy ketones.3 And also several
methods are available for the synthesis of quinoxalines from
phenacyl bromides,4 1,2-diketones,5 alkynes,6 epoxides,7
aryliminooximes8 with o-PDs.
Most of the methods reported above suffer from one or more
disadvantages such as poor substrate scope, harsh reaction
condition, laborious and complex work-up procedure, expensive
and moisture sensitive reagents, undesirable side products and
unsatisfactory yield. During the course of investigation, our
a.DOS In Chemistry, University Of Mysore, Mysuru-570006, India.
b.* Corresponding authors
c. E-mail:rangappaks@gmail.com,rangappaks@yahoo.com
d.Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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Scheme 1. Synthesis of 2,3-diphenyl quinoxaline (3e) from α- Scheme 2: Synthesis of quinoxalines from α- hydroxy ketones.
hydroxy ketone.
Table 1. T3P®-DMSO mediated synthesis of 3e under different
reaction conditions.
Entry. Solventa
T3P®(equiv)b Time(h)
T [0C]
Yieldc(%)of
3e
1.
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
CH2Cl2
CHCl3
1.0
1.5
2.0
2.5
3.0
3.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
10
6
0-25
0-25
0-25
0-25
0-25
0-25
0-25
0-25
0-25
0-25
0-25
0-25
0-25
50
25
2.
54
94
94
93
93
48
44
55
49
58
56
40
87
86
3.
6
4.
6
5.
6
6.
6
7.
6
T3P®(2.0 mmol), α-hydroxy ketone (1.2 mmol), 1,2 Diamine (1.0
mmol).
8.
6
9.
CH3CN
THF
6
10.
11.
12.
13.
14.
15.
6
ketones and o-PDs mediated by the T3P® in DMSO:EtOAc as a
solvent mixture to obtain the desired quinoxalines (3a-k). The o-PD
and α-hydroxy ketone without substitution afford good yield and
also α-hydroxy ketone containing electron-donating group favours
the formation of desired quinoxalines in high yield when compared
to o-PD contains electron-withdrawing group. The results are
summarized in scheme 2. The scope of the reaction was successfully
extended to other substrates such as electronically demanding α-
bromo ketones with o-PD or substituted o-PDs which also
underwent the title reaction under RT condition to obtain
corresponding quinoxalines (4a-x). Similarly, here also α-halo
ketone and o-PD containing without substitution favour the
formation of a slightly higher yield. when compared to substituted
α-halo ketones or o-PDs. The results are summarized in scheme 3.
We extended our studies to further increase the substrate scope.
We carried out the condensation of 1,2-dicarbonyl compounds with
o-PD under mild reaction condition at RT in presence of T3P® to
produce the desired quinoxaline derivatives (5a-p). Interestingly,
the reaction between aliphatic diketone and o-PD underwent the
title reaction to afford desired quinoxaline in lower yield. when
compared to aromatic 1,2-diketones. In the case of both aromatic
starting materials containing without substitution favour the
formation of quinoxalines in higher yield. The results are
summarized in scheme 4.
Toluene
Dioxane
Benzene
EtOAc
EtOAc
6
6
6
5.5
5
60
16.
17.
EtOAc
EtOAc
2.5
2.5
4
3
65
75
88
80
a
Reactions were performed with solvent and DMSO were taken in
2:1 volume ratio, 1mmol of 1a, 1.2 mmol of 2a in case of 3e.
b T3P® (50% solution in EtOAc) was used to carry out the reactions.
c Isolated yield after purified by column chromatography.
condition. The optimization results are summarized in table 1. Thus,
the clear optimization of the reaction conditions to obtain
quinoxalines from α-hydroxyl ketone with o-PDs was revealed from
our studies which had used 2.0 equivalent of T3P® and stirring the
reaction mixtures for 6 h at 0oC to RT, the product was isolated
initially washing the reaction mixture with water then followed with
brine and purified by the column chromatography by using 60:120
silica gel. The oxidation-condensation or cyclodehydrating property
of the T3P® helps to generalize the reaction procedure. Next we
carried out the reactions with electronically diversified α-hydroxy
2 | J. Name., 2012, 00, 1-3
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Scheme 3: Synthesis of quinoxalines from α-halo ketone.
COMMUNICATION
O
N
N
N
N
N
N
N
n-pr
O
O
P
N
P
O
5g, (96%)
rt, 5 hr
5h, (95%)
O
rt, 5 hr
5e, (90%)
rt, 5 hr
5f, (94%)
rt, 5 hr
Cl
n-pr
n-pr
P
NH2
NH2
O
N
R'
O
O
O
R
R
Br
N
N
R'
N
N
N
N
N
EtOAc
O0 ꢀRT
O
N
O
4a - x
Br
O
Br
Cl
N
R = H/Me/Br
R' = Aryl / Heteroaryl
5k, (96%)
rt, 5 hr
5l, (94%)
rt, 5 hr
5i, (94%)
rt, 5 hr
5j, (94%)
rt, 5 hr
N
N
N
F
N
N
N
O
O
Ph
O2N
N
Cl
N
N
N
N
N
N
N
N
N
O
5o, (91%)
rt, 5 hr
5n, (95%)
rt, 5 hr
5m, (94%)
rt, 5 hr
5p, (90%)
rt, 5 hr
4b, (96%)
rt, 5h
4c, (94%)
rt, 5h
4a, (98%)
rt, 5h
4d, (94%)
rt, 5h
a T3P®(2.0 mmol), 1,2-diketone (1.2 mmol), diamine(1.0 mol).
CN
NO2
Cl
Br
N
N
N
N
N
N
N
N
Cl
Selected quinoxaline compounds from schemes 1 and 3, such as 3k,
4o, 4p, 4q, 4r, 4s, 4t, 4u, 4v, 4w, 4x were evaluated as cytotoxic
agents against A549 human lung carcinoma cells, which have
frequently been choosen by our group,17 as a suitable cell culture to
perform cytotoxicity assays. Therefore, concentration-response
experiments were performed to establish the cytotoxicity activity of
each selected compound (fig 1).
4h, (95%)
rt, 5h
4g, (96%)
rt, 5h
4f, (94%)
rt, 5h
4e, (95%)
rt, 5h
CF3
N
N
O
N
N
N
S
N
N
N
N
4l, (94%)
rt, 5h
4k, (94%)
rt, 5h
4i, (96%)
rt, 5h
4j, (93%)
rt, 5h
N
N
N
N
Table 2. IC50 (µM) inhibitory concentrations with human lung
carcinoma cells (A549).
N
N
N
Br
4m, (95%)
rt, 5h
d4n, (94%)
rt, 5h
4o, (95%)
rt, 5h
F
O
quinoxaline 3k 4o
4p 4q 4r 4s 4t 4u 4v 4w 4x
F
N
N
N
O
N
IC50 (µM) 2.14 2.11 27.3 17.4 19.4 2.8 20.3 10.3 5.3 33.2 30.3
4p, (94%)
rt, 5h
4r, (92%)
rt, 5h
4q, (92%)
rt, 5h
N
N
F
We observed that quinoxalines 3k,4o,4s,4v,4u are the most
efficient cytotoxic agent when a high concentration (25µM) was
used resulting in the death of 74% of the A549 cells in case of 4o.
IC50 values expressed in µM, summarized in table 2, establish the
relative order of effectiveness for the quinoxalines cytotoxicities: 3k
≈ 4o > 4s > 4v > 4u > 4q > 4r > 4t > 4p > 4x > 4w. From these results
we can conclude that the observed slight difference in cytotoxicity
might be due to differences in the nature of substituents present in
the core moiety and percentage uptake of the compounds by the
cells.
O
S
O
N
N
N
N
Cl
N
N
Cl
4u, (95%)
rt, 5h
4s, (93%)
rt, 5h
4t, (92%)
rt, 5h
F
CN
N
N
N
N
N
N
N
4w, (93%)
rt, 5h
4v, (92%)
rt, 5h
4x, (92%)
rt, 5h
N
N
T3P® (2.0 mmol), α-bromoketone(1.2 mmol), diamine(1.0 mmol)
d Mixture of regioisomers.
90
80
70
60
Scheme 4: Synthesis of quinoxalines from 1,2-diketone.
5µM
50
n-pr
O
O
P
P
40
30
20
10
0
10µM
25µM
O
n-pr
n-pr
R''
R"
N
H2N
H2N
R''
R"
O
O
P
O
O
O
R
R
EtOAc
OOCꢀ RT
N
5a-p
R = H/Br/Cl/F/Me/OMe/NO2/Ph
R" = H/Aryl/Heteroaryl
Concentration (µM)
O
O
N
N
N
N
N
N
N
N
5c, (96%)
rt, 5 hr
5b, (96%)
rt, 5 hr
5d, (92%)
rt, 5 hr
5a, (98%)
rt, 5 hr
Figure 1. Bar graph showing cytotoxicity activity of quinoxalines on
A549 cell line.
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standard (77.0 ppm). Mass spectra were recorded on Waters’ mass
spectrum.
Conclusion:
This synthetic methodology constitutes
a versatile, one-step
General procedure for the synthesis of quinoxalines from α-
hydroxyketones:
protocol for the preparation of libraries of quinoxalines with broad
substrate scope and high yield. The preliminary investigations in to
the cytotoxic effects of the studied quinoxalines compounds against
A-549 cancer cells, the lowest IC-50 value was observed with the
phenyl substituted o-PD part of the quinoxaline 3k and phenyl
substituted α-haloketone part of the quinoxaline 4o. These
promising results shows that application of DMSO-T3P® or T3P®
Mediated reactions gives new chemical space in the field of
synthetic organic chemistry and also in the exploration of new
synthetic strategies for the synthesis of biologically active
heterocyclic small molecules in the field of medicinal chemistry.
The stirred suspension of α-Hydroxy ketone (1.2mmol) in
DMSO:EtOAc as a solvent mixture in the ratio (2:1) was added to
ortho-phenylene diamine (1mmol). It was followed by the addition
0
of T3P® (2.0 mmol) under 0 C then reaction mixture was next kept
under RT for 6 hrs. Progress of the reaction was monitored by TLC.
The reaction mixture was quenched by ice cold water and the
extracted reaction mixture with EtOAc (×2), collected organic layer
was washed with brine solution and dried over anhydrous sodium
sulphate, organic layer was removed under reduced pressure to
afford desired quinoxalines which were purified by column
chromatography using hexane : ethylacetate as an eluent.
n-pr
O
R
O
O
O
S
O
General procedure for the synthesis of quinoxalines from α-
haloketone and 1,2-diketone:
H
P
O
R
O
P
O
O
O
P
O
n-pr
R1
S
O
P
S
P
n-pr
O
O
H
O
O
O
R1
n-pr
Stirred reaction mixture of α-bromoketone or 1,2-diketone
(
n-pr
pr-n
-Me2S
1.2mmol) and ortho phenyl diamine (1mmol) in ethyl acetate
followed by the addition of T3P® (2mmol) under O0C. Then, the
reaction mixture was kept under RT for 5 hr. Progress of the
reaction was monitored by TLC. The reaction mixture was quenched
by ice cold water reaction mixture with EtOAc (×2) was extracted.
The collected organic layer was washed with brine solution and
dried over anhydrous sodium sulphate. Organic layer was removed
under reduced pressure to afford the desired quinoxalines which
O
n-pr
O
NH2
R
O
H
N
n-pr n-pr n-pr
R
P
O
O
O
n-pr
O
n-pr
P
P
P
R1
P
P
O
O
OH
NH2 R1
O
O
O
O
O
O
NH2
n-pr n-pr n-pr
H
P
P
P
HO
R
O
O
OH
O
O
O
were purified by column chromatography using hexane
ethylacetate as an eluent.
:
N
N
R
R
N
N
R1
O
R1
O
2-phenylquinoxaline (3a or 4a): Pale yellow solid; yield 95%; (Rf =
H2O
R1
NH2
N
H
0.48 in hexanes/ EtOAc 95:05 v/v); MP 75-77 OC ; IR (KBr): 3055,
H
H
1
1545, 1480, 1445, 1312, 1035 cm-1; H NMR (CDCl3, 400 MHz): δ =
9.33 (s, 1H), 8.21-8.11 (m, 4H), 7.81-7.73 (m, 2H ), 7.59-7.52 (m,
3H); HRMS (ESI) [M+H]+ calculated C14H10N2 207.0877 found
207.0876
Scheme 5: Proposed mechanism for the formation of quinoxalines
in scheme 1.
2-(p-tolyl)quinoxaline (3b) : Yellow solid; yield 94%; (Rf = 0.46 in
hexanes/ EtOAc 95:05 v/v); MP 92-94 OC; IR (KBr): 3058, 1615,
Experimental Section
1
1554, 1475, 1445, 1310, 1040 cm-1; H NMR (CDCl3, 400 MHz): δ =
Materials and Instruments
9.40 (s, 1H), 8.55–8.38 (m, 4H), 8.37–8.20 (m, 2H), 7.88 (d, J = 8 Hz,
2H), 2.40 (s, 3H); HRMS (ESI) [M+H]+ calculated C15H12N2 221.1034
found 221.1035
Purification of reaction products was carried out by normal column
chromatography using Sorbent Technologies Standard Grade silica
gel (60-120 mesh). Analytical thin layer chromatography was
performed on merk silica gel 60 F254 plates. Visualization was
accomplished with UV light, potassium permanganate. Melting
points were recorded on a Thomas Hoover capillary melting point
apparatus and are uncorrected. Infrared spectra were recorded on
an ATI Mattson Genesis Series FT-Infrared spectrophotometer.
Proton nuclear magnetic resonance spectra (1HNMR) were
recorded on Agilent-400 MHz and are reported in ppm using CDCl3
as the internal standard (7.24 ppm). Proton-decoupled carbon
nuclear magnetic resonance spectra (13C-NMR) were recorded on a
Agilent-100 MHz and reported in ppm using CDCl3 as the internal
6,7-dimethyl-2-phenylquinoxaline (3c or 4m): Yellow solid; yield
92%; (Rf = 0.54` in hexanes/ EtOAc 95:05 v/v); MP 129-130 OC; IR
(KBr): 3055, 3040, 2965, 1535, 1480, 1445, 1310, 1210, 1020, 1005
cm-1; 1H NMR (CDCl3, 400 MHz): δ = 9.22 (s, 1H), 8.20 (d, J = 11.2 Hz,
2H), 7.89 (s, 1H), 7.88 (s, 1H), 7.65–7.36 (m, 3H), 3.41 (s, 6H); HRMS
(ESI) [M+H]+ calculated C16H14N2 235.1190 found 235.1191
6,7-dimethyl-2-(p-tolyl)quinoxaline (3d): Yellow solid; yield 92%;
(Rf = 0.62 in hexanes/ EtOAc 95:05 v/v); MP 113-115 OC; IR (KBr):
3025, 2973, 1605, 1530, 1480, 1442, 1315, 1045, 1025, 860, 825 cm-
1; 1H NMR (CDCl3, 400 MHz): δ = 9.36 (s, 1H), 8.13 (d, J = 7.2 Hz, 2H),
8.12 (s, 1H), 7.82 (s, 1H), 7.81 (s, 1H), 7.09 (d, J = 8 Hz, 2H), 2.63 (s,
4 | J. Name., 2012, 00, 1-3
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3H), 2.33 (s, 6H); HRMS (ESI) [M+H]+ calculated C17H16N2 249.13862 1H), 8.65 (s,1H), 8.37-8.34 (dd, J = 10.8 Hz, 2 Hz, 1H), 8.21-8.13 (m,
found 249.13858 2H), 8.03-7.99 (m, 2H), 7.90 (t, J = 3.6 Hz, 1H), 7.82-7.73 (m, 2H),
2, 3-diphenylquinoxaline (3e or 5a): Yellow solid; yield 94%; (Rf = 7.54-7.50 (m, 2H); HRMS (ESI) [M+H]+ calculated C18H12N2 257.1072
0.58 in hexanes/ EtOAc 95:05 v/v); MP 116-118OC; IR (KBr): 3056, found 257.1072
1635, 1475, 1440, 1345, 1075, 1055, 770, 695 cm-1; 1H NMR (CDCl3,
400 MHz): δ = 8.18 (dd, J = 6.8 Hz, 3.2 Hz, 2H), 7.77 (dd, J = 3.6 Hz,
2-(m-tolyl)quinoxaline (4c)
:
Yellow solid; yield 94%; (Rf = 0.52 in
hexanes/ EtOAc 95:05 v/v); MP 92-94 OC ; IR (KBr): 3054, 1612,
3.2 Hz, 2H), 7.53–7.50 (m, 4H), 7.38–7.31 (m, 6H); HRMS (ESI)
[M+H]+ calculated C20H14N2 283.1230 found 283.1231
1
1542. 1308 cm-1; H NMR (CDCl3, 400 MHz): δ = 9.33 (s, 1H), 8.19–
8.13 (m, 2H), 8.04 (s, 1H), 7.97 (d, J = 8 Hz, 1H), 7.98–7.75 (m, 2H),
7.47 (t, J = 8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 2.51 (s, 3H); HRMS (ESI)
[M+H]+ calculated C15H12N2 221.1034 found 221.1034
2-phenyl-3-p-tolylquinoxaline (3f or 5c): Yellow solid; yield 93%; (Rf
= 0.62 in hexanes/ EtOAc 95:05 v/v); MP 110-112 OC ; IR (KBr): 3055,
2915, 1614, 1553, 1519, 1470, 1438, 1388, 1345, 1056, 1020, 974,
754, 696 cm-1; 1H NMR (CDCl3, 400 MHz,): δ = 8.26–8.14 (m, 2H),
7.99–7.95 (m, 2H), 7.83–7.78 (m, 2H), 7.72 (d, J = 7.6 Hz, 2H), 7.69–
7.40 (m, 3H), 7.13 (d, J = 6.8 Hz, 2H), 2.42 (s, 3H); HRMS (ESI) [M+H]+
calculated C21H16N2 297.1386 found 297.1387
2-(3-methoxyphenyl)quinoxaline (4d): Pale yellow solid; yield 92%;
(Rf = 0.46 in hexanes/ EtOAc 95:05 v/v); MP 96-98 OC ; IR (KBr):
1
1604, 1539, 1442, 1186, 1031 cm-1; H NMR (CDCl3, 400 MHz): δ =
9.32 (s, 1H), 8.18-8.11 (m, 2H), 7.81-7.73 (m, 4H), 7.47 (t, J = 8 Hz,
1H), 7.07 (dd, J = 10.4 Hz, 2 Hz, 1H), 3.94 (s, 3H); HRMS (ESI) [M+H]+
calculated C15H12N2O 237.0983 found 237.0982
6-methyl-2,3-diphenylquinoxaline (3g or 5g): White solid; yield
92%; (Rf = 0.54 in hexanes/ EtOAc 95:05 v/v); MP 111-113 OC; IR
(KBr): 3054, 2938, 1617, 1485, 1444, 1200, 1056, 1021, 812. 768,
698 cm-1; 1H NMR (CDCl3, 400 MHz,): δ = 8.10 (d, J = 8.4 Hz, 1H), 8.09
(s, 1H), 7.92 (dd, J = 9.6 Hz, 1.6 Hz, 1H), 7.78–7.69 (m, 4H), 7.68–
7.31 (m, 6H), 2.77 (s, 3H); HRMS (ESI) [M+H]+ calculated C21H16N2
297.1386 found 297.1387
2-(4-bromophenyl)quinoxaline (4e): Pale yellow solid; yield 94%;
(Rf = 0.56 in hexanes/ EtOAc 95:05 v/v); MP 136-138 OC; IR (KBr):
1588, 1536, 1480, 1122, 1068, 1043 cm-1; 1H NMR (CDCl3, 400 MHz):
δ = 9.29 (s, 1H), 8.15-8.07 (m, 4H), 7.81-7.73 (m, 2H), 7.69 (d, J = 8.4
Hz, 2H); HRMS (ESI) [M+H]+ calculated C14H10BrN2O 285.0023 found
285.0022
6-methoxy-2,3-diphenylquinoxaline (3h or 5i): White solid; yield
92%; (Rf = 0.52 in hexanes/ EtOAc 95:05 v/v); MP 160ꢀ162 OC ; IR
(KBr): 2965, 2936, 1756, 1617, 1482 cmꢀ1; 1H NMR (CDCl3, 400
MHz): δ = 8.04 (d, J = 8.8 Hz, 1H), 7.95–7.92 (m, 4H), 7.91 (d, J =
2Hz, 1H), 7.59 (dd, J = 9.2 Hz, 2.8 Hz, 1H), 7.37–7.34 (m, 6H), 3.83
(s, 3H); HRMS (ESI) [M+H]+ calculated C21H16N2O 313.1296 found
313.1295
2-(3,4-dichlorophenyl)quinoxaline (4f): Yellow solid; yield 90%; (Rf
= 0.58 in hexanes/ EtOAc 95:05 v/v); MP 186-188 OC; IR (KBr): 1540,
1474, 1308, 1146, 1030 cm-1; 1H NMR (CDCl3, 400 MHz): δ = 9.31 (s,
1H), 8.43 (s, 1H), 8.09 (t, J = 6 Hz, 2H), 7.80 (d, J = 7.2 Hz, 1H), 7.80–
7.72 (m, 2H); HRMS (ESI) [M+H]+ calculated C14H9Cl2N2 275.0135
found 275.0135
6-bromo-2,3-diphenylquinoxaline (3i or 5j): Yellow solid; yield
94%; (Rf = 0.48 in hexanes/ EtOAc 95:05 v/v); MP 117-119 OC ; IR
(KBr); 3040, 1588, 1542, 1466, 1442, 1390, 1318, 1182, 1060, 1022,
973, 914, 828, 764, 694 cm-1; 1H NMR (CDCl3, 400 MHz): δ = 8.35 (s,
1H), 8.03 (d, J = 9.2 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 6.8
Hz, 4H), 7.39–7.31 (m, 6H); HRMS (ESI) [M+H]+ calculated
C20H13BrN2 361.0335 found 361.0334
2-(4-nitrophenyl)quinoxaline (4g): Colorless solid; yield 92%; (Rf =
0.64 in hexanes/ EtOAc 95:05 v/v); MP 191-193 OC ; IR (KBr): 3056,
1
1529, 1352, 1096 cm-1; H NMR (CDCl3, 400 MHz): δ = 9.11 (s, 1H),
8.40–8.37 (m, 4H), 8.21–7.84 (m , 2H), 7.83 (d, J = 8Hz, 2H); HRMS
(ESI) [M+H]+ calculated C14H9N3O2 252.0728 found 252.0727
4-(quinoxalin-2-yl)benzonitrile (4h): Pale yellow solid; yield 93%;
(Rf = 0.60 in hexanes/ EtOAc 95:05 v/v); MP 114-116 OC ; IR (KBr):
3058, 2230, 1548, 1480, 1435, 1322, 1036; 1H NMR (CDCl3, 400
MHz): δ = 9.36 (s, 1H), 8.35 (d, J = 8.8 Hz, 2H), 8.19–8.15 (m, 2H),
7.88-7.80 ( m, 4H); HRMS (ESI) [M+H]+ calculated C15H9N3 232.0830
found 232.0831
6-chloro-2,3-diphenylquinoxaline (3j or 5l): White solid; yield 80%;
(Rf = 0.46 in hexanes/ EtOAc 95:05 v/v); MP 118-120 OC ; IR (KBr):
3047, 1602, 1548, 1464, 1442, 1338, 1068, 828, 800, 764, 694 cm-1;
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.4 Hz, 1H), 7.90–7.64 (m,
5H), 7.60–7.34 (m. 6H), 2.77 (s, 3H), 2.48 (s, 3H); HRMS (ESI) [M+H]+
calculated C21H16N2 317.0840 found 317.0841
2-(4-(trifluoromethyl) phenyl) quinoxaline (4i): Pale yellow solid;
yield 92%; (Rf = 0.40 in hexanes/ EtOAc 95:05 v/v); MP 142-143 OC ;
IR (KBr): 3036, 1545, 1488, 1315, 1120, 645, 554 cm-1; 1H NMR
(CDCl3, 400 MHz): δ = 9.33 (s, 1H), 8.31 ( d, J = 8.4 Hz, 2H), 8.12–8.10
2,3-di(furan-2-yl)-6-phenylquinoxaline (3k or 5o): White solid; yield
91%; (Rf = 0.55 in hexanes/ EtOAc 95:05 v/v); MP 131-133 OC; IR
(KBr): 3356, 1614, 1538, 1438, 1081, 835, 1H NMR (CDCl3, 400 MHz):
δ = 8.31 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.94 (t, J = 4 Hz, 1H), 7.92 (t,
J = 3.6 Hz, 1H), 7.65-7.64 (m, 2H), 7.59 (dd, J = 7.2 Hz, 2.8 Hz, 2H),
7.39-7.34 (m, 1H), 7.17 (t, J = 9.6 Hz, 1H), 6.72-6.69 (m, 2H), 6.59-
6.58 (m, 2H); HRMS (ESI) [M+H]+ calculated C22H14N2O2 339.1088
found 339.1089
(m, 2H), 7.88–7.76
(
m, 4H); HRMS (ESI) [M+H]+ calculated
C15H10N2F3 275.0796 found 275.0798
2-(pyridin-3-yl)quinoxaline (4j): White solid; yield 90%; (Rf = 0.44 in
hexanes/ EtOAc 95:05 v/v); MP 110-112 oC; IR (KBr): 3052, 1612,
1
1588, 1542, 1491 1370, 1025, 1312; H NMR (CDCl3, 400 MHz): δ =
(naphthalen-2-yl)quinoxaline(4b); Yellow solid; yield 94%; (Rf =
0.60 in hexanes/ EtOAc 95:05 v/v); MP 136-138 OC; IR (KBr): 3038,
1546, 1488, 1306, 1196 cm-1; 1H NMR (CDCl3, 400 MHz): δ = 9.47(s,
9.35 (s, 1H), 9.34 (s, 1H), 8.77 (dd, J = 6 Hz, 1.2 Hz, 1H), 8.54 (dt, J =
12.4 Hz, 2 Hz, 1H), 8.20–8.12 (m, 2H), 7.85–7.77 (m, 2H), 7.53 – 7.50
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(m, 1H); HRMS (ESI) [M+H]+ calculated C13H9N3 208.0830 found 7.81–7.31 (m, 3H), 7.05 (dd, J = 11.6 Hz, 2.8 Hz, 1H), 3.99 (q, J = 16
208.0832
Hz, 7.2 Hz, 2H), 1.58 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz);
2-(thiophen-2-yl) quinoxaline (4k): Pale yellow solid; yield 94%; (Rf 157.47, 152.02, 141.81, 141.57, 140.67, 136.50, 132.29, 130.89,
o
= 0.42 in hexanes/ EtOAc 95:05 v/v); MP 116-118 C; IR (KBr): 3120, 130.47, 129.04, 128.24, 127.90, 126.53, 125.73, 121.04, 114.27,
1
3056, 1546, 1424, 1328, 1052 cm-1; H NMR (CDCl3, 400 MHz): δ = 110.08, 68.64, 15.47; HRMS (ESI) [M+H]+ calculated C22H17FN2O
9.16 (s, 1H), 8.08–7.87 (m, 2H), 7.78–7.68 (m, 3H), 7.58 (d, J = 4 Hz, 345.1358 found 345.1356
1H), 7.56 (dd, J = 6.4 Hz, 1.6 Hz, 1H); HRMS (ESI) [M+H]+ calculated
2-(2'-chloro-[1,1'-biphenyl]-4-yl)quinoxaline (4s): White solid; yield
93%; (Rf = 0.50 in hexanes/ EtOAc 95:05 v/v); MP 133-135 OC; IR
C12H9N2S 213.0483 found 213.0482
2-(furan-2-yl)quinoxaline (4l): Pale yellow solid; yield 93%; (Rf =
(KBr): 3052, 1528, 1480, 1476, 1416, 1312, 1051, 748 cm-1; 1H NMR
(CDCl3, 400 MHz): δ = 9.37 (s, 1H), 8.27 (d, J = 12 Hz, 2H), 8.17–8.11
(m, 2H), 7.77 (m, 2H), 7.65 (d, J = 8 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H),
7.40–7.29 (m, 3H); 13C NMR (CDCl3, 100 MHz) : δ = 151.4, 143.2,
142.3, 141.6, 141.3, 139.7, 136.0, 132.5, 131.2, 130.2, 130.0, 129.6,
129.5, 129.1, 128.9, 127.2, 126.9; HRMS (ESI) [M+H]+ calculated
C20H13ClN2 318.0737 found 318.0738
0.46 in hexanes/ EtOAc 95:05 v/v); MP 131-133 oC; IR (KBr): 3134,
3118, 1608, 1548, 1444, 1296, 1225, 1126, 1080 cm-1; 1H NMR
(CDCl3, 400 MHz): δ = 9.25 (s, 1H), 8.11-8.06 (m, 2H), 7.78-7.68 (m,
3H), 7.31 (d, J = 4 Hz, 1H), 6.63 (dd, J = 4.8 Hz, 1.2 Hz, 1H); HRMS
(ESI) [M+H]+ calculated C12H8N20 197.0670 found 197.0672
6-bromo-2-(pyridin-3-yl)quinoxaline (Regio isomers) (4n):
A
mixture of two region-isomers (1) and (2), not separable by column
chromatography, was obtained as white solid. The NMR spectra
indicated that it is a mixture.White solid; yield 92%; (Rf = 0.42 in
hexanes/ EtOAc 95:05 v/v); IR (KBr): 3066, 1608, 1548, 1490, 1318,
648 cm-1; 1H NMR (CDCl3, 400 MHz): δ = 9.46 (s,1H), 9.38 (s, 1H),
8.83 (s, 1H), 8.57-8.56 (t, J = 3.6 Hz, 1H), 8.36 (t, J = 2 Hz, 1H), 8.08-
8.03 (m, 1H), 7.94-7.88 (m, 1H), 7.58-7.54 (m, 1H)
2-(2'-chloro-5'-fluorobiphenyl-4-yl)quinoxaline (4t) : White solid;
yield 90%; (Rf = 0.42 in hexanes/ EtOAc 95:05 v/v); MP 141-143 OC ;
IR (KBr): 3060, 1532, 1484, 1416, 1316, 1050, 734, 688 cm-1; 1H
NMR (CDCl3, 400 MHz): δ = 9.37 (s, 1H), 8.26 (dd, J = 2 Hz, 8.8 Hz,
2H), 8.18-8.12 (m, 2H), 7.81-7.72 (m, 2H), 7.13 (dd, J = 2.8 Hz, 12 Hz,
1H), 7.06-7.02 (m, 1H), 6.94 (dd, J = 4 Hz, 13.2 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): δ = 158.3, 155.9, 152.7, 151.52, 143.3, 141.5,
139.4, 135.6, 130.3, 130.2, 129.6, 129.5, 129.1, 127.2; HRMS (ESI)
[M+H]+ calculated C20H12ClFN2 336.0643 found 336.0643
2-([1,1'-biphenyl]-4-yl)quinoxaline (4o): Colorless solid; yield 95%;
(Rf = 0.44 in hexanes/ EtOAc 95:05 v/v); MP 132-134 OC; IR (KBr):
3060, 1534, 1486, 1420, 1317, 1054 cm-1; 1H NMR (CDCl3, 400 MHz):
δ = 9.38 (s, 1H), 8.33 (d, J = 8Hz, 2H), 8.19–8.13 (m, 2H), 7.95 (t, J =
6.4 Hz, 2H), 7.83–7.75 (m, 2H), 7.69 (t, J = 7.6 Hz, 1H), 7.47–7.40 (m,
2H); 13C NMR (CDCl3, 100 MHz): δ = 150.99, 142.96, 142.36, 141.81,
141.57, 14.50, 140.67, 136.70, 132.19, 130.72, 130.47, 130.01,
129.63, 129.04, 128.24, 127.90, 126.43, 125.83, 121.04, 119.17;
HRMS (ESI) [M+H]+ calculated C20H14N2 283.1190 found 283.1191
2-(2'-methylbiphenyl-4-yl)quinoxaline (4p) : White solid; yield 94%;
(Rf = 0.46 in hexanes/ EtOAc 95:05 v/v); MP 128-130 OC; IR (KBr):
3065, 2910, 1560, 1480, 1415, 1312, 1052 cm-1; 1H NMR (CDCl3, 400
MHz): δ = 9.39 (s, 1H), 8.26 (dd, J = 2 Hz, 8.4 Hz, 2H), 8.19-8.13 (m,
2H), 7.83-7.75 (m, 2H), 7.55 (d, J = 8 Hz, 2H), 7.32-7.29 (m, 4H), 2.34
(s, 3H); 13C NMR (CDCl3, 100 MHz): δ = 151.7, 144.0, 143.3, 141.5,
141.0, 135.3, 135.2, 130.5, 130.1, 129.6, 129.5, 129.1, 127.6, 127.3,
125.9, 20.5; HRMS (ESI) [M+H]+ calculated C21H16N2 297.1347 found
297.1346
2-(3'-(methylsulfonyl) biphenyl-4-yl) quinoxaline (4u): Pale yellow
solid; yield 95%; (Rf = 0.48 in hexanes/ EtOAc 95:05 v/v); MP 137-
139 OC ; IR (KBr): 3062, 2886, 1530, 1488, 1414, 1317,1112, 1060
1
cm-1; H NMR (CDCl3, 400 MHz): δ = 9.39 (s, 1H), 8.34 (d, J = 8.8 Hz,
2H), 8.24 (t, J = 4 Hz, 1H), 8.21-8.14 (m, 2H), 7.99-7.95 (m, 2H), 7.83
(d, J = 8 Hz, 2H), 7.81-7.78 (m, 2H), 7.71 (t, J = 12 Hz, 1H), 7.48-7.40
(m, 2H), 3.14 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ = 156.9, 151.0,
143.0, 142.3, 141.7, 140.6, 136.6, 132.2, 130.7, 129.0, 128.2, 127.9,
126.4, 125.8, 121.1, 44.5; HRMS (ESI) [M+H]+ calculated
C21H16N2O2S 361.0966 found 361.0965
4'-(quinoxalin-2-yl)-[1,1'-biphenyl]-3-carbonitrile (4v): White solid;
yield 90%; (Rf = 0.46 in hexanes/ EtOAc 95:05 v/v); MP 129-131 OC ;
IR (KBr): 3056, 2228, 1531, 1482, 1417, 1319, 1052 cm-1; 1H NMR
(CDCl3, 400 MHz); δ = 9.57 (s, 1H), 9.37 (s, 1H), 9.21 (s, 1H), 8.50 (s,
1H), 8.32 (d, J = 8.4 Hz, 2H), 8.18–8.12 (m, 2H), 7.79 (d, J = 8.4 Hz,
2H); 13C NMR (CDCl3, 100 MHz): δ = 164.6, 162.2, 150.9, 145.9,
145.9, 145.84, 142.3, 141.6, 139.7, 139.6, 138.3, 136.5, 134.0,
2-(5'-fluoro-2'-methoxybiphenyl-4yl)quinoxaline (4q) : White solid;
yield 92%; (Rf = 0.42 in hexanes/ EtOAc 95:05 v/v); MP 134-136OC ;
IR (KBr): 3058, 2858, 1528, 1482, 1418, 1145, 1315, 1052, 686 cm-1;
1H NMR (CDCl3, 400 MHz): δ = 9.38 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H),
8.19-8.12 (m, 2H), 7.82-7.77 (m, 2H), 7.76-7.72 (m, 2H), 7.13 (dd, J =
2.8 Hz, 8.8 Hz, 1H), 7.07-6.93 (m, 2H), 3.8 (s, 3H); 13C NMR (CDCl3,
100 MHz): δ = 158.3, 155.9, 152.7, 151.5, 143.3, 142.3, 141.5, 139.4,
135.6, 130.3, 130.1, 129.6, 129.5, 129.1, 127.2, 56.2; HRMS (ESI)
[M+H]+ calculated C21H16N2 331.1202 found 331.1201
130.4, 129.6, 128.2, 115.6, 109.8, 109.4;
calculated C21H13N2 308.1143 found 308.1144
HRMS (ESI) [M+H]+
2-(4-(pyridin-4-yl)phenyl)quinoxaline (4w) : White solid; yield 91%;
(Rf = 0.44 in hexanes/ EtOAc 95:05 v/v); MP 138-140 OC ; IR (KBr):
3056, 1529, 1486, 1418, 1315, 1062 cm-1; 1H NMR (CDCl3, 400 MHz):
δ = 9.39 (s, 1H), 8.7 (d, J = 7.2 Hz, 1H), 8.51 (d, J = 2.4 Hz, 1H), 8.36
(dt, J = 2 Hz, 8.8 Hz, 2H), 8.20-8.14 (m, 2H), 7.83 (dd, J = 1.6 Hz, 8.4
Hz, 1H), 7.82–7.76 (m, 4H), 7.68 (dt, J = 2.8 Hz, 12 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): δ = 150.8, 144.0, 143.0, 142.32, 141.7, 138.0,
137.0, 130.4, 129.6, 129.1, 128.3, 127.9, 121.1, 120.9; HRMS (ESI)
[M+H]+ calculated C19H13N3 284.1143 found 284.1142
2-(2'-ethoxy-4'-fluoro-[1,1'-biphenyl]-4-yl)quinoxaline (4r): White
solid; yield 92%; (Rf = 0.42 in hexanes/ EtOAc 95:05 v/v); MP 136-
138 OC ; IR (KBr): 3052, 2890, 1532, 1483, 1427, 1319, 1055, 812 cm-
1; 1H NMR (CDCl3, 400 MHz): δ = 9.37 (s, 1H), 8.18 (d, J = 1.6 Hz, 1H),
8.15 (d, J =6.8 Hz, 2H), 8.14–8.05 (m, 2H), 8.04 (d, J = 8 Hz, 2H),
6 | J. Name., 2012, 00, 1-3
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2-(4-(5-fluoropyridin-3-yl)phenyl)quinoxaline (4x): White solid; 6-nitro-2,3-diphenylquinoxaline (5n): Yellow solid; yield 95%; (Rf =
yield 90%; (Rf = 0.46 in hexanes/ EtOAc 95:05 v/v); MP 139-141 OC ; 0.52 in hexanes/ EtOAc 95:05 v/v); MP 183-185 OC; IR (KBr): 3080,
1
IR (KBr): 3056, 1528, 1489, 1413, 1316, 1048, 694 cm-1; 1H NMR 3057, 1612, 1518, 1398, 1340, 1054, 1023, 810, 767, 698 cm-1; H
(CDCl3, 400 MHz): δ = 9.38 (s,1H), 8.52 (d, J = 2 Hz, 1H) ), 8.34 (d, J = NMR (CDCl3, 400 MHz): δ = 9.08 (d, J = 2.4 Hz, 1H), 8.54 (dd, J = 11.6
8.4 Hz, 2H ), 8.20-8.13 (m, 2H), 8.09-8.05 (m, 1H), 7.84-7.78 (m, 2H), Hz, 2.4 Hz, 1H), 8.30 (d, J = 9.2 Hz, 1H), 7.58–7.54 (m, 4H), 7.43–7.36
7.76 (d, J = 8.4 Hz, 2H), 7.07 (dd, J = 3.2 Hz, 12 Hz, 1H); 13C NMR (m, 6H); HRMS (ESI) [M+H]+ calculated C20H13Cl2N3O2 328.1081
(CDCl3, 100 MHz); δ = 150.9, 145.9, 145.8, 143.0, 141.6, 139.3, found 328.1082
136.5, 134.0, 130.5, 129.6, 129.1, 128.1, 128.2, 127.7, 109.8, 109.5; 2,3-diphenyl-4a,5,6,7,8,8a-hexahydroquinoxaline (5p): White solid;
HRMS (ESI) [M+H]+ calculated C19H12FN3 302.1048 found 302.1047
yield 90%; (Rf = 0.48 in hexanes/ EtOAc 95:05 v/v); MP 171–176 OC;
IR (KBr): 3048, 2936, 1612 cm-1; 1H NMR (CDCl3, 400 MHz): δ = 7.55-
7.49 (m, 4H), 7.28-7.20 (m, 6H), 2.84 (t, J = 9.2 Hz, 2H), 2.50 (d, J =
13.6 Hz, 2H), 1.89 (d, J = 9.2 Hz, 2H), 1.64–1.62 (m, 2H), 1.47-1.39
(m, 2H); HRMS (ESI) [M+H]+ calculated C20H20N2 289.1660 found
289.1661
2,3-bis(4-methoxyphenyl)quinoxaline (5b): White solid; yield 96%;
(Rf = 0.42 in hexanes/ EtOAc 95:05 v/v); MP 146-148 OC ; IR (KBr):
3008, 2964, 2842, 1604, 1508, 1460, 1392, 1346, 1286, 1240, 1172,
1
1024, 828, 764 cm-1; H NMR (CDCl3, 400 MHz,): δ = 8.14–7.91 (m,
2H), 7.6–7.37 (m, 3H), 7.34 (d, J = 8.4 Hz, 4H), 7.33 (d, J = 7.2 Hz,
4H), 3.82 (s, 6H); HRMS (ESI) [M+H]+ calculated C22H18N202
343.1441 found 343.1440
Acknowledgment:
KSR thanks UGC for providing UGC-BSR fellowship to KBH. We are
also thankful to Institute of Excellence (IOE) for providing NMR and
HRMS Facility, University of Mysore, Manasagangotri, Mysuru-
570006, India, for spectral data.
2-methyl-3-phenylquinoxaline (5d): White solid; yield 92%; (Rf =
0.44 in hexanes/ EtOAc 95:05 v/v); MP 54-56 OC ; IR (KBr): 3122,
1510, 1461, 1318, 1054, 719 cm-1; 1H NMR (CDCl3, 400 MHz): δ =
8.25–8.11 (m, 2H), 7.73–7.17 (m, 4H), 7.5–7.51 (m, 3H), 2.73 (s, 3H);
HRMS (ESI) [M+H]+ calculated C15H12N2 221.1034 found 221.1033
quinoxaline (5e): White solid; yield 90%; (Rf = 0.42 in hexanes/
EtOAc 95:05 v/v); MP 30-32 OC ; IR (KBr); 1498, 1364, 1202, 1128,
1028, 956 cm-1; 1H NMR (CDCl3, 400 MHz): δ = 8.82 (s, 2H), 8.12 (d, J
= 8 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H); HRMS (ESI) [M+H]+ calculated
C8H6N2 131.0564 found 131.0565
References:
1.
(a) A. Gomtsyan, E. K. Bayburt, R. G. Schmidt, G. Z. Zheng,
R. J. Perner, S. Didomenico, J. R. Koenig, S. Turner, T.
Jinkerson and I. Drizin, Journal of medicinal chemistry,
2005, 48, 744-752.(b) W. He, M. R. Myers, B. Hanney, A.
P. Spada, G. Bilder, H. Galzcinski, D. Amin, S. Needle, K.
Page and Z. Jayyosi, Bioorganic & medicinal chemistry
letters, 2003, 13, 3097-3100. (c) A. Jaso, B. Zarranz, I.
Aldana and A. Monge, Journal of medicinal chemistry,
2005, 48, 2019-2025. (d) R. Sarges, H. R. Howard, R. G.
Browne, L. A. Lebel, P. A. Seymour and B. K. Koe, Journal
of medicinal chemistry, 1990, 33, 2240-2254. (e) L. E.
Seitz, W. J. Suling and R. C. Reynolds, Journal of medicinal
chemistry, 2002, 45, 5604-5606.
2-(4-chlorophenyl)-3-phenylquinoxaline (5f): White solid; yield
94%; (Rf = 0.40 in hexanes/ EtOAc 95:05 v/v); MP 135-137 OC ; IR
(KBr): 3058, 2926, 1724, 1588, 1490, 1472, 1440, 1398,1342, 1087,
1056, 1012, 966, 848, 806, 760, 696 cm-1; 1H NMR (CDCl3, 400 MHz):
δ = 8.20-8.13 (m, 2H), 8.09–8.07 (m, 2H), 8.05–7.82 (m, 4H), 7.80–
7.78 (m, 3H), 7.75 (d, J = 8.4 Hz, 2H); HRMS (ESI) [M+H]+ calculated
C20H13Cl2N2 317.0840 found 317.0841
2,3-bis(4-methoxyphenyl)-6,7-dimethylquinoxaline (5h): Yellow
solid; yield 95%; (Rf = 0.42 in hexanes/ EtOAc 95:05 v/v); MP 122-
124 OC ; IR (KBr): 2930, 2833, 1603, 1508, 1455, 1417, 1340, 1298,
1172, 1023, 965, 828 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.82 (s,
2H), 7.60 (d, J = 8.4 Hz, 4H), 7.10 (d, J = 7.6 Hz, 4H), 3.92 (s, 6H), 2.42
(s, 6H); HRMS (ESI) [M+H]+ calculated C24H22Cl2N2O2 371.1754 found
371.1754
2.
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and L. M. Gutierrez-Tunstad, Organic letters, 2004, 6, 333-
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6-bromo-2,3-di(furan-2-yl)quinoxaline (5k) : White solid; yield 96%;
(Rf = 0.54 in hexanes/ EtOAc 95:05 v/v); MP 132–134 OC; IR (KBr):
3359, 1541, 1428, 1071, 835, 756 cm-1 1H NMR (CDCl3, 400 MHz): δ
;
= 8.36 (d, J = 1.6 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.86 (dd, J = 2.4 Hz,
2.4 Hz, 1H), 7.68 (t, J = 1.6 Hz, 2H), 6.76–6.75 (m, 2H), 6.63-6.61
(m.2H); HRMS (ESI) [M+H]+ calculated C16H9BrN2O2 341.9826 found
341.9824
6-chloro-7-fluoro-2,3-diphenylquinoxaline (5m): White solid; yield
94%; (Rf = 0.58 in hexanes/ EtOAc 95:05 v/v); MP 158-160 OC; IR
1
(KBr): 3418, 1466, 1344, 1216, 702 cm-1; H NMR (CDCl3, 400 MHz):
δ = 8.24 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.80–7.28 (m,
4H), 7.14–7.01 (m, 6H); HRMS (ESI) [M+H]+ calculated
C20H12Cl2N2FCl 335.0746 found 335.0748
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DOI: 10.1039/C6RA03078E
COMMUNICATION
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DOI: 10.1039/C6RA03078E
One-step Approach for Synthesis of Functionalized Quinoxalines Mediated by
T3P® - DMSO or T3P® via Tandem Oxidation – Condensation or Condensation
Reaction
Kachigere B. Harsha,a# Kanchugarkoppal S. Rangappa.a*