A facile synthesis of 3,4-dihydropyrimidinones/thiones and novel N-dihydro pyrimidinone-decahydroacridine-1,8-diones catalyzed by cellulose sulfuric acid

Article abstract of DOI:10.1016/j.molcata.2013.01.003

A new and efficient method has been developed for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/-thiones (DHPMs) through Biginelli reaction in aqueous media. Furthermore, a new series of N-dihydro pyrimidinone- decahydroacridine-1,8-diones (8a-m) have

Full text of DOI:10.1016/j.molcata.2013.01.003

Journal of Molecular Catalysis A: Chemical 370 (2013) 197–204
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A facile synthesis of 3,4-dihydropyrimidinones/thiones and novel N-dihydro
pyrimidinone-decahydroacridine-1,8-diones catalyzed by cellulose sulfuric acid
Abdul Rajacka,b,∗, K. Yuvarajua, Ch. Praveena, Y.L.N. Murthya
a Department of Organic Chemistry, Foods, Drugs & Water, Andhra University, Visakhapatnam 530 003, India
b Department of Chemistry, MVGR College of Engineering, Vijayanagaram 535 005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A new and efficient method has been developed for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/-
thiones (DHPMs) through Biginelli reaction in aqueous media. Furthermore, a new series of N-dihydro
pyrimidinone-decahydroacridine-1,8-diones (8a–m) have been synthesized by the Hantzsch reaction
of 5-Ethoxycarbonyl-4-(4-aminophenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-one 5 (DHPM), with
dimedone and aromatic aldehyde in acetonitrile under reflux conditions. All the products in both reactions
obtained in good to excellent yields by proceeding through a simple and efficient procedure employing
cellulose sulfuric acid (CSA) as a recyclable solid acid catalyst. All the newly synthesized compounds
structure has been established by advanced spectroscopic data.
Received 27 November 2012
Received in revised form
26 December 2012
Accepted 2 January 2013
Available online 23 January 2013
Keywords:
New N-dihydro pyrimidinone-
decahydroacridine-1,8-diones
Cellulose sulphuric acid
Biginelli reaction
© 2013 Elsevier B.V. All rights reserved.
Hantzsch reaction
Recyclable catalyst
1. Introduction
urea or an aromatic amine as a source of nitrogen [11]. Several
methodologies of these reactions were reported [12,13]. Most of
The development of multicomponent reactions [1] (MCRs) is
of increasing importance in organic and medicinal chemistry for
modern drug discovery. It was soon established the structural sim-
ilarity to hydrogenase coenzymes and the clinical use of DHPMs
and1,4-Dihydropyridines (DHPs) as calcium channel stimulating
drugs such as nefidine [2], attracted the attention of scholars [3].
DHPMs have wide spectrum of biological activities [4]. Acridines
have eclectic collection of biological activities such as antimalar-
ials [5] antibacterial [6], antifungal [7] and anti-HIV [8] agents.
They have exhibited excellent results in chemotherapy of cancer
[9]. Polyhydroacridine-1,8-diones are poly functionalized deriva-
tives of DHPs; DHPs are well-known compounds for their wide
range of biological activities [10]. The chemical modifications on the
DHP ring, such as different substituents 5 have allowed the study
of three dimensional quantitative structure activity relationships
(QSAR) and also provide the molecular interactions at the receptor
level. In the present context, polyhydro acridine-1,8-diones credits
special attention due to their similar properties with DHPs.
these reported methodologies suffer from draw backs such as harsh
reaction conditions, longer reaction times, use of large amounts of
expensive reagents, low yields, use of toxic solvents and catalysts.
Hence, there is a scope for efficient synthesis of these biologically
active molecules. In the present decade, the direction of science and
technology has been shifting toward eco-friendly, natural product
resources and reusable catalysts. Thus, natural biopolymers such
as cellulose are most abundant natural biopolymers, biodegradable
materials and a renewable resource. Because of its unique proper-
ties CSA has emerged as a promising biopolymeric recyclable solid
support acid catalyst for acid-catalyzed reactions.
We have made an attempt to study Beginelli and Hantzsch reac-
tions utilizing cellulose sulfuric acid as a solid catalyst, with an aim
to develop a simple practical method for the synthesis of a large
range of DHPMs and acridines.
2. Experimental
These compounds were prepared by the reactions of multi-
component condensation involving the one-pot, acid-catalyzed
reaction of aldehydes, ␤-dicarbonyl compounds and ammonia or
2.1. General procedure for the synthesis of DHPMs (4a–4m)
A mixture of aromatic aldehyde (0.01 moles), ethyl acetoacetate
(0.012 moles) and urea (0.01 moles) was stirred in water at 100 ◦C
utilizing CSA (0.05 g) for 3.5–6.5 h, the reaction was monitored by
thin layer chromatography (TLC) [6:4 hexane:ethyl acetate]. After
the completion of reaction, the reaction mixture was cooled and
∗
Corresponding author. Tel.: +91 9849229804; fax: +91 891 2713813.
E-mail address: abdulrazzack1@gmail.com (A. Rajack).
1381-1169/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2013.01.003

198
A. Rajack et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 197–204
R
X = O, S
O
O
R
X
Cellulose sulfuric acid
H2O 100 oC 3.5-6.5 h
H3CH2CO
+
H3CH2CO
NH
+
H2N
NH2
O
N
H
X
CHO
4a-4r
1
2
3
R = 3,4(OMe)2(4a,b); R = 4(OMe)2(4c,d); R = 4Cl2(4e,f); R = 4NO2(4g,h); R = 3,4,5(OMe)3(4i,j); R = H(4k,l);
R = 4 OH(4m,n); R = 3,4(NO)2(4o,p); R = 2Cl2(4q,r)
Scheme 1. Synthesis of 3,4 dihydro pyrimidinone utilizing cellulose sulfuric acid as a solid catalyst.
Table 1
washed with ice cooled water and the solid precipitate was sep-
arated by filtration and dried in vacuum, which was passed over
a column of silica gel (60–100 mesh) and then recrystallized from
methanol.
CSA – catalyzed synthesis of product (4g) in different solvents and under solvent-free
conditions at 100 ◦C.
Entry
Solvent
Amount (g)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
Methanol
Ethanol
Dioxane
Acetonitrile
Toluene
Water
Water
Water
Water
Solvent free
0.05
0.05
0.05
0.05
0.05
0.03
0.04
0.05
0.10
0.05
4.5
4.5
4.5
4.5
4.5
4.5
4.5
4.5
4.5
4.5
33
45
40
70
30
25
50
85
80
25
2.2. Reduction of compound (4g) to Ethyl 1,2,3,4-tetrahydro-6-
methyl-4-(4-aminophenyl)-2-oxopyrimidine-5-carboxylate
(5)
The compound 4g stirred with 10% Pd/C in a mixture of
solvents methanol (20%) ethyl acetate (80%) under hydrogen
balloon pressure for 2 h. After completion of the reaction (TLC
monitoring), reaction mixture was filtered on a celite belt. The
filtrate was concentrated under reduced pressure resulting in
a solid compound which was further purified by recrystalliza-
tion.
10
a
Isolated yields.
4. Results and discussion
We started our study with the CSA catalyzed synthesis of
DHPMs via the Biginelli reaction. The model reaction of p-nitro
benzaldehyde, ethyl acetoacetate and urea in water (Scheme 1)
was optimized by investigating various parameters such as CSA,
solvent and conditions. The optimized conditions required reflux
conditions with 0.05 g of CSA in aqueous medium for 4.5 h at
100 ◦C. A summary of the optimized experiments is listed in
Table 1. During the optimization, various amounts of CSA catalyst
were employed in the reaction. Evidently, the reaction with 0.04 g
(Table 1, Entry 7) of catalyst gave lower product yield than the one
with 0.05 g (Table 1, Entry 8) of catalyst. The efficiencies of several
organic solvents as reaction medium and solvent less system were
investigated (Fig. 1). Polar solvents such as ethanol, methanol
dioxane, and acetonitrile were better organic solvents to effect
the reaction. However, a significant improvement was observed in
aqueous media (Table 1, Entries 6–9).
2.3. General procedure for the synthesis of N-dihydro
pyrimidinone-decahydroacridine-1, 8-diones (8a–m)
A mixture of dimedone (0.02 moles), 4-amino phenyl-3,4-
dihydro pyrimidinone (5) (0.025 moles) and aromatic aldehydes
(0.01 moles) was refluxed at 100 ◦C in acetonitrile for 4–6 h uti-
lizing 0.05 g of cellulose sulfuric acid. After the completion of
reaction (TLC monitoring), the reaction mixture was poured in ice
cold water and extracted with ethyl acetate and then dried over
anhydrous magnesium sulphate, purified by column chromatog-
raphy. Melting points of all the compounds were determined in
open capillaries are uncorrected. IR spectra were recorded on a
Shimadzu IR Affinity-1 spectrometer in KBr. 1H and 13C NMR spec-
tra were recorded using a Bruker DRX 400 spectrometer 400 MHz
and 100 MHz respectively. NMR spectra were obtained in solution
DMSO-d6. Mass spectra were recorded on water XEVO QT of mass
spectrometer.
Product 4g
Product 8a
85
85
90
80
70
60
50
40
30
20
10
0
75
3. Preparation of cellulose sulfuric acid
60
45 45
To a magnetically stirred mixture of 5.00 g of cellulose in 20 ml of
n-hexane, 1.00 g of chlorosulfonic acid (9 mmol) was added in drop
wise at 0 ◦C for 2 h under nitrogen atmosphere. After the completion
of addition, immediately HCl gas was removed from the reaction
vessel and then stirred for further 2.5 h. Then, the mixture was
filtered and washed with 30 ml of acetonitrile and dried at room
temperature to obtain 5.33 g cellulose sulfuric acid as a white pow-
der. Sulfur content of sample obtained by conventional elemental
analysis, was 0.68 mmol/g. The number of H+ site on the cellulose
SO3H determined by acid–base titration was 0.60 mequiv/g, indi-
cating that most of the sulphur species about 0.94% are in the form
sulfonic acid groups.
40 40
40
40
33
30
Fig. 1. The effect of solvents: 1. Acetonitrile, 2. Water, 3. Ethanol, 4. Dioxan, 5.
Methanol, 6. Toluene: on the products 4g and 8a yields.a
Isolated yields of compound 4g and 8a.
a

A. Rajack et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 197–204
199
Table 2
The products obtained through the Biginelli type reaction utilizing CSA.
Entry
R-CHO
x
Product
Time (h)
3.5
Yield (%)a
70
mp. found
172–175
mp. reference
MeO
1
O
4a
175–177 [12b]
212–214 [12e]
MeO
MeO
MeO
2
S
4b
4
65
210–212
MeO
MeO
Cl
3
4
5
O
S
4c
4d
4e
4.5
5
72
69
72
200–203
149–151
211–214
202–203 [12a]
152–153 [12c]
210–212 [12f]
O
4.5
Cl
6
7
8
S
4f
5
68
85
90
180–182
230–232
200–201
184–185 [12f]
O2N
O2N
O
S
4g
4h
4.5
4.5
–
–
MeO
MeO
9
O
4i
6
90
178–181
180–182 [13a]
MeO
MeO
MeO
MeO
10
11
S
4j
6.5
5
82
80
200–202
201–203
202–204 [12d]
202–204 [13b]
O
4k
12
13
14
S
4l
5
72
78
66
199–202
234–235
192–194
200–205 [13b]
237–238 [12f]
193–195 [13b]
HO
HO
O
S
4m
4n
4
4.5
15
16
17
O
4o
5.5
80
229–230
230–232 [12b]
O2N
O2N
S
4p
4q
4r
6
78
88
81
204–205
210–212
218–220
206–207 [12b]
214–215 [12b]
219–221 [12b]
O
S
5
Cl
Cl
18
5.5
a
Isolated yields.
To define the scope and limitations of the catalyst performance
the reaction was carried out with various substituted aromatic
aldehydes in the optimized conditions (Table 2).
by the Hantzsch type condensation of 5-Ethoxycarbonyl-4-(4-
aminophenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-one 5,
with dimedone and aromatic aldehydes in acetonitrile under
reflux conditions (Scheme 2). Compound is the reduced
product of 5-Ethoxycarbonyl-4-(4-nitrophenyl)-6-methyl-3,
Furthermore,
a
new series of N-dihydro pyrimidinone-
5
decahydroacridine-1,8-diones 8a–m have been synthesized

200
A. Rajack et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 197–204
Table 3
Synthesis of various N-substituted decahydroacridine-1,8-diones using CSA in acetonitrile.
Entry
R-CHO
Time (h)
Compound
Yield (%)a
85
Cl
1
4.5
8a
2
3
6.5
4
8b
8c
60
70
NO2
OCH3
4
5
5
8d
8e
60
55
OCH3
5.5
OCH3
OCH3
OH
Cl
6
7
8
5
8f
55
65
70
5.5
6
8g
8h
Cl
O
O
CN
9
6
5
8i
8j
66
70
10
OCH3
OCH3
11
12
7
8k
78
OCH3
Br
5.5
6
8l
55
40
13
8m
NO2
a
Isolated and optimized yields.
4-dihydropyrimidine-2(1H)-one 4g (Scheme 2 step1). The reaction
was performed with 0.05 g of the catalyst at 100 ◦C in different sol-
vents viz. acetonitrile, ethanol, dioxane, toluene, water and under
solvent-free conditions, Surprisingly, the reaction in acetonitrile
solvent produced higher yields than the aqueous media (Fig. 1). To
define the scope and limitations, the efficiency of the catalyst, CSA
was examined with various aromatic aldehydes, dimedone and
4-amino-phenyl-3,4-dihydropyrimidinone (Table 3).
In order to show the significance of the cellulose sulfuric acid,
the efficiency of the reagent compared to various sulphur analog
acidic catalysts (Table 4). In this study it was found that cellulose
sulfuric acid is a more efficient and superior catalyst (Entry 1) over
other acidic catalysts (Entries 2–4) with respect to reaction time
Table 4
Comparative study of CSA for Biginelli (4g) and Hantzsch (8a) reactions to the
reported catalysts in water as solvent.
Entry
Catalyst
Time (h)
Yield (%)a
Time (h)
Yield (%)b
1
2
3
4
5
6
CSA
Dowex
Silica sulfuric acid
Amberlyst-15
PTSA
4.5
6.5
10
10
10
85
70
62
60
50
–
4.5
12
12
24
24
85
–
40
50
–
No catalyst
24
24
–
(–) No reaction.
a
Isolated yield of compound 4g.
Isolated yield of compound 8a.
b

A. Rajack et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 197–204
201
O
O S
H
CELLULOSE
O
O
O
O
O
OCH2CH3
OCH2CH3
-CSA
HO
OCH2CH3
H
+
O
H O
-H2O
O
O
:
O
OCH2CH3
NH2
O
HN
OCH2CH3
NH2 OH
O
H
O
NH2
HN
OCH2CH3
-H2O
-CSA
O
O
N
O
H
CELLULOSE O S
O
O
Fig. 2. The plausible mechanism involved in the synthesis of 3,4-dihydro pyrimidinone.
NH2
R
O
O
+
-H2O
O
NH
O
CELLULOSE
O S
O
O H
R
H
R
O
O
O
O
-H2O
OH
-CSA
O
O
H
O
O
O
O
H
:
O
HN
H+N
R
OH
O
R
H
O
CELLULOSE O S
O
O
- CSA
O
O
O
O
HN
R
N
OH
-H2O
NH
O
R
R
EtO
N
O
H
Fig. 3. The plausible mechanism involved in the synthesis of N-dihydro pyrimidinone-decahydroacridine-1,8-diones.

202
A. Rajack et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 197–204
6
7
R
O
O
O
O
NH2
NO2
R
N
O
Pd/C
O
CHO
O
Cellulose sulfuric acid
Acetonitrile 100 oC
4-7 h
H2 Baloon
NH
H3CH2CO
NH
H3CH2CO
N
H
O
N
H
O
i
ii
H3CH2CO
8a-8m
NH
5
N
H
O
4
Scheme 2. (i) Reduction of 4-nitro 3,4-dihydro pyrimidinone to 4-amino 3,4-dihydro pyrimidinone. (ii) Synthesis of N-dihydro pyrimidinone-decahydroacridine-1,8-diones
utilizing cellulose sulfuric acid as a solid catalyst.
Table 5
C, 55.08; H, 4.95; N, 13.76. Found: C, 53.20; H, 4.68; N, 12.21. m/z
306.0988 [M+H].
The effect of reusability of cellulose sulfuric acid catalyst on the products 4g and 8a
yield.a
Entry
Cycle
Yield (%)a
Yield (%)b
6.2. 4-(4-Amino-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
pyrimidine-5-carboxylicacid ethyl ester
(5)
1
2
3
4
0
1
2
3
85
82
80
77
85
80
78
75
mp 201–202 ◦C; IR (KBr): 3223, 3095, 2930, 1710, 1655; 1H
NMR (400 MHz, DMSO-d6): ı 1.15 (t, J = 7.2 Hz, 3H), 2.23 (s, 3H),
2.81 (s, 2H, NH2) 4.03 (q, J = 7.2 Hz, 2H), 5.12 (d, J = 3.0 Hz, 1H), 6.88
(d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.2 Hz), 8.29 (br s, N H), 8.76 (br s,
a
Isolated yield of compound 4g.
Isolated yield of compound 8a.
b
and yield of the desired products 4g (Beginelli) and 8a (Hantzsch).
It was also observed that both the reactions were not moved in
the absence of the cellulose sulfuric acid reagent in aqueous media
even after 24 h of reaction time (Entry 5).
N
H) ppm; 13C NMR (100 MHz, DMSO-d6): ı 13.4, 19.5, 45.9, 59.8,
101.1, 113.1, 127.4, 138.1, 146.9, 152.9, 159.1, 165.3; Calcd. For
C14H17N3O3 (%): C, 61.08; H, 6.22; N, 15.26. Found: C, 60.14; H,
5.98; N, 15.21. m/z 276.1534 [M+H].
The catalyst was separated from the reaction mixture by simple
filtration, washed thrice with DCM and dried at 80 ◦C for period of
6 h and reused. The recovered catalyst can be reused for four times
in subsequent reactions without any significant loss in its activity,
the results with recyclable CSA were summarized in Table 5.
The catalytic role of CSA was presented in the plausible
mechanism involved in the synthesis of 3,4 dihydro pyrimidi-
none and N-dihydro pyrimidinone-decahydroacridine-1,8-diones
in Figs. 2 and 3.
6.3. Ethyl-4-(4-(9-(4-chlorophenyl)-1,2,3,4,5,6,7,8-octahydro-
3,3,6,6-tetramethyl-1,8-dioxoacridin-10(9H)-yl)phenyl)-1,2,3,4-
tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylate
(8a)
mp 198–202 ◦C; IR (KBr): ꢀ (cm−1): 3224, 3116, 2970, 1697,
1558, 1489; 1H NMR (400 MHz, DMSO-d6): ı 0.99 (s, 6H), 1.12 (s,
6H), 1.15 (t, J = 7.2 Hz, 3H), 2.25 (s, 3H), 2.33 (s, 4H), 2.55 (s, 4H),
3.94 (q, J = 7.2 Hz, 2H), 4.96 (s, 1H), 5.15 (d, J = 3.2 Hz, 1H), 7.15 (d,
J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.39
(d, J = 8.4 Hz, 2H), 8.77 (s, 1H, NH), 9.24 (s, 1H, NH) ppm; 13C NMR
(100 MHz, DMSO-d6): ı 12.6, 14.1, 17.4, 20.5, 23.3, 28.5, 29.9, 42.2,
52.2, 59.9, 102.0, 108.4, 118.4, 126.8, 127.0, 129.0, 130.6, 133.1,
140.0, 144.6, 145.5, 149.2, 155.8, 168.3, 193.4 ppm; Anal. Calcd. For
C37H40ClN3O5 (%): C, 69.20; H, 6.28; N, 6.54. Found: C, 66.14; H,
5.98; N, 6.21. m/z 643.1020 [M+2].
5. Summary
We have developed a new protocol for the synthesis of DHPMs
in aqueous media. Further we have presented a synthesis of novel
N-dihydro pyrimidinone-decahydroacridine-1,8-diones, utilizing
cellulose sulfuric acid, which is an efficient, non-toxic, reusable, and
environmentally friendly solid acid catalyst. This modified method-
ology is prominent to existing methodologies for the synthesis of
3,4-dihydropyridinones and acridines.
6.4. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-
3,3,6,6-tetramethyl-1,8-dioxo-9-p-tolylacridin-10(9H)-
yl)phenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
(8b)
6. Spectral data
6.1. 4-(4-Nitro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
pyrimidine-5-carboxylicacid ethyl ester
(4g)
mp 254–256 ◦C; IR (KBr): ꢀ (cm−1): 3224, 3109, 2978, 1689,
1643, 1522, 1465; 1H NMR (400 MHz, DMSO-d6): ı 0.97 (s, 6H),
1.05 (s, 6H), 1.09 (t, J = 7.2 Hz, 3H) 2.12 (s, 3H), 2.20 (s, 3H), 2.31
(s, 4H), 2.42 (s, 4H), 3.88 (q, J = 7.2 Hz, 2H), 4.45 (s, 1H), 5.14 (d,
J = 3.2 Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 7.15 (d,
J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 8.88 (s, 1H, NH), 9.94 (s,1H,
NH) ppm; 13C NMR (100 MHz, DMSO-d6): ı 12.4, 16.9, 19.6, 22.3,
29.2, 29.9, 53.7, 60.1, 102.3, 108.7, 118.3, 126.7, 127.9, 129.7, 130.5,
133.3, 140.9, 144.6, 149.2, 155.4, 168.5, 193.5 ppm; Anal. Calcd. For
mp 230–232 ◦C; IR (KBr) ꢀ (cm−1): 3225, 3147, 3056, 2948,
1696, 1580; 1H NMR (400 MHz, DMSO-d6): ı 1.10 (t, J = 8.0 Hz, 3H),
2.28 (s, 3H), 3.99 (q, J = 8.0 Hz, 2H), 5.50 (s, 1H), 7.18 (s, 1H. N-H),
7.59 (d, J = 8.8 Hz, 2H), 8.36 (d, J = 8.8 Hz), 8.89 (s, N H) ppm; 13C
NMR (100 MHz, DMSO-d6): ı 13.0, 19.8, 48.6, 60.0, 109.3, 119.0,
128.7, 141.7, 147.8, 155.9, 159.0, 165.9; Calcd. For C14H15N3O5 (%):

A. Rajack et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 197–204
203
C38H43N3O5 (%): C, 73.40; H, 6.97; N, 6.76. Found: C, 70.87; H, 6.18;
N, 6.29. m/z 622.3609 [M+H].
2.36 (s, 4H), 2.48 (s, 4H), 3.98 (q, J = 7.2 Hz, 2H), 4.05 (s, 3H), 4.61 (s,
1H), 5.17 (d, J = 3.2 Hz, 1H), 6.42–6.50 (m, 1H), 6.63–6.71 (m, 1H),
6.79–6.84 (m, 1H), 7.14 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H),
8.72 (s, 1H, NH), 8.85 (s, 1H, OH), 9.03 (s, 1H, NH) ppm; 13C NMR
(100 MHz, DMSO-d6): ı 14.1, 17.6, 22.1, 29.2, 32.5, 37.4, 41.6, 52.5,
59.7, 102.3, 108.7, 118.3, 125.1, 126.7, 127.9, 129.7, 130.5, 133.3,
135.3, 140.9, 148.9, 149.2, 152.4, 168.7, 193.5 ppm; Anal. Calcd. For
6.5. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-
3,3,6,6-tetramethyl-9-(4-nitrophenyl)-1,8-dioxoacridin-10(9H)-
yl)phenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
(8c)
C
38H43N3O7 (%): C, 69.81; H, 6.63; N, 6.43. Found: C, 68.25; H, 6.35;
mp 228–232 ◦C; IR (KBr): ꢀ (cm−1): 3224, 3109, 2978, 1689,
1643, 1522, 1465; 1H NMR (400 MHz, DMSO-d6): ı 1.03(s, 6H),
1.09 (s, 6H), 1.12 (t, J = 7.6 Hz, 3H), 2.05 (m, 4H), 2.13 (s, 3H), 2.22
(m, 4H), 4.01 (q, J = 7.6 Hz, 2H), 4.60 (s, 1H), 4.96 (d, J = 3.2 Hz, 1H),
6.46 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz,
2H), 7.93 (d, J = 8.4 Hz, 2H), 8.62 (s, 1H, NH), 9.02 (s, 1H, NH) ppm;
13C NMR (100 MHz, DMSO-d6): ı 12.3, 16.0, 23.4, 28.0, 29.1, 30.0,
50.1, 57.4, 60.0, 111.0, 112.9, 119.0, 124.2, 125.2, 125.3, 126.3,
126.8, 127.4, 128.2, 129.3, 130.4, 145.0, 145.8, 150.4, 153.1, 157.2,
162.9, 194.0 ppm; Anal. Calcd. For C37H40N4O7 (%): C, 68.08; H,
6.18; N, 8.58. Found: C, 64.14; H, 5.98; N, 8.22. m/z 653.1274
[M+H].
N, 6.34. m/z 654.1312 [M+H].
6.9.
Ethyl-4-(4-(9-(2,4-dichlorophenyl)-1,2,3,4,5,6,7,8-octahydro-
3,3,6,6-tetramethyl-1,8-dioxoacridin-10(9H)-yl)phenyl)-1,2,3,4-
tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylate
(8g)
mp 244–246 ◦C; IR (KBr): ꢀ (cm−1): 3337, 3224, 3116, 2954,
1697, 1558, 1489, 1404; 1H NMR (400 MHz, DMSO-d6): ı 0.90
(s, 6H), 0.98 (s, 6H), 1.12 (t, 3H, J = 7.2 Hz), 2.05 (s, 3H,), 2.26
(s, 4H), 2.50 (s, 4H), 3.96 (q, J = 7.2 Hz, 2H), 4.32 (s, 1H), 4.96
(d, J = 3.2 Hz, 1H), 6.99 (d, J = 8.0 Hz, 2H), 7.11(d, J = 8.0 Hz, 2H),
7.29–7.35 (m, 1H), 7.48–7.60 (m, 1H), 8.78 (s, 1H, NH), 9.49
(s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO-d6): ı 14.3, 17.2,
20.6, 29.5, 32.7, 42.2, 53.8, 58.3, 100.4, 103.4, 108.4, 118.8, 120.0,
126.5, 127.0, 129.2, 130.1, 133.2, 140.0, 144.2, 145.5, 152.2,
6.6. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-9-
(4-methoxyphenyl)-3,3,6,6-tetramethyl-1,8-dioxoacridin-
10(9H)-yl)phenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
(8d)
168.4, 194.4 ppm; Anal. Calcd. C37H39Cl2N3O5 (%): C, 65.68; H,
5.81; N, 6.21. Found: C, 63.19; H, 5.78; N, 6.18. m/z 676.7139
[M+H].
mp 261–262 ◦C; IR (KBr): ꢀ (cm−1): 3235, 3036, 2970, 2954,
1697, 1558, 1489; 1H NMR (400 MHz, DMSO-d6): ı 0.94 (s, 6H),
0.98 (s, 6H), 1.10 (t, J = 8.0 Hz, 3H), 2.07 (s, 3H), 2.27 (s, 4H), 2.35
(s, 4H), 3.96 (q, J = 8.0 Hz, 2H), 4.32 (s, 3H), 4.33 (s, 1H), 4.96 (d,
J = 3.6 Hz, 1H), 6.46 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 6.91
(d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7.50 (s, 1H, NH), 9.01
(s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO-d6): ı 14.0, 17.6,
21.1, 25.4, 30.1, 31.1, 46.5, 53.5, 58.9, 61.9, 100.0, 103.3, 113.5,
114.4, 116.6, 126.9, 129.3, 129.8, 132.3, 144.6, 147.2, 147.7, 152.1,
165.4, 193.4 ppm; Anal. Calcd. For C38H43N3O6 (%): C, 71.56; H,
6.80; N, 6.59. Found: C, 69.09; H, 6.66; N, 6.27. m/z 638.7170
[M+H].
6.10. Ethyl-4-(4-(9-(benzo[d][1,3]dioxol-6-yl)-1,2,3,4,5,6,7,8-
octahydro-3,3,6,6-tetramethyl-1,8-dioxoacridin-10(9H)-
yl)phenyl)-1,2,3,4-tetrahydro-6-methyl-2-oxopyrimidine-5-
carboxylate
(8h)
mp 250–252 ◦C; IR (KBr): ꢀ (cm−1): 3257, 3027, 2978, 2925,
2845, 1702, 1642, 1647, 1555, 1460; 1H NMR (400 MHz, DMSO-
d6): ı 0.98 (s, 6H), 1.10 (s, 6H), 1.13 (t, J = 7.4 Hz, 3H), 2.26 (s,
3H), 2.31 (s, 4H), 2.52 (s, 4H), 3.98 (q, J = 7.4 Hz, 2H), 4.58 (s, 1H),
5.11 (d, J = 3.2 Hz, 1H), 5.60 (s, 2H), 6.66 (m, 1H), 6.84 (m, 1H),
6.93 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 8.76 (s, NH, 1H),
9.67 (s, NH, 1H) ppm; 13C NMR (100 MHz, DMSO-d6): ı 14.1, 17.4,
20.3, 28.1, 31.4, 43.3, 52.1, 60.4, 68.4, 100.1, 103.0, 110.5, 118.6,
120.0, 125.3, 128.6, 129.3, 132.3, 135.3, 140.3, 144.2, 147.7, 152.9,
168.2, 192.9 ppm; Anal. Calcd. For C38H41N3O7 (%): C, 70.03; H,
6.34; N, 6.45. Found: C, 69.14; H, 6.22; N, 6.41. m/z 652.3402
[M+H].
6.7. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-9-
(3,4-dimethoxyphenyl)-3,3,6,6-tetramethyl-1,8-dioxoacridin-
10(9H)-yl)phenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
(8e)
mp 235–238 ◦C; IR (KBr): ꢀ (cm−1): 3387, 3224, 3116, 2954,
1697, 1558, 1489, 1404; 1H NMR (400 MHz, DMSO-d6): ı 0.87 (s,
6H), 1.06 (s, 6H), 1.09 (t, J = 7.2 Hz, 3H), 2.24 (s, 3H), 2.36 (s, 4H),
2.48 (s, 4H), 3.98 (q, J = 7.2 Hz, 2H), 4.05 (s, 3H), 4.08 (s, 3H), 4.61
(s, 1H), 5.14 (d, J = 3.2 Hz, 1H), 6.32 (m, 1H), 6.68–6.72 (m, 1H),
6.86–6.93 (m, 1H), 7.15 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 8.72
(s, 1H, NH), 8.95 (s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO-d6):
ı 14.7, 17.3, 22.2, 26.1, 28.2, 29.5, 31.4, 40.2, 41.6, 52.5, 59.7, 102.3,
108.7, 118.3, 126.7, 127.9, 129.7, 130.5, 133.3, 140.9, 144.6, 145.2,
149.2, 168.8, 193.5 ppm; Anal. Calcd. C39H45N3O7 (%): C, 70.14;
H, 6.79; N, 6.29. Found: C, 68.99; H, 6.55; N, 6.24. m/z 668.8210
[M+H].
6.11. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-
3,3,6,6-tetramethyl-9-(4-cynophenyl)-1,8-dioxoacridin-10(9H)-
yl)phenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
(8i)
mp 239–241 ◦C; IR (KBr): ꢀ (cm−1): 3250, 3031, 2970, 2931,
2843, 1658, 1639, 1555, 1460; 1H NMR (400 MHz, DMSO-d6): ı
0.98 (s, 6H), 1.05 (s, 6H), 1.10 (t, J = 7.0 Hz, 3H), 2.20 (s, CH3, 3H),
2.37 (s, 4H), 2.48 (s, 4H), 3.98 (q, J = 7.0 Hz, 2H), 4.59 (s, 1H),
5.14 (d, J = 3.2 Hz, 1H), 7.10 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz,
2H), 7.69 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 8.4 Hz, 2H), 8.77 (s, NH,
1H), 9.78 (s, 1NH, 1H) ppm; 13C NMR (100 MHz, DMSO-d6): ı
14.7, 17.1, 21.0, 29.2, 32.5, 41.6, 52.5, 59.7, 102.3, 108.7, 118.3,
126.7, 127.9, 129.7, 130.5, 133.3, 140.9, 144.6, 149.2, 152.4, 163.8,
168.7, 193.0 ppm; Anal. Calcd. For C38H40N4O5 (%): C, 72.13; H,
6.37; N, 8.85. Found: C, 71.14; H, 6.22; N, 8.41. m/z 633.0157
[M+H].
6.8. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-9-
(3-methoxy-4-hydroxyphenyl)-3,3,6,6-tetramethyl-1,8-
dioxoacridin-10(9H)-yl)phenyl)-6-methyl-2-oxopyrimidine-5-
carboxylate
(8f)
mp 218–222 ◦C; IR (KBr): ꢀ (cm−1): 3252, 3031, 2970, 2925,
2850, 1706, 1660, 1647, 1563, 1460; 1H NMR (400 MHz, DMSO-
d6): ı 0.85 (s, 6H), 1.06 (s, 6H), 1.08 (t, J = 7.2 Hz, 3H,), 2.21 (s, 3H),

204
A. Rajack et al. / Journal of Molecular Catalysis A: Chemical 370 (2013) 197–204
6.12. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-
3,3,6,6-tetramethyl-1,8-dioxo-9-phenylacridin-10(9H)-
yl)phenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
(8j)
1.10 (s, 6H), 1.12 (t, J = 7.4 Hz, 3H), 2.00 (s, 3H), 2.24 (s, 4H), 2.38
(s, 4H), 3.98 (q, J = 7.4 Hz, 2H), 4.81 (s, 1H), 5.20 (d, J = 3.2 Hz, 1H),
6.87 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 7.29–7.77 (m, 2H),
8.16 (dd, J = 8.0 Hz, J = 2.0 Hz, 1H), 8.28 (d, J = 2.0 Hz 1H), 8.50 (s, 1H,
NH), 9.65 (s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO-d6): ı 12.6,
15.0, 20.1, 28.1, 29.26, 51.44, 57.34, 60.02, 100.0, 110.8, 114.8, 116.9,
117.8, 118.0, 119.5, 123.0, 124.1, 125.5, 126.1, 127.3, 127.3, 1258.6,
130.0, 142.1, 145.1, 145.2, 149.7, 150.1, 157.2, 166.4, 192.7 ppm;
Anal. Calcd. For C37H40N4O7 (%): C, 68.08; H, 6.18; N, 8.58. Found:
C, 65.14; H, 5.78; N, 8.21. m/z 653.1122 [M+H].
mp 217–220 ◦C; IR (KBr): ꢀ (cm−1): 3201, 3062, 3024, 2954,
2870, 2731, 1689, 1859, 1489; 1H NMR (400 MHz, DMSO-d6): ı 0.95
(s, 6H), 0.99 (s, 6H), 1.01 (t, J = 7.0 Hz, 3H), 2.18 (s, 4H), 2.22 (s, 4H),
2.25 (s, 3H), 3.96 (q, J = 7.0 Hz, 2H), 4.52 (s, 1H), 4.97 (d, J = 3.2 Hz,
1H), 6.86 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 7.11–7.51 (m, 5H),
7.96 (s, NH, 1H), 9.03 (s, NH, 1H) ppm; 13C NMR (100 MHz, DMSO-
d6): ı 14.0, 17.6, 20.7, 24.3, 29.5, 30.0, 53.5, 55.8, 58.9, 100.0, 113.5,
115.4, 122.9, 126.8, 128.0, 128.6, 131.1, 132.2, 144.2, 147.7, 152.2,
165.4, 193.9 ppm; Anal. Calcd. C37H41N3O5 (%): C, 73.12; H, 6.80;
N, 6.91. Found: C, 71.14; H, 6.24; N, 6.86. m/z 608.0197 [M+H].
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.molcata.
2013.01.003.
6.13. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-9-
(3,4,5-trimethoxyphenyl)-3,3,6,6-tetramethyl-1,8-dioxoacridin-
10(9H)-yl)phenyl)-6-methyl-2-oxopyrimidine-5-carboxylate
(8k)
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6.14. Ethyl-4-(4-(9-(4-bromophenyl)-1,2,3,4,5,6,7,8-octahydro-
3,3,6,6-tetramethyl-1,8-dioxoacridin-10(9H)-yl)phenyl)-1,2,3,4-
tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylate
(8l)
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mp 194–196 ◦C; IR (KBr): ꢀ (cm−1): 3253, 3031, 2971, 2925,
1703, 1668, 1646, 1459; 1H NMR (400 MHz, DMSO-d6): ı 0.98 (s,
6H), 1.06 (s, 6H), 1.09 (t, J = 7.0 Hz, 3H) 2.25 (s, 3H), 2.36 (s, 4H),
2.48 (s, 4H), 4.00 (q, J = 7.0 Hz, 2H), 5.13 (d, J = 3.2 Hz, 1H), 7.00 (d,
J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.39
(d, J = 8.4 Hz, 2H), 8.76 (s, NH, 1H), 9.04 (s, NH, 1H) ppm; 13C NMR
(100 MHz, DMSO-d6): ı 14.7, 170.9, 24.6, 29.2, 32.5, 41.6, 52.5, 59.7,
102.3, 108.7, 118.3, 126.7, 127.9, 129.7, 130.5, 133.3, 140.9, 144.6,
149.2, 155.4, 168.7, 194.2 ppm; Anal. Calcd. For C37H40BrN3O5 (%):
C, 64.72; H, 5.87; N, 6.12. Found: C, 63.14; H, 5.58; N, 6.09. m/z
686.1831 [M+H].
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6.15. Ethyl-1,2,3,4-tetrahydro-4-(4-(1,2,3,4,5,6,7,8-octahydro-
3,3,6,6-tetramethyl-9-(3-nitrophenyl)-1,8
dioxoacridin-10(9H)-yl)phenyl)-6-methyl-2-oxopyrimidine-5-
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carboxylate
(8m)
mp 266–268 ◦C; IR (KBr): ꢀ (cm−1): 3232, 3062, 2954, 2870,
1689, 1581, 1484; 1H NMR (400 MHz, DMSO-d6): ı 0.98 (s, 6H),