A versatile method for the synthesis of heterocyclic ring-fused 1,2-oxazinones from the NHC-catalyzed reactions of 2-aroylvinylarylaldehydes with nitrosoarenes

Article abstract of DOI:10.1016/j.tet.2012.10.089

The NHC-catalyzed reactions of nitrosoarenes with 4-(2-aroylvinyl)furan-3- carbaldehydes, 4-(2-aroylvinyl) thiophene-3-carbaldehydes or 2-(2-aroylvinyl)nicotinaldehydes were studied, which produced novel furo [3,4-d][1,2]oxazin-4-ones, thieno[3,4-d][1,2]oxazin-4-ones or pyrido[3,2-d][1,2]oxazin-5-ones, respectively. This work developed a versatile method for the construction of different types of heterocyclic ringfused 1,2-oxazinones that are not easy accessible by other methods.

Full text of DOI:10.1016/j.tet.2012.10.089

Tetrahedron 69 (2013) 888e894
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A versatile method for the synthesis of heterocyclic ring-fused
1,2-oxazinones from the NHC-catalyzed reactions of
2-aroylvinylarylaldehydes with nitrosoarenes
*
Jing Qu, Ying Cheng
College of Chemistry, Beijing Normal University, Beijing 100875, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The NHC-catalyzed reactions of nitrosoarenes with 4-(2-aroylvinyl)furan-3-carbaldehydes, 4-(2-aroylvinyl)
thiophene-3-carbaldehydes or 2-(2-aroylvinyl)nicotinaldehydes were studied, which produced novel furo
[3,4-d][1,2]oxazin-4-ones, thieno[3,4-d][1,2]oxazin-4-ones or pyrido[3,2-d][1,2]oxazin-5-ones, respecti-
vely. This work developed a versatile method for the construction of different types of heterocyclic ring-
fused 1,2-oxazinones that are not easy accessible by other methods.
Received 27 June 2012
Received in revised form
25 September 2012
Accepted 9 October 2012
Available online 8 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
N-Heterocyclic carbene-catalysis
2-Aroylvinylarylaldehyde
Furo[3,4-d][1,2]oxazin-4-one
Thieno[3,4-d][1,2]oxazin-4-one
Pyrido[3,2-d][1,2]oxazin-5-one
1. Introduction
A few NHC-catalyzed reactions of carbonyl compounds with
nitrosoarenes have been reported, which led to the formation of
1,2-Oxazinone ring is widely present in numerous biologically
active compounds with potential applications in pharmaceuticals
or agrochemicals. For example, a number of 4-acyl-1,2-oxazin-3-
one derivatives have been prepared as herbicides,1,2 and some of
them also were tested as acaricides and plant growth regulators.2
4-Aryl-1,2-oxazin-3-one derivatives were found to have herbi-
cidal, insecticidal and acaricidal activities,3 and N-carboxymethyl-
1,2-oxazin-3-ones showed antibacterial activity.4 The allosteric
MEK inhibitor CH4987655, a novel 1,2-oxazin-3-one derivative, has
been synthesized as an orally available anticancer agent.5 Benzo[d]
[1,2]oxazin-4-one derivatives have been studied for their pesticidal
activity,6 or antidiabetic and hypolipidemic activities,7 while
quinoline-fused oxazinones have been evaluated for their in-
secticidal activity8a,b or for the treatment of metabolic disorders.8c
In literature, numerous studies on the 1,2-oxazinones and ben-
zoxazinones derivatives have been documented.1e7,9 However, ex-
cept a few work of the synthesis or bioactivities of pyrido[3,2-d]
[1,2]oxazinones having been reported,8 the heterocyclic ring-fused
1,2-oxazinones are still largely unexplored. The development of
simple, efficient, and versatile method for the construction of var-
ious heterocyclic ring-fused 1,2-oxazinones is of great importance.
N-arylhydroxamic acids, isoxazolidin-5-ones, isoxazol-5-ones,
-amino acid esters, benzo[b][1,4]oxazepin-2-ones or oxazetidi-
b
nones depending on the structures of reactants and carbene cata-
lysts.10 Very recently, we established an efficient method for the
synthesis of benzo[d][1,2]oxazin-4-ones from the NHC-catalyzed
reactions of ortho electron-deficient vinyl substituted benzalde-
hydes with nitrosoarenes.11 We envisioned that this reaction might
be developed into a versatile strategy for the construction of vari-
ous aromatic ring-fused 1,2-oxazinones by varying the structures
of aromatic aldehydes. Thus, we undertook the current study on
the reaction of nitrosoarenes with 4-(2-aroylvinyl)furan-3-
carbaldehydes, 4-(2-aroylvinyl)thiophene-3-carbaldehydes or 2-
(2-aroylvinyl)nicotinaldehydes.
2. Results and discussion
We started the work with the examination on the reaction
between 4-(2-benzoylvinyl)furan-3-carbaldehyde and nitro-
sobenzene. Initially, the reaction of (E)-4-(2-benzoylvinyl)furan-3-
carbaldehyde 1a with nitrosobenzene 2a (1a:2a¼1:1.5) catalyzed
by 20 mol % of different NHCs 4, which were generated in situ from
the corresponding azolium salts 3 with DBU, was examined in dry
chloroform at ambient temperature. It was found that 1,4-dimethyl-
* Corresponding author. E-mail address: ycheng2@bnu.edu.cn (Y. Cheng).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.089

J. Qu, Y. Cheng / Tetrahedron 69 (2013) 888e894
889
and 1,4-dibenzyltriazole carbenes 4a and 4b could promote the
reaction to produce furo[3,4-d][1,2]oxazin-4-one derivative 5a in
48% and 44% yields, respectively (Table 1, entries 1, 2). On the con-
trary, thiazole carbene 4c or imidazole carbene 4d was almost in-
efficient to this reaction under the same conditions. When catalyst
loading of triazole carbene 4a was increased to 30 mol %, the yield of
product 5a was improved to 59%. Under the catalysis of 30 mol % of
triazole carbene 4a, the reaction conditions were further optimized
by varying reaction temperature, solvents, and bases utilizing to
generate carbene catalyst. As summarized in Table 1, in dry chloro-
form, decreasing or elevating reaction temperature all caused the
diminishing of product 5a. Utilizing other solvents including ben-
zene, THF, acetonitrile and acetone, and other bases, such as t-BuOK,
NaH, and Cs2CO3, all decreased the yield of product 5a.
1 and nitrosoarenes 2, 4-(2-aroylvinyl)thiophene-3-carbaldehydes 6
did undergo the annulation reaction with nitrosoarenes 2 to give the
expected thieno[3,4-d][1,2]oxazin-4-ones 7, albeit in lower yields than
the corresponding furo[3,4-d][1,2]oxazin-4-ones 5 in most cases
(Table 3). It was found that, the reactions between thiophene-3-
carbaldehydes 6 and 1-methoxy-4-nitrosobenzene 2c or 1-methyl-4-
nitrosobenzene 2d were efficient to produce compounds 7feh in
63e69% yields. However, when reacted with nitrosobenzene 2a or
1-chloro-4-nitrosobenzene 2b, thiophene-3-carbaldehydes 6 could
not be totally consumed and about 30e70% of aldehydes 6 were re-
covered after the reactions proceeding for 15 h. The lower reactivity of
4-(2-aroylvinyl)thiophene-3-carbaldehydes 6 than 4-(2-aroylvinyl)fu-
ran-3-carbaldehydes 1 in this reaction was probably because the less
electronegative sulfur than oxygen atom deactivated the aldehyde
Table 1
Optimization of the reaction conditions
O
NO
CHO
NHC
precursor
N
O
3
O
O
+
Ph
base, solvent
O
Ph
5a
1a
1a 2a
2a
:
= 1:1.5
O
N
N
N
N
NHC
N
Br
N
N
I
N
Br
N
Br
Bn
S
Bn
Me
precursor 3:
Bn
Bn
Me
Bn
3d
3a
3b
3c
Entry
3
mol % of 3
Base
Solvent
Temp (ꢀC)
Time (h)
Yield of 5a (%)
1
2
3
4
5
7
8
10
11
12
13
14
15
16
3a
3b
3c
3d
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
20
20
20
20
30
30
30
30
30
30
30
30
30
30
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
NaH
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
Benzene
THF
CH3CN
CH3COCH3
CHCl3
CHCl3
CHCl3
rt
rt
rt
rt
15
15
20
20
10
15
15
18
15
18
18
15
18
15
48
44
Trace
Trace
59
46
29
26
43
37
35
45
26
rt
ꢁ20
Reflux
rt
rt
rt
rt
rt
rt
rt
t-BuOK
Cs2CO3
55
Bold values indicate the optimal condition.
With the optimized conditions established for the NHC-catalyzed
annulation between 4-(2-benzoylvinyl)furan-3-carbaldehyde 1a
and nitrosobenzene 2a, we turned our attention to investigate the
scope of this reaction (Table 2). A survey of different aroylvinyl
substituted furanaldehydes 1 and nitrosoarenes 2 indicated that
both substituents attached to the aroyl groups of 1 and the phenyls of
2 have influenceontheefficiencyof thereactions. Forexample, while
4-(2-aroylvinyl)furan-3-carbaldehydes 1aee that were attached by
benzoyl, 4-methylbenzoyl, 4-methoxybenzoyl, 4-bromobenzoyl or
2-methoxybenzoyl on the vinyl group reacted with nitrosobenzene
2a to provide furo[3,4-d][1,2]oxazin-4-ones 5aee in 56e63%
yields, the reaction between 4-(3-methoxybenzoylvinyl)furan-3-
carbaldehyde 1f and 2a only produced 31% yield of product 5f
(Table 2, entries 1e6). On the other hand, the electron-rich nitro-
soarenes 2c and 2d afforded higher yields of products than the
electron-deficient nitrosoarene 2b when reacting with 4-(2-
benzoylvinyl)furan-3-carbaldehyde 1a (Table 2, entries 7e9).
Following the reaction of 4-(2-aroylvinyl)furan-3-carbaldehydes 1
with nitrosoarenes 2, 4-(2-aroylvinyl)thiophene-3-carbaldehydes 6
were employed to react with nitrosoarenes. Under the similar condi-
tions for the reaction between 4-(2-aroylvinyl)furan-3-carbaldehydes
Table 2
The NHC-catalyzed reaction of 4-(2-aroylvinyl)furan-3-carbaldehydes
nitrosoarenes 2
1
with
O
NO
3a/DBU
30 mol %
CHO
N
O
X
O
O
+
Ar
CHCl3, rt
O
Ar
X
2
1 2
:
= 1:1.5
5
1
O
Entry
1
Ar
Ph
2
X
Time (h)
Yield of 5 (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1a
1a
1a
2a
2a
2a
2a
2a
2a
2b
2c
2d
H
H
H
H
H
H
Cl
OMe
Me
15
15
15
15
15
20
20
10
20
5a: 59
5b: 58
5c: 56
5d: 63
5e: 60
5f: 31
5g: 40
5h: 67
5i: 64
p-PhMe
p-PhOMe
p-PhBr
o-PhOMe
m-PhOMe
Ph
Ph
Ph

890
J. Qu, Y. Cheng / Tetrahedron 69 (2013) 888e894
Table 3
HO
CHO
The NHC-catalyzed reaction of 4-(2-aroylvinyl)thiophene-3-carbaldehydes 6 with
nitrosoarenes 2
N
N
N
X
n( )
N
N
X
n( )
Ar
Y
N
O
NO
3a/
DBU
Y
O
CHO
N
O
X
30 mol %
Ar
10
S
S
1
: n = 0, X = O, Y = C
: n = 0, X = S, Y = C
4a
+
Ar
6
Ar1 NO
2
O
CHCl3, rt
8: n = 1, X = C, Y = N
O
Ar
X
2
6:2 = 1:1.5
7
6
O
O
N
N
N
Ar1
X
n( )
N
OH
O
H
Entry
6
Ar
Ph
2
X
Time (h)
Yield of 7 (%)
4a
O
Ar1
-
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6a
6a
6a
6c
H
H
H
H
7a: 45a
7b: 31a
7c: 24a
7d: 36a
7e: 15a
7f: 69b
7g: 66b
7h: 63b
X
n( )
N
2a
2a
2a
2a
2b
2c
2d
2c
15
15
15
15
15
10
10
10
Y
p-PhMe
p-PhOMe
p-PhBr
Ph
Ar
Y
12
11
Ar
O
Cl
4a
DBU or NHC
Ph
Ph
OMe
Me
OMe
O
Ar1
acted as a base
O
O
p-PhOMe
Ar1
N
X
n( )
N
O
a
X
n( )
Thiophene-2-carbaldehydes 6 could not be totally consumed in the reactions
Y
with 2a or 2b. The yields of 7aee were calculated based on the ratios of 6:7 in crude
products detected by 1H NMR. Aldehydes 6 and the corresponding products 7 have
very similar polarities and were different to be separated using column chroma-
tography, and the pure products 7 were obtained by recrystallization from the
O
Y
Ar
Ar
O
O
13
mixtures of reactants 6 and products 7.
5
: n = 0, X = O, Y = C
b
Aldehydes
6 were totally consumed when reacted with 1-methoxy-4-
7
: n = 0, X = S, Y = C
nitrosobenzene 2c or 1-methyl-4-nitrosobenzene 2d.
9: n = 1, X = C, Y = N
groups of thiophene-3-carbaldehydes 6 toward nucleophilic carbene
catalyst.
Scheme 1.
Tofurtherextend the applicationof the NHC-catalyzedannulation
between o-aroylvinylarylaldehydes and nitrosoarenes 2, the reaction
of 2-(2-aroylvinyl)nicotinaldehydes 8 with nitrosoarenes 2 was also
studied. It was found that nicotinaldehydes 8 were more reactive
than furan-3-carbaldehydes 1 and thiophene-3-carbaldehydes 6 to-
ward nitrosoarenes 2 under the catalysis of NHC. Thus, the catalyst
loading of carbene 4a was then decreased to 20 mol %. As shown in
Table 4, all reactions between different substituted nicotinaldehydes
8 and nitrosoarenes 2 proceeded efficiently to produce pyrido[3,2-d]
[1,2]oxazin-5-ones 9 in moderated to good yields.
catalysis of a base like DBU or triazole carbene 4, N-hydroxylamides
12 undergoes an intramolecular oxo-Michael addition to afford
fused oxazinones 5, 7 or 9.
The multifunctional aryl-fused 1,2-oxazinones 5, 7 or 9 are useful
in the syntheses of novel furan, thiophene or pyridine derivatives. To
demonstrate their synthetic utility, we conducted their reductive
transformation. Under the catalysis of PdeC in THF, hydrogenation
of 1-(benzoylmethylene)-3-phenylfuro[3,4-d][1,2]oxazin-4-one 5a
produced 4-(1-hydroxy-3-oxo-3-phenylpropyl)-N-phenylfuran-3-
carboxamide 14 in 50% yield. The reduction of 1-(p-methylbenzoyl-
methylene)-3-phenylthieno[3,4-d][1,2]oxazin-4-one
7b
using
Table 4
The NHC-catalyzed reaction of 2-(2-aroylvinyl)nicotinaldehydes
nitrosoarenes 2
8
with
LiAlH4 in THF afforded 1-(2-hydroxy-2-phenylethyl)-3-(p-tolyl)
thieno[3,4-d][1,2]oxazin-4-one 15 in 61% yield (Scheme 2).
O
NO
3a/
DBU
3. Conclusions
CHO
N
O
X
20 mol %
+
Ar
In summary, we have studied the NHC-catalyzed reactions of
4-(2-aroylvinyl)furan-3-carbaldehydes, 4-(2-aroylvinyl)thiophene-
3-carbaldehydes, and 2-(2-aroylvinyl)nicotinaldehydes, with nitro-
soarenes, which provided novel furo[3,4-d][1,2]oxazin-4-ones,
thieno[3,4-d][1,2]oxazin-4-ones, and pyrido[3,2-d][1,2]oxazin-5-
ones, respectively. This work developed a versatile method for the
synthesis of different types of heterocyclicring-fused1,2-oxazinones
that are not easy accessible by other methods.
N
N
CHCl3, rt
O
Ar
X
2
8:2 = 1:1.5
8
9
O
Entry
8
Ar
Ph
2
X
Time (h)
Yield of 9 (%)
1
2
3
4
5
6
7
8a
8b
8c
8d
8a
8a
8a
2a
2a
2a
2a
2b
2c
2d
H
H
H
H
Cl
OMe
Me
10
10
15
10
10
10
15
9a: 70
9b: 67
9c: 53
9d: 70
9e: 65
9f: 77
9g: 75
p-PhMe
p-PhOMe
p-PhBr
Ph
4. Experimental section
Ph
Ph
4.1. General procedure for the reaction of 4-(2-aroylvinyl)fu-
ran-3-carbaldehydes 1 or 4-(2-aroylvinyl)thiophene-3-
carbaldehydes 6 with nitrosoarenes 2
A cascade mechanism is proposed to account for the formation
of heterocyclic ring-fused oxazinones 5, 7, and 9 (Scheme 1). The
interaction of NHC with heterocyclic aldehydes 1, 6 or 8 generates
Breslow intermediates 10. A nucleophilic addition of 10 to the
nitroso group of 2 forms intermediates 11. Intramolecular proton
shifting from CeOH to NeOH accompanied by the elimination of
NHC moiety from 11 produces N-hydroxylamides 12. Under the
Under nitrogen atmosphere and at ambient temperature (about
25e30 ꢀC), 4-(2-aroylvinyl)furan-3-carbaldehydes 112 or 4-(2-
aroylvinyl)thiophene-3-carbaldehydes 612 (0.5 mmol), nitro-
soarenes 213 (0.75 mmol), and N,N-dimethyl-1,2,4-triazolium salt
3a (0.15 mmol) were mixed in dry chloroform (10 mL), and then
DBU (0.2 mmol) was added using a microsyringe. The mixture was

J. Qu, Y. Cheng / Tetrahedron 69 (2013) 888e894
891
Z
CH3
O
O
O
N
O
N
H
N
O
X
O
S
Ph
H2 (g)/Pd-C
THF, rt, 4 h
LiAlH4/THF,
- 20 oC, 2 h
OH
Ph
O
Ph
O
OH
5a: X = O, Z = H
14: 50%
7b
15:
: X = S, Z = CH3
61%
Scheme 2.
stirred for 10e20 h at room temperature and then the solvent was
removed under vacuum. The residue was chromatographed on
a silica gel column eluting with a mixture of petroleum ether and
ethyl acetate (15:1 to 10:1) to afford products 5 or 7. In some cases,
the crude products contained the unconsumed aldehydes reactants
that could be removed from the products by recrystallization.
J¼7.8, 1.7 Hz, 1H), 7.62 (d, J¼7.7 Hz, 2H), 7.43 (td, J¼8.5, 1.7 Hz, 2H),
7.30 (t, J¼8.4 Hz, 2H), 7.26 (s, 1H), 7.11 (t, J¼7.4 Hz, 1H), 6.96 (t,
J¼7.3 Hz,1H), 6.90 (d, J¼8.4 Hz,1H), 5.81 (t, J¼6.3 Hz,1H), 3.80 (s, 3H),
3.71 (dd, J¼18.0, 6.3 Hz, 1H), 3.54 (dd, J¼17.9, 6.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d (ppm) 197.1,160.1,159.0,145.2,139.4,136.2,134.5,
130.5, 128.6, 127.0, 125.6, 125.1, 120.8, 117.8, 111.7, 73.8, 55.5, 46.8;
HRMS (ESI): [MþH]þ calcd for C21H18NO5: 364.1185; found: 364.1193.
4.1.1. 1-(Benzoylmethylene)-3-phenylfuro[3,4-d][1,2]oxazin-4-one
5a. Yield 59%, mp 89e90 ꢀC; IR
n
(cmꢁ1) 1689, 1665, 1551; 1H NMR
4.1.6. 1-(m-Methoxybenzoylmethylene)-3-phenylfuro[3,4-d][1,2]ox-
(400 MHz, CDCl3)
d
(ppm) 8.11 (s, 1H), 7.96 (d, J¼7.6 Hz, 2H), 7.68 (d,
azin-4-one 5f. Yield 31%, mp 110e111 ꢀC; IR (cmꢁ1) 1686, 1659,
n
J¼8.0 Hz, 2H), 7.61 (t, J¼7.3 Hz, 1H), 7.48 (t, J¼7.5 Hz, 2H), 7.37 (t,
J¼7.7 Hz, 2H), 7.35 (s, 1H), 7.19 (t, J¼7.3 Hz, 1H), 5.94 (t, J¼6.3 Hz,
1H), 3.77 (dd, J¼17.4, 6.0 Hz, 1H), 3.56 (dd, J¼17.4, 6.9 Hz, 1H); 13C
1613, 1594; 1H NMR (400 MHz, CDCl3)
d
(ppm) 8.03 (d, J¼1.3 Hz,
1H), 7.60 (d, J¼7.7 Hz, 1H), 7.43 (t, J¼7.7 Hz, 1H), 7.41 (s, 1H),
7.28e7.33 (m, 3H), 7.27 (s, 1H), 7.11 (t, J¼7.4 Hz, 1H), 7.07 (dd, J¼8.2,
2.0 Hz, 1H), 5.85 (t, J¼6.1 Hz, 1H), 3.79 (s, 3H), 3.68 (dd, J¼17.5,
6.1 Hz, 1H), 3.48 (dd, J¼17.5, 6.9 Hz, 1H); 13C NMR (100 MHz, CDCl3)
NMR (100 MHz, CDCl3)
d (ppm) 195.8, 160.2, 145.4, 139.3, 136.4,
136.3, 133.9, 128.8, 128.7, 128.2, 125.7, 124.8, 120.8, 117.7, 73.7, 41.5;
MS (EI): 105 (100), 333 (11%, Mþ). Anal. Calcd for C20H15NO4: C
72.06, H 4.54, N 4.20; found: C 71.72, H 4.92, N 4.07.
d
(ppm) 195.6, 160.2, 160.0, 145.4, 139.3, 137.6, 136.3, 129.8, 128.6,
125.7, 124.8,120.81, 120.77,120.3,117.7,112.4, 73.6, 55.4, 41.6; HRMS
(ESI): [MþH]þ calcd for C21H18NO5: 364.1185; found: 364.1193.
4.1.2. 1-(p-Methylbenzoylmethylene)-3-phenylfuro[3,4-d][1,2]ox-
azin-4-one 5b. Yield 58%, mp 125e127 ꢀC; IR
n
(cmꢁ1) 1681, 1600,
4.1.7. 1-(Benzoylmethylene)-3-(p-chlorophenyl)furo[3,4-d][1,2]ox-
1552; 1H NMR (400 MHz, CDCl3)
d
(ppm) 8.11 (d, J¼0.9 Hz, 1H), 7.86
azin-4-one 5g. Yield 40%, mp 148e150 ꢀC; IR (cmꢁ1) 1679, 1654;
n
(d, J¼8.2 Hz, 2H), 7.68 (d, J¼8.0 Hz, 2H), 7.37 (t, J¼7.9 Hz, 2H), 7.34 (s,
1H), 7.27 (d, J¼8.6 Hz, 2H), 7.19 (t, J¼7.4 Hz, 1H), 5.93 (t, J¼6.4 Hz,
1H), 3.74 (dd, J¼17.4, 6.0 Hz,1H), 3.53 (dd, J¼17.4, 7.0 Hz,1H), 2.42 (s,
1H NMR (400 MHz, CDCl3)
d
(ppm) 8.11 (s, 1H), 7.96 (d, J¼7.2 Hz,
2H), 7.65 (d, J¼9.0 Hz, 2H), 7.62 (t, J¼7.4 Hz, 2H), 7.49 (t, J¼7.9 Hz,
2H), 7.36 (s, 1H), 7.32 (d, J¼9.0 Hz, 2H), 5.94 (t, J¼5.6 Hz, 1H), 3.77
(dd, J¼17.5, 6.5 Hz, 1H), 3.53 (dd, J¼17.5, 6.4 Hz, 1H); 13C NMR
3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 195.4, 160.2, 145.4, 144.8,
139.3, 136.3, 133.8, 129.5, 128.6, 128.3, 125.7, 124.8, 120.8, 117.7, 73.7,
(100 MHz, CDCl3) d (ppm) 195.6, 160.0, 145.6, 137.9, 136.3, 136.2,
41.3, 21.7; MS (EI): 119 (100), 347 (8%, Mþ). Anal. Calcd for
133.9, 130.7, 128.9, 128.7, 128.1, 124.6, 121.6, 117.5, 73.7, 41.3; HRMS
C
21H17NO4: C 72.61, H 4.93, N 4.03; found: C 72.66, H 4.91, N 3.90.
(ESI): [MþH]þ calcd for C20H15ClNO4: 367.0690; found: 368.0696.
4.1.3. 1-(p-Methoxybenzoylmethylene)-3-phenylfuro[3,4-d][1,2]ox-
azin-4-one 5c. Yield 56%, mp 110e111 ꢀC; IR (cmꢁ1) 1680, 1664,
1603,1549; 1H NMR (400 MHz, CDCl3)
(ppm) 8.10 (d, J¼1.3 Hz,1H),
4.1.8. 1-(Benzoylmethylene)-3-(p-methoxyphenyl)furo[3,4-d][1,2]ox-
n
azin-4-one 5h. Yield 67%, mp 139e140 ꢀC; IR (cmꢁ1) 1678, 1670,
n
d
1615; 1H NMR (400 MHz, CDCl3)
d
(ppm) 8.02 (d, J¼1.3 Hz, 1H), 7.89
7.94 (d, J¼8.9 Hz, 2H), 7.68 (d, J¼8.1 Hz, 2H), 7.37 (t, J¼8.3 Hz, 2H),
7.33 (s, 1H), 7.18 (t, J¼7.4 Hz, 1H), 6.94 (d, J¼8.9 Hz, 2H), 5.92 (t,
J¼6.1 Hz, 1H), 3.88 (s, 3H), 3.72 (dd, J¼17.2, 6.0 Hz, 1H), 3.49 (dd,
(d, J¼7.2 Hz, 2H), 7.54 (t, J¼7.4 Hz, 1H), 7.48 (d, J¼9.1 Hz, 2H), 7.42 (t,
J¼7.6 Hz, 2H), 7.26 (s, 1H), 6.84 (d, J¼9.1 Hz, 2H), 5.86 (t, J¼6.0 Hz,
1H), 3.74 (s, 3H), 3.69 (dd, J¼17.4, 6.0 Hz, 1H), 3.49 (dd, J¼17.5,
J¼17.2, 7.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
(ppm) 194.2, 164.1,
7.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d (ppm) 195.8, 160.4, 158.0,
160.2,145.4,139.3,136.4,130.5,129.4,128.6,125.7,124.9,120.8,117.7,
114.0, 73.9, 55.5, 41.1; MS (EI): 135 (100), 363 (6%, Mþ). Anal. Calcd
for C21H17NO5: C 69.41, H 4.72, N 3.85; found: C 69.00, H 4.73, N 3.63.
145.1, 136.3, 133.8, 132.1, 128.8, 128.1, 124.8, 124.1, 117.6, 114.0, 73.4,
55.5, 41.5; MS (EI): 105 (100), 363 (9%, Mþ). Anal. Calcd for
C21H17NO5: C 69.41, H 4.72, N 3.85; found: C 69.54, H 4.74, N 3.73.
4.1.4. 1-(p-Bromobenzoylmethylene)-3-phenylfuro[3,4-d][1,2]oxazin-
4.1.9. 1-(Benzoylmethylene)-3-(p-tolyl)furo[3,4-d][1,2]oxazin-4-one
5i. Yield 64%, mp 105e106 ꢀC; IR (cmꢁ1) 1678, 1555; 1H NMR
(400 MHz, CDCl3)
4-one 5d. Yield 63%, mp 104e105 ꢀC; IR
n
(cmꢁ1) 1683, 1670, 1582,
n
1554; 1H NMR (400 MHz, CDCl3)
d
(ppm) 8.11 (s, 1H), 7.81 (d,
d
(ppm) 8.09 (d, J¼0.9 Hz, 1H), 7.95 (d, J¼7.4 Hz,
J¼8.4 Hz, 2H), 7.65 (d, J¼8.8 Hz, 2H), 7.62 (d, J¼8.2 Hz, 2H), 7.37 (t,
J¼7.0 Hz, 2H), 7.34 (s,1H), 7.19 (t, J¼7.3 Hz,1H), 5.92 (t, J¼6.5 Hz,1H),
3.74 (dd, J¼17.5, 6.3 Hz, 1H), 3.50 (dd, J¼17.5, 6.7 Hz, 1H); 13C NMR
2H), 7.60 (t, J¼7.4 Hz, 1H), 7.53 (d, J¼8.4 Hz, 2H), 7.48 (t, J¼7.7 Hz,
2H), 7.33 (s, 1H), 7.17 (d, J¼8.3 Hz, 2H), 5.92 (t, J¼6.4 Hz, 1H), 3.76
(dd, J¼17.4, 6.0 Hz, 1H), 3.55 (dd, J¼17.7, 7.1 Hz, 1H), 2.34 (s, 3H); 13
C
(100 MHz, CDCl3)
d
(ppm) 194.8, 160.2, 145.5, 139.2, 136.3, 135.0,
NMR (100 MHz, CDCl3) d (ppm) 195.8, 160.2, 145.2, 136.7, 136.4,
132.2, 129.6, 129.2, 128.7, 125.8, 124.6, 120.8, 117.7, 73.5, 41.4; MS
136.3, 135.9, 133.8, 129.2, 128.8, 128.1, 124.8, 121.4, 117.7, 73.5, 41.5,
21.0; MS (EI): 105 (100), 347 (10%, Mþ). Anal. Calcd for C21H17NO4: C
72.61, H 4.93, N 4.03; found: C 71.21, H 4.81, N 4.83.
(EI): 121 (100), 183/185 (64/63), 411/413 (11%, Mþ). Anal. Calcd for
C
20H14BrNO4: C 58.27, H 3.42, N 3.40; found: C 58.29, H 3.70, N 3.12.
4.1.5. 1-(o-Methoxybenzoylmethylene)-3-phenylfuro[3,4-d][1,2]ox-
azin-4-one 5e. Yield 60%, mp 85e87 ꢀC; IR (cmꢁ1) 1673,1617,1595;
1H NMR (400 MHz, CDCl3)
(ppm) 8.02 (d, J¼1.3 Hz, 1H), 7.72 (dd,
4.1.10. 1-(Benzoylmethylene)-3-phenylthieno[3,4-d][1,2]oxazin-4-
n
one 7a. Yield 45%, mp 110e112 ꢀC; IR (cmꢁ1) 1687, 1657, 1594; 1H
n
d
NMR (400 MHz, CDCl3)
d
(ppm) 8.24 (d, J¼2.9 Hz, 1H), 7.97 (d,

892
J. Qu, Y. Cheng / Tetrahedron 69 (2013) 888e894
J¼7.4 Hz, 2H), 7.71 (d, J¼8.0 Hz, 2H), 7.61 (t, J¼7.4 Hz, 1H), 7.48 (t,
J¼7.7 Hz, 2H), 7.36 (t, J¼8.0 Hz, 2H), 7.17 (t, J¼7.4 Hz, 1H), 7.13 (d,
J¼2.2 Hz, 1H), 6.04 (t, J¼6.2 Hz, 1H), 3.80 (dd, J¼17.4, 6.9 Hz, 1H),
J¼6.2 Hz, 1H), 3.79 (dd, J¼17.4, 6.7 Hz, 1H), 3.59 (dd, J¼17.4, 5.9 Hz,
1H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3)
(ppm) 195.8, 159.9,
140.1, 136.7, 136.4, 135.7, 133.8, 131.5, 131.0, 129.2, 128.8, 128.2, 121.0,
118.8, 76.5, 41.3, 21.0; MS (EI): 105 (100), 363 (15%, Mþ). Anal. Calcd
for C21H17NO3S: C 69.40, H 4.71, N 3.85; found: C 69.36, H 4.64, N 3.71.
d
3.59 (dd, J¼17.4, 5.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d (ppm)
195.8, 159.9, 140.1, 139.3, 136.4, 133.8, 131.7, 131.0, 128.8, 128.6,
128.2, 125.6, 120.5, 118.9, 76.6, 41.3; HRMS (ESI): [MþH]þ calcd for
C
20H16NO3S: 350.0851; found: 350.0852.
4.1.17. 1-(p-Methoxybenzoylmethylene)-3-(p-methoxyphenyl)thieno
[3,4-d][1,2]oxazin-4-one 7h. Yield 63%, mp 145e147 ꢀC; IR (cmꢁ1
n )
4.1.11. 1-(p-Methylbenzoylmethylene)-3-phenylthieno[3,4-d][1,2]ox-
azin-4-one 7b. Yield 31%, mp 138e140 ꢀC; IR (cmꢁ1) 1683, 1651,
1552; 1H NMR (400 MHz, CDCl3)
(ppm) 8.16 (d, J¼2.9 Hz, 1H), 7.80
1677, 1643, 1601; 1H NMR (400 MHz, CDCl3)
d (ppm) 8.21 (d,
n
J¼2.9 Hz, 1H), 7.95 (d, J¼8.8 Hz, 2H), 7.58 (d, J¼9.1 Hz, 2H), 7.10 (d,
J¼2.8 Hz, 1H), 6.94 (d, J¼8.9 Hz, 2H), 7.89 (d, J¼9.1 Hz, 2H), 6.01 (t,
J¼6.4 Hz, 1H), 3.88 (s, 3H), 3.80 (s, 3H), 3.73 (dd, J¼17.2, 6.8 Hz, 1H),
d
(d, J¼8.2 Hz, 2H), 7.64 (d, J¼8.6 Hz, 2H), 7.29 (t, J¼8.4 Hz, 2H), 7.20 (d,
J¼8.8 Hz, 2H), 7.10 (t, J¼7.4 Hz, 1H), 7.04 (d, J¼2.9 Hz, 1H), 5.95 (t,
J¼6.0 Hz, 1H), 3.69 (dd, J¼17.3, 6.8 Hz, 1H), 3.49 (dd, J¼17.3, 5.9 Hz,
3.53 (dd, J¼17.2, 5.9 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d (ppm)
194.2, 164.0, 160.1, 157.8, 140.3, 132.3, 131.2, 131.0, 130.5, 129.6,
123.6, 118.7, 113.9, 76.6, 55.52, 55.45, 41.0; HRMS (ESI): [MþH]þ
calcd for C22H20NO5S: 410.1062; found: 410.1056.
1H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 195.4, 159.9,
144.8,140.2,139.3,134.0,131.6,131.0,129.5,128.6,128.3,125.5,120.5,
118.8, 76.7, 41.2, 21.7; MS (EI): 119 (100), 363 (9%, Mþ). Anal. Calcd for
C
21H17NO3S: C 69.40, H 4.71, N 3.85; found: C 69.53 H 4.61, N 3.72.
4.2. General procedure for the reaction of 2-(2-aroylvinyl)
nicotinaldehydes 8 with nitrosoarenes 2
4.1.12. 1-(p-Methoxybenzoylmethylene)-3-phenylthieno[3,4-d][1,2]
oxazin-4-one 7c. Yield 24%, mp 171e173 ꢀC; IR (cmꢁ1) 1678, 1649,
1601; 1H NMR (400 MHz, CDCl3)
(ppm) 8.23 (d, J¼2.8 Hz, 1H), 7.95
n
Under nitrogen atmosphere and at ambient temperature (about
25e30 ꢀC), 2-(2-aroylvinyl)nicotinaldehydes 812 (0.5 mmol),
nitrosoarenes 2 (0.75 mmol), and N,N-dimethyl-1,2,4-triazolium
salt 3a (0.1 mmol) were mixed in dry chloroform (10 mL), and
then DBU (0.2 mmol) was added using a microsyringe. The mixture
was stirred for 10e15 h at room temperature and then the solvent
was removed under vacuum. The residue was chromatographed on
a silica gel column eluting with a mixture of petroleum ether and
ethyl acetate (10:1 to 6:1) to afford products 9.
d
(d, J¼8.8 Hz, 2H), 7.71 (d, J¼8.0 Hz, 2H), 7.35 (t, J¼8.0 Hz, 2H), 7.17 (t,
J¼7.4 Hz, 1H), 7.11 (d, J¼2.7 Hz, 1H), 6.94 (d, J¼8.8 Hz, 2H), 6.02 (t,
J¼6.3 Hz, 1H), 3.87 (s, 3H), 3.74 (dd, J¼17.1, 6.8 Hz, 1H), 3.53 (dd,
J¼17.1, 5.9 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d (ppm) 194.2, 164.0,
159.9, 140.2, 139.3, 131.6, 131.0, 130.6, 129.5, 128.6, 125.5, 120.4,
118.8, 113.9, 76.7, 55.5, 40.9; HRMS (ESI): [MþH]þ calcd for
C
21H18NO4S: 380.0957; found: 380.0963.
4.1.13. 1-(p-Bromobenzoylmethylene)-3-phenylthieno[3,4-d][1,2]ox-
azin-4-one 7d. Yield 36%, mp 126e127 ꢀC; IR (cmꢁ1) 1694, 1649,
1585; 1H NMR (400 MHz, CDCl3)
(ppm) 8.24 (d, J¼2.9 Hz,1H), 7.82 (d,
4.2.1. 8-(Benzoylmethylene)-6-phenylpyrido[3,2-d][1,2]oxazin-5-one
n
9a. Yield 70%, mp 101e103 ꢀC; IR (cmꢁ1) 1683, 1494; 1H NMR
n
d
(400 MHz, CDCl3)
d
(ppm) 8.70 (dd, J¼4.8, 1.3 Hz, 1H), 8.51 (dd,
J¼8.6 Hz, 2H), 7.69 (d, J¼7.9 Hz, 2H), 7.61 (d, J¼8.6 Hz, 2H), 7.36 (t,
J¼8.0 Hz, 2H), 7.18 (t, J¼7.4 Hz, 1H), 7.12 (d, J¼2.1 Hz, 1H), 6.02 (t,
J¼6.2 Hz, 1H), 3.76 (dd, J¼17.4, 7.2 Hz, 1H), 3.53 (dd, J¼17.3, 5.6 Hz, 1H);
J¼7.8, 1.4 Hz, 1H), 8.05 (d, J¼7.3 Hz, 2H), 7.83 (d, J¼7.8 Hz, 2H), 7.61
(t, J¼7.4 Hz, 2H), 7.48e7.52 (m, 3H), 7.39 (t, J¼7.8 Hz, 2H), 7.20 (t,
J¼7.4 Hz, 1H), 6.22 (dd, J¼8.8, 2.6 Hz, 1H), 4.18 (dd, J¼18.0, 2.8 Hz,
1H), 3.70 (dd, J¼18.0, 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
d (ppm) 194.8, 159.9, 139.8, 139.2, 135.0,
132.1,131.8,130.9,129.7,129.1,128.6,125.6,120.4,118.8, 76.4, 41.2; HRMS
d (ppm) 195.7, 160.9, 158.2, 152.3, 138.9, 136.6, 136.1, 133.6, 128.7,
(ESI): [MþH]þ calcd for C20H15BrNO3S: 427.9956; found: 427.9957.
128.3, 125.9, 123.8, 123.7, 120.3, 78.5, 38.8; HRMS (ESI): 345.1244
(Mþ1). Anal. Calcd for C21H17N2O3: 345.1239 (Mþ1).
4.1.14. 1-(Benzoylmethylene)-3-(p-chlorophenyl)thieno[3,4-d][1,2]
oxazin-4-one 7e. Yield 15%, mp 118e120 ꢀC; IR
n
(cmꢁ1) 1688, 1650,
4.2.2. 8-(p-Methylbenzoylmethylene)-6-phenylpyrido[3,2-d][1,2]ox-
1552; 1H NMR (400 MHz, CDCl3)
d
(ppm) 8.25 (d, J¼2.9 Hz, 1H), 7.97 (d,
azin-5-one 9b. Yield 67%, mp 108e110 ꢀC; IR (cmꢁ1) 1680, 1494;
n
J¼7.8 Hz, 2H), 7.68 (d, J¼9.0 Hz, 2H), 7.62 (t, J¼7.4 Hz, 1H), 7.49 (t,
J¼7.8 Hz, 2H), 7.31 (d, J¼9.0 Hz, 2H), 7.13 (d, J¼2.2 Hz, 1H), 6.03 (t,
J¼6.2 Hz, 1H), 3.79 (dd, J¼17.4, 7.3 Hz, 1H), 3.57 (dd, J¼17.4, 5.3 Hz, 1H);
1H NMR (400 MHz, CDCl3)
d
(ppm) 8.70 (dd, J¼4.8, 1.3 Hz, 1H), 8.48
(dd, J¼7.8, 1.4 Hz, 1H), 7.94 (d, J¼8.2 Hz, 2H), 7.83 (d, J¼8.0 Hz, 2H),
7.48 (dd, J¼7.7, 5.0 Hz, 1H), 7.39 (t, J¼8.0 Hz, 2H), 7.29 (d, J¼8.0 Hz,
2H), 7.20 (t, J¼7.4 Hz, 1H), 6.21 (dd, J¼8.9, 2.6 Hz, 1H), 4.12 (dd,
J¼18.0, 2.8 Hz, 1H), 3.65 (dd, J¼18.0, 9.0 Hz, 1H), 2.43 (s, 3H); 13C
13C NMR (100 MHz, CDCl3)
d(ppm) 195.6,159.8,139.9,137.8,136.3,133.9,
132.0,130.7,130.5,128.8,128.6,128.2,121.3,118.9, 76.6, 41.1; HRMS (ESI):
[MþH]þ calcd for C20H15ClNO3S: 384.0461; found: 384.0468.
NMR (100 MHz, CDCl3) d (ppm) 195.3, 160.9, 158.3, 152.4, 144.5,
138.9,136.0,134.1,129.4,128.7, 128.4,125.9,123.7,123.6,120.2, 78.6,
4.1.15. 1-(Benzoylmethylene)-3-(p-methoxyphenyl)thieno[3,4-d][1,2]
38.7, 21.7; MS (EI): 119 (100), 358 (2%, Mþ). Anal. Calcd for
oxazin-4-one 7f. Yield 69%, mp 160e161 ꢀC; IR
n
(cmꢁ1) 1677, 1661,
C22H18N2O3: C 73.73, H 5.06, N 7.82; found: C 73.73, H 5.52, N 7.64.
1602, 1513; 1H NMR (400 MHz, CDCl3)
d
(ppm) 8.21 (d, J¼2.9 Hz,
1H), 7.97 (d, J¼7.4 Hz, 2H), 7.61 (t, J¼7.5 Hz, 1H), 7.58 (d, J¼9.0 Hz,
2H), 7.48 (t, J¼7.8 Hz, 2H), 7.11 (d, J¼2.3 Hz, 1H), 6.89 (d, J¼9.0 Hz,
2H), 6.03 (t, J¼6.4 Hz, 1H), 3.80 (s, 3H), 3.78 (dd, J¼17.6, 6.8 Hz, 1H),
4.2.3. 8-(p-Methoxybenzoylmethylene)-6-phenylpyrido[3,2-d][1,2]
oxazin-5-one 9c. Yield 53%, mp 80e81 ꢀC; IR (cmꢁ1) 1674,1600; 1H
NMR (400 MHz, CDCl3)
(ppm), 8.69 (dd, J¼4.8,1.4 Hz,1H), 8.46 (dd,
n
d
3.59 (dd, J¼17.4, 5.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
(ppm)
J¼7.8, 1.4 Hz, 1H), 8.02 (d, J¼8.8 Hz, 2H), 7.84 (d, J¼8.0 Hz, 2H), 7.46
(dd, J¼7.7, 4.9 Hz,1H), 7.38 (t, J¼8.2 Hz, 2H), 7.19 (t, J¼7.4 Hz,1H), 6.93
(d, J¼8.8 Hz, 2H), 6.19 (dd, J¼8.9, 2.7 Hz,1H), 4.06 (dd, J¼17.8, 2.8 Hz,
1H), 3.88 (s, 3H), 3.62 (dd, J¼17.8, 9.0 Hz, 1H); 13C NMR (100 MHz,
195.8,160.1,157.8,140.1,136.4,133.8,132.2,131.4,130.9,128.8,128.2,
123.6, 118.8, 113.9, 76.4, 55.5, 41.3; HRMS (ESI): [MþH]þ calcd for
C
21H18NO4S: 380.0957; found: 380.0955.
CDCl3)
d (ppm) 194.1, 163.9, 160.9, 158.4, 152.4, 139.0, 136.0, 130.6,
4.1.16. 1-(Benzoylmethylene)-3-(p-tolyl)thieno[3,4-d][1,2]oxazin-4-
one 7g. Yield 66%, mp 110e111 ꢀC; IR (cmꢁ1) 1689, 1662, 1645; 1H
NMR (400 MHz, CDCl3)
J¼7.6 Hz, 2H), 7.61 (t, J¼7.4 Hz, 1H), 7.57 (d, J¼8.5 Hz, 2H), 7.48 (t,
J¼7.7 Hz, 2H), 7.17 (d, J¼8.3 Hz, 2H), 7.12 (d, J¼2.6 Hz, 1H), 6.03 (t,
129.7, 128.7, 125.8, 123.7, 123.6, 120.2, 113.9, 78.7, 55.5, 38.4; HRMS
(ESI): 375.1347 (Mþ1). Anal. Calcd for C22H20N2O4: 375.1345 (Mþ1).
n
d
(ppm) 8.22 (d, J¼2.9 Hz, 1H), 7.97 (d,
4.2.4. 8-(p-Bromobenzoylmethylene)-6-phenylpyrido[3,2-d][1,2]ox-
azin-5-one 9d. Yield 70%, mp 145e146 ꢀC; IR
n
(cmꢁ1) 1691, 1664,

J. Qu, Y. Cheng / Tetrahedron 69 (2013) 888e894
893
1585; 1H NMR (400 MHz, CDCl3)
d
(ppm) 8.70 (dd, J¼4.8,1.4 Hz,1H),
63.7, 46.2; HRMS (ESI): [MþH]þ calcd for C20H18NO4: 336.1236;
8.49 (d, J¼7.6 Hz, 1H), 7.91 (d, J¼8.6 Hz, 2H), 7.82 (d, J¼7.8 Hz, 2H),
7.64 (d, J¼8.6 Hz, 2H), 7.49e7.52 (m, 1H), 7.40 (t, J¼8.3 Hz,
2H), 7.22 (t, J¼7.4 Hz, 1H), 6.19 (dd, J¼8.7, 2.7 Hz, 1H), 4.13
(dd, J¼18.0, 2.8 Hz, 1H), 3.63 (dd, J¼18.0, 8.8 Hz, 1H); 13C NMR
found: 336.1241.
4.2.10. Reduction of 1-(p-methylbenzoylmethylene)-3-phenylthieno
[3,4-d][1,2]oxazin-4-one 7b using LiAlH4. At ꢁ20 ꢀC, the solution
of thieno[3,4-d][1,2]oxazin-4-one 7b (0.3 mmol) in dry THF (10 mL)
was added dropwise to LiAlH4 (0.66 mmol) in dry THF (10 mL) with
stirring. The reaction mixture was stirred for 2 h at ꢁ20 ꢀC, and then
the reaction was quenched by the addition of aqueous HCl (2 M)
until no hydrogen gas releasing. After removal of THF, the residue
was extracted with ethyl acetate (50ꢂ3 mL), and the combined
extraction was dried and evaporated. The residue was chromato-
graphed on a silica gel column eluting with a mixture of petroleum
ether and ethyl acetate (5:1) to give product 15 in 61% yield.
(100 MHz, CDCl3)
d (ppm) 194.7, 160.9, 158.0, 152.4, 138.9, 136.1,
135.3, 132.1, 129.8, 128.8, 128.7, 126.0, 123.9, 123.6, 120.3, 78.5, 38.8;
HRMS (ESI): 423.0342 (Mþ1). Anal. Calcd for C21H16BrN2O3:
423.0344 (Mþ1).
4.2.5. 8-(Benzoylmethylene)-6-(p-chlorophenyl)pyrido[3,2-d][1,2]
oxazin-5-one 9e. Yield 65%, mp 167e168 ꢀC; IR (cmꢁ1) 1693, 1676,
n
1489; 1H NMR (400 MHz, CDCl3)
d
(ppm) 8.71 (dd, J¼4.8,1.4 Hz,1H),
8.46 (dd, J¼7.8, 1.4 Hz, 1H), 8.05 (d, J¼7.3 Hz, 2H), 7.82 (d, J¼9.0 Hz,
2H), 7.62 (t, J¼7.4 Hz, 1H), 7.51 (t, J¼7.8 Hz, 2H), 7.48 (dd, J¼8.0,
5.0 Hz, 1H), 7.35 (d, J¼9.0 Hz, 2H), 6.18 (dd, J¼9.2, 2.3 Hz, 1H), 4.15
(dd, J¼18.2, 2.6 Hz, 1H), 3.64 (dd, J¼18.2, 9.2 Hz, 1H); 13C NMR
4.2.11. 1-(2-Hydroxy-2-phenylethyl)-3-(p-tolyl)thieno[3,4-d][1,2]ox-
azin-4-one 15. Yield 61%, mp 120e121 ꢀC; IR
n
(cmꢁ1) 3373, 1641,
(100 MHz, CDCl3)
d
(ppm) 195.7, 160.9, 158.1, 152.6, 137.5, 136.5,
1552, 1507, 1466; 1H NMR (400 MHz, CD3COCD3)
d (ppm) 8.30 (d,
136.1, 133.7, 130.9, 128.8, 128.3, 123.8, 123.4, 121.2, 78.6, 38.7;
J¼2.9 Hz, 1H), 7.59 (d, J¼8.5 Hz, 2H), 7.51 (dd, J¼2.8, 1.0 Hz, 1H), 7.43
(d, J¼7.2 Hz, 2H), 7.32 (t, J¼7.5 Hz, 2H), 7.25 (t, J¼7.2 Hz, 1H), 7.23 (d,
J¼8.3 Hz, 2H), 5.29 (t, J¼6.2 Hz, 1H), 4.98e5.01 (m, 1H), 4.59 (d,
J¼4.0 Hz, 1H), 2.47e2.51 (m, 2H), 2.34 (s, 3H); 13C NMR (100 MHz,
HRMS (ESI): 379.0846 (Mþ1). Anal. Calcd for
C21H16ClN2O3:
379.0849 (Mþ1).
4.2.6. 8-(Benzoylmethylene)-6-(p-methoxyphenyl)pyrido[3,2-d][1,2]
oxazin-5-one 9f. Yield 77%, mp 136e137 ꢀC; IR (cmꢁ1) 1686, 1659,
1504; 1H NMR (400 MHz, CDCl3)
(ppm) 8.69 (dd, J¼4.8,1.4 Hz,1H),
CD3COCD3) d (ppm) 160.5, 145.6, 141.8, 138.3, 135.8, 132.1, 132.0,
n
129.8, 129.2, 128.2, 127.0, 121.6, 120.0, 79.3, 71.3, 42.5, 20.9; HRMS
d
(ESI): [MþH]þ calcd for C21H20NO3S: 366.1164; found: 366.1173.
8.47 (dd, J¼7.8, 1.4 Hz, 1H), 8.05 (d, J¼7.3 Hz, 2H), 7.72 (d, J¼9 Hz,
2H), 7.61 (t, J¼7.4 Hz, 1H), 7.46e7.52 (m, 3H), 6.92 (d, J¼9.1 Hz, 2H),
6.22 (dd, J¼8.8, 2.7 Hz,1H), 4.15 (dd, J¼18.0, 2.8 Hz,1H), 3.82 (s, 3H),
Acknowledgements
3.66 (dd, J¼18.0, 8.9 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d (ppm)
This work was supported by the National Natural Science
Foundation of China (No. 21172021, 20972017 and 20832006),
Beijing Municipal Commission of Education and the Fundamental
Research Funds for the Central Universities (2009SC-1).
195.7, 160.8, 158.2, 157.9, 152.3, 136.6, 135.9, 133.5, 131.9, 128.7,
128.3, 123.7, 123.6, 123.2, 114.0, 78.5, 55.5, 38.8; MS (EI): 105 (67),
121 (100), 374 (27%, Mþ). Anal. Calcd for C22H18N2O4: C 70.58, H
4.85, N 7.48; found: C 70.59, H 5.04, N 7.47.
Supplementary data
4.2.7. 8-(Benzoylmethylene)-6-(p-tolyl)pyrido[3,2-d][1,2]oxazin-5-
one 9g. Yield 75%, mp 115e117 ꢀC; IR (cmꢁ1) 1692, 1669, 1509; 1H
n
Electronic Supplementary data (ESI): the methods for the syn-
theses of 4-(2-aroylvinyl)furan-3-carbaldehydes 1, 4-(2-aroylvinyl)
thiophene-3-carbaldehydes 6 and 2-(2-aroylvinyl)nicotinaldehydes
8, and the copies of 1H NMR and 13C NMR spectra of products 5, 7, 9,
14, and 15 are available. Supplementary data associated with this
article can be found in the online version, at http://dx.doi.org/
10.1016/j.tet.2012.10.089. These data include MOL files and InChi-
Keys of the most important compounds described in this article.
NMR (400 MHz, CDCl3)
d
(ppm) 8.68 (dd, J¼4.8,1.4 Hz,1H), 8.46 (dd,
J¼7.8, 1.4 Hz, 1H), 8.04 (d, J¼7.3 Hz, 2H), 7.69 (d, J¼8.5 Hz, 2H), 7.60
(t, J¼7.3 Hz, 1H), 7.49 (t, J¼7.8 Hz, 2H), 7.46 (dd, J¼7.8, 4.9 Hz,
1H), 7.19 (d, J¼8.4 Hz, 2H), 6.20 (dd, J¼8.8, 2.8 Hz, 1H), 4.12 (dd,
J¼18.0, 3.0 Hz, 1H), 3.65 (dd, J¼18.0, 8.9 Hz, 1H), 2.34 (s, 3H); 13C
NMR (100 MHz, CDCl3)
d (ppm) 194.7, 159.8, 157.2, 151.3, 135.6,
135.4, 134.9, 132.5, 128.3, 127.7, 122.7, 122.6, 119.7, 77.5, 37.7, 20.0;
HRMS (ESI): 359.1400 (Mþ1). Anal. Calcd for
C22H19N2O3:
359.1396 (Mþ1).
References and notes
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carboxamide 14. Yield 50%, mp 145e146 ꢀC; IR (cmꢁ1) 3292, 3137,
n
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d (ppm)
10.16 (s, 1H), 8.24 (d, J¼1.6 Hz, 1H), 8.04 (d, J¼7.2 Hz, 2H), 7.74 (d,
J¼7.6 Hz, 2H), 7.72 (d, J¼1.4 Hz, 1H), 7.62 (t, J¼7.4 Hz, 1H), 7.50 (t,
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shown in the Electronic Supplementary data.
8 were
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