100
M. Nasr-Esfahani et al. / Journal of Molecular Catalysis A: Chemical 382 (2014) 99–105
Therefore, in green point of view the search for the possibil-
FeCl3·6H2O (6.1 g, 0.02 mol) and FeCl2·4H2O (2.35 g, 0.01 mol) were
dissolved in 100 mL distilled water under magnetic stirring. After
10 min, the solution was heated to 90 ◦C under nitrogen atmo-
sphere. Subsequently, the ammonium hydroxide solution (10 mL,
25%) was added drop wise to a reaction mixture. After approxi-
mately 1 h, the reaction mixture was cooled to room temperature
and black precipitate isolated in a magnetic field from the reaction
mixture, repeatedly washed with de-ionized water several times
to remove the remaining impurities.
ity of performing multicomponent reactions under solvent-free
conditions with recoverable catalysts for the synthesis of these
for further improvement toward milder reaction conditions and
higher yields.
Nanoparticles have high surface-to-volume ratio and coordi-
nation sites compared to their bulk analogs, which provide a
larger number of active sites per unit area [29]. In recent years,
as an important family of separation materials, magnetic Fe3O4
nanoparticles (Fe3O4 MNPs) have attracted considerable interest in
chemistry and material sciences, due to their potential applications
properties of Fe3O4 nanoparticles enable the catalyst to be eas-
ily separated with an external magnetic field. Fe3O4 nanoparticles,
as an efficient catalyst in many organic reactions, such as synthe-
sis of 3-[(2-chloroquinolin-3-yl)methyl]pyrimidin-4(3H)ones [32],
propargylic amines [33], ␣-aminonitriles [34], quinoxalines [35],
rewritten around new approaches that search for products and pro-
cesses in the chemical industry that are environmentally acceptable
[40]. Multi-component reactions (MCRs) are of current interest to
organic chemists [41]. In fact MCR method has appeared as an effi-
cient and powerful tool in modern synthetic organic chemistry
allowing the facile creation of new bonds in a one-pot transfor-
mation. Inverse to the classical way to preparation of complex
allow the synthesis of molecules in one-pot and show a facile per-
formance, high atom-economy and high selectivity [42]. Therefore,
in the last decade, research in universities and industry has increas-
ingly emphasized the use of MCRs as well as domino reaction
sequences for a broad range of products [43].
2.2. General procedure for the preparation of
polyhydroquinolines
a round-bottomed flask the aldehyde (1 mmol), 1,3-
(1.5 mmol), -ketoester (1 mmol) and Fe3O4 NPs (0.016 g, equal to
7 mol%) were mixed thoroughly. The flask was heated at 60 ◦C with
concomitant stirring. After completion of the reaction confirmed
by TLC (eluent: EtOAc:n-hexane), hot ethanol (10 mL) was added
and separated solid catalyst by a normal magnet. The solvent
was evaporated and the crude products were recrystallized from
ethanol, gave the pure products in 84–96% yields based on the
starting aldehyde. The products were characterized by IR, 1H NMR,
13C NMR and via comparison of their melting points with the
reported ones. Spectroscopic data of new compounds.
Ethyl 4-cyclohexyl-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroq-
uinoline-3-carboxylate (4b). Mp: 222–224 ◦C; IR (KBr): 3282, 2923,
1693, 1643, 1605, 1224 cm−1 1H NMR (400 MHz, DMSO-d6) ı
;
(ppm): 0.80–1.00 (m, 11H), 1.11 (s, 3H), 1.30 (t, 3H, J = 7.2 Hz),
1.56–1.67 (m, 1H), 2.21–2.27 (m, 7H), 4.01 (d, 1H, J = 4.5 Hz),
4.10–4.25 (m, 1H), 5.96 (s, 1H); 13C NMR (100 MHz) ı (ppm): 14.39,
19.01, 26.62, 27.67, 26.70, 27.24, 29.12, 29.14, 29.93, 32.41, 34.98,
41.29, 45.87, 50.99, 59.70, 104.17, 110.03, 143.87, 149.97, 168.64,
196.22.
Ethyl 4-(3-ethoxy-4-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,
6,7,8-hexahydroquinoline-3-carboxylate (4h). Mp: 196–198 ◦C; IR
In view of substantial properties of Fe3O4 MNPs like envi-
ronmental friendly, greater selectivity, operational simplicity,
non-corrosive nature, moisture insensitive and ease of isolation, it
quinoline derivatives.
In conjunction with our studies on the utility of magnetically
separable Fe3O4 nanoparticles [44], and our interest in produc-
ing polyhydroquinolines [45], a study to revisit these reactions
in a parallel combinatorial fashion using the Fe3O4 nanoparticles
solvent-free synthesis approach was initiated.
(KBr): 3493, 3287, 2958, 1687, 1613, 1509, 1487, 1436, 1217 cm−1
;
1H NMR (400 MHz, DMSO-d6) ı (ppm): 0.97 (s, 3H), 1.10 (s, 3H),
1.23 (t, 3H, J = 6.8 Hz), 1.43 (t, 3H, J = 6.7 Hz), 1.60 (s, 3H), 2.34–2.38
(m, 4H), 4.07–4.11 (m, 4H), 4.98 (s, 1H), 5.51 (s, 1H), 5.71 (s, 1H),
6.71 (d, 1H, J = 8.0 Hz), 6.76 (d, 1H, J = 8.0 Hz), 6.94 (s, 1H).
Ethyl 4-cyclohexyl-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquino-
line-3-carboxylate (4k). Mp: 234–236 ◦C; IR (KBr): 3282, 2923,
1693, 1643, 1605, 1224 cm−1 1H NMR (400 MHz, DMSO-d6) ı
;
(ppm): 0.85–1.25 (m, 6H), 1.29 (t, 3H, J = 7.1 Hz), 1.55–1.98 (m, 5H),
2.03 (q, 2H, J = 4.7 Hz), 2.25–2.32 (m, 4H), 2.33 (s, 3H), 4.12 (d, 1H,
J = 4.2 Hz), 4.21 (q, 2H, J = 7.1 Hz), 6.74 (s, 1H); 13C NMR (100 MHz) ı
(ppm): 14.40, 19.01, 21.10, 26.59, 26.65, 26.66, 27.54, 28.88, 28.94,
34.82, 37.38, 45.55, 59.58, 104.19, 110.68, 143.99, 152.18, 168.75,
196.82.
2. Experimental
Chemicals were purchased from Merck, Fluka and Aldrich chem-
ical companies. X-ray diffraction analysis was carried out using a
D8 ADVANCE, Bruker X-ray diffractometer using Cu-K␣ radiation
2.3. General procedure for the preparation of
1,4-dihydropyridines
˚
(ꢀ = 1.5406 A). Transmission electron microscopy was studied using
a Philips, CM-10 TEM instrument operated at 100 kV. Melting points
were determined using a Barnstead Electrothermal (BI 9300) appa-
ratus and are uncorrected. IR spectra were obtained using a FT-IR
JASCO-680 spectrometer instrument. NMR spectra were taken with
a Bruker 400 MHz Ultrashield spectrometer at 400 MHz (1H) and
125 MHz (13C) using CDCl3 or DMSO-d6 as the solvent with TMS as
the internal standard.
A mixture of the alkyl or aryl aldehyde (1 mmol), -dicarbonyl
(2 mmol) and ammonium acetate (1.5 mmol) in the presence of
Fe3O4 NPs (0.024 g, equal to 10 mol%) was heated at 80 ◦C, with
stirring. The progress of the reaction was monitored by TLC (elu-
ent: EtOAc:n-hexane). After completion of the reaction, the mixture
was cooled to room temperature and then ethanol was added to
the resulting mixture and separated Fe3O4 NPs by a normal mag-
net. After evaporation of solvent, the solid product was filtered and
recrystallized from ethanol to give the pure products in 72–95%
yields based on the starting aldehyde. Physical and spectroscopic
data of new compounds:
2.1. Preparation of Fe3O4 NPs
Ferric and ferrous salts were employed as the precursors for the
synthesis of Fe3O4 NPs with methods modified from ref [46]. Briefly,