Synthesis of New 3-(Furan-2-yl)-Substituted Dibenzo-Diazepin-1-one Derivatives

Article abstract of DOI:10.1002/jhet.2408

A new series of 3-(furan-2-yl) dibenzo-diazepin-1-one derivatives were synthesized by condensation of 5-(furan-2-yl)-1,3-cyclohexanedione, o-phenylenediamine, and aromatic aldehydes, in which in some of them existed two very close isomer compounds. All the compounds were characterized by IR, MS,¹H NMR, and elemental analysis. Also presented were the crystal structures of 3a, 3b and 3e, which were obtained and determined by X-ray single-crystal diffraction.

Full text of DOI:10.1002/jhet.2408

Month 2015
Synthesis of New 3-(Furan-2-yl)-Substituted Dibenzo-Diazepin-
1-one Derivatives
a
a
a
a
a
b
*
Fang-Ming Wang, Dan Bao, Ming Wang, Qing-Huan Yin, Li-Zhuang Chen, and Guang-Fan Han
aSchool of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang,
Jiangsu 212003, China
bDepartment of Chemical Engineering, Zhen Jiang College, Zhenjiang, Jiangsu 212003, China
*
E-mail: wangfmzj@just.edu.cn
Additional Supporting Information may be found in the online version of this article.
Received October 15, 2014
DOI 10.1002/jhet.2408
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
A new series of 3-(furan-2-yl) dibenzo-diazepin-1-one derivatives were synthesized by condensation of
5-(furan-2-yl)-1,3-cyclohexanedione, o-phenylenediamine, and aromatic aldehydes, in which in some of
them existed two very close isomer compounds. All the compounds were characterized by IR, MS, 1H
NMR, and elemental analysis. Also presented were the crystal structures of 3a, 3b and 3e, which were
obtained and determined by X-ray single-crystal diffraction.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
In order to add the furan group to the benzodiaze-
pine system, herein, we reported a new series of
3-(furan-2-yl)-dibenzo-diazepin-1-one derivatives, which
were synthesized by condensation of 5-(furan-2-yl)-1,3-
cyclohexanedione, o-phenylenediamine, and aromatic
aldehydes (Scheme 1). Furthermore, three single crystals
were obtained and determined by X-ray diffraction analysis.
Benzodiazepines are well-known nitrogen heterocyclic
compounds, owing to their wide range of therapeutic and
pharmacological properties, and used as anticonvulsant,
anti-anxiety, analgesic, sedative, antidepressive, hypnotic,
and anti-inflammatory agents [1–3].
Nowadays, researches on synthesis of benzodiazepines
are mainly focused on two directions. Some researchers are
interested in the preparation methods of benzodiazepine
derivatives, including the catalyst method [4–7], solid state
reaction method [8], and microwave radiation method
[9,10]. Others focused on fusing benzodiazepines with other
heterocyclic systems, such as pyrrolo-, triazole-, isoxazolo-,
pyrazolo-, or oxazino-benzodiazepines [11–13]. They
looked for strengthening or inducing new pharmacological
activities for those benzodiazepines [14–16].
As to the furyl group, it is another potential biologically
active heterocyclic functional group that has been detected
in almost all organisms, including humans [17]. Recent re-
searches showed that furan moieties are formed upon deg-
radation of natural DNA and can further react by the
addition of nucleic acid bases [18,19]. During hydroxyl
radical oxidation, the C59 of deoxyribose in DNA has been
suggested to be a putative precursor of kinetin [20–22].
RESULTS AND DISCUSSION
5-(Furan-2-yl)-1,3-cyclohexanedione prepared by con-
densation of furfural, acetone, and diethyl malonate,
according to Ref. [23], reacted with o-phenylenediamine in
toluene under reflux for 8 h to afford intermediate enamine
2 with high yield. 2 reacted with different aromatic alde-
hydes under reflux in ethanol with acetic acid as catalyst to
yield the title compounds, 3-(furan-2-yl)-dibenzo-diazepin-
1-one derivatives.
All data of MS, IR, 1H NMR, and elemental analysis are
shown in the Experimental section. In the IR spectrum of
the intermediate 2, the broad absorption bands at
3452 cm-1 were the typical absorptions of the amino group.
1
The broad peak at δ: 4.92 in its H NMR spectrum can be
attributed to the two proton shifts of the same NH2 group,
© 2015 HeteroCorporation

F.-M. Wang, D. Bao, M. Wang, Q.-H. Yen, L.-Z. Chen, and G.-F. Han
Vol 000
Scheme 1. Synthesis of 3-(furan-2-yl)-dibenzo-diazepin-1-one derivatives. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
while the single peak at δ: 8.37 was attributed to the proton
shift of the imino group.
because of the influence of the methenyl group nearby. In
the ESI-MS spectrum, the ion adducts were usually ob-
served as the primary fragment peaks for the title
compounds.
When we used the column chromatography to purify the
crude products of 3g, there obtained two very close isomer
compounds, 3g-1 and 3g-2, which were testified by the use
of MS and 1H NMR spectrum, accordingly. Because there
existed two chiral carbon atoms, C3 and C11, there maybe
existence of some isomers. As to the other compounds, 3a
to 3f, we obtained only one structure.
As shown in the IR spectrum of the title 3-(furan-2-yl)-
dibenzo-diazepin-1-ones compounds, the broad absorption
bands at 3297–3332 cm-1 were the typical absorptions of
the imino group, and the absorption bands at 1591–
1604 cm-1 should be attributed to the absorptions of the
1
carbonyl group (C = O). In their H NMR spectrum, the
single peaks at δ: 8.84–9.09 were attributed to the proton
shifts of the imino group at 5-position. And the peaks at
δ: 5.92–6.52 should be attributed to the 10-imino group
Table 1
Crystallographic data for compounds 3a, 3b, and 3e.
3a
3b
3e
Empirical formula
CCDC No.
Formula weight
C
23H19 N2O2Cl
C23H21N2O3Cl
1009589
408.87
C24H22N2O3
1009590
386.44
1009588
390.85
Temperature
Wavelength
291(2) K
0.71073 Å
291(2) K
0.71073 Å
291(2) K
0.71073 Å
Crystal system and space group
Unit cell dimensions
Orthorhombic and Pbca
a = 12.399(3) Å
b = 13.886(3) Å
c = 21.879(5) Å
α = β = γ = 90°
Monoclinic and P21/c
a = 14.2967(11) Å
b = 8.0027(6) Å
c = 18.5928(15) Å
α = γ = 90°
Monoclinic and P21/c
a = 11.3413(13) Å
b = 19.154(2) Å
c = 9.2622(11) Å
α = γ = 90°
β = 105.6100(10)°
β = 106.585(2)°
Volume
3767.1(16) Å3
2048.8(3) Å3
1928.4(4) Å3
Z
8
4
4
Calculated density
Absorption coefficient
F(000)
1.378 g · cm-3
1.326 g · cm-3
1.331 g · cm-3
0.225 mm-1
1632
0.213 mm-1
856
0.088 mm-1
816
Crystal size
Theta range for data collection
Limiting indices
0.25 × 0.20 × 0.18 mm
1.86–26.00°
0.25 × 0.18 × 0.15 mm
1.48–25.00°
0.25 × 0.15 × 0.10 mm
2.13–25.00°
À15 ≤ h ≤ 15, À16 ≤ k ≤17,
À17 ≤ h ≤ 15, À9 ≤ k ≤9,
À13 ⩽ h ⩽ 7,À15 ⩽ k ⩽ 22,
À26 ≤ l ≤ 26
À22 ⩽ l ⩽ 18
À7 ⩽ l ⩽ 11
Reflections collected/unique
Completeness to theta = 25.00
Max. and min. transmission
Refinement method
27353/3694 ( Rint = 0.0252)
99.9%
11001/3589 ( Rint = 0.0257)
99.4%
7215/3316 ( Rint = 0.0476)
97.5%
0.960 and 0.948
Full-matrix least-squares on F2
3694/0/253
0.9687 and 0.9586
Full-matrix least-squares on F2
3589/0/262
0.990 and 0.984
Full-matrix least-squares on F2
3316/4/262
Data/restraints/parameters
Goodness-of-fit on F2
1.020
1.045
1.019
Final R indices [I > 2sigma(I)]
R indices (all data)
Largest diff. peak and hole
R1 = 0.0593 and wR2 = 0.1634
R1 = 0.0741 and wR2 = 0.1777
0.483 and À0.499 e. Å-3
R1 = 0.0620 and wR2 = 0.1869
R1 = 0.0847 and wR2 = 0.2038
0.741 and À0.391 e. Å-3
R1 = 0.0615 and wR2 = 0.1501
R1 = 0.0945 and wR2 = 0.1617
0.370 and À0.359 e. Å-3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis of 3-(Furan-2-yl)-Substituted Dibenzo-Diazepin-1-ones
(i)
(ii)
(iii)
Figure 1. ORTEP of compounds 3a(i), 3b(ii), and 3e(iii) showing 30% probability ellipsoids. [Color figure can be viewed in the online issue, which is
available at wileyonlinelibrary.com.]
Table 2
Selected Bond lengths (Å) and Bond Angles (°).
Compound 3a
Bond
Distance
1.353(3)
1.377(3)
1.505(4)
(°)
126.9(2)
112.5(2)
118.9(2)
Bond
C(7)–N(2)
C(8)–C(9)
Distance
1.479(3)
1.394(4)
Bond
C(8)–N(2)
C(9)–N(1)
Distance
1.395(4)
1.415(3)
C(5)–N(1)
C(5)–C(6)
C(6)–C(7)
Angle
N(1)-C(5)-C(6)
N(2)-C(7)-C(6)
C(8)-N(2)-C(7)
Angle
C(5)-C(6)-C(7)
C(8)-C(9)-N(1)
(°)
125.2(2)
123.6(2)
Angle
C(9)-C(8)-N(2)
C(5)-N(1)-C(9)
(°)
121.4(2)
133.5(2)
Compound 3b
Bond
Distance
1.349(3)
1.374(4)
1.496(4)
(°)
127.0(3)
124.8(2)
111.7(2)
Bond
C(7)–N(2)
C(8)–C(13)
Distance
1.494(3)
1.396(4)
Bond
C(8)–N(1)
C(13)–N(2)
Distance
1.421(4)
1.404(3)
C(5)–N(1)
C(5)–C(6)
C(6)–C(7)
Angle
N(1)-C(5)-C(6)
C(5)-C(6)-C(7)
N(2)-C(7)-C(6)
Angle
C(13)-C(8)-N(1)
C(5)-N(1)-C(8)
(°)
124.4(2)
133.4(2)
Angle
C(8)-C(13)-N(2)
C(13)-N(2)-C(7)
(°)
121.2(2)
118.3(2)
Compound 3e
Bond
Distance
1.360(4)
1.370(3)
1.503(4)
(°)
126.2(3)
124.3(2)
112.3(2)
Bond
C(7)–N(2)
C(8)–N(1)
Distance
1.478(3)
1.402(3)
Bond
C(8)–C(13)
C(13)–N(2)
Distance
1.414(4)
1.376(4)
C(5)–C(6)
C(5)–N(1)
C(6)–C(7)
Angle
C(6)-C(5)-N(1)
C(5)-C(6)-C(7)
N(2)-C(7)-C(6)
Angle
N(1)-C(8)-C(13)
N(2)-C(13)-C(8)
(°)
124.2(3)
122.2(3)
Angle
C(5)-N(1)-C(8)
C(13)-N(2)-C(7)
(°)
134.6(2)
119.9(2)
The single crystal structures of 3a, 3b, and 3e were
determined by X-ray diffraction analysis. All of their crys-
tallographic data were shown in Table 1. Their ORTEP and
packing diagrams were shown in Figure 1 and Figure S1.
The selected bond lengths and bond angles for compounds
3a, 3b, and 3e are listed in Table 2. Viewed in Figure 1, the
diazepine 7-member rings of 3a, 3b, and 3e had nearly
half-boat conformations. Meanwhile, the configurations
of the two chiral C3 and C11 atoms in 3a, 3b, and 3e were
very different. In 3a, they existed in an R,S-configuration
but showed an S,R-configuration in 3b and an R,R-
configuration in 3e, accordingly. It meant that their pre-
domination conformations were different.
CONCLUSIONS
In summary, there was a successful synthesis of a new se-
ries of 3-(furan-2-yl)-substituted 2,3,4,5,10,11-hexahydro-
1H-dibenzo[b,e][1,4]diazepin-1-one derivatives by the
condensation
reaction
of
5-(furan-2-yl)-1,3-
cyclohexanedione, o-phenylenediamine, and aromatic alde-
hydes. All the compounds were characterized and testified.
Moreover, we also obtained three crystal structures of 3a,
3b, and 3e through X-ray single-crystal diffraction. It
disclosed that their diazepine 7-member rings had nearly
half-boat conformations, while the configurations of two
chiral C3 and C11 atoms in 3a, 3b, and 3e were very
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

F.-M. Wang, D. Bao, M. Wang, Q.-H. Yen, L.-Z. Chen, and G.-F. Han
Vol 000
6.82(m, 1H, 5″-H), 6.98 (m, 1H, 3′-H), 7.03(m, 1H, 4′-H),
7.31( m, 1H, 5′-H), 7.61(s, 1H, 3″-H), 9.09(s, 1H, 5-NH). IR
(KBr) υ: 3297 br, 1596 m, 1542 s, 1388 s, 1332 m, 1168 m,
1035 w, 768 m. Anal. Calcd. for C23H19ClN2O2: C, 70.68; H,
4.90; N, 7.17. Found: C, 70.42; H, 4.57; N, 7.03. MS (ESI)
m/z: 391.1 (M + 1).
different. We believe that it would be very useful to study
the relationship between their biological activities and
structures eventually.
EXPERIMENTAL
3-(Furan-2-yl)-11-(4-chlorophenyl)-2,3,4,5,10,11-hexahydro-
5-(Furan-2-yl)-l,3-cyclohexanedione 1 was synthesized as the
Ref. [23]. Other chemicals were of analytical reagent grade
and purchased from commercial sources, which were used di-
rectly without further purification. Melting points were deter-
mined on a capillary tube method and the temperature was not
calibrated. IR spectra were recorded as thin films on KBr using
a Digilab FTS 2000 spectrophotometer (Marlborough, MA,
1H-dibenzo[b,e][1,4]diazepin-1-one (3b).
Yield 58%; m.p.
226–228°C. 1H NMR (DMSO-d6, 500MHz) δ: 2.56 (m, 2H,
2-H), 2.88 (dd, 1H, J1 = 11.0 Hz, J2 = 16.0Hz, 4a-H), 3.07 (dd,
1H, J1 = 11.0 Hz, J2 = 16.0 Hz, 4b-H), 3.49 (m, 1H, 3-H), 5.73
(d, 1H, J = 6.0 Hz, 11-H), 6.22 (m, 1H, 10-NH), 6.30–6.58 (m,
5H, Ph-H, 4′-H), 6.92 (d, 2H, J = 7.5Hz, 2″-H, 6″-H), 7.17 (m,
3H, 3′-H, 3″-H, 5″-H), 7.62 (s, 1H, 5-H), 8.94 (s, 1H, 5-NH).
IR (KBr) υ: 3309 br, 1602 m, 1529s, 1382s, 1276 w, 1149w,
738 m. Anal. Calcd. for C23H19ClN2O2: C, 70.68; H, 4.90; N,
7.17. Found: C, 70.35; H, 4.63; N, 6.99. MS (ESI) m/z: 391.1
(M+ 1).
1
USA). H NMR spectra were recorded on a Bruker AVANCE
III 500 (Billerica, MA, USA) spectrometer. Element analysis
was determined by Elementar Vario EL III analyzers (Hanau,
Germany). The ESI-MS was determined on an Aglient-6100
(Santa Clara, CA, USA) equipment. Crystallographic data of
3a, 3b, and 3e were collected using a Bruker SMART APEX II
CCD-based diffractometer (Billerica, MA, USA) with graphite-
monochromatic MoKα radiation (λ = 0.71073Å) at 291(2)K. Data
reductions and absorption corrections were performed with SAINT
and SADABS software packages [24], respectively. Structures
were solved by direct methods using the SHELXL-97 software
package [25]. Non-hydrogen atoms were refined anisotropically
using the full-matrix least-squares method on F2. All hydrogen
atoms were placed at calculated positions and refined, riding on
the parent atoms.
3-(Furan-2-yl)-11-(2-pyridyl)-2,3,4,5,10,11-hexahydro-1H-
dibenzo[b,e][1,4]diazepin-1-one (3c). Yield 43%; m.p. 224–
1
226°C. H NMR (DMSO-d6, 500 MHz) δ: 2.63 (m, 1H, 2a-H),
2.91 (m, 1H, 2b-H), 3.09 (dd, 2H, J1 = 3.5 Hz, J2 = 14.5 Hz,
4-H), 3.90 (m, 1H, 3-H), 5.79 (d, 1H, J = 6.0 Hz, 11-H),
6.15 (m, 1H, 10-NH), 6.22–6.56 (m, 7H, Ph-H, 3′-H, 4′-H,
6″-H), 6.92 (m, 2H, 5′-H, 4″-H), 7.50 (m, 1H, 5″-H), 8.37
(m, 1H, 3″-H), 8.95 (s, 1H, 5-NH). IR (KBr) υ: 3307 br,
1594 m, 1531 s, 1388 s, 1348 m, 1145 w, 1010 w, 746 m.
Anal. Calcd. for C22H19N3O2: C, 73.93; H, 5.36; N, 11.76.
Found: C, 73.68; H, 5.25; N, 11.63. MS (ESI) m/z: 358.1
(M + 1).
Synthesis of intermediate5-((2-amino-(furan-2-yl))amino)-
1,6-dihydro-[1,1′-biphenyl]- 3(2H)-one (2).
A mixture of
3-(Furan-2-yl)-11-(4-pyridyl)-2,3,4,5,10,11-hexahydro-1H-
dibenzo[b,e][1,4]diazepin-1-one (3d). Yield 51%; m.p. 188–
190°C. H NMR (DMSO-d6, 500 MHz) δ: 2.67 (m, 1H, 2a-H),
5-(furan-2-yl)-1,-cyclohexanedione (5 mmol) and o-
1
1
phenylenediamine (5 mmol) was dissolved in toluene and
refluxed for 8 h. When the reaction was completed, it was
cooled to room temperature. The yellowish solid product 2 was
collected by filtration and purified by recrystallization from 95%
ethanol. Yield 85%; m.p. 206–208°C. 1H NMR (DMSO-d6,
500 MHz) δ: 2.36 (m, 2H, 4-H), 2.42 (dd, 1H, J1 = 5.0 Hz,
J2 = 16.0 Hz, 6a-H), 2.73 (dd, 1H, J1 = 5.0Hz, J2 = 16.0 Hz, 6b-
H), 2.84 (m, 1H, 5-H), 4.67 (s, 1H, 2-H), 4.92 (br, 2H, 14-NH),
6.18–6.75 (m, 4H, Ph-H), 6.90 (m, 1H, 3′-H), 7.00 (m, 1H, 4′-
H), 7.58 (m, 1H, 5′-H), 8.37 (s, 1H, 7-NH). IR (KBr) υ: 3452
br, 3259 m, 1535 s, 1457 m, 1253 m, 1147 m, 742 s. Anal. Calcd.
for C16H16N2O2: C, 71.62; H, 6.01; N, 10.44. Found: C, 71.35;
H, 5.75; N, 10.26. MS (ESI) m/z: 269.1 (M + 1).
2.56 (m, 1H, 2b-H), 3.07 (dd, 2H, J1 = 4.5 Hz, J2 = 16.0 Hz,
4-H), 3.56 (m, 1H, 3-H), 5.66 (d, 1H, J = 6.0 Hz, 11-H), 6.17 (m,
1H, 10-NH), 6.41–6.59 (m, 4H, Ph-H), 6.65 (m, 1H, 3′-H), 6.88
(d, 2H, J = 5.5 Hz, 2″-H, 6″-H), 6.91 (m, 1H, 4′-H ), 7.62 (m,
1H, 5′-H), 8.22 (d, 2H, J = 5.5 Hz, 3″-H, 5″-H), 8.97 (s, 1H,
5-NH). IR (KBr) υ: 3305 br, 1598 m, 1527 s, 1392 s, 1334 m,
1263 w, 1164 w, 755 m. Anal. Calcd. for C22H19N3O2: C,
73.93; H, 5.36; N, 11.76. Found: C, 73.71; H, 5.11; N,
11.52. MS (ESI) m/z: 358.1 (M + 1).
3-(Furan-2-yl)-11-(4-methoxyphenyl)-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (3e).
Yield
1
58%; m.p. 217–220°C. H NMR (DMSO-d6, 500 MHz) δ: 2.54
(m, 1H, 2a-H), 2.65 (m, 1H, 2b-H), 3.01 (dd, 1H, J1 = 7.5 Hz,
J2 = 16.0 Hz, 4a-H), 3.02 (dd, 1H, J1 = 4.5Hz, J2 = 16.0 Hz, 4b-
H), 3.53 (m, 1H, 3-H), 3.60 (s, 3H, 4″-OCH3), 5.63 (d, 1H,
J = 6.0 Hz, 11-H), 6.23 (m, 1H, 10-NH), 6.24–6.84 (m, 9H,
Ph-H, 2′-H, 3″-H, 5′-H, 6″-H, 3′-H), 6.88 (m, 1H, 4′-H), 7.61
(m, 1H, 5′-H), 8.85 (s, 1H, 5-NH). IR (KBr) υ: 3324 br,
1591 m, 1542 s, 1386 m, 1240 w, 1170 w, 748 m. Anal. Calcd.
for C24H22N2O3: C, 74.59; H, 5.74; N, 7.25. Found: C,
74.32; H, 5.45; N, 7.13. MS (ESI) m/z: 387.0 (M + 1).
General synthesis route of 3-(furan-2-yl)-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4] diazepin-1-one (3).
The
intermediate (5 mmol) reacted with aromatic aldehydes
2
(5 mmol) using acetic acid (2.5 mL) as a catalyst under reflux
for 3–4 h. After cooling, the solvent was removed under
reduced pressure to get a pale-yellowish solid. The crude
products were purified by column chromatography (ethyl
acetate/cyclohexane = 2:1) to afford the title compounds. In
purifying the crude product 3 g, there obtained two very close
isomer compounds, 3g-1 and 3g-2, accordingly.
3-(Furan-2-yl)-11-(3,4-dimethoxyphenyl)-2,3,4,5,10,11-
3-(Furan-2-yl)-11-(2-chlorophenyl)-2,3,4,5,10,11-hexahydro-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (3f).
Yield
1
1H-dibenzo[b,e][1,4]diazepin-1-one (3a).
Yield 69%; m.p.
68%; m.p. 126–128°C. H NMR (DMSO-d6, 500 MHz) δ: 2.54
(m, 1H, 2a-H), 2.65 (m, 1H, 2b-H), 3.00 (dd, 1H, J1 = 7.5 Hz,
J2 = 16.0 Hz, 4a-H), 3.07 (dd, 1H, J1 = 4.5 Hz, J2 = 16.0 Hz, 4b-
H), 3.54 (m, 1H, 3-H), 3.59 (m, 6H, 3″-OCH3, 4″-OCH3), 5.62
(d, 1H, J = 6.0 Hz, 11-H), 6.16 (m, 1H, 10-NH), 6.17–6.50 (m,
4H, Ph-H), 6.59 (m, 3H, 6″-H, 3′-H, 4′-H), 6.81 (d, 1H,
144–146°C. 1H NMR (DMSO-d6, 500 MHz) δ: 2.47 (m, 1H,
2a-H), 2.63 (m, 1H, 2b-H), 3.07 (dd, 1H, J1 = 8.0 Hz,
J2 = 16.0 Hz, 4a-H), 3.13 (dd, 1H, J1 = 4.5 Hz, J2 = 16.0 Hz 4b-
H), 3.55 (m, 1H, 3-H) , 5.61 (d, 1H, J = 6.0 Hz, 11-H), 5.94–6.48
(m, 4H, Ph-H), 6.52 (m, 1H, 10-NH), 6.61(m, 2H, 4″-H, 6″-H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Synthesis of 3-(Furan-2-yl)-Substituted Dibenzo-Diazepin-1-ones
[2] Ramajayam, R.; Giridhar, R.; Yadav, M. R. Mini-Rev Med
Chem 2007, 7, 793.
[3] Kaur, N.; Kishore, D. Synth Commun 2014, 44, 1375.
[4] An, L. T.; Ding, F. Q.; Zou, J. P.; Lu, X. H. Synth Commun
2008, 38, 1259.
J=1.5Hz, 2″-H), 6.88 (d, 1H, J=8.0Hz, 5″-H), 7.61 ( m, 1H, 5′-H),
8.84 (s, 1H, 5-NH). IR (KBr) υ: 3332 br, 1691 m, 1604 s, 1531 s,
1327 m, 1147 m, 1024 s, 711 s. Anal. Calcd. for C25H24N2O4: C,
72.10; H, 5.81; N, 6.73. Found: C, 72.02; H, 5.55; N, 6.64. MS
(ESI) m/z: 417.1 (M + 1).
3-(Furan-2-yl)-11-(naphthalen-1-yl)-2,3,4,5,10,11-hexahydro-
1H-dibenzo[b,e][1,4]diazepin-1-one (3g). 3g-1: Yield 35%;
m.p. 156–158°C. 1H NMR (DMSO-d6, 500 MHz) δ: 2.56 (m, 2H,
2-H), 3.10 (dd, 1H, J1 = 8.5 Hz, J2 = 16.5 Hz, 4a-H), 3.17 (dd, 1H,
J1 = 4.5 Hz, J2 = 16.0 Hz, 4b-H), 3.59 (m, 1H, 3-H), 6.06 (m,
1H, 11-H), 6.07 (m, 1H, 10-NH), 6.16–6.42 (m, 6H, Ph-H,
3′-H, 4′-H), 7.51 (m, 1H, 5′-H), 7.61 (m, 4H, 4″-H, 5″-H, 8″-H,
9″-H), 7.84 (t, 2H, J = 9.5 Hz, 3″-H ,6″-H), 8.50 (d, 1H,
J = 8.5 Hz, 7″-H), 9.06 (s, 1H, 5-NH). IR (KBr) υ: 3310 br,
1598 m, 1523 s, 1388 s, 1290 m,1151 m, 1010 w, 796 m. Anal.
Calcd. for C27H22N2O2: C, 79.78; H, 5.46; N, 6.89. Found: C,
[5] Sabitha, G.; Reddy, G. S. K. K.; Reddy, K. B.; Reddy, N. M.;
Yadav, J. S. Adv Synth Catal 2004, 346, 921.
[6] Bandgar, B. P.; Bettigeri, S. V.; Joshi, N. S. Synth Commun
2004, 34, 1447.
[7] Chen, W. Y.; Lu, J. Synlett 2005, 8, 1337.
[8] Pasha, M. A.; Jayashankara, V. P. Heterocycles 2006, 68,
1017.
[9] Thakrar, S.; Bavishi, A.; Radadiya, A.; Parekh, S.; Bhavsar, D.;
Vala, H.; Pandya, N. Shah A J Heterocyclic Chem 2013, 50, 73.
[10] Kaboudin, B.; Navaee, K. Heterocycles 2001, 55, 1443.
[11] Lindner, A. S.; Geist, E.; Gjikaj, M.; Schmidt, A. J Heterocy-
clic Chem 2014, 51, 423.
[12] Kaur, N.; Tyagi, R.; Srivastava, M.; Kishore, D. J Heterocyclic
Chem 2014, 51, E50.
[13] Essaber, M.; Baouid, A.; Hasnaoui, A.; Benharreb, A.;
Lavergne, J. P. Synth Commun 2000, 28, 4097.
[14] Korneki, E.; Erlich, Y. H.; Lenox, R. H. Science 1984, 226,
1454.
[15] Ahmed, K.; Srinivasa Reddy, K.; Naseer, A.; Khan, M.;
Rajesh Shetti, V. C. R. N. C.; Janaki, R. M.; Pushpavalli, S. N. C. V. L.;
Chatla, S.; Manika, P. B.; Mukesh, C.; Narahari, S. G.; Aarti, J.; Surekha, Z.;
Madan, B. Bioorg Med Chem 2010, 18, 4747.
[16] Hsu, M. C.; Schutt, A. D.; Holly, M.; Slice, L. W.; Sherman,
M. I.; Richman, D. D.; Potash, J. M.; Volsky, D. F. Science 1991, 254,
1799.
[17] Barciszewski, J.Mielcarek, M.; Stobiecki, M.; Siboska, G.;
Clark, B. F. C. Biochem Biophys Res Commun 2000, 279, 69.
[18] Wyszko, E.; Barciszewska, M. Z.; Markiewicz, M.;
Szymanski, M.; Markiewicz, W. T.; Clark, B. F. C.; Barciszewski, J.
BBA-Gene Struct Expr 2003, 1625, 239.
79.52; H, 5.26; N, 6.84. MS (ESI) m/z: 407.2 (M + 1).
3g-2: Yield 30%; m.p. 156–158°C. 1H NMR (DMSO-d6,
500 MHz) δ: 2.64 (m, 1H, 2a-H), 2.98 (m, 1H, 2b-H), 3.22 (dd,
2H, J1 = 4.5 Hz, J2 = 16.5 Hz, 4-H), 3.51 (m, 1H, 3-H), 5.91
(m, 1H, 11-H), 5.92 (m, 1H, 10-NH), 6.24–6.44 (m, 4H, Ph-H),
6.55 (m, 1H, 3′-H), 6.63 (m, 1H, 4′-H), 6.97 (m, 5H, 5′-H, 4″-H,
5″-H, 8″-H, 9″-H), 7.13 (t, 1H, J = 7.5 Hz, 3″-H), 7.55 (m, 1H,
6″-H), 8.53 (m, 1H, 7″-H), 9.08 (s, 1H, 5-NH). IR (KBr) υ: 3310
br, 1598 m, 1523 s, 1388 s, 1290 m, 1151 m, 1010 w, 796 m. Anal.
Calcd. for C27H22N2O2: C, 79.78; H, 5.46; N, 6.89. Found: C,
79.61; H, 5.13; N, 6.78. MS (ESI) m/z: 407.2 (M + 1).
Acknowledgments. This work was supported by the National
Natural Science Foundation of China for Young Scholars (Grant
No. 21201087), the Natural Science Foundation of Jiangsu
Province (No. BK20131244), and a start-up grant from Jiangsu
University of Science and Technology, China.
[19] Carrette, L. L. G.; Madder, A. Chem Bio Chem 2014, 15, 103.
[20] Pogozelski, W. K.; Tullius, T. D. Chem Rev 1998, 98, 1089.
[21] Pratviel, G.; Pitie, M.; Bernadou, J.; Meunier, B. Angew Chem
Int Ed Engl 1995, 34, 746.
[22] Balasubramanian, B.; Pogozelski, W. K.; Tullius, T. D. Proc
Natl Acad Sci U S A 1998, 95, 9738.
[23] Han, G. F.; Dong, J. K.; Wang, F. M.; Xing, Z.; Zhao, Y. Y.
Chin J Org Chem 2008, 28, 750.
REFERENCES AND NOTES
[24] Software packages SMART and SAINT, Bruker AXS Inc.
Madison, WI, 2000.
[25] Sheldrick, G.M. SHELXL-97, Program for the Refinement of
Crystal Structure; University of Gottingen: Germany, 1997.
[1] Merluzzi, V. J.; Hargrave, K. D.; Labadia, M.; Grozinger, K.;
Skoog, M.; Wu, J. C.; Shih, C. K.; Eckner, K.; Hattox, S.; Adams, J.;
Rosenthal, A. S.; Faanes, R.; Eckner, R. J.; Koup, R. A.; Sullivan, J. L.
Science 1990, 250, 1411.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet