Synthesis and characterization of new 3-(3-hydroxyphenyl)-4- alkyl-3,4-dihydrobenzo[e][1,3]oxazepine-1,5-dione compounds

Article abstract of DOI:10.1002/cjoc.201180273

A series of 3-(3-hydroxyphenyl)-4-alkyl-3,4-dihydrobenzo[e][1,3]oxazepine- 1,5-dione compounds with general formula C_nH_2n+1CNO(CO) ₂C₆H₄(C₆H₄OH) in which n are even parity numbers from 2 to 18. The structure determinations on these compounds were performed by FT-IR spectroscopy which indicated that the terminal alkyl chain attached to the oxazepine ring was fully extended. Conformational analysis in DMSO at ambient temperature was carried out for the first time via high resolution ¹H NMR and ¹³C NMR spectroscopy. Copyright

Full text of DOI:10.1002/cjoc.201180273

FULL PAPER
Synthesis and Characterization of New 3-(3-Hydroxyphenyl)-4-
alkyl-3,4-dihydrobenzo[e][1,3]oxazepine-1,5-dione Compounds
Osman, Hasnah*
Mohammad, AbdulKarim-Talaq
Yeap, Guan-Yeow
Adam, Farook
School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
A series of 3-(3-hydroxyphenyl)-4-alkyl-3,4-dihydrobenzo[e][1,3]oxazepine-1,5-dione compounds with general
formula CnH2n＋1CNO(CO)2C6H4(C6H4OH) in which n are even parity numbers from 2 to 18. The structure deter-
minations on these compounds were performed by FT-IR spectroscopy which indicated that the terminal alkyl chain
attached to the oxazepine ring was fully extended. Conformational analysis in DMSO at ambient temperature was
carried out for the first time via high resolution 1H NMR and 13C NMR spectroscopy.
Keywords 3,4-dihydrobenzo[e][1,3]oxazepine-1,5-diones, synthetic method, structure elucidication
Introduction
chased from Aldrich and was used without further puri-
fication. Thin-layer chromatography (TLC) was per-
formed on silica-gel plates. Benzene and THF were
dried by standard method.
1,3-Oxazepinediones are a seven-membered ring
that contains nitrogen, oxygen, and two carbonyl groups.
The molecular properties of 1,4-benzoxazepine,
4,1-benzoxazepines, and 1,5-benzoxazepines have been
extensively studied due to their biological activity1-10
and their great importance in organic and medicinal
chemistry.11-16 There are no general procedures for the
synthesis of these compounds. However, benzoxa-
zepines with appropriate side chains must be synthe-
sized for drug research. The nitrogen heteroatom is a
convenient site for a side chain attachment to ben-
zoxazepine. This usually takes place via acylation.17,18
The N-alkylation of 2,3-dihydro-1,5-benzoxazepin-
4(5H)-one type compounds had been reported.19-21 Our
interest in [1,3]oxazepine-4,7-dione molecules arise
from our earlier observation of other heterocyclic
molecules which have liquid crystalline properties.22
This has encouraged us to build a new seven-membered
ring from easily acquired starting materials. The major
purpose of this paper is to report on new 3-(3-hydroxy-
phenyl)-4-alkyl-3,4-dihydrobenzo[e][1,3]-oxazepine-
1,5-dione compounds, 2ozpn— 18ozpn. The N atoms of
the heterocyclic ring next to 1,3-oxazepine fragments
were linked by an alkyl chain. To the best of our
knowledge, the synthesis and spectral data of these
molecules have not yet been reported.
Synthesis of 3,4-dihydrobenzo[e][1,3]oxazepine-1,5-
diones derivatives
All Compounds were prepared by the same method.
The synthetic route used to prepare the series of 3-(3-
hydroxyphenyl)-4-alkyl-3,4-dihydrobenzo[e][1,3]-oxa-
zepine-1,5-diones compounds is shown in Figure 1.
2ozpn
6ozpn
R＝C2H5
R＝C6H13
4ozpn
8ozpn
R＝C4H9
R＝C8H17
10ozpn R＝C10H21
14ozpn R＝C14H29
18ozpn R＝C18H37
12ozpn R＝C12H25
16ozpn R＝C16H33
Figure 1 General procedure for the synthesis of 2ozpn—
18ozpn.
A solution of phthalic anhydride (0.01 mol) in dry
benzene (10 mL) was added dropwise to a hot dry ben-
zene solution (20 mL) of 3-((ethylimino)alkyl)phenol
(0.01 mol), in a round bottom flask equipped with a
double surface condenser fitted with calcium chloride
guard tube. The reaction mixture was refluxed for 4 h.
The reaction was monitored by TLC and the solvent
Experimental
Material
The 3-((alkylimino)methyl)phenol derivatives were
prepared in our laboratory. Phthalic anhydride was pur-
*
E-mail: ohasnah@usm.my (Hasnah Osman); Tel: ＋604-6533262, Fax: ＋604-6574854
Received November 4, 2010; revised January 14, 2011; accepted March 15, 2011.
Project supported by the Universitiy Sains Malaysia and the Malaysian Government (No. 1001/PKIMIA/811133,USM-RU-PRGS,
1001/PKIMIA/842022).
1518
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1518— 1522

Synthesis and Characterization of New Compounds
was distilled off in vacuo. The solid product obtained
was filtered and washed with cold distilled water. The
resulting solid was recrystallized twice from
1,4-dioxane. The analytical data for the series of com-
pounds from 2ozpn to 18ozpn are summarized as fol-
lows.
168.83 (C-11), 128.91 (C-12), 130.87 (C-13), 138.49
(C-14), 123.45 (C-15), 40.91 (C-1'), 32.16 (C-2'), 29.66
—33.16 (C-3'—C-6'), 22.96 (C-x), 15.37 (C-y); IR (KBr)
ν: 3428, 3045, 2954, 2928, 2870, 2858, 1731, 1596,
1585, 1079, 1457, 1315, 3240, 2729, 871, 776, 722
－1
cm . Anal. calcd for C23H27NO4: C 72.42, H 7.13, N
2ozpn: Yield 66%. m.p. 90—92 ℃. 1H NMR
(DMSO) δ: 9.53 (s, OH), 8.25 (d, J＝8.1 Hz, H-12),
8.05 (s, H-7), 7.85 (t, J＝8.6 Hz, H-14), 7.78 (t, J＝7.8
Hz, H-13), 7.69 (d, J＝7.2 Hz, H-15), 7.16 (t, J＝8.6 Hz,
H-5), 7.09 (s, H-2), 6.89 (d, J＝7.9 Hz, H-6), 6.72 (d,
J＝8.1 Hz, H-4), 3.22 (q, H-1'), 1.28 (t, H-2'); 13C NMR
(DMSO) δ: 114.76—138.32 (Ar-C), 158.20 (Ar-C-O),
86.65 (C-7), 169.32 (C-8), 131.59 (C-9), 132.25 (C-10),
168.10 (C-11), 128.31 (C-12), 130.21(C-13), 138.42
(C-14), 123.74 (C-15), 33.86 (C-x), 13.83 (C-y); IR
(KBr) ν: 3410, 3214, 3017, 2945, 2932, 2862, 2789,
2728, 1－751, 1554, 1539, 1451, 1310, 1068, 860, 751,
3.67; found C 72.39, H 7.08, N 3.72.
1
10ozpn: Yield 61%. m.p. 99—101 ℃. H NMR
(DMSO) δ: 9.98 (s, OH), 8.32 (d, J＝8.5 Hz, H-12),
8.10 (s, H-7), 7.72 (t, J＝8.3 Hz, H-14), 7.56 (t, J＝7.4
Hz, H-13), 7.36 (d, J＝7.5 Hz, H-15), 7.23 (t, J＝8.7 Hz,
H-5), 7.16 (s, H-2), 7.14 (d, J＝7.8 Hz, H-6), 6.95 (d,
J＝8.7 Hz, H-4), 3.13 (t, H-1'), 1.77, (q, H-2'), 1.34
(H-x), 1.31 (m, H-3'—H-8'), 0.89 (H-y); 13C NMR
(DMSO) δ: 115.62—139.64 (Ar-C), 158.75 (Ar-C-O),
86.27 (C-7), 169.23 (C-8), 131.20 (C-9), 132.06 (C-10),
168.81 (C-11), 128.40 (C-12), 131.62 (C-13), 138.39
(C-14), 122.50 (C-15), 40.56 (C-1'), 32.18 (C-2'), 27.44
—32.24 (C3'—C8'), 22.95 (C-x), 14.83 (C-y); IR (KBr)
ν: 3411, 3012, 2952, 2918, 2857, 2828, 1726, 1577,
1523, 1080, 1431, 1312, 3213, 2760, 833, 770, 719.
Anal. calcd for C25H31NO4: C 73.32, H 7.63, N 3.42;
found C 73.40, H 7.51, N 3.49.
1
714 cm . Anal. calcd for C17H15NO4: C 68.68, H 5.09,
N 4.71; found C 68.76, H 5.18, N 4.64.
1
4ozpn: Yield 70%. m.p. 98—100 ℃. H NMR
(DMSO) δ: 9.68 (s, OH), 8.21 (d, J＝8.3 Hz, H-12),
8.03 (s, H-7), 7.81 (t, J＝8.2 Hz, H-14), 7.63 (t, J＝7.0
Hz, H-13), 7.51 (d, J＝7.0 Hz, H-15), 7.19 (t, J＝8.4 Hz,
H-5), 7.10 (s, H-2), 6.97 (d, J＝7.4 Hz, H-6), 6.81 (d,
J＝8.9 Hz, H-4), 3.17 (t, H-1'), 1.73 (q, H-2'); 13C NMR
(DMSO) δ: 115.74—139.83 (Ar-C), 158.89 (Ar-C-O),
86.85 (C-7), 169.74 (C-8), 131.63 (C-9), 132.59 (C-10),
168.92 (C-11), 128.43 (C-12), 130.47 (C-13), 138.66
(C-14), 123.46 (C-15), 40.99 (C-1'), 31.96 (C-2'), 21.13
(C-x), 14.23 (C-y); IR (KBr) ν: 3444, 3011, 2958, 2938,
2870, 2782, 1728, 1560,－1541, 1082, 1448, 1312, 3222,
1
12ozpn: Yield 59%. m.p. 97—99 ℃. H NMR
(DMSO) δ: 9.91 (s, OH), 8.35 (d, J＝8.6 Hz, H-12),
8.23 (s, H-7), 7.76 (t, J＝8.2 Hz, H-14), 7.51 (t, J＝7.3
Hz, H-13), 7.39 (d, J＝7.1 Hz, H-15), 7.21 (t, J＝8.9 Hz,
H-5), 7.17 (s, H-2), 6.92 (d, J＝7.9 Hz, H-6), 6.81 (d,
J＝8.6 Hz, H-4), 3.18 (t, H-1'), 1.73 (q, H-2'), 1.34
(H-x), 1.31 (m, H-3'—H-10'), 0.87 (H-y); 13C NMR
(DMSO) δ: 115.50—138.50 (Ar-C), 158.40 (Ar-C-O),
86.38 (C-7), 169.19 (C-8), 131.27 (C-9), 131.73 (C-10),
168.92 (C-11), 128.94 (C-12), 131.73 (C-13), 138.41
(C-14), 123.84 (C-15), 40.45 (C-1'), 32.15 (C-2'), 27.60
—32.48 (C-3'—C-10') 23.01 (C-x), 15.21 (C-y); IR
(KBr) ν: 3437, 3017, 2962, 2921, 2862, 2854, 1750,
1597, 1－573, 1081, 1453, 1315, 3218, 2725, 872, 824,
1
2734, 820, 751, 719 cm . Anal. calcd for C19H19NO4:
C 70.14, H 5.89, N 4.31; found C 70.10, H 5.83, N 4.38.
6ozpn: Yield 60%. m.p. 94—96 ℃. 1H NMR
(DMSO) δ: 9.96 (s, OH), 8.24 (d, J＝8.7 Hz, H-12),
8.14 (s, H-7), 7.76 (t, J＝8.3 Hz, H-14), 7.61 (t, J＝7.1
Hz, H-13), 7.43 (d, J＝6.90 Hz, H-15), 7.24 (t, J＝8.2
Hz, H-5), 7.14 (s, H-2), 7.13 (d, J＝7.5 Hz, H-6), 6.95
(d, J＝8.6 Hz, H-4), 3.15 (t, H-1'), 1.72, (q, H-2'); 13C
NMR (DMSO) δ: 115.36 — 139.62 (Ar-C), 158.60
(Ar-C-O), 86.95 (C-7), 169.64 (C-8), 131.42 (C-9),
132.83 (C-10), 168.73 (C-11), 128.57 (C-12), 130.36
(C-13), 138.54 (C-14), 122.82 (C-15), 40.84 (C-1'),
32.25 (C-2'), 29.53—33.10 (C-3'—C-4'), 22.86 (C-x),
15.22 (C-y); IR (KBr) ν: 3440, 3015, 2949, 2929, 2861,
2855, 1740, 1590, 1466, 1050, 1452, 1314, 3225, 2727,
1
785 cm . Anal. calcd for C27H35NO4: C 74.11, H 8.06,
N 3.20; found C 74.19, H 8.17, N 3.28.
1
14ozpn: Yield 63%. m.p. 122—124 ℃. H NMR
(DMSO) δ: 9.93 (s, OH), 8.25 (d, J＝8.3 Hz, H-12),
8.11 (s, H-7), 7.75 (t, J＝8.4 Hz, H-14), 7.56 (t, J＝7.1
Hz, H-13), 7.38 (d, J＝7.0 Hz, H-15), 7.28 (d, J＝7.6
Hz, H-6), 7.25 (t, J＝8.7 Hz, H-5), 7.20 (s, H-2), 7.18 (d,
J＝8.8 Hz, H-4), 3.19 (t, H-1'), 1.71, (q, H-2'), 1.38
(H-x), 1.35 (m, H-3'—H-12'), 0.88 (H-y); 13C NMR
(DMSO) δ: 115.51—139.61 (Ar-C), 158.84 (Ar-C-O),
86.21 (C-7), 169.18 (C-8), 131.15 (C-9), 131.94 (C-10),
168.84 (C-11), 128.97 (C-12), 130.45 (C-13), 138.52
(C-14), 122.84 (C-15), 40.78 (C-1'), 32.16 (C-2'), 27.62
—32.67 (C-3'—C-12') 23.03 (C-x), 14.95 (C-y); IR
(KBr) ν: 3437, 3059, 2958, 2920, 2861, 2850, 1690,
1597, 1561, 1081, 1463, 1316, 3211, 2723, 824, 785,
720. Anal. calcd for C29H39NO4: C 74.81, H 8.44, N
3.01; found C 74.88, H 8.39, N 3.01.
－1
872, 824, 783 cm . Anal. calcd for C21H23NO4: C
71.37, H 6.56, N 3.96; found C 71.27, H 6.61, N 3.94.
1
8ozpn: Yield 59%. m.p. 102—104 ℃. H NMR
(DMSO) δ: 9.98 (s, OH), 8.23 (d, J＝8.3 Hz, H-12),
8.21 (s, H-7), 7.74 (t, J＝8.0 Hz, H-14), 7.59 (t, J＝7.0
Hz, H-13), 7.38 (d, J＝7.0 Hz, H-15), 7.26 (t, J＝8.4 Hz,
H-5), 7.19 (s, H-2), 7.12 (d, J＝7.7 Hz, H-6), 6.97 (d,
J＝8.9 Hz, H-4), 3.12 (t, H-1'), 1.71, (q, H-2'), 1.35
(H-x), 1.32 (m, H-3'—H-6'), 0.88 (H-y); 13C NMR
(DMSO) δ: 115.01—139.85 (Ar-C), 158.82 (Ar-C-O),
86.87 (C-7), 169.24 (C-8), 131.58 (C-9), 132.43 (C-10),
1
16ozpn: Yield 60%. m.p. 116—118 ℃. H NMR
(DMSO) δ: 10.02 (s, OH), 8.29 (d, J＝8.2 Hz, H-12),
Chin. J. Chem. 2011, 29, 1518—1522
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1519

Osman et al.
FULL PAPER
Table 1 Acquisition parameter used in the NMR measure-
8.17 (s, H-7), 7.73 (t, J＝8.6 Hz, H-14), 7.58 (t, J＝7.1
Hz, H-13), 7.39 (d, J＝6.8 Hz, H-15), 7.24 (t, J＝8.9 Hz,
H-5), 7.2 (s, H-2), 7.19 (d, J＝7.3 Hz, H-6), 6.99 (d,
J＝8.7 Hz, H-4), 3.15 (t, H-1'), 1.78 (q, H-2'), 1.39
(H-x), 1.36 (m, H-3'—H-14'), 0.86 (H-y); 13C NMR
(DMSO) δ: 115.49—139.54 (Ar-C), 158.82 (Ar-C-O),
86.34 (C-7), 169.22 (C-8), 131.17 (C-9), 131.93 (C-10),
168.88 (C-11), 128.97 (C-12), 131.64 (C-13), 138.50
(C-14), 122.67 (C-15), 40.92 (C-1'), 32.14 (C-2'), 27.84
—32.78 (C-3'—C-14') 22.74 (C-x), 14.94 (C-y); IR
(KBr) ν: 3308, 3015, 2949, 2916, 2849, 2835, 1680,
1610, 1594, 1050, 1404, 1341, 3239, 2698, 837, 824,
784. Anal. calcd for C31H43NO4: C 75.42, H 8.78, N
2.84; found C 75.54, H 8.81, N 2.90.
mentsa
Parameter
SF/MHz
1H NMR
13C NMR
2D COSY
400.1
10
100.6
180
400.1
10
SW/10－
6
8.3
20.0
8.3
PW/µs
(30° flip angle) (90° flip angle) (90° flip angle)
AQ/s
D1/s
NS
4.0
1.0
16
1.3
2.0
0.3
2.0
20000
66 k
16
TD
66 k
F1＝256
F2＝2048
F1, 13C channel (except 2D COSY where F1 and F2 are H
channels); SF, spectrometer frequency; SW, spectral width; AQ,
acquisition time; DI, relaxation delay; NS, number; TD, number
of data point.
a
1
1
18ozpn: Yield 62%. m.p. 108—110 ℃. H NMR
(DMSO) δ: 10.02 (s, OH), 8.25 (d, J＝8.3 Hz, H-12),
8.12 (s, H-7), 7.74 (t, J＝8.4 Hz, H-14), 7.54 (t, J＝7.2
Hz, H-13), 7.37 (d, J＝7.1 Hz, H-15), 7.25 (t, J＝8.7 Hz,
H-5), 7.23 (s, H-2), 7.09 (d, J＝7.6 Hz, H-6), 6.84 (d,
J＝8.9 Hz, H-4), 3.13 (t, H-1'), 1.72, (q, H-2'), 1.37
(H-x), 1.34 (m, H-3'—H-16'), 0.89 (H-y); 13C NMR
(DMSO) δ: 115.73—139.85 (Ar-C), 158.90 (Ar-C-O),
86.26 (C-7), 169.83 (C-8), 131.27 (C-9), 131.84 (C-10),
168.64 (C-11), 128.83 (C-12), 131.59 (C-13), 138.49
(C-14), 122.71 (C-15), 40.96 (C-1'), 32.13 (C-2'), 27.71
—32.63 (C-3'—C-14') 22.84 (C-x), 14.71 (C-y); IR
(KBr) ν: 3307, 3094, 2953, 2918, 2867, 2850, 1675,
1594, 1581, 1051, 1469, 1313, 3246, 2725, 842, 796,
784. Anal. calcd for C33H47NO4: C 75.97, H 9.08, N
2.68; found C 75.88, H 9.05, N 2.62.
Figure 2 Molecular structure with numbering scheme for com-
pound 14ozpn.
Results and discussion
The condensation for the entire series of 3-[(alkyli-
mino)methyl]phenol derivatives with phthalic anhydride
produced the 3-(3-hydroxyphenyl)-4-alkyl-3,4-dihydro-
benzo[e][1,3]oxazepine-1,5-dione compounds with a
general formula CnH2n＋1CNO(CO)2C6H4(C6H4OH), in
which n is an even parity number from 2 to 18. The
synthesized compounds have two carbonyl groups in a
heterocyclic ring adjacent to the aromatic ring. To the
best of our knowledge, majority of these compounds has
not been reported in the literature. All title compounds
are stable solids with a sharp melting point. The mo-
lecular structure of the title compounds were investi-
gated by using FTIR analysis and further studied by
advanced NMR techniques.
Physical measurements
The elemental microanalyses (CHN) were performed
using a Perkin Elmer 2400 LS Series CHNS/O analyzer.
Melting points were recoded with a Gallenkamp digital
melting point apparatus.
Characterization
The FT-IR spectra of all the title compounds 2ozpn
—
18ozpn were recorded by using a Perkin Elmer
2000-FT-IR spectrophotometer in the frequency range
－1
4000—400 cm . The measurement was carried out
with the samples in KBr discs.
NMR spectra were recorded in DMSO at 298 K on a
Bruker 400 MHz UltrashiedTM FT-NMR spectrometer
equipped with a 5 mm BBI inverse gradient probe.
Chemical shifts were referenced to internal TMS. The
concentration of solute molecules was 50 mg in 1.0 mL
DMSO. Standard Bruker pulse programs23 were used
throughout the entire experiment. The spectroscopic
details (1H NMR and 13C NMR assignment) are sum-
marized in Table 1 for the diagnostic peaks. The NMR
assignments with respect to different nuclei in the title
compounds are accomplished based on the atomic-
numbering represented by compound 14ozpn (Figure
2).
Characterization by FT-IR spectroscopy
Compounds 2ozpn — 18ozpn were analyzed by
FT-IR, which show some important features with re-
spect to the nature of the functional groups. The
stretching frequencies of the lactone and lactam car-
bonyl groups υ O, gave rise to one intense band in the
C＝
－1
range 1675—1751 cm . However, as observed in o－ur
1
earlier study, a band in the range of 1310—1344 cm
22
was assigned to the bending of lactone υ
.
A me-
C—－
O
1
dium intense band at the 3307—3444 cm region is
attributed to the stretching of the O—H－group. The
1
bands at 1554—1610 and 1466—1594 cm are attrib-
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1518—1522

Synthesis and Characterization of New Compounds
uted to the stretc－hing of the phenyl ring24 while bands at
The downfield region of the spectrum is assigned to the
aromatic proton ring (A and B). Thus, a proton triplet at
δ 7.23 correlates with the doublet at δ 6.84 and 7.09.
These protons are assigned to the respective aromatic
ring proton (A) H-5, H-4, and H-6. Likewise, the aro-
matic ring proton (B) was observed through the correla-
tion between the signal that appears as a doublet at
δ 8.25 with the triplet at δ 7.54. The doublet at δ 7.37
correlates with the triplet at δ 7.74. However, COSY
data also reveals that the (OH) proton at δ 10.02 is cor-
related with the signal which is assigned to a singlet in
the region of δ 7.23 but not with the doublet at δ 6.84. A
proton at C-7 in the seven membered-ring shows a
singlet at δ 8.12 and does not show any correlation in
this spectrum. Long chain protons are established
through the correlation between the chain’s hydrogen,
which is exemplified by the correlation of H-1' located
at δ 3.13 with H-2' located at δ 1.72. In addition, the
alkyl protons exhibit complexity that can not be re-
solved using homonuclear decoupling. This phenome-
non was observed in our earlier publications.22
3011—3094 cm 1 are attributed to the aromatic C—H
stretching υ
H. Peaks in the range of 820—872, 751
CPh—
－1
—824, and 714—785 cm are ascribed to the out-of-
plane (γ H) bending.22,25 The titled compounds gave a
C—
－1
medium band at 1050—1081 cm due to υ N. A
C—
stretching band －from the benzene group appeared at
1
3211—3246 cm . The characteristic absorption bands
of the alkyl group (long chain) can be assigned by
symmetric, υ
and asymmetric, υ
as stretching
CH s
CH
3
3
which appe－ar within the range of 2949—2962 and 2916
1
—2938 cm . The absorption bands for υ
and υ
CH
CH s
3
2
as appear in the range of 2849—2870 and 2782—2858
－1
cm respectively.22,26 The band observed in the range
－1
of 1404—1469 cm is ascribed to the stretchin－g of
27
H
1
υ
and a very weak band at 2760—2698 cm is
C—
assigned to υ
.
H
C—
Characterization by NMR spectra
1
The H NMR, 13C NMR spectroscopy were used to
further substantiate the molecular structure of the title
compounds in DMSO at ambient temperature.
1H spectral assignment
Table 2 1H-1H correlation from 2D COSY for 2ozpn— 18ozpn
Compound
Atom H
H-2
COSY
OH
A complete assignment for the title compounds can
be made based on the representative compound, 14ozpn
(Figure 2). Two aromatic rings are differentiated by A
and B. The 1H NMR spectra for 2ozpn—18ozpn can be
separated into two different regions of chemical shift.
Signals of the aromatic proton A due to the H-2 proton
appears as a singlet at δ 7.09—7.28 whereas the H-4
proton appears as a doublet in the range of δ 6.72—7.18.
The occurrence of a doublet in the range of δ 6.89—
7.28 is attributed to the H-6 proton. A triplet at δ 7.16—
7.26 is assigned to the H-5 proton. The singlet in the
region of δ 9.53—10.02 corresponds to the hydroxyl
group (OH). In the same way, the chemical shift of the
aromatic ring B protons appears as a doublet in the
range of δ 8.21—8.35, which is assigned to the H-12
proton. Furthermore, two triplets exist at δ 7.51—7.78
and δ 7.72—7.85 which can be attributed to H-13 and
H-14, respectively. The signal for the H-15 proton ap-
pears as a doublet at δ 7.36—7.69. A singlet in the most
downfield region (δ 8.03—8.23) is assigned to H-7 from
the heterocyclic ring. The alkyl chain has four signals
that can be observed in the highfield region. There is
also a quintet at δ 1.28—1.78, which is attributed to the
H-2' proton. Two triplets assigned to the methyl proton
H-y and the methylene proton H-1' are observed at
δ 0.86—0.93 and δ 3.12—3.22, respectively. The alkyl
protons from H-3' to H-4'—H-16' atoms were confirmed
by multiplets in the range of δ 1.31—1.36.
H-4
H-5
H-5
H-4, H-6
H-5
H-6
O-H
H-7
H-2
—
2ozpn— 18ozpn
H-12
H-13
H-14
H-15
H-1'
H-2'
H-13
H-12
H-15
H-14
H-2'
H-1'
Characterization by 13C NMR spectroscopy
The structures of the compounds were further con-
firmed by 13C NMR and DEPT135 spectroscopy for the
protonated carbons. The 13C NMR spectra provide di-
rect information about the carbon skeleton of the mole-
cule. Detailed assignments of different resonance peaks
to their respective carbon atoms are based on the repre-
sentative compound 10ozpn. The 13C NMR spectra of
this series of compounds show similarities. Two signals
observed downfield at δ 169.188—169.832 and δ 168.102
—168.923 are attributed to the carbonyl carbon (C-8,
C-11) of the seven-membered ring. In addition, the sig-
nal of the hydroxyl carbon (C-3) appears at δ 158.203—
158.901. A signal at δ 13.832—15.371 is due to the ali-
phatic carbon (C-y) of the methyl group. Signals at
δ 40.454—40.992, 31.967—32.258, 27.446—32.785,
and δ 21.132—33.867 are attributed to C-1', C-2', C-3'
1
The assignments of H NMR spectra of these com-
pounds were subsequently confirmed with the aid of 2D
COSY experiments. The COSY experiments further
confirmed the correlation between the equivalent proton
pairs with adjacent protons. Cross peaks resulting from
these correlations appear in the same region (Table 2).
Chin. J. Chem. 2011, 29, 1518— 1522
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1521

Osman et al.
FULL PAPER
to C-4'—C-16', and C-x in the alkyl group, respectively.
The only difference is the increase in the number of
signals by two between 2ozpn— 18ozpn. The C-7 signal,
which is located in the heterocyclic ring, appears at
δ 86.213—86.953. The resonances due to the aromatic
ring A and B are located at δ 138.321—139.852,
114.765 — 115.734, 121.968 — 122.871, 129.114 —
129.848, 130.077 — 130.457, 131.127 — 131.632,
131.735 — 132.830, 128.318 — 128.978, 130.213 —
131.735, 138.396—138.663, and 122.503—123.843,
which are ascribed to C-1, C-2, C-4, C-5, C-6, C-9,
C-10, C-12, C-13, C-14, and C-15, respectively.
Aromatic quaternary carbons for all compounds
were established through the connectivities between
carbon and its neighboring proton by using a long-range
correlation HMBC experiment (Table 3). The spectra of
the compounds have similar correlations.
4
5
Ott, I.; Kircher, B.; Heinisch, G.; Matuszczak, B. J. Med.
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7
8
9
10 Ichikawa, M.; Igarashi, Y.; Ichikawa, Y. Tetrahedron Lett.
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Table 3 2D 1H-13C HMBC correlation for compounds 2ozpn—
18ozpn
13 Margolis, B. J.; Swidorski, J. J.; Rogers, B. N. J. Org. Chem.
2003, 68, 644.
14 Racker, R.; Doring, K.; Reiser, O. J. Org. Chem. 2000, 65,
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HMBC [J(C,H)]
Compound
Atom
2J
3J
4J
intraJ
H-2 C-3
H-4 C-5
C-4
C-6
—
—
—
C-2, C-6 C-1
H-5 C-4, C-6 C-1
C-2
C-3
C-6
—
H-6 C-5
OH C-4
C-4
C-1
—
C-15
C-15
H-7
—
—
—
17 Levai, A.; Ott, J.; Snatzke, G. Monatch. Chem. 1992, 123,
919.
2oznp— 18ozpn
H-12 C-9, C-13 C-10, C-14 C-15
18 Levai, A. J. Heterocyclic Chem. 2001, 38, 1011.
19 Matsumoto, Y.; Tsuzuki, R.; Matsuhisa, A.; Yoden, T.;
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H-13 C-12, C-14 C-9, C-15 C-8, C-10 C-2
H-14 C-13, C-15 C-10, C-12 C-9, C-11 —
H-15 C-10, C-14 C-13
H-1' C-2' C-3'
H-2' C-1', C-3' C-4'
C-12
C-5
—
—
—
—
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1522
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1518— 1522