Copper-assisted/copper-free synthesis of functionalized dibenzo[b,f]oxepins and their analogs via a one-pot tandem reaction

Article abstract of DOI:10.1002/hlca.201200116

A simple, convenient, and efficient method for the formation of functionalized dibenzo[b,f]oxepins and their analogs bearing both electron-donating and electron-withdrawing groups has been developed via a one-pot cascade reaction. Most starting materials are commercially available 2-(2-hydroxyphenyl)acetonitriles and 2-haloarylaldehydes. The procedure makes use of Cs₂CO₃ as the base, and DMF as solvent under copper-assisted/copper-free conditions. The reaction has a comprehensive group tolerance for substrates. Most of the reactions were complete within 1 h in good-to-excellent yields, and the reaction temperatures were relatively low. The protocol could be scaled up to grams without lowering the yield. A reaction mechanism was also proposed. Copyright

Full text of DOI:10.1002/hlca.201200116

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Helvetica Chimica Acta – Vol. 96 (2013)
Copper-Assisted/Copper-Free Synthesis of Functionalized
Dibenzo[b, f]oxepins and Their Analogs via a One-Pot Tandem Reaction
by Yuqin Wang, Yanhong Chen, Qian He, Yuyuan Xie, and Chunhao Yang*
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, SIBS, Chinese Academy
of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, P. R. China
(e-mail: chyang@simm.ac.cn)
A simple, convenient, and efficient method for the formation of functionalized dibenzo[b,f]oxepins
and their analogs bearing both electron-donating and electron-withdrawing groups has been developed
via a one-pot cascade reaction. Most starting materials are commercially available 2-(2-hydroxyphenyl)-
acetonitriles and 2-haloarylaldehydes. The procedure makes use of Cs2CO3 as the base, and DMF as
solvent under copper-assisted/copper-free conditions. The reaction has a comprehensive group tolerance
for substrates. Most of the reactions were complete within 1 h in good-to-excellent yields, and the
reaction temperatures were relatively low. The protocol could be scaled up to grams without lowering the
yield. A reaction mechanism was also proposed.
Introduction. – Dibenzo[b,f]oxepin is an important framework in medicinal
chemistry, and its derivatives occur in several medicinally relevant plants [1 – 6]. The
scaffold has attracted considerable attention due to its diverse biological features such
as anti-estrogenic [7], antidepressant [7 – 9], analgesic [10], anti-inflammatory
[3][11][12], antipsychotic [12 – 15], angiotensin II receptor antagonistic [16], antiox-
idant [17], antimycobacterial [4], antidiabetic [18], and antitumor activities [6], as well
as anti-apoptosis [19] properties (Fig.). The treatment of progressive neurodegener-
ative diseases [20] such as Parkinsonꢀs and Alzheimerꢀs diseases [21] with synthetic
dibenzo[b,f]oxepine derivatives is of particular interest.
Considerable efforts have been made to synthesize the dibenzo[b,f]oxepin skeleton
since the report of Manske and Ledingham [22][23]. The most widely applied
approaches to the synthesis of the scaffold involved constructing substrates in multiple
steps via the Ullmann coupling reaction and the FriedelꢀCrafts reaction (Scheme 1,
Examples A [17] and B [10][11][20][24]), but the total yields were not satisfying. Yang
et al. reported a method via benzoin condensation to prepare dibenzo[b,f]oxepine by
using the hypertoxic reagent KCN, and obtained the product in low yield (22 – 25%)
[25]. Another reported strategy for the formation of this fused seven-membered ring
involved the WagnerꢀMeerwein rearrangement of a number of structurally diverse 9-
(1-hydroxyalkyl)xanthenes (Scheme 1, Example C [26]). This procedure required 3 – 5
wt-equiv. of P2O5, toxic benzotrifluoride as the solvent, and a long reaction time (24 –
96 h) at reflux temperature and gave the products generally in low-to-moderate yields
(20 – 56%). Recently, Cong et al. reported a MnIII-based oxidative 1,2-radical rear-
rangement to form dibenzo[b,f]oxepins by using a large excess of Mn(OAc)3 (4 mol-
equiv.) in boiling glacial AcOH in moderate yields as well [27]. In 2001, Chernysheva
et al. [28] reported a one-pot procedure to prepare NO2-substituted dibenz[b,f]ox-
ꢁ 2013 Verlag Helvetica Chimica Acta AG, Zꢂrich

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297
Figure. Pharmacologically active dibenzo[b,f]oxepins
epines. However, this method involved explosive 2,4,6-trinitrotoluene as the starting
reagent. These existing methods have some inherent disadvantages, i.e., i) multiple
synthetic steps, ii) low total yields, iii) harsh and not environment-friendly conditions,
and iv) long reaction times, and they cannot provide fast and efficient access to a library
of functionalized dibenzo[b,f]oxepins and thus limit the molecular diversity for lead
optimization and drug screening. Considering the promising biological activities of
dibenzo[b,f]oxepins, a facile, practical, and versatile method that enables quick access
to dibenzo[b,f]oxepins is highly desirable.
Here, we report a convenient method for preparing dibenzo[b,f]oxepins with
various functional groups via a one-pot cascade reaction in good-to-excellent yields
under Cu-assisted as well as Cu-free conditions.
Results and Discussion. – We started with commercially available 2-bromobenzal-
dehyde (2a) and 2-(2-hydroxyphenyl)acetonitrile (1a), which was prepared from 2-(2-
methoxyphenyl)acetonitrile by deprotection of the methyl ether group with BBr3 [29],
as the model reaction. First, the reaction was catalyzed by CuI in dioxane and K2CO3 as
the base at 1008 (Table 1, Entry 1). The desired compound 3a was obtained only in 20%
yield. When DMF was used as the solvent, the reaction proceeded smoothly, resulting
in an 88% yield (Table 1, Entry 2). Next, the bases were investigated. As shown in
Table 1, the reaction went well with Cs2CO3, and the yield of 3a was quite high
(Entry 6). The yield was lower when DBU (¼1,8-diazabicyclo[5.4.0]undec-7-ene) was
used as base (Table 1, Entry 5), and the reaction was not complete at 1008 after 5 h.
With a prolonged time (12 h) and higher temperature (1508), the reaction afforded 3a
in 61% yield. The reaction did not work when EtONa and DMAP (¼4-(dimethyl-
amino)pyridine) were used as bases (Table 1, Entries 3 and 4). Then, the loading of CuI
was investigated. When the reaction was conducted in the presence of an increased

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Helvetica Chimica Acta – Vol. 96 (2013)
Scheme 1. Reported Synthesis of Dibenzo[b,f]oxepins
amount of CuI, the yield did not improve (Table 1, Entry 7). When the amount of CuI
was decreased to 0.05 equiv. (Table 1, Entry 8), a comparable yield was obtained. To
our delight, 0.01 equiv. of CuI (Table 1, Entry 9) was as effective without a prolonged
reaction time. The reaction was also studied under a Cu-free condition (Table 1,
Entry 14). Although 3a was obtained in 60% yield, the starting material was not
completely consumed, and the yield decreased with prolonged time. Next, the amount
of base was explored. By decreasing the amount of Cs2CO3 (Table 1, Entries 10 and 11),
a slightly lower yield of 3a was obtained. Finally, when the reaction temperature was
raised to 1208, the reaction was complete within 1 h, but the yield decreased (Table 1,
Entry 12). The yield of 3a was only 66% when the reaction was conducted at 808
(Table 1, Entry 13).
Under the optimal reaction conditions (0.01 equiv. of CuI, 3 equiv. of Cs2CO3,
DMF, 1008, 1 h), we investigated the scope and limitations of the reaction employing a
variety of ortho-haloarene-carbaldehydes and 2-(2-hydroxyphenyl)acetonitrile (1a).
As compiled in Table 2, a number of 2-bromobenzaldehydes bearing both electron-
donating (EDG) and electron-withdrawing groups (EWG) reacted very well. With 2-
bromo-3-fluorobenzaldehyde (2b), the reaction proceeded smoothly with an excellent
yield (Table 2, Entry 1). The effect of substitutions at C(4) of 2-bromobenzaldehyde

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299
Table 1. Optimization of the Reaction Conditionsa)
Entry
Base
CuI
Solvent
Time [h]
Temp. [8]
Yield [%]b)
1
2
3
4
5c)
6
7
8
9
10
11
12
13
14d)
K2CO3 (3 equiv.)
K2CO3 (3 equiv.)
EtONa (3 equiv.)
DMAP (3 equiv.)
DBU (3 equiv.)
Cs2CO3 (3 equiv.)
Cs2CO3 (3 equiv.)
Cs2CO3 (3 equiv.)
Cs2CO3 (3 equiv.)
Cs2CO3 (2 equiv.)
Cs2CO3 (1.2 equiv.)
Cs2CO3 (3 equiv.)
Cs2CO3 (3 equiv.)
Cs2CO3 (3 equiv.)
0.1 equiv.
0.1 equiv.
0.1 equiv.
0.1 equiv.
0.1 equiv.
0.1 equiv.
0.3 equiv.
0.05 equiv.
0.01 equiv.
0.01 equiv.
0.01 equiv.
0.01 equiv.
0.01 equiv.
0
Dioxane
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1
1
1
1
17
1
1
1
1
1
100
100
100
100
100 – 150
100
100
100
100
100
100
120
80
20
88
0
0
61
89
87
86
92
84
84
75
66
60
1
1
1
1
100
a) Reaction conditions: 1a (70 mg, 0.52 mmol), 2a (93 mg, 0.5 mmol), solvent (8 ml). b) Yield of
isolated 3a. c) The reaction required a prolonged time (17 h) and higher temperature (1508) to complete.
d) The amount of product decreased with a prolonged reaction time.
was then studied. A Me or MeO group had similar effects (Table 2, Entries 2 and 3).
The substrate with an EDG such as MeO at C(5) (Table 2, Entry 4) gave an excellent
yield, and the same results were obtained with an EWG at C(5) (Table 2, Entries 5 and
6). However, 2h with the potent EWG CF3 group at C(5) gave a slightly lower yield
(Table 2, Entry 7), as did the electron-deficient 2-bromonicotinaldehyde (2l; Table 2,
Entry 11). The polysubstituted 2-bromo-4,5-dimethoxybenzaldehyde (2i) was also a
suitable substrate, and the reaction could be scaled up to grams without lowering the
yields (Table 2, Entry 8). The bulky 1-bromonaphthalene-2-carbaldehyde (2k) reacted
just as well under the standard conditions as the other substrates (Table 2, Entry 10). To
our delight, the reaction of the electron-rich heterocyclic 3-bromothiophene-2-
carbaldehyde (2m) also went smoothly and gave a high yield of 3m (Table 2,
Entry 12). Moreover, 2-fluoro- and 2-chlorobenzaldehydes (2n and 2o, resp.) were also
tested as the substrates to react with 1a, and the yields were 76 (Table 2, Entry 13) and
61% (Table 2, Entry 14), respectively.
After having investigated the scope for ortho-haloarene-carbaldehydes, we then
studied the reactions of 2-(2-hydroxyphenyl)acetonitriles. Both substrates with EDGs
and EWGs, such as 2-(2-hydroxy-3-methoxyphenyl)acetonitrile (1b), 2-[2-hydroxy-4-
(trifluoromethyl)phenyl]acetonitrile (1c), and 2-(5-bromo-2-hydroxyphenyl)acetoni-
trile (1d), were tested under the optimal reaction conditions (Table 3). Most reactions
proceeded with high yields. When 1b was used as the substrate, the structurally

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Helvetica Chimica Acta – Vol. 96 (2013)
Table 2. One-Pot Cascade Reaction of 2-(2-Hydroxyphenyl)acetonitrile (1a) with Various ortho-
Haloarene-carbaldehydesa)
Entry
Substrate
Carbaldehyde
R
Product
Yield [%]b)
X
1
2
3
4
5
6
7
8c)
9
10
11
12
13
14
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
3-F
4-Me
4-MeO
5-MeO
5-F
Br
Br
Br
Br
Br
Br
Br
Br
Br
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3a
3a
98
86
93
98
92
95
79
98
98
94
65
81
76
61
5-Cl
5-CF3
4,5-(MeO)2
4,5-Dioxole
1-Bromonaphthalene-2-carbaldehyde
2-Bromopyridine-3-carbaldehyde
3-Bromothiophene-2-carbaldehyde
H
H
F
Cl
a) Reaction conditions: 1a (70 mg, 0.53 mmol), 2b – 2m (0.50 mmol), Cs2CO3 (488 mg, 1.5 mmol), CuI
(1 mg, 0.005 mmol), DMF (8 ml), reaction time (most of the reaction were complete within 1 h).
c
b) Yield of isolated 3. ) The reaction was scaled up to grams (1a (1.33 g, 10 mmol), 2i (2.45 g, 10 mmol),
Cs2CO3 (9.78 g, 30 mmol), CuI (20 mg, 0.1 mmol), and DMF (20 ml)); 97%.
hindered MeO group of 1b led to a decrease in the yields of the product compared with
the corresponding product of 1a (compounds 4a – 4e, 4h, 4i, and 4k vs. compounds 3a –
3e, 3h, 3i, and 3k), except for 4f, 4g, 4l, and 4m. Yields of 4f, 4g, and 4m were slightly
higher than those of 3f, 3g, and 3m, but the yield of 4l (92%) was dramatically higher
than that of 3l (65%). When 1c was treated with various 2-bromobenzaldehydes, the
EWG CF3 of 1c also led to a decrease in the yields (compounds 4n, 4o, and 4p vs.
compounds 3a, 3g, and 3e). In the case of 1d, substituted 2-bromobenzaldehydes, 2g
and 2e, gave higher yields than 2-bromobenzaldehyde (Table 3, Entries 17 and 18 vs.
Entry 16). Furthermore, 2-bromobenzaldehyde with a 5-MeO group (Table 3, En-
try 15) underwent the reaction in excellent yield (95%), while 2-bromobenzaldehyde
with a 5-Cl group led to a decreased yield (Table 3, Entries 14 vs. 13). As 2-(2-
aminophenyl)acetonitrile (1d) is an analog of 1a, 1d was treated with 2-bromobenz-
aldehyde under the standard conditions without any optimization, to give the
corresponding product in only 21% yield (Table 3, Entry 19).
We also tried another strategy to construct dibenzo[b,f]oxepin under the same
conditions (0.01 equiv. of CuI, 3 equiv. of Cs2CO3, DMF, 1008, 1 h; Scheme 2).

Helvetica Chimica Acta – Vol. 96 (2013)
301
Table 3. One-Pot Cascade Reaction of 2-(ortho-Hydroxy/ortho-Aminophenyl)acetonitriles with Substi-
tuted 2-Bromobenzaldehydesa)
Entry
1
R1
X
2
R2
Product
Yield [%]b)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
b
b
b
b
b
b
b
b
b
b
b
b
c
c
c
d
d
d
e
3-MeO
3-MeO
3-MeO
3-MeO
3-MeO
3-MeO
3-MeO
3-MeO
3-MeO
3-MeO
3-MeO
3-MeO
4-CF3
4-CF3
4-CF3
5-Br
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
NH2
a
b
c
d
e
f
g
h
i
k
l
m
a
g
e
a
g
e
a
H
3-F
4-Me
4-MeO
5-MeO
5-F
5-Cl
5-CF3
4,5-(MeO)2
4a
4b
4c
4d
4e
4f
4g
4h
4i
4k
4l
4m
4n
4o
4p
4q
4r
87
83
80
71
90
98
97
70
83
80
92
95
72
63
95
79
92
86
21
H
5-Cl
5-MeO
H
5-Cl
5-MeO
H
5-Br
5-Br
H
4s
4t [30]
a) Reaction conditions: 1a – 1d (0.53 mmol), 2a – 2m (0.50 mmol), Cs2CO3 (488 mg, 1.5 mmol), CuI
(1 mg, 0.005 mmol), and DMF (8 ml). b) Yield of isolated 4.
Unfortunately, we did not obtain any desired product. This can be explained by the
mechanism of the reaction. We presumed that the cascade includes two steps: the first
step is a Knoevenagel condensation, followed by the Ullmann ether formation
(Scheme 3). This was established by formation of the same intermediates, as revealed
by LC/MS, under Cu-assisted and Cu-free conditions. The intermediate in the
1
formation of 3d was confirmed by H- and 13C-NMR, and MS data (Scheme 3). This
intermediate could be converted to compound 3d via cyclization in two pathways.
When CuI was present, Ullmann ether formation occurred subsequently (Path A), or
the aromatic nucleophilic substitution reaction (Path B) would occur to give 3d under
Cu-free condition. However, Path A gave 3d with a preponderant high yield (92%; 56%

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Helvetica Chimica Acta – Vol. 96 (2013)
Scheme 2. Another Strategy to Form Dibenzo[b,f]oxepin
Scheme 3. Proposed Reaction Mechanism
for Path B; Table 1, Entries 9 and 14). When salicylaldehyde was used as the substrate
in the presence of the base, the phenoxy anion decreased the activity of aldehyde, and
Knoevenagel condensation could not occur under our conditions.
Conclusions. – We have developed a simple and efficient method for the synthesis
of the pharmacologically important dibenzo[b,f]oxepin scaffold via Cu-assisted/Cu-
free one-pot tandem reaction. Various substituted 2-(2-hydroxyphenyl)acetonitriles
and substituted 2-haloarene-carbaldehydes are tolerated well in the reaction. By this
procedure, a library of functionalized dibenzo[b,f]oxepins was achieved quickly with
good-to-excellent yields. This approach also provides a practical method, because it
could be easily scaled up to grams with excellent yields. Further studies for the synthesis
of novel dibenzo[b,f]oxepin analogs and their biological evaluation are currently in
progress.
Experiment Part
General. All the reagents, except 1a, are commercially available, and they were used without further
purification. Anal. TLC: HSGF 254 (0.15 – 0.2 mm thickness, Yantai Huiyou Company, China). Column
chromatography (CC): silica gel (200 – 300 mesh). M.p. Bꢀchi 510 melting-point apparatus; uncorrected.
1H- and 13C-NMR spectra: Varian Mercury-300 and/or Varian Mercury-400 spectrometers; d in ppm rel.
to Me4Si as internal standard, J in Hz. LR- and HR-MS: Finnigan/MAT-95 spectrometer.

Helvetica Chimica Acta – Vol. 96 (2013)
303
2-(2-Hydroxyphenyl)acetonitrile (1a) [29]. The corresponding 2-(2-methoxyphenyl)acetonitrile was
dissolved in anh. CH2Cl2, followed by slowly adding of 4n BBr3 in CH2Cl2 (4 – 5 equiv.) at 08. The mixture
was stirred at r.t. for a few h, then poured onto crushed ice, and the white precipitate was collected by
filtration. The product was obtained as white solid.
General Procedure for 3a – 3m, 4a – 4i, and 4k – 4s. To a mixture of 1 (0.53 mmol) and 2-
bromobenzaldehyde 2 (0.5 mmol) in a 25-ml two-necked reaction flask were added Cs2CO3 (1.5 mmol),
CuI (0.005 mmol), and DMF (8 ml). The mixture was degassed with Ar (3ꢁ) and then heated at 1008 for
0.5 – 1 h. Most of the reactions were complete within 1 h. Once the reaction was completed (monitored by
TLC), the mixture was poured onto crushed ice and then extracted with AcOEt (3ꢁ). The combined
org. layers were washed with brine and dried (Na2SO4). Concentration and purification by CC afforded
the products with desirable purities.
3-(2-Bromo-4-methoxyphenyl)-2-(2-hydroxyphenyl)prop-2-enenitrile (the intermediate in
1
Scheme 3). Yellow lamellar crystals. M.p. 154 – 1558. H-NMR (300 MHz, (D6)DMSO): 10.36 (s, 1 H);
7.96 (d, J ¼ 8.8, 1 H); 7.89 (s, 1 H); 7.40 (dd, J ¼ 7.7, 1.5, 1 H); 7.35 (d, J ¼ 2.6, 1 H); 7.25 (td, J ¼ 7.8, 1.6,
1 H); 7.13 (dd, J ¼ 8.8, 2.6, 1 H); 6.97 – 6.87 (m, 2 H); 3.83 (s, 3 H). 13C-NMR (125 MHz, (D6)DMSO):
161.44, 155.55, 144.14 (CH); 130.99 (CH); 130.78 (CH); 129.97 (CH); 126.80, 125.60, 121.26, 120.09
(CH); 118.60 (CH); 117.94, 116.82 (CH); 114.54 (CH); 110.70, 56.36 (Me). EI-MS: 329, 331 (40, Mþ),
250 (100, [M ꢀ Br]þ). HR-EI-MS: 329.0033 (Mþ, C16H12BrNOþ2 ; calc. 329.0051).
Dibenzo[b,f]oxepine-10-carbonitrile (3a). Compound 3a was obtained after the purification by flash
chromatography (FC; SiO2, 200 – 300 mesh; petroleum ether (PE)/AcOEt 100 :1). Yellowish needles.
1
M.p. 159 – 1608 ([31]: 159 – 1608). IR (KBr): 2219.67 (CN). H-NMR (300 MHz, (D6)DMSO): 7.92 (s,
1 H); 7.60 – 7.48 (m, 4 H); 7.42 – 7.27 (m, 4 H). 13C-NMR (100 MHz, (D6)DMSO): 158.00; 157.22; 143.85;
133.90; 132.85; 131.45; 128.18; 126.55; 126.21; 126.12; 122.54; 121.94; 118.76; 112.75. EI-MS: 219 (Mþ,
100). HR-EI-MS: 219.0681 (Mþ, C15H9NOþ; calc. 219.0684).
4-Fluorodibenzo[b,f]oxepine-10-carbonitrile (3b). Compound 3b was obtained after the purification
by FC (SiO2; PE/AcOEt 100 :1). White powder. M.p. 207 – 2088. IR (KBr): 2219.67 (CN). 1H-NMR
(300 MHz, (D6)DMSO): 8.00 (s, 1 H); 7.63 – 7.49 (m, 3 H); 7.44 – 7.26 (m, 4 H). 13C-NMR (125 MHz,
(D6)DMSO): 156.98; 153.91 (d, J ¼ 248, CꢀF); 144.69 (d, J ¼ 14, CꢀCꢀF); 142.95 (d, J ¼ 4, CꢀCꢀCꢀF);
133.18; 130.51; 128.63; 127.06; 126.84 (d, J ¼ 8, CꢀCꢀCꢀF); 126.73 (d, J ¼ 4, CꢀCꢀCꢀCꢀF); 126.01;
122.46; 120.22 (d, J ¼ 17.6, CꢀCꢀF); 118.51; 113.70. EI-MS: 237 (Mþ, 100). HR-EI-MS: 237.0593 (Mþ,
C15H8FNOþ; calc. 237.0590).
3-Methyldibenzo[b,f]oxepine-10-carbonitrile (3c). Compound 3c was obtained after the purification
1
by FC (SiO2; PE/AcOEt 70 :1). Yellowish powder. M.p. 139 – 1408. IR (KBr): 2213.88 (CN). H-NMR
(300 MHz, (D6)DMSO): 7.87 (s, 1 H); 7.58 – 7.47 (m, 2 H); 7.36 (m, 3 H); 7.20 (s, 1 H); 7.12 (d, J ¼ 7.7,
1 H); 2.34 (s, 3 H). 13C-NMR (100 MHz, (D6)DMSO): 157.50; 156.60; 144.35; 143.34; 132.17; 130.77;
127.62; 126.38; 125.99; 125.81; 125.00; 122.07; 121.87; 118.44; 111.30; 20.83. EI-MS: 233 (Mþ, 100). HR-
EI-MS: 233.0833 (Mþ, C16H11NOþ; calc. 233.0841).
3-Methoxydibenzo[b,f]oxepine-10-carbonitrile (3d). Compound 3d was obtained after the purifica-
tion by FC (SiO2; PE/AcOEt 40 :1). Yellowish powder. M.p. 149 – 1508. IR (KBr): 2211.95 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.81 (s, 1 H); 7.55 – 7.30 (m, 5 H); 6.99 (d, J ¼ 2.2, 1 H); 6.88 (dd, J ¼
8.6, 2.4, 1 H); 3.82 (s, 3 H). 13C-NMR (125 MHz, (D6)DMSO): 164.39; 159.47; 156.54; 143.70; 132.66;
132.43; 127.92; 126.56; 126.50; 122.69; 120.92; 119.18; 112.41; 109.88; 107.52; 56.33. EI-MS: 249 (Mþ,
100). HR-EI-MS: 249.0788 (Mþ, C16H11NOþ2 ; calc. 249.0790).
2-Methoxydibenzo[b,f]oxepine-10-carbonitrile (3e). Compound 3e was obtained after the purifica-
tion by FC (SiO2; PE/AcOEt 60 :1). Yellowish powder. M.p. 171 – 1728. IR (KBr): 2210.02 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.86 (s, 1 H); 7.58 – 7.48 (m, 2 H); 7.39 – 7.31 (m, 2 H); 7.28 (d, J ¼ 8.4,
1 H); 7.13 – 7.06 (m, 2 H); 3.74 (s, 3 H). 13C-NMR (125 MHz, (D6)DMSO): 157.13; 156.39; 151.27; 143.26;
132.42; 128.29; 127.78; 125.95; 125.63; 122.26; 121.92; 118.72; 118.35; 114.86; 112.66; 55.65. EI-MS: 249
(Mþ, 100). HR-EI-MS: 249.0792 (Mþ, C16H11NOþ2 ; calc. 249.0790).
2-Fluorodibenzo[b,f]oxepine-10-carbonitrile (3f). Compound 3f was obtained after the purification
by FC (SiO2; PE/AcOEt 100 :1). Yellowish powder. M.p. 218 – 2198. IR (KBr): 2217.74 (CN). 1H-NMR
(300 MHz, (D6)DMSO): 7.86 (s, 1 H); 7.63 – 7.47 (m, 2 H); 7.47 – 7.29 (m, 5 H). 13C-NMR (100 MHz,
(D6)DMSO): 158.86 (d, J ¼ 243, CF); 156.77; 153.74; 142.03; 132.68; 129.05 (d, J ¼ 9, CꢀCHꢀCꢀF);

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127.88; 126.21; 125.42; 123.18 (d, J ¼ 9, CHꢀCHꢀCꢀF); 121.99; 119.72 (d, J ¼ 24, CHꢀCꢀF); 118.01; 116.
68 (d, J ¼ 24, CHꢀCꢀF); 113.54. EI-MS 237 (Mþ, 100). HR-EI-MS: 237.0591 (Mþ, C15H8FNOþ; calc.
237.0590).
2-Chlorodibenzo[b,f]oxepine-10-carbonitrile (3g). Compound 3g was obtained after the purification
by FC (SiO2; PE/AcOEt 100 :1). White powder. M.p. 197 – 1988. IR (KBr): 2217.74 (CN). 1H-NMR
(300 MHz, (D6)DMSO): 7.86 (s, 1 H); 7.63 – 7.50 (m, 4 H); 7.42 – 7.33 (m, 3 H). 13C-NMR (100 MHz,
(D6)DMSO): 156.59; 156.23; 141.86; 132.76; 132.72; 130.11; 129.65; 129.32; 127.92; 126.32; 125.37;
123.31; 122.08; 117.98; 113.60. EI-MS: 253 (Mþ, 100). HR-EI-MS: 253.0302 (Mþ, C15H8ClNOþ; calc.
253.0294).
2-(Trifluoromethyl)dibenzo[b,f]oxepine-10-carbonitrile (3h). Compound 3h was obtained after the
purification by FC (SiO2; PE/AcOEt 100 :1). White powder. M.p. 107 – 1088. IR (KBr): 2223.52 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.99 – 7.89 (m, 3 H); 7.63 – 7.52 (m, 3 H); 7.47 – 7.35 (m, 2 H).
13C-NMR (125 MHz, (D6)DMSO): 160.58; 156.77; 142.43 (CH); 133.36 (CH); 130.65 (d, J ¼ 2.5,
CHꢀCꢀCF3); 128.95; 128.75 (d, J ¼ 2.5, CHꢀCꢀCF3); 128.48 (CH); 127.05 (CH); 126.68 (d, J ¼ 33,
CꢀCF3); 125.80; 125.14; 123.25 (CH); 122.98; 122.71 (CH); 118.39. EI-MS: 287 (Mþ, 100). HR-EI-MS:
287.0554 (Mþ, C16H8F3NOþ; calc. 287.0558).
2,3-Dimethoxydibenzo[b,f]oxepine-10-carbonitrile (3i). Compound 3i was obtained after the
purification by FC (SiO2; PE/AcOEt 10 :1). Yellow powder. M.p. 157 – 1588. IR (KBr): 2208.09 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.76 (s, 1 H); 7.57 – 7.45 (m, 2 H); 7.40 – 7.30 (m, 2 H); 7.07 (s, 1 H);
7.05 (s, 1 H); 3.84 (s, 3 H); 3.74 (s, 3 H). 13C-NMR (100 MHz, (D6)DMSO): 156.87; 153.46; 152.38;
146.45; 143.71; 132.37; 127.77; 126.44; 126.30; 122.43; 119.60; 119.12; 112.87; 110.28; 105.86; 56.41; 56.29.
EI-MS: 279 (Mþ, 100). HR-EI-MS: 279.0905 (Mþ, C17H13NO3þ ; calc. 279.0895).
[1,3]Dioxolo[4’,5’:4,5]benzo[1,2-b]benzo[f]oxepine-10-carbonitrile (¼1,3,5-Trioxabenzo[4,5]cyclo-
hept[1,2-f]indene-10-carbonitrile; 3j). Compound 3j was obtained after the purification by FC (SiO2;
PE/AcOEt 50 :1). Yellow powder. M.p. 199 – 2008. IR (KBr): 2219.67 (CN). 1H-NMR (300 MHz,
(D6)DMSO): 7.74 (s, 1 H); 7.57 – 7.45 (m, 2 H); 7.33 (dd, J ¼ 9.0, 3.0, 2 H); 7.08 (s, 1 H); 7.02 (s, 1 H); 6.11
(s, 2 H). 13C-NMR (100 MHz, (D6)DMSO): 156.14; 153.03; 151.60; 144.96; 143.13; 132.18; 127.28;
126.10; 126.06; 121.90; 120.69; 118.61; 110.25; 108.32; 103.16; 102.71. EI-MS: 263 (Mþ, 100). HR-EI-MS:
263.0584 (Mþ, C16H9NOþ3 ; calc. 263.0582).
Benzo[b]naphtho[2,1-f]oxepine-8-carbonitrile (3k). Compound 3k was obtained after the purifica-
tion by FC (SiO2; PE/AcOEt 50 :1). Yellow powder. M.p. 223 – 2248. IR (KBr): 2217.74 (CN). 1H-NMR
(300 MHz, (D6)DMSO): 8.67 (d, J ¼ 7.6, 1 H); 8.07 (s, 1 H); 8.01 (d, J ¼ 7.5, 1 H); 7.83 (d, J ¼ 8.5, 1 H);
7.77 – 7.52 (m, 6 H); 7.42 – 7.348 (t, J ¼ 7.5, 1 H). 13C-NMR (100 MHz, (D6)DMSO): 156.57; 153.20;
143.76; 135.71; 132.73; 128.39; 127.90; 127.80; 127.60; 126.50; 126.22; 125.12; 123.26; 122.71; 122.17;
118.31; 112.84. EI-MS: 269 (Mþ, 100). HR-EI-MS: 269.0839 (Mþ, C19H11NOþ; calc. 269.0841).
Benzo[6,7]oxepino[2,3-b]pyridine-6-carbonitrile (¼ [1]Benzoxepino[2,3-b]pyridine-6-carbonitrile;
3l). Compound 3l was obtained after the purification by FC (SiO2; PE/AcOEt 5 :1). White powder.
M.p. 207 – 2088. IR (KBr): 2219.67 (CN). 1H-NMR (300 MHz, (D6)DMSO): 8.43 (d, J ¼ 2.2, 1 H); 8.03
(d, J ¼ 7.5, 1 H); 7.92 (s, 1 H); 7.64 – 7.53 (m, 2 H); 7.45 – 7.35 (m, 3 H). 13C-NMR (100 MHz, (D6)DMSO):
161.14; 155.56; 151.70; 141.86; 141.59; 133.34; 128.40; 126.98; 125.48; 123.12; 123.08; 122.77; 118.41;
113.77. EI-MS: 220 (Mþ, 100). HR-EI-MS: 220.0633 (Mþ, C14H8N2Oþ; calc. 220.0637).
Benzo[b]thieno[2,3-f]oxepine-9-carbonitrile (¼ Thieno[3,2-b][1]benzoxepine-9-carbonitrile; 3m).
Compound 3m was obtained after the purification by FC (SiO2; PE/AcOEt 5 :1). Yellow powder.
M.p. 159 – 1608. IR (KBr): 2213.88 (CN). 1H-NMR (300 MHz, (D6)DMSO): 8.00 (d, J ¼ 4.6, 1 H); 7.83 (s,
1 H); 7.61 – 7.43 (m, 2 H); 7.40 – 7.33 (m, 1 H); 7.22 (d, J ¼ 8.1, 1 H); 7.02 (d, J ¼ 4.7, 1 H). 13C-NMR
(100 MHz, (D6)DMSO): 158.10; 156.03; 136.89; 133.42; 132.56; 128.39; 126.23; 126.04; 121.92; 121.72;
121.65; 118.51; 109.41. EI-MS: 225 (Mþ, 100). HR-EI-MS: 225.0240 (Mþ, C13H7NOSþ; calc. 225.0248).
6-Methoxydibenzo[b,f]oxepine-10-carbonitrile (4a). Compound 4a was obtained after the purifica-
tion by FC (SiO2; PE/AcOEt 60 :1). Yellowish powder. M.p. 171 – 1728. IR (KBr): 2210.02 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.93 (s, 1 H); 7.58 – 7.48 (m, 2 H); 7.33 – 7.24 (m, 4 H); 7.06 (m, 1 H);
3.90 (s, 3 H). 13C-NMR (100 MHz, (D6)DMSO): 157.54; 151.89; 144.61; 143.42; 133.24; 130.84; 128.13;
126.85; 126.12; 125.65; 121.69; 118.39; 114.96; 112.35; 56.25. EI-MS: 249 (Mþ, 100). HR-EI-MS: 249.0799
(Mþ, C16H11NOþ2 ; calc. 249.0790).

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4-Fluoro-6-methoxydibenzo[b,f]oxepine-10-carbonitrile (4b). Compound 4b was obtained after the
purification by FC (SiO2; PE/AcOEt 100 :1). Yellowish powder. M.p. 248 – 2498. IR (KBr): 2219.67
(CN). 1H-NMR (300 MHz, CDCl3): 7.46 (s, 1 H); 7.28 – 7.23 (m, 1 H); 7.19 – 7.11 (m, 3 H); 7.11 – 7.05 (m,
1 H); 7.02 (d, J ¼ 7.7, 1 H); 3.96 (s, 3 H). 13C-NMR (125 MHz, CDCl3): 155.74 (d, J ¼ 252, CF); 153.65;
147.51; 147.27 (d, J ¼ 13.9, CꢀCꢀF); 143.18 (d, J ¼ 3.8, CHꢀCHꢀCHꢀCꢀF); 132.17; 128.78; 127.58 (CH);
127.16 (d, J ¼ 7.6, CHꢀCHꢀCꢀF); 126.69 (d, J ¼ 3.8, CHꢀCꢀCꢀCꢀF); 121.13 (d, J ¼ 20.2, CHꢀCꢀF);
121.15 (CH); 119.80; 116.57; 116.48 (CH); 58.00 (Me). EI-MS: 267 (Mþ, 100). HR-EI-MS: 267.0694 (Mþ,
C16H10FNOþ2 ; calc. 267.0696).
6-Methoxy-3-methyldibenzo[b,f]oxepine-10-carbonitrile (4c). Compound 4c was obtained after the
purification by FC (SiO2; PE/AcOEt 20 :1). Yellowish powder. M.p. 164 – 1658. IR (KBr): 2215.81 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.87 (s, 1 H); 7.38 (d, J ¼ 7.7, 1 H); 7.27 – 7.24 (m, 2 H); 7.12 (s, 1 H);
7.10 (d, J ¼ 7.7, 1 H); 7.04 (m, 1 H); 3.90 (s, 3 H). 13C-NMR (100 MHz, (D6)DMSO): 157.51; 151.91;
144.54; 144.19; 143.44 (CH); 130.66 (CH); 126.98; 126.40 (CH); 126.09 (CH); 125.44; 122.10 (CH);
118.57; 118.36 (CH); 114.80 (CH); 111.38; 56.28 (Me); 20.93 (Me). EI-MS: 263 (Mþ, 100). HR-EI-MS:
263.0949 (Mþ, C17H13NOþ2 ; calc. 263.0946).
3,6-Dimethoxydibenzo[b,f]oxepine-10-carbonitrile (4d). Compound 4d was obtained after the
purification by FC (SiO2; PE/AcOEt 40 :1). Yellowish powder. M.p. 173 – 1748. IR (KBr): 2211.95 (CN).
1H-NMR (400 MHz, (D6)DMSO): 7.83 (s, 1 H); 7.44 (d, J ¼ 8.7, 1 H); 7.29 – 7.22 (m, 2 H); 7.02 (dd, J ¼
6.6, 2.6, 1 H); 6.90 (dd, J ¼ 8.6, 2.6, 1 H); 6.82 (d, J ¼ 2.6, 1 H); 3.89 (s, 3 H); 3.82 (s, 3 H). 13C-NMR
(100 MHz, (D6)DMSO): 163.66; 158.85; 151.97; 143.91; 143.21 (CH); 132.07 (CH); 127.20; 126.16 (CH);
120.91; 118.76; 118.17 (CH); 114.56 (CH); 111.61 (CH); 109.49; 107.34 (CH); 56.24 (Me); 55.81 (Me).
EI-MS: 279 (Mþ, 100). HR-EI-MS: 279.0888 (Mþ, C17H13NO3þ ; calc. 279.0895).
2,6-Dimethoxydibenzo[b,f]oxepine-10-carbonitrile (4e). Compound 4e was obtained after the
purification by FC (SiO2; PE/AcOEt 40 :1). Yellowish powder. M.p. 167 – 1688. IR (KBr): 2217.74
(CN). 1H-NMR (400 MHz, (D6)DMSO): 7.88 (s, 1 H); 7.27 – 7.25 (m, 2 H); 7.22 (d, J ¼ 9.1, 1 H); 7.12 –
7.03 (m, 3 H); 3.89 (s, 3 H); 3.74 (s, 3 H). 13C-NMR (100 MHz, (D6)DMSO): 156.29; 151.76; 151.26;
144.95; 143.28 (CH); 128.61; 126.76; 125.96 (CH); 122.35 (CH); 118.62 (CH); 118.43 (CH); 114.98 (CH);
114.65 (CH); 112.66; 56.22 (Me); 55.64 (Me). EI-MS: 279 (Mþ, 100). HR-EI-MS: 279.0904 (Mþ,
C17H13NOþ3 ; calc. 279.0895).
2-Fluoro-6-methoxydibenzo[b,f]oxepine-10-carbonitrile (4f). Compound 4f was obtained after the
purification by FC (SiO2; PE/AcOEt 50 :1). White powder. M.p. 211 – 2128. IR (KBr): 2217.74 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.85 (s, 1 H); 7.40 – 7.23 (m, 5 H); 7.08 – 7.02 (m, 1 H); 3.89 (s, 3 H).
13C-NMR (100 MHz, (D6)DMSO): 158.77 (d, J ¼ 243, CꢀF); 153.71; 151.80; 144.54; 142.13; 129.40 (d,
J ¼ 9.1, CꢀCHꢀCꢀF); 126.59; 126.31; 123.25 (d, J ¼ 9.1, CHꢀCHꢀCꢀF); 119.61 (d, J ¼ 24.3, CHꢀCꢀF);
118.50; 118.11; 116.59 (d, J ¼ 25.2, CHꢀCꢀF); 115.29; 113.56; 56.27 (Me). EI-MS: 267 (Mþ, 100). HR-EI-
MS: 267.0696 (Mþ, C16H10FNOþ2 ; calc. 267.0696).
2-Chloro-6-methoxydibenzo[b,f]oxepine-10-carbonitrile (4g). Compound 4g was obtained after the
purification by FC (SiO2; PE/AcOEt 50 :1). Yellowish powder. M.p. 235 – 2368. IR (KBr): 2217.74 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.89 (s, 1 H); 7.65 – 7.58 (m, 2 H); 7.35 – 7.28 (m, 3 H); 7.10 – 7.04 (m,
1 H); 3.90 (s, 3 H). 13C-NMR (100 MHz, (D6)DMSO): 156.16; 151.81; 144.35; 141.92 (CH); 132.64 (CH);
130.00 (CH); 129.67; 129.55; 126.54; 126.42 (CH); 123.37 (CH); 118.53 (CH); 118.08; 115.32 (CH);
113.61; 56.29 (Me). EI-MS: 283 (Mþ, 100). HR-EI-MS: 283.0402 (Mþ, C16H10ClNOþ2 ; calc. 283.0400).
6-Methoxy-2-(trifluoromethyl)dibenzo[b,f]oxepine-10-carbonitrile (4h). Compound 4h was obtained
after the purification by FC (SiO2; PE/AcOEt 50 :1). White powder. M.p. 180 – 1818. IR (KBr): 2219.67
(CN). 1H-NMR (300 MHz, (D6)DMSO): 7.97 (s, 1 H); 7.93 (s, 1 H); 7.88 (dd, J ¼ 8.3, 1 H); 7.47 (d, J ¼
8.4, 1 H); 7.31 – 7.27 (m, 2 H); 7.10 – 7.02 (m, 1 H); 3.90 (s, 3 H). 13C-NMR (100 MHz, (D6)DMSO):
160.01; 151.89; 144.00; 141.96; 130.00 (d, J ¼ 3.0, CHꢀCꢀCF3); 128.82; 128.14 (d, J ¼ 4.0, CHꢀCꢀCF3);
126.66; 126.38 (d, J ¼ 32, CꢀCF3); 126.51; 123.59 (d, J ¼ 270, CF3); 122.84; 118.57; 117.98; 115.47; 113.89;
56.33 (Me). EI-MS: 317 (Mþ, 100). HR-EI-MS: 317.0663 (Mþ, C17H10F3NOþ2 ; calc. 317.0664).
2,3,6-Trimethoxydibenzo[b,f]oxepine-10-carbonitrile (4i). Compound 4i was obtained after the
purification by FC (SiO2; PE/AcOEt 10 :1). Yellow powder. M.p. 208 – 2098. IR (KBr): 2211.95 (CN).
1H-NMR (300 MHz, (D6)DMSO): 7.79 (s, 1 H); 7.28 – 7.24 (m, 2 H); 7.11 (s, 1 H); 7.04 – 7.00 (m, 1 H);
6.87 (s, 1 H). 13C-NMR (100 MHz, (D6)DMSO): 152.87; 151.90; 151.84; 146.10; 144.41; 143.36 (CH);

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127.19; 125.99 (CH); 119.66; 118.82; 118.17 (CH); 114.66 (CH); 112.35 (CH); 109.99; 105.32 (CH); 56.29
(Me); 55.92 (Me); 55.92 (Me). EI-MS: 309 (Mþ, 100). HR-EI-MS: 309.0998 (Mþ, C18H15NOþ4 ; calc.
309.1001).
12-Methoxybenzo[b]naphtho[2,1-f]oxepine-8-carbonitrile (4k). Compound 4k was obtained after
the purification by FC (SiO2; PE/AcOEt 50 :1). Yellow power. M.p. 172 – 1738. IR (KBr): 2217.74 (CN).
1H-NMR (300 MHz, (D6)DMSO): 9.03 (d, J ¼ 8.4, 1 H); 8.00 (s, 1 H); 7.95 (d, J ¼ 8.4, 1 H); 7.80 (d, J ¼
8.5, 1 H); 7.73 – 7.63 (m, 2 H); 7.51 (d, J ¼ 8.5, 1 H); 7.32 – 7.28 (m, 2 H); 7.12 – 7.05 (m, 1 H); 3.96 (s, 3 H).
13C-NMR (100 MHz, (D6)DMSO): 154.44; 151.91; 145.61; 144.25 (CH); 135.74; 128.35 (CH); 127.46
(CH); 127.35; 126.98 (CH); 126.83; 126.66 (CH); 126.53 (CH); 125.26 (CH); 123.99 (CH); 123.54; 118.72
(CH); 118.47; 115.17 (CH); 113.00; 56.16 (Me). EI-MS: 299 (Mþ, 100). HR-EI-MS: 299.0948 (Mþ,
C20H13NOþ2 ; calc. 299.0946).
10-Methoxybenzo[6,7]oxepino[2,3-b]pyridine-6-carbonitrile (¼10-Methoxy[1]benzoxepino[2,3-
b]pyridine-6-carbonitrile; 4l). Compound 4l was obtained after the purification by FC (SiO2; PE/AcOEt
1
5 :1). Yellowish powder. M.p. 152 – 1538. IR (KBr): 2221.59 (CN). H-NMR (300 MHz, (D6)DMSO):
8.44 (d, J ¼ 4.0, 1 H); 8.04 (d, J ¼ 7.4, 1 H); 7.92 (s, 1 H); 7.45 (t, J ¼ 6.0, 1 H); 7.33 (d, J ¼ 4.2, 2 H); 7.10 (m,
1 H); 3.90 (s, 3 H). 13C-NMR (125 MHz, (D6)DMSO): 161.61; 152.70; 151.52 (CH); 144.10; 142.06 (CH);
141.50 (CH); 127.13 (CH); 126.66; 123.10; 122.97 (CH); 119.16 (CH); 118.55; 116.21 (CH); 113.90; 56.81
(Me). EI-MS: 250 (Mþ, 100) HR-EI-MS: 250.0736 (Mþ, C15H10N2Oþ2 ; calc. 250.0742).
5-Methoxybenzo[b]thieno[2,3-f]oxepine-9-carbonitrile (¼ 5-Methoxythieno[3,2-b][1]benzoxepine-
9-carbonitrile; 4m). Compound 4m was obtained after the purification by FC (SiO2; PE/AcOEt 5 :1).
Yellow powder. M.p. 180 – 1818. IR (KBr): 2211.95 (CN). 1H-NMR (300 MHz, (D6)DMSO): 7.95 (d, J ¼
5.4, 1 H); 7.86 (d, J ¼ 0.5, 1 H); 7.34 – 7.25 (m, 2 H); 7.07 – 6.99 (m, 1 H); 6.96 (dd, J ¼ 5.4, 0.5, 1 H); 3.87 (s,
3 H). 13C-NMR (100 MHz, (D6)DMSO): 158.25; 151.64; 144.11; 137.01 (CH); 133.41 (CH); 127.38;
126.30 (CH); 122.48; 121.55 (CH); 119.06 (CH); 118.65; 115.42 (CH); 109.54; 56.28 (Me). EI-MS: 255
(Mþ, 100). HR-EI-MS: 255.0354 (Mþ, C14H9NO2Sþ; calc. 255.0354).
7-(Trifluoromethyl)dibenzo[b,f]oxepine-10-carbonitrile (4n). Compound 4n was obtained after the
purification by FC (SiO2; PE/AcOEt 100 :1). Yellow powder. M.p. 108 – 1108. IR (KBr): 2219.67 (CN).
1H-NMR (300 MHz, (D6)DMSO): 8.10 – 8.01 (m, 1 H); 7.88 – 7.68 (m, 3 H); 7.66 – 7.46 (m, 3 H); 7.42 –
7.30 (m, 1 H). 13C-NMR (100 MHz, (D6)DMSO): 157.16; 156.57; 145.50 (CH); 138.35; 133.99 (CH);
132.08 (d, J ¼ 32, CꢀCF3); 131.31 (CH); 129.74; 129.00 (CH); 126.02 (d, J ¼ 273, CF3); 126.17 (CH);
122.87 (d, J ¼ 3, CHꢀCꢀCF3); 121.69 (CH); 119.36 (CHꢀCꢀCF3); 117.86; 114.52. EI-MS: 287 (Mþ, 100).
HR-EI-MS: 287.0554 (Mþ, C16H8F3NOþ; calc. 287.0558).
2-Chloro-7-(trifluoromethyl)dibenzo[b,f]oxepine-10-carbonitrile (4o). Compound 4o was obtained
after the purification by FC (SiO2; PE/AcOEt 100 :1). Yellow powder. M.p. 176 – 1778. IR (KBr): 2221.59
(CN). 1H-NMR (400 MHz, (D6)DMSO): 8.02 (s, 1 H); 7.89 (s, 1 H); 7.76 – 7.73 (m, 2 H); 7.69 – 7.64 (m,
2 H); 7.52 (d, J ¼ 8.3, 1 H). 13C-NMR (100 MHz, (D6)DMSO): 161.59; 161.03; 149.21 (CH); 138.52
(CH); 137.52 (d, J ¼ 32, CꢀCF3); 135.59 (CH); 135.28; 134.62; 134.41 (CH); 134.14; 128.43 (d, J ¼ 271,
CF3); 128.77 (CH); 128.32 (d, J ¼ 4.0, CHꢀCꢀCF3); 124.65 (d, J ¼ 4.0, CHꢀCꢀCF3); 122.78; 117.65. EI-
MS: 321 (Mþ, 100). HR-EI-MS: 321.0159 (Mþ, C16H7ClF3NOþ; calc. 321.0168).
2-Methoxy-7-(trifluoromethyl)dibenzo[b,f]oxepine-10-carbonitrile (4p). Compound 4p was obtained
after the purification by FC (SiO2; PE/AcOEt 50 :1). Yellowish powder. M.p. 181 – 1828. IR (KBr):
2221.59 (CN). 1H-NMR (400 MHz, (D6)DMSO): 8.02 (s, 1 H); 7.83 (s, 1 H); 7.75 – 7.68 (m, 2 H); 7.40 (d,
J ¼ 8.8, 1 H); 7.16 (dd, J ¼ 8.8, 3.1, 1 H); 7.12 (d, J ¼ 3.1, 1 H); 3.75 (s, 3 H). 13C-NMR (100 MHz,
(D6)DMSO): 156.92; 156.67; 150.83; 145.38 (CH); 132.10 (d, J ¼ 33, CꢀCF3), 129.69; 129.06 (CH);
127.94; 123.32 (d, J ¼ 272, CF3); 122.74 (d, J ¼ 3.0, CHꢀCꢀCF3); 122.51 (CH); 119.25 (CH); 119.17 (d,
J ¼ 3.0, CHꢀCꢀCF3); 117.89; 115.15 (CH); 111.51; 55.71 (Me). EI-MS: 317 (Mþ, 100). HR-EI-MS:
317.0656 (Mþ, C17H10F3NOþ2 ; calc. 317.0664).
8-Bromodibenzo[b,f]oxepine-10-carbonitrile (4q). Compound 4q was obtained after the purification
by FC (SiO2 ; PE/AcOEt 100 :1). Light yellow powder. M.p. 172 – 1738. 1H-NMR (300 MHz,
(D6)DMSO): 7.98 (s, 1 H); 7.72 (dd, J ¼ 8.6, 2.4, 1 H); 7.61 – 7.53 (m, 2 H); 7.51 (dd, J ¼ 7.7, 1.3, 1 H);
7.39 – 7.33 (m, 2 H); 7.31 (td, J ¼ 7.6, 1.2, 1 H). 13C-NMR (125 MHz, (D6)DMSO): 157.79; 156.44; 145.19
(CH); 135.44 (CH); 134.31 (CH); 131.74 (CH); 130.34 (CH); 128.33; 127.96; 126.53 (CH); 124.82 (CH);

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122.01 (CH); 118.42; 111.46. EI-MS: 297, 299 (Mþ, 100). HR-EI-MS: 296.9789 (Mþ, C15H8BrNOþ; calc.
296.9789).
8-Bromo-2-chlorodibenzo[b,f]oxepine-10-carbonitrile (4r). Compound 4r was obtained after the
purification by FC (SiO2; PE/AcOEt 100 :1). White powder. M.p. 194 – 1958. 1H-NMR (300 MHz,
(D6)DMSO): 7.92 (s, 1 H); 7.75 (dd, J ¼ 8.1, 1.8, 1 H); 7.65 – 7.57 (m, 3 H); 7.43 – 7.35 (m, 2 H). 13C-NMR
(125 MHz, (D6)DMSO): 156.47; 156.27; 143.68 (CH); 135.77 (CH); 133.64 (CH); 130.83 (CH); 130.53
(CH); 130.42; 129.54; 128.00; 124.84 (CH); 123.88 (CH); 118.68; 118.12; 112.76. EI-MS: 331, 333 (Mþ,
100). HR-EI-MS: 330.9399 (Mþ, C15H7BrClNOþ; calc. 330.9400).
8-Bromo-2-methoxydibenzo[b,f]oxepine-10-carbonitrile (4s). Compound 4s was obtained after the
purification by FC (SiO2; PE/AcOEt 100 :1). Light yellow powder. M.p. 175 – 1768. 1H-NMR (300 MHz,
(D6)DMSO): 7.91 (s, 1 H); 7.71 (dd, J ¼ 8.6, 2.3, 1 H); 7.56 (d, J ¼ 2.3, 1 H); 7.33 (d, J ¼ 8.6, 1 H); 7.28 (d,
J ¼ 8.7, 1 H); 7.10 (m, 2 H); 3.72 (s, 3 H). 13C-NMR (125 MHz, (D6)DMSO): 157.04; 156.77; 151.45;
145.03 (CH); 135.44 (CH); 130.37 (CH); 128.49; 128.26; 124.64 (CH); 122.78 (CH); 119.53 (CH); 118.41;
118.22; 115.57 (CH); 111.78; 56.17 (Me). EI-MS: 327, 329 (Mþ, 100). HR-EI-MS: 326.9896 (Mþ,
C16H11BrNOþ2 ; calc. 326.9895).
5H-Dibenzo[b,f]azepine-10-carbonitrile (4t) [30]. Compound 4t was obtained after the purification
by FC (SiO2; PE/AcOEt 3 :1). Brown powder. M.p. 218 – 2198. IR (KBr): 2217.74 (CN). 1H-NMR
(300 MHz, (D6)DMSO): 12.61 (s, 1 H); 8.03 – 7.96 (m, 2 H); 7.67 – 7.51 (m, 5 H); 7.33 (td, J ¼ 7.2, 1.1,
1 H); 7.26 (td, J ¼ 7.2, 1.1, 1 H). 13C-NMR (100 MHz, (D6)DMSO): 144.74; 135.51; 129.98 (CH); 129.33
(CH); 129.33 (CH); 129.33; 128.26; 126.97 (CH); 126.97 (CH); 123.93 (CH); 122.05 (CH); 118.37 (CH);
117.00; 112.66 (CH). EI-MS: 218 (Mþ, 100). HR-EI-MS: 218.0846 (Mþ, C15H10Nþ2 ; calc. 218.0844).
This work was financially supported by the ꢁInterdisciplinary Cooperation Teamꢂ Program for Science
and Technology Innovation of the Chinese Academy of Sciences, the National Natural Science Foundation
of China (21072205, SIMM1203ZZ-0103, and SIMM1105KF-02).
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Received March 8, 2012