Green synthesis and crystal structure of 4,7-diaryl-2-oxo(thio)-1,2,3,4,5, 6,7,8-octahydroquinazoline-5-one derivatives

Article abstract of DOI:10.1002/jhet.541

A green and convenient approach to the synthesis of novel 4,7-diaryl-2-oxo(thio)-1,2,3,4,5,6,7,8-octahydroquinazoline-5-one derivatives from appropriate aromatic aldehydes and 5-aryl-1,3-cyclohexanedione with urea or thiourea in the presence of dilute HCl as catalyst in water is described. This method provides several advantages such as environmental friendliness, low cost, high yields, and simple workup procedure. The structures of all compounds were characterized by elemental analysis, IR, MS, and ¹H NMR. The crystal and molecular structure of 4-(4′-chlorophenyl)-7-(4′-methoxyphenyl)- 1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione 5m have been determined by single crystal X-ray diffraction analysis. The crystal of compound 5m belongs to monoclinic with space group P-2₁/c, a = 1.4353 (4) nm, b = 1.4011 (4) nm, c = 0.9248 (3) nm, α = 90.00°, β = 101.242 (6)°, γ = 90.00°, Z = 4, V = 1.8241 (9) nm³, R₁ = 0.0448, and wR₂ = 0.1022.

Full text of DOI:10.1002/jhet.541

3
12
Green Synthesis and Crystal Structure of 4,7-Diaryl-2-oxo(thio)-
,2,3,4,5,6,7,8-octahydroquinazoline-5-one Derivatives
Vol 48
1
Guang-Fan Han,* Bin Cui, Li-Zhuang Chen, Rui-Hua Wang, and Yan Jin
School of Material Science and Engineering, Jiangsu University of Science and Technology,
Zhenjiang, Jiangsu 212003, China
*
E-mail: gf552002@yahoo.com.cn
Received March 7, 2010
DOI 10.1002/jhet.541
Published online 10 December 2010 in Wiley Online Library (wileyonlinelibrary.com).
A green and convenient approach to the synthesis of novel 4,7-diaryl-2-oxo(thio)-1,2,3,4,5,6,7,8-octa-
hydroquinazoline-5-one derivatives from appropriate aromatic aldehydes and 5-aryl-1,3-cyclohexane-
dione with urea or thiourea in the presence of dilute HCl as catalyst in water is described. This method
provides several advantages such as environmental friendliness, low cost, high yields, and simple
workup procedure. The structures of all compounds were characterized by elemental analysis, IR, MS,
1
0
0
and H NMR. The crystal and molecular structure of 4-(4 -chlorophenyl)-7-(4 -methoxyphenyl)-
,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione 5m have been determined by single crystal X-ray diffrac-
tion analysis. The crystal of compound 5m belongs to monoclinic with space group P-2 /c, a ¼ 1.4353
1
1
ꢀ
ꢀ
ꢀ
(
4) nm, b ¼ 1.4011 (4) nm, c ¼ 0.9248 (3) nm, a ¼ 90.00 , b ¼ 101.242 (6) , c ¼ 90.00 , Z ¼ 4,
1 2
3
V ¼ 1.8241 (9) nm , R ¼ 0.0448, and wR ¼ 0.1022.
J. Heterocyclic Chem., 48, 312 (2011).
INTRODUCTION
RESULTS AND DISCUSSION
Recently, much attention has been focused on the synthe-
sis of octahydroquinazolinone due to their significant bio-
logical activities, such as against staphylococcus aureus,
escherichiacoli, pseudomonas aeruginosa [1], and calcium
antagonist activity [2,3]. Many methods have been devel-
oped for the preparation of quinazolinone derivatives which
include the three-component coupling of an aldehyde with
ethyl acetoacetate and ammonia in acetic acid or in reflux-
ing alcohol [4,5], or using microwaves [6], ionic liquids [7],
or refluxing at high temperature with many catalysts [8–14].
However, many of these reagents or catalysts are expensive,
harmful, and difficult to handle especially on a large scale.
In this article, we report a clean and highly efficient
route for the one-pot synthesis of the title compounds
using dilute HCl as catalyst in water. This novel method
is not only environmental friendliness but also consis-
tently gives the corresponding products in good yields.
We also obtained the single crystal 5m, and the three-
dimensional structure was confirmed by the X-ray dif-
fraction analysis.
The synthetic pathway is shown in Scheme 1. The
5-aryl-1,3-cyclohexanedione were obtained from aro-
matic aldehyde, acetone, and diethyl malonate according
to the literature [15] method with slightly modifica-
tion. The 4,7-diaryl-2-oxo(thio)-1,2,3,4,5,6,7,8-octahy-
droquinazoline-5-one derivatives were obtained by the
Biginelli condensation reaction of 5-aryl-1,3-cyclohexa-
nedione with urea or thiourea and substituted benzalde-
hydes using two drops of concentrated HCl as catalyst
in water. As shown in Table 1, the reaction proceeded
smoothly to afford the corresponding products in good
yields. All aromatic aldhydes containing electron-with-
drawing groups (such as halide) or electron-donating
groups (such as methoxy) were used and reacted well to
give the corresponding product in good yields under
these conditions, so we conclude that the nature of the
substituents on the aromatic ring had no obvious effect
on the reaction.
Taking the reaction of benzaldehyde for example, we
investigated the effect of the amount of catalyst on the
reaction, which plays a crucial role in the success of the
V
C
2010 HeteroCorporation

March 2011
Green Synthesis and Crystal Structure of 4,7-Diaryl-2-oxo(thio)-1,2,3,4,5,6,7,
313
8-octahydroquinazoline-5-one Derivatives
Scheme 1
reaction in terms of the rate and the yields. It was found
that the reaction could not be carried out without the
catalyst, and with two drops of concentrate HCl(about
5.20 was the characteristic absorption proton peak of
the 4-H, two broad single peaks at d 7.88 and d 9.66
were observed. They disappeared after D O exchange
2
ꢀ
0
.1 mL) in 20 mL water at 70–80 C for 2 h, the reac-
and therefore were attributed to the two N-H of the
amino group. Because of the existence of intramolecu-
lar hydrogen bond between one proton of the amino
group and the oxygen atom of the carbonyl
group nearby (Table 3), its proton peak was drifted to
d 9.66.
tion could afford the corresponding product in good
yields. But with the catalyst increased, the yields show a
decreasing trend. These data indicated that two drops of
concentrate HCl in 20 mL water is quite suitable for
this reaction.
1
The data of H NMR, MS, and IR shown in the ex-
perimental section are in accordance with the chemical
The structures of these compounds were further sup-
ported by their IR spectra. Server typical absorption
bands at 1711 cm for (C ¼¼ O), 3275 cmꢁ1 for (N ¼¼ H)
were observed.
1
structures of the target compounds. In the H NMR
ꢁ1
spectrum of compound 4f, the single proton peak at d
Table 1
Synthesis of 4,7-diaryl-2-oxo(thio)-1,2,3,4,5,6,7,8-octahydroquinazoline-5-one.
ꢀ
a
Entry
Ar
X
R
M.P. ( C)
Yield (%)
Approximate ratio (4:5)
4
a
a
C
C
C
C
C
C
C
C
C
C
C
C
C
6
6
6
6
6
6
6
6
6
6
6
6
6
H
H
H
H
H
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
5
5
5
5
O
O
O
O
O
O
O
S
H
H
278–279
278–280
280–282
282–284
280–281
270–272
272–274
250–251
251–252
242–244
250–251
244–245
247–248
252–254
259–260
286–287
284–286
254–256
234–235
50
26
80
77
85
57
26
50
29
84
81
80
86
88
86
56
28
83
81
–
–
5
4
4
4
4
5
4
5
4
4
4
4
4
4
4
5
4
4
bþ5b
cþ5c
dþ5d
e
2-Cl
4-Cl
3-OCH
4-OCH
4-OCH
H
5:3
5:2
2:1
–
3
3
3
e
–
f
f
–
–
S
H
gþ5g
hþ5h
iþ5i
jþ5j
kþ5k
lþ5l
m
S
S
2-Cl
4-Cl
3-OCH
4-OCH
H
3:1
7:3
3:2
2:1
2:1
7:3
–
S
3
3
5
S
4-OCH
4-OCH
4-OCH
4-OCH
4-OCH
4-OCH
3
3
3
3
3
3
C
H
6 4
H
6 4
H
6 4
H
6 4
H
6 4
H
6 4
O
O
O
O
O
S
C
C
C
C
C
2-Cl
4-Cl
4-Cl
4-OCH
H
m
–
3:2
5:3
nþ5n
3
oþ5o
a
1
It was speculated from the integration area of the special position H in the H NMR spectrum.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

3
14
G.-F. Han, B. Cui, L.-Z. Chen, R.-H. Wang, and Y. Jin
Vol 48
Table 2
Crystallographic data for crystallographic data for complex 5m.
Empirical formula
Formula weight
Wavelength (nm)
Crystal system
Space group
a (nm)
21 2 3
C H19 Cl N O
382.83
0.071073
Monoclinic
P2 /c
1
1.4353(4)
1.4011(4)
0.9248(3)
90.00
b (nm)
c (nm)
ꢀ
a ( )
ꢀ
b ( )
101.242(6)
90.00
ꢀ
c ( )
Volume (nm )
3
1.8241(9)
4
1.394
Z
Calculated density (g cm
ꢁ
3
)
ꢁ
Figure 2. Packing diagram of compound 5m in unit-cell.
1
Absorption coefficient (mm
F (000)
Final R indices [I > 2sigma (I)]
)
0.234
800
and bond angles of primary hydrogen bonds were listed
in Table 3.
R
R
1
¼ 0.0448, wR
2
2
¼ 0.1022
¼ 0.1162
R indices (all data)
1
¼ 0.0769, wR
CONCLUSIONS
CRYSTAL STRUCTURE
A summary of the crystal data and structure refine-
In summary, we have described a general and highly effi-
cient procedure for the one-pot preparation of 4,7-diaryl-2-
oxo(thio)-1,2,3,4,5,6,7,8-octahydroquinazoline-5-one deriv-
atives catalyzed by two drops of concentrate HCl in water.
It is possible to apply tenets of green chemistry to the gener-
ation of interesting products using aqueous media methods
that are less expensive and less toxic than those with organic
solvent. Catalyst is very cheap, nontoxic and used in very
small amount. Moreover, the procedure offers several
advantages including high yields, low-cost, operational
simplicity, cleaner reactions, and minimal environmental
effects, which make it a useful and attractive process for the
synthesis of these compounds.
ment is presented in Table 2. A perspective view of
compound 5m with atomic numbering scheme was
shown in Figure 1. In compound 5m, The dihedral angle
between the bond lengths and bond angles are generally
normal in the phenyl and quinoline ring and the quino-
line ring [C(7), C(8), C(9), C(10), C(11), C(12), C(13),
C(14), N(1), N(2)] with plane equation 4.0780 (0.0027)
x þ 10.7892 (0.0071) y þ 4.6691 (0.0053) z ¼ 8.9674,
The benzene ring a [C(1), C(2), C(3), C(4), C(5), C(6)]
with plane equation 10.4240 (0.0095) x þ 3.3441
ꢀ
(
0.0130) y ꢁ 7.1571 (0.0059) z ¼ 11.7828 is 88.76 .
The benzene ring b [C(15), C(16), C(17), C(18), C(19),
C(20)] is coplanar with the conjunction C(14), whose
plane equation is ꢁ 2.5083 (0.0140) x þ 11.9234
EXPERIMENTAL
(
0.0087) y ꢁ 4.1769 (0.0084) z ¼ 0.8635. The dihedral
Melting points were determined on an electro-thermal appa-
ratus and the temperature was not calibrated. Microanalysis
was performed by the Perkin–Elmer 2400 Microanalytical
Service. Infrared spectra were recorded as thin films on KBr
using a Perking-Elmer 1700 spectrophotometer. The NMR
spectra were recorded by a Bruker ARX-300 spectrometer.
angles between the benzene ring b and quinoline ring
ꢀ
plane is 59.09 . The packing diagram of the 5m in a
unit cell was shown in Figure 2. X-ray analysis reveals
that there are intramolecular and intermolecular hydro-
gen bonds in the crystal. The intermolecular hydrogen
˚
bond N(1)–H(1)ꢂꢂꢂO(2) is 2.861(4) A, the structural anal-
Sample solutions were prepared in CDCl or DMSO contain-
3
ysis indicates that these molecular interactions play the
role of further stabilizing the structure. The bond lengths
ing TMS as an internal reference. Mass spectra were recorded
by JMS-DX300 at 70 eV.
All chemical reagents were commercially available and puri-
fied with standard methods before use. 5-aryl-1,3-cyclohexane-
dione were obtained from aromatic aldehyde, acetone, and
Table 3
˚
Inter and intramolecular interaction distances (A) for the compound
5m.
D–HꢂꢂꢂA
D–H HꢂꢂꢂA DꢂꢂꢂA D–HꢂꢂꢂA Symmetry
N(1)–H(1)ꢂꢂꢂO(2) 0.900 1.98 2.861 165.68
x, y, z
Figure 1. Molecular structure of compound 5m.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2011
Green Synthesis and Crystal Structure of 4,7-Diaryl-2-oxo(thio)-1,2,3,4,5,6,7,
-octahydroquinazoline-5-one Derivatives
315
8
diethyl malonate according to the literature [15] method with
slightly modification. A mixture of an 5-aryl-1,3-cyclohexane-
dione (1, 5 mmol), urea or thiourea(2, 5 mmol), aromatic alde-
hyde (3, 5 mmol) and two drops of 37% HCl (0.1 mL) in
(%): 334.18 (M-1, 100); Anal. Calcd. for C20H
71.83, H 5.42, N 8.38; found C 71.75, H 5.50, N 8.24.
18
N
2
OS: C
1
5f. H NMR (DMSO, 300 MHz) d: 2.38–2.86 (m, 4H, 6-H
þ 8-H), 3.36–3.48 (m, 1H, 7-H), 5.18 (s, 1H, 4-H), 7.18–7.41
(m, 9H, Ph-H), 7.83 (s, 1H, 3-NH), 9.60 (s, 1H, 1-NH); IR
ꢀ
water (20 mL) were stirred at 70–80 C for 2 h. Then the mix-
ꢁ
1
ture was cooled to room temperature; solid was filtered off
and washed with water. The crude products were purified by
recrystallization from ethanol (95%).
(KBr) m: 3276, 1709, 1683, 1624, 1512 cm ; MS (70eV) m/z
(%): 334.18 (M-1, 100); Anal. Calcd. for C20 OS: C
71.83, H 5.42, N 8.38; found C 71.95, H 5.51, N 8.22.
18 2
H N
1
1
Data of compounds are shown below.
4a. H NMR
4g 1 5g. H NMR (CDCl , 300 MHz) d: 2.60–2.99 (m, 3H,
3
(
2
6
DMSO, 300 MHz) d: 2.26–2.60 (m, 3H, 6-H þ 8-H), 2.70–
6-H þ 8-H), 3.47–3.66 (m, 1H, 6-H), 3.69–3.96 (m, 1H, 7-H),
5.44 and 5.54 (each s, 1H, 4-H), 6.56–7.41 (m, 9H, Ph-H),
9.70 and 9.76 (each s, 1H, 3-NH), 12.40 and 12.47 (each s,
1H, 1-NH); IR (KBr) m: 3293, 1693, 1632, 1500 cm ; MS
(70eV) m/z (%): 368.50 (M, 100); Anal. Calcd. for
.83 (m, 1H, 6-H), 3.41–3.47 (m, 1H, 7-H), 5.13 (s, 1H, 4-H),
.85–7.32 (m, 10H, Ph-H), 7.72 (s, 1H, 3-NH), 9.50 (s, 1H, 1-
ꢁ
1
ꢁ1
NH); IR (KBr) m: 3240, 1712, 1671, 1619, 1507 cm ; MS
70eV) m/z (%): 319.17 (M þ 1, 100); Anal. Calcd. for
C H N O : C 75.45, H 5.70, N 8.80; found C 75.37, H 5.62,
(
C H ClN OS: C 65.12, H 4.65, N 7.59; found C 65.32, H
20 17
20
18
2
2
2
N 8.87.
4.47, N 7.53.
1
1
5
a. H NMR (DMSO, 300 MHz) d: 2.36–2.66 (m, 3H, 6-H
þ 8-H), 2.71–2.86 (m, 1H, 6-H), 3.41–3.47 (m, 1H, 7-H),
.16(s, 1H, 4-H), 6.80–7.33 (m, 10H, Ph-H), 7.78 (s, 1H, 3-
NH), 9.56 (s, 1H, 1-NH); IR (KBr) m: 3243, 1715, 1671, 1629,
3
4h 1 5h. H NMR (CDCl , 300 MHz) d: 2.60–3.08 (m,
4H, 6-H þ 8-H), 3.33–3.56 (m, 1H, 7-H), 5.44 and 5.51 (each
s, 1H, 4-H), 7.12–7.57 (m, 9H, Ph-H), 12.08 and 12.11 (each
s, 1H, 3-NH), 12.40 and 12.45 (each s, 1H, 1-NH); IR (KBr)
5
ꢁ
1
ꢁ1
1508 cm ; MS (70eV) m/z (%): 319.17 (M þ 1, 100); Anal.
Calcd. for C H N O : C 75.45, H 5.70, N 8.80; found C
m: 3276, 1695, 1640, 1502 cm ; MS (70eV) m/z (%): 369.19
20
18
2
2
(M þ 1, 100); Anal. Calcd. for C H ClN OS: C 65.12, H
20 17
2
7
5.53, H 5.65, N 8.67.
1
4.65, N 7.59; found C 65.05, H 4.53, N 7.67.
1
4
b 1 5b. H NMR (CDCl , 500 MHz) d: 2.25–2.79 (m, 4H,
4i 1 5i. H NMR (DMSO, 300 MHz) d: 2.34–2.90 (m, 4H,
3
6
1
3
1
1
7
-H þ 8-H), 3.37–3.47 (m, 1H, 7-H), 5.58 and 5.62 (each s,
H, 4-H), 7.07–7.49 (m, 9H, Ph-H), 7.71 and 7.75 (each s, 1H,
-NH), 9.60 and 9.62 (each s, 1H, 1-NH); IR (KBr) m: 3255,
6-H þ 8-H), 3.27–3.47 (m, 1H, 7-H), 3.79 (s, 1H, -OCH ), 5.21
3
and 5.24 (each s, 1H, 4-H), 6.76–7.36 (m, 9H, Ph-H), 9.70 and
9.76 (each s, 1H, 3-NH), 10.65 and 10.72 (each s, 1H, 1-NH); IR
ꢁ
1
ꢁ1
693, 1632, 1500 cm ; MS (70eV) m/z (%): 352.50 (M,
00); Anal. Calcd. for C H ClN O : C 68.09, H 4.86, N
(KBr) m: 3301, 1680, 1624, 1501 cm ; MS (70eV) m/z (%):
2
0
17
2
2
365.04 (M þ 1, 100); Anal. Calcd. for C H N O S: C 69.20,
21 20 2 2
.94; found C 68.21, H 4.77, N 7.81.
4
H 5.53, N 7.69; found C 69.08, H 5.50, N 7.77.
1
c 1 5c. H NMR (CDCl
1
3
, 500 MHz) d: 2.61–2.86 (m, 4H,
4j 1 5j. H NMR (DMSO, 300 MHz) d: 2.30–2.96 (m, 4H,
6
1
3
1
-H þ 8-H), 3.32–3.47 (m, 1H, 7-H), 5.45 and 5.52 (each s,
H, 4-H), 7.07–7.49 (m, 9H, Ph-H), 8.13 and 8.17 (each s, 1H,
-NH), 9.50 and 9.52 (each s, 1H, 1-NH); IR (KBr) m: 3310,
6-H þ 8-H), 3.43–3.49 (m, 1H, 7-H), 3.71 (s, 1H, -OCH
3
), 5.13
and 5.17 (each s, 1H, 4-H), 6.77–7.43 (m, 9H, Ph-H), 9.66 and
9.73 (each s, 1H, 3-NH), 10.61 and 10.68 (each s, 1H, 1-NH); IR
ꢁ
1
ꢁ1
720, 1678, 1614, 1491 cm ; MS (70eV) m/z (%): 351.17
17ClN : C 68.09, H 4.86,
N 7.94; found C 68.15, H 4.95, N 7.82.
(KBr) m:3255, 1644, 1609, 1562, 1510 cm ; MS (70eV) m/z
(
M-1, 100); Anal. Calcd. for C20
H
2
O
2
20 2 2
(%): 364.15 (M, 100); Anal. Calcd. for C21H N O S: C 69.20,
H 5.53, N 7.69; found C 69.32, H 5.47, N 7.58.
1
1
4
d 1 5d. H NMR (CDCl , 500 MHz) d: 2.46–2.84 (m, 4H,
4k 1 5k. H NMR (DMSO, 300 MHz) d: 2.25–2.85 (m,
4H, 6-H þ 8-H), 3.10–3.30 (m, 1H, 7-H), 3.70 (s, 1H, -
3
6
1
3
1
-H þ 8-H), 3.38–3.53 (m, 1H, 7-H), 5.43 and 5.53 (each s,
H, 4-H), 6.71–7.49 (m, 9H, Ph-H), 8.00 and 8.03 (each s, 1H,
-NH), 9.00 and 9.05 (each s, 1H, 1-NH); IR (KBr) m: 3325,
3
OCH ), 5.17 and 5.18 (each s, 1H, 4-H), 6.80–7.32 (m, 10H,
Ph-H), 7.75 and 7.80 (each s, 1H, 3-NH), 9.79 and 9.55 (each
s, 1H, 1-NH); IR (KBr) m: 3270, 1714, 1606, 1597, 1514
cm ; MS (70eV) m/z (%): 347.34 (M-1, 100); Anal. Calcd.
ꢁ
1
711, 1674, 1621, 1489 cm ; MS (70eV) m/z (%): 347.17
ꢁ
1
(
M-1, 100); Anal. Calcd. for C H N O : C 72.40, H 5.79, N
2
1 20 2 3
8
.04; found C 72.48, H 5.70, N 8.13.
4
for C H N O : C 72.40, H 5.79, N 8.04; found C 72.32, H
5.87, N 8.12.
2
1 20 2 3
1
e. H NMR (DMSO, 300 MHz) d: 2.36–3.10 (m, 4H, 6-H
þ 8-H), 3.39–3.50 (m, 1H, 7-H), 3.70 (s, 3H, -OCH ), 5.13 (s,
H, 4-H), 6.76–7.38 (m, 9H, Ph-H), 7.73 (s, 1H, 3-NH), 9.51
s, 1H, 1-NH); IR (KBr) m: 3215, 1715, 1638, 1598, 1510
1
3
4 l 1 5 l. H NMR (DMSO, 300 MHz) d: 2.22–2.88 (m,
4H, 6-H þ 8-H), 3.22–3.44 (m, 1H, 7-H), 3.72 (s, 1H,
1
(
AOCH ), 5.59 and 5.60 (each s, 1H, 4-H), 6.84–7.40 (m, 8H,
3
ꢁ
1
cm ; MS (70eV) m/z (%): 349.49 (M þ 1, 100); Anal. Calcd.
for C21 : C 72.40, H 5.79, N 8.04; found C 72.25, H
.65, N 7.92.
Ph-H), 7.66 and 7.69 (each s, 1H, 3-NH), 9.56 and 9.62 (each
s, 1H, 1-NH); IR (KBr) m: 3291, 1717, 1636, 1596, 1498
H
20
N
2
O
3
ꢁ
1
5
cm ; MS (70eV) m/z (%): 383.12 (M þ 1, 100); Anal. Calcd.
for C21 19ClN : C 65.88, H 5.00, N 7.32; found C 65.93, H
4.90, N 7.23.
1
5
e. H NMR (DMSO, 300 MHz) d: 2.36–2.86 (m, 4H, 6-
H
2 3
O
H þ 8-H), 3.41–3.47 (m, 1H, 7-H), 5.16 (s, 1H, 4-H),
1
6
1
.80–7.33 (m, 9H, Ph-H), 7.78 (s, 1H, 3-NH), 9.56 (s, 1H,
;
4m. H NMR (DMSO, 300 MHz) d: 2.34–2.82 (m, 4H, 6-H þ
8-H), 3.27–3.40 (m, 1H, 7-H), 3.72 (s, 1H, AOCH ), 5.20 (s, 1H,
4-H), 6.85–7.27 (m, 8H, Ph-H), 7.80 (s, 1H, 3-NH), 9.57 (s, 1H, 1-
ꢁ
1
-NH); IR (KBr) m: 3218, 1715, 1628, 1600, 1511 cm
3
MS (70eV) m/z (%): 349.49 (M þ 1, 100); Anal. Calcd. for
ꢁ
1
C H N O : C 72.40, H 5.79, N 8.04; found C 72.48, H
5
NH); IR (KBr) m:3331, 1723, 1611, 1600, 1509 cm ; MS (70eV)
m/z (%): 381.26 (M-1, 100); Anal. Calcd. for C H ClN O : C
65.88, H 5.00, N 7.32; found C 65.82, H 5.07, N 7.25.
21 20 2 3
.68, N 8.12.
1
21
19
2 3
4
f. H NMR (DMSO, 300 MHz) d: 2.27–2.83 (m, 4H, 6-H
1
þ 8-H), 3.10–3.30 (m, 1H, 7-H), 5.20 (s, 1H, 4-H), 7.20–7.40
5m. H NMR (DMSO, 300 MHz) d: 2.40–2.75 (m, 4H, 6-H
þ 8-H), 3.35–3.43 (m, 1H, 7-H), 3.70 (s, 1H, -OCH ), 5.18 (s,
1H, 4-H), 6.80–7.37 (m, 8H, Ph-H), 7.78 (s, 1H, 3-NH), 9.54
(
(
m, 9H, Ph-H), 7.88 (s, 1H, 3-NH), 9.66 (s, 1H, 1-NH); IR
KBr) m: 3275, 1711, 1680, 1624, 1509 cm ; MS (70eV) m/z
3
ꢁ
1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

3
16
G.-F. Han, B. Cui, L.-Z. Chen, R.-H. Wang, and Y. Jin
Vol 48
(
s, 1H, 1-NH); IR (KBr) m: 3335, 1723, 1610, 1603, 1512
Hydrogen atoms were added according to the theoretical
methods.
ꢁ
1
cm ; MS (70eV) m/z (%): 381.26 (M-1, 100); Anal. Calcd.
for C21 19ClN : C 65.88, H 5.00, N 7.32; found C 65.81, H
.08, N 7.22.
H
2 3
O
5
4
1
4
n 1 5n. H NMR (DMSO, 300 MHz) d: 2.34–2.82 (m,
H, 6-H þ 8-H), 3.35–3.43 (m, 1H, 7-H), 3.69 (s, 1H,
), 3.72 (s, 1H, AOCH ), 5.15 and 5.18 (each s, 1H, 4-
REFERENCES AND NOTES
AOCH
3
3
[1] Kidwai, M.; Saxena, S.; Khan, K. R. M.; Thukral, S. S. Eur
J Med Chem 2005, 40, 816.
H), 6.74–7.27 (m, 8H, Ph-H), 7.73 and 7.79 (each s, 1H, 3-
NH), 9.48 and 9.54 (each s, 1H, 1-NH); IR (KBr) m: 3341,
1
[2] Yarim, M.; Sarac, S.; Kilic, F. S.; Erol, K. II Farmaco
2003, 58, 17.
ꢁ
1
712, 1637, 1608, 1515 cm ; MS (70eV) m/z (%): 377.33
(
7
M-1, 100); Anal. Calcd. for C22H : C 69.83, H 5.86, N
.40; found C 69.92, H 5.78, N 7.31.
22
N
2
O
4
[3] Yarim, M.; Sarac, S.; Ertan, M.; Kilic, F. S.; Erol, K. Arz-
neim Forsch 2002, 52, 27.
1
4
o 1 5o. H NMR (DMSO, 300 MHz) d: 2.28–2.87 (m,
[4] Hassan, H. Y.; Ismaiel, A. A. Eur J Med Chem 1991, 7, 743.
[
[
[
[
5] Dondoni, A.; Massi, A. Tetrahedron 2004, 60, 2311.
6] Agarwal, A.; Chanhan, M. S. Tetrahedron Lett 2005, 46, 1345.
7] Shao, G. Q. Chin J Synth Chem 2004, 12, 325.
3
7
6
1
1
1
H, 6-H þ 8-H), 3.16–3.31 (m, 1H, 6-H), 3.37–3.46 (m, 1H,
-H), 3.71 (s, 1H, -OCH ), 5.21 and 5.23 (each s, 1H, 4-H),
3
.81–7.37 (m, 8H, Ph-H), 9.67 and 9.73 (each s, 1H, 3-NH),
0.60 and 10.67 (each s, 1H, 1-NH); IR (KBr) m: 3358, 1701,
8] Tewari, N.; Dwivedi, N.; Tripathi, R. P. Tetrahedron Lett
ꢁ
1
2004, 45, 9011.
9] Sahitha, G.; Reddy, G. S. K. K. Tetrahedron Lett 2003, 44,
595, 1567, 1502 cm ; MS (70eV) m/z (%): 365.14 (M þ 1,
[
00); Anal. Calcd. for C H N O S: C 69.20, H 5.53, N 7.69;
2
1 20 2 2
4
129.
10] Wang, L. M.; Sheng, J.; Zhang, L.; Han, J. W. Tetrahedron
005, 61, 1539.
11] Ko, S.; Sastry, M. N. Y.; Lin, C.; Yao, C. F. Tetrahedron
Lett 2005, 46, 5771.
12] Maheswara, M.; Siddaiah, V. J Mol Catal A Chem 2006,
60, 179.
found C 69.33, H 5.46, N 7.75.
[
Determination of crystal structure. A colorless transparent
crystal of size 0.30 mm ꢃ 0.20 mm ꢃ 0.15 mm was selected
for the crystal structure measurement. The X-ray diffraction
intensities were recorded by a Bruker SMART APEX CCD
automatic diffractometer with graphite-monochromatized Mo
Ka radiation (k ¼ 0.071073 nm) at 291(2)K. In the range of
2
[
[
2
[
13] Ko, S.; Yao, C. F. Tetrahedron Lett 2006, 62, 7293.
2
.05 < y < 25.99, 9632 independent reflections were obtained.
[14] Yu, Y.; Liu, D.; Liu, C. S.; Luo, G. X. Bioorg Med Chem
The structures were solved by direct methods using SHELXL-
2
97 program. All the nonhydrogen atoms were refined on F
anisotropically with the full-matrix least squares method.
Lett 2007, 17, 3508.
[15] Han, G.-F.; Wang, J.-J; Jiang, G.-J. Chin J Org Chem 2003,
23, 1004 (in Chinese).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet