Synthesis of 5H-Dibenzo[c,e]azepine-5,7(6H)-diones from Benzamides via Palladium-Catalyzed Double C-H Bond Activation

Article abstract of DOI:10.1021/acs.joc.6b03087

A convenient and efficient method for the synthesis of 5H-dibenzo[c,e]azepine-5,7(6H)-diones from simple and readily available benzamides is described in this work. The palladium-catalyzed homocoupling of benzamides occurred via ortho-selective double C-H bond activation using the simplest amide CONH₂ as a directing group. The subsequent intramolecular condensation reaction proceeded smoothly to produce 5H-dibenzo[c,e]azepine-5,7(6H)-diones in satisfactory to excellent yields in one pot.

Full text of DOI:10.1021/acs.joc.6b03087

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Note
Synthesis of 5H-Dibenzo[c,e]azepine-5,7(6H)-diones from
Benzamides via Palladium-Catalyzed Double C–H Bond Activation
VIJAYAKUMAR KONDAPALLI, Xiaoqiang Yu, Yoshinori Yamamoto, and Ming Bao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b03087 • Publication Date (Web): 26 Jan 2017
Downloaded from http://pubs.acs.org on January 27, 2017
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Synthesis of 5H-Dibenzo[c,e]azepine-5,7(6H)-diones from Benzamides
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via Palladium-Catalyzed Double C–H Bond Activation
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Vijayakumar Kondapalli,† Xiaoqiang Yu,† Yoshinori Yamamoto,†,‡ and Ming Bao*,†
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian
†
116023, China
‡ WPIꢀAIMR (WPIꢀAdvanced Institute for Materials Research), Tohoku University,
Sendai 980ꢀ8577, Japan
mingbao@dlut.edu.cn (M. Bao)
ABSTRACT:
A
convenient and efficient method for the synthesis of
5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones from simple and readily available benzamides is
described in this work. The palladiumꢀcatalyzed homoꢀcoupling of benzamides occurred
via orthoꢀselective double C–H bond activation using the simplest amide CONH2 as a
directing group. The subsequent intramolecular condensation reaction proceeded
smoothly to produce 5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones in satisfactory to excellent
yields in one pot.
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The transitionꢀmetalꢀcatalyzed direct coupling between aromatic rings via double C–H
bond activation has recently emerged as an extremely powerful tool for the synthesis of
biaryl compounds.1,2 An appropriate directing group is usually required to control
regioselectivity in this type of Caryl–Caryl bond coupling reaction, which includes
crossꢀcoupling and homoꢀcoupling. Over the past decades, various directing groups, such
as heterocycles,3 acyl groups,4 carboxyl groups,5 Nꢀsubstitutedꢀamide groups,6 and
Nꢀsubstituted acetamide groups,7 have been successfully employed for this purpose.
Among the myriad directing groups utilized so far, Nꢀsubstitutedꢀamide groups, including
secondary and tertiary amide groups, have been frequently used not only for the
Caryl–Caryl bond coupling reaction, but also for other kinds of coupling reactions because
of their unique reactivities in transitionꢀmetalꢀcatalyzed C–H functionalizations.8 In
comparison with Nꢀsubstitutedꢀamide groups, the free form, namely, primary amide
group (CONH2), has been rarely utilized as a directing group in the C–H
functionalizations. Only two examples have been previously reported in the literature;
such studies used primary amide as the directing group in the orthoꢀarylation of
benzamides with aryl iodides9 as well as in the benzylation of benzamides with benzyl
bromides.10 The primary amideꢀdirecting group is more easily functionalized after the
desired operation. Therefore, the development of a new C–H functionalization method for
Caryl–Caryl bond coupling reaction, using primary amide as the directing group, is an
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important requirement. The direct homoꢀcoupling of benzamides can provide a new
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protocol with which to access 5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones (Scheme 1).
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Scheme 1. Methods for the synthesis of 5Hꢀdibenzo[c,e] azepineꢀ5,7(6H)ꢀdiones.
5HꢀDibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones represent an interesting structural motif found
frequently in biologically active compounds. As pharmaceuticals,
5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione derivatives and their analogues exhibit
remarkable properties, such as antihyperlipidemic
active,11
Pꢀglycoprotein(Pꢀgp)ꢀmediated multidrug resistance (MDR) reversal agents,12
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hypolipidemic agents in rats,13 histamine H3 receptor antagonists for the treatment of
obesity,14 potent inhibitors of the activity of human Tmolt4 T cell leukemia type IIIMP
dehydrogenase (IMPDH),15 and antiꢀepinephrine activity.16 Therefore, the development
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of
a
convenient
and
efficient
method
for
the
synthesis
of
5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones has attracted considerable attention. The
5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione skeleton is conventionally synthesized through a
sequence of steps, including aryl–aryl linkage through the homoꢀcoupling of 2ꢀamino
benzoic acids through azo intermediate, diphenicanhydride formation through
intramolecular dehydrative condensation of diphenic acid, nucleophilic substitution of
diphenicanhydride with ammonia, and intramolecular dehydrative cyclization (Scheme
1).11
Homoꢀcoupling products of benzamides have been observed as byproducts in small
amounts in the palladiumꢀcatalyzed direct orthoꢀarylation of benzamides with aryl
iodides.9 This finding indicates that the diarylated benzamides might be obtained as major
products after optimization of reaction conditions. Based on the literatures, the
palladiumꢀcatalyzed direct homoꢀcoupling of benzamides is speculated to proceed
through different two catalysis cycles (Scheme 2): one catalysis cycle involves Pd0 and
PdII species in the presence of weak oxidant,17 and another involves two sequential C–H
activation at PdII and PdIV, respectively, in the presence of strong oxidant.18 Satisfactory
yields of diarylated benzamides could not be obtained by using a weak oxidant.9 This
observation encourages further examination of the palladiumꢀcatalyzed direct
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homoꢀcoupling of benzamides by using a strong oxidant. The homoꢀcoupling of
benzamides occurred, as expected, in the presence of a strong oxidant to produce
5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones in one pot. The results are reported in the current
work.
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Scheme 2. Proposed reaction mechanism for palladiumꢀcatalyzed direct homoꢀcoupling
of benzamides.
The palladiumꢀcatalyzed homoꢀcoupling reaction of benzamide (1a) was selected as a
model reaction to optimize the reaction conditions in the initial studies. The optimization
included the selection of the most suitable precatalysts, oxidants, solvents, and reaction
temperature as shown in Table 1. Several palladium precatalysts, including Pd(OAc)2,
Pd(acac)2, PdCl2, Pd2(dba)3, and Pd(PPh3)2Cl2, were initially tested in the presence of a
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strong oxidant, potassium persulfate (K2S2O8), in trifluoroacetic acid (TFA) at 130 °C
(entries 1–5). The desired product, 5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3a), was
obtained in 43% yield by using Pd(OAc)2 as the precatalyst (entry 1), thus indicating that
the homoꢀcoupling reaction of 1a occurred as expected when a strong oxidant was
utilized. The oxidants were subsequently screened using Pd(OAc)2 as a precatalyst and
TFA as a solvent. Na2S2O8 proved to be the best among the tested oxidants, namely,
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K2S2O8,
ammonium
persulfate
[(NH4)2S2O8],
1,4ꢀbenzoquinone
(BQ),
2ꢀhydroperoxyꢀ2ꢀmethylpropane (tBuOOH), diꢀtertꢀbutyl peroxide (DTBP), and sodium
persulfate (Na2S2O8) (entry 1 vs. entries 6–10). The reaction time and temperature were
subsequently screened using Pd(OAc)2, Na2S2O8, and TFA as the precatalyst, oxidant,
and solvent, respectively. The 3a yield decreased or did not changed when the reaction
time was shortened to 12 h or prolonged to 36 h (entry 10 vs. entries 11 and 12); the 3a
yield was decreased to 52% or 60% when the model reaction was performed at 120 °C or
140 °C (entry 10 vs. entries 13 and 14). TFA proved to be the best solvent after screening.
Therefore, the subsequent double C–H activation reactions of various benzamides were
performed for 24 h in the presence of Pd(OAc)2 as a precatalyst and Na2S2O8 as an
oxidant in TFA at 130 °C.
Table 1. Reaction Condition Screeninga
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entry
1
catalyst
Pd(OAc)2
Pd(acac)2
PdCl2
oxidant
solvent yield (%)
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
(NH4)2S2O8
BQ
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
AcOH
dioxane
43b
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2
0c
3
0c
4
Pd2(dba)3
Pd(PPh3)2Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
0c
5
0c
6
tracec
0c
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8
tBuOOH
0c
0c
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DTBP
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Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
83
56d
83e
52f
60g
tracec
tracec
aReaction conditions: 1a (1.0 mmol, 121.1 mg), catalyst (5 mol%), oxidant (1.0 mmol) in solvent (2.0
mL) at 130 °C for 24 h under air atmosphere. b1H NMR yield; dibromomethane was used as an
internal standard. Starting material 1a was recovered. dThe reaction was performed for 12 h. The
reaction was performed for 36 h. fThe reaction was performed at 120 °C. gThe reaction was performed
at 140 °C.
c
e
The scope and limitation of this type of double C–H activation reaction were
determined under the optimal reaction conditions. The results are summarized in Table 2.
The reaction of substrate 1b bearing a methyl group on the paraꢀposition of benzene ring
proceeded smoothly under the optimized conditions, like the simplest substrate 1a, to
offer an excellent yield (90%) of the corresponding cyclic compound 3b (entries 1 and 2).
However, a methyl group linked on the metaꢀposition of benzamide substrate 1c led to
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the formation of cyclic compound 3c in a relatively low yield (entry 3, 73%).
Furthermore, no reaction was observed when the benzamide substrate 1d bearing a
methyl group on the orthoꢀposition of benzene ring was examined (entry 4). The
relatively low yield and nonꢀreaction observed can be attributed to the steric hindrance
caused by the metaꢀ or orthoꢀmethyl group linked on benzene ring. Meanwhile, a
moderate yield (64%) was observed when the benzamide substrate 1e bearing two methyl
groups on the metaꢀ and paraꢀpositions of benzene ring was treated under the optimized
conditions (entry 5). The reaction of benzamide substrate 1f proceeded smoothly to
produce the desired cyclic compound 3f in a good yield (87%), even though a bulky
substituent (tBu) was linked on the paraꢀposition of benzene ring (entry 6). The steric
effect of methoxy group (MeO) on the reactivity of benzamide substrate was more
evident than that of the methyl group (entry 7 vs. entry 3). A low yield (46%) was
observed in the reaction of metaꢀmethoxy benzamide (1g). Low yields (40% and 37%,
respectively) were observed in the reactions of benzamide substrates 1h and 1i containing
an electronꢀwithdrawing group (F) on the benzene ring (entries 8 and 9). The results
indicated that the reactivity of benzamide substrate was lowered by a strong
electronꢀwithdrawing group, and the substituent position did not exert significant
influence on reactivity. The reaction of paraꢀbrominated benzamide 1j or
paraꢀchlorinated benzamide 1l resulted in excellent yields (91% and 93%, respectively)
of the corresponding cyclic compounds 3j or 3l (entries 10 and 12). In addition, the
desired product, 3k, was obtained in a relatively low yield (43%) owing to the steric
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hindrance of metaꢀbromine atom (entry 11). Br and Cl atoms linked to the benzene ring
were notably maintained in the structures of products 3j−3l, suggesting that further
manipulation may produce more useful compounds. To further explore the reaction scope,
the fused aromatic ringꢀcontaining substrates, 2ꢀnaphthamide (1m) and 1ꢀnaphthamide
(1n), were examined under the optimized reaction conditions. The desired product, 3m,
was obtained in 57% yield (entry 13). However, no reaction was observed when the
1ꢀnaphthamide (1n) was examined (entry 14). This behavior was attributed to the steric
hindrance caused in the substrate molecule. No reaction was observed again when
4ꢀcyanobenzamide (1o) bearing a more stronger electronꢀwithdrawing group was treated
under the optimal reaction conditions; the starting material 1o was recovered in 26%
yield (entry 15).
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Table 2. Synthesis of 5HꢀDibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones from various Benzamidesa
entry
1
ketone 1
product 3
yield
(%)
H
O
O
N
1a
1b
1c
3a
3b
3c
83
90
2
3
73
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1d
1e
4
5
3d
3e
0
64
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O
NH2
6
1f
1g
1h
3f
3g
3h
87
46
40
t Bu
7
8
1i
1j
9
3i
3j
37
91
10
11
12
1k
1l
3k
3l
43
93
57
0
1m
1n
1o
13
14
15
3m
3n
3o
0
aReaction conditions: benzamide (1, 1.0 mmol), Pd(OAc)2 (11.2 mg, 5 mol%), and Na2S2O8 (238.11 mg, 1.0 mmol) in
TFA (2.0 mL) at 130 °C for 24 h under air atmosphere.
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Control experiments were conducted to gain insights into the mechanism of this type of
double C–H bond activation reaction. The palladiumꢀcatalyzed double C–H activation
reaction of benzylamide (1a) was conducted using Na2S2O8 as the oxidant in TFA at 130
°C for 6 h. The formation of small amount of intermediate 2a, namely, the
homoꢀcoupling product, was observed by HPLCꢀMS determination. The cyclic product,
3a, was separated and produced a 28% yield, whereas no formation of
Nꢀbenzoylbenzamide (4) was observed; the sarting material 1a was recovered in 46%
yield (Scheme3, Eq. 1). Intermediates 2a and 4 were prepared and treated under
optimized reaction conditions to further confirm the reaction mechanism (Scheme3, Eqs.
2 and 3). The target product, 3a, was obtained in 95% yield through the intramolecular
condensation of 2a. No reaction was observed when 4 was treated at the same conditions.
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These
results
demonstrated
that
the
desired
cyclic
products,
5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones, were formed via homoꢀcoupling products of
benzamides.
Scheme 3. Control experiments.
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In summary, a convenient and efficient method is developed for the synthesis of
5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdiones
through
palladiumꢀcatalyzed
direct
homoꢀcoupling reaction of benzamides and subsequent intramolecular condensation
reaction in one pot. The simplest amide CONH2 is succesfully used as a directing group
for Caryl–Caryl bond coupling reaction in the presence of a strong oxidant for the first time.
The wide availability of the starting materials and experimental simplicity could make the
present method more useful in future organic synthesis applications.
EXPERIMENTAL SECTION
General Information.
1
13
Solvents were purified by standard techniques without special instructions. H and C
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NMR spectra were recorded on a 400 spectrometer (400 MHz for 1H, 100 MHz for 13C);
DMSOꢀd6 was used as a solvent. The chemical shifts are reported in ppm (δ), and the
coupling constants J are given in Hz. The peak patterns are indicated as follows: s, singlet;
d, doublet; m, multiplet. IR spectra were recorded on a FTꢀIR spectrometer. High
resolution mass spectra were recorded on either a QꢀTOF mass spectrometer or a
GCꢀTOF mass spectrometer. TLC was carried out on SiO2, and the spots were located
with UV light. The starting materials 1a–1o are commercially available.
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Procedure for Preparation of 2,2'-Diphenyldicarboxamide
To diphenic acid (1.21g, 5 mmol) SOCl2 (8.0 ml) was slowly added at 0 °C. After the
mixture was refluxed for 4 h, the excess of SOCl2 was removed under reduced pressure.
Then, the crude product was treated with concentrated ammonia solution at 0 °C and
stirred at room temperature for 2 h. The crude product was extracted with ethyl acetate
(10 mL × 3), and the combined organic layers were washed with brine (10 mL × 2), dried
over Na2SO4. The solvent was removed under reduced pressure, and the residue was
purified via silica gel chromatography (eluent: petroleum ether/ethyl acetate = 5:1) to
afford the desired product 2a as a white solid (516 mg, 43% yield).Representative
Procedure for the Synthesis of 5H-Dibenzo[c,e]azepine-5,7(6H)-diones
A reaction flask was charged with a mixture of Pd(OAc)2 (11.2 mg, 0.05 mmol),
Na2S2O8 (238.1 mg, 1 mmol), benzamide (1a, 121.1 mg, 1 mmol), and trifluoroacetic
acid (2 mL). The reaction mixture was stirred at 130 °C for 24 h, and then was cooled to
room temperature. The solvent was removed under reduced pressure, and the residue
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obtained was neutralized with Et3N (1.0 mL). The crude product was dissolved in
saturated NaHCO3 solution followed by extraction with ether (10 mL × 3), and the
combined organic layers were dried over anhydrous Na2SO4. The solvent was removed
under vacuum. The crude product was purified by column chromatography (eluent, ethyl
acetate : petroleum ether = 1 : 5) to afford 3a as a white solid (92.5 mg, 83% yield).
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2,2'ꢀDiphenyldicarboxamide (2a):19 white solid (516 mg, 43% yield), mp 208–210 ºC.
1H NMR (400 MHz, DMSOꢀd6) δ: 7.97 (s, 2H), 7.55–7.46 (m, 2H), 7.46–7.37 (m, 4H),
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7.31 (s, 2H), 7.11–7.01 (m, 2H); C{1H} NMR (100 MHz, DMSOꢀd6)
δ: 171.6, 139.2,
137.1, 129.7, 129.4, 127.8, 127.5.
5HꢀDibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3a):20 white solid (92.5 mg, 83% yield), mp
1
184–186 ºC. H NMR (400 MHz, DMSOꢀd6) δ: 11.71 (s, 1H), 7.93 (dd, J = 7.8, 1.2 Hz,
2H), 7.83 (d, J = 7.8 Hz, 2H), 7.80–7.74 (m, 2H), 7.65–7.58 (m, 2H); 13C{1H} NMR (100
MHz, DMSOꢀd6) δ: 168.6, 135.4, 133.4, 133.3, 131.0, 130.5, 129.4; HRMSꢀAPCI (m/z):
[MꢀH]ꢀ Calculated for C14H8NO2, 222.0561; found, 222.0570.
2,10ꢀDimethylꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3b): pale yellow solid (113.0 mg,
1
90% yield), mp 222–224 ºC. H NMR (400 MHz, DMSOꢀd6) δ: 11.51 (s, 1H), 7.82 (d, J
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= 8.0 Hz, 2H), 7.65 (s, 2H), 7.40 (dd, J = 8.0, 0.8 Hz, 2H), 2.45 (s, 6H); C{1H} NMR
(100 MHz, DMSOꢀd6) δ: 168.4, 143.6, 135.5, 131.2, 130.8, 130.6, 130.0, 21.5; IR (KBr):
3453.7, 1697.2, 1658.7, 1602.3, 1353.1, 1297.4, 1269.2, 1152.7, 657.0 cmꢀ1;
HRMSꢀAPCI (m/z): [MꢀH]ꢀ Calculated for C16H12NO2, 250.0874; found, 250.0870.
3,9ꢀDimethylꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3c): white solid (91.6 mg, 73%
yield), mp 216–218 ºC. 1H NMR (400 MHz, DMSOꢀd6) δ: 11.62 (s, 1H), 7.73 (d, J = 1.1
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Hz, 2H), 7.70 (s, 1H), 7.68 (s, 1H), 7.56 (dd, J = 8.1, 1.4 Hz, 2H), 2.41 (s, 6H); C{1H}
NMR (100 MHz, DMSOꢀd6) δ: 168.6, 138.8, 134.1, 132.8, 132.8, 131.6, 130.2, 20.9; IR
(KBr): 3445.8, 1683.9, 1660.8, 1447.2, 1313.6, 823.0 cmꢀ1; HRMSꢀAPCI (m/z): [MꢀH]ꢀ
Calculated for C16H12NO2, 250.0874; found, 250.0869.
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2,3,9,10ꢀTetramethylꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3e): white solid (89.28 mg,
1
64% yield), mp 233–235 ºC. H NMR (400 MHz, DMSOꢀd6) δ: 11.44 (s, 1H), 7.70 (s,
2H), 7.62 (s, 2H), 2.37 (s, 6H), 2.32 (s, 6H); 13C{1H} NMR (100 MHz, DMSOꢀd6) δ:
167.9, 142.0, 137.1, 132.6, 131.3, 130.5, 129.9, 19.4, 18.8; IR (KBr): 3182.2, 3070.6,
1655.4, 1606.5, 1287.5 427.4 cmꢀ1; HRMSꢀAPCI (m/z): [MꢀH]ꢀ Calculated for
C18H16NO2, 278.1187; found, 278.1192.
2,10ꢀDiꢀtertꢀbutylꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3f): yellow denser liquid
(145.7 mg, 87%). 1H NMR (400 MHz, DMSOꢀd6) δ: 11.53 (s, 1H), 7.89 (s, 1H), 7.87 (s,
1H), 7.71 (d, J = 1.7 Hz, 2H), 7.66 (dd, J = 8.3, 1.7 Hz, 2H), 1.37 (s, 18H); 13C{1H}
NMR (100 MHz, DMSOꢀd6) δ: 168.3, 156.3, 135.7, 131.1, 130.7, 127.0, 126.5, 35.4,
31.1; IR (neat): 3336.4, 2961.9, 1678.9, 1158.6, 789.0, 700.0 cmꢀ1; HRMSꢀAPCI (m/z):
[MꢀH]ꢀ Calculated for C22H24NO2, 334.1813; found, 334.1814.
3,9ꢀDimethoxyꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3g): white solid (65.1 mg, 46%
yield), mp 217–219 ºC. 1H NMR (400 MHz, DMSOꢀd6) δ: 11.67 (s, 1H), 7.73 (d, J = 8.7
13
Hz, 2H), 7.40 (d, J = 2.9 Hz, 2H), 7.33 (dd, J = 8.7, 2.9 Hz, 2H), 3.87 (s, 6H); C{1H}
NMR (100 MHz, DMSOꢀd6) δ: 168.2, 159.2, 133.7, 131.9, 128.0, 120.1, 114.7, 56.0; IR
(KBr): 3446.1, 3179.3, 2924.4, 1601.6. 1486.7, 1337.1, 1239.0, 1042.0, 818.8, 760.6,
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624.3 cmꢀ1; HRMSꢀAPCI (m/z): [MꢀH]ꢀ Calculated for C16H12NO4, 282.0772; found,
282.0780.
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2,10ꢀDifluoroꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3h): white solid (51.8 mg, 40%
yield), mp 246–248 ºC. 1H NMR (400 MHz, DMSOꢀd6) δ: 11.76 (s, 1H), 7.99 (dd, J = 8.8,
6.1 Hz, 2H), 7.77 (dd, J = 10.5, 2.5 Hz, 2H), 7.52–7.44 (m, 2H); 13C{1H} NMR (100
MHz, DMSOꢀd6) δ: 166.8, 164.3 (d, JCꢀF = 199.6 Hz), 136.5 (d, JCꢀF = 7.2 Hz), 134.1 (d,
JCꢀF = 7.6 Hz), 129.4 (d, JCꢀF = 2.2 Hz), 116.8 (d, JCꢀF = 15.1 Hz), 116.7 (d, JCꢀF = 13.3
Hz); IR (KBr): 3449.0, 2920.4, 1702.2, 1670.1, 1364.9, 1300.6, 1210.7, 860.2 cmꢀ1;
HRMSꢀAPCI (m/z): [MꢀH]ꢀ Calculated for C14H6F2NO2, 258.0372; found, 258.0372.
3,9ꢀDifluoroꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3i): white solid (48.0 mg, 37%
yield), mp 236–238 ºC. 1H NMR (400 MHz, DMSOꢀd6) δ: 11.95 (s, 1H), 7.89 (dd, J = 8.6,
5.3 Hz, 2H), 7.74–7.58 (m, 4H); 13C{1H} NMR (100 MHz, DMSOꢀd6) δ: 166.5, 161.6 (d,
JCꢀF = 246.6 Hz), 134.5 (d, JCꢀF = 7.5 Hz), 132.9 (d, JCꢀF = 8.1 Hz), 130.7 (d, JCꢀF = 3.4
Hz), 120.2 (d, JCꢀF = 21.4 Hz), 116.8 (d, JCꢀF = 24.0 Hz); IR (KBr): 3179.9, 3074.9,
1679.2, 1587.0, 1420.1, 1313.8, 830.7, 769.6 cmꢀ1; HRMSꢀAPCI (m/z): [MꢀH]ꢀ
Calculated for C14H6F2NO2, 258.0372; found, 258.0365.
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2,10ꢀDibromoꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3j): white solid (173.3 mg, 91%
1
yield), mp 288–290 ºC. H NMR (400 MHz, DMSOꢀd6) δ: 11.83 (s, 1H), 8.11 (s, 2H),
13
7.84 (s, 4H); C{1H} NMR (100 MHz, DMSOꢀd6) δ: 167.6, 135.8, 133.2, 133.0, 132.8,
132.5, 127.3; IR (KBr): 3434.4, 3335.5, 3252.6, 1692.7, 1584.7, 1382.0, 1347.8, 1302.0,
1147.2, 840.6 cmꢀ1; HRMSꢀESI (m/z): [MꢀH]ꢀ Calculated for C14H6Br2NO2, 379.8751;
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found, 379.8750.
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3,9ꢀDibromoꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3k): white solid (82.0 mg, 43%
yield), mp 306–308 ºC. 1H NMR (400 MHz, DMSOꢀd6) δ: 11.96 (s, 1H), 8.02 (d, J = 2.2
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Hz, 2H), 7.96 (dd, J = 8.5, 2.2 Hz, 2H), 7.79 (s, 1H), 7.77 (s, 1H); C{1H} NMR (100
MHz, DMSOꢀd6) δ: 166.9, 136.2, 134.8, 133.7, 133.3, 132.6, 122.9; IR (KBr): 3449.1,
3065.3, 2890.6, 1667.4, 1398.5, 1306.2, 822.1, 685.3 cmꢀ1; HRMSꢀAPCI (m/z): [MꢀH]ꢀ
Calculated for C14H6Br2NO2, 379.8751; found, 379.8764.
2,10ꢀDichloroꢀ5Hꢀdibenzo[c,e]azepineꢀ5,7(6H)ꢀdione (3l): white solid (135.7 mg, 93%
yield), mp 270–272 ºC. 1H NMR (400 MHz, DMSOꢀd6) δ: 11.83 (s, 1H), 8.00 (d, J = 2.1
13
Hz, 2H), 7.94 (s, 1H), 7.92 (s, 1H), 7.71 (dd, J = 8.5, 2.1 Hz, 2H); C{1H} NMR (100
MHz, DMSOꢀd6) δ: 167.4, 138.3, 135.9, 133.3, 132.1, 130.2, 129.7; IR (KBr): 3443.3,
3072.4, 1669.6, 1387.8, 1309.1, 871.5, 840.2 cmꢀ1; HRMSꢀAPCI (m/z): [MꢀH]ꢀ
Calculated for C14H7Cl2NO2, 289.9781; found, 289.9786.
6HꢀDinaphtho[2,3ꢀc:2',3'ꢀe]azepineꢀ6,8(7H)ꢀdione (3m):21 white solid (92.0 mg, 57%
1
yield), mp. >300 ºC. H NMR (400 MHz, DMSOꢀd6) δ: 11.75 (s, 1H), 8.60 (s, 2H), 8.49
(s, 2H), 8.20–8.15 (m, 4H), 7.75–7.66 (m, 4H); C{1H} NMR (100 MHz, DMSOꢀd6) δ:
13
168.7, 135.1, 132.4, 132.1, 132.1, 131.5, 130.7, 129.4, 129.2, 128.6, 128.2.
ACKNOWLEDGMENT
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We are grateful to the National Natural Science Foundation of China [Nos. 21372035,
21573032, and 21361140375 (NSFCꢀIUPAC program)] for their financial support. This
work was also supported by the Fundamental Research Funds for the Central Universities
(DUT15LK37) and the Outstanding Young Scholars Development Growth Plan of
Universities in Liaoning Province (LJQ2015027).
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SUPPORTING INFORMATION
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Copies of H and C NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
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