Highly efficient synthesis of chromeno[2,3-b]pyridine using Graphene-Oxide/N1,N3-bis (pyridin-2-ylmethyl)propane-1,3-diamine-Copper nanocomposites as a novel catalyst

Article abstract of DOI:10.1002/aoc.5737

Recent studies about innovations in GO/N-Ligand-Cu Nano-Composites have been done. Graphene-Oxide is improved with N¹,N³-bis (pyridin-2-ylmethyl)propane-1,3-diamine and after that is matched with copper (Cu). The chemical composition and the structure of the catalyst were analyzed by TGA/DTG, EDX, XRD, FT-IR, TEM, and SEM. The results demonstrated that GO/N-Ligand-Cu was able to catalyze the chromeno[2,3-b]pyridine compounds to obtain high yields in short reaction time. The results of the present work are hoped to assist the growth of a new class of heterogeneous catalysts as the high-function candidate for industrial applications.

Full text of DOI:10.1002/aoc.5737

Received: 30 January 2020
DOI: 10.1002/aoc.5737
Revised: 28 March 2020
Accepted: 30 March 2020
F U L L P A P E R
Highly efficient synthesis of chromeno[2,3-b]pyridine using
Graphene-Oxide/N1,N3-bis (pyridin-2-ylmethyl)propane-
1,3-diamine-Copper nanocomposites as a novel catalyst
Zahra Karamshahi1
| Ramin Ghorbani-Vaghei1
| Hassan Keypour2
|
Mohammad Taher Rezaei2
1Department of Organic Chemistry,
Faculty of Chemistry, Bu-Ali Sina
Recent studies about innovations in GO/N-Ligand-Cu Nano-Composites have
been done. Graphene-Oxide is improved with N1,N3-bis (pyridin-2-ylmethyl)
propane-1,3-diamine and after that is matched with copper (Cu). The chemical
composition and the structure of the catalyst were analyzed by TGA/DTG,
EDX, XRD, FT-IR, TEM, and SEM. The results demonstrated that GO/N-
Ligand-Cu was able to catalyze the chromeno[2,3-b]pyridine compounds to
obtain high yields in short reaction time. The results of the present work are
hoped to assist the growth of a new class of heterogeneous catalysts as the
high-function candidate for industrial applications.
University, Box 65174, Hamedan, PO, Iran
2Department of Inorganic Chemistry,
Faculty of Chemistry, Bu-Ali Sina
University, Hamedan, Iran
Correspondence
Ramin Ghorbani-Vaghei, Department of
Organic Chemistry, Faculty of Chemistry,
Bu-Ali Sina University. PO Box 65174,
Hamedan, Iran.
Email: rgvaghei@yahoo.com
K E Y W O R D S
1,3-diamine, Chromeno[2,3-b]pyridine, graphene oxide, multi-component reactions,
nanocomposites
1 | INTRODUCTION
groups–i.e. hydroxyl group, epoxy, and carboxylic acid–
have been applied in order to alter/transform graphene
Regarding the significant features of green chemistry, it is
the catalysis which has been connected to the synthesis of
chemical products and has also been regarded as an impor-
tant tool in developing cleaner chemical processing. In this
sense, developing new catalysts which have advantages like:
lower input energies, higher selectivity, and decreasing toxic
agents during the synthesis of certain chemicals can be con-
sidered as the main function of catalytic science. Moreover,
it results in implementing simpler processes needed for and
required by the green chemistry.[1]
surface practicability.[5,6]
It is worth mentioning that the chemical and
mechanical properties of graphene and its derivatives –
i.e. the oxidized graphene–would significantly affect pro-
ducing novel materials in different scientific fields.[1]
In this sense, a wide variety of methods have been
organized in order to functionalize graphene
i.e. carboxylic acid group esterification responses,[7,8] the
nucleophilic ring-opening reaction of epoxy group,[9] iso-
cyanate cure, etc.[10]
Amongst disparate carbon materials, graphene with
two-dimensional structure due to its high specific surface
area, unique electrical conductivity, self-assembly behav-
ior, and mechanical flexibility has attracted widespread
attention.[2] The 21st century witnessed the arrival of a
new material known as Graphene which attained wider
attention after a work by Geim and his colleagues.[3,4] It
is on the GO Nano-Sheets that the oxygen functional
When practical groups are present on the GO, superfi-
cial structures would be constructed in such a way that it
will be capable of being utilized as an absorbent.[11] In
this regard, the ornamentation of inherent properties of
graphene with metal nanoparticles (NPs) would result in
their excellent adjustment to be applied for a wide variety
of uses i.e. catalyst, energy generation, and storage, opto-
electronics, and sensors.[12,13]
Appl Organomet Chem. 2020;e5737.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5737

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KARAMSHAHI ET AL.
During the last few years, much efforts have been
microscopy (SEM), Germany was performed on EM3200
instrument operated at 30 kV accelerating voltage. The
structure of the new LDHs@Propyl–ANDSA was charac-
terized using XRD, IR, SEM, EDX and TGA analysis.
Energy dispersive X-ray (EDX) , Nederland and Scanning
electron microscopy (SEM) analysis of the prepared cata-
lyst was fulfilled on a FESEM-SIGM (Germany) instru-
ment. Thermo-gravimetric analysis (TGA) was
accomplished on a DUPONT 951 TA, Texas City (Amer-
ica) Instruments. Transmission electron microscopy
(TEM), Germany was performed with a Zeiss-EM10C-100
KV.[21]
dedicated to synthesize libraries of small heterocyclic
molecules due to their great amount of structural variety
and broad function as healing agents.[14] In this study,
the detection of central structures has this potential and
not suffering from obvious overutilization is one of the
chief challenges for the medicinal business in its quest
for rich resources of recent molecular entities.[15,16]
Heterocyclic compounds have a chief part in devising
new classes of medicinally significant structural enti-
ties.[17] Chromenopyridines are bonded with heterocyclic
compounds that show a variety of biological happenings:
antibacterial, antiproliferative (cytotoxic activity against
the human solid tumor HT-29 cell lines), cancer chemo-
preventive, antirheumatic, antihistaminic, antimyopic
and antiasthmatic.[18,19] These scaffolds usually consist of
a rigid ring hetero-system with specially defined orienta-
tion of different functionalities for aim diagnosis[20] Mul-
ticomponent reactions (MCRs) are constantly effective
sources and environmentally suitable and consequently
greener in comparison to multistage reactions. Mul-
ticomponent reactions (MCRs) are greatly effective
approaches to attain the prompt gathering of complex
products, mainly progressive C-C and C–heteroatom
bond-forming reactions in the field of heterocycles and
healthy productions.[19] We have chosen the most appro-
priate approach for preparing chromeno[2,3-b]pyridine
compounds, those founded on multicomponent reactions
(MCRs) (Scheme 1).
2.2 | Preparation of GO
Initially, natural graphite powder (2 g) was added into a
250 ml flask having 46 ml H2SO4 (98%) and it was stirred
for 30 min. Then, NaNO3 (1 g) was added to the mixture
and stirred forcefully to prevent agglomeration. Subse-
quently, 6 g KMnO4 and 20 ml H2O2 solution (30%) was
progressively added into the flask and then cooled by put-
ting in an ice bath. The blend was stirred for 45 min, then
HCl (1 mol L−1) was used to wash the resulting suspen-
sion and it was gathered by centrifugation (Scheme 2).[22]
2 | EXPERIMENTAL
2.1 | Materials and methods
All commercial materials were purchased from Merck
and Fluka companies, and used without further purifica-
1
tions. H NMR and 13C NMR spectra were recorded on
Bruker BioSpin GmbH 250 MHz FT NMR spectrometers,
America. Fourier transform infrared (FT-IR) spectra were
recorded on a Shimadzu 435-U-04 FT spectrophotometer,
Columbia, Maryland from KBr tablets. Melting points
were measured on a BUCHI, Gilroy, California 510 appa-
ratus in open capillary tubes. Scanning electron
SCHEME 2 Schematic structure of graphene oxide (GO)
SCHEME 1 General synthesis of
ethyl-5,7-diamino-6-cyano-2-methyl-
4-(3-nitrophenyl)-4H-pyrano[2,3-b]
pyridine-3-carboxylate

KARAMSHAHI ET AL.
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2.3 | Preparation of N-ligand (A1)
2.4 | Preparation of GO/N-ligand-cu
nanocomposite
For the preparation of A1,
5
mmol (0/37 g)
propylenediamine was added to a solution of 10 mmol
(1.07 g) pyridine-2-carbaldehyde in a dry methanol solu-
tion and the solution was refluxed for 12 hr. As a result,
it opened up the Schiff as an intermediate product. In the
next step, 40 mmol (1.51 g) of sodium borohydride was
added to the above solution for 2 hr and sprayed into the
ice bath for 48 hr. After completion of the reaction time,
A1 was separated from water and chloroform
(Scheme 3).
GO (1 g) was spread in 250 ml distilled water through
stirring by using bath ultrasonication for 30 min. The GO
spreading was done to a 250 ml three-necked and round
end flask with a magnetic stirrer, and a reflux condenser,
then 4 g (15.6 mmol) N-Ligand and 6 ml ammonia were
added to the flask and the mixture was stirred for 24 hr
under reflux condition. Afterwards, the resulted (GO/N-
Ligand) was filtrated and cleaned by hot water and etha-
nol to get rid of unreacted elements. Then, this mixture
ꢀ
was secluded by filtration and dried in an oven at 100 C
for 24 hr. Dispersing 2 g GO/N-Ligand in 100 ml ethanol
SCHEME 3 Schematic structure of N1,N3-bis(pyridin-
2-ylmethyl)propane-1,3-diamine (N-Ligand)
SCHEME 4 Schematic structure of
GO/N-Ligand-Cu

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KARAMSHAHI ET AL.
was attained through ultrasonication for 15 min. Succes-
sively, 1 g cupric acetate was added to the mixture, then
stirred at reflux for 24 hr. The product was completely
washed with hot ethanol for manꢀy times. The obtained
GO/N-Ligand-Cu was dried at 80 C for 24 hr. The syn-
thetic way is shown in Scheme 4.[3,23]
NH2), 8.06–8.08 (d, J = 8 Hz, 2H, ArH), 8.79 (s, 2H,
NH2); 13C NMR (100 MHz, DMSO-d6): δ 14.9, 17.3,
36.3, 62.8, 69.3, 104.1, 106.7, 112.2, 116.7, 119.2, 129.3,
137.2, 154.8, 159.3, 164.5, 167.7, 170.0; MS (m/z):
380.25 (M+, 100%), 367.35, 350.2, 340.7, 335.15, 295.9,
281.05, 225.
2.5 | Preparation of chromeno[2,3-b]
pyridine: General procedure
2.7.2 | Methyl 5,7-diamino-6-cyano-
4-(2-hydroxyphenyl)-2-methyl-4H-
pyrano[2,3-b]pyridine-3-carboxylate (4b)
A blend of the aldehyde (1 mmol), malononitrile (2 mmol),
ethyl acetoacetate (1 mmol) and GO/N-Ligand-Cu
nanocomposites catalyst (0.05 g), in water (3 ml) was
refluxed for. The development of the reaction was followed
by TLC (n-hexane/acetone, 7:3). After the completion of
the reaction, the resulting precipitate was filtered to elimi-
nate the catalyst and the crude product was recrystallized
from ethanol to get the pure compound. The products
were characterized using physical and spectroscopic
(NMR, Ms) data (Supporting Information Data S1–S2).
Light yellow solid; Yield: 93% (930 mmol); M.p:
1
ꢀ
196–200 C H NMR (250 MHz, DMSO-d6): δ 1.14 (t, 3H,
CH3), 2.28 (s, 3H, CH3), 3.97 (q, 2H, CH2), 5.34 (s, 1H,
CH), 6.56 (s, 2H, NH2), 6.65–6.69 (d, J = 10, 1H, ArH),
7.02–7.12 (m, 2H, ArH), 7.23–7.27 (d, J = 10, 1H, ArH),
7.66 (s, 2H, NH2), 9.44 (s, 1H, OH); 13C NMR (62.5 MHz,
DMSO-d6): δ 14.9, 17.3, 36.3, 62.8, 64.9, 104.1, 106.8,
109.5, 112.5, 116.7, 119.2, 128.6, 137.2, 153.4, 154.8, 159.3,
164.5, 167.7, 170.0; MS (m/z): 366.3 (M+, 100%), 360.3,
350.1, 338.2, 320/2, 295.2, 225.3, 106.1.
2.6 | Evaluation of copper removal from
GO/N-ligand-cu catalyst surface in
chromeno[2,3-b]pyridine synthesis
2.7.3 | Methyl 5,7-diamino-6-cyano-
4-(2-methoxyphenyl)-2-methyl-4H-
pyrano[2,3-b]pyridine-3-carboxylate (4c)
Methyl 5,7-diamino-6-cyano-2-methyl-4-(4-nitrophenyl)-
4H-pyrano[2,3-b]pyridine-3-carboxylate derivative was
selected as the sample for this test. After 50 percent reac-
tion progress (15 min), the reaction was stopped, the reac-
tion was stopped and the catalyst was separated from the
reaction mixture by centrifugation. The reaction mixture
was placed under the same conditions for 15 min after sep-
aration of the catalyst and no significant progress was
observed in the reaction process. The results of this test
showed that copper nanocomposites were not released in
the reaction medium and remained on the surface of the
catalyst and as well as the catalyst was very stable in con-
trast to moisture, air and reaction conditions.
Light yellow solid; Yield: 90% (900 mmol); M.p:
1
ꢀ
216–218 C. H NMR (250 MHz, DMSO-d6): δ 1.15–1.20 (t,
3H, CH3), 2.28 (s, 3H, CH3), 3.81 (s, 3H, OCH3), 3.97 (q, 2H,
CH2), 4.98 (s, 1H, CH), 6.12 (s, 2H, NH2), 7.00–7.07 (m, 3H,
ArH), 7.30–7.34 (d, J = 10, 2H, ArH), 8.29 (s, 2H, NH2); 13
C
NMR (62.5 MHz, DMSO-d6): δ 14.3, 19.1, 21.5, 56.0, 60.1,
61.3, 79.5, 112.1, 113.8, 115.6, 121.3, 126.3, 129.1, 130.1,
138.5, 148.1, 151.6, 157.6, 164.5, 166.2; MS (m/z): 380.7 (M+,
100%), 352.8, 350.6, 301.7, 222, 184.05, 151.0.
2.7.4 | Methyl 5,7-diamino-6-cyano-
2-methyl-4-(m-tolyl)-4H-pyrano[2,3-b]
pyridine-3-carboxylate (4d)
2.7 | Analytical data of the selected
products
Light yellow solid; Yield: 91% (910 mmol); M.p:
220–224 ꢀC. 1H NMR (250 MHz, DMSO-d6): δ 1.23 (t, 3H,
CH3), 1.93 (s, 3H, CH3), 2.47 (s, 3H, CH3), 4.23 (q, 2H,
CH2), 4.93 (s, 1H, CH), 6.11 (s, 2H, NH2), 7.20–7.27(m,
1H, ArH), 7.30 (s, 1H, ArH), 7.42–7.44 (m, 2H, ArH), 9.21
(s, 2H, NH2); 13C NMR (62.5 MHz, DMSO-d6): δ 14.2,
20.7, 21.5, 48.2, 63.1, 64.2, 102.9, 113.4, 116.6, 125.7,
129.1, 130.2, 131.7, 136.9, 138.3, 158.9, 162.9, 163.9, 164.6,
164.9; MS (m/z): 364.4 (M+, 100%), 350, 320.15, 233.95,
231.95, 172.1, 153.1.
2.7.1 | Methyl 5,7-diamino-6-cyano-
2-methyl-4-(4-nitrophenyl)-4H-
pyrano[2,3-b]pyridine-3-carboxylate (4a)
Light yellow solid; Yield: 94% (940 mmol); M.p:
220–223 ꢀC. 1H NMR (400 MHz, DMSO-d6):
δ
1.20–2.53 (t, 3H, CH3), 4.19 (q, 2H, CH2), 4.65 (s, 1H,
CH), 7.38–7.40 (d, J = 8 Hz, 2H, ArH), 7.83 (s, 2H,

KARAMSHAHI ET AL.
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2.7.5 | Methyl 5,7-diamino-6-cyano-
4-(4-fluorophenyl)-2-methyl-4H-
pyrano[2,3-b]pyridine-3-carboxylate (4e)
CH), 7.31 (s, 2H, NH2), 7.49 (s, 2H, NH2), 7.65–7.67 (d,
J = 8 Hz, 2H, ArH), 8.12–8.14 (d, J = 8 Hz, 2H, ArH); 13C
NMR (100 MHz, DMSO-d6): δ 18.6, 19.2, 31.7, 57.1, 61.1,
82.7, 110.9, 112.7, 113.8, 129.4, 130.2, 131.06, 131.1, 132.2,
132.4, 132.9, 159, 160; MS (m/z): 430.2(M+, 100%), 431.8,
428.3, 399.25, 350.2, 322.4, 233, 232, 159.1.
Light yellow solid; Yield: 91% (910 mmol); M.p:
210–212 ꢀC. 1H NMR (250 MHz, DMSO-d6): δ 1.33 (t, 3H,
CH3), 3.08 (s, 3H, CH3), 4.12 (q, 2H, CH2), 4.99 (s, 1H,
CH), 6.18 (s, 2H, NH2), 6.82–6.86 (d, J = 10 Hz, 2H,
ArH)), 7.80–7.84 (d, J = 10 Hz, 2H, ArH), 8.03 (s, 2H,
NH2); 13C NMR (62.5 MHz, DMSO-d6): δ 14.9, 17.3, 36.3,
62.8, 69.3, 104.1, 106.7, 112.2, 116.7, 119.2, 137.2, 154.8,
159.3, 164.5, 167.7, 170.0; MS (m/z): 370.9 (M+, 100%),
369.55, 350.1, 294.3, 280.2.
2.7.9 | Ethyl 5,7-diamino-6-cyano-
4-(4-methoxyphenyl)-2-methyl-4H-
pyrano[2,3-b]pyridine-3-carboxylate (4i)
Light yellow solid; Yield: 91% (910 mmol); M.p:
230–233 ꢀC. 1H NMR (400 MHz, DMSO-d6): δ 1.21 (t, 3H,
CH3), 2.53 (s, 3H, CH3), 3.86 (s, 3H, OCH3), 4.17(q, 2H,
CH2), 5.00 (s, 1H, CH), 7.77–7.79 (d, J = 8 Hz, 2H, ArH),
7.90–7.92 (d, J = 8 Hz, 2H, ArH), 7.98 (s, 2H, NH2), 9.31
(s, 2H, NH2); 13C NMR (100 MHz, DMSO-d6): δ 14.2,
25.7, 29.6, 55.3, 55.8, 55.9, 113.8, 114.2, 114.5, 114.7,
115.2, 124.3, 130, 132, 133.7, 160.02, 164.6, 164.8, 190.8;
MS (m/z): 380.15(M+, 100%), 350.1, 320.8, 286.12, 221.25,
184.
2.7.6 | Methyl 5,7-diamino-6-cyano-
4-(2,4-dichlorophenyl)-2-methyl-4H-
pyrano[2,3-b]pyridine-3-carboxylate (4f)
Light yellow solid; Yield: 89% (890 mmol); M.p:
218–220 ꢀC. 1H NMR (250 MHz, DMSO-d6): δ 1.13 (t, 3H,
CH3), 2.61 (s, 3H, CH3), 3.99 (q, 2H, CH2), 5.38 (s, 1H,
CH), 6.14 (s, 2H, NH2), 7.00 (s, 2H, NH2), 7.02 (s, 1H,
ArH), 7.17 (1H, ArH), 7.40 (1H, ArH); 13C NMR
(62.5 MHz, DMSO-d6): δ 14.9, 17.3, 36.3, 61.3, 62.8, 104.1,
106.7, 112.2, 124.9, 130.4, 132.0, 137.2, 140.4, 142.6, 154.8,
159.3, 164.5, 167.7, 170.0; MS (m/z): 420.95 (M+, 100%),
419.45, 418, 398, 378.8, 350.2, 155.1.
2.7.10 | Ethyl 5,7-diamino-6-cyano-
2-methyl-4-(p-tolyl)-4H-pyrano[2,3-b]
pyridine-3-carboxylate (4j)
Light yellow solid; Yield: 89% (890 mmol); M.p:
220–223 ꢀC. 1H NMR (400 MHz, DMSO-d6): δ 1.20 (t, 3H,
CH3), 2.43 (s, 6H, CH3), 4.10 (q, 2H, CH2), 4.46 (s, 1H,
CH), 7.03 (s, 2H, NH2), 7.45–7.47 (d, J = 8 Hz, 2H, ArH),
7.88–7.90 (d, J = 8 Hz, 2H, ArH), 8.49 (s, 2H, NH2); 13C
NMR (100 MHz, DMSO-d6): δ 8.9, 14.5, 21.9, 57.1, 61.1,
80.42, 114, 114.9, 129.2, 129.6, 129.8, 130.1, 130.6, 131.2,
134.6, 148.2, 161.8; MS (m/z): 364.4(M+, 100%),
350, 320.15, 233.95, 231.95, 172.1.
2.7.7 | Ethyl 5,7-diamino-
4-(4-chlorophenyl)-6-cyano-2-methyl-4H-
pyrano[2,3-b]pyridine-3-carboxylate (4 g)
Light yellow solid; Yield: 91% (910 mmol); M.p:
225–229 ꢀC. 1H NMR (400 MHz, DMSO-d6): δ 1.21 (t, 3H,
CH3), 2.18 (s, 3H, CH3), 4.22 (q, 2H, CH2), 4.97 (s, 1H,
CH), 7.12 (s, 2H, NH2),7.49–7.51 (d, J = 8 Hz, 2H, ArH),
7.75 (s, 2H, NH2), 7.89–7.91 (d, J = 8 Hz, 2H, ArH); 13C
NMR (62.5 MHz, DMSO-d6): δ 8.7, 13.82, 14.1, 56.9, 61.5,
61.7, 111.2, 113.9, 128.1, 129.2, 129.5, 129.9, 131.0, 131.1,
132.3, 140.3, 159.9, 191.2; MS (m/z): 386.35 (M+, 100%),
384, 369.9, 350.7, 329.4, 322.5, 295.2, 229.2, 191.1, 159.1,
153.05.
3 | RESULT AND DISCUSSION
The initial stage for the chromeno[2,3-b]pyridine syn-
thetic approach is related to the development of the reac-
tion conditions and examination of the catalytic activity
of GO/N-Ligand-Cu nanocomposites. So that outline the
optimization conditions of the reaction, the catalytic
activity of several catalysts was studied in the exemplary
reaction.
The selection of catalyst has a high significance for
the reproduction of chromeno[2,3-b] pyridine, conse-
quently, the effect of several solvents, as well as of vari-
ous reaction temperature on the reaction of aldehydes 1,
1,3-diketone 2 and malononitrile 3 has been investigated.
2.7.8 | Ethyl 5,7-diamino-
4-(4-bromophenyl)-6-cyano-2-methyl-4H-
pyrano[2,3-b]pyridine-3-carboxylate (4 h)
Light yellow solid; Yield: 90% (900 mmol); M.p:
225–228 ꢀC. 1H NMR (400 MHz, DMSO-d6): δ 1.10 (t, 3H,
CH3), 2.19 (s, 3H, CH3), 4.13 (q, 2H, CH2), 5.00 (s, 1H,

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KARAMSHAHI ET AL.
TABLE 1
Catalytic activity of different catalysts on the synthesis of chromeno[2,3-b]pyridinea
Entry
Catalyst
Solvent
H2O
Time (min)
T (ꢀC)
100
Yieldb (%)
1
No catalyst
1440
-
-
94
90
97
98
94
78
85
88
20
35
53
20
25
34
2
Chitosan@citric acid
DMAP
CH3CH2OH
H2O
reflux
reflux
reflux
98
3
-
4
Fe3O4@SiO2–NH2
Et3N
H2O/EtOH
PrOH
-
5
-
6
GO/N-Ligand-Cu
GO/N-Ligand-Cu
GO/N-Ligand-Cu
GO/N-Ligand-Cu
GO/N-Ligand-Cu
GO/N-Ligand-Cu
GO/N-Ligand-Cu
GO
H2O
30
reflux
100
7
Solvent-free
CH3CH2OH
CHCl3
H2O
260
160
210
1440
1440
1440
720
720
720
8
80
9
65
10
11
12
13
14
15
r.t
H2O
50
H2O
75
H2O
reflux
reflux
reflux
GO/Cu
H2O
N-Ligand-Cu
H2O
aReaction conditions: 4-nitro benzaldehyde (1 mmol), malononitrile (2 mmol), ethyl acetoacetate (1 mmol), solvent (5 mL), GO/N-Ligand-Cu
(0.05 g).
bIsolated yield.
The catalytic results of various catalysts are displayed in
Table 1. It was verified by the outcomes once the reaction
is done without catalyst (Table 1, entry 1). Regardless of
the protracted reaction time, no product is obtained,
therefore it is highlighting the specific role of catalyst. To
investigate the effect of temperature on the reaction, we
performed the model reaction at r.t, 50 C, 75 C, and
reflux conditions (Table 1, entries 6 and 10–12). The
examination of the temperature showed that reflux con-
ditions proved to be the best. Thus, we determined our
best circumstances as shown in entry 6.
dissimilar catalyst such as GO/N-Ligand-Cu, and also
water would be a good option as a green solvent.
To further compare this method, we also performed
the model reaction in the presence of different catalysts.
After the reaction, it was found that the catalyst used in
this report performed better than other catalysts (Table 2,
entries 1–4).[21,27,28]
ꢀ
ꢀ
Combining many compounds of 4-nitro benzaldehyde
1, ethyl acetoacetate
2
and malononitrile 3,
chromeno[2,3-b]pyridines 4(a-j) was synthesized. We
realized that the reaction in the existence of GO/N-
Ligand-Cu increased the wanted product (96%) in less
reaction time (00:30 min) (Table 1, entries 6). The solvent
has a noticeable effect on the production and reaction
time (Table 1, entries 9–12) and the finest outcome was
attained in water solvent conditions. Additionally, we
also studied the influence of temperature (Table 1, entries
6–9). To investigate the effect of the catalyst on the reac-
tion, we designed a reaction in which the effects of GO,
GO/Cu[29] and N-ligand-Cu were studied separately.
In the presence of catalysts such as Chitosan@citric
acid,[24] DMAP,[25] Fe3O4@SiO2–NH2
and Et3N,[18]
[26]
application of high hazardous, odorous and expensive
materials such as thiols and alkyl phosphite ester is a
disadvantage of previous methods (Table 1, entries
2–5).
These observations resulted in finding measures and
means to decrease the time and cost of consumption.
Thus, it looks practical to think that we could use a
TABLE 2
Effect of various catalysts on yield of chromeno[2,3-b]pyridine
Entry
Catalyst (g)
T (ꢀC)
Reflux
Reflux
Reflux
Reflux
Time (min)
Yield (%)
Ref.
1
2
3
4
LDHs@Propyl-ANDSA (0.05)
LDH/Tris/Pd. (0.05)
50
45
65
30
68
82
70
94
1
2
3
Fe3O4@SiO2@Propyl–ANDSA (0.05)
GO/N-Ligand-Cu (0.05)
In work

KARAMSHAHI ET AL.
7 of 13
According to the results (Table 1, entries 13–15), it did
not have much effect on the reaction progress, con-
firming that the GO/N-Ligand-Cu catalyst worked well
and increased the efficiency and reduced reaction time
without side products. The oxidation state of Cu in
GO/N-ligand-Cu and cupric acetate on graphene oxide
nanoparticles is Cu (II), But once copper was deposited
on the GO/N-Ligand, in fact, greater amounts of copper
were placed on the surface of the catalyst.
As a result, the reaction rate is increased compared to
when we used N1,N3-bis (pyridin-2-ylmethyl) propane-1,-
3-diamine and cupric acetate on graphene oxide
nanoparticles composite.
Also, amount of catalyst (Table 3) in water solvent sit-
uations. There was considerable growth in the produc-
tion by a rise in the reaction temperature.
As result, a reflux for 00:30 min in water solvent con-
dition in the presence of 0.05 g catalyst is identified as
the ideal reaction condition. It is thought that a nano-
structure can be a good troth as a catalyst because of their
surface area developments strictly.
The catalyst activity of GO/N-Ligand-Cu apparently is
associated to: (1) nanostructured nature of the catalyst
and (2) catalytic activity of copper metal for triggering
the starting materials. The ideal amount of nano-catalyst
loading in this reaction, was measured to be 0.05 g
(Table 3, entry 3). By decreasing the catalyst loading to
0.025 g, the preferred product was acquired in low yield
(Table 2, entries 1) while with increasing of the catalyst
TABLE 3
Effect of catalyst amount on the reaction between
4-nitro benzaldehyde (1 mmol), malononitrile (2 mmol), ethyl
acetoacetate (1 mmol)a
Entry
Amount of cat. (g)
Yieldb (%)
1
2
3
4
0.025
0.03
0.05
0.1
35
84
94
96
aReaction conditions: 4-nitro benzaldehyde (1 mmol), malononitrile
(2 mmol), ethyl acetoacetate (1 mmol), H2O (5 mL),
GO/N-Ligand-Cu (0.05 g).
bIsolated yield.
TABLE 4
Synthesis of chromeno[2,3-b]pyridine derivatives using GO/N-Ligand-Cu as a catalysta
aReaction conditionsaldehyde (1 mmol), malononitrile (2 mmol), ethyl acetoacetate (1 mmol), H2O (5 mL), GO/N-ligand-Cu (0.05 g).

8 of 13
KARAMSHAHI ET AL.
loading to 0.1 g has no significant effect on reaction rate
and isolated yield of product (Table 3, entry 4).
catalysts; because this method was undertaken at 100 ꢀC,
with high yields in short reaction time.
Many methods directed towards the synthesis of
methyl-5,7-diamino-6-cyano-2-methyl-4-(3-nitrophenyl)-
4H-pyrano[2,3-b]pyridine-3-carboxylate have therefore
been developed; this method has attracted much interest
concerning the available methods catalyzed by different
It can be seen that 89–94% yield of products is
obtained at 100 ꢀC in the presence of 0.05 g GO/N-
Ligand-Cu after 00:35 to 1:40 min (Table 4).
As an attempt to expand the range of our method,
afterward, we used several aldehydes as the substrates for
this reaction. The items in Table 4 reveal that the cataly-
sis progressed well for a wider variety of aryl aldehydes,
given that the corresponding chromeno[2,3-b]pyridine to
be in high yields. The results indicated that an electron-
donating group or an electron-withdrawing group on aryl
aldehydes does not have a distinguished outcome and
SCHEME 5 Suggested mechanism for the synthesis of
chromeno[2,3-b]pyridine catalyzed by GO/N-Ligand-Cu
FIGURE 2 XRD patterns: a) GO, b) GO/N-Ligand-Cu
FIGURE 1 FT-IR spectra: a) GO, b) N-
Ligand, c) GO/N-Ligand, d) GO/N-Ligand-Cu

KARAMSHAHI ET AL.
9 of 13
gives proper yields. Thus, the best acting catalyst to reach
methyl-5,7-diamino-6-cyano-2-methyl-4-(4-nitrophenyl)-
4H-pyrano[2,3-b]pyridine-3-carboxylate is the nano
GO/N-Ligand-Cu catalyst, causes great yields of up to
94%. The recognized compounds were described by their
physical and spectral data in comparison with the reports
in the literature.
Considering the achieved data and our current results
on the multicomponent synthesis of chromeno[2,3-b]pyr-
idine from aldehydes, malononitrile and ethyl
acetoacetate the succeeding scheme for the synthesis of
chromeno[2,3-b]pyridine is proposed (Scheme 5).
GO/N-Ligand-Cu nanocomposites as a novel catalyst
was prepared based on the subsequent procedure
(Scheme 1) (see the experimental section).
The properties of GO/N-Ligand-Cu catalyst were
approved several microscopic and spectroscopic methods
like transmission electron microscopy (TEM), scanning
electron microscopy (SEM), thermal gravimetric analysis
(TGA), X-ray diffraction (XRD) and FT-IR spectroscopies.
Inductively coupled plasma optical emission spectroscopy
(ICP/OES) analysis of the catalyst found that the weight
percentage of Cu to be 25.8 wt% Cu in the catalyst.
Firstly, we utilized the FT-IR spectrum to describe the
functionalized GO/N-Ligand-Cu. The FT-IR spectrum of
graphene oxide, N-Ligand and functionalized GO/N-
Ligand-Cu are presented in Figure 1. The results reveal
that the characteristic bands of badge GO are detected at
1725 cm−1(C=O stretching in carboxylic acid),
1622 cm−1(C-C stretching in the aromatic ring),
1230 cm−1(C–O stretching in epoxy), and 1060 cm−1 (C–
O stretching in alkoxy). Two absorption bands about
3290 cm−1 and 1354 cm−1 were related to the NH
stretching vibrations and the bending vibration absorp-
tion peak of N–H. On the other hand, after func-
tionalization, the bending vibration absorption peak of
N–H at about 3290 cm−1 vanished or shifted, which was
shown as the copper coordination of the ligand.
Knoevenagel condensation of aldehyde
1
and
malononitrile 2 is the first step of the domino process.
Subsequently, the Michael addition of ethyl acetoacetate
3 to intermediate A provides the intermediate B which
then undergoes tautomerization and later intramolecular
cyclization twice, lastly, the addition of another corre-
spondent of malononitrile 4 leads into chromeno[2,3-b]
pyridine.
The X-ray diffraction pattern of graphene oxide
nanosheets and after GO/N-Ligand-Cu is shown in
Figure 2.
As can be seen in spectrum a, the peak values of
2θ = 25ꢀ and 45ꢀ, correspond to the standard XRD spec-
trum of graphene oxide nanosheets and in Figure b, the
indicator peak with values of 25ꢀ, 35ꢀ, 43ꢀ, 55ꢀ and 72ꢀ
confirms the presence of Cu on graphene oxide
nanoparticles (35ꢀ, 55ꢀ, 72ꢀ peaks of copper metal).
FIGURE 3 TGA curve of GO/N-Ligand-Cu
FIGURE 4 SEM of GO/N-Ligand-Cu

10 of 13
KARAMSHAHI ET AL.
The thermal decomposition of GO, GO/N-Ligand-Cu
obviously shows that the degradation of the catalyst con-
tinues in three stages and the parallel spectrum is pres-
ented in Figure 3.
In the TGA and DTG thermogram, the first weight
loss is about 25–50 as a result of the loss of water mole-
was investigated by using thermogravimetric methods.
The thermogram was documented in the temperature
ranges of 25–600 ꢀC with a heating rate of 10 degrees per
minute. The data from the thermogravimetric analysis
FIGURE 5 TEM of GO/N-Ligand-Cu
FIGURE 6 The particle size distribution histograms of the GO/N-Ligand-Cu

KARAMSHAHI ET AL.
11 of 13
cules and dopant, the second decomposition in the tem-
perature range 50–130 is because of the loss of copper
metal and the third weight loss occurred from 130–250 is
because of the degradation of N-Ligand and the final
weight loss related to GO.
oxygen functional group in the GO layers also play part
in its thermal variability at high temperature. Addition-
ally, TEM pictures show that Cu nanoparticles were dis-
tributed consistently on the graphene plane.[31]
At a closer look, as shown in the particle size dis-
tribution histograms (Figure 6), the sizes of the
nanoparticles are between 5–40 nm and the average
particle size is estimated at about 24.87 nm, while
more than 70% of the catalyst particles have an aver-
age size of about 5–55 nm.
The EDX data for the GO/N-Ligand-Cu (Figure 7)
verified the existence of the anticipated elements car-
bon, oxygen, nitrogen, and especially copper in the
catalyst.
The scheme and mixture of recoverable catalysts is a
really difficult interdisciplinary field of study, it needs
incorporating chemistry, the science of materials engi-
neering, economics and environmental purposes. Consid-
ering the proper outcomes achieved from the catalyst
activity throughout the reaction, we made a decision to
examine the catalyst constancy by examining their recy-
clability and activity in the experiment. By using
By using SEM and TEM the morphology of the
GO/N-Ligand-Cu is investigated, they are shown in
Figures 3 and 4. The morphology and structure (SEM)
of the GO/N-Ligand-Cu nanosheets are illustrated in
Figure 4. The image of the GO formed showed thin
and wrinkle nanosheets. Moreover, the SEM images of
GO/N-Ligand-Cu was verified that the catalyst was
composed of uniform nanometer-sized particles.[30]
It is observable that GO/N-Ligand-Cu wrinkles and
can be recognized to the folding of the sheets as shown in
the TEM image. You may describe this by the thermody-
namic instability of exfoliated 2-D structure of GO sheets
along with the van der Waals attractions between the
graphene oxide layers (Figure 5).
The exfoliated GO sheets are joined to each other to
make thick layers become steady because of the thermo-
dynamic instability. Furthermore, the incidence of
FIGURE 7 EDX of GO/N-Ligand-Cu
FIGURE 8 Recyclability test of GO/N-
Ligand-Cu

12 of 13
KARAMSHAHI ET AL.
FIGURE 9 SEM Spectrum of catalyst after
use GO/N-Ligand-Cu
4-nitrobenzaldehyde as the model substrate, recycling
research was executed. The reaction situations utilized in
these experiments were equal to the described experi-
ments; besides the reaction development was examined
by TLC. Following completing each course (45 min), the
reaction combination was permitted to get room temper-
ature, and the solid catalyst was divided by centrifuga-
tion, washed with acetone, dried, and used again in the
later run. This practice might be conducted 5 times with
no noticeable variation in the product. It shows similar
action in each run without any remarkable loss of its cat-
alytic activity (Figure 8).
MCRs has been newly investigated and establishes an
active study area. Moreover, in this paper, a new catalyst
synthesized by N1,N3-bis (pyridin-2-ylmethyl)propane-1,-
3-diamine and cupric acetate on graphene oxide
nanoparticles composite were used for chromeno[2,3-b]
pyridines.
This nanocomposite profits from favorable extrac-
tion qualities of graphene oxide (high surface field and
worthy extraction ability) and time-saving. Ultimately,
this process was utilized for the synthesis of
chromeno[2,3-b]pyridines and satisfactory outcomes
were acquired.
In the first run, 94% GO/N-Ligand-Cu was recycled,
and the pureness and structure of recovered GO/N-
Ligand-Cu remain unchanged on the basis of the SEM
result (Figure 9).
ACKNOWLEDGEMENT
The authors wish to thank Bu-Ali Sina University, Center
of Excellence Developmental of Environmentally
Friendly Methods for Chemical Synthesis (CEDEFMCS).
CONCLUSIONS
ORCID
Multicomponent procedures show important superiori-
ties over old step by step methods, for instance, easier
synthetic processes, lower costs, environmentally
friendly, effectiveness, and great bond-forming effective-
ness. By the way, the impression of heterocycles on
Zahra Karamshahi https://orcid.org/0000-0003-2777-
6629
Ramin Ghorbani-Vaghei https://orcid.org/0000-0001-
8322-6299

KARAMSHAHI ET AL.
13 of 13
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How to cite this article: Karamshahi Z,
Ghorbani-Vaghei R, Keypour H, Rezaei MT.
Highly efficient synthesis of chromeno[2,3-b]
pyridine using Graphene-Oxide/N1,N3-bis (pyridin-
2-ylmethyl)propane-1,3-diamine-Copper
nanocomposites as a novel catalyst. Appl
Organomet Chem. 2020;e5737. https://doi.org/10.
1002/aoc.5737