Microwave-assisted synthesis of substituted dibenzo[b,f][1,4]thiazepines, dibenzo[b,f][1,4]oxazepines, benzothiazoles, and benzimidazoles

Article abstract of DOI:10.1002/jhet.2003

A highly efficient synthesis for possessing 7-membered rings with two heteroatoms is described, using efficient microwave-assisted one-pot method to synthesize (substituted) dibenzo[b,f][1,4]thiazepines [1] and dibenzo[b,f][1,4]oxazepines [2] in high yields (up to 99%) by cyclocondensations of o-aminothiophenol or o-aminophenol with o-halobenzaldehydes, o-fluoroacetophenone, and o-fluorobenzophenone. In the absence of base, o-aminothiophenol reacted with o-halobenzaldehydes to afford benzothiazoles.

Full text of DOI:10.1002/jhet.2003

808
Microwave-Assisted Synthesis of Substituted Dibenzo[b,f ][1,4]thiazepines,
Dibenzo[b,f ][1,4]oxazepines, Benzothiazoles, and Benzimidazoles
Vol 51
*
Yu-Chin Lin, Ni-Ching Li, and Yie-Jia Cherng
Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology,
Taichung 40605, Taiwan
*
E-mail: yjcherng@ctust.edu.tw
Received January 19, 2013
DOI 10.1002/jhet.2003
Published online 6 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
A highly efficient synthesis for possessing 7-membered rings with two heteroatoms is described, using efficient
microwave-assisted one-pot method to synthesize (substituted) dibenzo[b,f][1,4]thiazepines [1] and dibenzo[b, f ]
[1,4]oxazepines [2] in high yields (up to 99%) by cyclocondensations of o-aminothiophenol or o-aminophenol
with o-halobenzaldehydes, o-fluoroacetophenone, and o-fluorobenzophenone. In the absence of base,
o-aminothiophenol reacted with o-halobenzaldehydes to afford benzothiazoles.
J. Heterocyclic Chem., 51, 808 (2014).
INTRODUCTION
the solvent of DMF, DMSO, or NMP using t-BuOK as
the base. The reaction mixture was heated at 100ꢀC under
microwave irradiation for 3–7 min to afford 53–82%
yield of dibenzo[b,f][1,4]thiazepine (1a) (entries 1–3,
pt?>Table 1). The yield of 1a was greatly increased at elevated
reaction temperature. Thus, the cyclocondensation was
achieved by microwave irradiation at 120–140ꢀC for 1–3min
in DMF in the presence of t-BuOK to afford 1a in 99% yield
(entries 5 and 6, Table 1). In this case, use of a mild base
NaHCO3 was inferior, requiring a prolonged reaction time
(14 min) to give a moderate yield (57%) of the desired product
1a (entry 7, Table 1).
The cyclocondensations of o-aminothiophenol with
o-chlorobenzaldehyde, o-bromobenzaldehyde, and
o-iodobenzaldehyde were similarly carried out (entries
8–10, Table 1). Of the four o-halobenzaldehydes
studied, the relative reactivity of 1a formation
appeared to decrease in the order of F > Cl > Br > I.
This is a typical example of element effect. The reaction
was considered to proceed with an imine intermediate,
followed by intramolecular nucleophilic attack of sulfide to
halide (path A). The order of the reaction (F> Cl> Br > I)
suggested that an SNAr mechanism was operating, in which
the rate determining step was favored by the nucleophilic
substitution at the less hindered and more electronegative
floride atom.
Many important physiological materials comprise thiazepines
[1], oxazepines [2], benzothiazoles, benzimidazoles [3], and
the related structures. Dibenzo[b,f][1,4]thiazepine and
dibenzo[b,f][1,4]oxazepine, the analogs of thiazepine
and oxazepine having an additional fused aromatic ring,
have also received intensive attention. These compounds
possessing 7-membered rings with two heteroatoms have
been prepared through various synthetic routes. For example,
dibenzo[b,f][1,4]thiazepine has been prepared from 9H-
thioxanthen-9-ol with o-mesitylenesulfonylhydroxylamine
[4] . 1,4-Dibenzothiazepine has been synthesized by reaction
of lithiated 2-aminodiphenyl sulfide with DMF [5]. Cycliza-
tion of o-nitrobenzene halides with o-thiosalicylic acid
esters, followed by reduction and dehydration, also afford
dibenzothiazepine products [6]. We describe herein a novel
and efficient synthesis of dibenzo[b,f][1,4]thiazepines and of
the related heteroaromatic derivatives in one-pot procedure.
RESULTS AND DISCUSSION
In an attempt to find the optimized condition for the
microwave-assisted synthesis of 1,4-benzothiazepine,
the cyclocondensations of o-aminothiophenol with
o-halobenzaldehyde were investigated in details with
varied reaction factors including time, temperature, sol-
vent, and base (Scheme 1 and Table 1). The microwave-
assisted cyclocondensations of o-aminothiophenol with
o-fluorobenzaldehyde were successfully conducted in
To our surprise, the microwave-assisted reactions of
o-aminothiophenol with o-halobenzaldehydes produced
good yields (up to 97%) of 2-(o-halophenyl)benzothiazoles in
the absence of base (entries 11–13, Table 1). Because of the
© 2013 HeteroCorporation

May 2014
Microwave-Assisted Synthesis of Substituted Dibenzo[b, f][1,4]thiazepines, Dibenzo[b, f]
809
[1,4]oxazepines, Benzothiazoles, and Benzimidazoles
Scheme 1
high nucleophilicity of thiophenol, attack of imine might
be favored to form a benzothiazoline intermediate
(path B), which was readily converted to benzothiazoline
2a–c by autoxidation.
dibenzo[b,f][1,4]diazepine was formed whether in the
presence or absence of base. This microwave-assisted method
thus provided an alternative synthesis of 2-arylbenzimidazoles
from o-phenylenediamine and appropriate aldehydes using air
as oxidant without any catalyst [10].
Various methods for the synthesis of dibenzo[b, f][1,4]
oxazepines have been reported in the literature [7–9]. The
microwave-assisted cyclocondensation of o-aminophenol
with o-fluorobenzaldehyde always gave dibenzo[b,f][1,4]
oxazepine (3a) whether in the presence or absence of base
(Scheme 2 and entries 1–3 in Table 2). Phenoxide is a
weaker nucleophile than thiophenoxide, so that the forma-
tion of 3a required a prolonged time (20 min) at 140ꢀC in
comparison with the reaction of o-aminothiophenol
(entries 6 and 7, Table 1). The relative reactivity of
o-halobenzaldehydes in 3a formation (entries 3–6,
Table 2) followed the similar trend (F > Cl > Br > I). Unlike
o-aminothiophenol, no side product of 2-(o-halophenyl)
benzoles was observed in the microwave-assisted condensa-
tion of o-aminothiophenol with o-halobenzaldehydes.
In sharp contrast, the microwave-assisted reactions
of o-phenylenediamine with 2-fluorobenzaldehyde
and 2-chlorobenzaldehyde in DMF delivered only
2-arylbenzimidazoles in 93% and 89% yields,
respectively (Scheme 2 and entries 8 and 9 in Table 2). No
We next explored the effects of substituents on the nucleo-
phile and aldehyde components. The 2-halobenzaldehydes
bearing nitro, trifluoromethyl, or methoxy substituents reacted
with o-aminothiophenol and o-aminophenol under micro-
wave irradiation to give the corresponding cyclocondensation
products in 51–85% yields (Table 3). The benzaldehydes
bearing electron-withdrawing groups (NO2 or CF3) inclined
to give higher yields of cyclocondensation products than the
benzaldehydes bearing electron-donating substituent
(OCH3). The electron donating substituent might retard the
efficiency of the incoming S- and O-nucleophiles. Attempts
to carry out the similar cyclocondensation of 6-bromo-
3,4-dimethoxybenzaldehyde failed even by microwave
irradiation at 200ꢀC for 80 min.
Using substituted nucleophiles in the cyclocondensation
reactions with substituted o-fluorobenzaldehydes would
provide a straightforward method to generate libraries of
dibenzo[b,f][1,4]thiazepines and dibenzo[b,f][1,4]oxazepines.
To demonstrate this application, 2-amino-4-methylphenol and
Table 1
Reactions of o-halobenzaldehydes with o-aminothiophenol under microwave irradiation.
Entry
X
Base
Solvent
Temperature (ꢀC)
Time (min)
Product (yield, %)
1
2
3
4
5
6
7
8
F
F
F
F
F
F
F
Cl
Br
I
F
Cl
Br
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
NaHCO3
t-BuOK
t-BuOK
t-BuOK
–
DMF
DMSO
NMP
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
100
100
100
110
120
140
140
120
120
140
140
140
140
7
4
3
3
3
1
14
4
1a (82)
1a (65)
1a (53)
1a (85)
1a (99)
1a (99)
1a (57)
1a (99)
1a (99)
1a (93)
2a (97)
2b (92)
2c (90)
9
5
10
11
12
13
10
16
16
16
–
–
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DOI 10.1002/jhet

810
Y.-C. Lin, N.-C. Li, and Y.-J. Cherng
Vol 51
2-amino-4-chlorophenol were used to react with
(substituted) o-fluorobenzaldehydes under microwave irradia-
tion at 140ꢀC to afford good yields (60–86%) of the desired
cyclocondensation products 5a–h (Table 4).
In addition to (substituted) o-fluorobenzaldehydes,
the microwave-assisted cyclocondensation reactions of
o-fluorophenones were also achieved (Table 5). Using
t-BuOK as the base, o-aminothiophenol was reacted
with o-fluorobenzophenone under microwave irradia-
tion at 180ꢀC for 20–30 min in NMP to give 67%
yield of 11-phenyldibenzo[b,f][1,4]thiazepine. The yield
was increased to 87% when the reaction was conducted at
higher temperature (200ꢀC). The reaction of o-aminophenol
with o-fluorobenzophenone in the presence of t-BuOK
occurred in a similar manner to afford a 49% yield of
11-phenyldibenzo[b,f][1,4]oxazepine (entry 3, Table 5).
The microwave-assisted reaction of o-aminophenol with
o-fluoroacetophenone in NMP occurred at 180ꢀC to give
the corresponding 11-methyldibenzo[b,f][1,4]oxazepine
in 62% yield (entry 4, Table 5). In general, the
cyclocondensation reactions of phenones required higher
reaction temperature and longer times than the reactions
of benzaldehydes. The yields of the cyclocondensations
appeared to decrease with bulkier substrates.
In conclusion, we have successfully demonstrated a
novel and efficient microwave-assisted one-pot method to
synthesize (substituted) dibenzo[b,f][1,4]thiazepines and
dibenzo[b,f][1,4]oxazepines in high yields (up to 99%) by
cyclocondensations of o-aminothiophenol or o-aminophenol
with o-halobenzaldehydes, o-fluoroacetophenone, and
o-fluorobenzophenone. In the absence of base, o-
aminothiophenol and o-phenylenediamine reacted with
o-halobenzaldehydes to afford benzothiazoles and benz-
imidazoles.
Scheme 2
Table 2
Reactions of o-aminophenol and o-phenylenediamine with
o-halobenzaldehydes in DMF at 140ꢀC for 20 min under
microwave irradiation.
Product (yield,
Entry
X
Nucleophile
Base
%)
1
2
3
4
5
6
7
8
9
F
F
F
Cl
o-Aminophenol
o-Aminophenol
o-Aminophenol
o-Aminophenol
t-BuOK
NaHCO3
3a (55)
3a (82)
3a (74)
3a (39)
3a (30)
3a (14)
4a (72)
4a (93)
4b (89)
–
–
–
–
–
–
–
Br o-Aminophenol
I
F
F
Cl
o-Aminophenol
o-Phenylenediaminea
o-Phenylenediamine
o-Phenylenediamine
aNMP was used as solvent.
Table 3
Reactions of substituted o-halobenzaldehydes with o-aminothiophenol and o-aminophenol in DMF at 140ꢀC under microwave irradiation.
Entry
X
Y
Z
Base
Time (min)
Product (yield, %)
1
2
3
4
5
6
7
8
Cl
F
F
F
F
F
Cl
F
F
F
5-NO2
4-OMe
4-CF3
5-CF3
6-CF3
6-CF3
5-NO2
4-OMe
4-CF3
5-CF3
6-CF3
S
S
S
S
S
t-BuOK
10
30
15
15
10
10
18
20
30
30
30
74
52
67
79
85
67
73
51
60
73
72
NaHCO3
NaHCO3
NaHCO3
NaHCO3
t-BuOK
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
S
O
O
O
O
O
9
10
11
F
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2014
Microwave-Assisted Synthesis of Substituted Dibenzo[b, f][1,4]thiazepines, Dibenzo[b, f]
811
[1,4]oxazepines, Benzothiazoles, and Benzimidazoles
Table 4
reactor. The desired products were purified by silica gel
chromatography eluting with a mixture of hexane and ethyl acetate.
Reactions of p-methyl-o-aminophenol and p-chloro-o-aminophenol
with substituted o-fluorobenzaldehydes in DMF at 140ꢀC under
microwave irradiation.
Dibenzo[b,f][1,4]thiazepine. (1a).
Yield: 0.021 g (99%);
yellow solid, mp 130–132ꢀC; IR (v, cmÀ1, KBr) 2923, 1616,
1577, 1496; 1H NMR (600 MHz, DMSO-d6) d8.95 (s, 1H),
7.58–7.56 (m, 2H), 7.34–7.29 (m, 3H), 7.27–7.22 (m, 3H); 13C
NMR (150 MHz, DMSO-d6) d162.6, 148.2, 138.2, 136.8,
132.6, 131.9, 131.3, 129.9, 129.6, 128.8, 128.0, 127.3, 126.5;
MS m/e 211 (M+), 179, 167, 91, 69; HRMS m/e Calcd for
211.2868, found 211.0461. Anal. Calcd for C13H9NS; C, 73.90;
H, 4.29; N, 6.63. Found: C, 74.42; H, 4.44; N, 6.65.
2-Nitrodibenzo[b,f][1,4]thiazepine. (1b).
Yield: 0.019 g
(74%); yellow solid, mp 199–201ꢀC; IR (v, cmÀ1, KBr) 2921,
Product
1
1617, 1456, 1317, 1112. H NMR (600 MHz, DMSO-d6) d9.05
Entry
R
Y
Base
Time (min)
(yield, %)
(s, 1H, NCH), 8.51 (d, J = 2.4 Hz, 1H), 8.29 (dd, J = 9.0, 2.4 Hz,
1H),, 7.74 (d, J = 9.0 Hz, 1H), 7.49–7.44 (m, 2H), 7.32–7.28
(m, 2H); 13C NMR (150 MHz, DMSO-d6) d161.1, 147.9, 147.6,
146.2, 137.3, 133.0, 132.7, 130.3, 127.9, 126.7, 126.5, 126.2,
124.9; MS m/e 256 (M+), 210, 166, 69; HRMS m/e Calcd for
256.2824, found 256.0301. Anal. Calcd for C13H8N2O2S;
C, 60.92; H, 3.14; N, 10.93. Found: C, 60.75; H, 3.01; N, 10.81.
3-Methoxydibenzo[b,f][1,4]thiazepine. (1c). Yield: 0.013 g
(52%); yellow liquid; IR (v, cmÀ1, KBr) 2924, 1655, 1596, 1253,
1025. 1H NMR (600 MHz, DMSO-d6) d8.82 (s, 1H, NCH), 7.54
(d, J = 8.4 Hz, 1H), 7.42 (dd, J = 8.4, 1.2 Hz, 1H), 7.39 (td, J = 8.4,
1.2 Hz, 1H), 7.25–7.22 (m, 2H), 7.04–7.02 (m, 2H), 3.80 (s, 3H);
13C NMR (150 MHz, DMSO-d6) d162.0, 161.9, 148.5, 139.6,
132.6, 131.8, 129.7, 129.6, 127.6, 127.1, 126.6, 116.0, 114.6,
55.8; MS m/e 241 (M+), 149, 135, 121, 107; HRMS m/e Calcd
for 241.3126, found 241.0565. Anal. Calcd for C14H11NOS;
C, 69.68; H, 4.59; N, 5.80. Found: C, 69.82; H, 4.68; N, 5.83.
1
2
3
4
5
6
7
8
9
Me
Me
Me
Me
Me
Cl
Cl
Cl
Cl
H
H
4-OMe
5-CF3
6-CF3
H
4-OMe
5-CF3
6-CF3
–
20
20
20
20
20
14
20
30
25
5a (76)
5a (86)
5b (84)
5c (63)
5d (78)
5e (71)
5f (66)
5g (60)
5h (83)
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
EXPERIMENTAL
1H NMR spectra were measured in DMSO-d6 solution on a
Varian Inova 600 (California, USA) spectrometer. Reactions were
monitored by analytical thin-layer chromatography using silica gel
60 F-254 (0.2 mm layer thickness). Flash chromatography was
carried out by utilizing silica gel 60 (70–230 mesh ASTM).
General procedure for the reaction of o-halobenzaldehydes
3-(Trifluoromethyl)dibenzo[b,f][1,4]thiazepine. (1d).
Yield:
0.019 g (67%); white solid, mp 79–81ꢀC; IR (v, cmÀ1, KBr) 2936,
1587, 1480, 1227, 1025. 1H NMR (600 MHz, DMSO-d6) d9.06
(s, 1H, NCH), 7.88–7.84 (m, 2H), 7.83 (br, 1H), 7.48 (dd, J=7.8,
1.2 Hz, 1H), 7.44 (td, J = 7.8, 1.2 Hz, 1H), 7.31 (dd, J = 7.8,
1.2 Hz, 1H), 7.28 (td, J = 7.8, 1.2 Hz, 1H); 13C NMR (150MHz,
DMSO-d6) d161.7, 148.0, 140.0, 139.6, 132.9, 130.9, 130.1,
127.9 (2C), 127.7, 127.2, 126.6, 125.8 (2C); MS m/e 279 (M+),
149, 135, 69, 57; HRMS m/e Calcd for 279.2854, found
279.0336. Anal. Calcd for C14H8NSF3; C, 60.21; H, 2.89; N,
5.02; Found: C, 60.52; H, 2.99; N, 5.13.
with nucleophiles.
In a reaction vessel (12 mL), a nucleophile
(0.11 mmol) and an o-halobenzaldehyde (0.1 mmol) in an
appropriate solvent (1 mL) were placed. A base t-BuOK or
NaHCO3 (2.0 equiv versus nucleophile) could be added in
appropriate cases. The reaction vessel was then placed into the
cavity of a focused monomode microwave reactor (CEM Discover)
and irradiated for the period listed in Tables 1–5. The reaction
temperature was maintained by modulating the power level of the
Table 5
Reactions of o-aminothiophenol and o-aminophenol with phenones in NMP under microwave irradiation.
Entry
Nucleophile
Base
W
Z
Temperature (ꢀC)
Time (min)
Product (yield, %)
1
2
3
4
o-Aminothiophenol
o-Aminothiophenol
o-Aminophenol
t-BuOK
t-BuOK
t-BuOK
NaHCO3
Ph
Ph
Ph
Me
S
S
O
O
180
200
200
180
20
30
60
30
67
87
49
62
o-Aminophenol
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DOI 10.1002/jhet

812
Y.-C. Lin, N.-C. Li, and Y.-J. Cherng
Vol 51
2-(Trifluoromethyl)dibenzo[b,f][1,4]thiazepine. (1e).
Yield:
8.42 (dd, J = 9.0, 3.0 Hz, 1H), 7.51(d, J = 9.0 Hz, 1H), 7.38–7.35
(m, 2H), 7.31–7.29 (m, 2H); 13C NMR (150 MHz, DMSO-d6)
d164.1, 159.3, 151.1, 144.7, 139.7, 129.6, 129.0, 128.9, 127.3,
126.7, 126.5, 122.1, 121.6; MS m/e 240 (M+), 194, 166, 139;
HRMS m/e Calcd for 240.2178, found 240.0544. Anal. Calcd
for C13H9N2O3; C, 65.00; H, 3.25; N, 11.66. Found: C, 64.88;
H, 3.29; N, 11.73.
3-Methoxydibenzo[b,f][1,4]oxazepine. (3c). Yield: 0.012 g
(51%); yellow liquid, IR (v, cmÀ1, KBr) 2923, 1603, 1499,
1208, 1029; 1H NMR (600 MHz, DMSO-d6) d8.48 (s, 1H,
NCH), 7.49 (d, J = 8.4 Hz, 1H), 7.29–7.27 (m, 2H), 7.24–7.19
(m, 2H), 6.88 (dd, J = 8.4, 2.4 Hz, 1H), 6.85 (d, J = 2.4 Hz, 1H),
3.82 (s, 3H); 13C NMR (150 MHz, DMSO-d6) d163.9, 161.1,
160.4, 151.8, 140.5, 131.9, 128.7, 128.6, 125.9, 121.4, 119.9,
111.5, 105.8, 55.9; MS m/e 225 (M+), 149, 135, 107; HRMS
m/e Calcd for 225.2456, found 225.0787. Anal. Calcd for
C14H11NO2; C, 74.65; H, 4.92; N, 6.22. Found: C, 74.52; H,
5.33; N, 6.12.
0.022 g (79%); yellow liquid; IR (v, cmÀ1, KBr) 2926, 1587, 1482,
1
1327, 1120. H NMR (600 MHz, DMSO-d6) d9.02 (s, 1H, NCH),
8.07 (d, J=1.8Hz, 1H), 7.86 (dd, J=8.4, 1.8Hz, 1H), 7.70
(d, J= 8.4 Hz, 1H), 7.48–7.42 (m, 2H), 7.31–7.26 (m, 2H); 13C
NMR (150 MHz, DMSO-d6) d161.6, 148.0, 143.3, 137.2, 132.9,
132.3, 130.1, 128.3 (2C), 127.7, 127.0, 126.9 (2C), 126.6; MS m/e
279 (M+), 210, 135, 69, 57; HRMS m/e Calcd for 279.2854, found
279.0338. Anal. Calcd for C14H8NSF3; C, 60.21; H, 2.89; N, 5.02;
Found: C, 60.45; H, 3.01; N, 5.07.
1-(Trifluoromethyl)dibenzo[b,f][1,4]thiazepine. (1f).
Yield:
0.024 g (85%); white solid, mp 144–146ꢀC; IR (v, cmÀ1, KBr)
2923, 1606, 1460, 1327, 1120. 1H NMR (600 MHz, DMSO-d6)
d9.13 (s, 1H, NCH), 7.84 (d, J= 7.8 Hz, 2H), 7.69 (t, J=7.8Hz,
1H), 7.49 (dd, J= 7.8, 1.2 Hz, 1H), 7.43 (td, J= 7.8, 1.2 Hz, 1H),
7.29 (dd, J=7.8, 1.2Hz, 1H), 7.24 (td, J= 7.8, 1.2 Hz, 1H); 13C
NMR (150 MHz, DMSO-d6) d159.0, 147.9, 142.8, 136.0,
132.8, 132.5, 131.9, 130.1, 127.6 (2C), 127.1, 126.7, 126.6, 125.1;
MS m/e 279 (M+), 210, 135, 69, 57; HRMS m/e Calcd for
279.2854, found 279.0338. Anal. Calcd for C14H8NSF3; C, 60.21;
H, 2.89; N, 5.02; Found: C, 60.57; H, 2.96; N, 5.09.
3-(Trifluoromethyl)dibenzo[b,f][1,4]oxazepine. (3d).
Yield:
0.016 g (60%); yellow solid, mp 48–50ꢀC; IR (v, cmÀ1, KBr) 2925,
1621, 1423, 1325, 1127; 1H NMR (600 MHz, DMSO-d6) d8.74
(s, 1H, NCH), 7.83 (d, J = 7.8 Hz, 1H), 7.73–7.72 (m, 2H),
7.38–7.32 (m, 3H), 7.30–7.27 (m, 1H); 13C NMR (150 MHz,
DMSO-d6) d159.9, 159.6, 151.5, 139.9, 131.7, 130.2, 129.5,
128.8, 126.4, 122.4 (2C), 121.5, 117.8 (2C); MS m/e 263 (M+),
149, 69, 57; HRMS m/e Calcd for 263. 2181, found 263.0550.
Calcd for C14H8NOF3; C, 63.88; H, 3.06; N, 5.32. Found: C,
63.92; H, 3.26; N, 5.25.
2-(2-Fluorophenyl)benzo[d]thiazole. (2a).
Yield: 0.022 g
(97%); white solid, mp 95–98ꢀC; IR (v, cmÀ1, KBr) 2924,
1
1630, 1582, 1453; H NMR (600 MHz, DMSO-d6) d 8.39–8.36
(m, 1H), 8.20–8.19 (m, 1H), 8.13–8.12 (m, 1H), 7.67–7.63
(m, 1H), 7.60–7.58 (m, 1H), 7.52–7.48 (m, 2H), 7.46–7.43
(m, 1H); 13C NMR (150 MHz, DMSO-d6) d160.7, 159.0, 152.0,
133.2, 133.1, 129.3, 126.7, 125.7, 125.4, 123.0, 122.2, 116.8,
116.6; MS m/e 229 (M+), 108, 69; HRMS m/e Calcd
for 229.2773, found 229.0358. Anal. Calcd for C13H8NSF;
C, 68.10; H, 3.52; N, 6.10. Found: C, 68.01; H, 3.38; N, 5.96.
2-(Trifluoromethyl)dibenzo[b,f][1,4]oxazepine. (3e).
Yield:
0.019 g (73%); yellow solid, mp 80–82ꢀC; IR (v, cmÀ1, KBr) 2919,
1617, 1473, 1335, 1116. 1H NMR (600 MHz, DMSO-d6) d8.71
(s, 1H, NCH), 8.06 (d, J= 2.4 Hz, 1H), 7.96 (dd, J= 8.4, 2.4 Hz,,
1H), 7.49 (d, J= 8.4 Hz, 1H), 7.37–7.34 (m, 2H), 7.30–7.28
(m, 2H); MS m/e 263 (M+), 244, 235, 166, 139, 69, 57; 13C NMR
(150 MHz, DMSO-d6) d162.3, 159.7, 151.4, 139.9, 130.7 (2C),
129.4, 128.9, 128.1 (2C), 127.3, 126.4, 121.7, 121.5; HRMS m/e
Calcd for 263.2181, found 263.0552. Anal. Calcd for C14H8NOF3;
C, 63.88; H, 3.06; N, 5.32. Found: C, 63.99; H, 3.28; N, 4.93.
2-(2-Chlorophenyl)benzo[d]thiazole. (2b).
Yield: 0.023 g
(92%); white solid, mp 90–92ꢀC; IR (v, cmÀ1, KBr) 2925,
1631, 1580, 1454; 1H NMR (600 MHz, DMSO-d6) d 8.20
(d, J = 1.2 Hz, 1H), 8.18 (d, J = 1.2 Hz, 1H), 8.12 (d, J = 8.4 Hz,
1H), 7.71–7.69 (m, 1H), 7.61–7.51 (m, 4H); 13C NMR
(150 MHz, DMSO-d6) d163.5, 152.1, 135.5, 132.3, 131.8,
131.6, 131.5, 131.0, 128.0, 126.9, 126.0, 123.3, 122.3; MS m/e
245 (M+), 210, 108; HRMS m/e Calcd for 245.7259, found
245.0067. Anal. Calcd for C13H8NSCl; C, 63.54; H, 3.28; N,
5.70. Found: C, 63.18; H, 3.07; N, 5.38.
1-(Trifluoromethyl)dibenzo[b,f][1,4]oxazepin. (3f).
Yield:
0.018 g (72%); white solid, mp 96–101ꢀC; IR (v, cmÀ1, KBr) 2923,
1
1455, 1314, 1116. H NMR (600 MHz, DMSO-d6) d8.85 (s, 1H,
2-(2-Bromophenyl)benzo[d]thiazole. (2c).
Yield: 0.026 g
NCH), 7.81 (t, J=7.8Hz, 1H), 7.73 (d, J=7.8Hz, 1H), 7.69
(d, J=7.8Hz, 1H), 7.39 (dd, J=7.8, 1.2Hz, 1H), 7.37–7.29
(m, 3H); 13C NMR (150 MHz, DMSO-d6) d161.9, 156.1, 151.4,
139.9, 134.1, 129.1, 127.7, 126.5, 125.6, 123.4, 123.3 (2C), 121.0
(2C); MS m/e 263 (M+), 147, 69, 57; HRMS m/e Calcd for
263.2181, found 263.0552. Anal. Calcd for C14H8NOF3; C, 63.88;
H, 3.06; N, 5.32. Found: C, 63.95; H, 3.35; N, 5.21.
(90%); pale yellow solid, mp 63–65ꢀC; IR (v, cmÀ1, KBr)
1
2924, 1629, 1580, 1454; H NMR (600 MHz, DMSO-d6) d 8.18
(d, J = 7.8 Hz, 1H), 8.11 (d, J = 7.8 Hz, 1H), 8.00 (dd, J = 7.8,
1.2 Hz, 1H), 7.85 (d, J= 8.4 Hz, 1H), 7.60–7.56 (m, 2H), 7.53–7.48
(m, 2H); 13C NMR (150MHz, DMSO-d6) d165.1, 152.4, 135.6,
134.2, 133.8, 132.3, 132.2, 128.3, 126.8, 126.0, 123.3, 122.3,
121.3; MS m/e 289 (M+), 210, 108; HRMS m/e Calcd for
290.1769, found 288.9564. Anal. Calcd for C13H8NSBr; C, 53.81;
H, 2.78; N, 4.82. Found: C, 53.64; H, 2.49; N, 4.98.
2-(2-Fluorophenyl)-1H-benzo[d]imidazole. (4a).
Yield:
0.020 g (93%); white solid, mp 232–235ꢀC; IR (v, cmÀ1, KBr)
2919, 1622, 1584, 1220; 1H NMR (600 MHz, DMSO-d6)
d12.61 (s, 1H, NCH), 8.23 (td, J = 7.8, 1.8 Hz, 1H), 7.69
(d, J=7.8Hz, 1H), 759–7.55 (m, 2H), 7.46–7.38 (m, 2H), 7.26–7.20
(m, 2H) ; 13C NMR (150 MHz, DMSO-d6) d160.3, 158.7, 146.5,
143.0, 135.1, 131.9, 130.3, 125.2, 122.9, 122.0, 119.0, 116.5,
112.0; MS m/e 212 (M+), 193, 91, 75; HRMS m/e Calcd for
212.2259, found 212.0748. Anal. Calcd for C13H9N2F; C, 73.57;
H, 4.27; N, 13.20. Found: C, 73.78; H, 4.62; N, 13.03.
Dibenzo[b,f][1,4]oxazepine [8]. (3a). Yield: 0.014 g (74%);
1
yellow solid, mp 70–72ꢀC, (lit. 67–70ꢀC); H NMR (600 MHz,
DMSO-d6) d8.63 (s, 1H), 7.62–7.60 (m, 1H), 7.51–7.47
(m, 3H), 7.45–7.44 (m, 1H), 7.41–7.38 (m, 1H), 7.28–7.26
(m, 1H), , 7.25–7.22 (m, 1H) ; 13C NMR (150 MHz, DMSO-d6)
d160.9, 159.6, 152.1, 140.3, 133.8, 130.5, 128.9, 128.6, 126.9,
125.9, 125.5, 121.3, 120.4; MS m/e 195 (M+), 167, 139, 89;
HRMS m/e Calcd for 195.2258, found 195.0677.
2-(2-Chlorophenyl)-1H-benzo[d]imidazole. (4b).
Yield:
2-Nitrodibenzo[b,f][1,4]oxazepine. (3b).
Yield: 0.018 g
0.020 g (89%); white solid, mp 246–248ꢀC; IR (v, cmÀ1, KBr)
(73%); white solid, mp 160–162ꢀC; 1H NMR (600 MHz,
DMSO-d6) d8.72 (s, 1H, NCH), 8.54 (d, J = 3.0 Hz, 1H),
2923, 1622, 1590, 1230, 1055; H NMR (600 MHz, DMSO-d6)
1
d12.72 (s, 1H, NCH), 7.90 (dd, J = 7.8, 1.8 Hz, 1H), 7.73
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2014
Microwave-Assisted Synthesis of Substituted Dibenzo[b, f][1,4]thiazepines, Dibenzo[b, f]
813
[1,4]oxazepines, Benzothiazoles, and Benzimidazoles
(d, J = 7.8 Hz, 1H), 7.65 (dd, J = 7.8, 1.8 Hz, 1H), 7.58–7.50
(m, 3H), 7.26–7.22 (m, 2H); 13C NMR (150 MHz, DMSO-d6)
d149.1, 143.2, 134.6, 132.1, 131.6, 131.2, 130.3, 130.0, 127.4,
122.7, 121.7, 119.1, 111.7; MS m/e 228.5 (M+), 193, 114, 75;
HRMS m/e Calcd for 228.5505, found 228.0448. Anal. Calcd
for C13H9N2Cl; C, 68.26; H, 3.96; N, 12.26. Found: C, 68.58;
H, 4.09; N, 12.11.
d8.41 (s, 1H, NCH), 7.43 (d, J = 8.4Hz, 1H), 7.29 (dd, J = 8.4,
2.4 Hz, 1H), 7.24 (d, J = 2.4Hz, 1H), 7.19 (d, J = 8.4 Hz, 1H), 6.84
(dd, J = 8.4, 1.8 Hz, 1H), 6.80 (d, J = 1.8 Hz, 1H), 3.75 (s, 3H,
OCH3); 13C NMR (150 MHz, DMSO-d6) d165.9, 163.8, 162.2,
151.9, 141.9, 133.9, 131.4, 130.0, 128.7, 124.5, 120.5, 113.1,
107.2, 57.1; MS m/e 259 (M+), 244, 196, 63. HRMS m/e Calcd
for 259.6916, found 259.0393; Anal. Calcd for C14H10NO2Cl; C,
8-Methyldibenzo[b,f][1,4]oxazepine. (5a).
Yield: 0.018 g
(86%); pale yellow liquid; IR (v, cmÀ1, KBr) 2923, 1604, 1478;
1H NMR (600 MHz, DMSO-d6) d8.61 (s, 1H, NCH), 7.57–7.55
(m, 2H), 7.32–7.29 (m, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.13
(s, 1H), 7.09 (br, 2H) , 2.26 (s, 3H); 13C NMR (150 MHz,
DMSO-d6) d160.9, 159.7, 149.9, 139.9, 135.2, 133.7, 130.5,
129.3, 128.8, 126.9, 125.4, 120.9, 120.3, 20.1; MS m/e 209
(M+), 180, 58; HRMS m/e Calcd for 209.2466, found 209.0848.
Anal. Calcd for C14H11NO; C, 80.36; H, 5.30; N, 6.69. Found:
C, 80.19; H, 5.08; N, 6.38.
64.75; H, 3.88; N, 5.39. Found: C, 64.96; H, 4.03; N, 5.11.
8-Chloro-2-(trifluoromethyl)dibenzo[b,f][1,4]oxazepine. (5g).
Yield: 0.018 g (60%); yellow solid, mp 79–81ꢀC; IR (v, cmÀ1, KBr)
2922, 1672, 1496, 1324, 1109. 1H NMR (600 MHz, DMSO-d6)
d8.75 (s, 1H, NCH), 8.09 (d, J= 1.8Hz, 1H), 7.99 (dd, J=8.4,
1.8 Hz, 1H), 7.50 (d, J=8.4Hz, 1H), 7.42–7.40 (m, 2H), 7.34–7.32
(m, 1H); 13C NMR (150 MHz, DMSO-d6) d162.1, 161.3, 150.3,
141.0, 131.1 (2C), 130.2, 128.9, 128.4 (2C), 128.1, 127.2, 123.2,
121.9; MS m/e 297 (M+), 239, 191, 69, 57; HRMS m/e Calcd for
297.6629, found 297.0163. Anal. Calcd for C14H7NOClF3; C,
56.49; H, 2.37; N, 4.70. Found: C, 56.62; H, 2.57; N, 4.49.
8-Chloro-1-(trifluoromethyl)dibenzo[b,f][1,4]oxazepin. (5h).
Yield: 0.025 g (83%); white solid, mp 90–92ꢀC; IR (v, cmÀ1, KBr)
2923, 1624, 1455, 1311, 1107. 1H NMR (600 MHz, DMSO-d6)
d8.88 (s, 1H, NCH), 7.83 (t, J=7.8Hz, 1H), 7.75 (d, J=7.8, 1H),
7.71 (d, J=7.8Hz, 1H), 7.47 (d, J= 2.4 Hz, 1H), 7.43–7.38
(m, 2H); 13C NMR (150 MHz, DMSO-d6) d161.8, 157.7, 150.8,
140.9, 134.5, 130.3, 128.8, 127.0 125.7, 123.7, 123.6, 123.2, 122.8,
122.2; MS m/e 297 (M+), 262, 242, 234, 63; HRMS m/e Calcd for
297.6629, found 297.0165. Anal. Calcd for C14H7NOClF3; C,
56.49; H, 2.37; N, 4.70. Found: C, 56.71; H, 2.59; N, 4.71.
8-Methyl-3-methoxydibenzo[b,f][1,4]oxazepine. (5b).
Yield:
0.020 g (84%); yellow liquid; IR (v, cmÀ1, KBr) 2924, 1602, 1483,
1
1124; H NMR (600 MHz, DMSO-d6) d8.45 (s, 1H, NCH), 7.47
(d, J= 8.4 Hz, 1H), 7.09–7.07 (m, 3H), 7.59 (s, 1H), 6.86
(dd, J= 8.4, 2.4Hz, 1H), 6.81 (d, J= 2.4 Hz, 1H), 3.81 (s, 3H), 2.62
(s, 3H); 13C NMR (150 MHz, DMSO-d6) d163.8, 161.2, 160.3,
149.6, 140.1, 135.1, 131.9, 128.9, 128.8, 121.0, 119.9, 111.3,
105.7, 55.8, 20.1; MS m/e 239 (M+), 210, 149, 135, 57;
HRMS m/e Calcd for 239.2724 found 239.0945. Anal. Calcd
for C15H13NO2; C, 75.29; H, 5.48; N, 5.85. Found: C, 75.13;
H, 5.38; N, 5.66.
8-Methyl-2-(trifluoromethyl)dibenzo[b,f][1,4]oxazepine. (5c).
Yield: 0.018 g (63%); white solid, mp 68–70ꢀC; IR (v, cmÀ1, KBr)
2922, 1612, 1456, 1373, 1123. 1H NMR (600 MHz, DMSO-d6)
d8.66 (s, 1H, NCH), 8.01 (d, J= 1.8 Hz, 1H), 7.92 (dd, J=9.0,
1.8 Hz, 1H), 7.44 (d, J=9.0Hz, 1H), 7.15–7.13 (m; 3H), 2.27
(s, 3H); 13C NMR (150 MHz, DMSO-d6) d162.6, 159.9, 149.5,
139.6, 136.1, 130.9, 130.0, 129.2, 128.3, 127.6, 126.5, 126.3,
121.9, 121.3, 20.3; MS m/e 277 (M+), 258, 248, 69, 57;
HRMS m/e Calcd for 277.2457, found 277.0722. Anal. Calcd
for C15H10NOF3; C, 64.98; H, 3.63; N, 5.05. Found: C,
65.12; H, 3.90; N, 4.89.
8-Methyl-1-(trifluoromethyl)dibenzo[b,f][1,4]oxazepine. (5d).
Yield: 0.022 g (78%); white solid, mp 75–77ꢀC; IR (v, cmÀ1, KBr)
2923, 1603, 1455, 1315, 1118. 1H NMR (600 MHz, DMSO-d6)
d8.82 (s, 1H, NCH), 7.79 (t, J= 7.8 Hz, 1H), 7.71 (d, J=7.8Hz,
1H), 7.66 (d, J= 7.8 Hz, 1H), 7.21–7.19 (m, 2H), 7.14 (dd, J=7.8,
1.8 Hz, 1H) , 2.28 (s, 3H); 13C NMR (150 MHz, DMSO-d6)
d162.0, 156.0, 149.7, 139.5, 135.9, 134.0, 129.5 (2C),, 127.8,
125.6, 123.5, 123.2 (2C), 120.6, 20.2; ; MS m/e 277 (M+), 248,
149, 57; HRMS m/e Calcd for 277.2457, found 277.0721. Anal.
Calcd for C15H10NOF3; C, 64.98; H, 3.63; N, 5.05. Found: C,
65.11; H, 3.77; N, 5.16.
11-Phenyldibenzo[b,f][1,4]thiazepine. (6a).
Yield: 0.025 g
(87%); Yellow solid, mp 118–120ꢀC; IR (v, cmÀ1, KBr) 2923,
1610, 1578, 1443; 1H NMR (600 MHz, DMSO-d6) d7.73–7.71
(m, 2H), 7.61 (dd, J=7.8, 1.2, 1H), 7.56–7.53 (m, 2H), 7.52–7.49
(m, 3H), 7.44–7.38 (m, 2H), 7.33–7.32 (m, 1H), 7.21 (dd, J=7.8,
1.2, 1H), 7.16 (td, J = 7.8, 1.2, 1H); 13C NMR (150 MHz,
DMSO-d6) d167.8, 148.3, 140.1, 139.7, 136.5, 132.3, 132.0,
131.6, 131.0, 130.3, 129.6, 129.2 (2C), 128.5, 128.4 (2C),
127.9, 126.0, 125.2; MS m/e 287 (M+), 254, 167, 91, 77;
HRMS m/e Calcd for 287.3824, found 287.0762. Anal. Calcd
for C19H13NS; C, 79.41; H, 4.56; N, 4.87; Found: C, 79.50; H,
5.05; N, 4.47.
11-Phenyldibenzo[b,f][1,4]oxazepine. (6b).
Yield: 0.013 g
(49%); yellow liquid; IR (v, cmÀ1, KBr) 2924, 1594, 1447; 1H
NMR (600 MHz, DMSO-d6) d7.78–7.77 (m, 2H), 7.65–7.63
(m, 1H), 7.57 (t, J= 7.2Hz, 1H), 7.52 (t, J= 7.2 Hz, 2H), 7.43–7.40
(m, 2H), 7.32–7.30 (m, 1H), 7.29–7.26 (m, 3H), 7.19 (dd, J=7.8,
1.2 Hz, 1H); 13C NMR (150 MHz, DMSO-d6) d166.3, 161.3,
151.9, 140.3, 139.2, 133.7, 130.9, 130.8, 129.3 (2C), 128.4 (2C),
127.9, 127.6, 126.4, 125.9, 125.1, 121.0, 120.8; MS m/e 271 (M+),
241, 139, 77; HRMS m/e Calcd for 271.3174, found 271.0988;
Anal. Calcd for C19H13NO; C, 84.11; H, 4.82; N, 5.16. Found: C,
84.42; H, 4.95; N, 5.01.
8-Chlorodibenzo[b,f][1,4]oxazepine. (5e).
Yield: 0.016 g
(71%); yellow solid, mp 74–76ꢀC; IR (v, cmÀ1, KBr) 2922,
1
11-Methyldibenzo[b,f][1,4]oxazepine. (6c).
Yield: 0.013 g
1605, 1468; H NMR (600 MHz, DMSO-d6) d8.68 (s, 1H, NCH),
(62%); White solid, mp 94–96ꢀC; IR (v, cmÀ1, KBr) 2919, 1597,
1444, 1366; 1H NMR (600 MHz, DMSO-d6) d7.66 (dd, J=7.8,
1.2 Hz, 1H), 7.54 (td, J=7.8, 1.2Hz, 1H), 7.31–7.29 (m, 2H),
7.24–7.18 (m, 4H), 2.59 (s, 3H); 13C NMR (150 MHz, DMSO-d6)
d167.4, 160.1, 152.0, 140.4, 133.3, 129.0, 128.4, 127.4, 127.3,
125.8, 125.6, 120.7, 120.6, 27.4; MS m/e 209 (M+), 194, 180, 139;
HRMS m/e Calcd for 209.2466, found 209.0833. Anal. Calcd for
C14H11NO; C, 80.36; H, 5.29; N, 6.69. Found: C, 80.62; H, 5.54;
N, 6.43.
7.62–7.59 (m, 2H), 7.37–7.33 (m, 3H), 7.28–7.26 (m, 2H); 13C
NMR (150 MHz, DMSO-d6) d162.5, 159.4, 150.9, 141.4, 134.2,
130.8, 129.6, 128.5, 127.9, 126.7, 125.8, 123.0, 120.5; MS m/e 229
(M+), 201, 166, 139; HRMS m/e Calcd for 229.6646, found
229.0301. Anal. Calcd for C13H8NOCl; C, 67.98; H, 3.51; N, 6.10.
Found: C, 68.15; H, 4.01; N, 5.72.
8-Chloro-3-methoxydibenzo[b,f][1,4]oxazepine. (5f).
Yield:
0.017 g (66%); pale yellow solid, mp 100–102ꢀC; IR (v, cmÀ1, KBr)
1
2925, 1608, 1468, 1291, 1130. H NMR (600MHz, DMSO-d6)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

814
Y.-C. Lin, N.-C. Li, and Y.-J. Cherng
Vol 51
[5] Narasimhan, N. S.; Chandrachood, P. S.; Synthesis 1979,
8, 589.
REFERENCES AND NOTES
[6] Jaques, R.; Rossi, A.; Urech, E.; Bein, H. J.; Hoffmann,
K. Helv Chim Acta 1959, 42, 1265.
[1] Norio, H.; Hiromitsu, S.; Hiroshi, O.; Michio, T. Yakubutsu
Seishin Kodo 1988, 8, 61.
[7] Fakhraian, H.; Nafary, Y. J Heterocycl Chem 2009, 46, 988.
[8] Jorapur, Y. R.; Rajagopal, G.; Saikia, P. J.; Pal, R. R. Tetrahedron
Lett 2008, 49, 1495.
[9] Gutch, P. K.; Acharya, J. Heterocycl Commun 2007, 13, 393.
[10] Songnian, L.; Lihu, Y. Tetrahedron Lett 2005, 46, 4315.
Gogoi, P.; Konwai, D. Tetrahedron Lett 2006, 47, 79.
[2] Gijsen, H. J. M.; Berthelot, D.; Zaja, M.; Brone, B.; Geuens,
I.; Mercken, M. J Med Chem 2010, 53, 7011.
[3] Zauhar, R. L.; Guillerma, M.; Lifang, T.; Zhijian, L.; Welsh,
W. J. J Med Chem 2003, 46, 5674.
[4] Takayoshi, F.; Wei, H.; Toshiaki, Y. Heteroat Chem 2004,
15, 246.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet