MeOTf- and TBD-Mediated Carbonylation of ortho-Arylanilines with CO2 Leading to Phenanthridinones

Article abstract of DOI:10.1021/acs.joc.6b01318

Carbonylation of o-arylanilines utilizing CO₂ as a carbonyl source for the synthesis of important phenanthridinones with a free (NH)-lactam motif has been described under metal-free condition. A range of o-arylanilines were transformed to the corresponding phenanthridinones in high yields.

Full text of DOI:10.1021/acs.joc.6b01318

Article
pubs.acs.org/joc
MeOTf- and TBD-Mediated Carbonylation of ortho-Arylanilines with
CO2 Leading to Phenanthridinones
Sheng Wang,† Peng Shao,† Gaixia Du,† and Chanjuan Xi*,†,‡
†Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry,
Tsinghua University, Beijing 100084, China
‡State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
S
* Supporting Information
ABSTRACT: Carbonylation of o-arylanilines utilizing CO2 as a carbonyl
source for the synthesis of important phenanthridinones with a free (NH)-
lactam motif has been described under metal-free condition. A range of o-
arylanilines were transformed to the corresponding phenanthridinones in high
yields.
Scheme 1. Approach to Phenanthridinones Using C1
Synthons
INTRODUCTION
■
CO2 is a green, abundant, and inexpensive one-carbon source,
which has attracted a great attention in organic synthesis.1
However, inertia in kinetics and stability in thermodynamics
restrict its utilization. On the other hand, as a waste material of
combustion, CO2 emitted to the atmosphere is also threatening
the balance of carbon cycle. As a result, research focused on
activation and transformation of CO2 fulfilling the demand of
sustainable development is necessary. Recently, utilization of
CO2 for synthesis of carboxylic acid,2 carbonate,3 formamide4
and aldehyde5 have been well studied. However, carbonylation
reaction employing CO2 has been rarely reported.6 Compared
with CO,7 which was extensively utilized in transition metal-
catalyzed C−H carbonylation reaction, CO2 seems to be a more
promising carbonyl source in organic synthesis considering
safety and feasibility. Consequently, application of CO2 in the
carbonylation reactions may provide a better choice for the
synthesis of lactam and lactone.
RESULTS AND DISCUSSION
■
At the outset, we used o-phenylaniline 1a as a starting material to
react with CO2 in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-
ene (TBD) in dichloroethane (DCE) at 140 °C, the reaction did
not proceed after 12 h (Table 1, entry 1). As part of our ongoing
project using MeOTf,13 two equivalents of MeOTf was added
under the same reaction condition and the desired phenan-
thridinone 2a was obtained in 30% yield (entry 2). When three
equivalents of MeOTf was added, the yield of 2a was increased to
63% (entry 3), while addition of four equivalents of MeOTf
reduced the yield of 2a to 58% (entry 4). Then different bases,
such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), K2CO3,
Cs2CO3, and tBuOK, were screened (entries 5−8). TBD showed
an excellent performance as a base in this reaction (entry 3). The
solvents were also evaluated in the reaction. 1,2-Dichloroben-
zene (o-DCB) was superior to DCE, PhCl, and toluene (entries
3, 9−11). The reaction showed a dependence on the
temperature. When the reaction was treated at 160 °C, 130 °C,
and 120 °C, respectively, the yield of 2a was obtained in 79%,
58%, and 22% (entries 12−14). Notably, the reaction was treated
at 160 °C for 3 and 8 h, the yield of product 2a was obtained in
65% and 45%, respectively.
Phenanthridinone is a significant scaffold widely existing in
natural product8a and valuable compounds with biological
activities, such as antitumor,8b,c anti-HIV,8d and antileukemic.8e
Traditionally, the phenanthridinone could be obtained from
several paths, such as Beckmann rearrangement of oxime,
intramolecular C−C formation of N-arylbenzamide,9 and
intermolecular C−C and C−N formation between benzoamide
and arene10 or aryne.11 Recently, transition metal-catalyzed
directly C−H activation to obtain phenanthridinones has been
reported. In 2013, Zhu,7a Zhang,7b and Chuang’s group,7f
independently described the carbonyl reaction of ortho-arylani-
line catalyzed by palladium catalyst using CO as carbonyl source
in the presence of copper or silver salts to yield the
phenanthridinones (Scheme 1, right).
With optimized reaction condition in hand, we used a range of
o-arylanilines to investigate substrate scope, and the representa-
tive results are summarized in Table 2. Electronic property of
As part of our ongoing project on CO2,12 we herein reported a
metal-free method to synthesize the phenanthridinones from
ortho-arylaniline using atmospheric CO2 as the carbonyl source
with the assistance of MeOTf and TBD (Scheme 1, left), which
extend the utilization of CO2 as C1 synthons.
Received: June 1, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b01318
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substituents is the determinate factor in the reaction. Substrates
with electron-donating group in aryl moiety, such as 1b−1f and
1k, demonstrated higher reactivity and afforded the correspond-
ing products 2 in high yields, while electron-withdrawing group
decreased the yield dramatically, such as formation of the
corresponding products 2g−2j. The steric effect is unobvious in
this reaction, ortho-substituted substrates, such as 1d and 1e,
could react with CO2 smoothly to give the desired product 2d
and 2e in 58% and 80% yield, respectively. When meta-
substituted substrate as 1f was used, mixture of two isomers
(2f, 2f′) in 1:1 ratio were isolated. When two methyl groups
located in the meta-position of aryl moiety, the product 2k was
obtained in 79% yield. Notably, 2-(naphthalen-1-yl)aniline 1l
and 2-heteroarylanilines, such as 1m, 1n, and 1o, were well
subjected in this reaction and delivered the corresponding
products 2l, 2m, 2n, and 2o in good yields, respectively. In
addition, substituents such as −Me, −Cl, and, −F could also be
tolerated in the aniline ring to afford phenanthridinones 2p, 2q,
and 2r in moderate yields.
Table 1. Optimization of Reaction of o-Phenylaniline 1a with
CO2
a
b
entry MeOTf (x equiv)
base
TBD
solvent
temp (°C) yield (%)
1
DCE
140
140
140
140
140
140
140
140
140
140
140
160
130
120
160
160
0
2
2
3
4
3
3
3
3
3
3
3
3
3
3
3
3
TBD
TBD
TBD
DBU
K2CO3
Cs2CO3
tBuOK
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
DCE
30
63
58
5
3
DCE
4
DCE
5
DCE
6
DCE
0
7
DCE
0
8
DCE
0
9
PhCl
59
80 (73)
27
79
58
22
65
10
11
12
13
14
15
16
o-DCB
Toluene
o-DCB
o-DCB
o-DCB
o-DCB
o-DCB
Furthermore, we have tried to extend this method to synthesis
of seven-membered lactams, and the products were isolated in
low yield (eq 1).
c
d
45
a
b
Reactions were carried out with 0.1 mmol o-phenylaniline. NMR
yield was detected using dibromomethane as internal standard,
c
d
isolated yield in parentheses. Reaction time 3 h. Reaction time 8 h.
a
Table 2. Carbonylation of o-Arylanilines with CO2
To gain more information for the reaction mechanism, more
experiments were conducted. Initially, o-phenylaniline 1a was
treated with CO2 in the presence of one equivalent TBD and one
equivalent of MeOTf at room temperature for 1 h, and o-methyl
[1,1′-biphenyl]-2-ylcarbamate 3a was isolated in 93% yield (eq
2). Undoubtly, CO2 was fixated in the first step to generate the
carbamate 3a. Then the product 3a was treated by two
equivalents of MeOTf at 140 °C for 12 h, and the
phenanthridinone 2a was obtained in 82% yield with N,N-
dimethyl-[1,1′-biphenyl]-2-amine 4a in 12% yield (eq 3). The
formation of dimethylated product 4a indicated that the
carbamate 3a could be converted into 1a under high temper-
ature. Namely, the reaction of 1a with CO2 to form carbamate 3a
in the presence of TBD and MeOTf at 140 °C is a reversible
reaction. In addition, when the carbamate 3a was tested by GC-
MS, 2-isocyanato-1,1′-biphenyl 5 was observed. This result
supported the possibility of isocynate as a key intermediate in this
reaction.
a
Reactions were carried out with 0.3 mmol o-arylaniline. All yields are
On the basis of the experimental results as well as the known
reports,14 the reaction mechanism was proposed as follows
(Scheme 2). First, the o-arylaniline 1 attacks adduct of TBD and
CO2 to generate the carbamate 3 with the aid of MeOTf. Then,
isolated yields.
B
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Na2SO4, evaporated, and purified by flash chromatography (petroleum
ether/EtOAc).
Scheme 2. Plausible Reaction Mechanism
Synthesis of 2-Benzylaniline (1s). Sealed tube containing 1-
(bromomethyl)-2-nitrobenzene (5 mmol), phenylboronic acid (15
mmol), Pd(OAc)2 (0.15 mmol), PPh3 (0.3 mmol), and K3PO4 (20
mmol) was evacuated and backfilled with N2. Under N2 flows, degassed
toluene (30 mL) was added. The tube was closed and stirred vigorously
at 80 °C for 18 h. Then, the mixture was cooled to room temperature,
diluted by H2O and extracted by EtOAc three times. The combined
organic layer was dried by Na2SO4. The solution was evaporated and
used for the next step without purification. To the solution of crude
product in 25 mL EtOAc was added 25 mmol SnCl2·2H2O at room
temperature for 18 h. The reaction was quenched by NaOH and
extracted by EtOAc three times. The organic layer was dried over
Na2SO4, evaporated, and purified by flash chromatography (petroleum
ether/EtOAc).
2-Phenoxyaniline (1t) was synthesized according to reported
literature.15
General Procedure for the Carbonylation of 2-Arylaniline
with CO2. TBD (41.7 mg, 0.3 mmol) and aniline (0.3 mmol) were
added into sealed tube. The tube was evacuated and backfilled under
CO2 flow three times, and o-DCB was added into system under CO2
flow. The solution was stirred vigorously under atmospheric CO2 at
room temperature for 1 h. Then, MeOTf (147.6 mg, 0.9 mmol) was
added into solution under CO2 flow and the sealed tube was closed and
heated in 140 °C for 12 h. Hydrolyzed by 1 M HCl 5 mL and extracted
with EtOAc (5 × 5 mL), the combined organic solution was dried by
Na2SO4, evaporated, and purified by flash chromatography (petroleum
ether/EtOAc).
the carbamate 3 tends to lose MeOH to produce isocynate 5 at
high temperature.14b Next, cyclization occurs in the presence of
MeOTf to form the 6-methoxyphenanthridine 7 via intermediate
6. Finally, the intermediate 7 is hydrolyzed in situ to afford
phenanthridinone 2. Addition of excess MeOTf may be
attributed to interactions with product.
CONCLUSION
■
Phenanthridin-6(5H)-one (2a).7b White solid, 41 mg, yield: 73%,
mp: > 300 °C.1H NMR (400 MHz, DMSO-d6): δ 11.69 (br s, 1H), 8.50
(d, J = 8.2 Hz, 1H), 8.38 (d, J = 8.0 Hz, 1H), 8.32 (dd, J = 7.9, 1.0 Hz,
1H), 7.88−7.83 (m, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.51−7.46 (m, 1H),
7.38−7.35 (m, 1H), 7.29−7.24 (m, 1H); 13C NMR (151 MHz, DMSO-
d6): δ 161.0, 136.6, 134.4, 133.0, 129.7, 128.1, 127.6, 125.7, 123.4, 122.7,
122.5, 117.7, 116.3; IR (neat) νmax cm−1: 1659.
In conclusion, we have developed a carbonylation reaction of o-
arylanilines applying CO2 as the ideal carbonyl source to
synthesize phenanthridinones containing a free (NH)-lactam
motif under metal-free conditions. A range of functionalized
phenanthridinone products are obtained in high yields.
8-Methoxyphenanthridin-6(5H)-one (2b).7b White solid, 50 mg,
yield: 74%, mp: 262−264 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.71
(br s, 1H), 8.43 (d, J = 8.9 Hz, 1H), 8.29 (d, J = 8.0 Hz, 1H), 7.75 (d, J =
2.7 Hz, 1H), 7.43 (dt, J = 11.2, 5.5 Hz, 2H), 7.34 (d, J = 7.9 Hz, 1H), 7.24
(t, J = 7.5 Hz, 1H), 3.90 (s, 3H); 13C NMR (151 MHz, DMSO-d6) δ
160.7, 159.1, 135.5, 128.5, 127.7, 127.1, 124.7, 122.7, 122.4, 121.7, 117.8,
116.1, 108.7, 55.5; IR (neat) νmax cm−1: 1662.
EXPERIMENTAL SECTION
■
General information. DMF (N,N-dimethylformamide), o-DCB
(ortho-dichlorobenzene), DCM (dichloromethane), and DCE (1,2-
dichloroethane) were dried by 4 Å molecular sieves. Unless otherwise
mentioned, all reagents commercially available were used without
1
further purification. H NMR and 13C NMR spectra were recorded
utilizing 600 MHz spectrometer and 400 MHz spectrometer and d6-
DMSO was selected as the solvent. Chemical shifts (δ), recorded in
ppm, were referenced using the residual proton resonance of d6-DMSO
8-Phenylphenanthridin-6(5H)-one (2c). White solid, 62 mg, yield:
76%, mp: > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.77 (br s, 1H),
8.61−8.55 (m, 2H), 8.42 (d, J = 7.9 Hz, 1H), 8.17 (dd, J = 8.4, 2.1 Hz,
1H), 7.84−7.80 (m, 2H), 7.57−7.48 (m, 3H), 7.46−7.37 (m, 2H),
7.32−7.26 (m, 1H); 13C NMR (101 MHz, DMSO-d6) δ 160.9, 139.4,
138.9, 136.6, 133.4, 131.1, 129.7, 129.2, 128.1, 126.8, 126.2, 124.9, 123.6,
123.4, 122.4, 117.4, 116.2; IR (neat) νmax cm−1: 1662; HRMS (ESI):
calcd for C19H13NO [M + H] + 272.1070, found: 272.1072.
10-Methoxyphenanthridin-6(5H)-one (2d).7a Pale gray solid, 39
mg, yield: 58%, mp: 228−230 °C. 1H NMR (400 MHz, DMSO-d6) δ
11.73 (br s, 1H), 9.07 (d, J = 7.8 Hz, 1H), 8.02 (dd, J = 7.8, 1.2 Hz, 1H),
7.61 (t, J = 8.0 Hz, 1H), 7.51 (dd, J = 8.1, 1.0 Hz, 1H), 7.43−47 (m, 1H),
7.37 (dd, J = 8.1, 1.3 Hz, 1H), 7.20−7.24 (m, 1H), 4.06 (s, 3H); 13C
NMR (151 MHz, DMSO-d6) δ 160.6, 157.7, 136.4, 128.8, 128.5, 128.3,
127.8, 123.4, 122.1, 119.7, 117.3, 115.9, 115.4, 56.2; IR (neat) νmax cm−1:
1654.
1
(2.50) in H NMR and carbon resonance of d6-DMSO (39.5) in 13C
NMR. Coupling constants (J) were obtained in Hertz (Hz). The terms s,
d, t, and m represent singlet, doublet, triplet, and multiplet. HRMS were
obtained with ESI in positive ion mode on IT-TOF instrument.
General Procedure for Synthesis of 2-Arylaniline 1. Sealed tube with
2-bromoaniline (3 mmol), aryboronic acid (4.5 mmol), K2CO3 (9
mmol), and PdCl2(PPh3)2 (0.3 mmol) was evacuated and backfilled
with N2. DMF/H2O (15 mL/3 mL) was added under N2 flow. The tube
was closed and the mixture was stirred for 24 h at 90 °C. Then, the
reaction was cooled to room temperature, diluted with H2O and
extracted with EtOAc three times. The combined organic layer was
washed with saturated NaCl solution two times, dried by Na2SO4,
evaporated, and purified by flash chromatography (petroleum ether/
EtOAc).
Synthesis of 2-(1H-Pyrrol-1-yl)aniline (1o). 1-Fluoro(chloro)-2-
nitrobenzene (10 mmol), pyrrole (10 mmol), and NaOH (10 mmol) in
10 mL DMSO were stirred vigorously at room temperature for 1.5 h.
After completion of the reaction, the mixture was cooled to room
temperature, diluted by H2O, and extracted by EtOAc three times. The
combined organic layer was washed with saturated NaCl solution two
times and dried by Na2SO4. The solution was evaporated and used for
the next step without purification. To the solution of crude product in 50
mL EtOAc was added 50 mmol SnCl·2H2O at room temperature, and
the solution was stirred for 18 h. The reaction was quenched by NaOH
and extracted by EtOAc three times. The organic layer was dried by
10-Methylphenanthridin-6(5H)-one (2e).7b White solid, 50 mg,
yield: 80%, mp: 294−296 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.71
(br s, 1H), 8.44 (d, J = 8.3 Hz, 1H), 8.31 (dd, J = 7.9, 1.4 Hz, 1H), 7.73−
7.70 (m, 1H), 7.56−7.46 (m, 2H), 7.40 (dd, J = 8.1, 1.4 Hz, 1H), 7.24−
7.28 (m, 1H), 2.93 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 161.0,
137.1, 137.0, 135.2, 133.3, 128.8, 127.5, 127.4, 127.3, 126.1, 121.8, 118.8,
116.3, 25.7; IR (neat) νmax cm−1: 1649.
9-Methylphenanthridin-6(5H)-one (2f).16 White solid, 23 mg yield:
37.5%, mp: 254−256 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.57 (s,
1H), 8.36 (d, J = 7.8 Hz, 1H), 8.31 (s, 1H), 8.20 (d, J = 8.1 Hz, 1H),
7.49−7.43 (m, 2H), 7.35 (dd, J = 8.2, 1.0 Hz, 1H), 7.27−7.22 (m, 1H),
C
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2.53 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 160.8, 143.0, 136.7,
134.2, 129.4, 129.1, 127.5, 123.4, 123.2, 122.5, 122.1, 117.5, 116.1, 21.5.
IR (neat) νmax cm−1: 1652.
122.7, 122.7, 118.2, 116.6, 115.1, 112.9, 111.5; IR (neat) νmax cm−1:
1652.
2-Methylphenanthridin-6(5H)-one (2p).7b White solid, 41 mg,
yield: 66%, mp: 259−261 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.60
(br s, 1H), 8.45 (d, J = 8.1 Hz, 1H), 8.30 (dd, J = 8.0, 1.2 Hz, 1H), 8.16 (s,
1H), 7.80−7.84 m, 1H), 7.59−7.64 (m, 1H), 7.24−7.31 (m, 2H), 2.39
(s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 1601.0, 134.5, 134.4, 133.0,
131.6, 130.8, 128.0, 127.7, 125.8, 123.2, 122.7, 117.6, 116.2, 20.9; IR
(neat) νmax cm−1: 1647.
7-Methylphenanthridin-6(5H)-one (2f′).16 White solid, 23 mg yield:
37.5%, mp: 249−251 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.41 (s,
1H), 8.33 (dd, J = 11.1, 8.2 Hz, 2H), 7.66 (t, J = 7.8 Hz, 1H), 7.46−7.41
(m, 1H), 7.38 (d, J = 7.4 Hz, 1H), 7.33−7.30 (m, 1H), 7.22−7.17 (m,
1H), 2.86 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 162.0, 141.2,
136.7, 135.8, 131.9, 131.2, 129.4, 123.8, 123.5, 121.9, 120.7, 117.7, 115.4,
23.7. IR (neat) νmax cm−1:1650.
2-Chlorophenanthridin-6(5H)-one (2q).17 Pale yellow solid, 34 mg,
yield: 50%, mp: > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.77 (br s,
1H), 8.46 (d, J = 8.1 Hz, 1H), 8.39 (d, J = 8.7 Hz, 1H), 8.30 (dd, J = 7.9,
1.3 Hz, 1H), 7.83−7.87 (m, 1H), 7.63.7.67 (m, 1H), 7.38 (d, J = 2.2 Hz,
1H), 7.28 (dd, J = 8.6, 2.2 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ
160.9, 137.7, 133.8, 133.6, 133.1, 128.4, 127.6, 125.5, 125.3, 122.9, 122.2,
116.6, 115.4; IR (neat) νmax cm−1: 1664.
8-Bromophenanthridin-6(5H)-one (2g). White solid, 49 mg, yield:
60%, mp: > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.83 (br s, 1H),
8.44 (d, J = 8.8 Hz, 1H), 8.38−8.33 (m, 2H), 7.98 (dd, J = 8.7, 2.2 Hz,
1H), 7.51 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.29−7.24 (m,
1H); 13C NMR (151 MHz, DMSO-d6) δ 159.8, 136.6, 135.8, 133.6,
130.3, 129.8, 127.5, 125.5, 123.6, 122.8, 121.3, 117.1, 116.49; IR (neat)
2-Fluorophenanthridin-6(5H)-one (2r).17 White solid, 26 mg, yield:
40%, mp: > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.73 (br s, 1H),
8.49 (d, J = 8.1 Hz, 1H), 8.31 (dd, J = 7.9, 1.2 Hz, 1H), 8.21−8.26(m,
1H), 7.82−7.88 (m, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.35−7.39 (m, 2H);
13C NMR (151 MHz, DMSO-d6) δ 160.7, 158.0 (d, J = 237.7 Hz), 133.7,
133.2, 133.1, 128.8, 127.6, 125.9, 123.3 (d, J = 6.4 Hz), 119.0 (d, J = 8.2
Hz), 118.0 (d, J = 7.3 Hz), 117.4 (d, J = 24.1 Hz), 109.3 (d, J = 24.0 Hz);
IR (neat) νmax cm−1: 1687.
+
νmax cm−1: 1669; HRMS (ESI): calcd for C13H8BrNO [M + H]
273.9862, found: 273.9860
8-Chlorophenanthridin-6(5H)-one (2h).7b White solid, 33 mg,
1
yield: 48%, mp: 292−294 °C. H NMR (400 MHz, DMSO-d6) δ
11.84 (br s, 1H), 8.52 (d, J = 8.8 Hz, 1H), 8.35 (d, J = 7.5 Hz, 1H), 8.22
(d, J = 2.4 Hz, 1H), 7.86 (dd, J = 8.7, 2.6 Hz, 1H), 7.48−7.52 (m, 1H),
7.35−7.37 (m, 1H), 7.25−7.29 (m, 1H); 13C NMR (151 MHz, DMSO-
d6) δ 159.8, 136.5, 133.2, 132.9, 132.8, 130.1, 127.2, 126.7, 125.3, 123.5,
122.7, 117.0, 116.4; IR (neat) νmax cm−1: 1670.
5H-Dibenzo[b,e]azepin-6(11H)-one (2s). White solid, 16 mg, yield:
25%, mp: 200−202 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.45 (br s,
1H), 7.70 (d, J = 7.7 Hz, 1H), 7.46 (t, J = 7.4 Hz, 1H), 7.29−7.38 (m,
3H), 7.04−7.19 (m, 3H), 3.89 (s, 2H); 13C NMR (101 MHz, DMSO-
d6) δ 168.2, 141.5, 136.8, 133.1, 132.3, 132.2, 130.1, 128.2, 127.2, 127.2,
126.9, 124.6, 121.0, 37.9; IR (neat) νmax cm−1: 1668; HRMS (ESI): calcd
for C14H11NO [M + H] + 210.0913, found: 210.0910.
8-Fluorophenanthridin-6(5H)-one (2i).7b White solid, 17 mg, yield:
26%, mp: 282−284 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.82 (br s,
1H), 8.58−8.53 (m, 1H), 8.32 (d, J = 8.0 Hz, 1H), 7.95 (dd, J = 9.3, 2.9
Hz, 1H), 7.68−7.73 (m, 1H), 7.51−7.45 (m, 1H), 7.34−7.38 (m, 1H),
7.24−7.29 (m, 1H); 13C NMR (151 MHz, DMSO-d6) δ 161.73 (d, J =
246.7 Hz), 160.19 (d, J = 2.2 Hz), 136.13, 131.24, 129.72 (d, J = 4.2 Hz),
127.73 (d, J = 7.4 Hz), 126.07 (d, J = 6.7 Hz), 123.44 (d, J = 4.1 Hz),
122.80 (d, J = 7.4 Hz), 121.23 (d, J = 20.3 Hz), 117.26, 116.40 (d, J = 7.1
Hz), 112.68 (d, J = 22.4 Hz); IR (neat) νmax cm−1: 1680.
Dibenzo[b,f][1,4]oxazepin-11(10H)-one (2t).18 White solid, 30 mg,
yield: 47%, mp: 214−216 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.53
(br s, 1H), 7.77 (dd, J = 7.7, 1.7 Hz, 1H), 7.58−7.63 (m, 1H), 7.29−7.35
(m, J = 7.9 Hz, 3H), 7.09−7.18 (m, 3H); 13C NMR (101 MHz, DMSO-
d6) δ 165.9, 159.0, 150.5, 134.5, 131.4, 131.2, 126.0, 125.8, 125.5, 125.3,
121.7, 121.4, 120.7; IR (neat) νmax cm−1: 1666
7,9-Dimethylphenanthridin-6(5H)-one (2k).16 White solid, 53 mg,
yield: 79%, mp: 276−278 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.31
(br s, 1H), 8.30 (d, J = 8.0 Hz, 1H), 8.16 (s, 1H), 7.45−7.40 (m, 1H),
7.28 (d, J = 7.2 Hz, 1H), 7.22−7.16 (m, 2H), 2.80 (s, 3H), 2.45 (s, 3H);
13C NMR (151 MHz, DMSO-d6) δ 162.1, 142.1, 141.2, 136.9, 135.9,
132.6, 129.5, 123.6, 122.0, 121.6, 120.9, 117.8, 115.5, 23.7, 21.4; IR
(neat) νmax cm−1: 1671.
Methyl [1,1′-biphenyl]-2-ylcarbamate (4).19 White solid, 63 mg,
yield: 93%. 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 7.2 Hz, 1H), 7.49
(t, J = 7.3 Hz, 2H), 7.43−7.36 (m, 4H), 7.22 (dd, J = 7.6, 1.6 Hz, 1H),
7.16−7.11 (m, 1H), 6.67 (s, 1H), 3.72 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 154.1, 138.2, 134.9, 131.5, 130.2, 129.4, 129.2, 128.6, 128.0,
123.4, 119.6, 52.4.
Benzo[k]phenanthridin-6(5H)-one (2l). Pale yellow solid, 62 mg,
yield: 85%, mp: 285−287 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.96
(br s, 1H), 8.91−8.96 (m, 1H), 8.61 (d, J = 8.2 Hz, 1H), 8.31 (d, J = 8.6
Hz, 1H), 8.13−8.17 (m, 1H), 8.09 (d, J = 8.6 Hz, 1H), 7.74−7.79 (m,
2H), 7.54−7.58 (m, 1H), 7.49−7.52 (m, 1H), 7.33−7.37 (m, 1H); 13C
NMR (151 MHz, DMSO-d6) δ 161.0, 137.4, 135.9, 133.0, 129.4, 129.1,
128.7, 128.4, 128.3, 128.0, 127.5, 127.4, 124.6, 122.9, 122.2, 117.6,
116.5; IR (neat) νmax cm−1: 1645; HRMS (ESI): calcd for C17H11NO
[M + H] + 246.0913, found: 246.0916.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b01318.
■
S
NMR spectra for all compounds (PDF)
Benzofuro[3,2-c]quinolin-6(5H)-one (2m).17 Pale yellow solid, 39
mg, yield: 55%, mp: > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 12.02
(br s, 1H), 8.08−8.12 (m, 1H), 8.03−8.07 (m, 1H), 7.84 (d, J = 7.8 Hz,
1H), 7.59−7.64 (m, 1H), 7.45−7.54 (m, 3H), 7.32−7.36 (m, 1H); 13C
NMR (151 MHz, DMSO-d6) δ 159.2, 158.0, 154.9, 138.5, 131.0, 126.5,
124.8, 123.9, 122.6, 121.4, 121.3, 116.3, 112.0, 110.9, 110.1.
AUTHOR INFORMATION
Corresponding Author
*Email: cjxi@tsinghua.edu.cn
■
Notes
The authors declare no competing financial interest.
Benzo[4,5]thieno[3,2-c]quinolin-6(5H)-one (2n). White solid, 47
mg, yield: 63%, 225 °C decomposed. 1H NMR (400 MHz, DMSO-d6) δ
12.01 (br s, 1H), 8.77−8.80 (m, 1H), 8.15 (dd, J = 7.0, 1.5 Hz, 1H), 7.91
(d, J = 7.6 Hz, 1H), 7.49−7.61 (m, 4H), 7.30−7.34 (m, 1H); 13C NMR
(151 MHz, DMSO-d6) δ 158.9, 148.0, 137.5, 136.9, 136.6, 130.7, 126.4,
125.9, 124.7, 124.30, 123.4, 123.0, 122.7, 116.3, 116.0; IR (neat) νmax
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (21472106 and 21272132) and the
National Key Basic Research Program of China (973 program)
(2012CB933402).
+
cm−1: 1665; HRMS (ESI): calcd for C15H9NOS [M+H] 252.0478,
found: 252.0482.
Pyrrolo[1,2-a]quinoxalin-4(5H)-one (2o).17 Pale yellow solid, 41
1
REFERENCES
mg, yield: 75%, mp: 257−259 °C. H NMR (400 MHz, DMSO-d6) δ
■
11.27 (br s, 1H), 8.16−8.19 (m, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.28 (d, J
= 6.0 Hz, 2H), 7.18−7.23 (m, 1H), 7.01−7.04 (m, 1H), 6.66−6.70 (m,
1H); 13C NMR (101 MHz, DMSO-d6) δ 155.1, 128.6, 125.8, 123.3,
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