Facile and efficient protocols for C–C and C–N bond formation reactions using a superparamagnetic palladium complex as reusable catalyst

Article abstract of DOI:10.1007/s11164-019-03754-y

Abstract: Facile and efficient protocols for some multicomponent coupling reactions such as the Suzuki reaction and synthesis of polyhydroquinoline and 2,3-dihydroquinazoline-4-(1H)-one derivatives using a superparamagnetic palladium complex as catalyst have been developed. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-019-03754-y

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03754-y
Facile and efcient protocols for C–C and C–N bond
formation reactions using a superparamagnetic palladium
complex as reusable catalyst
Mohammad Ali Karimi Zarchi1 ·
Seyed Shahab Addin Darbandizadeh Mohammad Abadi1
Received: 10 September 2018 / Accepted: 28 January 2019
© Springer Nature B.V. 2019
Abstract
Facile and efcient protocols for some multicomponent coupling reactions such as
the Suzuki reaction and synthesis of polyhydroquinoline and 2,3-dihydroquinazo-
line-4-(1H)-one derivatives using a superparamagnetic palladium complex as cata-
lyst have been developed.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-03754-y) contains supplementary material, which is available to authorized users.
*
Mohammad Ali Karimi Zarchi
makarimi@yazd.ac.ir
1
Department of Organic Chemistry, Faculty of Chemistry, Yazd University, P.O. Box 89195-741,
Yazd, Iran
Vol.:(0123456789)
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M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Graphical abstract
Keywords C–C bond formation · C-N bond formation · Palladium · Schif base ·
Magnetite nanoparticles
Introduction
In recent years, heterogeneous catalysts have attracted increasing interest due to their
outstanding characteristics of easy recovery and reusability [1, 2]. In this regard,
magnetic nanoparticles (MNPs) deserve special attention [3]. Indeed, their high sur-
face area, large number of active sites [4–6], high stability, low toxicity, and simple
separation from the reaction mixture using magnetic forces [7, 8] have attraction
attention in various felds such as electronics [9], biotechnology [10], biomedicine
[11], medicine [12], metal ion extraction [13], optical imaging [14], magnetic reso-
nance imaging (MRI) [15], targeted drug delivery [16], and catalysis [17]. Despite
these widespread applications of MNPs in diverse felds, particular properties of
bare nanoparticles are degraded because of their high aggregation afnity, suscepti-
bility to oxidation, poor morphology, and particle size distribution [18–20].
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Facile and efcient protocols for C–C and C–N bond formation…
A strategy to solve these problems is to coat the nanoparticles with silica [21–23],
polymer [24–28], carbon [29, 30], and precious metals [31, 32]. More importantly,
transition-metal ion complexes with a Schif base have attracted considerable atten-
tion due to their various felds of applications, showing medicinal, industrial, and
catalytic activities [33].
Palladium plays a pivotal role in the synthesis of organic compounds, especially
as a catalyst in the feld of carbon–carbon coupling [34, 35]. Because of the harsh
conditions required for purifcation of the fnal product and nonreusability of homo-
geneous palladium catalysts [35–37], heterogeneous palladium has been applied to
overcome these problems.
Recently, multicomponent reactions (MCRs) have attracted prime interest for
synthesis of heterocyclic compounds, due to the ability to design and discover new
biologically active molecules in a single step [38]. The polyhydroquinolines are an
important class of heterocyclic compounds that possess a broad spectrum of applica-
tions, making them privileged in the heterocyclic compound feld, e.g., as calcium-
channel blockers, vasodilators, hepatoprotective agents, antiatherosclerotic agents,
bronchodilators, antitumor agents, geroprotective agents, and antidiabetic agents
[39–41]. Several kinds of approaches, including use of solar thermal energy [42],
grinding [43], and microwave irradiation [44], as well as many types of catalyst such
as Yb(OTf)3 [45], ionic liquids [46], and HClO4–SiO2 [47] have been reported for
synthesis of polyhydroquinolines.
2,3-Dihydroquinazoline-4-(1H)-one derivatives are another important class of
heterocyclic compounds that have attracted signifcant attention due to their broad
spectrum of applications in the feld of organic synthesis, showing biological activ-
ity including anticonvulsant, anticancer [48], antifungal [49], and antibacterial
[50] efects. Recently, a large number of catalytic approaches have been developed
for preparation of 2,3-dihydroquinazoline-4-(1H)-ones, including some based on
NH4Cl [51], Brønsted and phosphoric acids [52, 53], tetra-n-butylammonium bro-
mide (TBAB) [54], TiCl4–Zn [55], and CuCl2 [56].
C–C bond formation has been widely applied in diverse areas such as production
of many manmade products [55] as well as synthesis of natural products, agrochem-
icals, pharmaceuticals, biologically active compounds, advanced materials [56, 57],
polymers and material science [58, 59], and many organic building blocks, therapeu-
tic drugs, and their intermediates [60]. The Suzuki–Miyaura [61], Heck–Mizoroki
[62], Sonogashira–Hagihara [63], Kumada [64], Hiyama [65], and Still [48] cou-
pling reactions have been utilized as powerful methodologies for C(sp2)- C(sp2) bond
formation [66]. Traditionally, the mentioned reactions are carried out in organic sol-
vents in presence of palladium salt [50], palladium supported on polymers [67–70],
or palladium–Schif base complexes [71–73].
To address some of the disadvantages of the mentioned methods, such as unsat-
isfactory yield, use of toxic solvent, and harsh conditions for catalyst recovery,
we report herein the use of a superparamagnetic palladium complexed dendrimer
(abbreviated as Pd-Schif-Base@Fe3O4 MNPs) as catalyst for C–C and C–N bond
formation reactions in a few multicomponent reactions, such as synthesis of poly-
hydroquinoline and 2,3-dihydroquinazoline-4-(1H)-one derivatives and the Suzuki
reaction (Scheme 1).
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M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Scheme 1 Synthesis of polyhydroquinoline (1) and 2,3-dihydroquinazoline-4-(1H)-one derivatives (2)
and Suzuki reaction (3) using Pd-Schif-Base@Fe3O4 MNPs as catalyst
Experimental
Materials and instruments
All chemicals were commercial products. All reactions were monitored by thin-
layer chromatography (TLC), and yields refer to isolated products. Melting points
1
were obtained on Büchi B-450 apparatus and are uncorrected. H and 13C nuclear
magnetic resonance (NMR) spectra were recorded in dimethylsulfoxide (DMSO)-
d6 on a Bruker AC AV ANCEDPX 500 spectrometer. Infrared (IR) spectra of
the catalysts and reaction products were recorded on a Bruker FT-IR Equinax-55
single-beam spectrophotometer. Scanning electron microscopy (SEM) images
were recorded using a TESCAN model VEGA3 FESEM. Transmittance electron
microscopy (TEM) imaging was performed using a Zeiss EM10C at 10 kV. X-ray
difraction (XRD) patterns were recorded on a PANalytical X’Pert PRO. Thermo-
gravimetric analysis (TGA) was carried out under Ar up to 1000 °C at 10 °C/min
using a STA504 (Bahr, Germany). The N2 adsorption–desorption isotherm obtained
using a PHS-1020 (PHS China) was used to determine the specifc surface area by
Brunauer–Emmett–Teller (BET) method, the total pore volume, and the mean pore
diameter by Barrett–Joyner–Halenda (BJH) method.
Preparation of Fe3O4 MNPs
Fe3O4 magnetic nanoparticles were prepared by coprecipitation technique [57].
In a typical procedure, FeCl2.4H2O (1.99 g, 10 mmol) and FeCl3.6H2O (5.41 g,
20 mmol) were dissolved in distilled water (30 mL). The solution was heated to
60 °C under nitrogen while being stirred by a mechanical stirrer for about 30 min,
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Facile and efcient protocols for C–C and C–N bond formation…
followed by slow addition of 25 % ammonia solution (35 mL). The mixture was
stirred for 30 min. After that, the reaction mixture was cooled to room tempera-
ture, then the resulting black precipitate was separated using an external magnet and
washed with deionized water (3×100 mL). The precipitate was dried at 80 °C in an
oven for 2 h (abbreviated as Fe3O4 MNPs).
Preparation of Pd‑Schif‑Base@Fe3O4 MNPs
Fe3O4 MNPs (1 g) were dispersed in 50 mL ethanol/water (1:1) solution under ultra-
sonic irradiation for 60 min. Thereafter, 1.5 mL 3-chloropropyltrimethoxysilane
(CPTMS) was added to the reaction mixture. The reaction mixture was stirred using
mechanical stirring under nitrogen atmosphere at 40 °C for 12 h. The precipitate
was recovered by magnetic separation, washed with ethanol, and dried at 80 °C in
an oven for 2 h. The resulting solid (CPTMS@Fe3O4 MNPs) was then refuxed with
1 g diethylenetriamine (DETA) in ethanol for 12 h under nitrogen atmosphere. After
this period of time, the reaction mixture was cooled, separated by magnetic decan-
tation, washed with ethanol, and dried at 80 °C in an oven for 2 h (abbreviated as
DETA-PTMS@Fe3O4 MNPs). Then, the obtained DETA-PTMS@Fe3O4 MNPs
were refuxed in ethanol (20 mL) overnight under nitrogen atmosphere in presence
of 0.5 g diacetyl monoxime (DAM). The solid product (DAM-DETA-PTMS@Fe3O4
MNPs) was obtained by magnetic separation, then washed with ethanol, and dried at
80 °C in an oven for 2 h. Finally, for preparation of Pd-Schif-Base@Fe3O4 MNPs,
210 mg PdCl2 dissolved in 70 mL pure acetone was refuxed with the complex pre-
pared in the previous step (DAM-DETA-PTMS@Fe3O4 MNPs) overnight under
nitrogen atmosphere. The Schif base complex of palladium was separated using an
external magnet and dried under vacuum at 60 °C.
General procedure for synthesis of biphenyls
A mixture of halobenzene (1 mmol), K2CO3 (2 mmol), phenylboronic acid
(1 mmol), and Pd-Schif-Base@Fe3O4 MNPs (5 mg) as catalyst was taken in a 5-mL
round-bottomed fask in dimethylformamide (DMF) and heated at 90 °C. After reac-
tion completion (monitored by TLC), the mixture was cooled to room temperature
and the catalyst was separated from the reaction mixture using an external mag-
net and washed with diethyl ether. The reaction mixture was extracted with water
and diethyl ether. The organic layer was dried over Na2SO4. Then, the solvent was
evaporated under reduced pressure, and pure biphenyl derivatives were obtained in
high yields. Further purifcation was achieved by column chromatography using
n-hexane:EtOAc (8:2).
General procedure for synthesis of polyhydroquinolines
A mixture of an aryl aldehyde (1 mmol), dimedone (1 mmol), ammonium acetate
(1.5 mmol), ethyl acetoacetate or ethyl cyanoacetate (1 mmol), and Pd-Schif-
Base@Fe3O4 MNPs (3 mg) was taken in a 5-mL round-bottomed fask and stirred at
70 °C under solvent-free conditions. After reaction completion (monitored by TLC),
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M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
the mixture was cooled to room temperature. Boiling EtOH (3 mL) was added to
the mixture. The catalyst was separated from the reaction mixture using an external
magnet and washed with EtOH. The fnal product was obtained after evaporation of
solvent under reduced pressure. Pure polyhydroquinoline derivatives were obtained
by recrystallization in ethanol with high yields.
General procedure for synthesis of 2,3‑dihydroquinazoline‑4‑(1H)‑ones
A mixture of an aryl aldehyde (1 mmol), anthranilamide (1 mmol), and Pd-Schif-
Base@Fe3O4 MNPs (3 mg) was taken in a 5-mL round-bottomed fask in H2O as
solvent and stirred at 90 °C. After reaction completion (monitored by TLC), the
reaction mixture was cooled to room temperature and the catalyst was separated
from the reaction mixture using an external magnet and washed with H2O:EtOH
(1:1). The solvent was evaporated under reduced pressure, and all products were
recrystallized in ethanol, obtaining the fnal pure 2,3-dihydroquinazoline-4-(1H)-
one derivatives in high yields.
Physical and spectroscopic data for selected biphenyl,
2,3‑dihydroquinazoline‑4‑(1H)‑one, and polyhydroquinoline derivatives
Biphenyls (6a–c)
FT-IR (KBr): vmax (cm−1)=3032, 1473, 1271, 1090, 1003, 723, 690.
1H NMR (400 MHz, DMSO-d6): δ (ppm)=7.36 (t, J=7.2 Hz, 2H), 7.46 (t,
J=8 Hz, 4H), 7.66 (d, J=7.2 Hz, 4H).
13C NMR (100 MHz, DMSO-d6): δ (ppm)=126.747, 127.388, 128.915, 140.342.
2-Aminobiphenyl (6l)
FT-IR (KBr): vmax (cm−1)=3480, 3387, 3023, 1614, 1500, 1480, 1434, 1284,
1156, 1071, 1007, 753, 704, 564, 480.
1H NMR (400 MHz, DMSO-d6): δ (ppm)=4.71 (s, NH2, 2H), 6.60 (t, J=7.2 Hz,
1H), 6.7 (d, J=8 Hz, 1H), 6.9 (d, J=8 Hz, 1H), 7 (t, J=8 Hz, 1H), 7.3 (m, 1H),
7.38 (m, 4H).
13C NMR (100 MHz, DMSO-d6): δ (ppm)=115.601, 117.287, 126.272, 126.980,
128.462, 128.946, 130.323, 139.963, 145.055.
4,4′-Biphenol (6n)
FT-IR (KBr): vmax (cm−1)=3351, 1610, 1591, 1497, 1424, 1382, 1296, 1237,
1174, 818, 512.
1H NMR (400 MHz, DMSO-d6): δ (ppm)=6.9 (dd, J=8, 2 Hz, 4H), 7.46 (dd,
J=8, 2 Hz, 4H), 9.48 (s, OH, 2H).
13C NMR (100 MHz, DMSO-d6): δ (ppm)=116.742, 128.055, 132.277, 157.248.
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Facile and efcient protocols for C–C and C–N bond formation…
Ethyl
4-(3-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydro-
quinoline-3-carboxylate (7o)
FT-IR (KBr); vmax (cm−1) = 3300, 3079, 2662, 2930, 1697, 1646, 1610, 1484,
1380, 1309, 1278, 1265, 1213, 1172, 1151, 1109, 1070, 1037, 1000, 862, 804,
773, 732, 696, 625, 587, 520.
1H NMR (400 MHz, CDCl3): δ (ppm) = 0.95 (s, 3H), 1.07 (s, 3H), 1.2 (t,
J = 8 Hz, 3H), 2.2 (m, 4H), 2.35 (s, 3H), 3.75 (s, 3H), 4.06 (q, J = 7.2 Hz, 2H),
5.04 (s, 1H), 6 (br, NH, 1H), 6.6 (ddd, J = 8.2, 2.8, 0.8 Hz, 1H, ArH), 6.86 (m,
1H), 6.9 (d, J = 7.6 Hz, 1H, ArH), 7.11 (dd, J = 8, 7.8 Hz, 1H, ArH).
13C NMR (100 MHz, CDCl3): δ (ppm) = 19.250, 24.070, 32.074, 34.407,
37.560, 41.536, 45.586, 55.780, 59.980, 64.751, 110.612, 115.875, 116.410,
119.147, 125.518, 133.690, 149.099, 153.780, 154.682, 164.242, 172.557,
200.920.
Ethyl
4-(2,4-dichlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahyd-
roquinoline-3-carboxylate (7i)
FT-IR (KBr): vmax (cm−1) = 3212, 3081, 2954, 1704, 1612, 1494, 1220, 759.
Mass m/z (%): 393, 359, 334, 316, 301, 248.
Ethyl
2,7,7-trimethyl-5-oxo-4-(4-nitrophenyl)-1,4,5,6,7,8-hexahydroqui-
noline-3-carboxylate (7b)
FT-IR (KBr): vmax (cm−1) = 3274, 3075, 2965, 1702, 1648, 1494, 1519, 1216,
831.
1H NMR (400 MHz, CDCl3): δ ppm = 0.92 (s, 3H, CH3), 1.10 (s, 3H, CH3),
3
1.20 (t, 3H, J = 7.2 Hz, OCH2), 2.13–2.37 (m, 4H, 2CH2), 2.41 (s, 3H, CH3),
4.05 (q, 2H, OCH2CH3), 5.18 (s, 1H, CH), 6.58 (s, 1H, NH), 7.51 (d, 2H,
ArH), 8.10 (d, 2H, 3J = 8.8 Hz, ArH).
13C NMR (100 MHz, CDCl3): δ ppm = 14.22, 19.44, 27.07, 29.40, 32.74,
37.24, 40.96, 50.62, 60.11, 104.87, 111.03, 123.36, 128.99, 144.60, 146.20,
149.03, 154.49, 166.90, 195.51.
Mass m/z (%): 370, 355, 239, 324, 311, 284.
Ethyl
4-(4-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydro-
quinoline-3-carboxylate (7c)
FT-IR (KBr): vmax (cm−1) = 3274, 3244, 3207, 3077, 2959, 2935, 1706, 1649,
1605, 1489, 1421, 1382, 1311, 1280, 1214, 1191, 1167, 1154, 1141, 1108,
1091, 1072, 1032, 857, 844, 771, 608, 535.
1H NMR (400 MHz, CDCl3): δ ppm = 0.94 (s, 3H, CH3), 1.08 (s, 3H, CH3),
3
1.22 (t, 3H, J = 7.2 Hz, OCH2), 2.14–2.32 (m, 4H, 2CH2), 2.37 (s, 3H, CH3),
4.09 (q, 2H, OCH2CH3), 5.05 (s, 1H, CH), 6.93 (s, 1H, NH), 7.18 (d, 2H,
ArH), 7.27 (d, 2H, 3J = 8 Hz, ArH).
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M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
13C NMR (100 MHz, CDCl3): δ ppm = 14.26, 19.30, 27.07, 29.49, 32.68,
36.30, 40.80, 50.75, 59.94, 105.61, 111.53, 128.01, 129.45, 131.62, 144.05,
145.74, 149.17, 167.35, 195.83.
2-(4-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one (8b)
FT-IR (KBr): vmax (cm−1) = 3309, 3192, 3062, 1655, 1610, 1510, 1485, 1385,
1153, 1093, 1017, 753, 666, 504.
1H NMR (400 MHz, CDCl3): δ ppm = 4.39 (br, NH, 1H), 5.79 (s, NH, 1H),
5.93 (s, CH, 1H), 6.71 (d, 1H, ArH), 6.95 (t, 1H, ArH), 7.38 (t, 1H, ArH), 7.45
(d, 3J = 8.4, 2H, ArH), 7.58 (d, 3J = 8.4, 2H, ArH), 7.97 (d, 1H, ArH).
13C NMR (100 MHz, CDCl3): δ ppm = 68.50, 114.65, 115.60, 119.96, 128.76,
128.86, 129.40, 134.18, 136.13, 137.11, 147.00, 164.60
2-(4-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one (8f)
FT-IR (KBr): vmax (cm−1) = 3099, 3194, 3066, 1655, 1609, 1509, 1484, 1385,
1153, 1074, 1014, 753, 679.
1H NMR (400 MHz, CDCl3): δ ppm = 4.41 (br, NH, 1H), 5.85 (s, NH, 1H),
5.91 (s, CH, 1H), 6.71 (d, 1H, ArH), 6.94 (t, 1H, ArH), 7.36 (t, 1H, ArH), 7.51
(d, 3J = 8.4, 2H, ArH), 7.61 (d, 3J = 8.4, 2H, ArH), 7.96 (d, 1H, ArH).
13C NMR (100 MHz, CDCl3): δ ppm = 68.56, 114.66, 115.60, 119.97, 124.31,
128.76, 129.13, 132.38, 134.18, 137.64, 146.97, 164.58.
2-(4-Nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (8l)
FT-IR (KBr): vmax (cm−1) = 3267, 3163, 30,636, 1606, 1617, 1458, 1346, 1107,
853, 809, 748, 694.
1H NMR (400 MHz, DMSO-d6): δ (ppm) = 5.91 (s, CH, 1H), 6.67–6.71 (m,
1H, ArH), 6.77 (d, J = 8.4, 1H, ArH), 7.24–7.28 (m, 1H, ArH), 7.34 (br, NH,
1H), 7.60–7.62 (1H, ArH), 7.74 (d, J = 9.2, 1H, ArH), 7.62 (d, J = 5.6, 1H,
ArH), 8.34 (s, NH, 1H).
13C NMR (100 MHz, DMSO-d6): δ (ppm) = 65.2, 114.5, 114.8, 123.5, 117.4,
127.3, 127.9, 133.5, 147.1, 147.3, 149.2, 163.4.
2-(p-Tolyl)-2,3-dihydroquinazolin-4(1H)-one (8q)
FT-IR (KBr): vmax (cm−1) = 3462, 3320, 2942, 2826, 1661, 1589, 1521, 1458,
1421, 1387, 1323, 1233, 1125, 1066, 1006, 812, 770, 713, 691, 658.
1H NMR (400 MHz, DMSO-d6): δ (ppm) = 2.29 (s, CH3, 3H), 5.70 (s, CH,
1H), 6.64–6.68 (m, 1H, ArH), 6.77 (d, J = 8.0, 1H, ArH),.7.06 (br, NH, 1H),
7.19 (d, J = 8.0, 2H, ArH), 7.21–7.25 (m, 1H, ArH), 7.37 (d, J = 8.0, 2H, ArH),
7.604(d, J = 9.2, 1H, ArH), 8.24 (s, NH, 1H).
13C NMR (100 MHz, DMSO-d6): δ (ppm) = 20.8, 66.3, 114.9, 117.0, 120.8,
127.6, 129.8, 141.4, 147.8, 163.5.
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Facile and efcient protocols for C–C and C–N bond formation…
Results and discussion
The morphology of Fe3O4 MNPs and Pd-Schif-Base@Fe3O4 MNPs was stud-
ied and compared by scanning electron microscopy (SEM) (Fig. 1). As shown in
Fig. 1, although the Fe3O4 MNPs showed modifed structure, Pd-Schif-Base@
Fe3O4 MNPs remained uniform.
The FT-IR spectra of bare Fe3O4 MNPs, CPTMS@Fe3O4 MNPs, DETA-
PTMS@Fe3O4 MNPs, DAM-DETA-PTMS@Fe3O4 MNPs, and Pd-Schif-Base@
Fe3O4 MNPs are shown in Fig. 2. The FT-IR spectrum of Fe3O4 MNPs (spec-
trum a) exhibited characteristic peaks at 590 and 628 cm−1 corresponding to
Fe–O band in tetrahedral sites of bare magnetic nanoparticles [58] and a broad
band at 3392 cm−1 assigned to asymmetric and symmetric stretching vibrations
of –OH band of the surface of the magnetic nanoparticles. Also, a peak appearing
at 1624 cm−1 was assigned to bending vibration of OH band or stretching vibra-
tional mode of an adsorbed water layer [59]. In the FT-IR spectrum of CPTMS@
Fe3O4 MNPs (spectrum b), the presence of the anchored Cl-propyl group was
confrmed by C–H stretching vibrations appearing at 2853 and 2925 cm−1, the
peak at 892 cm−1 being attributed to Fe–O–Si stretching vibration. The obser-
vation of the characteristic C–N stretching at 1012 and 1117 cm−1 for DETA-
PTMS@Fe3O4MNPS (spectrum c) provides evidence confrming the formation
of the desired ligand [60]. A peak at 1624 cm−1 in the spectrum of DAM-DETA-
PTMS@Fe3O4 MNPs is due to C=N bond formation.
In the spectrum of Pd-Schif-Base@Fe3O4 MNPs (spectrum e), the C=N bond
absorption shifts to lower frequency (1580 cm−1) compared with the spectrum for
DAM-DETA-PTMS@Fe3O4 MNPs (spectrum d), due to successful bond forma-
tion between palladium and C=N bond.
TEM micrographs of the synthesized catalyst (Pd-Schif-Base@Fe3O4 MNPs)
are shown in Fig. 3. Generally, the nanoparticles showed spherical morphology
with size in varying ranges, as summarized in Fig. 4.
Fig. 1 SEM images of Fe3O4 MNPs and Pd-Schif-Base@Fe3O4 MNPs
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M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Fig. 2 FT-IR spectra of bare Fe3O4 MNPs (a), CPTMS@Fe3O4 MNPs (b), DETA-PTMS@Fe3O4 MNPs
(c), DAM-DETA-PTMS@Fe3O4 MNPs (d), and Pd-Schif-Base@Fe3O4 MNPs (e)
Fig. 3 TEM images of Pd-Schif-Base@Fe3O4 MNPs
To determine the crystal phase of the Pd-Schif-Base@Fe3O4 MNPs, x-ray dif-
fraction (XRD) analysis (Fig. 5) was performed. As shown in Fig. 5, iron oxide
phase was identifed by peaks at 30.3° (220), 35.67° (311), 43.39° (400), 53.66°
(422), 57.34° (511), and 62.93° (440), in agreement with the standard XRD pattern
for magnetite [61]. Also, the peaks at 40.21°, 47.15°, and 68.01° confrm the pres-
ence of palladium species [62, 63].
The energy-dispersive X-ray (EDX) spectra of Pd-Schif-Base@Fe3O4 MNPs
are shown in Fig. 6. EDX spectra taken at diferent points of the images confrmed
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Facile and efcient protocols for C–C and C–N bond formation…
Fig. 4 Particle size range of Pd-Schif-Base@Fe3O4 MNPs
Fig. 5 XRD pattern of Pd-Schif-Base@Fe3O4 MNPs
the presence of Pd in the catalyst; the percentage contents of C, N, O, Fe, Cl, and
Pd species obtained by atomic absorption spectroscopy are also shown. For further
study, we determined the exact amount of palladium supported on the catalyst by
inductively coupled plasma atomic emission spectroscopy (ICP-AES). The amount
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M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Fig. 6 EDX spectra of Pd-Schif-Base@Fe3O4 MNPs
of palladium immobilized on the Pd-Schif-Base-Fe3O4 MNPs support was found to
be 1.92 mmol g−1.
TGA is an efcient and fascinating technique to investigate the thermal stability
of the immobilized catalyst relative to magnetic nanoparticles. Also, the bond for-
mation between Fe3O4 MNPs and Pd-Schif-Base@Fe3O4 MNPs can be interpreted
and verifed by TGA. The TGA curve for Pd-Schif-Base@Fe3O4 MNPs shows the
mass loss corresponding to decomposition of organic functional groups upon heat-
ing. As shown in Fig. 7, the TGA curve of Pd-Schif-Base@Fe3O4 MNPs shows a
small amount of weight loss below 250 °C, due to desorption of physically adsorbed
solvents and surface hydroxyl groups. A weight loss of about 5 % occurs from 250
to 700 °C, due to decomposition of immobilized organic species on the surface of
the Fe3O4 MNPs.
The magnetic properties of Fe3O4 MNPs and Pd-Schif-Base@Fe3O4 MNPs
were characterized by vibrating-sample magnetometry (VSM). As shown in
Fig. 8, VSM measurements on Fe3O4 MNPs revealed a saturation magnetization
1 3

Facile and efcient protocols for C–C and C–N bond formation…
Fig. 7 TGA curve of Pd-Schif-Base@Fe3O4 MNPs
Fig. 8 Magnetization curves of Fe3O4 MNPs and Pd-Schif-Base@Fe3O4 MNPs
(Ms) of 62.10 emu g−1, while the Ms value of Pd-Schif-Base@Fe3O4 MNPs
decreased to 54.04 emu g−1 due to the anchored palladium complex.
The ability to separate the catalyst magnetically from the reaction medium was
evaluated by placing an external magnet near the reaction mixture vessel. The
Pd-Schif-Base@Fe3O4 MNPs were attracted towards the external magnet in 5 s
(Fig. 9).
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Fig. 9 Photograph of aqueous solution A with dispersed Pd-Schif-Base@Fe3O4 MNPs and B after 5 s of
applied magnetic feld
Figure 10 shows the XPS elemental survey scan of Pd-Schif-Base@Fe3O4
MNPs, in which peaks corresponding to palladium, carbon, nitrogen, chlorine,
oxygen, iron, and silicon are clearly observed.
Figure 11 shows the iron binding energy of Pd-Schif-Base@Fe3O4 MNPs.
This spectrum exhibits two major peaks centered at 711 and 724.3 eV, which are
assigned to Fe 2p3/2 and Fe 2p1/2 for Fe3O4, respectively [64–67]. Also, a satellite
peak at 719.8 eV corresponds to Fe3+ ions in γ-Fe3O4 [68], possibly due to partial
oxidation of Fe3O4 MNPs.
Fig. 10 Full XPS spectrum of Pd-Schif-Base@Fe3O4 MNPs
1 3

Facile and efcient protocols for C–C and C–N bond formation…
Fig. 11 Fe 2p XPS spectrum of
Pd-Schif-Base@Fe3O4 MNPs
To determine the Fe3+/Fe2+ ratio, the Fe 2p1/2 and Fe 2p3/2 peaks were decon-
voluted (Fig. 12), revealing an Fe3+/Fe2+ ratio of 1.8 based on the area under the
curves [69]. This value is acceptable in comparison with the experimental results.
To study the types of carbon covalent bonds, the C 1s signal was also decon-
voluted (Fig. 13), revealing three peaks at 285, 286.7, and 288.9 eV that corre-
spond to carbon–carbon single bond (C–C), carbon–nitrogen double bond (C=N),
Fig. 12 Deconvoluted Fe 2p XPS spectrum of Pd-Schif-Base@Fe3O4 MNPs
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Fig. 13 C 1s XPS spectrum of Pd-Schif-Base@Fe3O4 MNPs
Fig. 14 N 1s XPS spectrum of Pd-Schif-Base@Fe3O4 MNPs
1 3

Facile and efcient protocols for C–C and C–N bond formation…
and carbon–nitrogen single bond (C–N), respectively [70–72]. Also, as shown in
Fig. 14, the peaks at 389.5. 400.6, and 403 eV refect the bonding structure of the
carbon–nitrogen double bond (C=N), carbon–nitrogen single bond (C–N), and
nitrogen–oxygen single bond (N–O), respectively [72, 73].
Figure 15 shows the palladium binding energy of Pd-Schif-Base@Fe3O4
MNPs. This spectrum exhibits two prominent peaks at 338.3 and 343.5 eV, read-
ily assigned to Pd 3d3/2 and Pd 3d3/2, respectively [74, 75].
A structure for the catalyst, based on combined information from the experi-
mental results and characterization data, is proposed in Scheme 2.
C–C and C–N coupling reactions including the Suzuki reaction and synthesis
of polyhydroquinolines, 2,3-dihydroquinazolin-4(1H)-ones, and biphenyls were
used to evaluate the catalytic performance of Pd-Schif-Base@Fe3O4 MNPs.
In our primary experiments, the Suzuki reaction between iodobenzene and
phenylboronic acid was selected as model reaction to optimize the efects of sol-
vent, base and its amount, temperature, and amount of catalyst.
Table 1 presents the results of optimization of conditions. To investigate the
efect of temperature, the model reaction was performed at various temperatures
(Table 1, entries 1–5). The best result was obtained at 90 °C. We also found that
the amount of catalyst had a signifcant efect on the reaction course (Table 1,
entries 6–8). It was found that 5 mg of Pd-Schif-Base@Fe3O4 MNPs gave
the best result. In order to determine the best base for the Suzuki reaction, the
model reaction was performed in presence of triethylamine, sodium hydroxide,
potassium hydroxide, potassium carbonate, and trisodium phosphate (Table 1,
entries 2, 9–12). The results showed that potassium carbonate was very efec-
tive for these conditions. Also, the efects of various solvents on the model reac-
tion were studied by using EtOH, H2O, EtOH:H2O, and DMSO instead of DMF
Fig. 15 Pd 3d XPS spectrum of
Pd-Schif-Base@Fe3O4 MNPs
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Scheme 2 Synthesis of Pd-Schif-Base@Fe3O4 MNPs
(Table 1, entries 16–20). The results showed that DMF was more efective than
other solvents.
In the second part, the catalytic performance of Pd-Schif-Base@Fe3O4 MNPs
was investigated in the four-component one-pot reaction of dimedone, aldehydes,
ethyl acetoacetate, and ammonium acetate for synthesis of polyhydroquinolines.
Initially, optimization experiments were performed using the reaction of dimedone
(1 mmol), benzaldehyde (1 mmol), ethyl acetoacetate (1 mmol), and ammonium ace-
tate (1.5 mmol) as model reaction in various solvents and in the presence of various
amounts of catalyst at 60–80 °C (Table 2). As expected, no product was obtained in
absence of catalyst even after 1 day (Table 2, entry 15). As is evident from Table 2,
the best results were observed in presence of 3 mg of Pd-Schif-Base@Fe3O4 MNPs
at 70 °C under solvent-free conditions (Table 2, entry 2).
1 3

Facile and efcient protocols for C–C and C–N bond formation…
Table 1 Optimization of reaction conditions for synthesis of biphenyl
Entry Solvent
Temp. (°C) Catalyst (mg) Base/amount (mmol) Time (min) Yield (%)a
1
2
3
4
5
6
7
8
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
EtOH
H2O
80
90
100
110
120
90
90
90
90
90
90
90
90
90
90
90
Refux
90
5
5
5
5
5
2
7
10
5
5
5
5
5
5
5
5
5
K2CO3/2
K2CO3/2
K2CO3/2
K2CO3/2
K2CO3/2
K2CO3/2
K2CO3/2
K2CO3/2
Et3N/2
75
40
40
39
60
90
40
65
60
95
70
40
120
60
100
240
120
150
150
600
1440
98
98
98
98
85
92
97
92
80
79
87
83
81
90
86
40
92
89
85
0.0
0.0
9
10
11
12
13
14
15
16
17
18
19
20
21
NaOH/2
KOH/2
Na3PO4/2
K2CO3/1
K2CO3/1.5
K2CO3/3
K2CO3/2
K2CO3/2
K2CO3/2
K2CO3/2
K2CO3/2
K2CO3/2
5
5
5
0.0
EtOH:H2O (1:1) 90
Solvent-free
DMF
90
90
aYield refers to isolated pure product
In the fnal part, to determine the best catalytic activity for synthesis of
2,3-dihydroquinazolin-4(1H)-ones, the two-component reaction of anthranila-
mide and benzaldehyde was used as model reaction and optimized in terms of
various parameters such as temperature, solvent, and amount of catalyst. In the
preliminary stage of this investigation, synthesis of 2-phenyl-2,3-dihydroquina-
zolin-4(1H)-one (8a) in H2O was performed using diferent amounts of catalyst.
As shown in Table 3, for lower catalyst amount (2 mg), 96 % yield of compound
8a was obtained after 19 min (Table 3, entry 4). On increasing the catalyst weight
to 3 mg, the yield of compound 8a increased to 97 % after 15 min (Table 3, entry
2). This increase in product yield with an increase in the catalyst weight can be
attributed to an increase in the availability of catalytically active sites required
for this coupling reaction. On further increasing the amount of catalyst, namely
for amounts greater than 3 mg, no appreciable change or improvement in prod-
uct yield was observed after 15 min (Table 3, entries 5, 6). The results collected
in Table 3 clearly demonstrate that the reaction rate and product yield not only
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Table 2 Optimization of reaction conditions for synthesis of ethyl 2,7,7-trimethyl-5-oxo-4-phenyl-
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
Entry Catalyst
Temp. (°C) Catalyst (mg) Solvent
Time (min) Yield (%)a
1
Pd-Schif-Base@Fe3O4
60
70
80
70
70
70
70
70
70
70
70
3
3
3
2
4
5
3
3
3
3
3
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
EtOH
32
25
89
93
90
94
93
90
90
67
70
76
62
MNPs
2
Pd-Schif-Base@Fe3O4
MNPs
3
Pd-Schif-Base@Fe3O4
25
MNPs
4
Pd-Schif-Base@Fe3O4
30
MNPs
5
Pd-Schif-Base@Fe3O4
25
MNPs
6
Pd-Schif-Base@Fe3O4
35
MNPs
7
Pd-Schif-Base@Fe3O4
40
MNPs
8
Pd-Schif-Base@Fe3O4
H2O
60
MNPs
9
Pd-Schif-Base@Fe3O4
MeOH
120
240
280
MNPs
10
11
Pd-Schif-Base@Fe3O4
CHCl3
MNPs
Pd-Schif-Base@Fe3O4
CH2Cl2
MNPs
12
13
Fe3O4 MNPs
70
70
3
3
Solvent-free
Solvent-free
65
55
91
90
DAM-DETA-PTMS@
Fe3O4 MNPs
14
15
Pd-DAM-DETA-PTMSa
–
70
70
3
0.0
Solvent-free
Solvent-free 1440
35
85
0.0
aYield refers to isolated pure product
depended strongly on the amount of catalyst (Table 3, entries 2, 4), but also that
the presence of catalyst was pivotal to this process, with only 6 % yield of the
desired product being obtained after 24 h in the absence of catalyst (Table 3,
entry 15). To optimize the temperature, the model reaction was performed at vari-
ous temperatures; according to the obtained results (Table 3, entry 1–3), 90 °C
was chosen as the optimized temperature. To investigate the efect of solvent in
the reaction, the model reaction in presence of 3 mg of Pd-Schif-Base@Fe3O4
MNPs at 90 °C was carried out in diferent solvents (Table 3, entries 2, 7–11).
However, it was noticed that the highest yield and shortest time were achieved
1 3

Facile and efcient protocols for C–C and C–N bond formation…
Table 3 Optimization of reaction conditions for synthesis of 2-phenyl-2,3-dihydroquinazolin-4(1H)-one
Entry Catalyst
Temp. (°C) Catalyst (mg) Solvent Time (min) Yield (%)a
1
2
3
4
5
6
7
8
Pd-Schif-Base@Fe3O4 MNPs
Refux
90
80
90
90
90
90
90
90
90
90
90
90
3
3
3
2
4
5
3
3
3
3
3
3
3
H2O
H2O
H2O
H2O
H2O
H2O
–
EtOH
MeOH
CH3CN 130
15
15
26
19
15
15
39
32
60
93
97
97
96
92
84
93
96
81
90
73
90
90
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Pd-Schif-Base@Fe3O4 MNPs
Fe3O4 MNPs
9
10
11
12
13
DMF
H2O
H2O
90
34
29
DAM-DETA-PTMS@Fe3O4
MNPs
14
15
Pd-DAM-DETA-PTMSa
None
90
90
3
3
H2O
H2O
18
300
89
6
aYield refers to isolated pure product
when using H2O as solvent. Also, to establish the true role of palladium and the
magnetic support, the model reaction was performed in presence of various cata-
lysts (Table 3, entries 12–14).
The above-determined optimized reaction conditions were then applied to explore
the Suzuki reaction and synthesis of polyhydroquinolines and 2,3-dihydroquinazo-
lin-4(1H)-ones; the results are summarized in Tables 6, 7, and 8. As exemplifed in
Tables 6, 7, and 8, these protocols are rather general, being applicable for a wide
variety of electron-rich as well as electron-defcient compounds.
The metal leaching from and heterogeneity of the Pd-Schif-Base@Fe3O4
MNPs catalyst were studied by hot fltration test and ICP analysis. To determine
Table 4 Palladium leaching
Cycle
Residual palladium (mmol/g) Palladium leaching (%)
study of Pd-Schif-Base@Fe3O4
MNPs
PHQ
Suzuki
DHQZ
PHQ
Suzuki
DHQZ
1
2
3
4
5
1.885
1.878
1.875
1.873
1.871
1.895
1.890
1.887
1.886
1.886
1.898
1.894
1.892
1.892
1.892
1.82
0.37
0.16
0.10
0.10
1.30
0.26
0.16
0.05
0.00
1.14
0.21
0.10
0.00
0.00
PHQ polyhydroquinoline, DHQZ 2,3-dihydroquinazolin-4(1H)-one
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Table 5 BET results for Fe3O4
MNPs and Pd-Schif-Base@
Fe3O4 MNPs
Sample
BET surface
Pore diameter
Pore
area (m2 g−1
)
(DBJH) (nm)
volume
(cm3/g)
Fe3O4 MNPs
178.2
1.72
1.17
0.3
0.22
Pd-Schif-Base@ 149.1
Fe3O4 MNPs
the palladium leaching from the catalyst, we considered model reaction condi-
tions without reagents as a new condition. A mixture of catalyst (Pd-Schif-Base@
Fe3O4 MNPs), solvent (EtOH for solvent-free conditions), and additive (if any)
was taken in a 5-mL round-bottomed fask at the stated optimized conditions.
After reaction completion (optimized time for model reaction), the catalyst was
separated using an external magnet and washed with EtOH, then dried in an oven
at 120 °C for 2 h. The amount of palladium in solution was determined by ICP-
AES. This experiment was repeated for fve times of recycling. This procedure
was performed for synthesis of 6a, 7a, and 8a, and the results are summarized
in Fig. 16 and Table 4, indicating negligible leaching of the Pd catalyst. Further-
more, the heterogeneity of the catalyst was confrmed by hot fltration test in syn-
thesis of 6a, 7a, and 8a. The results showed that the yield of the products in half
of the reaction time was 59, 57, and 57 % for 6a, 7a, and 8a, respectively. Then,
the reaction was repeated, and at half the reaction time, the catalyst was recovered
and the fltrate allowed to react further. The yield of the reactions in this stage was
63, 60, and 59 % for 6a, 7a, and 8a, respectively, confrming that no leaching of
palladium occurred.
To study the reusability of Pd-Schif-Base@Fe3O4 MNPs, the magnetic nano-
catalyst was easily recovered from the reaction mixture and reused for synthesis of
polyhydroquinoline, 2,3-dihydroquinazolin-4(1H)-one, and biphenyl derivatives.
The recyclability of the catalyst was examined in synthesis of 6a, 7a, and 8a under
the optimized reaction conditions. The catalyst was separated from the reaction mix-
ture using an external magnet and reused six times, showing negligible loss of activ-
ity. The partial loss of activity may be due to slight leaching of palladium from the
catalyst (Figs. 17, 18).
Some textural and physicochemical properties of the synthesized samples includ-
ing pore diameter (DBJH), BET surface area, and pore volume are presented in
Table 5. As seen, an obvious decrease in the BET surface area, pore volume, and
pore diameter was detected after the modifcation, confrming grafting of the ligand
onto the surface of the Fe3O4 MNPs.
1 3

Facile and efcient protocols for C–C and C–N bond formation…
Table 6 Synthesis of biphenyls catalyzed by Pd-Schif-Base-Fe3O4 MNPs
Entry
Substrate (1)
Substrate (2)
Product
M.P. °C
Time Yield
(min) (%)a
Found
68–70
Report
6a
69–70 [76]
40
98
6b
6c
68–70
69–70 [76]
60
98
68–70
69–70 [76]
90
99
84–85
83–85 [77]
30
100
6d
84–85
57–58
83–85 [77]
57–59 [77]
45
55
93
89
6e
6f
6g
57–58
57–58
57–59 [77]
57–59 [77]
70
91
83
120
6h
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Table 6 (continued)
Entry Substrate (1)
Substrate (2)
Product
M.P. °C
Report
Time Yield
(min) (%)a
Found
119–122
[78]
119–121
6i
6j
80
94
158–161
157–160
[79]
35
96
158–161
47–50
157–160
[79]
6k
6l
50
90
90
87
48–50 [77]
6m
53–54
53–54 [80]
85
88
95
6n
6o
279–280
39–43
280–282
[81, 82]
30
40–41
[83]
i110
81
1 3

Facile and efcient protocols for C–C and C–N bond formation…
Table 6 (continued)
Entry
Substrate (1)
Substrate (2)
Product
M.P. °C
Time Yield
(min) (%)a
Found
Report
119–120
119–121
[84]
100
83
6p
6q
6r
6s
110–112
111–113
[80]
28
84
47
55
89
94
103–110
103–110
110–115
[85]
110–115
[85]
aYield refers to isolated pure product
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Table 7 Synthesis of polyhydroquinolines catalyzed by Pd-Schif-Base-Fe3O4 MNPs
Entry
Substrate (1)
Product
M.P. °C
Time Yield
(min) (%)a
Found
Report
7a
200–203
242–243
200–202
[86]
25
93
85
7b
7c
241–243
[86]
8
244–246
244–246
[86]
25
96
7d
231–234
231–234
[86]
35
97
7e
7f
247–250
176–177
247–248
[87]
30
15
95
90
176–178
[86]
1 3

Facile and efcient protocols for C–C and C–N bond formation…
Table 7 (continued)
Entry
Substrate (1)
Product
M.P. °C
Time Yield
(min) (%)a
Found
Report
7g
207–208
206–208
[86]
20
89
7h
202–205
204–205
[59]
43
88
7i
205–206
[88]
32
25
35
84
79
98
204–205
228–231
7j
230–232
[59]
7k
227–229
260–263
228–230
[89]
259–261
[90]
15
99
7l
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Table 7 (continued)
Entry
Substrate (1)
Product
M.P. °C
Time Yield
(min) (%)a
Found
Report
7m
342–344
343–345
[90]
22
98
7n
367–369
367–369
[90]
30
99
7o
7p
198–200
[91]
36
98
198–200
184–186
184–186
[59]
25
99
7q
20
96
280–283
281–283
[90]
aYield refers to isolated pure product
1 3

Facile and efcient protocols for C–C and C–N bond formation…
Table 8 Synthesis of 2,3-dihydroquinazolin-4(1H)-ones catalyzed by Pd-Schif-Base-Fe3O4 MNPs
Entry
Substrate (1)
Product
M.P. °C
Time Yield
(min) (%)a
Found
Report
8a
214–
216
245–217
[89]
15
11
7
93
93
97
8b
236–
238
235–237
[89]
277–
278
275–280
[92]
8c
8d
7
93
87
208–
211
212–214
[93]
8e
190–
192
190–192
[59]
40
198–
197–199
8f
12
15
11
94
96
89
199
[59]
8g
189–
194
191–193
[94]
8h
200–
202
200–202
[95]
1 3

M. A. Karimi Zarchi, S. S. A. Darbandizadeh Mohammad Abadi
Table 8 (continued)
Entry Substrate (1)
Product
M.P. °C
Time Yield
(min) (%)a
Found
Report
8i
197–199
[59]
196–
199
7
99
8j
231–
232
231–233
[89]
12
6
96
98
188–
190
188–190
[96]
8k
201–
204
200–202
[95]
8l
32
92
8m
15
95
321–
326
Not Found
8n
8o
200–
203
200–203
[92]
47
8
82
99
190–
192
190–192
[59]
1 3