Facile synthesis of indolizines using layered double hydroxides?poly(p-phenylenediamine) as a catalyst with a green tool (neat technology)

Article abstract of DOI:10.1002/aoc.5347

The three-component reaction of phenacyl bromide, dimethyl acetylenedicarboxylate and pyridine is catalyzed by layered double hydroxides?poly(p-phenylenediamine) (LDHs?PpPDA), in a one-pot reaction, in order to give the corresponding indolizines in excell

Full text of DOI:10.1002/aoc.5347

Received: 9 July 2019
DOI: 10.1002/aoc.5347
Revised: 13 October 2019
Accepted: 16 October 2019
F U L L P A P E R
Facile synthesis of indolizines using layered double
hydroxides@poly(p-phenylenediamine) as a catalyst with a
green tool (neat technology)
Zahra Karamshahi
| Ramin Ghorbani-Vaghei
Department of Organic Chemistry,
Faculty of Chemistry, Bu-Ali Sina
University, Hamedan, 6517838683, Iran
The three-component reaction of phenacyl bromide, dimethyl ace-
tylenedicarboxylate and pyridine is catalyzed by layered double
hydroxides@poly(p-phenylenediamine) (LDHs@PpPDA), in a one-pot reac-
Correspondence
Ramin Ghorbani-Vaghei, Department of
Organic Chemistry, Faculty of Chemistry,
Bu-Ali Sina University, 6517838683,
Hamedan, Iran.
tion, in order to give the corresponding indolizines in excellent yields.
K E Y W O R D S
1
,3-dipolar cycloaddition, DMAD, indolizine, polymer, pyrazine
Email: rgvaghei@yahoo.com
1
| INTRODUCTION
earliest reported conductive polymers and are known for
their environmental constancy in a conducting form,
novel electronics, electrochemistry, optical properties,
electromagnetic shielding, reversible redox activity, sens-
Advanced materials that can meet the high demands in
the domain of industrial applications (e.g. cosmetics,
pharmaceuticals, meteorology and microelectronics) are
highly sought. Polymers are regarded as very large mol-
ecules, or macromolecules, composed of many repeating
subunits. Proteins and nucleic acids in the human
body, fibers used in clothing, the starch we eat, foam
insulation, dishes, furniture and tubes are all made of
ing
properties,
intrinsic
features
and
high
[1]
[10–12]
conductivity.
But nowadays, due to the lack of solu-
bility in most organic solvents and poor processability
[2]
[13–16]
and rigidity, their application has been limited.
Aromatic diamine polymers with free amino group in
a duplicate unit of polymer chains can be considered as a
[3,4]
[17,18]
polymers.
Polymers may be organic, inorganic or
suitable substitute for polymers such as PANI.
organometallic. Polymers, depending on how they have
Moreover, the high proportion of polymers based on aro-
matic diamines remaining after thermal treatment led to
the use of poly(p-phenylenediamine) (PpPDA) as a
nitrogen-rich carbon precursor. According to the litera-
ture, the preparation of polymer-derived carbon networks
using a facile integrated oxidation and catalytic carboni-
zation strategy has been rarely reported. In this sense, we
envisage interesting and functional features for a carbon-
[4]
been formed, may be artificial or natural. Differences
in polymers depend on a variety of chemical details, and
due to these dissimilarities, their performances will
also vary.
Polyaniline (PANI), which is a nitrogen-doped carbon
nanomaterial, is of interest due to its ready availability
among heteroatom-doped materials and, in comparison
to other polymers, its consistency and ease of
[
5]
fiber network structure produced using PpPDA.
[5,6]
preparation.
Phenylenediamines can be used to make new conges-
tion polymers. They can be synthesized by chemical poly-
Use of nitrogen-containing reactants (such as NH3,
nitric acid and amines) or direct carbonization of
nitrogen-rich carbon precursors (such as polyacryloni-
trile, melamine, PANI), which include nitrogen-
containing functional groups, gives rise to the production
[
17,19,20]
merization.
Chan and Rawat and their respective
co-workers reported oxidative and electrochemical poly-
[
21,22]
merization of various aromatic diamines.
A large
classification of two-dimensional anionic clay materials is
the layered double hydroxides (LDHs) with the formula
[7–9]
of carbon structures.
Monoamino polymers, such as
2+
3+
n−
[23,24]
PANI, also known as black aniline, are among the
[M (1−x)Mx (OH) ](A ) ꢀzH O.
LDHs
or
2
x/n
2
Appl Organometal Chem. 2019;e5347.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5347

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KARAMSHAHI AND GHORBANI-VAGHEI
hydrotalcite-like compounds, due to their layered and
evenly divided structure, extensive surface area, high
porosity, controllability of layer intervals and anionic
exchange, have been used to absorb colored wastes. In
order to enhance the adsorption efficiency, many studies
considered chemical modifications or combination of
synthetic pharmaceutically active compounds is consid-
[
33,34]
ered as a special heterocyclic nucleus.
Indolizines,
as a vital class of N-heterocycles with 10 π-delocalized
electrons, have received much attention due to their
molecular structure and important biological activi-
[
35]
ties.
applications, including as anti-tuberculosis agents,
antibacterial agents, anticancer agents, anti-
inflammatory agents, antihistaminic agents, phosphatase
Indolizine derivatives have many pharmaceutical
[25]
LDHs with other functional materials.
Notwithstanding, LDHs are naturally abundant and
can be extracted easily from the environment. LDHs have
some specific benefits, including a simple preparation
methodology from low-cost and recoverable raw mate-
rials, convenient synthesis, environmental coordination,
thermal stability, being active catalysts and being recycla-
ble and reusable catalysts. In addition, the formation of
LDHs from metal salts as starting materials, as compared
to preparation from metals, involves the removal of one
phase (the oxidation phase), as a result of which the time
and cost of using the material decrease. Outstanding
issues regarding LDH compositions and structures
involve (a) the range of possible divalent and trivalent
ions and (b) the inclusion of various anions and also their
rich chemistry which make them good catalysts or cata-
[
36]
inhibitors, aromatase inhibitors, etc.
Therefore,
straightforward and valuable strategies for the synthesis
[
37]
of indolizine derivatives are highly desired.
In a multicomponent reaction (MCR), a chemical
reaction, three or more components react to create a
product. MCRs are reactions by which more than two
reactants mix in a successive order to provide extremely
selective products that maintain most of the atoms of the
initial material. The development of new MCRs is
attracting increasing attention in investigations done by
industrial chemistry groups as it introduces a challenge
for organic chemists. The movement in the direction of
the perfect synthesis takes up the step numbers, prefera-
bly only one product and preferably 100%, and has been
followed actively from the time scholars started to make
[26,27]
lyst precursors.
In the work reported here, we aimed at synthesizing
LDHs@PpPDA catalyst (Figure 1) using the emulsion
polymerization method and also investigating the forma-
tion of indolizine compounds. The importance and strong
demand for these heterocycles are because of their versa-
[
38,39]
molecules.
According to the literature, several methods have
been suggested for the synthesis of indolizine. In this
sense, we aimed at synthesizing indolizines by employing
a three-component reaction consisting of acyl bromide,
pyridine and acetylene (Scheme 1).
[
28–32]
tile photochemical features and biological activities.
The activation of indolizine in many natural and
FIGURE 1 Layered double
hydroxide@poly(p-
phenylenediamine) structure

FACILE SYNTHESIS OF INDOLIZINES
3 of 12
SCHEME 1 General synthesis of
dimethyl 3-(4-nitrobenzoyl)indolizine-
1
,2-dicarboxylate
2
2
| EXPERIMENTAL
2.3 | Synthesis of LDHs@PpPDA
.1 | General information and methods
LDHs@PpPDA,
at
room
temperature,
were
synthesized by emulsion polymerization as follows. In
a routine experiment, 0.75 g of LDHs was poured into
a 250 ml flask and 20 ml of chloroform and 30 ml of
distilled water were added. Then, the contents were
dispersed for about 30 min in an ultrasonic bath at
room temperature. Afterwards, a solution containing
pPDA monomer (1 g) in 30 ml of HCl (1 M) was
added to the aqueous solution. Then, an oxidizing
solution prepared with 1.5 g (6.5 mmol) of ammonium
persulfate (APS) in 20 ml of deionized water for
30 min at room temperature was added to the reaction
mixture. After 24 h, the resulting precipitate was
washed several times with deionized water. Finally,
All commercial materials were purchased from Merck
and Fluka, and used without further purifications. H
1
13
NMR and C NMR spectra were recorded with Bruker
BioSpin 400 MHz FT NMR spectrometers. Fourier trans-
form infrared (FT-IR) spectra were recorded with a
Shimadzu 435-U-04 FT-IR spectrophotometer from KBr
pellets. Melting points were measured with a BUCHI
5
10 apparatus in open capillary tubes. Scanning electron
microscopy (SEM) was performed with an EM3200
instrument operated at an accelerating voltage of 30 kV.
The structure of the new LDHs@PpPDA was character-
ized using X-ray diffraction (XRD), FT-IR spectroscopy,
ꢁ
SEM
and
thermogravimetric
analysis
(TGA).
the precipitate was dried in a vacuum oven at 50 C
Wavelength-dispersive X-ray spectroscopy was performed
using a TESCAN Mira3. SEM analysis of the prepared
catalyst was performed with a FESEM-SIGM (Germany)
for 24 h.
instrument. TGA was performed with
51 (TA Instruments).
a
DuPont
2.4 | General procedure for synthesis of
1-(3-(4-nitrobenzoyl)indolizin-1-yl)ethane-
9
1-one
2
.2 | Synthesis of LDHs
The process for the preparation of 1-(3-(4-nitrobenzoyl)
indolizin-1-yl)ethane-1-one was as follows. A mixture
of phenacyl bromide (0.20 g, 1 mmol), pyridine
(0.12 ml, 1.5 equiv.), acetylenedicarboxylate (0.15 ml,
1.5 equiv.) and 0.05 g of LDHs@PpPDA catalyst at
Zn–CrNO − LDH was synthesized using the co-
precipitation method. LDHs can be synthesized in base
3
2+
3+
solutions using metal salts containing M and M .
ꢁ
First, Zn(NO ) ꢀ6H O and Cr(NO ) ꢀ9H O in a ratio of
50 C was stirred. The reaction was monitored using
3
2
2
3 3
2
2
:1 were dissolved in deionized water, and then, drop by
TLC (n-hexane–acetone, 8:2). After the completion of
the reaction, the precipitate was filtered. The resulting
jelly-like product was then purified with diethyl ether.
After adding the diethyl ether and creating scratches
or rubbing the surface of the jelly-like product, a pure
powder was obtained. The products were characterized
using physical and spectroscopic data (Supporting
Information Data S1–S4).
drop, a solution of 2 M NaOH was added at a pH value of
1.5 (LDHs are highly insoluble materials, at least at the
1
relatively high pH used in their preparation). Afterwards,
the reaction was set at 65 C for 18 h without being
stirred. Then, the resulting green slurry was filtered,
washed several times with distilled water and dried at
ꢁ
ꢁ
[23]
6
0 C in an oven for 24 h.

4
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KARAMSHAHI AND GHORBANI-VAGHEI
2
.5 | General procedure for synthesis of
2.6.3 | Dimethyl-3-(4-methylbenzoyl)
indolizine-1,2-dicarboxylate (4c)
tetramethyl-3,8-bis(4-(nitrooxy)benzoyl)
dipyrrolo[1,2-a:2 ,1 -c]pyrazine-1,2,9,10-
tetracarboxylate
0
0
ꢁ
Light yellow solid; yield: 88%; m.p. 121–124 C. FT-IR
−1
−1 1
(
KBr, νmax, cm ): 2949, 1735, 1691, 1634 cm . H NMR
The process for the preparation of tetramethyl-3,-
(400 MHz, DMSO-d , δ, ppm): 2.45 (s, 3H, CH ), 3.58 (s,
6
3
0
0
8
1
-bis(4-(nitrooxy)benzoyl)dipyrrolo[1,2-a:2 ,1 -c]pyrazine-
,2,9,10-tetracarboxylate was as follows. A mixture of
6H, OCH ), 6.40–6.48 (m, 1H, ArH), 7.47 (m, 1H, ArH),
3
8.01 (d, J = 8 Hz, 2H, ArH), 8.29 (d, J = 8 Hz, 20, 2H, ArH),
phenacyl bromide (0.40 g, 2 mmol), pyrazine (0.08 g,
8.75 (d, J = 8 Hz, 1H, ArH), 9.03 (d, J = 8 Hz, 1H, ArH).
C NMR (100 MHz, DMSO-d , δ, ppm): 21.3, 66.1, 126.6,
6
13
1
0
mmol), acetylenedicarboxylate (0.3 ml, 3 equiv.) and
.1 g of LDHs@PpPDA catalyst at 50 C was stirred. The
ꢁ
127.7, 127.8, 128.3, 128.4, 128.5, 128.6, 128.9, 129.3, 129.6,
131.0, 143.4, 143.5, 144.4, 145.4, 146.3, 146.4, 189.7, 190.2.
MS: m/z 351. Anal. Calcd for C H NO (%): C, 68.37; H,
reaction was monitored using TLC (n-hexane–acetone,
:3), and the resulting precipitate was filtered. The
7
20
17
5
resulting jelly-like product was then purified using
diethyl ether. After adding the ethyl ether and creating
scratches or rubbing the surface of the jelly-like product,
a pure powder was obtained. The product was character-
ized using physical and spectroscopic data (FT-IR, NMR
and MS).
4.88; N, 3.99. Found (%): C, 68.56; H, 5.07; N, 4.18.
2.6.4 | Tetramethyl-3,8-bis
0
0
(4-methylbenzoyl)dipyrrolo[1,2-a:2 ,1 -c]
pyrazine-1,2,9,10-tetracarboxylate (4d)
ꢁ
Light yellow solid; yield: 92%; m.p. 129–131 C. FT-IR
−
1
1
2.6 | Analytical data of selected products
(KBr, νmax, cm ): 2952, 1735, 1605. H NMR (400 MHz,
DMSO-d , δ, ppm): 2.51 (s, 6H, CH ), 3.64 (s, 12H,
6
3
2
1
.6.1 | 3-Benzyl-1,2-dimethylindolizine-
,2,3-tricarboxylate (4a)
OCH ), 7.55 (d, J = 8 Hz, 2H, ArH), 8.03 (d, J = 8 Hz, 2H,
ArH), 8.31–8.33 (m, 2H, ArH), 8.73–8.75 (m, 2H, ArH),
3
8
.91 (d, J = 8 Hz, 1H, ArH), 9.06 (d, J = 8 Hz, 1H, ArH).
C NMR (100 MHz, DMSO-d , δ, ppm): 21.3, 30.7, 66.1,
6
ꢁ
13
Light yellow solid; yield: 90%; m.p. 124–129 C. FT-IR
−
1
1
(
(
(
KBr, νmax, cm ): 2953, 1739, 1618, 1557. H NMR
400 MHz, DMSO-d , δ, ppm): 3.72 (s, 6H, OCH ), 5.23
s, 2H, CH ), 6.56–6.60 (m, 1H, ArH), 7.43 (m, 4H,
127.8, 128.3, 129.6, 130.9, 145.5, 146.2, 146.3, 190.1. MS:
m/z 624. Anal. Calcd for C H N O (%): C, 65.38; H,
6
3
34 28 2 10
4.52; N, 4.49. Found (%): C, 65.57; H, 4.71; N, 4.68.
2
ArH), 7.92 (m, 1H, ArH), 8.40 (d, J = 8 Hz, 1H, ArH),
13
8
.65 (d, J = 8 Hz, 2H, ArH). C NMR (100 MHz,
DMSO-d , δ, ppm): 66.16, 69.2, 127.7, 127.8, 128.6,
2.6.5 | Dimethyl-3-(2,4,6-
trichlorobenzoyl)indolizine-1,2-
dicarboxylate (4e)
6
1
1
28.9, 129.3, 129.6, 131.0, 143.4, 143.5, 144.5, 145.4,
46.3, 190.1. MS: m/z 367. Anal. Calcd for C H NO
6
20
17
(%): C, 65.39; H, 4.66; N, 3.81. Found (%): C, 65.58; H,
ꢁ
1
4
.85; N, 4.01.
Light brown solid; yield: 93%; m.p. 120–122 C. FT-IR
(
−
1
KBr, νmax, cm ): 2951, 1735, 1634, 1582. H NMR
(
400 MHz, DMSO-d , δ, ppm): 4.15 (s, 6H, OCH ), 7.79 (s,
6
3
2
.6.2 | 3,8-Dibenzyl-1,10,2,9-
2H, ArH), 7.97 (d, J = 8 Hz, 1H, ArH), 8.31–8.33 (m, 1H,
ArH), 8.70 (d, J = 8 Hz, 1H, ArH), 9.07(d, J = 8 Hz, 1H,
ArH). C NMR (100 MHz, DMSO-d , δ, ppm): 58.7,
6
0
0
tetramethyldipyrrolo[1,2-a:2 ,1 -c]pyrazine-
1
13
,2,3,8,9,10-hexacarboxylate (4b)
127.7, 128.3, 129.6, 131, 145.4, 146.2, 146.3, 184.3, 190.1.
ꢁ
Light yellow solid; yield: 89%; m.p. 139–141 C. FT-IR
Anal. Calcd for C H Cl NO (%): C, 51.79; H, 2.74; N,
19
12
3
5
−
1
1
(
(
(
KBr, νmax, cm ): 2946, 1740, 1711, 1624, 1609. H NMR
400 MHz, DMSO-d , δ, ppm): 3.47 (s, 12H, OCH ), 6.26
s, 4H, CH ), 7.23–7.18 (m, 5H, ArH), 7.66–7.75 (m, 5H,
3.18. Found (%): C, 51.98; H, 2.93; N, 3.37.
6
3
2
13
ArH), 8.79 (d, J = 8 Hz, 2H, ArH). C NMR (100 MHz,
DMSO-d , δ, ppm): 66.2, 73.5, 127.7, 127.8, 128.3, 128.4,
2.6.6 | Tetramethyl-3,8-bis(2,4,6-
trichlorobenzoyl)dipyrrolo[1,2-a:2 ,1 -c]
pyrazine-1,2,9,10-tetracarboxylate (4f)
0
0
6
1
1
28.5, 128.6, 128.9, 129.3, 129.6, 131.0, 143.4, 143.5, 144.4,
45.4, 146.3, 146.4, 186.4, 190.2. MS: m/z 656. Anal. Calcd
ꢁ
for C H N O (%): C, 62.20; H, 4.30; N, 4.27. Found
Light yellow solid; yield: 95%; m.p. 126–130 C. FT-IR
34
28 2 12
−
1
1
(%): C, 62.39; H, 4.49; N, 4.46.
(KBr, νmax, cm ): 3061, 1706, 1637, 1583. H NMR

FACILE SYNTHESIS OF INDOLIZINES
5 of 12
(
(
(
400 MHz, DMSO-d , δ, ppm): 4.13 (s, 12H, OCH ), 8.31
2.6.10 | Tetramethyl-3,8-bis(3-
methoxybenzoyl)dipyrrolo[1,2-a:2 ,1 -c]
pyrazine-1,2,9,10-tetracarboxylate (4j)
6
3
0
0
d, J = 8 Hz, 2H, ArH), 8.48 (d, J = 8 Hz, 2H, ArH), 8.79
13
d, J = 8 Hz, 2H, ArH). C NMR (100 MHz, DMSO-d , δ,
6
ppm): 66.1, 127.7, 128.3, 129.6, 131, 143.7, 145.4, 146.2,
46.3, 184.3, 190.1. Anal. Calcd for C H Cl N O
6 2 10
ꢁ
1
1
Light yellow solid; yield: 90%; m.p. 133–135 C. H NMR
(400 MHz, DMSO-d , δ, ppm): 3.77 (s, 6H, OCH , 4.02 (s,
32
18
(%): C, 47.85; H, 2.26; N, 3.49. Found (%): C, 48.04; H,
6
3
2
.45; N, 3.68.
12H, OCH ), 8.32 (d, J = 8 Hz, 4H, ArH), 8.48 (d,
3
1
3
J = 8 Hz, 4H, ArH), 9.08 (d, J = 8 Hz, 2H, ArH).
C
NMR (100 MHz, DMSO-d , δ, ppm): 51.3, 55.6, 127.8,
6
2
.6.7 | Dimethyl-3-(4-nitrobenzoyl)
128.3, 129.6, 135.7, 138.5, 145.5, 146.2, 146.3, 161.42,
indolizine-1,2-dicarboxylate (4g)
164.8, 193.3. Anal. Calcd for C H N O (%): C,
28 2 12
34
62.20; H, 4.30; N, 4.27. Found (%): C, 62.39; H, 4.49; N,
ꢁ
Light yellow solid; yield: 92%; m.p. 126–130 C. FT-IR
4.46.
−
1
1
(KBr, νmax, cm ): 2942, 1706, 1637, 1602, 1525. H NMR
(
400 MHz, DMSO-d , δ, ppm): 4.44 (s, 6H, OCH ),
6
3
8
.30–3.32 (m, 1H, ArH), 8.33–8.34 (m, 1H, ArH), 8.48 (d,
2.6.11 | Dimethyl-3-(4-cyanobenzoyl)
indolizine-1,2-dicarboxylate (4k)
J = 8 Hz, 2H, ArH), 8.77 (d, J = 8 Hz, 1H, ArH), 9.09 (d,
J = 8 Hz, 1H, ArH). C NMR (100 MHz, DMSO-d , δ,
ppm): 66.4, 124.1, 127.9, 129.8, 138.2, 146.3, 146.6, 150.6,
13
6
ꢁ
1
Light yellow solid; yield: 93%; m.p. 125–128 C. H NMR
(400 MHz, DMSO-d , δ, ppm): 3.93 (s, 6H, OCH ), 8.33
1
5
7
90. MS: m/z 382. Anal. Calcd for C H N O (%): C,
19 14 2 7
6
3
9.69; H, 3.69; N, 7.33. Found (%): C, 59.88; H, 3.88; N,
.52.
(d, J = 8 Hz, 2H, ArH), 8.41–8.47 (m, 2H, ArH), 8.77–8.79
13
(m, 2H, ArH), 9.08 (d, J = 8 Hz, 2H, ArH). C NMR
(
100 MHz, DMSO-d , δ, ppm): 30.8, 109.3, 115.2, 115.2,
6
116.5, 118.1, 125.6, 129.8, 132.7, 142.8, 152.4, 153.2, 181.3,
2
.6.8 | Tetramethyl-3,8-bis(4-
197.5.
0
0
nitrobenzoyl)dipyrrolo[1,2-a:2 ,1 -c]
pyrazine-1,2,9,10-tetracarboxylate (4h)
2
.6.12 | Tetramethyl-3,8-bis(4-
ꢁ
1
0
0
Light yellow solid; yield: 93%; m.p. 130–135 C. FT-IR
methoxybenzoyl)dipyrrolo[1,2-a:2 ,1 -c]
pyrazine-1,2,9,10-tetracarboxylate (4l)
−
1
(
(
(
(
KBr, νmax, cm ): 3020, 1689, 1636, 1524. H NMR
400 MHz, DMSO-d , δ, ppm): 6.66 (s, 12H, OCH ), 8.31
d, J = 8 Hz, 4H, ArH), 8.48 (d, J = 8 Hz, 4H, ArH), 9.08
d, J = 8 Hz, 2H, ArH). C NMR (100 MHz, DMSO-d , δ,
6
3
ꢁ
1
Light yellow solid; yield: 90%; m.p. 130–133 C. H NMR
(400 MHz, DMSO-d , δ, ppm): 3.38 (s, 6H, OCH ), 3.82 (s,
13
6
6
3
ppm): 60.3, 127.7, 128.3, 129.6, 130.9, 139.8, 141.8, 145.5,
46.2, 146.3, 185.2, 190.1. MS: m/z 686. Anal. Calcd for
C H N O (%): C, 59.69; H, 3.69; N, 7.33. Found
12H,COOCH ), 8.29 (d, J = 8 Hz, 4H, ArH), 8.72–8.78
(m, 4H, ArH), 9.08 (d, J = 8 Hz, 2H, ArH). C NMR
3
13
1
(100 MHz, DMSO-d , δ, ppm): 31.6, 46.6, 98.9, 99.7,
32
22
4
14
6
(%): C, 59.87; H, 3.88; N, 7.51.
100.1, 128.1, 130.2, 131.1, 133.2, 178.3, 184.2, 197.5.
2
.6.9 | Dimethyl-3-(3-methoxybenzoyl)
3 | RESULTS AND DISCUSSION
indolizine-1,2-dicarboxylate (4i)
3
.1 | Catalyst texture, structure and
ꢁ
1
Light yellow solid; yield: 93%; m.p. 120–122 C. FT-IR
(
morphology
−
1
KBr, νmax, cm ): 2924, 1697, 1637, 1523. H NMR
(
6
1
(
400 MHz, DMSO-d , δ, ppm): 3.71 (s, 3H, OCH ), 3.93 (s,
FT-IR spectroscopy was utilized to investigate the chemi-
cal components of the synthesized samples. The common
features of pure PpPDA polymer are well known in the
literature. As seen in Figure 2, the symmetric and asym-
metric stretching vibrations of N&bond;H bond of NH2
group of polymeric chains appeared at 3650 and
6
3
H, OCH ), 6.52 (d, J = 8 Hz, 1H, ArH), 7.42–7.47 (m,
3
H, ArH), 7.61 (s, 1H, ArH), 7.62–7.66 (m, 1H, ArH), 7.73
d, J = 8 Hz, 1H, ArH), 8.30–8.34 (m, 1H, ArH), 8.79 (d,
13
J = 8 Hz, 1H, ArH), 9.04 (d, J = 8 Hz, 1H, ArH).
NMR (100 MHz, DMSO-d , δ, ppm): 51.3, 55.6, 127.8,
1
1
3
C
6
−
1
−1
28.3, 129.6, 135.7, 138.5, 146.2, 146.3, 161.42, 164.8,
93.3. Anal. Calcd for C H NO (%): C, 59.69; H,
2961 cm . The peaks at about 3371 cm are related to
the N&bond;H stretching vibration of the secondary
20
17
6
[
6]
.69; N, 7.33. Found (%): C, 59.88; H, 3.88; N, 7.52.
amine group. Two broad bands in the regions of 1500

6
of 12
KARAMSHAHI AND GHORBANI-VAGHEI
FIGURE 2 FT-IR spectra: a) LDHs, b)
LDHs@PpPDA
and 1567 cm− respectively correspond to the stretching
vibrations of C&dbond;C and C&dbond;N in the quinoid
and benzenoid rings in the PpPDA polymer structure.
Moreover, the peaks at about 1407 and 1261 cm− are
related to the C&bond;N&bond;C stretching vibra-
1
composition. As shown in Figure 4, elemental mapping
can clearly illustrate the presence of elements such as Zn,
Cr, N, O and C.
SEM imaging of LDHs@PpPDA demonstrated that it
has a flat surface and hexagonally shaped structure
(Figure 5). In addition to the structural morphology, par-
ticle size can be estimated using SEM.
1
[16]
tions.
Frequently, the broad band of hydroxyl groups
OH stretching, 3430 cm ) is noticeable in the FT-IR
−1
(
spectra of LDH sheets. In short, the absence of OH peaks
proved the successful synthesis of the LDHs@PpPDA
catalyst.
In the TGA and differential thermogravimetry curves
(Figure 6), the initial mass loss at about 100–200 C shows
the evaporation of the entrapped water. On the other
ꢁ
XRD was used for studying the crystallinity and parti-
cle size. The powder XRD patterns of LDHs and
LDHs@PpPDA are presented in Figure 3. The XRD pat-
terns of LDHs and LDHs@PpPDA show a series of sharp
hand, the observed decomposition in the range
ꢁ
240–340 C is because of oligomer loss. Finally, the weight
ꢁ
loss in the range 300–450 C is related to the dedoping
procedure and thermal degradation of PpPDA chains.
ꢁ
ꢁ
ꢁ
lines in the regions of 10 , 30 and 40 illustrating the fact
that the synthesized polymer samples have high crystal-
[40]
linity and long-range ordering.
3.2 | Catalytic activity
The mean diameter of LDHs@PpPDA particles was
measured from the Scherer equation.
The EELS elemental mapping technique was applied
to record the structural elements of the synthesized
The reaction of 2-bromo-1-(4-nitrophenyl)ethan-1-one (1)
with acetylenedicarboxylate (2) and pyridine was investi-
gated to screen the reaction conditions (Table 1).
FIGURE 3 XRD patterns: LDHs and
LDHs@PpPDA

FACILE SYNTHESIS OF INDOLIZINES
7 of 12
FIGURE 4 WDX images of LDHs@PpPDA
FIGURE 5 Morphology and particle size
of LDHs@PpPDA
Compound 1 (1 mmol) was treated with 2 (0.15 ml, 1.5
the reaction. As evident from Table 1, the best results
were achieved when the reaction was run using 0.05 g of
catalyst (Table 1, entry 3). In the absence of the
LDHs@PpPDA catalyst, the yield of the reaction was
only 20% (entry 7). Examination of the temperature
equiv.) and pyridine (0.12 ml, 1.5 equiv.), in the presence
ꢁ
of LDHs@PpPDA (0.05 g) at 50 C for 4 h under neat con-
ditions. The desired product 4g was obtained in 92% yield
(
Table 1, entry 3). The structure of 4g was confirmed by
1
13
ꢁ
its H NMR and C NMR spectra and mass spectrum.
The catalytic activity of LDHs@PpPDA was crucial for
showed that 50 C proved to be the best, affording 4g in
92% isolated yield. Thus, we determined the optimal

8
of 12
KARAMSHAHI AND GHORBANI-VAGHEI
FIGURE 6 TGA curve of LDHs@PpPDA
a
TABLE 1 Optimization of reaction conditions
ꢁ
b
Entry
Catalyst (g)
0.05
Solvent
—
Temp. ( C)
Time (min)
340
Yield (%)
1
2
3
4
5
6
7
8
9
100
25
75
0.05
—
1440
100
Trace
92
0.05
—
50
0.1
—
50
90
90
0.06
—
50
420
89
0.025
—
—
50
1440
1440
180
60
—
50
Trace
80
0.05
CH
3
COCH
3
56
0.05
H
2
O
100
90
1440
1440
33
1
0
0.05
C
2
H
5
OH
45
a
Reaction conditions: 2-bromo-1-(4-nitrophenyl)ethan-1-one (1 mmol), acetylenedicarboxylate (0.15 ml), pyridine (0.12 ml), catalyst, solvent
5 ml).
Isolated yield.
(
bb
conditions as in entry 3. Several organic solvents were
also screened (entries 8–10). The results obtained show
that acetone produces acceptable results as compared to
the other solvents, but, as noted above, the lack of solvent
The main benefit of the present results is the use of
neat conditions. A neat reaction is a chemical procedure
without a solvent minimizing the auxiliary substance
(solvent). In addition, the benefits of neat reactions in
chemistry are: (a) they are more economic (save costs on
solvent), (b) ease of work-up and purification (not neces-
sary to eliminate a solvent post-synthesis), (c) high reac-
tion rate (due to high concentration of reactants) and
(entry 3) reduces the reaction time and increases the
reaction efficiency.
With the optimized settings in hand, a series of eth-
yne and organic bromides were utilized to establish the
range and generality of the protocol. All of the reactions
proceeded smoothly to afford the desired products in
moderate to excellent yields. The use of pyrazine instead
of pyridine (Table 2) in the synthesis of indolizine leads
to the creation of new structures of indolizine. The men-
tioned structures have not been synthesized previously,
so we were able to synthesize these compounds for the
first time.
[42]
(d) environmental friendliness (solvent is not needed).
Regarding these benefits, organic reactions without
the use of conventional organic solvents have attracted
the attention of synthetic organic chemists. Even though
a number of so-called modern green solvents, such as
fluorous media, ionic liquids and water, have been
[
43]
broadly investigated,
definitely the best.
“no solvent is the best solvent” is
In the present study, our attempt to reach green
chemistry or sustainable chemistry has been discussed.
Chemical engineering has focused on the design of prod-
ucts and processes that minimize the use and generation
As evident from Table 2, phenacyl bromides with
electron-withdrawing groups provided moderate to excel-
lent yields of products (4e, 4f, 4g, 4h, 4k, 4l), but phen-
acyl bromides with electron-donating groups gave lower
yields in the reaction (4c, 4d, 4i, 4j) presumably because
[41]
of hazardous substances.

FACILE SYNTHESIS OF INDOLIZINES
9 of 12
TABLE 2 Substrate scope of dimethyl indolizine-1,2-dicarboxylate
ꢁ
Reaction conditions: phenacyl bromide (1 mmol), acetylenedicarboxylate (0.15 ml), pyridine (0.12 ml) or pyrazine (0.05 mmol), LDHs@PpPDA (0.05 g), 50 C.
of their higher LUMO compared to electron-
deficient ones.
the literature. It is clear that the previously reported pro-
cedures suffer from one or more disadvantages,
e.g. longer reaction time, the use of expensive and
unattainable materials and the application of high-boil-
ing-point and organic solvents such as DMF. As com-
pared to the other catalysts, not only does LDHs@PpPDA
shorten the reaction time, but it also provides thermal
stability, convenient synthesis and environmental coordi-
nation. Besides, it can be reused several times with no
significant loss of its catalytic activity.
In 2016, Wang and co-workers used rhodium(III) as a
catalyst. This catalyst allows the synthesis of indolizines
ꢁ
[32]
at a temperature of over 120 C and a period of 18 h.
Benzylated indolizines were synthesized using Pd (dba)3
2
catalyst under reflux conditions with dimethylformamide
[44]
(DMF) solvent for 16 h.
Also, various indolizines have
been synthesized through one-pot, two-step 1,3-dipolar
cycloadditions in recyclable [Omim]Br with high yields
[45]
and a broad substrate scope.
A palladium-catalyzed
Treatment of
1
with pyridine afforded the
direct arylation of 2-arylimidazo[1,2-a]pyridines with o-
dihaloarenes via double C&bond;H activation has been
reported. The process afforded benzo[a]imidazo[5,1,2-cd]
corresponding pyridinium bromide salt 2 in quantitative
yield (Scheme 2). The structure of the isolated bromide
salt 2 was confirmed from spectral data as well as chemi-
cal transformations (Figure 7). In the next step, the cata-
lyst causes dissociation of the hydrogen identified on the
pyridinium salt and forms an intermediate (3). Then, the
[46]
indolizine derivatives in DMF and good yields.
The efficiency of LDHs@PpPDA as the catalyst for
the synthesis of the model indolizine compounds was
compared to that of the best of the well-known data from
intermediate
3
was
treated
with
dimethyl

10 of 12
KARAMSHAHI AND GHORBANI-VAGHEI
SCHEME 2 Suggested
mechanism for the synthesis of
dimethyl 3-(4-nitrobenzoyl)
indolizine-1,2-dicarboxylate
catalyzed by LDHs@PpPDA
FIGURE 7 FT-IR spectra: Isolated bromide salt
ꢁ
acetylenedicarboxylate (DMAD) as dipolarophile at 50 C,
furnishing only one isolable product based on TLC
analysis.
The indolizine derivative 4g is assumed to be
formed via the 1,3-dipolar cycloaddition of DMAD to
the nitrogen ylide 3 (which was formed in situ through
The structure of the reaction product was ascertained
the reaction of the pyridinium salt
2
with
ꢁ
on the basis of elemental analysis and spectral data as 4g
LDHs@PpPDA at 50 C) in order to give the nonisolable
intermediate 5. Finally, product 4g was obtained with
the involvement of oxygen and catalyst from the struc-
ture 5. At this point, oxygen causes the oxidation of
5 and the product 4g.
1
(
Scheme 2). The H NMR spectrum of 4g revealed two
singlet signals at 4.42 ppm due to two methyl ester
groups. The FT-IR spectrum showed three carbonyl
−
1
absorptions at 1706, 1637 and 1602 cm .
FIGURE 8 Recyclability test of
LDHs@PpPDA

FACILE SYNTHESIS OF INDOLIZINES
11 of 12
FIGURE 9 IR Spectrum of catalyst
after use
Finally, LDHs@PpPDA was separated by simple
extraction and reused for the next run. The process could
be repeated five times without an obvious change in
yields (Figure 8). In the first run, 94% LDHs@PpPDA
was recycled, and the pureness and structure of the
recovered LDHs@PpPDA remained unchanged on the
basis of the FT-IR result (Figure 9).
[4] C. E. Carraher Jr., Seymour/Carrahers Polymer Chemistry,
CRC Press, 2003.
[
[
[
5] H. Peng, G. Ma, K. Sun, J. Mu, Z. Zhang, Z. Lei, J. Phys. Chem.
C 2014, 118, 29507.
6] I. Amer, T. Mokrani, L. Jewell, D. A. Young, H. C. M. Vosloo,
Polymer 2015, 66, 230.
7] X. Wang, J. S. Lee, Q. Zhu, J. Liu, Y. Wang, S. Dai, Chem.
Mater. 2010, 22, 2178.
[
[
8] W. Shen, W. Fan, J Mater. Chem. A 2013, 1, 999.
9] D.S. Yuan, T.X. Zhou, S.I. Zhou, W.J. Zhou, S.S. Mo, N.N. Xia,
Electrochem. Commun. 2011, 13, 242.
4
| CONCLUSIONS
[
[
10] R. P. Kingsborough, T. M. Swager, Adv. Mater. 1998, 10, 1100.
11] V. Svetlicic, A. J. Schmidt, L. L. Miller, Chem. Mater. 1998, 10,
Taking everything into account, an effective synthesis of
indolizine derivatives catalyzed by LDHs@PpPDA has
been described. The initial materials are facilely accessi-
ble, and the reactions have a wide substrate range. The
reaction overcomes some of the disadvantages of previ-
ously reported indolizine synthetic approaches and pro-
vides a new effective path to indolizine derivatives. Also,
the catalyst can be easily recovered from the reaction and
recycled. Also, the reaction rate is increased due to the
3
305.
[
[
12] S. Sukeerthi, A. Q. Contractor, Anal. Chem. 1999, 71, 2231.
13] E. Erdem, M. Karakla, M. Sacak, Eur. Polym. J. 2004, 40, 785.
[14] A. Ray, G. E. Asturias, D. I. Kershner, A. F. Richter,
A. G. MacDiarmid, A. J. Epstein, Synth. Met. 1989, 29, 141.
15] N. Plesu, G. Ilia, A. Pascariu, G. Vlase, Synth. Met. 2006,
[
1
56, 230.
[
[
16] S. Ramaprabhu, Mater. Chem. 2012, 22, 18775.
17] X.G. Li, M.R. Huang, W. Duan, Y.L. Yang, Chem. Rev. 2002,
102, 2925.
existence of NH and NH functional groups in the poly-
2
[
18] Q. L. Pham, Y. Haldorai, V. H. Nguyen, D. Tuma, J.J. Shim,
Bull. Mater. Sci. 2011, 34, 37.
mer structure of the catalyst.
[19] K. Ogura, M. Kokura, J. Yano, H. Shiigi, Acta 1995, 40, 2707.
ACKNOWLEDGMENTS
[20] X.G. Li, W. Duan, M.R. Huang, Y.L. Yang, D.Y. Zhao, Q.
Z. Dong, Polymer 2003, 44, 5579.
21] H. S. O. Chan, S. C. Ng, T. S. A. Hor, J. Sun, K. L. Tan,
B. T. G. Tan, Eur. Polym. J. 1991, 27, 1303.
22] B. Rawat, S. S. Kansara, H. S. Rama, Polym. Int. 1991, 26, 233.
23] N. Hirata, K. Tadanaga, M. Tatsumisago, Mater. Res. Bull.
The authors thank Bu-Ali Sina University, Center of
Excellence Developmental of Environmentally Friendly
Methods for Chemical Synthesis (CEDEFMCS) and Iran
National Science Foundation (INSF) for financial support
to carry out this research.
[
[
[
2015, 62, 1.
[24] M. Behrens, I. Kasatkin, S. Khl, G. Weinberg, Chem. Mater.
ORCID
2009, 22, 386.
Zahra Karamshahi https://orcid.org/0000-0003-2777-
[25] P. M. Pardeshi, A. K. Mungray, A. A. Mungray, Desalination
017, 421, 149.
2
6
629
Ramin Ghorbani-Vaghei https://orcid.org/0000-0001-
322-6299
[
[
[
26] S. M. Auerbach, K. A. Carrado, P. K. Dutta, Handbook of Lay-
ered Materials, CRC Press, 2004.
27] M. AdachiPagano, C. Forano, J.P. Besse, Chem. Commun.
8
2000, 91–92.
REFERENCES
28] U. Bora, A. Saikia, R. C. Boruah, Org Lett 2003, 5, 435.
[
1] J. M. G. Cowie, V. Arrighi, Polymers: Chemistry and Physics of
Modern Materials, CRC Press, 2007.
[29] S. Mahesh, R. V. Anand, Eur. J. Org. Chem. 2017, 2698.
[30] W. Lwowski and A. R. Katritzky. Comprehensive Heterocyclic
Chemistry: The Structure, Reactions, Synthesis and Uses of Het-
erocyclic Compounds, Vol. 7, Pergamon Press, 1984.
[
[
2] A. G. MacDiarmid, Angew. Chem. Int. Ed. 2001, 40, 2581.
3] C.H. Liu, K.T. Liao, H.J. Huang, Anal. Chem 2000, 72, 2925.

12 of 12
KARAMSHAHI AND GHORBANI-VAGHEI
[
[
[
31] V. Sharma, V. Kumar, Med. Chem. Res. 2014, 23, 3593.
32] B. Shen, B. Li, B. Wang, Org. Lett. 2016, 18, 2816.
33] A. Ramazani, Y. Ahmadi, M. Rouhani, N. Shajari, A. Souldozi,
Heteroatom CHEM. 2010, 21, 368.
M. K. Nazeeruddin, J. H. Delcamp, Adv. Energy Mater. 2015, 5,
1401629.
[45] A. Ramazani, Y. Ahmadi, N. Fattahi, H. Ahankar, M. Pakzad,
H. Aghahosseini, A. Rezaei, S. T. Fardood, S. W. Joo, Phospho-
rus Sulfur Silicon 2016, 191, 1057.
[
[
[
34] A. Ramazani, A. T. Mahyari, M. Rouhani, A. Rezaei, Tetrahe-
dron Lett. 2009, 50, 5625.
35] M. M. Lakouraj, E. N. Zare, P. N. Moghadam, Adv. Polym.
Technol. 2014, 33.
36] M. V. Reddy, N. T. K. Lien, G. C. S. Reddy, K. T. Lim,
Y. T. Jeong, Green Chem. 2016, 18, 4228.
[46] S. Taghavi Fardood, A. Ramazani, Z. Golfar, S. W. Joo, Appl.
Organometal. Chem. 2017, 31, e3823.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
[
[
37] M. Kidwai, P. Mothsra, Synth. Commun. 2006, 36, 817.
38] Z. Andrade, K. Carlos, L. M. Alves, Curr. Org. Chem. 2005,
9, 195.
[
[
[
39] Y. Yang, T. Wu, Y. Fang, Synlett 2018, 29, 1909.
40] X. Zhang, Eng. 2017, 5, 9279.
41] H. Wang, C. Chen, Z. Huang, L. Yao, B. Li, J. Peng, J. Synthesis
How to cite this article: Karamshahi Z,
Ghorbani-Vaghei R. Facile synthesis of indolizines
using layered double hydroxides@poly(p-
phenylenediamine) as a catalyst with a green tool
neat technology). Appl Organometal Chem. 2019;
2
015, 47, 2457.
[
[
[
42] A. J. Huckaba, A. Yella, P. Brogdon, J. S. Murphy,
M. K. Nazeeruddin, M. Grtzel, J. H. Delcamp, Chem. Commun.
2
016, 52, 8424.
(
43] A. J. Huckaba, A. Yella, L. E. McNamara, A. E. Steen,
J. S. Murphy, C. A. Carpenter, G. D. Puneky, N. I. Hammer,
M. K. Nazeeruddin, M. Grtzel, Chem. Eur. J. 2016, 22, 15536.
44] A. J. Huckaba, F. Giordano, L. E. McNamara, K. M. Dreux,
N. I. Hammer, G. S. Tschumper, S. M. Zakeeruddin, M. Grtzel,
e5347. https://doi.org/10.1002/aoc.5347