ARTICLE IN PRESS
JID: MOLSTR
[m5G;October 15, 2020;13:31]
L.H.R. Alponti, M. Picinini, E.A. Urquieta-Gonzalez et al.
Journal of Molecular Structure xxx (xxxx) xxx
Light yellow solid (0.154g, 87%), m.p. 249-251°C. 1H NMR
(CDCl3, 400 MHz, ppm) δ 6.95 (bs, 1H), 4.05 (s, 1H), 2.42-2.20 (m,
9H), 1.62 (t, J = 14.8 Hz, 5H), 1.40-1.19 (m, 3H), 1.14 (s, 6H), 1.09
(s, 6H), 0.91-0.81 (m, 2H).
of the products was performed by a flash chromatographic column,
using silica gel 60, 230-400 mesh ASTM Merck and silica gel 60
A, 70-230 mesh AldrichCo. The thin layer chromatography anal-
yses were carried out on silica gel 60 F254 plates supported on
aluminum sheets and developed under ultraviolet light and / or
stained in an acid vanillin. The solvent excess was evaporated in
Buchi Rotavapor R-114 with BuchiWatherbath B-490 bath. The Nu-
clear Magnetic Resonance spectra (1H and 13C NMR) were recorded
on the Bruker ARX 400 MHz spectrometers. The chemical shifts (δ)
are expressed in ppm and the coupling constants (J) in Hertz (Hz).
To indicate the multiplicity of signs, the following abbreviation
was used: s (singlet), d (doublet), dd (double doublet), t (triplet),
m (multiplet). Mass Spectra were recorded on a Shimadzu GCMS-
QP5000. The reactions using microwaves were performed using a
CEM Discovery equipment making use of the equipment’s cooling
system in all reactions.
3,3,6,6-tetramethyl-9-heptyl-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione (4g) [8]:
Yellow solid (0.133g, 72%), m.p. 109-111°C. 1H NMR (CDCl3, 400
MHz, ppm) δ 7.63 (s, 1H), 4.06 (t, J = 4.9 Hz, 1H), 2.42-2.19 (m,
8H), 1.44-1.14 (m, 12H), 1.10 (s, 6H), 1.09 (s, 6H), 0.82 (t, J = 6.8
Hz, 3H).
3,3,6,6-tetramethyl-9-nonyl-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione (4h):
Yellow solid (0.159g, 80%), m.p. 134-137°C. 1H NMR (CDCl3, 400
MHz, ppm) δ 7.06 (bs, 1H), 4.07 (t, J = 4.8 Hz, 1H), 2.37-2.23 (m,
8H), 1.44-1.16 (m, 16H), 1.10 (s, 6H), 1.09 (s, 6H), 0.87 (t, J = 6.8 Hz,
3H). 13C NMR (101 MHz; CDCl3) δ 196.1, 149.8, 112.7, 51.0, 41.1, 35.1,
32.5, 31.9, 30.0, 29.7, 29.7, 29.6, 29.3, 27.2, 27.1, 25.4, 22.7, 14.1. GC-
MS (70 eV) m/z (%): 434.4 (100), 406.3, 398.3, 339.1, 325.1, 311.2.
3,3,6,6-tetramethyl-9-(thiophen-2-yl)-3,4,6,7,9,10-
4.2.1. General procedure
In a sealed tube, a mixture of diketone or β-ketoester (1.0 mol),
aldehyde (0.5 mol) and ammonium acetate or p-toluidine (1.25
mol) was carried out with the zeolite catalyst USY (50 mg) at 0.5
mL of ethanol, heated to 110°C (300 W) in an oil bath or under
microwave irradiation (300 W) for the time required for product
formation. The progress of the synthesis was verified by TLC. Af-
ter completing the time proposed in the optimization of the reac-
tion, the reaction mixture was diluted with ethanol (5-6 mL) and
the catalyst was separated by centrifugation, along 3 processes fol-
lowed by washing of the mixture composed of the desired product
diluted in ethanol and the heterogeneous catalyst, this solvent be-
ing eliminated by vacuum, resulting in a solid that was purified by
column chromatography using hexane / ethyl acetate as eluent.
For the catalyst recycling study, the zeolite was separated from
the reaction mixture and washed 4-5 times with ethanol followed
by centrifugations for 5 min at 5000 W. At the end of each wash-
ing process, the zeolite was placed in the kiln to remove the re-
maining ethanol and then weighed to be reused. In all cycles the
catalyst was practically fully recovered, that is, in all syntheses it
was possible to use approximately 50 mg of USY zeolite.
hexahydroacridine-1,8 (2H,5H)-dione (4i) [9]:
Light orange solid (0.155g, 80%); m.p. 284-286°C. 1H NMR
(CDCl3, 400 MHz, ppm) δ 6.98 (d, J = 4.9 Hz, 1H), 6.92 (d, J = 3.1
Hz, 1H), 6.83-6.80 (m, 1H), 6.12 (bs, 1H), 5.40 (s, 1H), 2.37-2.25 (m,
8H), 1.10 (s, 6H), 1.04 (s, 6H).
3,3,6,6-tetramethyl-9-(pyridin-2-yl)-3,4,6,7,9,10-
hexahydroacridine-1,8 (2H,5H)-dione (4j) [9]:
Light orange solid (0.148g, 85%), m.p. 299-301°C. 1H NMR
(CDCl3, 400 MHz, ppm) δ 8.81 (d, J = 4.6 Hz, 1H), 7.61 (d, J = 7.7
Hz, 1H), 7.54 (t, J = 7.6 Hz, 1H), 7.01-6.96 (m, 1H), 6.55 (bs, 1H),
5.20 (s, 1H), 2.35-2.15 (m, 8H), 1.07 (s, 6H), 0.98 (s, 6H).
Diethyl-2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-
Light yellow solid (0.168g, 90%), m.p. 155-157°C. 1H NMR
(CDCl3, 400 MHz, ppm) δ 7.24 (d, J = 1.9 Hz, 2H), 7.17 (t, J = 7.4 Hz,
2H), 7.09 (t, J = 7.2 Hz, 1H), 5.58 (bs, 1H), 4.96 (s, 1H), 4.10-4.01
(m, 4H), 2.30 (s, 6H), 1.19 (t, J = 7.1 Hz, 6H).
Diethyl-4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (4l) [21]:
Light yellow solid (0.148g, 83%); m.p. 164-166°C. 1H NMR
(CDCl3, 400 MHz, ppm) δ 7.19 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.1
Hz, 2H), 5.70 (bs, 1H), 4.92 (s, 1H), 4.13-4.04 (m, 4H), 3.74 (s, 3H),
2.31 (s, 6H), 1.22 (t, J = 7.1 Hz, 6H).
4.2.2. Compounds characterization
3,3,6,6-tetramethyl-9-phenyl-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione (4a) [8]:
Light yellow solid (0.167g, 96%), m.p.190-192°C. 1H NMR (CDCl3,
400 MHz, ppm) δ 8.00 (bs, 1H), 7.33 (d, J = 7.8 Hz, 2H), 7.18 (t,
J = 7.4 Hz, 2H), 7.06 (t, J = 7.2 Hz, 1H), 5.08 (s, 1H), 2.32-2.10 (m,
8H), 1.05 (s, 6H), 0.94 (s, 6H).
Diethyl-4-(3-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-
Yellow solid (0.153g, 75%), m.p. 112-114°C. 1H NMR (CDCl3, 400
MHz, ppm) δ 7.45 (bs, 1H), 7.35-7.29 (m, 2H), 7.07 (t, J = 7.8 Hz,
1H), 5.98 (s,1H), 4.94 (s, 1H), 4.12-4.05 (m, 4H), 2.31 (s, 6H), 1.21
(t, J = 6.8 Hz, 6H).
9-(4-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8(2H,5H)-dione (4b) [10b]:
Light yellow solid (0.180g, 95%), m.p. 270-272°C. 1H NMR
(CDCl3, 400 MHz, ppm) δ 7.96 (bs, 1H), 7.22-7.26 (m, 2H), 6.71 (d,
J = 8.4 Hz, 2H), 5.03 (s, 1H), 3.66 (s, 3H), 2.11-2.27 (m, 8H), 1.05
(s, 6H), 0.94 (s, 6H).
Diethyl-4-(4-cyanophenyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (4n) [21]:
Brown solid (0.138g, 78%); m.p. 192-194°C. 1H NMR (CDCl3, 400
MHz, ppm) δ 7.50 (d, J = 7.8 Hz, 2H), 7.39 (d, J = 7.6 Hz, 2H), 5.80
(bs, 1H), 5.03 (s, 1H), 4.12-4.04 (m, 4H), 2.34 (s, 6H), 1.20 (t, J = 7.1
Hz, 6H).
9-(3-bromophenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-
hexahydroacridine-1,8 (2H,5H)-dione (4c) [8]:
Light yellow solid (0.170g, 83%), m.p. 286-288°C. 1H NMR
(CDCl3, 400 MHz, ppm) δ 7.44 (bs, 1H), 7.35 (bs, 1H), 7.25 (d,
J = 7.6 Hz, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.00 (t, J = 7.8 Hz, 1H),
4.98 (s, 1H), 2.28-2.18 (m, 4H), 2.18–2.06 (m, 4H), 1.01 (s, 6H), 0.91
(s, 6H).
Diethyl-4-cyclohexyl-2,6-dimethyl-1,4-dihydropyridine-3,5-
Orange solid (0.100g, 60%); m.p. 112-114°C. 1H NMR (CDCl3, 400
MHz, ppm) δ 5.61(bs,1H), 4.23–4.12 (m, 4H), 3.91 (d, J=5.4 Hz, 1H);
2.29 (s, 6H), 1.54 (d, J = 12.0 Hz, 4H), 1.29 (t, J =7.1 Hz, 9H), 1.06
(d, J =7.2 Hz, 4H).
4-(3,3,6,6-tetramethyl-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-
decahydroacridin-9-yl) benzonitrile (4d) [14]:
Diethyl-4-heptyl-2,6-dimethyl-1,4-dihydropyridine-3,5-
Light yellow solid (0.155g, 83%), m.p. 298-300°C. 1H NMR
(CDCl3, 400 MHz, ppm) δ 7.47 (dd, J = 18.6, 8.0 Hz, 4H), 6.00 (bs,
1H), 5.03 (s, 1H), 2.40-2.16 (m, 8H), 1.03 (s, 6H), 0.89 (s, 6H).
9-cyclohexyl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-
1,8(2H,5H)-dione (4f) [12]:
Orange oil (0.112g, 64%). 1H NMR (CDCl3, 400 MHz, ppm) δ 5.62
(bs, 1H), 4.23-4.11 (m, 4H), 3.91 (t, J = 5.8 Hz, 1H), 2.27 (s, 6H),
1.35-1.25 (m, 12H), 1.20 (bs, 6H), 0.85 (t, J = 7.0 Hz, 3H).
6