Synthesis, characterization and application of α-Ca3 (PO4)2 as a heterogeneous catalyst for the synthesis of 2.3-diphenylquinoxaline derivatives and knoevenagel condensation under green conditions

Article abstract of DOI:10.1016/j.molstruc.2021.131449

Green chemistry is now paramount in modern life and industrial sector. It has become a research priority and a scientific challenge. In this study, alpha-tricalcic phosphate was prepared as a green catalytic medium. This medium has been characterized by v

Full text of DOI:10.1016/j.molstruc.2021.131449

Journal of Molecular Structure 1248 (2022) 131449
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Synthesis, characterization and application of α-Ca (PO ) as a
3
4 2
heterogeneous catalyst for the synthesis of 2.3-diphenylquinoxaline
derivatives and knoevenagel condensation under green conditions
a
b
a
a,∗
a
Haddou Anahmadi , Majda Fathi , Fatima El hajri , Zakaria Benzekri , Sarra Sibous ,
b
a
a
a
Brahim Chafik El Idrissi , Mohamed Salahdine El youbi , Abdelaziz Souizi , Said Boukhris
a
Laboratory of Organic Chemistry, Catalysis and Environment, Department of Chemistry, Faculty of Sciences, Ibn Tofail University PO Box 133, Kenitra
14000, Morocco
b
Advanced Materials and Process Engineering, Faculty of Sciences, Ibn Tofaïl University, PO Box 133, Kenitra 14000, Morocco
a r t i c l e i n f o
a b s t r a c t
Article history:
Green chemistry is now paramount in modern life and industrial sector. It has become a research prior-
ity and a scientific challenge. In this study, alpha-tricalcic phosphate was prepared as a green catalytic
medium. This medium has been characterized by various techniques such as X-ray diffraction (XRD),
Fourier Transformed Infrared Spectroscopy (FT-IR), Scanning Electron Microscope (SEM) in combination
with dispersive energy X-ray microanalysis (EDX). Furthermore, we studied the catalytic performance of
α-Ca3 (PO4)2 on knoevenagel condensation and the synthesis of 2.3-dipphennylquinoxaline derivatives.
These methodologies present several beneficial ones such as mild conditions, increased reaction speed,
excellent yields, ease of implementation and insulation of products. In addition, this new phosphate-
based catalytic medium can be recycled several times without losing either their activity or selectivity.
Received 3 June 2021
Revised 6 August 2021
Accepted 4 September 2021
Available online 6 September 2021
Keywords:
Green chemistry
Heterogeneous catalyst
Tricalcic phosphate α-TCP
Knoevenagel condensation
©
2021 Elsevier B.V. All rights reserved.
2.3-diphenylquinoxalines
1
. Introduction
tion is also carried out by various heterogeneous catalysts includ-
ing natural phosphate and trisodium phosphate (TSP) [16].
The synthesis of the activated alkenes is performed under mild
conditions using natural phosphate alone, doped by potassium flu-
oride or modified by sodium nitrate in methanol at room temper-
ature [17]. We represent the different methods of alkenes synthe-
sis (Knoevenagel condensation) by the use of different varieties of
catalysts [18–22]. The quinoxalins are bicyclic heterocycles com-
pounds containing a benzene nucleus fused to a pyrazine ring [23–
25].
Calcium phosphates are widely used in different areas, like the
phosphate fertilizer manufacturing industry [1]. In addition, cal-
cium phosphates have electronic properties, are widely used in the
design of fluorescent lamps [2] and laser materials [3]. Similarly,
they are also used in chromatography for the separation and pu-
rification of organic molecules [4–5].
Therefore, apatitic calcium phosphates having a great activity
in the biomaterials field. Indeed, thanks to their chemical com-
position close to the mineral phase of bone tissues, their biocom-
patibility and bio-activity properties make them usable in various
forms: bone substitutes, active-principle release system, ceramics
and cements [6–9]. Also, calcium phosphates are widely used in
organic synthesis in shaves of their diversity of properties.
One of their important applications is their uses as catalysts in
organic synthesis [10–13]. The Knoevenagel condensation is discov-
ered by Knoevenagel [14] who caused benzaldehyde to react with
ethyl acetoacetate to form ethyl benzylidene acetoacetate [15].
This reaction is one of the most common for the formation of
functionalized alkynes in the presence of a weak base. The reac-
The chemistry of quinoxalins has recently undergone consid-
erable development, due to the evidence of applications, of sev-
eral quinoxalins derivatives in various fields, be it in pharmaceu-
tical chemistry [26–28], or in agrochemicals [29,30]. The stud-
ies have shown that quinoxalins exhibit biological activities such
as anticancer, antimicrobial, antibiotic, antiviral, anti-inflammatory,
antibacterial and antiproliferative [31–35]. Also, they are used as
dyes, luminescent materials, semi-conductors and corrosion in-
hibitors [36–39]. But before exposing our own synthesis methods,
it seemed appropriate to cite the different procedures allowing ac-
cess to quinoxalins and derivatives [40–44]. In this context, the
heterogeneous catalysis is one of the pillars of clean chemistry.
Therefore, we continued our axis of research using the α-Ca (PO )
3
4 2
∗
as a heterogeneous catalyst for the synthesis of alkene and 2.3-
diphenylquinoxalines derivatives.
Corresponding author.
E-mail address: zakariachimist2014@hotmail.com (Z. Benzekri).
https://doi.org/10.1016/j.molstruc.2021.131449
0
022-2860/© 2021 Elsevier B.V. All rights reserved.

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
2
. Experimental
ture for a time (Table 5). The reaction was followed by TLC us-
ing n-hexane/EtOAc (5:1) as an eluent. After the reaction is com-
pleted, the resulting crude product is dissolved in CH Cl . The α-
2
.1. Materials and equipment
2
2
Ca (PO )
was then recovered by a simple filtration. The pure
products were obtained after recrystallization in ethanol.
3
4 2
All chemicals and solvents used were obtained from Sigma
Aldrich and Merck without any additional purification. The X-ray
diffraction analysis of our catalytic medium was performed un-
der ambient pressure and temperature conditions, performed on a
PANalytical X’Pert 3 Powder diffractometer using the source of the
Cu K-radiation (1.54178) source generated at 45 KV and 40 mA.
The infrared absorption spectrum of our catalyst was recorded on
a VERTEX 70v DTGS type device. The sample was analyzed as a
potassium bromide (KBr) pellet. The analysis is carried out at room
2
.3. General procedure of the synthesis of 2.3-diphenylquinoxalines
derivatives
1.2-diamine 4 (1 mmole) and benzile 2 (1 mmole) were mixed
in 2 ml of ethanol in the presence of α-Ca (PO ) (2.56 mg) as
3
4 2
a catalyst. The reaction mixture was stirred at room tempera-
ture for an illustrious time in Table 6. When the reaction is com-
pleted [TLC control (elected: Ethyl acetate: n-Hexane (1:9)))]. Then,
Dichloromethane was added to the mixture to recover the catalyst
−
1
−1
temperature on a spectral domain of 400 cm to 4000 cm . The
surface morphology of the used catalyst was determined using a
type scanning electron microscopy (TESCAN-VEGA3) equipped with
a complete EDAX-type microanalysis detector to analyze the chem-
ical composition of a sample. The progression and follow-up of all
reactions were monitored by thin-film aluminum chromatography
covered with silica gel 60 F254 (0.2 mm thick) were carried out on
Merck plates. The revelation was carried out by observation under
ultraviolet lamp (UV 254 nm). The melting points of the synthe-
sized compounds were determined using a previously calibrated
kofler bench. The structural analysis of the synthesized compounds
was carried out by the Nuclear Magnetic Resonance (NMR) of pro-
ton 1H and carbon 13C. The NMR 1H and 13C spectra were recorded
on a BRUKER DPX 250 spectrometer operating at frequencies of
by simple filtration. After removing the CH Cl2 by simply evapora-
2
tion of the solvent. The obtained crude solid is well recrystallized
in EtOH.
2
.4. Spectroscopic characterization data
-(4-chlorophenylmethylene) malononitrile (3a): Colorless
2
−1
1
solid, mp 160–162 °C; IR (KBr, cm ): 2222 (CN), 1585 (C = C). H
NMR (300 MHz, DMSO–d ) δppm 8.49 (s, 1H, C=CH), 7.92 (d, 2H,
6
13
J = 8.7 Hz), 7.67 (d, 2H, J = 8.7 Hz). C NMR (75 MHz, DMSO–d )
6
δppm 160.5, 139.5, 132.5, 131.6, 130.1, 114.4, 113.4, 82.7.
3
00 and 75 MHz, respectively. The chemical movements (δ) are ex-
2
-(phenylmethylene) malononitrile (3b): Colorless solid, mp
pressed in part per million (ppm) compared to the tetramethylsi-
lane (TMS) signal used as a reference.
−1
1
8
0–81 °C; IR (KBr, cm ): 2225 (CN), 1560 (C = C). H NMR
(
300 MHz, DMSO–d ) δppm 8.50 (s, 1H, C=CH), 7.59 (d, 2H,
6
13
J = 7.7 Hz, ArH), 7.57–7.70 (m, 3H, ArH). C NMR (75 MHz, DMSO–
2
.2. General protocol of Knoevenagel condensation
d ) δppm 155.7, 134.8, 131.7, 131.6, 130.9, 129.9, 114.6, 113.5, 82.0.
6
2
-(p-tolylmethylene) malononitrile (3c): White solid, mp 118–
−
1
In a beaker of 50 ml added aromatic aldehyde (1) (1 mmole),
119 °C; IR (KBr, cm 1): 2222 (CN), 1593 (C = C). H NMR (300 MHz,
malononitrile (1 mmole), ethyl cyanoacetate or methyl cyanoac-
etate (2) with 2.56 mg of α-Ca (PO ) as a catalyst in 2 ml
DMSO–d ) δppm 8.39 (s, 1H, C=CH), 7.82 (d, J = 8.5 Hz, 2H), 7.38
6
13
(d, J = 8.5 Hz, 2H), 2.37 (s, 3H). C NMR (75 MHz, DMSO–d )
3
4
2
6
of ethanol. The reaction mixture was stirred at room tempera-
δppm 161.6, 146.1, 131.1, 130.5, 129.1, 114.8, 113.8, 80.3, 21.5.
Fig. 1. Catalyst preparation steps α-Ca3 (PO4)2.
2

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
Fig. 2. X-ray diagram of α-Ca3(PO4)2.
Fig. 3. FT-IR absorption spectrum of α-Ca3(PO4)2.
Table 1
Positions and modes of vibration (FT-IR) of α-Ca3(PO4)2.
Wave number (cm 1)
−
Functional grouping
H2O
Normal modes
Reference
[47]
3
1
1
5
4
500
Elongation vibrations.
637
Deformation in the plane of the water molecule adsorbed on the particles surface.
Triple degenerate antisymmetric vibration mode.
Antisymmetric bending triply degenerte.
[47]
[45]
[45]
[45]
027–1083
70
P – O
P – O
P – O
53
Symmetric bending doubly degenerte.
3

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
Fig. 4. SEM of α-Ca3(PO4)2.
Fig. 5. Spectroscopy of dispersive energy (EDS) of α-Ca3(PO4)2.
Fig. 6. Long durability of α-Ca3(PO4)2 in the formation of products 3a and 6a.
4

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
Scheme 1. Model topical: condensation of 4-chlorobenzaldehyde 1a and malononitrile 2a.
Scheme 2. Ideal reaction: condensation of o-phenylenediamine 4a and benzil 5.
Table 2
Table 4
Catalytic test on model tropical.
Study of the difference of the mass of the catalyst on the formation of products 3a
and 6a.
Time (min)b
Yield%a
Entry
Catalyseur
Entry
α-Ca3(PO4)2 (mol%)/(mg)
Yield(%) of 3aa
Yield(%) of 6aa
3a
6a
3a
6a
1
2
3
4
5
6
7
8
9
1/0.32
2/0.64
3/0.96
4/1.28
5/1.60
6/1.92
7/2.24
8/2.56
9/2.88
10/3.20
20/6.44
59
60
61
62
74
78
80
94
94
91
86
54
68
73
76
78
80
89
95
95
95
89
1
2
No catalyst
60
30
10
10
54
91
47
95
α-Ca3(PO4)2
a
Isolated yields.
b
Determined by TLC.
Table 3
Study of the effect of solvent on model reactions.
1
1
0
1
Time (min)b
Yield(%)a
3a
Entry
Solvent
3a
6a
6a
a
Isolated yields.
1
2
3
4
EtOH
MeOH
THF
30
30
45
40
10
12
20
15
91
90
86
67
95
92
—-
—-
CH3CN
13
O–CH ). C NMR (75 MHz, DMSO–d ) δppm 162.1, 153.1, 149.8,
3
6
a
137.6, 132.1, 131.0, 124.4, 115.1, 107.0, 53.9.
Isolated yields.
b
Determined by TLC.
Ethyl-3-(4-chlorophenyl)−2-cyanoacrylate (3i): Colorless solid,
−
1
1
mp 89–90 °C; IR (KBr, cm ): 2230 (CN), 1725(C = O). H NMR
(
300 MHz, DMSO–d ) δppm 8.33 (s, 1H, C=CH), 8.00 (d, 2H,
6
2-(4-nitrophenylmethylene) malononitrile (3d): Yellow solid,
J = 8.7 Hz, ArH), 7.61 (d, 2H, J = 8.7 Hz, ArH), 4.29 (q, 2H,
−
1
1
13
mp 161–162 °C; IR (KBr, cm ): 2225 (CN), 1600(C = C). H NMR
J = 7.2 Hz, O–CH2–CH3), 1.28 (t, 3H, J = 7.2 Hz, O–CH2–CH3).
C
(
300 MHz, DMSO–d ) δppm 8.67 (s, 1H, C=CH), 8.29 (d, J = 8.7 Hz,
NMR (75 MHz, DMSO–d6) δppm 162.0, 154.0, 138.5, 132.8, 130.5,
129.8, 115.7, 103.5, 62.9, 14.3.
6
1
3
2
H), 8.11 (d, J = 8.7 Hz, 2H). C NMR (75 MHz, DMSO–d ) δppm
6
1
59.7, 150.1, 137.1, 131.9, 124.8, 114.0, 112.9, 82.4.
Ethyl-2-cyano-3-p-tolylacrylate (3k): White solid, mp 91–
92 °C; IR (KBr, cm 1): 2235 (CN), 1730(C = O). 1H NMR (300 MHz,
DMSO–d6) δppm 8.05 (s, 1H, C=CH), 7.90 (d, J = 7.2 Hz, 2H), 7.79
(d, J = 7.5 Hz, 2H), 4.34 (q, J = 7.4 Hz, 2H, O–CH2–CH3), 2.37
−
Methyl-3-(4-chlorophenyl)−2-cyanoacrylate (3e): White solid,
−
1
1
mp 120–121 °C; IR (KBr, cm ): 2230 (CN), 1720 (C = O).
H
NMR (300 MHz, DMSO–d ) δppm 8.38 (s, 1H, C=CH), 8.04 (d, 2H,
6
13
J = 8.4 Hz, ArH), 7.65 (d, 2H, J = 8.4 Hz, ArH), 3.84 (t, 3H, O–CH ).
(s, 3H, O–CH2–CH3), 1.31 (t, J = 7.2 Hz, 3H, Ar-CH3). C NMR
(75 MHz, DMSO–d6) δppm 163.0, 155.5, 144.9, 131.4, 130.4, 129.1,
116.2, 101.2, 63.1, 14.3, 21.3.
3
1
3
C NMR (75 MHz, DMSO–d ) δppm 162.5, 154.2, 138.5, 132.5,
6
1
30.6, 129.9, 115.8, 103.4, 53.8.
Methyl-2-cyano-3-phenylacrylate (3f): White solid, mp 84–
Ethyl-2-cyano-3-(4-nitrophenyl) acrylate (3l): Yellow solid, mp
168–169 °C; IR (KBr, cm ): 2230 (CN), 1720 (C = O). 1H NMR
(300 MHz, DMSO–d6) δppm 8.35 (s, 1H, C=CH), 8.02 (d, 2H,
J = 8.4 Hz, ArH), 7.62 (d, 2H, J = 8.4 Hz, ArH), 4.29 (q, 2H,
−
−1
8
5 °C; IR (KBr, cm 1): 2235 (CN), 1725(C = O). 1H NMR (300 MHz,
DMSO–d ) δppm 8.38 (s, 1H, C=CH), 8.01–8.04 (m, 2H, ArH),
6
13
7
.54–7.65 (m, 3H, ArH), 3.84 (t, 3H, O–CH ). C NMR (75 MHz,
3
13
DMSO–d ) δppm 162.8, 155.6, 133.9, 131.7, 131.6, 129.8, 115.0,
J = 7,2 Hz, O–CH2–CH3), 1.28 (t, 3H, J = 7.2 Hz, O–CH2–CH3).
C
6
1
02.8, 53.8.
NMR (75 MHz, DMSO–d6) δppm 162.0, 154.0, 138.4, 132.8, 130.6,
129.9, 115.8, 103.6, 62.9, 14.4.
Methyl-2-cyano-3-(4-nitrophenyl) acrylate (3 h): Yellow solid,
mp 172–173 °C; IR (KBr, cm ): 2232 (CN), 1722(C = O). 1H
−1
2,3-diphenylquinoxaline (6a) :White solid, mp 126–128 °C;
IR (KBr, cm 1): 2971, 1712, 1461, 1299, 767. H NMR (DMSO–d6,
−
1
NMR (300 MHz, DMSO–d ) δppm 8.48 (s, 1H, C=CH), 8.34 (d,
6
2
H, J = 7.1 Hz, ArH), 8.19 (d, 2H, J = 7.1 Hz, ArH), 3.88 (s, 3H,
300 MHz, δ ppm) δ 8.11–8.14 (m, 2H), 7.83–7.86 (m, 2H), 7.43–7.46
5

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
Table 5
Knoevenagel condensation via condensation of the various aromatic aldehyde substituted with the active methylene
compound catalyzed by α-Ca3 (PO4)2.
Table 6
Synthesis of 2,3-diphenylquinoxaline between the condensation of various o-phenylenediamine substituted with benzil in the presence of α-Ca3
PO4)2.
(
Scheme 3. Recycling of α-Ca3 (PO4)2 tricalcium phosphate in the formation of product 3a.
(
m, 4H), 7.32–7.37 (m, 6H). 13C NMR (DMSO–d , 75 MHz, δ ppm)
2H), 8.29–8.32 (m, 4H), 7.32–7.49 (m, 5H). 13C NMR (DMSO–d6,
75 MHz, δ ppm) δ 156.5, 143.4, 139.6, 138.4, 136.0, 131.2, 130.2,
129.9, 125.3.
6
δ 153.5, 140.9, 139.2, 132.0, 130.9, 130.2, 129.2, 128.5.
-methyl-2,3-diphenylquinoxaline (6b) :White solid, mp 122–
6
1
24 °C; IR (KBr, cm 1): 3405, 1623, 1451, 1350, 1063, 759, 697. 1
−
H
NMR (DMSO–d , 300 MHz, δ ppm) δ 7.90–7.99 (m, 2H), 7.66–7.69
3. Results and discussion
6
(
m, 2H), 7.44–7.66 (m, 4H), 7.28–7.44 (m, 5H), 2.47 (s, 3H, CH ).
3
1
3
C NMR (DMSO–d , 75 MHz, δ ppm) δ 153.3, 141.0, 139.3, 133.0,
3.1. The preparation and characterization of α-Ca (PO )
4 2
6
3
130.1, 129.1, 128.8, 127.9, 21.8.
6
-Nitro-2,3-diphenylquinoxaline (6c) : Red solid, mp 140–
The reaction conditions for the preparation of α-Ca (PO )
3 4 2
by the slightly modified wet chemical method were ini-
tially optimized. The analytical grade calcium nitrate tetrahy-
−
1
42 °C; IR (KBr, cm 1): 3413, 1768, 1526, 1345, 1064, 755. 1H NMR
(
DMSO–d , 300 MHz, δ ppm) δ 8.85–8.86 (m, 2H), 8.48–8.52 (m,
6
6

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
Scheme 4. Recycling tricalcic phosphate (α-Ca3 (PO4)2) in model condensation 6a.
Table 7
Comparative study between the catalytic performance of α-Ca3(PO4)2 with other catalysts.
Entry
Catalyst
Reaction conditions
Yield(%)
Condensation of knoevenagel
1
2
3
4
5
6
7
8
9
Mesoporous Amino-silica
HAP- γ - Fe2O3
20 mg, EtOH, r.t, 6 h
64–90 [48]
60–99 [49]
48–98 [50]
80–98 [51]
85–98 [52]
54–98 [53]
84–96 [13]
82–97 [58]
83–96
0.025 g, H2O, 30 °C, 1h
mpg-C3N4-tBu
50 mg, CH3CN, 70 °C, 2h
Na-A-PW9
0.25 mol%, MeOH, r.t, 6h
R2 (1MCl-2NaPO3) (2%)
(N2H5)2SiF6
6 mg, 3 mL EtOH,r.t,3–30min
0.1 mol% ,2 mL EtOH ,r .t , 30–60min
10 mg, 3 mL EtOH, r.t, 10 min
6 mg, 3 mL EtOH, r.t, 10–65 min
2.56 mg/8 mol%, 2 mL EtOH, r.t, 30–60 min
CaHPO4, 2H2O (DCPD)
Na2Ca(HPO4)2
α-Ca3(PO4)2
2
,3-diphenylquinoxalins
1
1
1
1
1
1
0
1
2
3
4
5
Fe3O4@SiO2-imid-PMAn
RHA-SO3H
0,05 g, 5 mL EtOH, r.t, 5–25 min
15 mg, Free-solvent, r.t, 5–30 min
0.03 g, 10 mL EtOH, 80 °C, 20 min
1 mol%, 5 mL EtOH, r.t, 90 min
3 mg, 2 mL EtOH, r.t, 2 min
89–95 [54]
90–98 [55]
90–91 [56]
88–98 [57]
97–99 [59]
90–98
ZrO2-Al2O3
Co NPs
Ca(H2PO4)2.H2O
α-Ca3(PO4)2
2.56 mg/8 mol%, 2 mL EtOH, r.t, 10–15 min
−
+
,
drate [Ca(NO ) ·4H O] and diammonium hydrogen phosphate
washed repeatedly with distilled water to remove NO3 and NH4
3
2
2
[
(NH ) HPO ] were dissolved individually in distilled water pre-
followed by drying in an air atmosphere at 60 °C for 24 h. The
obtained cake after drying was powdered with agate mortar and
pestle, and then calcined into alumina crucible at 800 °C for 2 h.
The product was determined to be pure β -TCP. Afterwards, the
prepared β –TCP was calcined at 1200 °C followed by quenching
to room temperature (r.t). The calcination is performed as follows:
β –TCP powders are heated from r.t to 1200 °C for 4 h, soaked
at 1200 °C for 3 h, followed by quenching, in the furnace, from
4
2
4
heated at 37 °C. The Ca(NO ) ·4H O solution was added drop-
3
2
2
wise into (NH ) HPO solution under constant stirring to reach
4
2
4
the Ca/P molar ratio of 1.50. The temperature of the opaque so-
lution is maintained at 37 °C. The pH was adjusted by the ad-
dition of the concentrated ammonium hydroxide (NH OH) solu-
4
tion at around 8. The milky solution is stirred for 2 h at 37 °C.
The formed precipitates are then filtered out of the mother liquor,
7

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
1
200 °C to r.t for 4 h (Fig. 1). The X-ray diffraction showed the
presence of all characteristic peaks at a single phase of α-Ca3
PO4)2 (Fig. 2). Their intensities indicate that it has been well
is type α-Ca (PO ) . In addition, no trace of impurity was detected
in the EDS spectrum.
3
4 2
(
crystallized and its crystalline structure is monoclinical with P2 /a
1
3.2. Catalytic performance of α-Ca (PO ) on Knoevenagel
3
4 2
space group (JCPDS 00–009–0348) [45,46]. The crystalline param-
eters determined using the ‘High Score plus’ software are a of
condensation and the synthesis of 2.3-diphenylquinoxaline
˚
˚
˚
a = 12,859(2) A, b = 27,354(2)A, c = 15,222(3)A, α=γ =90°, β=
26,35° The FT-IR analysis of the catalytic support allowed us to
identify the absorption bands of the different groups characteris-
tic of α-Ca (PO ) (Fig. 3). All bands have been listed in Table 1.
The α-Ca3 (PO4)2 is prepared and characterized successfully.
Then, we studied their catalytic performance in the Knoevenagel
condensation and the synthesis of 2,3-diphenylquinoxaline. We
performed the condensation of p-chlorobenzaldehyde 1a, and the
malononitrile 2a in 2 ml of ethanol at room temperature as
model reaction (Scheme 1). Similarly, we accomplished the syn-
thesis of 2,3-diphenylquinoxaline via condensation between the o-
phenylenediamine 4a with the benzile 5a (Scheme 2) in 2 ml of
EtOH at room temperature.
1
3
4 2
−1
Moreover, a less intense band at 725 cm
is corresponding to
the P O7 grouping [12]. Based on the scanning electron microscopy
2
(
SEM) analysis of our catalytic support, the α-Ca (PO ) with dif-
ferent enlargements 5, 10, 20 and 50 μm are shown in Fig. 4. The
obtained micrographs showed clearly that the α-Ca (PO ) surface
3 4 2
3
4 2
had a heterogeneous microstructure is mainly composed of irregu-
lar geometry particles in agglomerated form. Furthermore, the sur-
face of these agglomerates is moderately smooth with a low visible
porosity. To determine the nature of the elements in the studied
sample, a dispersive energy spectroscopy (EDS) analysis was per-
formed. From the EDS analysis of our support, showed clearly the
presence of the characteristic peaks of the elements Ca, P, O and
C (Fig. 5). This results confirmed that the structure of our support
This reaction is considered a model reaction. The results are
grouped in Table 2. The results show that in the absence of the
catalyst product 3a is obtained with a yield of 54% after 60 min
(
(
Table 2, Entry 1) and product 6a with a yield of 47% for 10 min
Table 2, Entry 1). On the other hand, both reactions are performed
in the presence of catalyst leads to the desired product 3a with a
yield of 91% during 30 min of agitation (Table 2, Entry 2) and pro-
vides the desired product 6a after 10 min of agitation with a very
Scheme 5. Suggested transformation mechanism for the synthesis of alkenes catalyzed by α-Ca3 (PO4)2.
8

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
good yield (Table 2, Entry 2). This showed clearly that our catalyst
exhibits significant catalytic activity in both reactions. To choose
the most suitable solvent for the preparation of products 3a and
Ca (PO ) in 2 mL of ethanol at room temperature. The optimal
3 4 2
reaction conditions were subsequently applied in the generaliza-
tion of Knoevenagel condensation using substituted aromatic alde-
hydes and malononitrile, ethyl cyanoacetate and methyl cyanoac-
etate. The results are listed in Table 5. Based on the present re-
sults, we have noticed that the condensation of aromatic aldehy-
des with malononitrile has resulted in the desired products (3a–d)
with good yields (91–96%) in very short times. The same remark is
made when malononitrile is replaced with methyl cyanoacetate or
ethyl cyanoacetate (3e–l). Certainly, the desired products are also
obtained with good yields that are varied between 83 and 94% in
processing times greater than 30 min which is reflected in the fact
that methyl cyanoacetate or ethyl cyanoacetate is less reactive than
malononitrile. According to the present results, it can be inferred
that the substitutes nature of the aldehyde level has no influence
on yields and processing times. After optimizing the conditions of
the model reaction on the 6a product formation, this process was
generalized for the synthesis of series of 2.3-diphenylquinoxalines
derivatives. Indeed, the reaction was achieved from the condensa-
tion of various o-phenylenediamine substituted 4 with benzile 2.
The results are listed in Table 6. Based on the results represented
in Table 6, we found that optimal conditions remaining still ef-
fective for the synthesis of 2.3-diphenylquinoxaline drifts. In ad-
dition, the desired products are obtained with good to excellent
yields in front the shorter reaction times regardless of the nature
of the 1.2-diamine substitutions (Product 6a–c). The catalyst effi-
ciency depends also on its long durability, i.e. the possibility of be-
ing reused without any significant loss of catalytic activity even af-
ter several cycles of use. To do this, the reuse of α-Ca (PO ) stud-
6a. We have carried out model reactions in different solvents. The
results are represented in Table 3. According to Table 2, the syn-
thesis of products 3a and 6a in protic polar solvents (MeOH and
EtOH) with excellent yields (Table 3, Entry 1). On the other hand,
the reaction in the apolar solvent (THF) allows the product 3a to be
obtained with a good performance for 45 min (Table 3, Entry 2).
For the aprotic polar solvent such as acetonitrile, the desired prod-
uct 3a is obtained with a moderate yield for 40 min (Table 3, En-
try 3). Therefore, ethanol is chosen as an adequate ecological sol-
vent for both moderate point-of-view performance reactions and
very short time. To study the effect of α-Ca (PO ) mass on the
3
4 2
performance of products 3a and 6a. We performed model conden-
sation by varying the amount of our catalyst from 0.5 to 20 mg
in the operating conditions described above. The results are re-
ported in the Table 4. The obtained results showed that a catalytic
quantity of 8 mol%/2.56 mg was sufficient to give very good yields
for the formation of products 3a and 6a (Table 4, Entry 8). When
you exceed the optimum mass, the yields remain almost constant
(
Table 4, Entries 9 and 10). But for the mass of 20 mol%/6.44 mg
there is a slight decrease in yield (Table 4, Entry 11). Therefore,
this decrease in the α-Ca (PO ) mass has a slight influence on
3
4 2
the yields of products 3a and 6a. This results can be explained by
the decrease in α-Ca (PO ) in reactions which can influence the
3
4 2
interaction between substrates and our catalyst. Finally, we found
that the best results are obtained when the formation of products
3a and 6a is carried out in the presence of 8 mol%/2.56 mg of α-
3
4 2
Scheme 6. Proposed transformation mechanism for the synthesis of 2,3-diphenylquinoxaline derivatives in the presence of α-Ca3 (PO4)2.
9

H. Anahmadi, M. Fathi, F. El hajri et al.
Journal of Molecular Structure 1248 (2022) 131449
ied was carried out under optimal conditions for product forma-
tion 3a (Scheme 3) and 6a (Scheme 4). The catalyst removed from
the reaction mixture by simple filtration was thoroughly washed
with ethanol and dried at 80 °C. The recycled catalyst can be used
for subsequent reactions without loss of catalytic activity. The re-
sults are grouped in Fig. 6. The results show clearly that the cat-
alyst α-Ca (PO ) could be recycled five times in a run without
and Sarra Sibous performed part of the manuscript. Said Boukhris,
Brahim Chafik El Idrissi, Mohamed Salahdine El youbi and Abde-
laziz Souizi designed the work and were part of the manuscript
writ-up.
Declaration of Competing Interest
3
4 2
any significant loss of catalytic activity (Fig. 6). According to our
knowledge, the reuse of this catalyst is significantly superior to
most catalysts reported in the literature. The experimental stud-
ies conducted during this work were accompanied by a compara-
tive study between the efficacy of α-Ca (PO ) and those of other
The authors of this manuscript report that there are no conflicts
of interest relevant to this research work.
Supplementary materials
3
4 2
announced catalysts dabs the literature regarding knoevenagel con-
densation and the synthesis of 2.3-diphenylquinoxaline. The results
are grouped in Table 7. From the table results, it can be concluded
that heterogeneous catalyst α-Ca (PO ) has a very interesting cat-
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.molstruc.2021.131449.
3
4 2
alytic activity compared to other catalysts. Moreover, the procedure
described remains remarkable and comparable to other methods in
terms of mild conditions, very short reaction times, excellent yields
and the amount of catalyst used. For a better understanding the
role played by the present catalyst in the activation of substrates.
An alkene formation mechanism in the presence of α-Ca (PO )
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