One-pot synthesis of 13-acetyl-9-methyl-11-oxo(or thioxo)-8-oxa-10,12- diazatricyclo[7.3.1.02,7]trideca-2,4,6-trienes under microwave irradiation

Article abstract of DOI:10.1002/jhet.978

Oxygen-bridged monastrol analogs, 13-acetyl-9-methyl-11-oxo(or thioxo)-8-oxa-10,12-diazatricyclo[7.3. 1.0^2,7]trideca-2,4,6-trienes, were synthesized by one-pot three component condensation reaction of substituted salicylaldehyde, acetylacetone

Full text of DOI:10.1002/jhet.978

1352
One‐Pot Synthesis of 13‐Acetyl‐9‐methyl‐11‐oxo(or thioxo)‐
8‐oxa‐10,12‐diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐trienes
under Microwave Irradiation
Vol 49
a
b
b
b
Qingfang Cheng,a,b Qifa Wang, Tin Tan, Na Chen, and Mei Shuai
*
aJiangsu Key Laboratory of Marine Biotechnology, Huaihai Institute of Technology,
Lianyungang 222005, China
bDepartment of Chemical Technology, Huaihai Institute of Technology, Lianyungang,
Jiangsu 222005, China
*
E-mail: spring817191@sina.com
Received February 13, 2011
DOI 10.1002/jhet.978
View this article online at wileyonlinelibrary.com.
Oxygen‐bridged monastrol analogs, 13‐acetyl‐9‐methyl‐11‐oxo(or thioxo)‐8‐oxa‐10,12‐diazatricyclo[7.3. 1.02,7
]
trideca‐2,4,6‐trienes, were synthesized by one‐pot three component condensation reaction of substituted salicylalde-
hyde, acetylacetone and urea or thiourea with nontoxic, inexpensive, and easily available NaHSO4 as catalyst under
microwave irradiation and solvent‐free conditions in short time with good yields. The structures of the products were
characterized by IR, 1H NMR, 13C NMR spectra, and elemental analyses.
J. Heterocyclic Chem., 49, 1352 (2012).
INTRODUCTION
thioxo)‐8‐oxa‐10,12‐diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene
(3) depending on the ester alkyl group (Scheme 1).
3,4‐Dihydropyrimidin‐2‐(1H)‐ones(DHPMs) and their
derivatives are an important class of heterocyclic com-
pounds having important biological and pharmacological
activities [1–4]. Monastrol, one of DHPMs, ethyl 6‐
methyl‐4‐(3‐hydroxyphenyl)‐2‐thioxo‐1,2,3,4‐tetrahydro-
pyrimidine‐5‐carboxylate(1), is a recently highlighted
compound [5,6], which showed promise in a new strategic
approach to cancer research and has been found to affect
the function of mitotic kinesin Eg5, a motor protein responsi-
ble for spindle bipolarity [7,8]. Thus, kinesin spindle protein
represents an attractive target for biochemical studies because
human Eg5 inhibitors induce cell death via apoptosis [9]. One
of the simple and direct method for the synthesis of monastrol
analogs known as Biginelli reaction involves the one‐pot con-
densation of an aldehyde with a hydroxyl, a β‐ketoester and
urea or thiourea. Lewis acids and transition metal salts such
as Sr(OTf)2 [10], p‐TsOH [11], HPA [12], NiCl2·6H2O
[13], LaCl3 [14], InBr3 [15], Bakers’ yeast [16] have been
used to catalyze this Biginelli reaction. Obviously, most of
these catalysts and solvents are not acceptable in the context
of green synthesis and the procedure involved harsh condi-
tion, long reaction time and low yield etc. We reported
[17,18] the three‐component heterocyclization of salicylalde-
hyde or substitued salicylaldehyde, β‐ketoester and urea or
thiourea catalyzed by nontoxic, inexpensive NaHSO4 under
solvent‐free conditions, the reaction formed two different
products, 4‐(2‐hydroxyphenyl) pyrimidines(2) and oxygen‐
bridged pyrimidine derivatives, 9‐methyl‐11‐oxo(or
This oxygen‐bridged pyrimidine structures were not dis-
cussed in several recent reports [12–14], but were supported
by others [15,16,19]. Microwave‐assisted reactions have
received a great deal of attention since 1986 [20], because
microwave‐assisted reactions are efficient, higher yields,
clean, safe, and greater selectivity for the targeted product
under milder reaction conditions [21,22]. We have reported
one‐pot, three‐component reaction of aromatic aldehydes,
malononitrile, and barbituric acid under microwave irradiation
successfully [23]. Thus, as a part of our program towards envi-
ronment‐friendly multicomponent reactions(MCRs) [24,25],
we would like to report herein, a simple one‐pot, three‐
component reaction of substitued salicylaldehydes with
urea(or thiourea, phenylurea) and acetylacetone, as active
methylene component for the synthesis of some new monastrol
analogs under microwave irradiation and solvent‐free condi-
tions using NaHSO4 as a nontoxic, inexpensive, and easily
available catalyst. However, the obtained products will be oxy-
gen‐bridged monastrol analogs, 13‐acetyl‐9‐methyl‐11‐thioxo‐
8‐oxa(or thioxo)‐10,12‐ diazatricyclo[7.3.1.02,7] trideca‐2,4,
6‐triene derivatives rather than free hydroxyl compounds.
The three‐component cyclocondensation reaction of
salicylaldehyde, acetylacetone and thiourea was first
performed to examine the effectiveness of NaHSO4
(Scheme 2). This three‐component cyclocondensation
reaction may be performed under relatively simple reaction
conditions by heating together the three components,
© 2012 HeteroCorporation

November 2012
One‐Pot Synthesis of 13‐Acetyl‐9‐methyl‐11‐oxo(or thioxo)‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐trienes under Microwave Irradiation
1353
was supported by 13C NMR, there are three carbon signals
at 46.0, 81.5, and 52.2 ppm in the 13C NMR spectrum of
5a, assigned to C‐1, C‐9, and C‐13, respectively. This
oxygen‐bridged pyrimidine structures were not discussed
in previous article [27], but were supported by the other [26].
To evaluate the effectiveness of the catalyst in inducing
this Biginelli three component condensation reaction and
confirm the structures of oxygen‐bridged products, we
initiated a series of exploratory experiments involving
substituted salicylaldehyde, acetylacetone and urea(or thiourea,
phenylurea) with NaHSO4 as catalyst under microwave irra-
diation and solvent‐free conditions (Scheme 3). The results
presented in the Table 1 indicate the scope and generality
of the method, which is efficient, not only for urea or
thiourea, phenylurea, but also for salicylaldehyde as well as
substituted salicylaldehydes. In most cases, the reactions
proceeded smoothly to produce the corresponding monastrol
analogs in short time (10–15 min) with good yields. The
products will be oxygen‐bridged compounds, 13‐acetyl‐9‐
methyl‐11‐thioxo‐8‐oxa(or thioxo)‐10,12‐diazatricyclo[7.3.1.02,7]
trideca‐2,4,6‐trienes 5b‐p (Scheme 3).
Scheme 1
Scheme 2
1
Selected H and 13C NMR spectral datas of 5a‐p are
1
summarized in Table 2. It was found that in the H NMR
spectrum of compounds 5a‐p, the signals of H‐13 appeared
at range of 3.31–3.54 ppm and the signals of H‐1 appeared
at range of 4.21–4.62 ppm; in the 13C NMR spectrum of
compounds 5a‐p, the carbon signal of C‐1 appeared at
range of 41.2–45.6 ppm, the carbon signal of C‐9 appeared
at range of 81.5–84.9 ppm and the carbon signal of C‐13
appeared at range of 45.3–56.5 ppm. This oxygen‐bridged
salicylaldehyde, acetylacetone and thiourea, in the ratio of
1:1:1.5 and NaHSO4 (20 mol %), to 85°C under microwave
irradiation. After the completion of the reaction, the reaction
mixture was poured onto crushed ice. From which the monas-
trol derivative were isolated by filtration and recrystallized
from ethanol.
1
structures are supported by both of H and 13C NMR.
In conclusion, we have described a high‐yield one‐pot
three‐component cyclocondensation reaction method for
the preparation of some new oxygen‐bridged monastrol
derivatives by the Biginelli of substituted salicylaldehyde,
acetylacetone with thiourea(or urea, phenylurea) using
nontoxic, cheap, and easily available NaHSO4 catalyst
under microwave irradiation and solvent‐free conditions.
Compared to other methods, this new method has the
advantage of good yields, mild reaction conditions, inex-
pensive reagents, short reaction time, and environmentally
friendly reaction conditions. Additionally, the products are
oxygen‐bridged monastrol analogs, 13‐acetyl‐9‐methyl‐11‐
thioxo‐8‐ oxa(or thioxo)‐10, 12‐diazatricyclo[7.3.1.02,7] tri-
deca‐2,4,6‐trienes rather than free hydroxyl compounds.
The product showed a NMR spectra inconsistent with
the expected free hydroxyl dihydropyrimidinone 4 when
1
the structure of the product was characterized by H, 13C
1
NMR. Both of H NMR and 13C NMR spectra showed
the Biginelli product will be an oxygen‐bridged com-
pound, 13‐acetyl‐9‐methyl‐11‐thioxo‐8‐oxa‐10,12‐diaza-
tri‐cyclo [7.3.1.02,7]trideca‐ 2,4,6‐triene 5a (Scheme 2).
Structure 5a is assigned to this oxygen‐bridged product
on the basis of comparisons of its 1H and 13C NMR spectra
with those of a similar structural dihydropyrilnidinone 4,
reported in the previous article [26]. The presence of a
new proton signal at 3.37–3.44 ppm in the 1H NMR spec-
trum of compound 5a was assigned to H‐13, implying the
proton was connected to a sp carbon and the lack of a
double bond between C‐9 and C‐13, or the presence of
all oxygen‐bridge. This conclusion was supported by the
presence of a proton signal at 4.31 ppm, assigned to H‐1.
In the case of 4, The corresponding signal appeared at
about 5.25 ppm for the proton at C‐4. These facts indicate
that there is no double bond between C‐9 and C‐13 in the
Scheme 3
1
molecule of 5a. The above conclusion from H NM R
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1354
Q. Cheng, Q. Wang, T. Tan, N. Chen, and M. Shuai
Vol 49
Table 1
The results on the reaction of substituted salicylaldehyde, acetylacetone and urea (or thiourea, phenylurea).
Productsa
R1
R2
R3
X
Time (min)
Yieldb (%)
Mp (°C)
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
H
H
Ph
H
H
Ph
H
H
Ph
H
S
O
O
S
O
O
S
O
O
S
O
O
S
10
10
12
12
12
15
12
12
15
15
15
15
15
15
10
10
91
93
86
90
92
84
89
91
82
87
88
82
86
89
90
92
202–204
250–252
168–170
>300
Cl
Cl
Cl
Br
Br
Br
NO2
NO2
NO2
H
220–222
145–147
255–257
287–289
155–157
210–212
235–237
165–167
260–262
240–242
123–125
181–183
NO2
NO2
C(CH3)3
C(CH3)3
H
H
H
H
O
S
O
C(CH3)3
C(CH3)3
aProducts were characterized by 1H, 13C NMR, IR, and elemental analyses.
bIsolated yield.
temperature was set at 85°C) for the time period as indicated in
Table 1. After cooled, ice water was added to the mixture, and
the crude products collected by filtration were recrystallised
from EtOH, to give the products 5a‐p (Table 1). All products
were characterized by 1H, 13C NMR, IR, and by elemental
analyses.
13‐Aacetyl‐9‐methyl‐11‐thioxo‐8‐oxa‐10,12‐diazatricyclo
[7.3.1.02,7]trideca‐2,4,6‐triene (5a). Yellow powder, yield 91%,
mp 202–204°C, IR(KBr), (nmax/cm−1): 3351, 3229, 1706. 1H NMR
(DMSO‐d6) δH: 9.17(s, 1H, NH), 6.78–7.16 (m, 5H, ArH, NH),
4.27(dd, J = 3.5, 2.9 Hz, 1H, H‐1), 3.37–3.44 (m, 1H, H‐13), 2.27
(s, 3H, CH3), 1.66 (s, 3H, CH3). 13C NMR (DMSO‐d6) δC: 26.4,
31.3, 41.2, 46.0, 81.5, 117.3, 121.4, 124.7, 129.9, 130.1, 152.1,
EXPERIMENTAL
IR spectra were recorded on a Nicolet FT IR‐500 spectrometer.
1H NMR and 13C NMR spectra were recorded on a Bruker
AVANCE 400 MHz spectrometer at 400 MHz and 75 MHz. Ele-
mental analysis was performed on an Elementar Vario EL III
analyzer. Melting points were determined on a XT‐5A digital
melting‐points apparatus and are uncorrected.
General procedure for the synthesis of oxygen‐bridged
Monastrol derivatives 5a‐p. A mixture of the appropriate
salicylaldehyde (2 mmol), acetylacetone(2 mmol), urea or
thiourea (3 mmol), and NaHSO4 (0.4 mmol) was refluxed in a
sealed Discover reaction vessel under microwave irradiation (the
Table 2
Selected 1H and 13C NMR spectral datas of 5a‐p.
δ (ppm)
C‐1
Products
R1
R2
R3
X
H‐1
4.27
H‐13
C‐9
C‐13
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
H
H
Ph
H
H
Ph
H
H
Ph
H
S
O
O
S
O
O
S
O
O
S
O
O
S
3.37–3.44
3.36–3.42
3.32–3.51
3.37–3.44
3.33–3.45
3.31–3.52
3.39–3.45
3.35–3.46
3.32–3.54
3.35–3.40
3.32–3.43
3.43–3.52
3.35–3.40
3.39–3.46
3.41–3.47
3.43–3.48
41.2
41.2
43.2
45.6
44.0
44.7
44.9
44.7
44.3
43.8
43.1
44.1
44.3
45.6
43.7
44.1
81.5
83.1
83.6
82.6
84.1
84.5
83.6
83.3
83.9
83.5
84.7
84.3
83.6
84.9
82.3
82.7
46.0
45.3
53.8
53.9
55.2
55.8
53.1
56.5
56.5
54.7
55.6
55.9
55.2
56.4
52.3
52.9
4.23
4.21
4.54
4.52
4.47
4.42
4.36
4.32
4.62
4.53
4.53
4.62
4.39
4.43
4.46
Cl
Cl
Cl
Br
Br
Br
NO2
NO2
NO2
H
H
NO2
NO2
C(CH3)3
C(CH3)3
H
H
H
O
S
O
C(CH3)3
C(CH3)3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2012
One‐Pot Synthesis of 13‐Acetyl‐9‐methyl‐11‐oxo(or thioxo)‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐trienes under Microwave Irradiation
1355
176.9, 205.3. Anal. Calcd. for C13H14N2O2S: C, 59.52; H, 5.38; N,
10.68. Found: C, 59.59; H, 5.41; N, 10.64.
C13H13N2O2BrS: C, 45.76; H, 3.84; N, 8.21. Found: C, 45.71; H,
3.88; N, 8.28.
13‐Aacetyl‐9‐methyl‐11‐oxo‐8‐oxa‐10,12‐diazatricyclo
[7.3.1.02,7]trideca‐2,4,6‐triene (5b). Yellow powder, yield
93%, mp 250–252°C, IR(KBr), (nmax/cm−1): 3372, 3232, 1713.
1H NMR (DMSO‐d6) δH: 7.45(s, 1H, NH), 6.72–7.16 (m, 5H,
ArH, NH), 4.23(dd, J = 3.6, 3.1 Hz, 1H, H‐1), 3.36–;3.42 (m,
1H, H‐13), 2.13 (s, 3H, CH3), 1.59 (s, 3H, CH3). 13C NMR
(DMSO‐d6) δC: 27.3, 33.1, 41.2, 45.3, 83.1, 117.3, 121.0, 126.6,
129.6, 129.8, 152.3, 156.0, 204.9. Anal. Calcd. for C13H14N2O3:
C, 63.39; H, 5.73; N, 11.38. Found: C 63.32; H, 5.71; N, 11.31.
13‐Aacetyl‐9‐methyl‐10‐phenyl‐11‐oxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5c). Green powder,
yield 86%, mp 168–170°C, IR(KBr), (nmax/cm−1): 3211, 3098,
1709, 1679. 1H NMR (DMSO‐d6) δH: 7.53 (s, 1H, NH),
6.79∼7.32 (m, 9H, arom), 4.21(dd, J = 2.2, 2.9 Hz, 1H, H‐1),
3.32–3.51 (m, 1H, H‐13), 2.29 (s, 3H, CH3), 1.66 (s, 3H, CH3).
13C NMR (DMSO‐d6) δC: 25.9, 30.8, 43.2, 53.8, 83.6, 113.1,
116.9, 118.2, 121.3, 123.3, 128.7, 129.9, 131.2, 150.9, 151.3,
155.7, 205.1. Anal. Calcd. for C19H18N2O3: C, 70.79; H, 5.63; N,
8.69. Found: C, 70.72; H, 5.56; N, 8.61.
13‐Aacetyl‐9‐methyl‐4‐chlor‐11‐thioxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5d). Yellow powder,
yield 90%, mp > 300°C, IR(KBr), (nmax/cm−1): 3316, 3239, 3089,
1719. 1H NMR (DMSO‐d6) δH: 9.04(s, 1H, NH), 7.63(s, 1H,
NH), 7.16(t, J = 7.1 Hz, 1H, ArH), 6.91(s, 1H, ArH), 6.64(t,
J = 7.1 Hz, 1H, ArH), 4.54(dd, J = 3.0, 2.6 Hz, 1H, H‐1),
3.37–3.44(m, 1H, H‐13), 2.19(s, 3H, CH3), 1.67 (s, 3H, CH3). 13C
NMR (DMSO‐d6) δC: 25.9, 32.1, 45.6, 53.9, 82.6 114.8, 120.3,
126.8, 130.4, 131.5, 150.8, 178.2, 206.2. Anal. Calcd. for
C13H13N2O2ClS: C, 52.61; H, 4.42; N, 9.44. Found: C, 52.54; H,
4.50; N, 9.36.
13‐Aacetyl‐9‐methyl‐4‐chlor‐11‐oxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5e). Gray powder,
yield 92%, mp 220–222°C, IR(KBr), (nmax/cm−1): 3241, 3098,
1721, 1692. 1H NMR (DMSO‐d6) δH: 7.51(s, 1H, NH), 7.41(s, 1H,
NH), 7.30(t, J = 7.0 Hz, 1H, ArH), 7.06(s, 1H, ArH), 6.76 (t,
J = 7.0 Hz, 1H, ArH), 4.52(dd, J = 3.4, 2.9 Hz, 1H, H‐1),
3.33–3.45(m, 1H, H‐13), 2.23 (s, 3H, CH3), 1.65(s, 3H, CH3). 13C
NMR (DMSO‐d6) δC: 26.2, 31.8, 44.0, 55.2, 84.1, 113.6, 120.7,
128.9, 130.9, 131.5, 150.8, 156.8, 205.8. Anal. Calcd. for
C13H13N2O3Cl: C, 55.62; H, 4.67; N, 9.98. Found: C, 55.55; H,
4.62; N, 9.91.
13‐Aacetyl‐9‐methyl‐4‐chlor‐10‐phenyl‐11‐oxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5f). Green powder,
yield 84%, mp 145–147°C, IR(KBr), (nmax/cm−1): 3202, 3071,
1701, 1669. 1H NMR (DMSO‐d6) δH: 7.58 (s, 1H, NH),
6.79–8.38 (m, 8H, arom), 4.47(dd, J=3.0, 2.8 Hz, 1H, H‐1),
3.31–3.52(m, 1H, H‐13), 2.22(s, 3H, CH3), 1.66(s, 3H, CH3). 13C
NMR (DMSO‐d6) δC: 26.7, 32.3, 44.7, 55.8, 84.5, 113.8, 117.2,
118.4, 121.5, 123.7, 128.9, 130.9, 131.8, 150.8, 151.5, 156.8,
205.4. Anal. Calcd. for C19H17N2O3Cl: C, 63.96; H, 4.80; N, 7.85.
Found: C, 63.91; H, 4.86; N, 7.79.
13‐Aacetyl‐9‐methyl‐4‐bromo‐11‐oxo‐8‐oxa‐10,12‐diazatricyclo
[7.3.1.02,7]trideca‐2,4,6‐triene (5h). Yellow powder, yield 91%, mp
287–289°C, IR(KBr), (nmax/cm−1): 3236, 3084, 1715, 1688. 1H NMR
(DMSO‐d6) δH: 7.56(s, 1H, NH), 7.32(s, 1H, NH), 7.22 (d, J = 7.0
Hz, 1H, ArH), 7.16(s, 1H, ArH), 6.74(d, J = 7.0 Hz, 1H, ArH), 4.36
(dd, J = 3.5, 3.1Hz, 1H, H‐1), 3.35–3.46(m, 1H, H‐13), 2.16 (s, 3H,
CH3), 1.64 (s, 3H, CH3). 13C NMR (DMSO‐d6) δC: 26.7, 32.3, 44.7,
56.5, 83.3, 111.6, 119.4, 128.7, 131.8, 131.9, 151.3, 155.5, 205.2.
Anal. Calcd. for C13H13N2O3Br: C, 48.02; H, 4.03; N, 8.62. Found:
C, 48.07; H, 3.98; N, 8.66.
13‐Aacetyl‐9‐methyl‐4‐bromo‐10‐phenyl‐11‐oxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5i). Green powder,
yield 82%, mp 155–157°C, IR(KBr), (nmax/cm−1): 3209, 3081,
1708, 1672. 1H NMR (DMSO‐d6) δH: 7.55 (s, 1H, NH), 6.89–8.21
(m, 8H, arom), 4.32(dd, J = 3.0, 2.7 Hz, 1H, H‐1), 3.32–3.54
(m, 1H, H‐13), 2.16(s, 3H, CH3), 1.63(s, 3H, CH3). 13C NMR
(DMSO‐d6) δC: 26.1, 31.9, 44.3, 56.5, 83.9, 112.6, 117.9, 119.4,
121.2, 122.6, 128.5, 130.8, 131.2, 150.5, 151.3, 155.5, 204.8. Anal.
Calcd. for C19H17N2O3Br: C, 56.87; H, 4.27; N, 6.98. Found: C,
56.80; H, 4.21; N, 6.91.
13‐Aacetyl‐9‐methyl‐4‐nitro‐11‐thioxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5j). Yellow powder,
yield 87%, mp 210–212°C, IR(KBr), (nmax/cm−1): 3341, 3247,
3109, 1726. 1H NMR (DMSO‐d6) δH: 9.32(s, 1H, NH), 8.13(s, 1H,
NH), 8.10(s, 1H, ArH), 7.08 (d, J = 7.0 Hz, 1H, ArH), 7.05 (d,
J = 7.0 Hz, 1H, ArH), 4.62(dd, J = 3.6, 2.9 Hz, 1H, H‐1), 3.35–3.40
(m, 1H, H‐13), 2.33 (s, 3H, CH3), 1.73 (s, 3H, CH3). 13C NMR
(DMSO‐d6) δC: 26.9, 32.7, 43.8, 54.7, 83.5, 115.4, 123.8, 124.7,
124.9, 140.8, 165.9, 179.6, 206.7. Anal. Calcd. for C13H13N3O4S:
C, 50.80; H, 4.26; N, 13.68. Found: C, 50.89; H, 4.2 1; N, 13.62.
13‐Aacetyl‐9‐methyl‐4‐nitro‐11‐oxo‐8‐oxa‐10,12‐diazatricyclo
[7.3.1.02,7]trideca‐2,4,6‐triene (5k). Yellow powder, yield 88%, mp
235–237°C, IR(KBr), (nmax/cm−1): 3259, 3121, 1735, 1699. 1H
NMR (DMSO‐d6) δH: 8.32(s, 1H, NH), 7.69(s, 1H, NH), 8.21
(s, 1H, ArH), 7.35 (d, J = 7.0 Hz, 1H, ArH), 7.13 (d, J = 7.0 Hz,
1H, ArH), 4.53(dd, J = 3.3, 2.7 Hz, 1H, H‐1), 3.32–3.43 (m, 1H,
H‐13), 2.31 (s, 3H, CH3), 1.71 (s, 3H, CH3). 13C NMR (DMSO‐d6)
δC: 27.1, 32.3, 43.1, 55.6, 84.7, 114.8, 123.4, 124.1, 124.8, 140.7,
157.9, 166.3, 206.4. Anal. Calcd. for C13H13N3O5: C, 53.60; H,
4.50; N, 14.43. Found: C, 53.53; H, 4.59; N, 14.48.
13‐Aacetyl‐9‐methyl‐4‐nitro‐10‐phenyl‐11‐oxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5l). Green powder,
yield 82%, mp 165–167°C, IR(KBr), (nmax/cm−1): 3189, 3059,
1691, 1663. 1H NMR (DMSO‐d6) δH: 8.39 (s, 1H, NH),
7.01–8.31 (m, 8H, arom), 4.53(dd, J = 3.1, 2.6 Hz, 1H, H‐1),
3.43–3.52(m, 1H, H‐13), 2.30 (s, 3H, CH3), 1.70 (s, 3H, CH3).
13C NMR (DMSO‐d6) δC: 26.8, 32.5, 44.1, 55.9, 84.3, 113.8,
115.1, 117.6, 123.5, 124.3, 124.7, 129.3, 141.1, 151.4, 158.2,
166.9. Anal. Calcd. for C19H17N3O5: C, 62.12; H, 4.66; N, 11.44.
Found: C, 62.07; H, 4.61; N, 11.38.
13‐Aacetyl‐9‐methyl‐6‐nitro‐11‐thioxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5m). Yellow powder,
yield 86%, mp 260–262°C, IR(KBr), (nmax/cm−1): 3322, 3251,
3114, 1728. 1H NMR (DMSO‐d6) δH: 9.32(s, 1H, NH), 8.13
(s, 1H, NH), 8.10(d, 1H, ArH), 7.41–7.53(m, 1H, ArH), 7.01
(d, 1H, ArH), 4.62(dd, J = 3.3, 2.7 Hz, 1H, H‐1), 3.35–3.40 (m,
1H, H‐13), 2.27(s, 3H, CH3), 1.73 (s, 3H, CH3). 13C NMR
(DMSO‐d6) δC: 26.5, 32.4, 44.3, 55.2, 83.6, 114.5, 121.5, 125.3,
134.3, 135.5, 155.6, 178.7, 206.9. Anal. Calcd. for C13H13N3O4S:
C,50.80; H, 4.26; N, 13.68. Found: C, 50.86; H, 4.22; N, 13.61.
13‐Aacetyl‐9‐methyl‐4‐bromo‐11‐thioxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5g). Yellow powder,
yield 89%, mp 255–257°C, IR(KBr), (nmax/cm−1): 3323, 3229,
3078, 1709. 1H NMR (DMSO‐d6) δH: 9.11(s, 1H, NH), 7.28
(s, 1H, NH), 7.26 (d, J = 7.0 Hz, 1H, ArH), 7.14(s, 1H, ArH),
6.74 (d, J = 7.0 Hz, 1H, ArH), 4.42(dd, J = 3.1, 2.8 Hz, 1H, H‐1),
3.39–3.45(m, 1H, H‐13), 2.28 (s, 3H, CH3), 1.67 (s, 3H, CH3).
13C NMR (DMSO‐d6) δC: 26.1, 31.2, 44.9, 53.1, 83.6, 112.9,
119.4, 127.9, 130.8, 131.7, 150.5, 177.5, 205.9. Anal. Calcd. for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1356
Q. Cheng, Q. Wang, T. Tan, N. Chen, and M. Shuai
Vol 49
[3] Grover, G. J.; Dzwonczyk, S.; Mc Multen, D. M.; Normandin,
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13‐Aacetyl‐9‐methyl‐6‐nitro‐11‐oxo‐8‐oxa‐10,12‐diazatricyclo
[7.3.1.02,7]trideca‐2,4,6‐triene (5n). Yellow powder, yield 89%, mp
240–242°C, IR(KBr), (nmax/cm−1): 3265, 3125, 1739, 1698. 1H
NMR (DMSO‐d6) δH: 8.15 (s, 1H, NH), 7.52 (s, 1H, NH), 8.26
(d, 1H, ArH), 7.51–7.62(m, 1H, ArH), 7.16(d, 1H, ArH), 4.39(dd,
J = 3.5, 2.9 Hz, 1H, H‐1), 3.39–3.46 (m, 1H, H‐13), 2.29(s, 3H,
CH3), 1.69 (s, 3H, CH3). 13C NMR (DMSO‐d6) δC: 26.8, 31.3,
45.6, 56.4, 84.9, 115.1, 121.7, 125.8, 134.8, 135.7, 155.8, 156.8,
206.1. Anal. Calcd. for C13H13N3O5: C, 53.60; H, 4.50; N, 14.43.
Found: C, 53.55; H, 4.57; N, 14.51.
13‐Aacetyl‐9‐methyl‐4,6‐dit‐butyl‐11‐thioxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5o). Yellow powder,
yield 90%, mp 123–125°C, IR(KBr), (nmax/cm−1): 3327, 3209,
3054, 1697. 1H NMR (DMSO‐d6) δH: 11.71(s, 1H, NH), 9.98
(s, 1H, NH), 7.64(s, 1H, ArH), 7.56 (s, 1H, ArH), 4.43(dd, J = 2.5,
2.1 Hz, 1H, H‐1), 3.41–3.47(m, 1H, H‐13), 2.21 (s, 3H, CH3),
1.54 (s, 3H, CH3), 1.38(s, 9H, CH3), 1.29(s, 9H, CH3). 13C NMR
(DMSO‐d6) δC: 24.7, 29.6, 31.5, 32.3, 34.5, 35.0, 43.7, 52.3, 82.3,
120.7, 128.9, 131.6, 137.0, 141.9, 158.3, 199.4, 204.7. Anal.
Calcd. for C21H30N2O2S: C, 67.34; H, 8.07; N, 7.48. Found: C,
67.41; H, 8.01; N, 7.42.
13‐Aacetyl‐9‐methyl‐4,6‐dit‐butyl‐11‐oxo‐8‐oxa‐10,12‐
diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐triene (5p). Yellow powder,
yield 92%, mp 181–183°C, IR(KBr), (nmax/cm−1): 3221, 3069,
1703, 1682. 1H NMR (DMSO‐d6) δH: 9.78(s, 1H, NH), 9.64(s,
1H, NH), 7.65(s, 1H, ArH), 7.57 (s, 1H, ArH), 4.46(dd, J = 2.7,
2.4 Hz, 1H, H‐1), 3.43–3.48 (m, 1H, H‐13), 2.33 (s, 3H, CH3),
1.57 (s, 3H, CH3), 1.39(s, 9H, CH3), 1.30(s, 9H, CH3). 13C NMR
(DMSO‐d6) δC: 25.3, 29.36, 31.9, 32.7, 34.7, 35.2, 44.1, 52.9,
82.7, 120.6, 127.6, 131.8, 136.7, 140.6, 157.2, 158.6, 204.3. Anal.
Calcd. for C21H30N2O3: C, 70.36; H, 8.44; N, 7.82. Found: C,
70.30; H, 8.41; N, 7.89.
Acknowledgments. The authors gratefully acknowledge the
financial support from the Foundation of Jiangsu Key Laboratory of
Marine Biotechnology (grant No. 2009HS04).
[23] Cheng, Q. F.; Xu, X. Y.; Wang, Q. F.; Zhang, J. L.; Zhang, L.;
Yang, X. J. Chin J Appl Chem 2010, 27, 673.
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REFERENCES AND NOTES
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet