Novel multi-component synthesis of 1,4-disubstituted pyrrolo[1,2-a]quinoxalines through palladium-catalyzed coupling reaction/hetero-annulation in water

Article abstract of DOI:10.1016/j.tet.2016.08.067

1,4-Disubstituted pyrrolo[1,2-a]quinoxalines were prepared through the one-pot multi-component reactions of 3-substituted-2-chloroquinoxalines, propargyl alcohol, and secondary amines, catalyzed by Pd/Cu, in the presence of K₂CO₃and sodium dodecyl sulfate (SDS) in water. This process provided a facile, eco-friendly, and highly efficient method for the synthesis of new pyrrolo[1,2-a]quinoxalines in water with good yields.

Full text of DOI:10.1016/j.tet.2016.08.067

Accepted Manuscript
Novel multi-component synthesis of 1,4-disubstituted pyrrolo[1,2-a]quinoxalines
through palladium-catalyzed coupling reaction/hetero-annulation in water
Ali Keivanloo, Shaghayegh Sadat Kazemi, Hossein Nasr-Isfahani, Abdolhamid
Bamoniri
PII:
S0040-4020(16)30852-3
10.1016/j.tet.2016.08.067
TET 28048
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 May 2016
Revised Date: 6 August 2016
Accepted Date: 23 August 2016
Please cite this article as: Keivanloo A, Kazemi SS, Nasr-Isfahani H, Bamoniri A, Novel multi-component
synthesis of 1,4-disubstituted pyrrolo[1,2-a]quinoxalines through palladium-catalyzed coupling reaction/
hetero-annulation in water, Tetrahedron (2016), doi: 10.1016/j.tet.2016.08.067.
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ACCEPTED MANUSCRIPT
Novel multi-component synthesis of 1,4-disubstituted pyrrolo[1,2-
a]quinoxalines through palladium-catalyzed coupling reaction/hetero-
annulation in water
Ali Keivanloo*, Shaghayegh Sadat Kazemi, Hossein Nasr-Isfahani, Abdolhamid Bamoniri
1,4-Disubstituted pyrrolo[1,2-a]quinoxalines were prepared through the one-pot multi-
component reactions of 3-substituted-2-chloroquinoxalines, propargyl alcohol, and secondary
amines, catalyzed by Pd/Cu, in the presence of K2CO3 and sodium dodecyl sulfate (SDS) in
water. This process provided a facile, eco-friendly, and highly efficient method for the synthesis
of new pyrrolo[1,2-a]quinoxalines in water with good yields.

ACCEPTED MANUSCRIPT
Novel multi-component synthesis of 1,4-disubstituted pyrrolo[1,2-
a]quinoxalines
through
palladium-catalyzed
coupling
reaction/hetero-annulation in water
Ali Keivanlooa*, Shaghayegh Sadat Kazemia, Hossein Nasr-Isfahania, Abdolhamid
Bamonirib
a School of Chemistry, University of Shahrood , Shahrood, Iran
b Chemistry Faculty, University of Kashan, Kashan, Iran
Abstract- 1,4-Disubstituted pyrrolo[1,2-a]quinoxalines were prepared through the
one-pot multi-component reactions of 3-substituted-2-chloroquinoxalines, propargyl
alcohol, and secondary amines, catalyzed by Pd/Cu, in the presence of K2CO3 and
sodium dodecyl sulfate (SDS) in water. This process provided a facile, eco-friendly,
and highly efficient method for the synthesis of new pyrrolo[1,2-a]quinoxalines in
water with good yields.
1. Introduction
Multi-component reactions1 (MCRs) are powerful and popular chemical methods for
the construction of novel molecular structures and for drug discovery2 in modern
synthetic organic chemistry. The main advantages of MCRs are high atom economy,
energy saving, low cost, short reaction time, and avoiding time-consuming
purification processes.3 Typically, MCRs are environmentally friendly, allowing
access to a large number of compounds with diverse functionalities, without any
* Corresponding Author. Fax: +98 23323395441
E-mail addresses: akeivanloo@yahoo.com and keivanloo@shahroodut.ac.ir
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protection and deprotection steps, for possible combinatorial surveys of structural
variations.4 Therefore, the discovery of new MCRs and improving known MCRs are
area of current significant interest.
Nitrogen countaing heterocycles are present in a wide spectrum of organic molecules,
and they are foremost in synthetic chemistry. Quinoxalines, which are an important
class of nitrogen-containing heterocyclic compounds, have diverse biological
properties such as anti-HIV,5 anti-cancer,6 and anti-inflammatory7. Pyrrolo[1,2-
a]quinoxalines and their analogues have outstanding roles in natural products,8
displaying broad pharmacological activities such as anti-tumor,9 adenosine A3
receptor modulator,10 anti-parasitic,11 and anti-HIV.12 Moreover, they are significant
intermediates for the construction of 5-HT3 receptor agonists.13 Consequently, the
progression of novel and highly efficient methods for the synthesis of pyrrolo[1,2-
a]quinoxaline derivatives is highly favorable for drug discovery.
Cross-coupling reactions catalyzed by transition metals are important processes for
building new carbon-carbon bonds.14 Recently, the palladium-catalyzed coupling
reactions of terminal acetylenic compounds with aromatic halides have been used in
the synthesis of different compounds such as heterocycles, a number of natural
products,15 and pharmaceuticals.16
Organic solvents are usually used as the reaction media in most catalytic reactions,
mostly causing a great deal of safety, health, and environmental hazards due to their
toxicity, flammability, and volatility. Due to the economic and environmental
viewpoints, it is favorable to avoid the use of hazardous and expensive organic
solvents. One of the most economically and environmentally viable alternatives to
organic solvents is the use of water as the solvent or aqueous medium for the
reactions catalyzed by palladium salts.17
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Many methods have been reported for the synthesis of pyrrolo[1,2-a]quinoxaliens
such as the 1,3-dipolar cycloaddition reaction,18 three-component reaction of 1,2-
diamines, ethyl pyruvate, and α-bromo ketones,19 hydroamination and hydroarylation
of pyrrolo-substituted anilines and alkynes by gold catalyst,20 reaction of α-amino
acids with 1-(2-halophenyl)-1H-pyrroles via a copper catalyst in aerobic oxidative
domino reaction,21 and one-pot coupling/hydrolysis/condensation of 2-
halotrifluoroacetanilides with pyrrolo-2-carboxylate esters.22
2. Results and discussion
Continuing our studies directed toward efficient and straightforward synthesis of
biologically-active molecules based on the quinoxaline ring system through
palladium-catalyzed reactions,23-26 we carried out the synthesis of new derivatives of
1,4-disubstituted pyrrolo[1,2-a]quinoxaline via MCRs of
3-substituted-2-
chloroqunoxalines, propargyl alchohol, and secondary amines, catalyzed by Pd/Cu, in
water, as the solvent (Scheme 1).
Scheme 1. Palladium-catalyzed coupling reaction/hetero-annulation of 3-substituted 2-
chloroquinoxaline with propargyl alcohol and secondary amines in watera.
a Reaction conditions: 2a-e (1 mmol), 3 (1.2 mmol), a secondary amine (3 mmol), K2CO3 (3
mmol), Pd(PPh3)2Cl2 (0.05 mmol), CuI (0.1 mmol), SDS (10 mol%), distilled H2O (5 mL),
80 ºC, 18 h, argon atmosphere.
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In order to introduce two substituents to the pyrrolo[1,2-a]quinoxaline-fused ring
system, our retrosynthetic analysis revealed the use of a 3-substituted 2-
chloroquioxaline, propargyl alcohol, and a secondary amine as the starting materials
(Scheme 2). The palladium-catalyzed cross-coupling reaction is the key step in this
process.
Scheme 2. Retrosynthetic analysis of 1,4-disubstituted-5H-pyrrolo[1,2-a]quinoxaline system.
Treatment of 2,3-dichloroquinoxaline with secondary amines in acetonitrile at 80 °C
or sodium alkoxides in related alcohols at room temperature produced 3-substituted 2-
dichloroquioxalines 2a-e in 70-90% yields.24,27 The results obtained are shown in
Table 1 (Scheme 3).
Scheme 3. Synthesis of 3-substituted 2-chloroquioxalines from 2,3-dichloroquinoxaline and
secondary amines or sodium alkoxidesa.
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a Conditions: 2,3-Dichloroquinoxaline (1 mmol), an amine (2 mmol) at 80 °C in acetonitrile
or sodium alkoxide (1 mmol) at room temperature in alcohol.
Table 1.
Melting points and yields of 3-substituted 2-chloroquinoxalines 2a-e obtained from
reactions of 2,3-dichloroquinoxaline with secondary amines or alkoxides.a
Entry
Amine/Alkoxide
Morpholine b
Piperidine b
Pyrrolidine b
Methoxide c
Ethoxide c
Product
2a
MP (°C)
77-79
64-66
71-73
65-67
52-54
Yield (%)
1
2
3
4
5
90
85
75
85
70
2b
2c
2d
2e
a Conditions: 2,3-Dichloroquinoxaline (1 mmol), an amine (2 mmol) or sodium
alkoxide (1 mmol).
b At 80 °C in acetonitrile.
c At room temperature in methanol or ethanol.
When 2-chloro-3-morpholinoquinoxaline (2a) was reacted with propargyl alcohol (3)
and morpholine in the presence of bis-triphenylphosphine palladium(II) chloride,
copper(I) iodide, and Et3N at 80 °C in DMF, 1,4-di(morpholin-4yl)pyrrolo[1,2-
a]quinoxaline (4a) was obtained in 60% yield (Table 2, entry 1).
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Table 2: Optimization table for one-pot synthesis of 1-morpholino-4-(piperidin-1-
yl)pyrrolo[1,2-a]quinoxaline.a
O
O
H
N
N
N
N
OH
catalyst
solvent
N
N
N
+
+
base
O
additive
Cl
N
3
4a
2a
O
Entry
Solvent
Base
Et3N
Catalyst
Co-
SDS
Yield
Catalyst
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
-
1
2
DMF
DMF
DMF
CH3CN
CH3CN
CH3CN
CH3CN
H2O
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd/C (10 mol%)
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd/C (10 mol%)
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
-
60
75
45
60
75
55
30
66
87
10
20
25
40
Morpholine
K2CO3
Et3N
-
3
-
4
-
5
Morpholine
DIPEA
Et3N
-
6
-
7
-
8
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
5 mol%
10 mol%
10 mol%
10 mol%
-
9
H2O
10
11
12
13
H2O
H2O
H2O
CuI
CuI
H2O
10 mol%
a Reaction conditions: 2a (1 mmol), 3 (1.2 mmol), secondary amine (3 mmol), morpholine (3
mmol), catalyst (0.05 mmol), CuI (0.1 mmol), SDS, distilled solvent (5 mL), 80 ºC, 18 h,
argon atmosphere.
The effects of the solvent, base, and catalyst used were studied, and the results
obtained were tabulated in Table 2. We screened DMF, CH3CN, and water as the
solvent in the presence of an organic or inorganic base such as Et3N, morpholine,
DIPEA, and carbonate salts. Surprisingly, we found that water was an efficient
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solvent for the reaction in the presence of sodium dodecyl sulfate (SDS). Potassium
carbonate was found to be the most suitable base, giving a cleaner product and a
better yield. The Pd(PPh3)2Cl2-CuI catalytic system was found to be the optimal.
Moreover, the use of CuI was found to be essential for the reaction progress; the
reaction carried out without CuI led to only a 20% product. The effect of surfactant
was also studied, and the surfactant inclusion was found to be critical for the success
of the reaction; the product yield decreased significantly when no surfactant was used.
In order to explore the scope and generality of this protocol, compounds 2a-e were
reacted with propargyl alcohol (3) and various secondary amines in the presence of
bis-triphenylphosphine palladium(II) chloride, copper(I) iodide, sodium dodecyl
sulfate (SDS), and potassium carbonate at 80 °C in water. 1,4-disubstituted
pyrrolo[1,2-a]quinoxalines 4a-h were obtained in moderate to high yields. The results
obtained are shown in Table 3. The reactions were performed under an argon
atmosphere and degassed water.
Table 3: Synthesis of 1,4-disubstituted pyrrolo[1,2-a]quinoxalines.
3-Substituted 2-
chloroquinoxaline
Yield
(%)
Entry
Product
Mp (°C)
133-135
O
N
N
O
87
N
N
N
N
N
1
Cl
O
4a
N
N
N
N
116-117
65
N
N
2
N
Cl
O
4b
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N
N
N
3
119-120
71
N
N
N
N
Cl
4c
O
N
N
O
N
4
122-123
121-122
68
70
N
N
N
N
Cl
4d
N
N
N
N
N
5
6
7
N
N
Cl
4e
N
OCH3
N
OCH3
N
N
116-118
123-125
119-121
75
70
78
N
Cl
O
4f
N
N
N
OCH2CH3
Cl
OCH2CH3
N
N
4g O
O
N
N
O
N
N
N
8
N
N
Cl
4h
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a Reaction conditions: 2 (1 mmol), 3 (1.2 mmol), secondary amine (3 mmol), K2CO3 (3
mmol), Pd(PPh3)2Cl2 (0.05 mmol), CuI (0.1 mmol), SDS (10 mol%), distilled H2O (5 mL),
80 ºC, 18 h, argon atmosphere.
The structural assignments of compounds 4a-h were based on the NMR spectroscopic
data and mass analysis. The 1H NMR spectrum for 1,4-di(morpholin-4yl)pyrrolo[1,2-
a]quinoxaline (4a) showed a doublet at δ 9.05, which is characteristic of an aromatic
proton at position 9 of the heterocyclic system; it was deshielded by the diamagnetic
pyrrole ring current. The other three aromatic protons in the quinoxaline ring
appeared at δ 7.25-7.67. The two doublets at δ 6.71 and δ 6.38 were assigned to the
two protons at positions 2 and 3 of the fused pyrrole ring. In the aliphatic region, we
observed 16 protons of two morpholine substituents at positions 1 and 4 of this
heterocyclic system at δ 2.92-4.03.
A plausible multi-step mechanism can be suggested for the reaction (Scheme 4). First
a standard Sonogashira coupling takes place by a Pd0/CuI catalyzed reaction, followed
by a Cu(I)-catalyzed isomerization to the allene intermediate A, continuing to an
enone aldehyde B, an iminium ion C, the intramolecular cyclization to the fused ring
system D, and finally, a base-induced aromatization to afford the product.
Scheme 4. Proposed mechanism for formation of 1,4-disubstituted pyrrolo[1,2-a]quinoxalines
from 3-substituted 2-chloroquinoxalines, propargyl alcohol, and secondary amines.
9

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Conclusion
We have demonstrated an efficient and successful process for the synthesis of 1,4-
disubstituted pyrrolo[1,2-a]quinoxalines via the multi-component reactions of 3-
substituted-2-chloroqunoxalines, propargyl alcohol, and secondary amines, catalyzed
by Pd/Cu, in water, as the solvent. Since water-based syntheses are safer and
environmentally-friendly, the method described may hold promise in organic
chemistry.
3. Experimental
3.1. General method
Palladium(II) chloride and propargyl alcohol were purchased from Sigma Aldrich
Chemical Company. Triphenylphosphine, N,N-dimethylformamide, triethylamine,
secondary amines, thin-layer chromatography (TLC) plates, silica gel (particle size,
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100-200 mesh), and all the solvents used for the reactions were purchased from
1
Merck. NMR spectra were recorded on Bruker 400 MHz H NMR, 100 MHz 13C
1
NMR, 300 MHz H NMR, and 75 MHz 13C NMR spectrometers. 1H NMR spectra
13
were reported relative to Me4Si (δ 0.0) or residual CHCl3 (δ 7.26). C NMR spectra
were reported relative to CDCl3 (δ 77.16). IR spectra were recorded on a Shimadzu
IR-435 grating spectrophotometer. Mass spectra were recorded on a 5975C
spectrometer manufactured by Agilent Technologies Company. Elemental analyses
were performed on a Eager 300 for EA1112 microanalyzer.
1.1. Experimental procedures
Synthesis of 2-chloro-3-amino quinoxalines 2a-c
A mixture of 2,3-dichloroquinoxaline (1 mmol, 0.199 g) and a secondary amine (2
mmol) in acetonitrile was refluxed for 5 h. The complete consumption of the starting
materials was monitored by TLC. After evaporation of the solvent, the resulting
precipitate was washed with H2O; it did not require any further purification.
Synthesis of 2-chloro-3-alkoxyquinoxalines 2d-e
A mixture of sodium (1 mmol, 0.023 g) and alcohol (3 mL) was stirred for 15 min at
room temperature. Then 2,3-dichloroquinoxaline (1 mmol, 0.199 g) was added to the
mixture until the complete consumption of the starting materials, monitored by TLC.
After evaporation of the solvent, the resulting precipitate was washed with H2O; it did
not require any further purification.
Synthesis of 1,4-disubstituted pyrrolo[1,2-a]quinoxalines 4a-h
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A mixture of a 3-substituted-2-chloroquinoxaline 2 (1 mmol), a secondary amine (3
mmol), Pd(PPh3)2Cl2 (0.05 mmol, 0.036 g), CuI (0.1 mmol, 0.019 g), sodium dodecyl
sulfate (0.1 mmol, 0.029 g), and K2CO3 (3 mmol, 0.414 g) was stirred in H2O (5 mL)
at room temperature under an argon atmosphere. Propargyl alcohol (1.2 mmol, 0.067
g) was then added, and the resulting mixture was stirred at 80 °C for 18 h. After
completion of the reaction, the mixture was filtered, and the resulting solid was
washed with H2O and dried. The crude product was purified by column
chromatography (silica gel 100) using CHCl3–CH3OH (99:1) as the eluent.
1,4-di(morpholin-4yl)pyrrolo[1,2-a]quinoxaline 4a
1
Yellow solid; mp 133-135 °C; H NMR (400 MHz, CDCl3): δ 2.92-3.05 (m, 4H,
2NCH2), 3.67-4.03 (m, 12H, 2NCH2, 4OCH2), 6.38 (d, J = 4.4 Hz, 1H, CH of
pyrrole), 6.71 (d, J = 4.4 Hz, 1H, CH of pyrrole), 7.25-7.46 (m, 2H, 2CH of
quinoxaline), 7.67 (m, 1H, CH of quinoxaline), 9.05 (d, J = 7.6 Hz, 1H, CH of
quinoxaline); 13C NMR (75 MHz, CDCl3): δ 49.2, 52.8, 66.8, 66.8, 67.0, 101.1, 105.5,
115.9, 116.9, 123.6, 124.8, 127.3, 127.6, 136.9, 153.5; IR (KBr): 2950, 2840, 1610,
1500, 1120 cm–1; MS (EI), m/z [M]+ 338; Anal. Calcd for C19H22N4O2: C, 67.44; H,
6.55; N, 16.56%. Found: C, 67.32; H, 6.52; N, 16.50%.
1-(morpholin-4-yl)-4-(piperidin-1-yl)pyrrolo[1,2-a]quinoxaline 4b
1
Yellow solid; mp 116-117 °C; H NMR (400 MHz, CDCl3): δ 1.63-2.05 (m, 6H,
3CH2), 2.94-3.00 (m, 2H, NCH2), 3.16-3.19 (m, 2H, NCH2), 3.61-3.79 (m, 4H,
2NCH2), 3.90-4.01 (m, 4H, 2OCH2), 6.35 (d, J = 4.0 Hz, 1H, CH of pyrrole), 6.72 (d,
J = 4.0 Hz, 1H, CH of pyrrole), 7.20-7.31 (m, 2H, 2CH of quinoxaline), 7.64-7.73 (m,
13
1H, CH of quinoxaline), 9.03 (d, J = 7.6 Hz, 1H, CH of quinoxaline); C NMR (75
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MHz, CDCl3): δ 25.1, 26.1, 49.8, 52.8, 66.8, 100.8, 105.6, 115.9, 117.3, 122.9, 124.7,
126.9, 127.4, 137.2, 142.7, 154.1; IR (KBr): 2940, 2850, 1600, 1510, 1100 cm–1; MS
(EI), m/z [M]+ 336; Anal. Calcd for C20H24N4O: C, 71.40; H, 7.19; N, 16.65%.
Found: C, 71.19; H, 7.14; N, 16.68%.
1,4-di(piperidin-1-yl)pyrrolo[1,2-a]quinoxaline 4c
1
Light brown solid; mp 119-120 °C; H NMR (400 MHz, CDCl3): δ 1.95-2.10 (m,
12H, 6CH2), 2.91-2.97 (m, 2H, NCH2), 3.16-3.19 (m, 2H, NCH2), 3.93-3.99 (m, 4H,
2NCH2), 6.33 (d, J = 4.0 Hz, 1H, CH of pyrrole), 6.79 (d, J = 4.4 Hz, 1H, CH of
pyrrole), 7.07-7.11 (m, 1H, CH of quinoxaline), 7.22-7.30 (m, 1H, CH of
quinoxaline), 7.47-7.54 (m, 1H, CH of quinoxaline), 9.01 (d, J = 8.4 Hz, 1H, CH of
quinoxaline); 13C NMR (75 MHz, CDCl3): δ 24.0, 25.1, 25.7, 26.2, 49.9, 53.8, 100.4,
105.7, 116.2, 116.8, 122.8, 124.4, 126.6, 127.7, 137.0, 144.5, 154.1; IR (KBr): 2930,
2850, 1615, 1510, 1490 cm–1; MS (EI), m/z [M]+ 334; Anal. Calcd for C21H26N4: C,
75.41; H, 7.84; N, 16.75%. Found: C, 75.25; H, 7.79; N, 16.66%.
4-(morpholin-4-yl)-1-(piperidin-1-yl)pyrrolo[1,2-a]quinoxaline 4d
1
Brown solid; mp 133-135 °C; H NMR (300 MHz, CDCl3): δ 1.82-1.95 (m, 6H,
3CH2), 2.62-2.70 (m, 2H, NCH2), 3.28-3.36 (m, 2H, NCH2), 3.71-3.72 (m, 4H,
NCH2), 3.91-3.92 (m, 4H, 2OCH2), 6.33 (d, J = 3.6 Hz, 1H, CH of pyrrole), 6.71 (d, J
= 3.9 Hz, 1H, CH of pyrrole), 7.26-7.34 (m, 2H, 2CH of quinoxaline), 7.66-7.68
13
(m,1H, CH of quinoxaline), 9.06 (d, J = 7.8 Hz, 1H, CH of quinoxaline); C NMR
(75 MHz, CDCl3): δ 24.0, 25.7, 49.2, 53.8, 67.0, 100.5, 105.47, 116.2, 116.4, 123.4,
124.5, 127.0, 127.9, 136.8, 144.7, 153.6; IR (KBr): 2950, 2850, 1615, 1520, 1105
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cm–1; MS (EI), m/z [M]+ 336; Anal. Calcd for C20H24N4O: C, 71.40; H, 7.19; N,
16.65%. Found: C, 71.63; H, 7.23; N, 16.53%.
1-(piperidin-1-yl)-4-(pyrrolidin-1-yl)pyrrolo[1,2-a]quinoxaline 4e
1
Yellow solid; mp 121-122 °C; H NMR (300 MHz, CDCl3): δ 1.90-1.94 (m. 10H,
5CH2), 2.78-2.95 (m, 2H, NCH2), 3.06-3.10 (m, 2H, NCH2), 3.81-3.87 (m, 4H,
2NCH2), 6.23 (d, J = 4.5 Hz, 1H, CH of pyrrole), 6.81 (d, J = 4.6 Hz, 1H, CH of
pyrrole), 6.97-7.03 (m, 1H, CH of quinoxaline), 7.12-7.20 (m, 1H, CH of
quinoxaline), 7.47 (m, 1H, CH of quinoxaline), 8.90-8.94 (d, J = 7.5 Hz, 1H, CH of
quinoxaline); 13C NMR (75 MHz, CDCl3): δ 25.5, 40.6, 45.8, 49.1, 52.6, 100.5, 106.8,
115.9, 116.8, 121.0, 124.8, 125.5, 126.3, 138.1, 143.0, 150.0; IR (KBr): 2950, 2850,
1600, 1510, 1330 cm–1; MS (EI), m/z [M]+ 320; Anal. Calcd for C20H24N4: C, 74.97;
H, 7.55; N, 17.48%. Found: C, 75.10; H, 7.59; N, 17.50%.
4-methoxy-1-(morpholin-4-yl)pyrrolo[1,2-a]quinoxaline 4f
Light brown solid; mp 116-118 °C; 1H NMR (300 MHz, CDCl3): δ 2.85-2.92 (m, 2H,
NCH2), 3.06-3.10 (m, 2H, NCH2), 3.60-3.81 (m, 4H, 2OCH2), 3.88 (s, 3H, OCH3),
6.28 (d, J = 3.6 Hz, 1H, CH of pyrrole), 6.61 (d, J = 3.9 Hz, 1H, CH of pyrrole), 7.15-
7.25 (m, 2H, 2CH of quinoxaline), 7.56-7.59 (m, 1H, CH of quinoxaline), 8.96 (d, J =
7.8 Hz, 1H, CH of quinoxaline); 13C NMR (75 MHz, CDCl3): δ 52.8, 55.2, 66.6,
101.3, 105.6, 115.7, 116.9, 123.5, 124.9, 127.3, 127.6, 136.8, 143.0, 153.5; IR (KBr):
2940, 2850, 1610, 1500, 1110 cm–1; M (EI), m/z [M]+ 283, Anal. Calcd for
C16H17N3O2: C, 67.83; H, 6.05; N, 14.83%. Found: C, 67.65; H, 6.01; N, 14.75%.
4-ethoxy-1-(morpholin-4-yl)pyrrolo[1,2-a]quinoxaline 4g
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Dark yellow solid; mp 123-125 °C; 1H NMR (300 MHz, CDCl3): δ 1.17-1.26 (m, 3H,
CH3), 2.87-2.88 (m, 2H, NCH2), 3.06-3.10 (m, 2H, NCH2), 3.55-3.91 (m, 6H,
3OCH2), 6.28 (d, J = 4.2 Hz, 1H, CH of pyrrole), 6.62 (d, J = 4.2 Hz, 1H, CH of
pyrrole), 7.16-7.24 (m, 1H, CH of quinoxaline), 7.30-7.40 (m, 1H, CH of
quinoxaline), 7.44-7.64 (m, 1H, CH of quinoxaline), 8.95 (d, J = 8.2 Hz, 1H, CH of
quinoxaline); 13C NMR (75 MHz, CDCl3): δ 14.8, 52.8, 66.4, 66.9, 101.1, 105.8,
115.9, 116.9, 123.6, 124.8, 127.2, 127.5, 136.6, 143.1, 153.1; IR (KBr): 2950, 2850,
1610, 1500, 1115 cm–1; MS (EI) m/z [M]+ 297; Anal. Calcd for C17H19N3O2: C,
68.67; H, 6.44; N, 14.13%. Found: C, 68.46; H, 6.42; N, 14.21%.
1-morpholino-4-(pyrrolidin-1-yl)pyrrolo[1,2-a]quinoxaline 4h
1
Yellow solid; mp 119-121 °C; H NMR (300 MHz, CDCl3): δ 1.89-1.94 (m, 4H,
2CH2), 2.80-2.88 (m, 2H, NCH2), 3.06-3.10 (m, 2H, NCH2), 3.80-3.87 (m, 8H,
2NCH2, 2OCH2), 6.23 (d, J = 4.2 Hz, 1H, CH of pyrrole), 6.80 (d, J = 4.2 Hz, 1H, CH
of pyrrole), 6.97-7.03 (m, 1H, CH of quinoxaline), 7.12-7.18 (m, 1H, CH of
quinoxaline), 7.44-7.47 (m, 1H, CH of quinoxaline), 8.91 (d, J = 7.8 Hz, 1H, CH of
quinoxaline); 13C NMR (75 MHz, CDCl3): δ 25.6, 49.1, 52.6, 66.81, 100.4, 106.6,
115.9, 116.9, 121.0, 124.8, 125.6, 126.4, 138.3, 142.9, 150.1; IR (KBr): 2940, 2850,
1615, 1520, 1110 cm–1; MS (EI), m/z [M]+ 322; Anal. Calcd for C19H22N4O: C,
70.78; H, 6.88; N, 17.38%. Found: C, 70.85; H, 6.82; N, 17.44%.
Acknowledgment
We wish to express our thanks to the Research Council of the Shahrood University of
Technology for the financial support of this work.
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Supporting Information
1
13
Supporting information for this article is available. Copies of the H and C spectra
of all new compounds were provided.
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