A highly divergent Pictet-Spengler approach for pyrrolo[1,2-a]quinoxalines from aryl amine using 1,2-dinitrobenzene as an oxidant

Article abstract of DOI:10.1016/j.tetlet.2019.151250

A convenient Pictet-Splengler approach for the synthesis of substituted pyrrolo[1,2-a]quinoxalines from aryl amine and 1-(2-aminoaryl)-pyrrole has been developed. This is the first domino protocol involving formation of benzaldehyde as an intermediate from benzyl amines and benzyl alcohols using 1,2-DNB as an oxidant, followed by its endo cyclization with 1-(2-aminophenyl)-pyrrole to furnish the pyrrolo[1,2-a]quinoxalines. Notably, this procedure exhibits good functional group tolerance as well as good to moderate yield of pyrrolo[1,2-a]quinoxaline.

Full text of DOI:10.1016/j.tetlet.2019.151250

Journal Pre-proofs
A Highly Divergent Pictet-Spengler Approach for Pyrrolo[1,2-a]quinoxalines
from Aryl Amine Using 1,2-Dinitrobenzene as an Oxidant
Sachin D. Pardeshi, Bhausaheb N. Patil, Prashant Patil, Atul C. Chaskar
PII:
S0040-4039(19)31030-5
DOI:
https://doi.org/10.1016/j.tetlet.2019.151250
TETL 151250
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
24 July 2019
27 September 2019
2 October 2019
Please cite this article as: Pardeshi, S.D., Patil, B.N., Patil, P., Chaskar, A.C., A Highly Divergent Pictet-Spengler
Approach for Pyrrolo[1,2-a]quinoxalines from Aryl Amine Using 1,2-Dinitrobenzene as an Oxidant, Tetrahedron
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Graphical Abstract
A Highly Divergent Pictet-Spengler Approach for Pyrrolo Leave this area blank for abstract info.
[1,2-a]quinoxalines from Aryl Amine Using
1
,2-Dinitrobenzene as an Oxidant
a,†
a,†,
b
a,
Sachin D. Pardeshi , Bhausaheb N. Patil * Prashant Patil and Atul C. Chaskar *
Het.
N
1,2-DNB (1.0 equiv.),
diglyme (2.0 mL),
N
RI
NH2
Het.
NH2
N
RI
1
30 oC, 9 h
R
R
1,2-Dinitrobenzene as an oxidant
Transition-metal free, Easy work up
Gram scale synthesis
Wide scope, excellent functional group compatibility

1
Tetrahedron Letters
journal homepage: www.elsevier.com
A Highly Divergent Pictet-Spengler Approach for Pyrrolo[1,2-a]quinoxalines
from Aryl Amine Using 1,2-Dinitrobenzene as an Oxidant
a,†
a,†,
b
a,
Sachin D. Pardeshi , Bhausaheb N. Patil * Prashant Patil and Atul C. Chaskar *
a
National Centre for Nanosciences and Nanotechnology, University of Mumbai, Mumbai 400098, India.
VERTChemmieNaupada, Thane 400062, India.
b
Tel.: +91-7507375261; E-mail: achaskar25@gmail.com, manishpatil241187@gmail.com,
†
Authors contributed equally to this work.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A convenient Pictet-splengler approach for the synthesis of substituted pyrrolo[1,2-
a]quinoxaline from aryl amines and 1-(2-aminoaryl)-pyrrole has been developed. This is the first
domino protocol involving formation of benzaldehyde as an intermediate from benzyl amines
and benzyl alcohols using 1,2-DNB as an oxidant, followed by its endo cyclization with 1-(2-
aminophenyl)-pyrrole to furnish the pyrrolo[1,2-a]quinoxaline. Notably, this procedure exhibits
good functional group tolerance as well as good to moderate yield of pyrrolo[1,2-a]quinoxaline.
Available online
Keywords:
Pictet-Spengler reaction,
2
009 Elsevier Ltd. All rights reserved.
1
,2-Dinitrobenzene,
Benzyl amine,
Pyrrolo[1,2-a]quinoxalines,
Diglyme.
antiproliferative activity in GPER expressing cell line.13 Owing
to these characteristic features, in last few decades enormous
progress has been accomplished towards the synthesis of
pyrroloquinoxaline. 4-phenylpyrrolo[1,2-a] quinoxalines are
mainly synthesized via condensation or oxidative cyclization of
Introduction
Over the years, nitro arenes are potentially used for nitro-aldol
and nitro-Mannich reaction leading to construction of carbon-
carbon bonds. Along with this, various nitro groups are converted
into α-aminocarbonyl via Nef reaction.1 In addition, nitro
compounds play vital role in catalytic processes such as Nitro-
Grela catalyst for synthesis of 1,4-benzodioxines via ring closing
1
-(2-aminophenyl)-pyrrole. The condensation of 1-(2-
14
15
aminophenyl)-pyrrole with aryl ketone, aromatic aldehyde,
arylacetic acid,
acid and cyclic ether produces the desired product i.e. 4-
phenylpyrrolo[1,2-a] quinoxalines. Whereas, oxidative
16
17
1,3-diphenylpropane-1,3-dione,
α-amino
2
metathesis and Cobalt-Nitro complex in diglyme for catalytic
18
19
oxidation of palladium bound ethylene to acetaldehyde by
molecular oxygen. Further, 1,2-dinitrobenzene showed proton
transfer rate around 5.0 M S in voltammetric anylysis of
dihomooxacalix[4]arene bidentate urea. In addition to cyclic
voltammetric analysis 1,2-DNB forms anion radical and a
dianion owing to homogenous electron transfer and electro-
reduction process. 1,2-DNB (1,2 –Dinitrobenzene) shows very
3
cyclization of 1-(2-aminophenyl)-pyrrole could be achieved
-1 -1
20
through use of aryl amine. Tongxin Liu and co-workers
4
reported iron-catalyzed intramolecular cyclization of 1-(1-
21
phenyl-H-pyrrol-2-yl)ethan-1-one O-acetyl oxime. Roberto
Sanzet. et. al. synthesized pyrroloquinoxaline from 1-(2-
5
22
nitrophenyl)pyrroles, nitroarene and glycol. In 2008, Guillon et.
6
strong hydrogen bonding towards 1,3-diphenylurea. S. Martínez-
al. synthesized 4-phenylpyrrolo [1,2-a] quinoxaline from 2-
Silvestre and co-workers reported synthesis of 2-
12
nitroaniline via multistep synthesis. Hitherto, reported methods
methylquinoxaline from 1,2-dinitrobenzene and 1,2-propanediol.7
for the synthesis of pyrrolo[1,2-a]quinoxaline are associated with
some shortcomings too, such as use of Lewis acid or metal
catalyst, formation of harmful byproducts, longer reaction time
and high reaction temperature (Figure 1).
Pyrrolo[1,2-a]quinoxaline is considered to be a significant
constituent of many N-heteroarenes and important building block
in synthesis of various bioactive molecules and drugs.
Pyrrolo[1,2-a]quinoxaline derivatives have a broad range of
In this context, Pictet-Spengler is the most promising
approach for the synthesis of pyrrolo[1,2-a]quinoxalines. Herein
benzaldehyde, a key precursor is generated from aryl amine using
8
biological activities such as anti-malarial, glucagon receptor
9
10
3
antagonist, 5-HT receptor, etc. Moreover, structure analogues
of pyrrolo[1,2-a]quinoxaline exhibit proliferation of the human
leukemic cell line and breast cancer cell line.11 Furthermore, a
series of 4-substituted pyrrolo [1,2-a] quinoxaline derivative
show in-vitro antiparasitic activity on Leishmaniaamazonensis
1
,2-dinitrobenzene as an oxidant and eventually condensed in
situ with 1-(2-aminophenyl)-pyrrole to furnish pyrrolo[1,2-
a]quinoxaline (Figure 1). The significant feature of this protocol
is its metal free C-H functionalization mediated formation of
benzaldehyde from air stable aryl amine and tandem synthesis of
N-Heteroarene.
1
2
strain.
In
continuation
to
this,
8-chloro-4-(4-
exhibited
chlorophenyl)pyrrole[1,2-a]quinoxaline

2
amines, bearing -Cl substituent’s at the ortho, meta and para
positions reacted smoothly with (2a) and formed the
corresponding pyrroloquinoxalines 3ba, 3ca and 3da with 85%,
7
9% and 82% of yields, respectively.
1) Pictet-Spengler approach reaction :
Previous Report :
Table 1. Optimization of reaction condition.a
O
N
H
N
NH2
N
N
NH2
Catalyst, Solvent
Temperature
N
NH2
N
1
) AlCl3 (10 mol%), THF, 25 oC, 10 h
Ref. 15a
3aa
1a
2a
OR
2
)
I) p-DBSA, EtOH-H2O, 25 oC ii) KMnO4, 25 o
C
Ref. 15b
Ref. 15c
OR
Temp
(oC)
Yield
Oxidant
O-Xylene, 140 oC, 24 h
Solventc
3)
Entry
(equiv.)
(%)d
This Work :
1
2b
3
-
Diglyme
Diglyme
Diglyme
Diglyme
Diglyme
Xylene
130
130
130
110
90
n.r.
trace
83
N
NH2
1,2-DNB (1.0 equiv.)
diglyme, 130 oC, 9 h
N
1,2-DNB
1,2-DNB
1,2-DNB
1,2-DNB
1,2-DNB
1,2-DNB
1,2-DNB
TEMPO
NH2
N
1a
2a
3aa
4
65
5
50
Figure 1. Synthesis of pyrrolo[1,2-a]quinoxaline.
6
130
130
130
130
130
130
130
70
7
Chlorobenzene
DMF
40
As 1,2-dinitrobenzene is less explored as an oxidant and in
continuation of our interest in metal-free C-H functionalization
mediated tandem synthesis of N-heteroarene23 herein, we report
the synthesis of pyrrolo[1,2-a]quinoxalines from readily available
benzyl amines and 2-aminophenyl pyrrole using 1,2-
dinitrobenzene as an oxidant.
8
trace
70
9
Diglyme
Diglyme
Diglyme
Diglyme
1
0
K
2
S
2
O
8
68
11
Na
2
S
2
O
8
61
1
2
PhI(OAc)
2
72
Results and Discussion
At the outset, we began our studies by optimizing various
reaction parameters such as different oxidants, solvents and
temperature, for the course of reaction (Table 1) The reaction of
[a]Reaction conditions unless specified otherwise: benzyl amine 1a (1.0
mmol), 1,-(2-aminophenyl)pyrrole 2a (1.0 mmol), oxidant (1.0 equiv.) and
1
-(2-aminophenyl)-pyrrole with benzyl amine using diglyme as
solvent (2.0 mL) were heated at 130
o
C for 9 h. [b]0.5 equiv. of 1,2-DNB
o
[c]
solvent at 130 C did not produce pyrrolo[1,2-a]quinoxaline 3aa
Table 1, entry 1). When the same reaction was carried out using
Abbrevations:Diglyme = diethylene glycol dimethyl ether, nr = No
[d]
reaction. Yield of isolated product after column chromatography.
(
0
3
.5 equiv. of 1,2-dinitrobenzene trace amount of desired product
aa was obtained. (Table 1, entry 2). Notably, up to 83%
Pyrroloquinoxalines like 3ea and 3fa were obtained from
reaction of 4-Chloro and 4-Fluoro substituted aryl amine with 2-
aminophenylpyrrole (2a) and both products were obtained with
the percentage yield 86% and 80%, respectively. While,
enhancement in the yield was noticed in the presence of 1.0
equiv. 1,2-dinitrobenzene (Table 1 entry 3) this implies that 1,2-
dinitrobenzene has successfully led C-H functionalization of
benzyl amine. To check the feasibility of the reaction at lower
temperature than 130 C, we carried out the reaction at 110 C
and 90 C respectively and observed that the yield has dropped
drastically with decrease in temperature (Table 1, entry 4 and 5).
To understand the role of solvent, apart from diglyme we used
different solvents viz. xylene, chlorobenzene and DMF for the
reaction but they exhibited good to poor performance. (Table1,
entry 6, 7 and 8). Further, we screened different oxidants such as
(
2,4dichlorophenyl)methanamine on reaction with 1-(2-
aminophenyl)-pyrrole gave 3ga in 84% yield. However, aryl
amine with electron donating substituents (2-OH, 3-OPh, 4-CH
o
o
o
3
and 4-OMe) produced pyrroloquinoxalines 3ha-3ka in good to
excellent yield (74% - 87%) whereas aryl amine bearing electron
withdrawing group as 4-NO has formed 3la in 71% yield. To
2
extend the role of aryl amine we further screened heteroaryl
amine such as 3-pyrrolyl methanamine and 4-pyridinyl
methanamine, and as expected they had produced 3ma and 3na
in 73% and 89% yield under optimized conditions.
TEMPO, K
8% and 61% respectively (Table 1, entry 9, 10 and 11). While,
in presence of PhI(OAc) 72% yield of 3aa was obtained (Table
, entry 12).
2 2 8 2 2 8
S O as well as Na S O which furnished 3aa in70%,
6
2
To widen the substrate scope further we used substituted 1-(2-
aminophenyl)-pyrroles such as 5-methyl-2-pyrrolylaniline, 5-
1
methoxy-2-pyrrolylaniline
and
5-chloro-2-(1H-pyrrol-1-
The wider acceptability of this method would be possible only
when it is generalized with respect to different substituents. So,
we decided to perform the reaction of aryl amines (1a-1n) and 1-
2-aminophenyl)-pyrroles (2a-2c) under optimized conditions
Scheme 2). The reaction was found to be robust and unaffected
by the nature as well as the position of the substituents present on
the aromatic ring. The reaction of benzyl amine (1a) with 1-(2-
aminophenyl)-pyrrole (2a) under optimized conditions offered
3% yield of 3aa. To check the effect of substituents on the
reaction, we used different substituents with various positions of
aryl amine as well as 1-(2-aminophenyl)-pyrrole. In which aryl
yl)aniline with benzyl amine under optimized condition. Notably
they offered 3ab, 3ac and 3ad in 76%, 75% and 66% of yields,
respectively. Moreover, substituted aryl amine also screened. (4-
Nitrophenyl)methanamine reacted smoothly with 5-methyl-2-
pyrrolylaniline and 5-methoxy-2-pyrrolylaniline and furnished
(
(
3
ae and 3af with percentage yield of 74% and 62%. Further, (4-
methoxyphenyl)methanamine reacted efficiently with 5-chloro-2-
pyrrolylaniline and formed 3ag in 72% yield. To explore role of
8
1
,2-DNB as an oxidant for aryl alcohol and to check substrate
scope we performed reaction of substituted aryl alchols like (4-
dimethylamino)phenyl)methanol,4-(hydroxymethyl)benzonitrile
(

3
with 1-(2-aminophenyl)-pyrrole and they had produced 4aa and
ba with 81% and 75% yield (Scheme 3).
the present protocol can also be applied for the gram scale
synthesis of pyrrolo[1,2-a]quinoxaline.
4
Scheme 2. Scope of Various Aryl Amine and 1-(2-
Scheme 3. Scope of various aryl alcohol and 1-(2-
aminophenyl)-pyrrole for the Synthesis of Pyrrolo[1,2-
aminophenyl)-pyrrole for the synthesis of Pyrrolo[1,2-
a,b
a,b
a]quinoxaline
a]quinoxaline
Ar
N
Ar
N
Ar
NH2
1,2-DNB (1.0 equiv.)
diglyme, 130 oC, 9 h
N
Ar
OH
1,2-DNB (1.0 equiv.)
diglyme, 130 oC, 9 h
N
NH2
NH2
N
N
R2
R2
R2
R2
1
a-1n
2a-2c
3aa-3na
3ab-3ag
3a-3b
2a-2d
4aa-4ba
4ab-4ad
R2 : Me, OMe, Cl
R2 : Me, OMe, Cl
N
N
N
N
N
Cl
N
N
N
N
N
N
Cl
N
N
CN
NO2
3aa, 83%
3ba, 85%
3ca, 79%
4aa, 81%
4ba, 75%
4ab, 77%
N
N
N
N
N
N
N
N
N
N
MeO
Cl
F
Br
3da, 82%
3ea, 86%
3fa, 80%
OMe
OMe
4ac, 64%
4ad,
7
3%
N
N
N
N
N
N
OH
Cl
[a]Reaction conditions: arylalcohol 3 (1.0 mmol), 1-(2-aminoaryl) pyrrole) 2
OPh
o
(1.0 mmol), 1,2-DNB (1.0 equiv.), diglyme (2.0 mL) were heated at 130 C
for 9 h. [b]Isolated yields
Cl
3ga, 84%
3ha, 74%
3ia, 81%
To gain more insight into the reaction mechanism, few control
N
N
N
N
N
N
experiments (Scheme 4) had been performed. When benzyl
amine was treated with 1,2-DNB at 130 C for 6 h, benzaldehyde
o
(B) was formed exclusively (Scheme 4a). This has confirmed
OMe
NO2
that the reaction proceeded through direct formation of
3
ja, 78%
3ka, 87%
3la, 71%
benzaldehyde (B) instead of N-benzylphenylmethanimine which
2
0
2
is earlier produced from benzylamine in presence of I catalyst.
N
N
N
N
N
N
This phenomenon adds to the advantage of our protocol as
benzaldehyde can serve as an intermediate for various other
reactions as well unlike the N-benzylphenylmethanimine, which
can not be used elsewhere. Indeed, benzaldehyde reacted
smoothly with 1-2-aminophenylpyrrole in absence of 1,2-DNB
and furnished the product 3aa within 6 h (Scheme 4b) however
in presence of 1,2-DNB it took only 3 h. This implies that
electron deficient nature of 1,2-DNB leads to polarization of
C=O bond of aldehyde as well as abstraction of proton in
aromatization of 4-phenyl-4,5-dihydropyrrolo[1,2-a]quinoxaline,
which eventually enhance the rate of reaction. Moreover,
substituted benzyl amines, N-methyl-1-phenylmethanamine 3o
and N,N-dimethyl-1-phenylmethanamine 3p failed to produce
H
N
N
3
ma, 73%
3na, 89%
3ab, 76%
N
N
N
N
N
N
MeO
Cl
NO2
3
ae, 74%
3
ac, 75%
3ad, 66%
N
N
N
N
MeO
Cl
NO2
o
benzaldehyde in presence of 1,2-DNB at 130 C for 6 h (Scheme
OMe
3
af, 62%
3ag, 72%
4c), this clearly implies that 1,2-DNB can oxidise only primary
amines.
[a]Reaction conditions: arylamine 1 (1.0 mmol), 1-(2-aminoaryl) pyrrole) 2
o
Scheme 4.Control experiments
(
1.0 mmol), 1,2-DNB (1.0 equiv.), diglyme (2.0 mL) were heated at 130 C
for 9 h. [b]Isolated yields
O
NH2
1,2-DNB (1.0 equiv.)
diglyme, 130 oC, 6 h
H
N
(a)
Moreover, substituted aryl alcohol also reacted proficiently
with substituted 1-(2-aminophenyl)-pyrrole and formed
substitued pyrrolo[1,2-a]quinoxaline 4ab, 4ac and 4ad with
percentage yield upto 81%, 75% and 77%, respectively. In view
of the broad substrate scope, the present method eventually was
evaluated for the gram scale synthesis of pyrrolo[1,2-
a]quinoxaline. Gratifyingly, 1 g of benzyl amine produced 0.76
gm of pyrrolo[1,2-a]quinoxaline i.e. 83% interms of percentage
yield under the optimized reaction conditions. This implies that
B
1
a
9
5 % conversion
Not Observed
O
N
diglyme,
oC, 6 h
H
N
NH2
(b)
N
130
B
2a
3aa
9
7 % conversion
O
R1
N
1,2-DNB (1.0 equiv.)
diglyme, 130 oC, 6 h
H
(c)
R2
B
3o-3p
R1 = H R2 = CH3
Not observed
R1 = CH3 R2 = CH3

4
6
616-6618
.
[
[
[
[
4] E. Martínez-González, F. J. González, J. R. Ascenso, P. M. Marcos, C.
Frontana, J. Org. Chem., 2016, 81, 6329-6335.
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Scheme 5. Proposed reaction mechanism
7
08.
6] C. Chan-Leonor, S. L. Martin, D. K. Smith, J. Org. Chem., 2005, 70,
0817-10822.
N
1
H2N
7] M. J. Climent, A. Corma, J. C. Hernández, A. B. Hungría, S. Iborra, S.
O
Martínez-Silvestre, J. Catal., 2012, 292, 118-129.
DNB
DNB
N
2
a
NH2
NH
H
N
[8] (a) J. Guillon, P. Grellier, M. Labaied, P. Sonnet, J. -M. Leger, R. D.
Poulain, I. F. Bares, P. K. Dallemagne, N. Lemaitre, F. Pehourcq, J.
Rochette, C. Sergheraert, C. Jarry, J. Med. Chem., 2004, 47,1997-2009;
SET
A
B
1a
NH3
H2O
C
(b) J. Guillon, E. Mouray, S. Moreau, C. Mullie, I. Forfar, V. Desplat, S.
Belisle-Fabre, N. Pinaud, F. Ravanello, A. Le- Naour, J. -M. Leger, G.
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N
N
O
NH
N
2
011, 46, 2310-2326.
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D
3aa
[
10] a) S. Butini, R. Budriesi, M. Hamon, E. Morelli, S. Gemma, M. Brindisi,
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1
,2-DNB oxidised C-N bond of benzyl amine in situ to
generate aldehyde. Thus, based on our previously reported work
and on the basis of control experiments a plausible mechanism is
depicted in (Scheme 5). Owing to electron deficient character
,2-DNB acts as an acceptor24 and form radical anion while
25
1
benzyl amine acts as donor and form radical cation during single
electron transfer (SET) mechanism.26 Strong hydrogen bonding
tendency of 1,2-DNB converts benzyl amine (1a) into iminium
ion that further undergoes oxidation to generate radical cation [A]
which eventually gets converted into benzaldehyde B under
aerobic condition. The dehydrative condensation of 1-(2-
aminophenyl) pyrrole (2a) and benzaldehyde B leads to
formation of imine [C]15 which follows intramolecular C-C bond
formation by 6-endo-dig attack on C-2 position of the N-
heteroarene to form [D]. Finally oxidative aromatization of [D]
gives the desired product 3aa.
[
[
[
[
[
11] V. Desplat, A. Geneste, M. -A. Begorre, S. B. Fabre, S. Brajot, S.
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Asian J. Org. Chem., 2017, 6, 1579-1583.
Conclusion
We have developed a simple, efficient and one-pot practical
approach to synthesize of pyrrolo[1,2-a]quinoxalines (3aa). Best
of our knowledge 1,2-DNB is used for the first time for
transformation of arylamines (1) and arylalchols (3) into
corresponding aldehydes (B). This protocol could also be used
for gram-scale synthesis. Further, we strongly believe that this
protocol will serve as advancement to the existing methods and
will be widely used for the synthesis of biologically important N-
heteroarene.
[
[
[
[
[
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Zhang, H. Zhai, Asian J. Org. Chem., 2015, 4, 866-869; b) M.
Ramamohan, R. Sridhar, K. Raghavendrarao, N. Paradesi, K. B.
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Acknowledgments
S.D.P. thanks Council of Scientific & Industrial Research,
New Delhi, India for providing a CSIR-SRF fellowship. B.N.P.
thanks UGC for providing SRF fellowship. A.C.C. thanks
[21] Z. Zhang, J. Li, G. Zhang, N. Ma, Q. Liu, T. Liu, J. Org. Chem., 2015,
8
0, 6875-6884.
[22] R. Rubio-Presa, M. R. Pedrosa, M. A. Fernandez-Rodríguez, F. J.
Defence
Research
and
Development
Organization
Arnaiz, R. Sanz, Org. Lett., 2017, 19, 5470-5473.
(
ERIP/ER/1503212/M/01/1666), New Delhi, India for financial
[23] (a) J. J. Lade, B. N. Patil, P. A. Sathe, K. S. Vadagaonkar, P. Chetti, A.
C. Chaskar, ChemistrySelect, 2017, 2, 6811-6817; (b) J. J. Lade, B. N.
Patil, K. S. Vadagaonkar, A. C. Chaskar, Tet. Lett., 2017, 58, 2103-2108;
support. Authors thank Director, National Centre for
Nanosciences and Nanotechnology, University of Mumbai for his
generous support. Authors gratefully acknowledge Department of
Chemistry, University of Mumbai for their generous help and
support.
(c) S. D. Pardeshi, P. A. Sathe, K. S. Vadagaonkar, A. C. Chaskar, Adv.
Synth. Catal., 2017, 359, 4217-4226; (d) S. D. Pardeshi, K.
S
Vadagaonkar, J. J. Lade, L. Melone, A. C. Chaskar, ChemistrySelect,
2017, 2, 5409-5413; (e) S. D. Pardeshi, P. A. Sathe, B. V. Pawar, K. S.
Vadagaonkar, A. C. Chaskar, Eur. J. Org. Chem., 2018, 2018, 2098-
Appendix A. Supplementary data
2
102; (f) S. D. Pardeshi, P. A. Sathe, K. S. Vadagaonkar, L. Melone, A.
C. Chaskar, Synth., 2018, 50, 361-370; (g) P. A. Sathe, K. S.
Vadagaonkar, M. V. Vhatkar, L. Melone, A. C. Chaskar,
ChemistrySelect, 2018, 3, 277-283; (h) B. N. Patil, J. J. Lade, A. S.
Karpe, B. Pownthurai, K. S. Vadagaonkar, V. Mohanasrinivasan, A. C.
Chaskar, Tet. Lett., 2019, 60, 891-894.
Supplementary data to this article can be found online at
References and notes
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[27] General experimental procedure:
[3] B. S. Tovrog, F. Mares, S. E. Diamond, J. Am. Chem. Soc., 1980, 21,

5
A round-bottom flask equipped with a magnetic stirring bar with
arylamine (1) (1.0 mmol), 1,2-DNB(1.0 equiv.) and Diglyme (2.0 mL) at
room temperature. 1-(2-aminoaryl)pyrrole(2) (1.0 mmol) was added to
2 4
over anhydrous Na SO and concentrated under reduced pressure. The
residue obtained was purified by column chromatography on 100-120
mesh silica gel by using n-hexane:ethyl acetate (9:1) as the eluent to
afford pyrrolo [1,2-a] quinoxaline (3aa).
o
this mixture and the resulting mixture was heated at 130 C for 9 h. The
reaction progress was monitored by using TLC. After completion of the
reaction, water was added to the reaction mixture and the aqueous layer
was extracted with ethyl acetate (10 mLx3). The organic layer was dried
Click here to remove instruction text...
Highlight of this work

This method show conversion of arylamine
and aryl alcohol to pyrrolo[1,2-
a]quinoxaline by using 1,2-DNB.
This protocol show gram scale synthesis of
the Pyrrolo[1,2-a]quinoxaline.
This method show wide functional group
tolerance.



Synthesis of hetero aromatic aldehyde was
reported from arylamine and arylalcohol.