Study of 1,3-dipolar cycloaddition and ring contraction of new 1,4-phenylene-bis[1,5]benzothiazepine derivatives

Article abstract of DOI:10.1002/jhet.1880

Some 1,4-phenylene-bis[1,2,4]oxadiazolo-[5,4-d][1,5]benzothiazepine derivatives (4a-c) were synthesized by 1,3-dipolar cycloaddition reaction of benzohydroximinoyl chloride with 1,4-phenylene-bis(4-aryl)- 2,3-dihydro[1,5]benzothiazepine (2a-c); meanwhile,

Full text of DOI:10.1002/jhet.1880

1764
Study of 1,3-Dipolar Cycloaddition and Ring Contraction of New
Vol 51
1,4-Phenylene-bis[1,5]benzothiazepine Derivatives
b
Fei Chen,a Fang-Ming Liu,a,b and Zhi-Qiang Dong
*
aCollege of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, People’s Republic of China
bCollege of Materials and Chemical Engineering, Hangzhou Normal University, Hang Zhou 310036, People’s Republic of China
*
E-mail: fmliu859@sohu.com
Received June 27, 2012
DOI 10.1002/jhet.1880
Published online 13 May 2014 in Wiley Online Library (wileyonlinelibrary.com).
CHO
R
COCH3
O
C
O
C
H
C
H
R
R
C
C
C
H
H
NaOH
OHC
1a-c
SH
NH 2
R
R
O
N
S
O
O
S
CH3 COCCH 3
N
N
N
Pyridine
S
S
O
R
3a-c
R
2a-c
Cl
OH
C
N
R
Et3
N
N
O
S
N
N
O
S
2a , R= H; 2b , R=OMe; 2c , R= Cl
3a , R= H; 3b , R=OMe; 3c , R= Cl
4a , R= H; 4b , R=OMe; 4c , R= Cl
N
R
4a-c
Some 1,4-phenylene-bis[1,2,4]oxadiazolo-[5,4-d][1,5]benzothiazepine derivatives (4a–c) were synthesized
by 1,3-dipolar cycloaddition reaction of benzohydroximinoyl chloride with 1,4-phenylene-bis(4-aryl)-
2,3-dihydro[1,5]benzothiazepine (2a–c); meanwhile, compounds 2a–c also occurred ring contraction under
acylating condition to obtain bis[2-aryl-20-(b-1,4-phenylenevinyl)-3-acetyl]-2,3-dihydro[1,5]benzothiazoles
1
(3a–c). The structures of some novel compounds were confirmed by IR, H-NMR, elemental, and X-ray
crystallographic analysis.
J. Heterocyclic Chem., 51, 1764 (2014).
INTRODUCTION
to the thiazepine system could induce an increase of the
ring inversion barrier and consequently modify the activity
profile [5,6].
The synthesis of benzothiazepine derivatives had at-
tracted considerable attention because of their broad
spectrum of biological activities, such as cardiovascular
modulator, coronary vasodilators, ACE inhibitors, anti-
HIV, antihypertensive, antidepressant, antibacterial, and
anticancer activity [1–3]. Diltiazem and Clentiazem were
widely used as calcium channel blockers. Recently, prog-
ress had been made into fix an additional heterocycle on
the heptatomic nucleus of 1,5-benzothiazepine for the
preparation of tricyclic compounds that were found to be
very potent nonnucleoside reverse transcriptase inhibitors
[4]. The presence of the conformational preferences of
the seven-membered ring was possibly correlated with
biological activity and the fusion of a heterocyclic nucleus
1,2,4-Oxadiazole ring was also a major five-membered
heterocyclic ring, which served as the core component of
many substances that displayed a wide range of biological
activities including apoptosis inducers, anticancer [7], anti-
HIV [8], and selective cathepsin inhibitors [9]. In addition,
many thiazoles had emerged as active pharmaceutical
ingredients in several drugs because of their potential
anti-inflammatory, antitumor [10], antihyperlipidemic,
and antihypertensive [11] properties. Several methods for
the synthesis of thiazoles had been developed, in particular
for the 2-substituted benzothiazole. Most common synthetic
methods used for their preparation were based on the con-
densation of 2-aminothiophenol with substituted carboxylic
© 2014 HeteroCorporation

Study of 1,3-Dipolar Cycloaddition and Ring Contraction of New 1,4-Phenylene-bis
[1,5]benzothiazepine Derivatives
November 2014
1765
acids, acyl chlorides, aldehydes, and nitriles [12]. Literature
had reported a simple and convenient method of the
synthesis of 2,3-dihydrobenzothiazoles by ring contrac-
tion of 2,3-dihydro[1,5]benzothiazepines under acylating
reaction conditions [13]. But the study of the 1,3-dipolar
cycloaddition and ring contraction of bis-2,3-dihydro[1,5]
benzothiazepines were scarcely.
Inspired by the result of a research that dimers had
shown more excellent activities than a monomer [14], the
present investigation deals with the synthesis of novel
1,4-phenylene-bis(4-substituted phenyl)benzothiazepines
and study their 1,3-dipolar cycloaddition and ring contraction
as outlined in Scheme 1. These compounds might have useful
biological and therapeutic activities. The crystal structure
of 4c determined by single-crystal X-ray diffraction was
reported.
cycloadducts 4a–c, yet underwent ring contraction with
acetic anhydride leading to the formation of ring contrac-
tion products 3a–c. The mechanism of ring contraction of
simple 2,4-diaryl-2,3-dihydro-1,5-benzothiazepines had
been proposed by Lévai, A., previously [15]. According to
their interpretation, conversion of 2,4-diaryl-2,3-dihydro-
1,5-benzothiazepines (2) into 2-styrylbenzothiazole (3) may
start with acetylation of the nitrogen atom of benzothiazepine,
followed either by heterolytic S—(C-2) bond scission and
subsequent nucleophilic attack of the sulfur atom at C-4
affording an ally1 cation, or by a nucleophilic attack of sulfur
as mentioned earlier giving rise to a cyclic sulfonium salt,
deprotonation of which furnishes 3 (Scheme 2). The
structures of all the synthesized compounds were estab-
lished on the basis of their spectroscopic data; there was
not 1H-NMR data of the compounds 4a–c because of their
poor solubility.
In IR spectra, the synthesized final compounds 3a–c
showed a strong stretching vibration at 1672–1673 cmꢀ1
because of the presence of C═O; compounds 4a–c showed
a strong stretching vibration at 1605–1608cmꢀ1 because of
the presence of C═N. The 1H-NMR spectrum revealed two
distinct doublets at d 6.86–6.90 and 6.51–6.54ppm were
attributed to CH═CH for compounds 3a–c, respectively,
and J = 15.7 Hz, which indicated the transconfiguration.
The presence of a singlet at d 2.09ppm was attributed to
the COCH3. In MS spectra, molecular ions peaks of all target
compounds were attained from EIMS. The molecular
RESULTS AND DISCUSSION
A series of novel bis-benzodiazepine derivatives con-
taining 1,2,4-oxadiazole moiety was synthesized using
terephthalic aldehyde as a starting material. The intermediate
compounds, bis-benzodiazepine derivatives 2a–c, were
synthesized by reacting of a,b-unsaturated ketone 1a–c with
double equivalent o-aminobenzenethiol in ethanol using
acetic acid as catalyst. Finally, the compounds 2a–c
underwent 1,3-dipolar cycloaddition with benzohydroximinoyl
chloride in the presence of Et3N leading to the formation of
Scheme 1. Synthetic process of the title compounds.
CHO
R
COCH3
O
C
O
C
H
C
H
R
R
C
C
C
H
H
NaOH
OHC
1a-c
SH
NH 2
R
R
O
N
S
O
O
S
CH3 COCCH 3
N
N
N
Pyridine
S
S
O
R
3a-c
R
2a-c
Cl
OH
C
N
R
Et3
N
N
O
S
N
N
O
S
2a , R= H; 2b , R=OMe; 2c , R= Cl
3a , R= H; 3b , R=OMe; 3c , R= Cl
4a , R= H; 4b , R=OMe; 4c , R= Cl
N
R
4a-c
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1766
F. Chen, F.-M. Liu, and Z.-Q. Dong
Vol 51
Scheme 2. The mechanism of ring contraction.
EXPERIMENTAL SECTION
structure of compound 4c was also confirmed by X-ray
diffraction analysis, as shown in Figure 1. Detailed informa-
tion about the crystal data and structure determination was
summarized in Table 1. Selected interatomic distances and
bond angles were tabulated in Table 2. Intermolecular
interactions (Å) were listed in Table 3.
Although the compound 4c had an abundance of
conventional hydrogen-bond acceptors, it was a complete
lack of donors. Thus, the packing features C—H group
acted as donor in weak hydrogen-bond; however, the
crystal was stabilized by weak offset face-to-face pꢁꢁꢁp
interactions between cyclical 1 and cyclical 2, which was
shown in Table 3, Figure 2. Other weak forces such as
hydrophobic and dipole–dipole interactions also contributed
to stabilization, but documenting them had proved to be
more challenging than the study of H-bonding [16], the
associated centroid–centroid distance between the benzene
ring of Cg3│Cg3 was 3.6503 Å.
Suitable single crystals of the complex of dimension
0.67 ꢂ 0.52 ꢂ 0.28 mm3, single-crystal diffraction data for
4c were collected on a Bruker Smart Apex Duo diffrac-
tometer (Germany Bruker Company’s Single Crystal Diffrac-
tion) at 296(2) K with Mo–Ka radiation (k = 0.71073 Å).
Semiempirical absorption corrections were applied using
SADABS program. All the structures were solved by direct
methods using the SHELXS program of the SHELXTL pack-
age and refined by full-matrix least-squares methods on F2
with SHELXL 97 [17]. Molecular structure was checked
using PLATON [18]. 1,5-Benzothiazepine ring that was
characterized by the endocyclic torsion angles adopts a boat-
like conformation, The four atoms of C(17), C(25), N(1),
and S(1) were closely coplanar; C(1), C(6), and C(30) were
above the plane, with their deviations being ꢀ1.2236,
ꢀ1.1852, and ꢀ0.6417 Å, respectively. The five-membered
ring plane adopted an envelope conformation with atom C
(17) deviating from the plane defined by C(8) N(1), N(2),
and O(1) of 0.4993 Å. Cg(2) [center of gravity of the
benzene ring (C1–C6)] was almost perpendicular with Cg(3)
that dihedral angle was 91.0ꢃ, dihedral angle between oxadia-
zole ring Cg(1) and Cg(4) [center of gravity of the benzene
ring (C18–C23)] was 91.0ꢃ, whereas with Cg(3) was 28.7ꢃ.
All reagents were of commercial availability. Reactions were
monitored by TLC. Melting points were measured on a mettler
FP-5 capillary melting point apparatus and were uncorrected.
Elemental analyses were conducted on a Perkin-Elmer 2400
elemental analyzer. The IR spectra were determined as potassium
bromide pellet on a Bruker Equinox 55 FTIR spectrophotometer.
Mass spectra were recorded on an Agilent 5975 apparatus
(EI, 70 eV). X-ray crystal structure was obtained using R-AXIS
SPIDER X-ray diffraction. Compounds 1a–c [19,20] and
benzenecarboximidoyl chloride [21] were synthesized according
to the reported literatures.
General procedure for the synthesis of compounds 2a–c.
A mixture of bischalcone (1) (5 mmol) and o-aminothiophenol
(12 mmol) in anhydrous ethanol (50 mL) was heated under
reflux for 8 h in the presence of acetic acid (1.0 mL). The
mixture was cooled to RT, and then the solid product was
separated by filtration and recrystallized from DMF/H2O to give
corresponding compounds 2a–c.
1,4-Phenylene-bis(4-phenyl)-2,3-dihydro[1,5]benzothiazepine (2a).
Pale yellow solid (70%); mp 199–200ꢃC; FTIR n 1610 (C═N), 1324
(C—N), 1241 (C—O—C) cmꢀ1; 8.09–7.16 (m, 22H, ArH), 4.98
(dd, 2H, H2x, Jax =9.2Hz, Jbx = 2.0 Hz), 3.33 (dd, 2H, H3b,
Jbx =2.0Hz, Jab = 4.5 Hz), 3.06 (dd, 2H, H3a, Jax =9.2Hz,
Jab = 4.5 Hz); MS (ESI): m/z 553 (M+ +1); Anal. Calcd for
C36H28N2S2: C, 78.22; H, 5.11; N, 5.07; S, 11.60; Found: C, 78.20;
H, 5.11; N, 5.08; S, 11.61.
1,4-Phenylene-bis(4-chlorophenyl)-2,3-dihydro[1,5]benzo
thiazepine (2b).
n 1606 (C═N), 1318 (C—N), 1244 (C—O—C) cmꢀ1
Pale white solid (75%); mp 224–225ꢃC; FTIR
;
1H-
NMR d 7.97–7.15 (m, 20H, ArH), 4.95 (dd, 2H, H2x,
Jax = 9.6 Hz, Jbx = 2.6 Hz), 3.24 (dd, 2H, H3b, Jbx = 2.6 Hz,
Jab = 8.5 Hz), 3.04 (dd, 2H, H3a, Jax = 9.6 Hz, Jab = 8.5 Hz); MS
(ESI): m/z 621 (M+ + 1); Anal. Calcd for C36H26Cl2N2S2: C,
69.56; H, 4.22; Cl, 11.41; N, 4.51; S, 10.32; Found: C, 69.57;
H, 4.21; Cl, 11.42; N, 4.50; S, 10.32.
1,4-Phenylene-bis(4-methoxyphenyl)-2,3-dihydro[1,5]
benzothiazepine (2c).
228ꢃC; FTIR n 1597 (C═N), 1349 (C—N), 1261 (C—O—C)
cmꢀ1 1H-NMR d 8.02–7.16 (m, 20H, ArH), 4.97 (dd, 2H,
Pale yellow solid (72%); mp 226–
;
H2x, Jax = 9.1 Hz, Jbx = 2.6 Hz), 3.83 (s, 6H, —OCH3), 3.30
(dd, 2H, H3b, Jbx = 2.6 Hz, Jab = 4.6 Hz), 3.04 (dd, 2H, H3a,
Jax = 9.1 Hz, Jab = 4.6 Hz); MS (ESI): m/z 613 (M+ + 1); Anal.
Calcd for C38H32N2O2S2: C, 74.48; H, 5.26; N, 4.57; O,
5.22; S, 10.47; Found: C, 74.47; H, 5.26; N, 4.56; O, 5.23;
S, 10.47.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2014
Study of 1,3-Dipolar Cycloaddition and Ring Contraction of New 1,4-Phenylene-bis
[1,5]benzothiazepine Derivatives
1767
cyclical 1
cyclical 2
Figure 1. ORTEP representation and packing diagram of compound 4c. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
General procedure for the synthesis of compounds 3a–c
[16]. A mixture of 1,4-phenylene-bis(4-substituented phenyl)
[1,5]benzothiazepine (2) (5 mmol), acetic anhydride (15 mL),
and anhydrous pyridine (8 mL) was maintained at 80ꢃC for
8–10 h (monitored by TLC ) and then poured into water. The
precipitate was filtered off, washed with water, and purified
by silica gel column chromatography (ethylacetate/petroleum
ether = 1:5, v/v) to afford the desired products 3a–c.
637 (M+ +1); Anal. Calcd for C40H32N2O2S2: C, 75.44; H, 5.06; N,
4.40; O, 5.02; S, 10.07; Found: C, 75.43; H, 5.05; N, 4.42; O, 5.02;
S, 10.07.
Bis[2-chlorophenyl-20-(b-1,4-phenylenevinyl)-3-acetyl]-2,3-
dihydrobenzothiazole (3b). Pale white solid (75%); mp
134–135ꢃC; FTIR n 1673 (C═N), 1320 (C—N), 970 (CH═CH,
trans) cmꢀ1 1H-NMR d 7.03–7.62 (m, 20H, ArH), 6.85–6.90
;
(d, J = 15.7Hz, 2H, benzothiazole ring—CH═), 6.51–6.54
(d, J = 15.7Hz, 2H, benzene ring—CH═), 2.09 (s, 6H, COCH3);
MS (ESI): m/z 705 (M+ + 1); Anal. Calcd for C40H30Cl2N2O2S2:
C, 68.08; H, 4.28; Cl, 10.05; N, 3.97; O, 4.53; S, 9.09; Found: C,
68.07; H, 4.28; Cl, 10.05; N, 3.98; O, 4.53; S, 9.09.
Bis[2-phenyl-20-(b-1,4-phenylenevinyl)-3-acetyl]-2,3-dihydro
benzothiazole (3a). Pale yellow solid (74%); mp 119–120ꢃC;
FTIR n 1672 (C═O), 1319 (C—N), 970 (CH═CH, trans) cmꢀ1
;
1H-NMR
d 7.04–7.62 (m, 22H, ArH), 6.86–6.91 (d, 2H,
J= 15.7 Hz, benzothiazole ring—CH═), 6.51–6.56 (d, J= 15.7 Hz,
2H, benzene ring—CH═), 2.09 (s, 6H, COCH3); MS (ESI): m/z
Bis[2-methoxyphenyl-20-(b-1,4-phenylenevinyl)-3-acetyl]-2,3-
dihydrobenzothiazole (3c). Pale yellow solid (68%); mp
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1768
F. Chen, F.-M. Liu, and Z.-Q. Dong
Vol 51
Table 1
Crystal data and structure refinement of compound 4c.
Formula
Crystal color
C52 H46 N4 O6 S2
Colorless
Formula weight
887.05
Temperature (K)
296(2)
Crystal size (mm)
Crystal system
Space group
a(Å)
0.67 ꢂ 0.52 ꢂ 0.28
Monoclinic
P21/c
12.6667(7)
15.6290(9)
13.1282(7)
90.00
118.2320(10)
90.00
2289.8(2)
2
b(Å)
c(Å)
a(ꢃ)
b(ꢃ)
g(ꢃ)
V(Å3)
Z
Figure 2. Weak offset face-to-face pꢁꢁꢁp interactions between cyclical 1
Dc(mg mꢀ3
)
1.287
1.82–27.50
0.172
and cyclical 2.
θ range (ꢃ)
m(mmꢀ1
)
Et3N (1 mL) in the same solvent (10 mL) was added dropwise
slowly. The mixture was kept under stirring for 36 h at RT. Then,
the triethylamine hydrochloride byproduct was removed by
filtration. Solvent was evaporated in vacuo, and the remaining
materials were purified by silica gel column chromatography
(ethylacetate/petroleum ether = 1:4, v/v) to afford the desired
products 4a–c.
Reflections collected
Data/restraints/parameters
Final R indices [I > 2s(I)]
R indices (all data)
CCDC
19652
5242/0/298
R1 = 0.0614, oR2 = 0.1938
R1 = 0.0814, oR2 = 0.2207
806204
137–138ꢃC; FTIR n 1672 (C═N), 1320 (C—N), 971 (CH═CH,
trans) cmꢀ1 1H-NMR d 7.03–7.64 (m, 20H, ArH), 6.85–6.91
2,2’-(1,4-Phenylene)-bis[3a-(4-phenyl)-4,5-dihydro-3aH-(3-phenyl-
;
[1,2,4]oxadiazolo)-[5,4-d][1,5]benzothiazepine].
Pale yellow
solid (23%); mp 302–304ꢃC; FTIR n 1605 (C═N), 1350 (C—N),
1249 (C—O—C), 693 (C—S—C) cmꢀ1; MS (EI): m/z 790 (M+);
Anal. Calcd for C50H38N4O2S2: C, 75.92; H, 4.84; N, 7.08; O,
4.05; S, 8.11; Found (%):C, 75.93; H, 4.83; N, 7.08; O, 4.04; S, 8.12.
2,2’-(1,4-Phenylene)-bis[3a-(4-chlorophenyl)-4,5-dihydro-3aH-
(d, J = 15.8 Hz, 2H, benzothiazole ring—CH═), 6.51–6.55
(d, J = 15.8Hz, 2H, benzene ring—CH═), 3.85 (s, 3H, —OCH3),
2.10 (s, 6H, COCH3); MS (ESI): m/z 697 (M+ + 1); Anal. Calcd
for C42H36N2O4S2: C, 72.39; H, 5.21; N, 4.02; O, 9.18; S, 9.20;
Found (%): C, 72.39; H, 5.20; N, 4.01; O, 9.18; S, 9.22.
General procedure for the synthesis of compounds 4a–c.
To a stirred solution of compounds 2 (0.5 mmol) and benzohy-
droximinoyl chlorides (1.5 mmol) in CH2Cl2 (50 mL), a solution of
(3-phenyl-[1,2,4]oxadiazolo)-[5,4-d][1,5]benzothiazepine].
Pale
white solid (20%); mp 322–324ꢃC; FTIR n 1606 (C═N), 1351
(C—N), 1249 (C—O—C), 692 (C—S—C) cmꢀ1; MS (EI): m/z
Table 2
Selected bond lengths (Å), bond angle (ꢃ), and torsion angle (ꢃ) of compound 4c.
S(1)—C(25)
1.848(3)
C(1)—S(1)—C(25)
102.73(12)
N(2)—O(1)—C(17)—C(18)
83.2(2)
O(1)—C(17)
O(1)—N(2)
N(1)—C(8)
N(1)—C(17)
1.452(3)
1.429(3)
1.429(3)
1.474(3)
C(26)—C(25)—C(30)
C(8)—N(1)—C(17)
N(92)—O(1)—C(17)
C(18)—C(17)—C(30)
111.6(2)
100.36(17)
104.9(2)
C(17)—N(1)—C(8)—N(2)
C(25)—S(1)—C(1)—C(2)
C(6)—N(1)—C(17)—C(30)
C(8)—N(1)—C(17)—C(18)
158.6(2)
ꢀ117.0(3)
18.4(3)
ꢀ84.6(2)
113.00(19)
Table 3
Intermolecular interactions (Å) in compound 4c.
D—HꢁꢁꢁA
D—H
HꢁꢁꢁA
DꢁꢁꢁA
∠D—HꢁꢁꢁA
C(3)—H(3)aꢁꢁꢁO(2)
0.930
0.930
0.930
2.522
2.649
2.862
3.392(4)
3.374
3.610
155.8
135.3
140.2
C(14)—H(14b)bꢁꢁꢁO(2)
C(28)—H(10B)cꢁꢁꢁCg3
Cg3 is the center of gravity of ring C(9)—C(10)—C(11)—C(12)—C(13)—C(14)
a1 ꢀ X, 1/2 + Y, 1/2 ꢀ Z
b1 + X, Y, Z
cX, 1/2 ꢀ Y, 1/2 + Z
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2014
Study of 1,3-Dipolar Cycloaddition and Ring Contraction of New 1,4-Phenylene-bis
[1,5]benzothiazepine Derivatives
1769
858 (M+); Anal. Calcd for C50H36Cl2N4O2S2: C, 69.84; H, 4.22; Cl,
8.25; N, 6.52; O, 3.72; S, 7.46; Found (%): C, 69.84; H, 4.22; Cl,
8.25; N, 6.51; O, 3.73; S, 7.46.
2,2’-(1,4-Phenylene)-bis[3a-(4-methoxyphenyl)-4,5-dihydro-
3aH-(3-phenyl-[1,2,4]oxadiazolo)-[5,4-d][1,5]benzothiazepine].
Colorless crystals (30%); mp 314–316ꢃC; FTIR n 1608 (C═N),
1351 (C—N), 1249 (C—O—C), 694 (C—S—C) cmꢀ1; MS
(EI): m/z 850 (M+); Anal. Calcd (%) for C52H42N4O4S2: C,
73.39; H, 4.97; N, 6.58; O, 7.52; S, 7.54; Found (%): C, 73.39;
H, 4.96; N, 6.58; O, 7.53; S, 7.54.
[3] Singh, P. K.; Srivastava, V.; Singh, J.; Siddiqui, I. R. Indian J
Chem 2005, 44B, 2178.
[4] Di Santo, R.; Costi, R. II Farmaco 2005, 60, 385.
[5] Greco, G.; Novellino, E.; Fiorini I.; Nacci V.; Campiani, G.;
Ciani, S. M.; Garofalo, A.; Bernasconi, P.; Mennini, T. A. J Med Chem
1994, 37, 4100.
[6] Sarro, G. D.; Chimirri, A.; Sarro, A. D.; Gitto, R.; Grasso, S.;
Zappala, M. Eur J Med Chem 1995, 30, 925.
[7] Zhang, H. Z.; Kasibhatla, S.; Kuemmerle, J.; Kemnitzer, W.;
Crogan-Grundy, C.; Tseng, B.; Drewe, J.; Cai, S.X. J Med Chem 2005,
48, 5215.
[8] Sakamoto, T.; Cullen, M. D.; Hartman, T. L.; Karen M.;
Watson, K. M.; Buckheit, R. W.; Pannecouque, C.; Clercq, E. D.;
Cushman, M. J Med Chem 2007, 50, 3314.
CONCLUSION
[9] Frizler, M.; Lohr, F.; Furtmann, N.; Klas, J.; Gutschow, M. J
Med Chem 2011, 54, 396.
In summary, the present study described the synthesis of
some novel 1,4-phenylene-bis[1,2,4]oxadiazolo[5,4-d][1,5]
benzothiazepines (4a–c) via nitrile oxide cycloaddition. The
bis[2-aryl-20-(b-1,4-phenylenevinyl)-3-acetyl]-2,3-dihydro[1,5]
benzothiazoles (3a–c) were also newly synthesized through
ring contraction. The structural identities of compounds 4 was
further confirmed by X-ray analysis of compound 4c as typical
example of the new bis-1,5-benzothiazepine derivatives with
symmetrical structure.
[10] Mortimer, C. G.; Wells, G.; Crochard, J-P.; Erica, L.; Stone, E.
L.; Tracey, D.; Bradshaw, T. D.; Stevens, M. F. G.; Westwell, A. D. J
Med Chem 2006, 49, 179.
[11] Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.;
Helio, G.; Bonacorso, H. G. Chem Rev 2008, 108, 2015.
[12] Martins, M. A. P.; Frizzo, C.P.; Moreira, D. N.; Buriol, L.;
Machado, P. Chem Rev 2009, 109, 4140.
[13] Lévai, A. J Heterocycl Chem 2004, 41, 399.
[14] Park, I. H.; Xie, S.; Shapiro, T. A.; Labonte, T.; Narducci, S.
A. A.; Baege, A. C.; Posner, G. H. J Med Chem 2006, 30, 925.
[15] Tóth, G.; Lévai, A.; Balázs, B.; Andras Simon, A. Liebigs
Ann.lRecueil 1997, 995.
[16] Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; John
Wiley & Sons, Ltd.: Chichester, 2000.
Acknowledgments. We are grateful to the Key SCI-Tech
Innovation Team of Zhejiang Province (2010R50017) for
financial help.
[17] Sheldrick, G. M. SHELX97, Program for X-ray crystal
structure solution and refinement. Göttingen University Germany,
1997.
[18] Spek, AL. PLATON molecular graphics program. J Appl
Cryst 2003, 36, 7.
[19] Zhou, J. F.; Zhou, J. F.; Zou, Z. C.; Feng, J. C. Synthetic
Communications 2002, 32, 3389.
REFERENCES AND NOTES
[20] Shao, Q.; Liu, H.; Wang, T. T.; Zeng, H. P. J Heterocyclic
Chem 2011, 48, 1434.
[21] Sanders, B. C.; Friscourt, F.; Ledin, P. A.; Mbua, N. E.;
Arumugam, S.; Gou, J.; Boltje, T. J.; Popik, V. V.; Boons, G. J. J Am
Chem Soc 2011, 133, 949.
[1] Bariwal, J. B.; Upadhyay, K. D.; Manvar, A. T.; Trivedi, J. C.;
Singh, J. S.; Jain, K. S.; Shah, A. K. Eur J Med Chem 2008, 43, 2279.
[2] Slade, J.; Stanton, J. L.; Ben-David, D.; Mazzenga, G. C. J
Med Chem 1985, 28, 1517.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet