A regioselective biginelli-like reaction controlled by the size of alicyclic mono-ketones

Article abstract of DOI:10.1002/jhet.1893

A regioselective Biginelli-like reaction of alicyclic mono-ketones, aromatic aldehydes, and urea in ionic liquid [BPY]BF₄ has been investigated. The process is controlled by the size of alicyclic mono-ketones and the steric hindrance of aromatic aldehydes. The reaction of cyclopentanone with urea and aromatic aldehydes afforded 7-arylidene-3,4,6,7-tetrahydro-4-aryl- 1H-cyclopenta[d]pyrimidin-2(5H)-ones (4). When cyclohexanone was used as the source of active methylene to react with urea and aldehydes with slight steric hindrance groups under the same condition, 8-arylidene-3,4,5,6,7, 8-hexahydro-4-arylquinazolin-2(1H)-ones (6), a homologue of 4, were yielded, whereas 4,8-bisaryloc-tahydro-1H-pyrimido[5,4-i]-quinazoline-2,10(3H,11H)-diones (7) were obtained via the simple one-pot reaction of cyclohexanone, urea, and aromatic aldehydes with high steric hindrance groups. The possible transitional states and mechanism of the regioselective process were discussed.

Full text of DOI:10.1002/jhet.1893

Month 2014
A Regioselective Biginelli-like Reaction Controlled by the Size of Alicy-
clic Mono-ketones
Yu Wan,a,b Rui Yuan,a,b Hua-hong Xu,a,b Chao Wang,a,b Jin-long Qi,a,b and Hui Wua,b
*
aSchool of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou, 221116, People’s Republic of China
bKey Laboratory of Biotechnology on Medical Plant of Jiangsu Province, Xuzhou, 221116, People’s Republic of China
*
E-mail: wuhui72@126.com
Received September 26, 2012
DOI 10.1002/jhet.1893
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A regioselective Biginelli-like reaction of alicyclic mono-ketones, aromatic aldehydes, and urea in ionic
liquid [BPY]BF4 has been investigated. The process is controlled by the size of alicyclic mono-ketones and
the steric hindrance of aromatic aldehydes. The reaction of cyclopentanone with urea and aromatic aldehydes
afforded 7-arylidene-3,4,6,7-tetrahydro-4-aryl-1H-cyclopenta[d]pyrimidin-2(5H)-ones (4). When cyclohexa-
none was used as the source of active methylene to react with urea and aldehydes with slight steric hindrance
groups under the same condition, 8-arylidene-3,4,5,6,7, 8-hexahydro-4-arylquinazolin-2(1H)-ones (6), a homo-
logue of 4, were yielded, whereas 4,8-bisaryloc-tahydro-1H-pyrimido[5,4-i]-quinazoline-2,10(3H,11H)-diones
(7) were obtained via the simple one-pot reaction of cyclohexanone, urea, and aromatic aldehydes with high
steric hindrance groups. The possible transitional states and mechanism of the regioselective process
were discussed.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
aromatic ketones and alicyclic1,3-diketones for efficiently
providing access to dihydropyrimidinethiones [8–12].
In contrast, the Biginelli and Biginelli-like reactions of
alicyclic mono-ketones with lower a-H activity have been a
long-standing challenge. Only a few of Biginelli reaction
using alicyclic mono-ketones as the source of active methy-
lene have been reported [13–17]. However, some shortcom-
ings such as using violent toxic organic solvents and
expensive low-selective catalysts, rigorous condition, high
reaction temperature, and long reaction times limited the
scope of appropriate substrates. Especially, different reaction
conditions always gave the same or analogous framework,
which means poor structural diversity [18–20].
Selective synthesis of different products from the same
materials by just choosing different reaction conditions, such
as catalysis, substrates, and so on, is an interesting research
topic for chemists [1–3].
Biginelli and Biginelli-like reactions, the most useful
multicomponent reactions that assemble aldehydes,
urea/thiourea, and enolizable carbonyls into dihydro-
pyrimidinethiones provide robust tools for the creation
of these important structural motifs [4–7]. Because the
first description of the Biginelli reaction over a century
ago [4], the research interest has long been focused on
© 2014 HeteroCorporation

Y. Wan, R. Yuan, H.-H. Xu, C. Wang, J.-L. Qi, and H. Wu
Vol 000
RESULTS AND DISCUSSION
than that of cyclopentanone, because of the lower reactivity
and more crowded conformation of cyclohexanone.
Interestingly, we found that the size of alicyclic mono-
ketones is able to control the process of the Biginelli-like
reaction. The reaction of cyclopentanone with urea and
aromatic aldehydes mainly afforded 7-arylidene-3,4,6,7-
tetrahydro-4-aryl-1H-cyclopenta[d]pyrimidin-2(5H)-ones (4).
When cyclohexanone was used, under the same condition,
two kinds of product were obtained via two proposed routes
as outlined in Scheme 2. Aromatic aldehydes with slight steric
hindrance groups (entries 1–5, Table 2) mainly gave 8-aryl-
benzylidene-3,4,5,6,7,8-hexahydro-4-aryl-quinaznolin-2
(1H)-ones (6), whereas 4,8-bisaryloctahy1H-pyrimido[5,
4-i]-quinazoline-2,10(3H,11H)-diones (7) were obtained as
the main product.
From Scheme 3, we thought that D is the key intermediate
in controlling the type of product. When cyclopentanone
was used, the most stable conformation of D should be the
uncrowded trans-transition state I; hence, the steric hindrance
of aryl has little influence on the process of the reaction, so
4 is the main-product. Furthermore, –OH and –H are at
trans-position, the elimination reaction seems to be favored.
When cyclohexanone was used, there are two possible
transition states II and III. II is more suitable for the
aromatic aldehydes with slight steric hindrance groups
because the two fused six-membered rings of II are at
trans-position, and the distance between –H on the bridge
bond and benzene ring is far enough, as well as the distance
between –NH2 and carbonyl on pyrimidinone ring. Its –OH
and –H are also at trans-position like I, so the elimination
reaction is favored and 6 was afforded.
In this paper, we reported the HCl (catalytic amount)
catalyzed regioselective Biginelli-like reactions of alicyclic
mono-ketones (cyclopentanone or cyclohexanone), aromatic
aldehydes, and urea in ionic liquid [BPY]BF4, which
provided an efficient method to access 4, 6, and 7 via control-
lable reaction condition with structural diversity.
After the optimization of reaction conditions, we found
that aromatic aldehydes 1, urea 2, and cyclopentanone 3 were
stirred in a presence of a catalytic amount (0.04 mol%)
of HCl at 80ꢀC in [BPY]BF44 for 3–15 h to give the
corresponding 7-arylidene-3,4,6,7-tetrahydro-4-aryl-1H-cyclo-
penta[d] pyrimidin-2(5H)-ones (4) (Scheme 1, Table 1) in
moderate to high yields. The results in Table 1 indicated that
the yields were badly influenced by steric hindrance and
electronic effect of aromatic aldehyde. Aromatic aldehydes
bearing group at ortho-position (entries 12–15, Table 1)
gave lower yields and needed obvious longer reaction time.
Meanwhile, aromatic aldehydes with electron-withdrawing
group (entries 2, 4, and 6–9, Table 1) gave a higher yield than
the ones with electron-donating group (entries 3, 5, 10, and 11,
Table 1).
The results prompted us to use another alicyclic mono-
ketone cyclohexanone (Scheme 2, Table 2). The results
in Table 2 indicated that cyclohexanone can also display
good function, but the reaction time was distinctly longer
Scheme 1
By contraries, III is less crowded than II and favored for
aromatic aldehydes with high steric hindrance (for example,
ortho-substituted ones). So, substitution reaction mainly
took place and compound 7 was obtained.
Table 1
The synthesis of 4 in [BPY]BF4.
Entry
Ar
Compound
Time/h
Isolated yield/%
1
2
3
4
5
6
7
8
C6H5
4-FC6H4
4-CH3C6H4
4-NO2C6H4
4-IC6H4
4-CNC6H4
3-NO2C6H4
3-BrC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
5
4
5
4
5
3
5
5
5
6
6
6
6
15
12
87
84
68
89
75
85
86
81
87
79
74
58
54
55
59
9
3-FC6H4
10
11
12
13
14
15
3,4-OCH2OC6H5
4-CH3OC6H4
2-CH3OC6H4
2,3-(CH3O)2C6H3
2-BrC6H4
2-ClC6H4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
A Regioselective Biginelli-like Reaction Controlled by the Size of Alicyclic Mono-ketones
Scheme 2
Table 2
EXPERIMENTAL
Synthesis of 6 and 7 in [BPY]BF4.
All reagents were purchased from commercial sources and
used without further purification. NMR spectra were measured
in DMSO-d6 with Me4Si as the internal standards on a Bruker
Avance DPX-400 (Bruker Corporation, Germany) at room tem-
perature. IR spectra were recorded on Bruker FTIR spectrometer,
absorbance were reported in reciprocal centimeter. Mass spectra
were determined by using a Bruker TOF-MS high-resolution
mass spectrometer.
General procedure for the synthesis of 4 in ionic liquid. A
mixture of aromatic aldehyde 1 (4.0 mmol), urea 2 (5.0 mmol), and
cyclopentanone 3 (2.0 mmol), 2% HCl (0.04 mol%) was simply
stirred in [BPY]BF4 (2 mL) at 80ꢀC for 3–15 h (monitored by
TLC). Upon and on completion, the reaction mixture was poured
into water and [BPY]BF4 was removed by filtration. The product
was purified by recrystallization with EtOH (95%)-DMF (10:1).
General procedure for the synthesis of 6 and 7 in ionic
liquid. A mixture of aromatic aldehyde 1 (4.0mmol), urea 2
(5.0mmol), cyclohexanone 5 (2.0 mmol), and 2% HCl (0.04 mol
%) was simply stirred in [BPY]BF4 (2 mL) at 80ꢀC for 6–15 h
(monitored by TLC). The following procedures were same as the
synthesis of 4.
The known compounds (4a, 4b, 4c, 4d, 4f, 4g, 4i, 4k, 4l, 4o, 4n
in Table 1 and 6a, 7a, 7b, 7c, 7e, 7h, 7i, 7j in Table 2) have been
identified by comparison of spectral data with literature [18,20].
Isolated yield/
%
Time/
h
Entry Product
Ar
6
7
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6a
6b
7c
7d
7e
7f
C6H4
4-NO2C6H4
4-ClC6H4
10
12
8
82
—
—
—
—
—
—
—
82
84
87
82
79
67
68
62
81
79
85
82
86
78
—
—
—
—
—
—
—
—
4-BrC6H4
6
4-CH3C6H4
4-FC6H4
4-IC6H4
10
10
14
9
15
8
3,4-OCH2OC6H3
3,4,5-(CH3O)3C6H2
3-NO2C6H4
3-BrC6H4
9
10
11
12
13
14
15
8
7g
7h
7i
3-FC6H4
8
2-CH3OC6H4
2-FC6H4
2-ClC6H4
12
15
12
7j
Therefore, we supposed that the high regioselective reac-
tion is mainly determined by the size and special preponder-
ant conformation of alicyclic mono-ketones, whereas
aromatic ketones did not have these characteristics.
The spectral data of new products are given in the succeeding text
In summary, we have discovered that the size of two
alicyclic mono-ketones (cyclopentanone or cyclohexanone)
is able to control the process of the Biginelli-like reaction.
The reaction of cyclopentanone with urea and aromatic
aldehydes mainly afforded 7-arylidene-3,4,6,7-tetrahydro-
4-aryl-1H-cyclopenta[d] pyrimidin-2(5H)-ones (4). When
cyclohexanone was used, by changing the steric hindrance
of substituent on aromatic aldehydes, under the same condi-
tion, two kinds of product were obtained via different ways.
8-arylbenzylidene-3,4,5,6,7,8-hexahydro-4-aryl-quinazolin-2
(1H)-ones (6) could be derived from aromatic aldehydes with
slight steric hindrance groups, whereas 4,8-bisaryloctahydro-
1H-pyrimido[5,4-i]-quinazoline-2,10(3H,11H)-diones (7) were
obtained as the main product in a simple one-pot process.
These reactions have an advantage of obtaining complex pro-
ducts with a various of structural diversity via simple method.
7-(4-iodobenzylidene)-3,4,6,7-tetrahydro-4-(4-iodophenyl)-1H-
cyclopenta[d]pyrimidin-2(5H)-one (4e). mp: 267–268ꢀC; IR (KBr,
n, cmÀ1): 3317, 2925, 1658, 1582, 1028, 976, 774; 1H NMR
(400 MHz, DMSO-d6) (d, ppm): 8.80 (1H, s, NH), 7.74–7.76
(2H, d, J = 8.2 Hz, ArH), 7.68–7.70 (2H, d, J = 8.2 Hz, ArH), 7.24
(1H, s, C2–H), 7.08–7.16 (4H, m, ArH), 6.58 (1H, s, NH), 5.14
(1H, s, C14–H), 2.71–2.90 (2H, m, CH2), 2.36–2.42 (1H, m,
CH2), 1.96–2.02(1H, m, CH2); 13C NMR (100 MHz, DMSO-d6)
d: 53.03, 142.99, 141.86, 140.13, 137.83, 137.50, 137.33, 137.23,
137.19, 136.08, 129.92, 128.86, 118.72, 115.84, 93.34, 91.47,
90.85, 56.91, 28.34, 28.20; HRMS: m/z calcd for C20H16I2N2O
[M+ 1], 554.9352; found, 554.9345.
7-(3-bromobenzylidene)-4-(3-bromophenyl)-3,4,6,7-tetrahydro-
1H-cyclopenta[d]pyrimidin-2(5H)-one (4h). mp: 286–288ꢀC; IR
(KBr, n, cmÀ1): 3352, 2906, 1634, 1579, 1546, 768; 1H NMR
(400 MHz, DMSO-d6) (d, ppm): 8.84 (1H, s, NH), 7.49–7.52
(1H, m, ArH), 7.46 (2H, s, ArH), 7.29–7.38 (6H, m, ArH),
6.62 (1H, s, NH), 5.22 (1H, s, C14–H), 2.77–2.89 (2H, m, CH2),
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DOI 10.1002/jhet

Y. Wan, R. Yuan, H.-H. Xu, C. Wang, J.-L. Qi, and H. Wu
Vol 000
Scheme 3
2.40–2.44 (1H, m, CH2), 1.99–2.05 (1H, m, CH2) 13C NMR
(100 MHz, DMSO-d6) d: 162.26, 153.00, 145.90, 140.81, 140.10,
136.11, 130.87, 130.60, 130.36, 130.02, 129.17, 128.67, 126.77,
125.61, 121.88, 118.98, 115.48, 56.78, 35.76, 30.77, 28.28,
28.22; HRMS: m/z calcd for C20H16Br2N2O [M + 1], 457.9629;
found, 457.9605.
7-((benzo[d][1,3]dioxol-5-yl)methylene)-4-(benzo[d][1,3]dioxol-
6-yl)-3,4,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-2(5H)-one (4j).
mp: 280–282ꢀC; IR (KBr, n, cmÀ1): 3351, 2906, 1628, 1529, 749;
1H NMR (400MHz, DMSO-d6) (d, ppm): 8.67 (1H, d, J = 0.4 Hz,
NH), 7.14 (1H, s, ArH), 7.17–7.20 (3H, m, ArH), 6.73–6.81
(3H, m, ArH), 6.55 (1H, s, NH), 6.01 (2H, d, J = 2.0 Hz, ArH)
5.07 (1H, s, C15–H), 2.77–2.80 (2H, m, CH2), 2.33–2.39 (1H, m,
CH2), 2.00–2.06 (1H, m, CH2) 13C NMR (100 MHz, DMSO-d6)
d: 153.10, 147.46, 147.42, 146.52, 145.49, 137.53, 137.26,
135.89, 132.07, 122.18, 119.69, 117.71, 116.49, 108.44, 108.12,
107.37, 106.81, 100.98, 100.91, 57.04, 28.24, 28.16; HRMS:
m/z calcd for C22H18N2O5 [M+ 1], 391.1216; found, 391.1208.
Journal of Heterocyclic Chemistry
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Month 2014
A Regioselective Biginelli-like Reaction Controlled by the Size of Alicyclic Mono-ketones
7-(2,3-dimethoxybenzylidene)-3,4,6,7-tetrahydro-4-(2,3-
dimethoxyphenyl)-1H-cyclopenta[d]pyrimidin-2(5H)-one (4m).
mp: 247–248ꢀC; IR (KBr, n, cmÀ1): 3328, 2925, 1667, 1524,
130.25, 129.34, 128.64, 128.54, 128.41, 128.37, 128.32, 128.29,
128.12, 123.78, 120.92, 111.92, 58.71, 26.35, 25.85, 22.14; HRMS:
m/z calcd for C21H18N2O [M + 1], 385.0796; found, 385.0779.
4,8-bis(4-iodophenyl)octahydro-1H-pyrimido[5,4-i]-quinazoline-
2,10(3H,11H)-dione (7d). mp: >300ꢀC; IR (KBr, n, cmÀ1): 3357,
3274, 2932, 1589, 1667, 1551, 764; 1H NMR (400 MHz, DMSO-
d6) (d, ppm): 7.70–7.74 (4H, m, ArH), 7.27 (1H, d, J = 0.8 Hz,
NH), 7.09–7.11 (4H, d, J = 8.4 Hz, ArH), 6.87 (1H, s, NH), 6.63
(1H, s, NH), 6.56 (1H, d, J = 0.4 Hz, NH), 4.92 (1H, d, J = 2.8 Hz,
R3CH), 4.51–4.54 (1H, d, J= 15.2 Hz, R3CH), 1.91–1.99 (2H, m,
CH2), 1.36–1.46 (2H, m, CH2), 1.20–1.24 (1H, m, R3CH), 1.11–
1.15 (1H, m, R3CH), 0.82–0.89 (2H, m, CH2); 13C NMR
(100 MHz, DMSO-d6) d: 180.20, 159.20, 153.02, 149.44, 142.99,
140.13, 137.32, 137.23, 137.18, 136.08, 129.91, 128.85, 119.07,
118.72, 115.84, 112.72, 111.92, 93.33, 91.47, 56.90, 28.21; HRMS:
m/z calcd for C22H22I2N4O2[M + 1], 628.9832; found, 628.9825.
4,8-bis(3-bromophenyl)octahydro-1H-pyrimido[5,4-i]-
quinazoline-2,10(3H,11H)-dione (7f).. mp: >300ꢀC; IR
(KBr, n, cmÀ1): 3327, 2895, 1661, 1543, 797, 753; 1H NMR
(400 MHz, DMSO-d6) (d, ppm): 7.46–7.52 (4H, m, ArH),
7.30–7.36 (4H, m, ArH), 7.29 (1H, s, NH), 6.85 (1H, d, J=6.0Hz,
NH), 6.70 (1H, s, NH), 6.63 (1H, d, J= 1.2 Hz, NH), 4.96 (1H, d,
J=3.2Hz, R3CH), 4.60 (1H, d, J= 11.2 Hz, R3CH), 1.98–2.04 (2H,
m, CH2), 1.40–1.49 (2H, m, CH2), 1.24–1.28 (1H, m, R3CH),
1.10–1.17 (1H, m, R3CH), 0.82–0.91 (2H, m, CH2); 13C NMR
(100 MHz, DMSO-d6) d: 160.94, 160.85, 159.08, 155.33, 153.98,
144.60, 143.20, 130.42, 130.33, 130.01, 129.92, 123.57, 123.54,
122.73, 114.61, 114.40, 114.14, 113.93, 113.72, 113.50, 67.33,
52.65, 52.37, 42.68, 42.18, 35.77, 21.86, 21.46, 18.14; HRMS:
m/z calcd for C22H22Br2N4O2 [M + 1], 533.0110; found, 533.0100.
4,8-bis(3-fluorophenyl)octahydro-1H-pyrimido[5,4-i]-
quinazoline-2,10(3H,11H)-dione (7g).. mp: >300ꢀC; IR
(KBr, n, cmÀ1): 3312, 2901, 1659, 1530, 787, 756; 1H NMR
(400 MHz, DMSO-d6) (d, ppm): 7.38–7.45 (2H, m, ArH), 7.30
(1H, s, NH), 7.09–7.16 (6H, m, ArH), 6.88 (1H, s, NH), 6.70
(1H, s, NH), 6.63 (1H, s, NH), 5.00 (1H, d, J = 3.2 Hz, R3CH),
4.61–4.63 (1H, d, J = 11.2Hz, R3CH), 2.01–2.04 (2H, m, CH2),
1.40–1.47 (2H, m, CH2), 1.23–1.26 (1H, m, R3CH), 1.13–1.18
(1H, m, R3CH), 0.84–0.91 (2H, m, CH2); 13C NMR (100MHz,
DMSO-d6) d: 160.94, 160.85, 159.08, 155.33, 153.98, 144.60,
143.20, 130.42, 130.33, 130.01, 129.92, 123.57, 123.54, 122.73,
114.61, 114.40, 114.14, 113.93, 113.72, 113.50, 67.33, 52.65,
52.37, 42.68, 42.18, 35.77, 21.86, 21.46, 18.14; HRMS: m/z calcd
for C22H22F2N4O2[M+ 1], 413.1711; found, 413.1700.
1
767; H NMR (400 MHz, DMSO-d6) (d, ppm): 8.94 (1H, NH),
7.07–7.11 (1H, t, J = 6.0 Hz, ArH), 6.95–7.02 (4H, m, ArH),
6.88–6.91 (1H, t, J = 4.8 Hz, C2–H), 6.83 (1H, dd, J = 6.4 Hz,
ArH), 6.73 (1H, s, NH), 3.79–3.81 (6H, d, J = 6.8 Hz, 2*OCH3),
3.74 (3H, s, OCH3), 3.71 (3H, s, OCH3), 2.70–2.76 (2H, m,
CH2), 2.30–2.36 (1H, m, CH2), 1.93–1.99 (1H, m, CH2); 13C
NMR (100 MHz, DMSO-d6) d: 153.49, 152.53, 152.14, 146.37,
145.67, 139.86, 136.65, 136.13, 131.73, 124.23, 123.54, 119.89,
119.54, 118.38, 111.86, 111.03, 110.97, 60.43, 60.35, 55.69,
55.61, 51.57, 28.29, 28.16; HRMS: m/z calcd. for C24H26N2O5
[M+ 1], 422.1842; found, 422.1833.
4-(benzo[d][1,3]dioxol-5-yl)-8-((benzo[d][1,3]dioxol-5-yl)
methylene)-3,4,5,6,7,8-hexahydroquinazolin-2(1H)-one (6a). mp:
280–281ꢀC; IR (KBr, n, cmÀ1): 3326, 2897, 1664, 1548, 787, 763;
1H NMR (400MHz, DMSO-d6) (d, ppm): 8.01 (1H, s, NH), 7.15
(1H, s, NH), 6.86–6.92 (3H, m, ArH), 6.78–6.80 (3H, m, ArH),
6.75–6.77 (1H, dd, J = 8.0 Hz, C2–H), 6.01 (4H, d, J = 2.8 Hz,
2*OCH2O), 4.69 (1H, s, C16–H), 2.56–2.61 (1H, m, CH2), 2.38–
2.45 (1H, m, CH2), 1.98–2.04 (1H, m, CH2), 1.75–1.83 (1H, m,
CH2), 1.52–1.58 (2H, m, CH2); 13C NMR (100MHz, DMSO-d6)
d: 153.11, 147.45, 147.07, 146.57, 145.81, 138.14, 131.25,
128.87, 128.51, 123.04, 121.69, 119.97, 111.54, 109.18, 108.08,
106.98, 100.96, 100.90, 59.09, 26.46, 25.88, 22.23; HRMS:
m/z calcd for C23H20N2O5 [M+ 1], 405.1372; found, 405.1360.
8-(3,4,5-trimethoxybenzylidene)-3,4,5,6,7,8-hexahydro-4-(3,4,5-
trimethoxyphenyl)quinazolin-2(1H)-one (6b). mp: 273–275ꢀC; IR
1
(KBr, n, cmÀ1): 3246, 2893, 1645, 1612, 1558, 743; H NMR
(400MHz, DMSO-d6) (d, ppm): 8.03 (1H, s, NH), 7.15 (1H, s,
NH), 6.83 (1H, s, C2–H), 6.60 (4H, s, ArH), 4.77 (1H, s, C18–H),
3.77 (12H, d, J = 3.2Hz, 4*OCH3), 3.66 (6H, d, J = 4.4 Hz,
2*OCH3), 2.65–2.70 (1H, m, CH2), 2.48–2.49 (1H, m, CH2),
2.03–2.09 (1H, m, CH2), 1.84–1.89 (1H, m, CH2), 1.55–1.62 (2H,
m, CH2); 13C NMR (100 MHz, DMSO-d6) d: 153.18, 152.94,
152.49, 139.45, 137.03, 136.46, 132.80, 129.50, 128.71, 122.07,
112.71, 111.48, 109.07, 106.80, 105.90, 104.22, 60.10, 60.05, 60.00,
59.55, 56.12, 56.09, 55.96, 55.87, 26.53, 25.99, 22.34; HRMS: m/z
calcd for C27H32N2O7 [M + 1], 497.2210; found, 497.2198.
8-(4-bromobenzylidene)-4-(4-bromophenyl)-3,4,5,6,7,8-
hexahydroquinazolin-2(1H)-one (6c). mp: 274–275ꢀC; IR
(KBr, n, cmÀ1): 3324, 2895, 1659, 1528, 798, 763; 1H NMR
(400MHz, DMSO-d6) (d, ppm): 8.16 (1H, s, NH), 7.53–7.59
(4H, m, ArH), 7.24–7.29 (5H, m, ArH), 6.86 (1H, s, NH), 4.79
(1H, d, J = 1.2 Hz, C15–H), 2.53–2.58 (1H, m, CH2), 2.36–2.42
(1H, m, CH2), 2.02–2.07 (1H, m, CH2), 1.71–1.77 (1H, m, CH2),
1.52–1.55 (2H, m, CH2); 13C NMR (100MHz, DMSO-d6) d:
153.07, 143.27, 136.42, 132.29, 131.47, 131.18, 131.05, 130.98,
130.85, 130.68, 129.00, 128.67, 120.98, 120.57, 119.60, 111.90,
58.77, 26.35, 25.84, 22.13; HRMS: m/z calcd for C21H18Br2N2O
[M+ 1], 472.9786; found, 472.9778.
8-(4-chlorobenzylidene)-4-(4-chlorophenyl)-3,4,5,6,7,8-
hexahydroquinazolin-2(1H)-one (6e). mp: 269–270ꢀC; IR
(KBr, n, cmÀ1): 3321, 2886, 1637, 1526, 793, 753; 1H NMR
(400MHz, DMSO-d6) (d, ppm): 8.16 (1H, s, NH), 7.40–7.46
(4H, m, ArH), 7.32 (4H, d, J = 8.4 Hz, ArH), 7.29 (1H, s, C2–H),
6.89 (1H, s, NH), 4.81 (1H, d, J = 1.2 Hz, C15–H), 2.54–2.61 (1H,
m, CH2), 2.36–2.43 (1H, m, CH2), 2.02–2.09 (1H, m, CH2),
1.72–1.79 (1H, m, CH2), 1.52–1.56 (2H, m, CH2); 13C NMR
(100 MHz, DMSO-d6) d: 153.10, 142.87, 136.07, 132.22, 132.05,
131.53, 131.14, 131.05, 130.85, 130.77, 130.62, 130.53, 130.48,
Acknowledgments. We are grateful to the foundation of the “Priority
Academic Program Development of Jiangsu Higher Education
Institutions,” “Key Basic Research Project in Jiangsu University”
(No. 10KJA430050, 11KJB150017), the “Graduate Innovation
Project in Jiangsu Province” (No. CXZZ11_0904, CXZZ12_0979),
and “College Students’ Practice Innovation Training Program in
Jiangsu Province” for financial support.
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