Microwave-assisted multi-component reaction in water leading to highly regioselective formation of benzo[f]azulen-1-ones

Article abstract of DOI:10.1016/j.tet.2011.05.002

Microwave-assisted three-component reaction has been established for the regioselective synthesis of benzo[f]azulen-1-ones. The reaction was performed in aqueous media under microwave irradiation by using readily available and inexpensive starting materials. A total of 38 examples were examined to show a broad substrate scope and good overall yields (70-89%). The present new synthesis shows attractive green chemistry characteristics, such as the use of water as reaction media, concise one-pot conditions, short reaction periods (7-24 min), easy work-up/purification, and reduced waste production without the use of any strong acids or metal promoters.

Full text of DOI:10.1016/j.tet.2011.05.002

Tetrahedron 67 (2011) 4485e4493
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Microwave-assisted multi-component reaction in water leading to highly
regioselective formation of benzo[f]azulen-1-ones
,
b
Shu-Liang Wang a, Chuang Cheng a, Fei-Yue Wu a, Bo Jiang a, Feng Shi a, Shu-Jiang Tu a , Trideep Rajale ,
*
,
Guigen Li b
*
a School of Chemistry and Chemical Engineering, Laboratory of Green Synthetic Chemistry for Functional Materials, Xuzhou Normal University, Xuzhou 221116, Jiangsu, PR China
b Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Microwave-assisted three-component reaction has been established for the regioselective synthesis of
benzo[f]azulen-1-ones. The reaction was performed in aqueous media under microwave irradiation by
using readily available and inexpensive starting materials. A total of 38 examples were examined to show
a broad substrate scope and good overall yields (70e89%). The present new synthesis shows attractive
green chemistry characteristics, such as the use of water as reaction media, concise one-pot conditions,
short reaction periods (7e24 min), easy work-up/purification, and reduced waste production without the
use of any strong acids or metal promoters.
Received 21 March 2011
Received in revised form 29 April 2011
Accepted 2 May 2011
Available online 7 May 2011
Keywords:
Tetronic acid
Benzo[f]azulen-1-ones
Microwave-assisted multi-component
reaction
Ó 2011 Elsevier Ltd. All rights reserved.
Aqueous media
Green synthesis
1. Introduction
steps, long reaction times, low overall yields, and environmental
unfriendly and uneconomical. So far, there have been a few benzo[f]
Heterocycles containing benzodiazepine rings belong to im-
portant building blocks because of their remarkable depressant
activity in central nervous system1 and their being one of the most
widely prescribed class of psychotropics.1h,i In addition, some of
these compounds also possess bioactivities on analgesic, sedative,
and antidepressive as well as hypnotic activities.2 On the other
hand, the derivatives of tetronic acid (tetrahydrofuran-2,4-dione)
play an essential role in medicinal chemistry3 by serving as HIV-1
protease inhibiting,4 anti-inflammatory,5 antifungal,6 antibiotic,7
insecticidal,8 analgesic,9 anticoagulant,10 and antiepileptic11
agents. Consequently, benzoazulen-1-one derivatives containing
both benzodiazepine and tetronic acid motifs would provide novel
leading structures for combinatorial drug-discovery research.
A careful literature survey revealed that benzo[f]azulen-1-one
derivatives have been synthesized by the condensation reaction of
4-(2-aminophenylamino)furan-2(5H)-one with aldehyde in normal
organic solvents.12 However, the substrate scope of this reaction is
limited. It also suffered by other shortcomings, such as multiple
azulen-1-one compounds produced via this method. The continu-
ing search for new efficient approaches to benzo[f]azulen-1-ones in
terms of mild reaction conditions, operational simplicity, economic
viability, eco-friendliness, and selectivity remains challenging.
In the past several years, our groups and several others have
developed a series of multi-component domino reactions (MDRs)
that can provide easy accesses to multi-functionalized heterocyclic
structures of chemical and pharmaceutical interest.13ꢀ16 Especially,
we established a new four-component domino reaction for an ef-
ficient synthesis of multi-functionalized quinazoline derivatives.13a
The reaction is easily performed by simply mixing readily available
starting materials, aromatic aldehydes, cyclopentanone, and cya-
noacetamide with K2CO3 in ethylene glycol under microwave (MW)
irradiation. Interestingly, when aliphatic aldehydes were employed
to replace their aromatic counterparts for the above MDR reaction,
the reaction was found to undergo along another pathway leading
to the formation of multi-functionalized tricyclo[6.2.2.01,6]dodec-
anes.13b Recently, we have also found that the MDR of Meldrum’s
acid, aromatic aldehydes, and electron-rich heteroaryl-amines in
aqueous phase under microwave (MW) irradiation led to the multi-
functionalized spiro{[1,3]dioxanes-pyridine}-4,6-dione with high
chemo,- regio,- and stereoselectivity and good yields.13d
* Corresponding authors. Tel./fax: þ1 806 742 3015 (G.L.); tel./fax: þ86 516
83500065 (S.-J.T.); e-mail addresses: laotu@xznu.edu.cn (S.-J. Tu), guigen.li@ttu.edu
(G. Li).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.002

4486
S.-L. Wang et al. / Tetrahedron 67 (2011) 4485e4493
As a continuation of our research devoted to the development of
(Table 2, entry 9) still displayed high reactivity and clean conver-
sion under this condition. The similar situation exists for the use of
4-chlorobenzene-1,2-diamine 1b for reactions that occurred rap-
idly to give the desired products 4jen in 76e84% yields (Table 2,
entries 10e14). It is worth noting that these reactions showed high
regioselectivity; only one single regioisomer was generated when
3,4-diaminobenzoic acid and 4-chlorobenzene-1,2-diamine were
employed as substrates. The reason for this excellent selectivity is
that the amino group attached on meta-position of carboxyl group
on the phenyl ring shows higher nucleophilic than that on para
position, favoring to condense with tetronic acid. While the halo-
gen substitution has an orthoepara directing effect, the amino
group on the para position of chloro group shows higher reactivity
than that on meta-position, preferring to form enaminones from
the reaction with tetronic acid.
multi-component domino reactions,13ꢀ15 in this communication
we would like to report a new green chemistry approach to benzo
[f]azulen-1-one derivatives that are of chemical and biomedical
importance (Scheme 1). This reaction was achieved by reacting
benzene-1,2-diamines, tetronic acid, and aldehydes in aqueous
phase under microwave irradiation without use of any metal cat-
alyst as represented in Scheme 1.
R1
O
R1
O
2
R2
R3
NH2
NH2
O
NH
Water
O
+
R3
R2
0.1 equiv. HOAc
MW
O
N
O
H
4
1
3
1a, R2 =COOH, R3 =H; 1b, R2 =H, R3 =Cl;
1c, R2 = R3 = H; 1d, R2 = R3 = Cl
Scheme 1. The synthesis of benzoazulen-1-one derivatives.
Table 2
Regioselective synthesis of product 4aen under MW
R1
H
N
H
N
R1
Cl
O
O
COOH
O
N
H
O
N
H
2. Results and discussion
4a-4i
4j-4n
We started this methodology by subjecting 3,4-diaminobenzoic
acid 1a to the reaction with 4-chlorobenzaldehyde 2a and tetronic
acid 3 as the model case for condition optimization. As shown in
Table 1, the use of glacial acetic acid (HOAc) as reaction media at
90 ꢁC allowed the direct conversion of 3,4-diaminobenzoic acid 1a
into the corresponding benzo[f]azulen-1-ones 4a in a chemical
yield of 55% under microwave irradiation (Table 1, entry 4). Other
organic solvents, such as benzene, DCE, DMF, THF, ethanol and
glycol gave much lower yields of 10%e45% at the same temperature
(Table 1, entries 1e3); this is due to the fact that the benzo[d]im-
idazoles 5 were generated as by-products. Since water is an effi-
cient absorber for microwave irradiation, it often leads to many
successful reactions under environmentally friendly conditions.17,18
Under this aqueous system, the three-component reaction of 1a
with 2a and 3 resulted in benzo[f]azulen-1-ones 4a with a chemical
yield of 51%. The reaction proceeded rapidly to completion at 110 ꢁC
within a few minutes. Increasing reaction temperature did not
improve chemical yields. Pleasantly, we found that a higher yield of
4a (86%) was obtained when the reaction was conducted in pres-
ence of 0.1 equiv of HOAc at 110 ꢁC.
Entry
4
R1
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4-Chlorophenyl (2a)
4-Bromophenyl (2b)
2,4-Dichlorophenyl (2c)
4-Nitrophenyl (2d)
4-Methylphenyl (2e)
4-Methoxyphenyl (2f)
2,3-Dimethoxyphenyl (2g)
2-Thienyl (2h)
Benzyl (2i)
4-Chlorophenyl (2a)
2,4-Dichlorophenyl (2b)
4-Methylphenyl (2e)
2-Thienyl (2h)
12
12
12
11
15
15
15
12
16
10
10
13
11
15
86
85
83
89
83
81
78
74
70
87
84
81
80
76
9
10
11
12
13
14
Benzyl (2i)
After we achieved the above mono-substituted benzene-
1,2-diamine-based multi-component reaction, we then subjected
symmetric benzene-1,2-diamine (including 1c and 1d) to the re-
action with aromatic aldehydes 2 and tetronic acid under the
similar conditions. As shown in Table 3, the corresponding products
4 were generated in good to excellent yields of 81e92% (Scheme 2).
The reaction is compatible with various substrates including alde-
hydes with aromatic, heteroaromatic, and aliphatic ones and aro-
matic diamine component with both Cl and COOH substituents. The
products have been unambiguously determined by X-ray structural
analysis of single crystals of 4g and 4u, which were obtained by
carefully evaporating solvents (Figs. 1 and 2).
Table 1
Optimization of solvent and temperature for the synthesis of 4a
Entry
Solvent
T (ꢁC)
Time (min)
Yield (%)
4a
5
1
2
3
4
5
6
7
8
Benzene
DCE
THF
90
90
90
90
90
90
90
90
16
16
16
16
16
16
14
16
10
15
24
34
45
40
55
51
61
57
48
26
21
24
Trace
Trace
DMF
EtOH
Glycol
HOAc
Water
To expand the substrate scope of this reaction, the 2-for-
mylbenzoic acid 2v and 2-formyl-4,5-dimethoxybenzoic acid 2w
were employed to react with benzene-1,2-diamine (1c, 1d, or
4,5-dimethylbenzene-1,2-diamine 1e)andtetronicacid3(Scheme3).
To our delight, under the above optimized conditions, these reactions
proceeded smoothly to give pentacyclic isoindole-fused furo[1,4]
diazepines 5aef in good to excellent yields (Table 4, entries 1e6).
Excellent regioselectivity was observed in this three-component re-
action involving 3,4-diaminobenzoic acid and 2-formylbenzoic acid
(Table 4, entries 7 and 8). It is worth noting that this result is signifi-
cant with no literature precedent regarding the synthesis of highly
functionalized isoindole-fused furo[1,4]diazepines.
We then investigated the substrate scope of this reaction by
subjecting a series of aromatic aldehyde 2bei to the reaction with
3,4-diaminobenzoic acid 1a under the optimal condition. As shown
in Table 2, the reaction of thiophene-2-carbaldehyde with
3,4-diaminobenzoic acid 1a was finished within 12 min to give
thienyl-substituted benzo[f]azulen-1-ones 4h in 85% yield. Simi-
larly, benzo[f]azulen-1-ones 4beg were formed within 12e15 min
in good to excellent yields of 74e89% (Table 2, entries 2e7).
Moreover, aliphatic aldehydes, such as 2-phenylacetaldehyde
Similar to our previousmulti-component dominoprocesses,13 the
present reaction also showed the following attractive characteristics:

S.-L. Wang et al. / Tetrahedron 67 (2011) 4485e4493
4487
Table 3
Synthesis of products 4oell under MW
H
N
R1
R1
H
N
Cl
Cl
O
O
O
N
H
O
N
H
4t-4ll
4o-4s
Entry
4
R1
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
4o
4p
4q
4r
4s
4t
4u
4v
2,4-Dichlorophenyl (2c)
4-Nitrophenyl (2d)
4-Methylphenyl (2e)
2-Thienyl (2h)
10
9
13
12
15
9
9
8
7
9
81
83
78
80
75
86
86
88
85
84
87
89
83
82
79
76
73
79
73
72
70
72
76
75
Benzyl (2i)
4-Chlorophenyl (2a)
4-Bromophenyl (2b)
2,4-Dichlorophenyl (2c)
4-Nitrophenyl (2d)
2-Chlorophenyl (2j)
3-Nitrophenyl (2k)
4-Cyanophenyl (2l)
Phenyl (2m)
4-Methylphenyl (2e)
2-Methoxyphenyl (2n)
3,4,5-Trimethoxyphenyl (2o)
4-Dimethylaminophenyl (2p)
2-Thienyl (2h)
9
4w
4x
4y
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
7
8
4z
4aa
4bb
4cc
4dd
4ee
4ff
4gg
4hh
4ii
11
12
12
15
14
11
15
16
16
17
17
16
Fig. 2. ORTEP diagram of 4u.
Benzyl (2i)
Isobutyl (2q)
sec-Butyl (2r)
1-Methylbutyl (2s)
Cyclohexyl (2t)
R4
4jj
4kk
4ll
R4
R4
Isopropyl (2u)
R4
N
COOH
CHO
2
O
O
R2
R3
NH2
NH2
O
Water
O
R1
O
+
R3
R1
0.1 equiv. HOAc
MW
O
N
R1
H
N
NH
R3
O
O
R2
H
5
2a
N
O
R2
R3
NH2
NH2
R3
R2
O
MW
1
3
+
+
O
N
Scheme 3.
H
O
R2
4a
1a
3
5
chemistry;19ꢀ20 (4) readily available starting materials of aldehydes,
substituted benzene-1,2-diamine and tetronic acid.
R
1 = 4-Chlorophenyl, R2 = COOH, R3 =H,
In according to a similar mechanism,12 the formation of 4 is
likely to proceed via initial condensation of benzene-1,2-diamine
1 and tetronic acid 3 to give enaminone 6. The following addition
of aldehydes 2 to enaminone 6 furnishes the formation of in-
termediate 7, which is then converted into the final product
4 through intramolecular cyclization (Scheme 4). The carbonyl
substituent on the aromatic ring 2 was dehydrated upon the
treatment with amino group, leading to the formation of penta-
cyclic isoindole-fused furo[1,4]diazepines. Based on this mecha-
nism, the regioselectivity is controlled by the strong nucleophilicity
of amino group on starting material 1, i.e., the formation of 4aen
depends on the higher nucleophilicity of the amino group in the
meta-position of carboxyl group than in that on para position.
Scheme 2.
Table 4
Synthesis of products 5 under MW
Fig. 1. ORTEP diagram of 4g.
Entry
Product
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
5a, R4¼R2¼R3¼H
15
18
20
24
18
18
15
16
85
83
88
86
84
82
81
80
5b, R4¼OMe, R2¼R3¼H
5c, R4¼H, R2¼R3¼Me
(1) fast reaction rates, which enable the reaction to be completed
within 7e17 min, which can save energy and manpower for future
industrial production; (2) the environmentally friendly process in
which water is used as a solvent; (3) the convenient work-up, which
only needs simple filtration since the products directly precipitate
out after the reaction is finished, which belongs to GAP
5d, R4¼OMe, R2¼R3¼Me
5e, R4¼H, R2¼R3¼Cl
5f, R4¼OMe, R2¼R3¼Cl
5g, R4¼H, R2¼COOH, R3¼H
5h, R4¼OMe, R2¼COOH, R3¼H

4488
S.-L. Wang et al. / Tetrahedron 67 (2011) 4485e4493
O
O
temperature, filtered to give the crude product, which was further
washed by 50% EtOH to give pure product 4a.
O
O
O
3
R1
H
H2N
R3
R2
R2
R3
NH2
NH2
2
4.2.1. 10-(4-Chlorophenyl)-1-oxo-3,4,9,10-tetrahydro-1H-2-oxa-4,9-
diaza-benzo[f]azulene-6-carboxylic acid 4a. Pale white solid, mp:
281e282 ꢁC; IR (KBr): 3373, 3323, 3134, 1725, 1691,1672,1601,1571,
O
N
H
1
6
1390, 1197, 1164, 1133, 1051, 1012, 832, 820 cmꢀ1
;
1H NMR
R1
H
R1
H
R1
O
O
(400 MHz, DMSO-d6): 12.53 (s, 1H, COOH), 10.10 (s, 1H, NH), 7.57 (d,
J¼1.6 Hz, 1H, ArH), 7.31e7.27 (m, 3H, ArH), 7.16 (d, J¼8.8 Hz, 2H,
ArH), 6.71e6.68 (m, 2H, ArH and NH), 5.08 (d, J¼4.4 Hz, 1H, CH),
4.91 (s, 2H, CH2). HRMS (ESI) m/z: calcd for [MþHþ] C18H14ClN2O4:
357.0637; found: 357.0649.
N
N
R3
R2
R3
R3
R2
HN
_
O
O
H
R2
R4
O
N
H
N
H
O
N
H
7
4
R4
R4
R4
R1
=
4.2.2. 10-(4-Bromophenyl)-1-oxo-3,4,9,10-tetrahydro-1H-benzo[b]
furo[3,4-e][1,4]diazepine-6-carboxylic acid 4b. Pale white solid, mp:
272e273 ꢁC; IR (KBr): 3360, 3294,1726,1705,1650,1570,1516,1505,
O
HOOC
-H2O
O
O
N
R3
R2
1418, 1406, 1357, 1232, 1184, 1125, 1111, 1039, 1008, 827 cmꢀ1 1H
;
N
NMR (400 MHz, DMSO-d6): 12.55 (s, 1H, COOH), 10.10 (s, 1H, NH),
7.58 (1H, d, J¼1.6 Hz, ArH), 7.41 (2H, d, J¼8.4 Hz, ArH), 7.30 (dd, J¼1.6,
16.0 Hz, 1H, ArH), 7.10 (d, J¼8.4 Hz, 2H, ArH) 6.71e6.69 (m, 2H, ArH
and NH), 5.07 (d, J¼4.4 Hz,1H, CH), 4.91 (s, 2H, CH2). HRMS (ESI) m/z:
calcd for [MþHþ] C18H14BrN2O4: 401.0132; found: 401.0105.
H
5
R2 = H, R3 = Cl; R2 = COOH, R3 = H; R2 = R3 = H, Cl
Scheme 4.
3. Conclusion
4.2.3. 10-(2,4-Dichlorophenyl)-1-oxo-3,4,9,10-tetrahydro-1H-benzo
[b]furo[3,4-e][1,4]diazepine-6-carboxylic acid 4c. Pale white solid,
mp: 285e287 ꢁC; IR (KBr): 3379, 3322, 1724, 1692, 1660, 1571, 1511,
1463, 1392, 1358, 1198, 1167, 1137, 1046, 880, 855, 821, 756 cmꢀ1; 1H
NMR (400 MHz, DMSO-d6): 12.58 (s, 1H, COOH), 10.21 (s, 1H, NH),
7.61 (d, J¼1.6 Hz, 2H, ArH), 7.29 (dd, J¼1.6, 16.8 Hz, 1H, ArH), 7.17
(dd, J¼2.0, 16.8 Hz, 1H, ArH), 6.83 (d, J¼8.4 Hz, 1H, ArH), 6.72 (d,
J¼8.4 Hz, 1H, ArH), 6.36 (d, J¼4.4 Hz, 1H, NH), 5.45 (d, J¼4.4 Hz, 1H,
CH), 4.94 (s, 2H, CH2). HRMS (ESI) m/z: calcd for [MþHþ]
C18H13Cl2N2O4: 391.0247; found: 391.0219.
In conclusion, a new microwave-assisted multi-component re-
action have been established to afford benzo[f]azulen-1-one and
isoindole-fused furo[1,4]diazepine derivatives that can serve as
versatile building blocks for both organic and medicinal research.
The reactions were conducted in aqueous solution under microwave
irradiation using readily available and inexpensive starting mate-
rials. The directing effects of substituents on benzene-1,2-diamine
ring have been proven to control regioselectivity efficiently. This
green synthesis shows several attractive characteristics, such as the
use of water as reaction media, concise conditions, short reaction
periods, easy work-up, and reduced waste production without the
use of any strong acids or metal promoters.
4.2.4. 10-(4-Nitrophenyl)-1-oxo-3,4,9,10-tetrahydro-1H-2-oxa-4,9-
diazabenzo[f]azulene-6-carboxylic acid 4d. Pale white solid, mp:
>300 ꢁC; IR (KBr): 3358, 3316, 3137,1727,1686,1667,1602,1572,1521,
1509, 1240, 1199, 1185, 1163, 1129, 1049, 1017, 820 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 12.58 (s, 1H, COOH), 10.21 (s, 1H, NH), 8.10 (d,
J¼8.8Hz,1H,ArH), 7.62(s,1H,ArH), 7.41(d, J¼8.8Hz,2H,ArH), 7.31(d,
J¼8.4Hz, 1H, ArH), 6.84 (d, J¼4.4 Hz, 1H, NH), 6.72 (d, J¼8.4 Hz, 1H,
ArH), 5.21 (d, J¼4.0 Hz,1H, CH), 4.94 (s, 2H, CH2); 13C NMR (100 MHz,
4. Experimental section
4.1. General
DMSO-d6, 25 ꢁC) (
d, ppm): 172.9,167.3,159.2,151.7,146.8,141.3,130.4,
Microwave irradiation was carried out with microwave oven
EmrysÔ Creator from Personal Chemistry, Uppsala, Sweden. Melt-
ing points were determined in open capillaries and were un-
corrected. IR spectra were taken on an FT-IR-Tensor 27
spectrometer in KBr pellets and reported in cmꢀ1. 1H NMR spectra
were measured on a Bruker DPX 400 MHz spectrometer in DMSO-
128.6,124.8,124.0,122.5,122.5,121.8, 96.0, 66.7, 57.0. HRMS(ESI)m/z:
calcd for [MþHþ] C18H14N3O6: 368.0878; found: 368.0865.
4.2.5. 1-Oxo-10-p-tolyl-3,4,9,10-tetrahydro-1H-2-oxa-4,9-dia-
zabenzo[f]azulene-6-carboxylic acid 4e. Pale white solid, mp:
278e280 ꢁC; IR (KBr): 3361, 1724, 1702, 1650, 1570, 1513, 1359, 1186,
d6 with chemical shift (d) given in parts per million relative to TMS
1170, 1123, 1039, 1008, 754 cmꢀ1 1H NMR (400 MHz, DMSO-d6):
;
as internal standard. HRMS (ESI) was determined by using
microTOF-Q II HRMS/MS instrument (Bruker).X-ray crystallo-
graphic analysis was performed with a Siemens SMART CCD and
a Siemens P4 diffractometer.
12.49 (s, 1H, COOH), 10.02 (s, 1H, NH), 7.56 (s, 1H, ArH), 7.28 (d,
J¼8.0 Hz, 1H, ArH), 7.02 (t, J¼8.4 Hz, 4H, ArH), 6.69 (d, J¼8.4 Hz, 1H,
ArH), 6.65 (d, J¼4.0 Hz, 1H, NH), 5.05 (d, J¼4.0 Hz, 1H, CH), 4.90 (s,
2H, CH2), 2.19 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d,
ppm): 173.1, 167.3, 158.7, 142.2, 141.2, 136.3, 130.5, 129.2, 127.2,
124.6, 122.7, 122.4, 121.5, 97.3, 66.5, 57.1, 21.0. HRMS (ESI) m/z: calcd
for [MþNaþ] C19H16NaN2O4: 359.1003; found: 359.0991.
4.2. General procedure for the synthesis of benzo[f]azulen-1-
ones 4a
In a 10-mL reaction vial, the benzene-1,2-diamine 1a (1 mmol),
tetronic acid 3 (1 mmol), acetic acid (0.1 mmol), and water (2 mL)
were mixed and then stirred for 30 min. Subsequently, the alde-
hydes 2a (1 mmol) was added to the reaction mixture, and the
reaction vial was capped and pre-stiring for 20 s. The mixture was
subjected to microwave irradiation at 200 W (initial power 100 W,
maximum power 200 W) at 110 ꢁC, for a given time. Upon com-
pletion, monitored by TLC, the reaction mixture was cooled to room
4.2.6. 10-(4-Methoxyphenyl)-1-oxo-3,4,9,10-tetrahydro-1H-benzo[b]
furo[3,4-e][1,4]diazepine-6-carboxylic acid 4f. Pale white solid, mp:
251e253 ꢁC; IR (KBr): 3361, 3079, 1724, 1651, 1570, 1511, 1410, 1347,
1252, 1177, 1114, 1038, 1008, 831, 760 cmꢀ1 1H NMR (400 MHz,
;
DMSO-d6): 12.46 (s, 1H, COOH), 10.02 (s, 1H, NH), 7.55 (d, 1H,
J¼1.6 Hz, ArH), 7.27 (dd, J¼1.6, 16.8 Hz, 1H, ArH), 7.05 (d, J¼8.8 Hz,
2H, ArH), 6.75 (d, J¼8.8 Hz, 1H, ArH), 6.68 (d, J¼8.4 Hz, 1H, ArH),
6.63 (d, J¼4.4 Hz, 1H, NH), 5.02 (d, J¼4.4 Hz, 1H, CH), 4.89 (s, 2H,

S.-L. Wang et al. / Tetrahedron 67 (2011) 4485e4493
4489
CH2), 3.65 (s, 3H, CH3). HRMS (ESI) m/z: calcd for [MþHþ]
(s, 3H, CH3). HRMS (ESI) m/z: calcd for [MþHþ] C18H16ClN2O2:
C19H17N2O5: 353.1132; found: 353.1119.
327.0895; found: 327.0878.
4.2.7. 10-(2,3-Dimethoxyphenyl)-1-oxo-3,4,9,10-tetrahydro-1H-
benzo[b]furo[3,4-e][1,4]diazepine-6-carboxylic acid 4g. Pale white
solid, mp: >300 ꢁC; IR (KBr): 3366, 3326, 3250, 3074, 2973, 1720,
1643, 1574, 1514, 1484, 1415, 1393, 1348, 1280, 1259, 1053, 1041,
4.2.13. 7-Chloro-10-(2-methoxyphenyl)-3,4,9,10-tetrahydro-1H-
benzo[b]furo[3,4-e][1,4]diazepin-1-one 4m. Pale white solid, mp:
248e251 ꢁC; IR (KBr): 3357, 3248, 3154, 1717, 1672, 1617, 1572, 1503,
1408, 1368, 1064, 1053, 1013, 1000, 777 cmꢀ1 1H NMR (400 MHz,
;
1000, 852 cmꢀ1
;
1H NMR (400 MHz, DMSO-d6): 12.51 (s, 1H,
DMSO-d6): 9.96 (s, 1H, NH), 7.18e7.12 (m, 1H, ArH), 7.00 (d,
J¼8.0 Hz, 1H, ArH), 6.87 (d, J¼8.4 Hz, 1H, ArH), 6.75 (dd, J¼8.4,
2.0 Hz, 1H, ArH), 6.68e6.60 (m, 3H, ArH), 5.75 (d, J¼4.4 Hz, 1H, NH),
5.34 (d, J¼4.4 Hz, 1H, CH), 4.98e4.89 (m, 2H, CH2), 3.90 (s, 3H, CH3).
HRMS (ESI) m/z: calcd for [MþNaþ] C18H15ClN2O3Na 365.0664;
found: 365.0654.
COOH), 10.10 (s, 1H, NH), 7.60 (d, 1H, J¼1.6 Hz, ArH), 7.25 (dd, J¼2.0,
16.4 Hz, 1H, ArH), 6.86e6.83 (m, 1H, ArH), 6.77 (t, J¼8.0 Hz, 1H,
ArH), 6.66 (d, J¼8.4 Hz, 1H, ArH), 6.26e6.24 (m, 1H, ArH), 6.12 (d,
J¼4.4 Hz, 1H, NH), 5.42 (d, J¼4.4 Hz, 1H, CH), 4.91 (s, 2H, CH2), 3.89
(s, 3H, CH3), 3.78 (s, 3H, CH3). HRMS (ESI) m/z: calcd for [MþNaþ]
C20H18NaN2O6: 405.1058; found: 405.1073.
4.2.14. 7-Chloro-10-thien-2-yl-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4n. Pale yellow solid, mp: 294e296 ꢁC; IR
(KBr): 3337, 3244, 3069, 1716, 1667, 1617, 1567, 1499, 1413, 1365,
1190,1000, 868, 849, 808 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): 9.99
(s, 1H, NH), 7.28e7.27 (m, 1H, ArH), 6.90e6.86 (m, 2H, ArH),
6.83e6.79 (m, 3H, Thienyl-H), 6.77e6.69 (m, 2H, ArH), 6.43 (d,
J¼4.4 Hz, 1H, NH), 5.27 (d, J¼4.4 Hz, 1H, CH), 4.87 (dd, J¼15.6,
20.0 Hz, 2H, CH2). HRMS (ESI) m/z: calcd for [MþHþ]
C15H12ClN2O2S: 319.0303; found: 319.0290.
4.2.8. 1-Oxo-10-thien-2-yl-3,4,9,10-tetrahydro-1H-2-oxa-4,9-dia-
zabenzo[f]azulene-6-carboxylic acid 4h. Pale white solid, mp:
285e286 ꢁC; IR (KBr): 3336, 3305, 1720, 1696, 1652, 1572, 1508,
1404, 1353, 1267, 1227, 1144, 1043, 1007, 891, 828 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 12.56 (s, 1H, COOH), 10.07 (s, 1H, NH), 7.55 (d,
J¼0.8Hz, 1H, Thienyl-H), 7.35e7.33 (m, 1H, ArH), 7.26e7.25 (m, 1H,
ArH), 6.85 (t, J¼4.0 Hz, 2H, Thienyl-H), 6.80 (d, J¼8.4 Hz, 1H, ArH),
6.77 (d, J¼4.8 Hz, 1H, NH), 5.30 (d, J¼4.4 Hz, 1H, CH), 4.88 (dd,
J¼15.6, 17.8 Hz, 2H, CH2). HRMS (ESI) m/z: calcd for [MþHþ]
C16H12N2NaO4S: 351.0410; found: 351.0409.
4.2.15. 10-Benzyl-7-chloro-3,4,9,10-tetrahydro-2-oxa-4,9-diaza-
benzo[f]azulen-1-one 4o. White solid, mp: 234e235 ꢁC; IR (KBr):
3379, 3276, 3107, 3027, 1721, 1637, 1569, 1496, 1490, 11,417, 1362,
4.2.9. 10-Benzyl-1-oxo-3,4,9,10-tetrahydro-1H-2-oxa-4,9-dia-
zabenzo[f]azulene-6-carboxylic acid 4i. Pale white solid, mp:
249e250 ꢁC; IR (KBr): 3524, 3350, 3299, 3132, 1688, 1637, 1573,
1516, 1497, 1422, 1353, 1277, 1252, 1231, 1190, 1129, 1047, 1027,
980 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): 12.46 (s, 1H, COOH), 9.81
(s, 1H, NH), 7.51 (d, J¼1.6 Hz, 1H, ArH), 7.37 (dd, J¼2.0, 8.0 Hz, 1H,
ArH), 7.24e7.21 (m, 2H, ArH), 7.18e7.14 (m, 1H, ArH), 7.03 (d,
J¼7.2 Hz, ArH), 6.78 (1H, d, J¼8.4 Hz, ArH), 6.22 (1H, d, J¼4.4 Hz, 2H,
NH), 4.80 (d, J¼15.2 Hz, CH2), 4.69 (d, J¼15.2 Hz, CH2), 4.15e4.11 (m,
1H, CH), 2.85e2.81 (m, 1H, CH2), 2.71e2.65 (m, 1H, CH2). HRMS
(ESI) m/z: calcd for [MþHþ] C19H17N2O4: 337.1183; found: 337.1190.
1339, 1190, 1037, 1028, 983 cmꢀ1 1H NMR (400 MHz, DMSO-d6):
;
9.77 (s,1H, NH),7.27 (t, J¼7.2 Hz, 2H, ArH), 7.19 (t, J¼7.8 Hz,1H, ArH),
7.06 (d, J¼7.2 Hz, 2H, ArH), 6.87 (d, J¼8.4 Hz, 1H, ArH), 6.82e6.78
(m, 2H, ArH), 5.87 (d, J¼4.4 Hz, 1H, NH), 4.77 (dd, J¼15.2, 20.2 Hz,
2H, CH2), 4.11e4.06 (m, 1H, CH), 2.79e2.75 (m, 1H, CH2), 2.68e2.63
(m, 1H, CH2). HRMS (ESI) m/z: calcd for [MþHþ] C18H16ClN2O2:
327.0895; found: 327.0911.
4.2.16. 6,7-Dichloro-10-(2,4-dichloro-phenyl)-3,4,9,10-tetrahydro-2-
oxa-4,9-diazabenzo[f]azulen-1-one 4p. Pale white solid, mp:
211e213 ꢁC; IR (KBr): 3371, 3242, 3074,1724,1643,1563,1483,1342,
4.2.10. 7-Chloro-10-(4-chlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-
diazabenzo[f]azulen-1-one 4j. Pale white solid, mp: 250e252 ꢁC; IR
(KBr): 3345, 3273, 3140, 3095, 1715, 1666, 1621, 1563, 1499, 1420,
1183, 1148, 1105, 1042, 1013, 879, 868 cmꢀ1 1H NMR (400 MHz,
;
DMSO-d6): 10.21 (s, 1H, NH), 7.64 (d, 1H, J¼2.0 Hz, ArH), 7.21 (dd,
J¼2.0, 16.8 Hz, 1H, ArH), 7.13 (s, 1H, ArH), 6.91 (s, 1H, ArH), 6.83 (d,
J¼8.4 Hz, 1H, ArH), 6.19 (d, J¼4.4 Hz, 1H, NH), 5.41 (d, J¼4.4 Hz, 1H,
CH), 4.95 (dd, J¼15.6, 17.4 Hz, 2H, CH2). HRMS (ESI) m/z: calcd for
[MþHþ] C17H11Cl4N2O2: 414.9570; found: 414.9551.
1398, 1363, 1186, 1057, 1031, 1014, 999, 872 cmꢀ1
;
1H NMR
(400 MHz, DMSO-d6): 10.00 (s, 1H, NH), 7.31e7.29 (m, 2H, ArH),
7.15e7.13 (m, 2H, ArH), 6.90 (d, J¼8.4 Hz, 1H, ArH), 6.80e6.78 (m,
1H, ArH), 6.68e6.67 (m,1H, ArH), 6.36 (d, J¼4.4 Hz,1H, NH), 5.05 (d,
J¼4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2). HRMS (ESI) m/z: calcd for
[MþHþ] C17H13Cl2N2O2: 347.0349; found: 347.0343.
4.2.17. 6,7-Dichloro-10-(4-nitro-phenyl)-3,4,9,10-tetrahydro-2-oxa-
4,9-diazabenzo[f]azulen-1-one4q. Pale yellow solid, mp: 296e297 ꢁC;
IR (KBr): 3367, 3256, 3093, 1721, 1647, 1570, 1518, 1488, 1405, 1348,
4.2.11. 7-Chloro-10-(2,4-dichlorophenyl)-3,4,9,10-tetrahydro-2-oxa-
1244, 1185, 1152, 1049, 1017, 875, 861 cmꢀ1 1H NMR (400 MHz,
;
4,9-diazabenzo[f]azulen-1-one
272e274 ꢁC; IR (KBr): 3387, 3274, 3088,1722,1710,1628,1569,1501,
1464, 1411, 1354, 1331, 1237, 1184, 1103, 1046, 967, 868 cmꢀ1 1H
NMR (400 MHz, DMSO-d6): 10.13 (s, 1H, NH), 7.64 (d, J¼2.0 Hz, 1H,
ArH), 7.19 (dd, J¼2.0, 8.4 Hz, 1H, ArH), 6.96 (d, J¼8.8 Hz, 1H, ArH),
6.84 (dd, J¼2.4, 8.6 Hz, 1H, ArH), 6.82 (d, J¼8.4 Hz, 1H, ArH), 6.72 (d,
J¼2.4 Hz, 1H, ArH), 6.05 (d, J¼4.4 Hz, 1H, NH), 5.41 (d, J¼4 Hz, 1H,
CH), 4.94 (s, 2H, CH2). HRMS (ESI) m/z: calcd for [MþNaþ]
C17H11Cl3N2NaO2: 402.9779; found: 402.9796.
4k. Pale
white
solid,
mp:
DMSO-d6): 10.21 (s, 1H, NH), 8.13 (d, J¼8.4 Hz, 2H, ArH), 7.40
(d, J¼8.8 Hz, 2H, ArH), 7.12 (s, 1H, ArH), 6.89 (s, 1H, ArH), 6.64
(d, J¼4.4 Hz, 1H, NH), 5.21 (d, J¼4.0 Hz, 1H, CH), 4.96 (dd, J¼15.6,
18.6 Hz, 2H, CH2). HRMS (ESI) m/z: calcd for [MþHþ] C17H12Cl2N3O4:
392.0200; found: 392.0178.
;
4.2.18. 6,7-Dichloro-10-p-tolyl-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4r. Pale white solid, mp: 282e284 ꢁC; IR
(KBr): 3350, 3286, 3093, 1724, 1646, 1566, 1487, 1403, 1344, 1328,
1242, 1183, 1149, 1044, 1008, 873 cmꢀ1; 1H NMR (400 MHz, DMSO-
d6): 10.03 (s, 1H, NH), 7.05e6.98 (m, 5H, ArH), 6.83 (s, 1H, ArH), 6.44
(d, J¼4.4 Hz, 1H, NH), 5.01 (d, J¼4.4 Hz, 1H, CH), 4.91 (s, 2H, CH2),
2.21 (s, 3H, CH3). HRMS (ESI) m/z: calcd for [MþHþ] C18H15Cl2N2O2:
361.0506; found: 361.0495.
4.2.12. 7-Chloro-10-p-tolyl-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4l. Pale white solid, mp: 287e289 ꢁC; IR
(KBr): 3346, 3248, 3092, 1716, 1667, 1654, 1564, 1499, 1420, 1405,
1364, 1331, 1187, 1057, 1032, 998, 867 cmꢀ1 1H NMR (400 MHz,
;
DMSO-d6): 9.94 (s, 1H, NH), 7.04e6.99 (m, 4H, ArH), 6.88 (d,
J¼8.4 Hz,1H, ArH), 6.77e6.75 (m,1H, ArH), 6.66 (s,1H, ArH), 6.31 (d,
J¼4.4 Hz, 1H, NH), 5.01 (d, J¼4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2), 2.21
4.2.19. 6,7-Dichloro-10-thien-2-yl-3,4,9,10-tetrahydro-2-oxa-4,9-di-
azabenzo[f]azulen-1-one 4s. Pale white solid, mp: 261e263 ꢁC; IR

4490
S.-L. Wang et al. / Tetrahedron 67 (2011) 4485e4493
(KBr): 3335, 3247, 3096, 2943, 1718, 1665, 1639, 1561, 1487, 1407,
1342, 1255, 1227, 1177, 1143, 1039, 1006, 876 cmꢀ1 1H NMR
96.0, 66.7, 57.4. HRMS (ESI) m/z: calcd for [MþHþ] C17H14N3O4:
;
324.0979; found: 324.0956.
(400 MHz, DMSO-d6): 10.08 (s, 1H, NH), 7.29 (d, 1H, J¼5.2 Hz,
Thienyl-H), 7.06 (s, 1H, ArH), 6.96 (s, 1H, ArH), 6.88 (m, 1H, Thienyl-
H), 6.83 (d, J¼2.8 Hz, 1H, ArH), 6.55 (d, J¼4.4 Hz, 1H, NH), 5.28 (d,
J¼4.4 Hz, 1H, CH), 4.89 (dd, J¼15.2, 23.6 Hz, 2H, CH2). HRMS (ESI) m/
z: calcd for [MþNaþ] C15H10Cl2NaN2O2S: 374.9733; found: 374.9731.
4.2.25. 10-(2-Chlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4y. White solid, mp: 233e235 ꢁC; IR (KBr):
3395, 3156, 3063, 2989, 2952, 2930, 2899, 1725, 1652, 1574, 1506,
1484, 1444, 1398, 1363, 1233, 1122, 1046, 985 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 9.98 (s, 1H, NH),7.43 (d, J¼4.0 Hz, 1H, ArH),
7.16 (t, J¼7.2 Hz, 1H, ArH), 7.03 (t, J¼7.6 Hz, 1H, ArH), 6.96 (d,
J¼7.6 Hz, 1H, ArH), 6.79 (t, J¼7.6 Hz, 2H, ArH), 6.68 (t, J¼7.2 Hz, 1H,
ArH), 6.56 (d, J¼7.6 Hz, 1H, ArH), 5.63 (d, J¼4.4 Hz, 1H, NH), 5.47 (d,
J¼4.4 Hz, 1H, CH), 4.95 (s, 2H, CH2); 13C NMR (100 MHz, DMSO-d6,
4.2.20. 10-Benzyl-6,7-dichloro-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4t. White solid, mp: 276e277 ꢁC; IR (KBr):
3353, 3299, 3141, 3100, 3028, 1715, 1647, 1602, 1566, 1486, 1416,
1338, 1246, 1187, 1140, 1043, 1028, 987, 870 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 9.83 (s, 1H, NH), 7.27e7.23 (m, 2H, ArH),
7.20e7.17 (m, 1H, ArH), 7.05 (d, J¼7.2 Hz, 2H, ArH), 7.01 (s, 1H, ArH),
6.93 (s, 1H, ArH), 6.03 (d, J¼4.4 Hz, 1H, NH), 4.78 (dd, J¼15.2,
23.6 Hz, 2H, CH2), 4.12e4.08 (m, 1H, CH), 2.82e2.77 (m, 1H, CH2),
2.70e2.65 (m, 1H, CH2). HRMS (ESI) m/z: calcd for [MþHþ]
C18H15Cl2N2O2: 361.0506; found: 361.0491.
25 ꢁC) (
d, ppm): 172.8, 160.4, 140.4, 136.7, 133.7, 132.6, 130.0, 129.2,
128.0,127.1,123.7,123.6,122.0,120.0, 96.4, 66.7, 55.3. HRMS (ESI) m/
z: calcd for [MþHþ] C17H14ClN2O2: 313.0739; found: 313.0724.
4.2.26. 10-(3-Nitrophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4z. Yellow solid, mp: 252e255 ꢁC; IR (KBr):
3352, 3247, 3150, 3104, 3083,1716,1670,1617,1595,1568,1478,1454,
4.2.21. 10-(4-Chlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,5,9-tri-
azabenzo[f]azulen-1-one 4u. White solid, mp: 262e264 ꢁC; IR
(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568,
1438, 1403, 1365, 1062, 1032, 1011, 774 cmꢀ1 1H NMR (400 MHz,
;
DMSO-d6): 9.97 (s, 1H, NH), 8.09 (s, 1H, ArH), 8.00 (d, J¼8.0 Hz, 1H,
ArH), 7.55e7.47 (m, 2H, ArH), 6.94 (d, J¼7.6 Hz, 1H, ArH), 6.79e6.70
(m, 2H, ArH), 6.62 (d, J¼8.0 Hz, 1H, ArH), 6.25 (d, J¼4.4 Hz, 1H, NH),
5.22 (d,1H, J¼4 Hz, CH), 4.95 (s, 2H, CH2); 13C NMR (100 MHz, DMSO-
1508, 1478, 1390, 1365, 1062, 1052, 1032, 1011 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 9.87 (s, 1H, NH), 7.25 (d, J¼8.0 Hz, 2H, ArH),
7.15 (d, J¼8.4 Hz, 2H, ArH), 6.90 (d, J¼7.6 Hz,1H, ArH), 6.77e6.69 (m,
2H, ArH), 6.59 (d, J¼7.2 Hz, 1H, ArH), 6.09 (d, J¼4.4 Hz, 1H, NH), 5.06
(d, J¼4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2); 13C NMR (100 MHz, DMSO-
d6, 25 ꢁC) (
d, ppm): 173.2,159.9,148.1,146.4,137.1,133.9,132.2,130.0,
123.7, 123.4, 122.4, 122.2, 121.8, 120.3, 96.1, 66.7, 57.4. HRMS (ESI) m/
z: calcd for [MþHþ] C17H14N3O4: 324.0979; found: 324.0957.
d6, 25 ꢁC) (
d, ppm): 173.2, 159.5, 143.1, 137.5, 132.1, 131.7, 129.4,
128.4, 123.5, 123.4, 121.4, 120.1, 96.7, 66.6, 57.2. HRMS (ESI) m/z:
4.2.27. 4-(1-Oxo-3,4,9,10-tetrahydro-1H-2-oxa-4,9-diazabenzo[f]
azulen-10-yl)-benzonitrile 4aa. Palewhite solid, mp: 279e281 ꢁC; IR
(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1508,
calcd for [MþHþ] C17H14ClN2O2: 313.0739; found: 313.0712.
4.2.22. 10-(4-Bromophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4v. White solid, mp: >300 ꢁC; IR (KBr):
3352, 3247, 3150, 3104, 1716, 1670, 1617, 1595, 1568, 1508, 1478,
1478, 1454, 1438, 1390, 1365, 1334, 1062, 1032, 774 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 9.96 (s, 1H, NH),7.68 (d, J¼8.4 Hz, 2H, ArH),
7.32 (d, J¼8.0 Hz, 2H, ArH), 6.93 (d, J¼7.2 Hz,1H, ArH), 6.79e6.70 (m,
2H, ArH), 6.59 (d, J¼7.6 Hz, 1H, ArH), 6.22 (d, J¼4.0 Hz, 1H, NH), 5.12
(d, J¼4 Hz, 1H, CH), 4.92 (s, 2H, CH2); 13C NMR (100 MHz, DMSO-d6,
1454, 1403, 1390, 1365, 1334, 1062, 1052, 774 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 9.88 (s, 1H, NH), 7.39 (d, J¼8.0 Hz, 2H, ArH),
7.09 (d, J¼8.4 Hz, 2H, ArH), 6.90 (d, J¼7.6 Hz, 1H, ArH), 6.77e6.69
(m, 2H, ArH), 6.59 (d, J¼7.6 Hz, 1H, ArH), 6.09 (d, J¼4.4 Hz, 1H, NH),
5.04 (d, J¼4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2); 13C NMR (100 MHz,
25 ꢁC) (
d, ppm): 173.1, 159.7, 149.7, 137.2, 132.5, 132.0, 128.5, 123.6,
123.3,121.6,120.2,119.2,109.9, 96.0, 66.7, 57.6. HRMS (ESI) m/z: calcd
for [MþHþ] C18H14N3O2: 304.1081; found: 304.1071.
DMSO-d6, 25 ꢁC) (
d, ppm): 173.2, 159.5, 143.6, 137.5, 132.1, 131.3,
129.8, 123.5, 123.4, 121.4,120.2,120.1, 96.7, 66.6, 57.3. HRMS (ESI) m/
4.2.28. 10-Phenyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azu-
len-1-one 4bb. White solid, mp: 290e291 ꢁC; IR (KBr): 3352, 3247,
3150, 3104, 3083, 1716, 1670, 1617, 1595,1568,1508,1478, 1403,1390,
1334,1062,1052,1011, 774 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): 9.83
(s, 1H, NH), 7.20e7.09 (m, 5H, ArH), 6.89 (d, J¼7.8 Hz, 1H, ArH),
6.75e6.66 (m, 2H, ArH), 6.59 (d, J¼6.8 Hz, 1H, ArH), 6.07 (d, J¼4.4 Hz,
1H, NH), 5.05 (d, J¼4.4 Hz, 1H, CH), 4.90 (s, 2H, CH2); 13C NMR
z: calcd for [MþNaþ] C17H13BrNaN2O2: 379.0053; found: 379.0037.
4.2.23. 10-(2,4-Dichlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4w. White solid, mp: 204e205 ꢁC; IR (KBr):
3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568, 1508,
1478, 1403, 1390, 1365, 1334, 1062, 1032, 774 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 10.00 (s, 1H, NH),7.60 (s, 1H, ArH), 7.14 (d,
J¼8.0 Hz, 1H, ArH), 6.96 (d, J¼8 Hz, 1H, ArH), 6.81 (m, 2H, ArH), 6.71
(t, J¼7.6 Hz, 1H, ArH), 6.58 (d, J¼7.6 Hz, 1H, ArH), 5.71 (d, J¼4.0 Hz,
1H, NH), 5.41 (d, J¼4.4 Hz, 1H, CH), 4.94 (s, 2H, CH2); 13C NMR
(100 MHz, DMSO-d6, 25 ꢁC) (
d, ppm): 173.3, 159.2, 144.2, 137.8, 131.9,
128.4,127.5,127.0,123.3, 123.3, 121.1,120.0, 97.2, 66.5, 57.8. HRMS (ESI)
m/z: calcd for [MþHþ] C17H15N2O2: 279.1129; found: 279.1127.
(100 MHz, DMSO-d6, 25 ꢁC) (
d, ppm): 172.7, 160.4, 139.6, 136.6,
4.2.29. 10-p-Tolyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azu-
len-1-one 4cc. White solid, mp: 287e288 ꢁC; IR (KBr): 3351, 3246,
3202, 3149, 3102, 3083, 2965, 1717, 1645, 1639, 1568, 1509, 1487,
134.6, 132.7, 132.7, 129.3, 129.3, 127.2, 123.8, 122.2, 120.1, 96.0, 66.8,
54.8. HRMS (ESI) m/z: calcd for [MþHþ] C17H13Cl2N2O2: 347.0349;
found: 347.0347.
1387, 1197, 1061, 1033, 995, 851, 845 cmꢀ1 1H NMR (400 MHz,
;
DMSO-d6): 9.81 (s, 1H, NH), 7.00 (dd, J¼8.0, 14.4 Hz, 4H, ArH), 6.89
(d, J¼7.6 Hz, 1H, ArH), 6.74e6.66 (m, 2H, ArH), 6.58 (d, J¼7.2 Hz, 1H,
ArH), 6.03 (d, J¼4.0 Hz, 1H, NH), 5.02 (d, J¼4.0 Hz, 1H, CH), 4.89 (s,
4.2.24. 10-(4-Nitrophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4x. Yellow solid, mp: 219e220 ꢁC; IR (KBr):
3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568, 1508,
2H, CH2), 2.18 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d,
1478, 1403, 1390, 1365, 1334, 1062, 1032, 774 cmꢀ1
;
1H NMR
ppm): 173.2, 159.5, 143.6, 137.5, 132.1, 131.3, 129.8, 123.5, 123.4,
121.4, 120.2, 120.1, 96.7, 66.6, 57.3. HRMS (ESI) m/z: calcd for
[MþHþ] C18H17N2O2: 293.1285; found: 293.1279.
(400 MHz, DMSO-d6): 9.99 (s, 1H, NH), 8.08 (d, J¼8.0 Hz, 2H, ArH),
7.40 (d, J¼8.4 Hz, 2H, ArH), 6.94 (d, J¼7.6 Hz, 1H, ArH), 6.78 (t,
J¼7.2 Hz, 1H, ArH), 6.72 (d, J¼7.2 Hz, 1H, ArH), 6.61 (d, J¼7.6 Hz, 1H,
ArH), 6.26 (d, J¼4.4 Hz, 1H, NH), 5.18 (d, J¼4.4 Hz, 1H, CH), 4.94 (s,
4.2.30. 10-(2-Methoxyphenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4dd. White solid, mp: 247e259 ꢁC; IR
(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568,
2H, CH2); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d, ppm): 173.1,
159.7, 151.8, 146.7, 137.1, 132.0, 128.7, 123.7, 123.7, 123.3, 121.7, 120.3,

S.-L. Wang et al. / Tetrahedron 67 (2011) 4485e4493
4491
1508, 1478, 1438, 1403, 1390, 1062, 1052, 1032, 1011, 774 cmꢀ1
;
1H
(m, 1H, CH2), 0.88 (d, J¼6.4 Hz, 3H, CH3), 0.83 (d, J¼6.4 Hz, 3H, CH3).
HRMS (ESI) m/z: calcd for [MþNaþ] C15H18NaN2O2: 281.1261;
found: 281.1274.
NMR (400 MHz, DMSO-d6): 9.88 (s, 1H, NH), 7.39 (d, J¼8.0 Hz, 2H,
ArH), 7.09 (d, J¼8.4 Hz, 2H, ArH), 6.90 (d, J¼7.6 Hz, 1H, ArH),
6.77e6.69 (m, 2H, ArH), 6.59 (d, J¼7.6 Hz, 1H, ArH), 6.09 (d,
J¼4.4 Hz, 1H, NH), 5.04 (d, J¼4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2); 13
C
4.2.36. 10-sec-Butyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]
azulen-1-one 4jj. White solid, mp: 173e175 ꢁC; IR (KBr): 3355,
3293, 3109, 2963, 2929, 2874, 1731, 1651, 1567, 1490, 1437, 1393,
NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d, ppm): 173.2, 159.5, 143.6, 137.5,
132.1, 131.3, 129.8, 123.5, 123.4, 121.4, 120.2, 120.1, 96.7, 66.6, 57.3.
HRMS (ESI) m/z: calcd for [MþHþ] C18H17N2O3: 309.1234; found:
309.1220.
1359, 1335, 1186, 1151, 1122, 1043, 772 cmꢀ1 1H NMR (400 MHz,
;
DMSO-d6): 9.65 (s, 1H, NH), 6.90e6.84 (m, 2H, ArH), 6.82e6.78 (m,
1H, ArH), 6.75e6.72 (m, 1H, ArH), 5.83e5.80 (m, 1H, NH), 4.77 (s,
2H, CH2), 3.92e3.87 (m, 1H, CH), 3.60e3.54 (m, 1H, CH), 1.56e1.26
(m, 2H, CH2), 1.17e0.94 (m, 1H, CH), 0.81e0.72 (m, 6H, CH3). HRMS
(ESI) m/z: calcd for [MþNaþ] C15H18N2NaO2: 281.1261; found:
281.1276.
4.2.31. 10-(3,4,5-Trimethoxyphenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-
diazabenzo[f]azulen-1-one 4ee. Pale white solid, mp: 259e260 ꢁC;
IR (KBr): 3323, 3301, 3105, 2994, 2945, 2832, 1716, 1661, 1627, 1603,
1565, 1485, 1418, 1390, 1305, 1252, 1153, 1047, 783 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 9.83 (s, 1H, NH), 6.91e6.89 (m, 1H, ArH),
6.78e6.71 (m, 2H, ArH), 6.67e6.64 (m, 1H, ArH), 6.41 (s, 2H, ArH),
6.01 (d, J¼4.4 Hz, 1H, NH), 4.97 (d, J¼4.0 Hz, 1H, CH), 4.90 (d,
J¼15.6 Hz, 1H, CH2), 4.86 (d, J¼15.6 Hz, 1H, CH2), 3.58 (s, 6H, CH3),
3.55 (s, 3H, CH3). HRMS (ESI) m/z: calcd for [MþNaþ]
C20H20NaN2O5: 391.1265; found: 391.1262.
4.2.37. 10-(1-Methylbutyl)-3,4,9,10-tetrahydro-2-oxa-4,9-dia-
zabenzo[f]azulen-1-one 4kk. White solid, mp: 173e174 ꢁC; IR (KBr):
3352, 2963, 2930, 2871, 1731, 1651, 1566, 1488, 1436, 1393, 1360,
1333, 1186, 1153, 1042, 1030, 986, 772, 756 cmꢀ1
;
1H NMR
(400 MHz, DMSO-d6): 9.66 (s, 1H, NH), 6.91e6.85 (m, 2H, ArH),
6.82e6.79 (m, 1H, ArH), 6.77e6.73 (m, 1H, ArH), 5.82 (d, 1H,
J¼4.8 Hz, NH), 4.76 (m, 2H, CH2), 3.56e3.53 (m, 1H, CH), 1.51e1.26
(m, 3H, CH and CH2), 1.13e0.96 (m, 2H, CH2), 0.80e0.71 (m, 6H,
CH3). HRMS (ESI) m/z: calcd for [MþNaþ] C16H20N2NaO2: 295.1417;
found: 295.1410.
4.2.32. 10-(4-Dimethylaminophenyl)-3,4,9,10-tetrahydro-2-oxa-
4,5,9-triazabenzo[f]azulen-1-one 4ff. Pale white solid, mp:
273e276 ꢁC; IR (KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670,
1617, 1595, 1568, 1508, 1454, 1438, 1390, 1365, 1334, 1062, 1011,
774 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): 9.74 (s, 1H, NH), 6.94 (d,
J¼8.4 Hz, 2H, ArH), 6.87 (d, J¼7.2 Hz, 1H, ArH), 6.73e6.66 (m, 2H,
ArH), 6.60 (d, J¼7.2 Hz, 1H, ArH), 6.53 (d, J¼8.8 Hz, 2H, ArH), 5.94 (d,
J¼4.4 Hz, 1H, NH), 4.96 (d, J¼4.0 Hz, 1H, CH), 4.87 (s, 2H, CH2), 2.79
4.2.38. 10-Cyclohexyl-3,4,9,10-tetrahydro-2-oxa-4,9-diaza-benzo[f]
azulen-1-one 4ll. White solid, mp: 256e257 ꢁC; IR (KBr): 3483,
3350, 3325, 3058, 2934, 2853, 1731, 1706, 1654, 1616, 1565, 1508,
(s, 6H, CH3); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d, ppm): 173.4,
1486, 1434, 1393, 1191, 1178, 1041, 801 cmꢀ1 1H NMR (400 MHz,
;
158.9, 149.6, 138.2, 132.0, 128.2, 123.3, 123.2, 119.8, 112.4, 197.9, 66.4,
57.2. HRMS (ESI) m/z: calcd for [MþHþ] C19H20N3O2: 322.1551;
found: 322.1551.
DMSO-d6): 9.64 (s, 1H, NH), 6.89e6.84 (m, 2H, ArH), 6.80 (t,
J¼7.6 Hz, 1H, ArH), 6.76e6.72 (m, 1H, ArH), 5.83 (d, J¼4.8 Hz, 1H,
NH), 4.78 (d, J¼15.2 Hz, 1H, CH2), 4.73 (d, J¼15.2 Hz, 1H, CH2), 3.49
(dd, J¼4.8, 15.2 Hz,1H, CH), 1.85e1.84 (m, 1H, CH), 1.62e1.39 (m, 4H,
CH2), 1.15e0.98 (m, 4H, CH2), 0.94e0.87 (m, 2H, CH2). HRMS (ESI)
m/z: calcd for [MþHþ] C17H21N2O2: 285.1598; found: 285.1595.
4.2.33. 10-Thien-2-yl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]
azulen-1-one 4gg. Pale yellow solid, mp: 282e283 ꢁC; IR (KBr):
3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1508, 1478,
1454, 1403, 1390, 1365, 1062, 1052, 1032, 774 cmꢀ1
;
1H NMR
4.2.39. 10-Isopropyl-3,4,9,10-tetrahydro-2-oxa-4,9-diaza-benzo[f]
azulen-1-one 4mm. White solid, mp: 254e256 ꢁC; IR (KBr): 3469,
3329, 3276, 3152, 3101, 2960, 1708, 1652, 1570, 1508, 1479, 1435,
(400 MHz, DMSO-d6): 9.88 (1H, s, NH),7.39 (d, J¼8.0 Hz, 2H, ArH),
7.09 (d, J¼8.4 Hz, 2H, ArH), 6.90 (d, J¼7.6 Hz, 1H, ArH), 6.77e6.69
(m, 2H, ArH), 6.59 (d, J¼7.6 Hz, 1H, ArH), 6.09 (d, J¼4.4 Hz, 1H, NH),
5.04 (d, J¼4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2); 13C NMR (100 MHz,
1395, 1364, 1333, 1232, 1045, 998, 849 cmꢀ1 1H NMR (400 MHz,
;
DMSO-d6): 9.66 (s, 1H, NH), 6.91e6.85 (m, 2H, ArH), 6.82e6.79 (m,
1H, ArH), 6.77e6.73 (m, 1H, ArH), 5.82 (d, J¼4.8 Hz, 1H, NH), 4.77 (s,
2H, CH2), 3.46 (dd, J¼4.8, 8.4 Hz, 1H, CH), 1.53e1.44 (m, 1H, CH),
0.86 (d, J¼6.4 Hz, 3H, CH3), 0.82 (d, J¼6.8 Hz, 3H, CH3). HRMS (ESI)
m/z: calcd for [MþNaþ] C14H17N2O2: 245.1285; found: 245.1289.
DMSO-d6, 25 ꢁC) (
d, ppm): 173.0, 159.1, 148.6, 137.6, 132.1, 127.0,
125.1, 123.7, 123.5, 121.6, 120.1, 98.2 66.5, 53.3. HRMS (ESI) m/z:
calcd for [MþNaþ] C15H12N2NaO2S: 307.0512; found: 307.0513.
4.2.34. 10-Benzyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azu-
len-1-one 4hh. White solid, mp: 229e231 ꢁC; IR (KBr): 3349, 3287,
3154, 3101, 1720, 1640, 1568, 1507, 1489, 1438, 1396, 1335, 1192,
1047, 766, 747, 702 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): 9.66 (s,1H,
NH), 7.28 (t, J¼7.4 Hz, 2H, ArH), 7.20 (t, J¼7.2 Hz, 1H, ArH), 7.09 (d,
J¼7.2 Hz, 2H, ArH), 6.90 (d, J¼7.2 Hz, 1H, ArH), 6.86e6.78 (m, 2H,
ArH), 6.72 (d, J¼7.2 Hz,1H, ArH), 5.43 (d, J¼4.0 Hz,1H, NH), 4.76 (dd,
J¼15.2, 4.0 Hz, 2H, CH2), 2.78e2.73 (m, 1H, CH2), 2.64e2.58 (m, 1H,
4.3. General procedure for the synthesis of products 5a
In a 10-mL reaction vial, the benzene-1,2-diamine 1a (1 mmol),
tetronic acid 3 (1 mmol), acetic acid (0.1 mmol), and water (2 mL)
were mixed and then stirred for 10 min. Subsequently, the 2-for-
mylbenzoic acids 2 (1 mmol) was added to the reaction mixture,
and the reaction vial was capped and pre-stirred for 20 s. The
mixture was subjected to microwave irradiation at 200 W (initial
power 100 W, maximum power 200 W) at 150 ꢁC, for 15 min. Upon
completion, monitored by TLC, the reaction mixture was cooled to
room temperature, filtered to give the crude product, which was
further washed by 50% EtOH to give pure product 5a.
CH2); 13C NMR (100 MHz, DMSO-d6 25 ꢁC) (
d, ppm): 173.1, 158.5,
139.1, 137.3, 131.8, 129.8, 128.7, 126.6, 123.7, 123.2, 121.0, 120.1, 98.6,
66.5, 55.7, 44.3. HRMS (ESI) m/z: calcd for [MþHþ] C18H17N2O2:
293.1285; found: 293.1287.
4.2.35. 10-Isobutyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azu-
len-1-one 4ii. White solid, mp: 208e210 ꢁC; IR (KBr): 3346, 2952,
2926,1737,1666,1560,1502,1475,1390,1363,1337,1186,1030,1011,
969, 758, 647 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): 9.64 (s, 1H, NH),
6.88 (d, J¼7.2 Hz, 2H, ArH), 6.83e6.76 (m, 2H, ArH), 5.69 (d,
J¼4.4 Hz, 1H, NH), 4.77 (dd, J¼15.2, 18.8 Hz, 2H, CH2), 3.92e3.87 (m,
1H, CH), 1.72e1.65 (m, 1H, CH), 1.28e1.22 (m, 1H, CH2), 1.12e1.05
4.3.1. 4bH-Benzo[2,3]furo[30,40:5,6][1,4]diazepino[7,1-a]isoindole-
5,14(7H,8H)-dione 5a. White solid, mp: 286e289 ꢁC; IR (KBr): 3277,
3220, 3147, 3108, 1734, 1704, 1688, 1730, 1595, 1543, 1506, 1397,
1348, 1194, 1045, 1023, 766 cmꢀ1 1H NMR (400 MHz, DMSO-d6):
;
9.99 (s, 1H, NH), 8.41 (d, 1H, J¼8.0 Hz, ArH), 7.78 (d, 1H, J¼7.6 Hz,
ArH), 7.70e7.66 (m, 1H, ArH), 7.59e7.55 (m, 1H, ArH), 7.40e7.34 (m,

4492
S.-L. Wang et al. / Tetrahedron 67 (2011) 4485e4493
2H, ArH), 7.21e7.14 (m, 2H, ArH), 5.74 (s, 1H, CH), 4.83 (d, J¼15.2 Hz,
1H, CH2), 4.78 (d, J¼15.2 Hz, 1H, CH2); 13C NMR (100 MHz, DMSO-
HRMS (ESI) m/z: calcd for [MꢀHþ] C20H13Cl2N2O5: 432.0196;
found: 432.0199.
d6, 25 ꢁC) (
d, ppm): 171.8, 165.8, 158.5, 143.9, 136.8, 131.6, 130.7,
130.6, 128.8, 128.2, 126.3, 123.3, 123.1, 119.4, 94.4, 66.6, 59.3. HRMS
4.3.7. 5,14-Dioxo-5,7,8,14-tetrahydro-4bH-benzo[2,3]furo[30,40:5,6]
[1,4]diazepino[7,1-a]isoindole-10-carboxylic acid 5g. Pale white
solid, mp: >300 ꢁC; IR (KBr): 3340, 3116,1748,1701,1687,1616,1562,
(ESI) m/z: calcd for [MꢀHþ] C18H11N2O3:303.0764; found: 303.0761.
4.3.2. 1,2-Dimethoxy-4bH-benzo[2,3]furo[30,40:5,6][1,4]diazepino
1516, 1404, 1390, 1342, 1268, 1314, 1182, 1058, 1023, 771 cmꢀ1 1H
;
[7,1-a]isoindole-5,14(7H,8H)-dione
291e293 ꢁC; IR (KBr): 3251, 3201, 3141, 3092,1752,1677,1655,1596,
1557, 1497, 1376, 1337, 1272, 1062, 1040, 1011, 773 cmꢀ1 1H NMR
5b. White
solid,
mp:
NMR (400 MHz, DMSO-d6): 13.21 (s, 1H, COOH), 10.17 (s, 1H, NH),
8.43 (d, 1H, J¼7.6 Hz, ArH), 7.83 (d, 1H, J¼2.0 Hz, ArH), 7.80 (d, 1H,
J¼7.6 Hz, ArH), 7.73e7.68 (m, 2H, ArH), 7.61e7.57 (m, 1H, ArH), 7.52
(d, 1H, J¼8.0 Hz, ArH), 5.80 (s, 1H, CH), 4.90 (d, J¼15.2 Hz, 1H, CH2),
;
(400 MHz, DMSO-d6): 9.93 (s, 1H, NH), 8.06 (d, 1H, J¼8.4 Hz, ArH),
7.37e7.32 (m, 3H, ArH), 7.19e7.13 (m, 2H, ArH), 5.58 (s,1H, CH), 4.87
(d, J¼15.2 Hz, CH2), 4.83 (d, J¼15.2 Hz, CH2), 4.87 (d, J¼15.2 Hz, 1H,
CH2), 4.85 (d, J¼15.2 Hz, 1H, CH2), 3.85 (s, 3H, OCH3), 3.83 (s, 3H,
4.81 (d, J¼15.2 Hz,1H, CH2); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d,
ppm): 171.6,166.4,165.9,158.3,143.9,136.7,135.9,131.9,131.0,130.4,
130.3,130.0,128.9,126.4,123.4,120.5, 94.7, 66.5, 59.2. HRMS (ESI) m/
z: calcd for [MꢀHþ] C19H11N2O5: 347.0662; found: 347.0659.
OCH3); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d, ppm): 171.8, 163.9,
158.3, 152.4, 146.3, 137.1,136.8,130.9,128.1,126.4,123.0,121.6,119.4,
116.8, 95.1, 66.5, 61.6, 58.0, 56.4. HRMS (ESI) m/z: calcd for [MꢀHþ]
C20H15N2O5:363.0975; found: 363.0976.
4.3.8. 1,2-Dimethoxy-5,14-dioxo-5,7,8,14-tetrahydro-4bH-benzo[2,3]
furo[30,40:5,6][1,4]diazepino[7,1-a]isoindole-10-carboxylic
acid
5h. Pale white solid, mp: 277e280 ꢁC; IR (KBr): 3313, 3138, 1750,
1689,1672,1558,1499,1400,1275,1061,1047, 783, 774, 755 cmꢀ1; 1H
NMR (400 MHz, DMSO-d6): 13.18 (s,1H, COOH),10.11 (s,1H, NH), 8.08
(d, 1H, J¼8.4 Hz, ArH), 7.81 (s, 1H, ArH), 7.68e7.66 (m, 1H, ArH),
7.51e7.49 (m, 1H, ArH), 7.38 (d, 1H, J¼8.4 Hz, ArH), 5.62 (s, 1H, CH),
4.89 (d, J¼15.2 Hz, 1H, CH2), 4.78 (d, J¼15.2 Hz, 1H, CH2), 3.85 (s, 3H,
4.3.3. 10,11-Dimethyl-4bH-benzo[2,3]furo[30,40:5,6][1,4]diazepino
[7,1-a]isoindole-5,14(7H,8H)-dione 5c. White solid, mp: >300 ꢁC; IR
(KBr): 3270, 3186, 3124, 3082, 1753, 1687, 1653, 1614, 1510, 1398,
1362, 1340, 1211, 1195, 1141, 1115, 1065, 1024, 760 cmꢀ1 1H NMR
;
(400 MHz, DMSO-d6): 9.94 (s, 1H, NH), 8.40 (d, 1H, J¼7.6 Hz, ArH),
7.75 (d, 1H, J¼7.2 Hz, ArH), 7.67 (t, 1H, J¼7.6 Hz, ArH), 7.58e7.54 (m,
1H, ArH), 7.14 (s, 1H, ArH), 6.95 (s, 1H, ArH), 5.67 (s, 1H, CH), 4.84 (d,
J¼15.2 Hz, 1H, CH2), 4.74 (d, J¼15.2 Hz, 1H, CH2), 2.24 (s, 3H, CH3),
2.20 (s, 3H, CH3). HRMS (ESI) m/z: calcd for [MꢀHþ]
C20H15N2O3:331.1077; found: 331.1075.
OCH3), 3.84 (s, 3H, OCH3); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d,
ppm): 171.7, 166.4, 163.9, 158.1, 152.4, 146.4, 136.9, 136.7, 131.1, 130.3,
130.1,123.3,122.8,121.7,120.5,117.0, 95.2, 66.5, 61.6, 57.8, 56.4. HRMS
(ESI) m/z: calcd for [MꢀHþ] C21H15N2O7: 407.0874; found: 407.0880.
Crystal data for 4g: C26H32N4O8, pale white, crystal dimen-
sion 0.40ꢂ0.35ꢂ0.14 mm, monoclinic, space group P2(1)/c,
4.3.4. 1,2-Dimethoxy-10,11-dimethyl-4bH-benzo[2,3]furo[30,40:5,6]
[1,4]diazepino[7,1-a]isoindole-5,14(7H,8H)-dione 5d. White solid,
mp: >300 ꢁC; IR (KBr): 3255, 3196, 3127, 3088, 3001, 1749, 1682,
a¼11.9237(11) A, b¼14.1491(13) A, c¼16.7626(14) A,
¼
g
¼90 ꢁC,
ꢀ
ꢀ
3
ꢀ
ꢀ
a
ꢁ
b
¼99.5980(10) C, V¼2788.4(4) A , Mr¼528.56, Z¼4, Dc¼1.259 Mg/
m3,
l
¼0.71073,
m
(Mo K
a
)¼0.094 mmꢀ1, F (000)¼1120, R¼0.0552,
1667, 1620, 1557, 1448, 1400, 1270, 1197, 1117, 1060, 1015, 958 cmꢀ1
;
wR2¼0.1182, S¼1.036, largest diff. Peak andhole: 0.508 and ꢀ0.324 e/
3
ꢀ
1H NMR (400 MHz, DMSO-d6): 9.77 (s, 1H, NH), 8.05 (d, J¼8.4 Hz,
1H, ArH), 7.34 (d, J¼8.4 Hz, 1H, ArH), 7.11 (s, 1H, ArH), 6.93 (s, 1H,
ArH), 5.51 (s, 1H, CH), 4.83 (d, J¼15.2 Hz, 1H, CH2), 4.72 (d,
J¼15.2 Hz, 1H, CH2), 3.84 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 2.23 (s,
A . CCDC-823409 contains the supplementary crystallographic data
for this paper.
Crystal data for 4u: C17H13BrN2O2, pale white, crystal dimen-
sion 0.35ꢂ0.20ꢂ0.11 mm, monoclinic, space group P2(1)/c,
3H, CH3), 2.20 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d
,
a¼14.6324(15) A, b¼12.0632(12) A, c¼8.5627(9) A,
¼g
¼90 ꢁC,
ꢀ
ꢀ
ꢀ
a
3
ꢀ
ppm): 171.9, 163.9, 158.4, 152.3, 146.2, 138.8, 136.4, 134.5, 131.1,
131.0, 123.8, 123.0, 121.6, 120.0, 116.6, 94.4, 66.4, 61.6, 58.0, 56, 4,
19.1, 18.5. HRMS (ESI) m/z: calcd for [MꢀHþ] C22H19N2O5: 391.1288;
found: 391.1284.
b
¼94.7470(10) ꢁC, V¼1506.2(3) A , Mr¼357.20, Z¼4, Dc¼1.575 Mg/
m3,
l¼0.71073,
m
(Mo K
a
)¼2.737 mmꢀ1, F (000)¼720, R¼0.0320,
wR2¼0.0630, S¼1.011, largest diff. Peak and hole: 0.279 and
3
ꢀ
ꢀ0.343 e/A . CCDC-823410 contains the supplementary crystallo-
graphic data for this paper.
4.3.5. 10,11-Dichloro-4bH-benzo[2,3]furo[30,40:5,6][1,4]diazepino
[7,1-a]isoindole-5,14(7H,8H)-dione 5e. Pale white solid, mp:
>300 ꢁC; IR (KBr): 3330, 3281, 3134, 3102, 1747, 1715, 1662, 1626,
Acknowledgements
1597, 1557, 1487, 1408, 1259, 1179, 1135, 1014, 871 cmꢀ1 1H NMR
;
We are grateful for financial support from the National Science
Foundation of China (Nos. 20928001, 21072163, and 21002083),
Science Foundation in Interdisciplinary Major Research Project of
Xuzhou Normal University (No. 09XKXK01), Doctoral Research
Foundation of Xuzhou Normal Univ. (XZNU, No.10XLR20), Robert A.
Welch Foundation (D-1361), NIH (R03DA026960), and PAPD of
Jiangsu Higher Education Institutions for their generous support.
(400 MHz, DMSO-d6): 10.18 (s, 1H, NH), 8.41 (d, J¼7.6 Hz, 1H, ArH),
7.80 (d, J¼7.6 Hz,1H, ArH), 7.73e7.69 (m, 2H, ArH), 7.61e7.57 (m,1H,
ArH), 7.39 (s, 1H, ArH), 5.76 (s, 1H, CH), 4.91 (d, J¼15.2 Hz, 1H, CH2),
4.79 (d, J¼15.2 Hz,1H, CH2); 13C NMR (100 MHz, DMSO-d6, 25 ꢁC) (
d,
ppm): 171.6,165.9,157.8,143.7,137.1,132.1,132.0, 130.2,130.5,129.0,
126.3, 124.0, 123.5, 120.4, 112.7, 95.6, 66.6, 59.0. HRMS (ESI) m/z:
calcd for [MꢀHþ] C18H9Cl2N2O3: 370.9984; found: 370.9982.
Supplementary data
4.3.6. 10,11-Dichloro-1,2-dimethoxy-4bH-benzo[2,3]furo[30,40:5,6]
[1,4]diazepino[7,1-a]isoindole-5,14(7H,8H)-dione 5f. Pale white
solid, mp: 263e265 ꢁC; IR (KBr): 3249, 1747, 1681, 1672, 1592, 1537,
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2011.05.002.
1489, 1474, 1393, 1342, 1194, 1134, 1111, 1055, 1027, 742 cmꢀ1 1H
;
NMR (400 MHz, DMSO-d6): 10.10 (s, 1H, NH), 8.06 (d, J¼8.4 Hz, 1H,
ArH), 7.68 (s, 1H, ArH), 7.39e7.37 (m, 2H, ArH), 5.59 (s, 1H, CH), 4.90
(d, J¼15.2 Hz, 1H, CH2), 4.76 (d, J¼15.2 Hz, 1H, CH2), 3.85 (s, 3H,
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