Transition-Metal-Free Synthesis of Phenanthridinones through Visible-Light-Driven Oxidative C–H Amidation

Article abstract of DOI:10.1002/ejoc.201900536

The treatment of N-aryl biphenylcarboxamide, 1-chloroanthraquinone (1-Cl-AQN) catalyst, and K₂CO₃ in CHCl₃ under visible light irradiation affords phenanthridinone via radical cyclization. This reaction proceeds under transition-metal-free condition, room temperature, and direct C–H amidation. Mechanistic studies indicate that amidyl radical generation proceeds by visible light induced proton coupled electron transfer (PCET) from N–H bond of the amide.

Full text of DOI:10.1002/ejoc.201900536

A Journal of
Accepted Article
Title: Transition-Metal-Free Synthesis of Phenanthridinones through
Visible-Light-Driven Oxidative C–H Amidation
Authors: Kaoru Usami, Eiji Yamaguchi, Norihiro Tada, and Akichika
Itoh
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900536
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10.1002/ejoc.201900536
European Journal of Organic Chemistry
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Transition-Metal-Free Synthesis of Phenanthridinones through
Visible-Light-Driven Oxidative C–H Amidation
Kaoru Usami, [a] Dr. Eiji Yamaguchi, [a] Dr. Norihiro Tada[a] and Prof. Dr. Akichika Itoh *[a]
Abstract: The treatment of N-aryl biphenylcarboxamide, 1-
chloroanthraquinone (1-Cl-AQN) catalyst, and K2CO3 in CHCl3 under
visible light irradiation affords phenanthridinone via radical cyclization.
This reaction proceeds under transition-metal-free condition, room
temperature, and direct C–H amidation. Mechanistic studies indicate
that amidyl radical generation proceeds by visible light induced proton
coupled electron transfer (PCET) from N–H bond of the amide.
photocatalyzed C–H amidation, the process required an
expensive iridium photocatalyst at 60°C. Moreover, this
reaction was not attempted with an electron-deficient
aromatic ring as the substituent on the nitrogen atom of the
amide.
From this perspective, we reported AQNs[10] catalyzed
radical imidation of a heteroaromatic ring, which proceeded
by generating an imidyl radical using oxidative PCET.[11] We
therefore
assumed
that
a
transition-metal-free
phenanthridinone synthesis could be developed using an
AQN photocatalyst possessing a high oxidation potential
rather than the iridium catalyst (Scheme 1(d)).[12] Herein, we
have developed a mild and transition-metal-free oxidative
phenanthridinone synthesis using an inexpensive
commercial organophotocatalyst and a base under visible
light irradiation. Moreover, in this reaction, we successfully
used nitrogen atoms substituted with electron-deficient
aromatic rings and heterocycles as substrates for the first
time in a phenanthridinone synthesis under photoredox
conditions.
Introduction
Phenanthridinones are important structural motifs in organic
chemistry as they are present in many natural products and
bioactive compounds.[1] Additionally, they can be converted
into structures possessing functional groups at the ortho
position of the biphenyl by hydrolysis of the lactam moiety.
Generally, the lactam backbone is constructed via
intramolecular amidation. To perform this, it is necessary to
introduce an amino and a carboxyl group into the molecule.
Notably, no ortho-position-selective intermolecular amination
has been reported. Thus, to introduce an amino group into
biphenyl, it is necessary to employ a stepwise approach that
introduces a leaving group such as a halogen followed by
coupling reactions, e.g., Buchwald–Hartwig amination,[2]
Chan–Lam–Evans coupling,[3] and aromatic nucleophilic
substitution.[4] For synthesizing phenanthridinone, many
methods involving C–C coupling from N-phenylbenzamide
have been reported, but this requires introducing a leaving
group and using expensive transition metals (Scheme
1(a)).[5] However, phenanthridinone formation involving C–H
amidation was recently reported, allowing direct skeleton
formation from carboxamide (Scheme 1(b)). C–H amidation
is economical because it is unnecessary to introduce a
leaving group such as a halogen to the substrate.[6] In 2013,
Yu’s group reported a phenanthridinone synthetic method
using copper iodide catalyst.[7] Additionally, Shiiya’s group in
2013 and Xue’s group in 2017 reported phenanthridinone
synthesis by transition metal-free C–H amidation using a
hypervalent iodine reagent, but the substrates were limited
to N-alkoxy and N-phthaloyl compounds.[8] In 2018, Hong’s
group reported the intramolecular C–H amidation of biphenyl
using a photocatalyst (Scheme 1(c)).[9] Although this is the
first report of phenanthridinone formation using visible-light-
Scheme 1. Various Methods for Constructing Phenanthridinones
Results and Discussion
We demonstrated intramolecular C–H amidation using N-
phenyl biphenylcarboxamide (1a) as a model substrate
(Table 1). We initially attempted cyclization reaction using
the conditions for imidyl radical generation that we reported
previously. N-phenyl biphenylcarboxamide (1a) provided the
corresponding phenanthridinone (2a) in 35% yield in the
presence of 2-tBu-AQN as a photocatalyst and K2CO3 as an
additive in DMF under visible light irradiation (entry 1). We
[a] Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu 501-
1196, Japan. E-mail: itoha@gifu-pu.ac.jp
http://sv1.gifu-pu.ac.jp/lab/gousei/
Supporting information for this article is given via a link at the end of the
document.
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10.1002/ejoc.201900536
European Journal of Organic Chemistry
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then tuned the reaction conditions to improve the yield. When
this reaction was performed in polar solvents, a moderate
yield was achieved, and using chloroform as the reaction
solvent afforded a good yield (entries 2–4). These results
indicated that the solubility of the substrate and catalyst
significantly influenced the reactivity. As photocatalysts,
AQNs generally showed good reactivity (entries 5–7).
Moreover, the catalyst loading could be reduced to 1 mol%
(entry 7). When the reaction was conducted without the base,
the substrate was not completely consumed (entry 8).
Although various inorganic bases accelerated the cyclization
reaction, adding triethylamine did not affect the yield (entries
9–10). After finely tuning the reaction conditions, a 96% yield
of phenanthridinone was obtained with 0.01 equiv of 1-Cl–
AQN as the photosensitizer, 0.1 equiv of K2CO3 as the
additive, and 2 mL of chloroform as the solvent under visible
light irradiation (entry 11).
heterocyclic ring such as benzothiazole (2j). In a previous
report by Hong, no cyclization reaction was reported of
substrates with electron-deficient aromatic rings or
heterocycles. However, no product was obtained with a
substrate substituted with an alkyl group
(2k, 2l).
Subsequently, studies were conducted on substrates with a
substituent on the biphenyl skeleton. In substrates with a
substituent at the 4′ position, the yield of the target substance
was not significantly affected by the electronic and steric
actions of the substituents (2m–2q). Conversely, substrates
with substituents at the 4-position afforded the corresponding
phenanthridinones in good yields (2r, 2s).
R2
R2
1-Cl-AQN (0.01 equiv.)
K2CO3 (0.1 equiv.)
R1
R1
CHCl3 (2 mL)
rt, 20 h
NHR
NR
visible light
O
O
1b-s (0.15 mmol)
2b-s
N
N
N
N
Table 1. Optimization of the Reaction Conditions[a,b]
O
O
O
O
2e: 89%[c]
OMe
Me
Br
F
Cl
2b: 92%[c]
2c: 94%[c]
2d: 92%[c]
Br
N
N
N
N
O
O
O
O
Br
CF3
entry
1
photocatalyst
2-tBu-AQN
2-tBu-AQN
2-tBu-AQN
2-tBu-AQN
AQN
base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
-
solvent
DMF
yield (%)
35
2f: 88%[c]
2g: 93%
2h: 71%
2i: 86%
OMe
2
MeCN
MeOH
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
71
N
N
N
N
S
3
63
Me
tBu
O
N
O
O
O
4
91
2j: 84%
2k: 0%
2l: 0%
2m: 99%
5
85
tBu
Ph
Cl
CF3
6
1-Cl-AQN
1-Cl-AQN
1-Cl-AQN
1-Cl-AQN
1-Cl-AQN
1-Cl-AQN
94
7[c]
8[c]
9[c]
10[c]
11[c,d]
97
N
N
O
N
O
N
54
O
O
NaOAc
Et3N
92
2n: >99%
2o: 90%[d]
2p: 89%[c]
2q: 69%[c]
58
K2CO3
(96)
N
N
Ph
Br
O
O
[a] Reaction conditions: A solution of 1a (0.15 mmol), photocatalyst (0.1
equiv.), and base (0.5 equiv.) in solvent (2 mL) was irradiated with
fluorescent lamp (23 W × 4) under air atmosphere and stirred for 20 h. [b]
Yield was determined by 1H NMR analysis of the crude reaction mixture.
The number in parentheses is the isolated.
2r: 83%
2s: 72%
[a] Reaction conditions: A solution of 1 (0.15 mmol), 1-Cl-AQN (0.01 equiv), and
K2CO3 (0.1 equiv) in CHCl3 (2 mL) was irradiated with fluorescent lamp (23 W ×
4) under air atmosphere and stirred for 20 h. [b] Yields refer to the isolated yield.
[c] K2CO3 (0.3 equiv). [d] K2CO3 (0.5 equiv).
Having optimized the reaction conditions, we studied the
scope and limitations of the reaction (Scheme 2). We initially
performed experiments using substrates with different
substituents on the nitrogen atom of the carboxamide. Those
possessing an electron-rich aryl group provided excellent
Scheme 2. Synthesis of Various Phenanthridinones[a,b]
When using a photocatalyst with a high oxidation potential,
multiple routes are conceivable as potential reaction mechanisms.
To further investigate the primary reaction mechanism, several
control experiments were performed. When this reaction was
yields (2b, 2c). Phenanthridinones with halogen substituents
were produced in good yields (2d–2h). These products
enabled further functionalization at these positions.
Surprisingly, changes in bulkiness according to the
substitution position did not significantly influence the yield
conducted with
a
radical scavenger, such as 2,2,6,6-
tetramethylpiperidine 1-oxyl (TEMPO), it did not proceed (Table 2,
entry 1). This indicates that the reaction proceeds via a radical
pathway. Moreover, we confirmed the role of the photocatalyst.
When no 1-Cl–AQN was used in this cyclization, a large quantity
of starting material remained unreacted (Table 2, entry 2).
Furthermore, the desired phenanthridinone product was not
(
2g
substituted trifluoromethylphenyl group afforded 86% yield
2i). This reaction can also be applied to a substrate with a
, 2h). Moreover, a substituent with a carboxamide-
(
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10.1002/ejoc.201900536
European Journal of Organic Chemistry
FULL PAPER
detected in the dark (Table 2, entry 3). Based on these results, it
was suggested that the visible-light-excited photocatalyst was
involved in forming reactive species. Besides nitrogen atoms,
aromatic rings of biphenyl are also potential sites for oxidation by
the photocatalyst. In 2015, Nicewicz reported arene C–H
amination using an acridinium salt as an organophotoredox
catalyst, which proceeded via single-electron oxidation of the
arene.[13,14] This reaction did not proceed with a substrate
possessing an alkyl group on the nitrogen atom, indicating that
the pathway of nucleophilic addition following single-electron
oxidation to arenes did not progress (Scheme 5, path b).
were confirmed (Table 2, entry 4), indicating that oxygen was
involved in the reaction. However, since no new oxygen atoms
were present in the product structure, it was believed that the
oxygen promoted rearomatization in this reaction and was
converted to hydrogen peroxide. Thus, we conducted iodometry
to detect peroxide generated by the reaction (Scheme 4 (A)). As
the result, approximately one equivalent of peroxide was detected.
Furthermore, we confirmed that the peroxide was not related to
the N–H bond activation (Scheme 4 (B)).
Table 2. Control Experiments[a]
entry
altered reaction conditions
added TEMPO (1.0 equiv)
1-Cl-AQN (0 equiv)
yield (%)[a]
1
2
3
4
0
0
0
5
[a] Yield was determined by iodometry (A) or 1H NMR analysis (B) of the
crude reaction mixture.
under dark
under argon atmosphere
Scheme 4. Study of Involvement of the Peroxide[a]
[a] Yield was determined by 1H NMR analysis of the crude reaction mixture.
Based on the above results, we proposed a plausible
pathway (Scheme 5). The AQN photocatalyst is initially
excited by visible light irradiation. The excited photocatalyst
We also performed
a
time-course experiment with
intermittent light intervals (Scheme 3). This indicated that the
reaction rate did not change and that the product was only
generated during light irradiation with a fluorescent lamp.
Thus, it was suggested that the generated phenanthridinone
or photoexcited substance did not affect the progress of the
reaction.
promotes
biphenylcarboxamide
corresponding amidyl radical (
resultant amidyl radical ( ) yields the radical intermediate (
via intramolecular radical cyclization. Subsequently, the
radical intermediate ( ) captures oxygen, inducing single-
electron transfer with the AQN anion radical, whereby the
corresponding phenanthridinone 2a is formed, and
homolytic
N–H
1a with base to afford the
) via a PCET event. The
bond
activation
of
(
)
A
A
B)
B
(
)
simultaneously, the hydroperoxide anion is generated.
Scheme 5. Plausible Reaction Mechanism
1
[a] Yield was determined by H NMR analysis of the crude reaction
mixture.
Conclusions
Scheme 3. Time-Course Experiment[a]
In conclusion, we have reported a transition-metal-free
phenanthridinone synthesis using an organophotocatalyst.
This is the first method of phenanthridinone synthesis that
When this reaction was performed under an argon atmosphere,
significant decreases in the yield and unreacted starting materials
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10.1002/ejoc.201900536
European Journal of Organic Chemistry
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progresses direct C–H amidation without using a transition
metal under visible light irradiation, and the reaction
proceeds under mild conditions at low cost. Moreover, this
has expanded the applicability of the substrates to a greater
extent than previous photooxidative methods.
crushed ice was poured into the reaction mixture to precipitate the
solid. The precipitated solid was filtered and washed with cold water.
The solid was dissolved in EtOAc and the organic layer was washed
with water and brine, dried with Na2SO4. The organic layer was
filtered and concentrated in vacuo. The solid residue was used in the
next step without any purification. To the solid residue in DMF (25
mL) at room temperature was added K2CO3 (4.15 g, 30.0 mmol 1.2
equiv). After gas evolution ceased, CH3I (1.71 mL, 27.5 mmol, 1.1
equiv) was added dropwise and the reaction mixture was stirred at
room temperature overnight. H2O was added to the reaction mixture
and the aqueous phase was extracted with Et2O. The organic layers
were combined, washed with H2O, brine, and dried with MgSO4. The
organic layer was filtered and concentrated in vacuo. The residue
was purified by column chromatography to afford methyl 5-bromo-2-
iodobenzoate (79%, 6.7 g, 2 steps).
Experimental Section
General Information
Unless otherwise noted, all reactants or reagents including dry
solvents were obtained from commercial suppliers and used as
received. Flash column chromatography was performed with Kanto
silica gel 60N (Spherical, Neutral, 40–50 mm). Analytical thin-layer
chromatography (TLC) was carried out using 0.25 mm commercial
silica gel plates (Merck silica gel 60 F254). The developed
Methyl 5-bromo-2-iodobenzoate (3r): The product was afforded as
a colorless oil. Rf = 0.34 (7% EtOAc in n-Hexane) 1H NMR (500 MHz,
CDCl3) δ 7.92 (d, J = 2.3 Hz, 1 H), 7.89-7.77 (m, 1 H), 7.27-7.23 (m,
1 H), 3.90 (s, 3 H) 13C{1H} NMR (125 MHz, CDCl3) δ 165.5, 142.7,
136.5, 135.8, 134.0, 122.3, 92.4, 52.9. Data in accordance with the
literature.[15]
chromatogram was analyzed by UV lamp (254 nm). 1H NMR and 13
C
1
NMR spectra were obtained on a JEOL ECA 500 (500 MHz for H
NMR, 125 MHz for 13C NMR and 470 MHz for 19F NMR). Chemical
shifts (δ) are expressed in parts per million and are internally
referenced [0.00 ppm (tetramethylsilane) for 1H NMR and 77.0 ppm
(CDCl3) for 13C NMR. Infrared spectra were taken on a Perkin Elmer
Spectrum 100 FTIR and are reported in reciprocal centimeters (cm-
1). High-resolution mass spectra (HRMS) were obtained on a JEOL
JMS-T100TD and JEOL JMS-T100GC and are reported as m/z
(relative intensity). Melting points were measured on a Yanaco Micro
Melting Point Apparatus and are uncorrected.
General procedure for the Suzuki-Miyaura cross-coupling
A flask was refilled with argon. The boronic acids (1.1 equiv),
palladium acetate (0.01 equiv) and sodium carbonate (3.5 equiv)
were added. Then the solution of methyl 2-iodobenzoate (2.0 mmol)
in MeCN (4.8 mL) and H2O (2.4 mL) was added in the flask. The
reaction mixture was warmed up to 60 ºC (oil bath) and stirred
overnight. After the reaction was completed, the reaction mixture was
cooled dawn to room temperature. Then the mixture was
concentrated in vacuo until MeCN was removed. The residue was
diluted with CH2Cl2 and H2O and extracted with CH2Cl2. The
combined organic layers were washed with H2O, dried over MgSO4,
filtered and concentrated in vacuo. Purification of the crude product
by column chromatography on silica gel provided methyl biphenyl-2-
carboxylates.
Substrate Preparation
General procedure for the synthesis of methyl 2-iodobenzoate
To the solution of 2-iodobenzoic acid (6.2 g, 25.0 mmol, 1.0 equiv) in
DMF (1 M) was added K2CO3 (4.15 g, 30.0 mmol, 1.2 equiv). After
gas evolution ceased, methyl iodide (1.71 mL, 27.5 mmol, 1.1 equiv)
was added dropwise and the reaction mixture was stirred at room
temperature overnight. H2O was added to the reaction mixture and
the aqueous phase was extracted with Et2O. The combined organic
layers were washed with H2O, brine, dried over MgSO4, filtered and
concentrated in vacuo. Without any purification to afford methyl 2-
iodobenzoate (90%, 5.9 g).
Methyl 4’-methoxy-[1,1’-biphenyl]-2-carboxylate (4m): Methyl 2-
iodobenzoate (299.5 µL, 2.0 mmol) gave Methyl 4’-methoxy-[1,1’-
biphenyl]-2-carboxylate (quant., 507.9 mg) as a pale yellow oil. Rf =
0.10 (5% EtOAc in n-Hexane) 1H NMR (500 MHz, CDCl3) δ 7.78 (d,
J = 7.5 Hz, 1 H), 7.50 (td, J = 1.1, 7.5 Hz, 1 H), 7.37 (t, J = 8.0 Hz, 2
H), 7.25 (d, J = 8.6 Hz, 2 H), 6.93 (d, J = 8.6 Hz, 2 H), 3.84 (s, 3 H),
3.66 (s, 3 H) 13C{1H} NMR (125 MHz, CDCl3) δ 169.5, 159.1, 142.1,
133.7, 131.3, 130.9, 130.8, 129.8, 129.5, 126.9, 113.6, 55.3, 52.1.
Data in accordance with the literature.[2]
Methyl 2-iodobenzoate (3m): The product was afforded as a pale
yellow oil. Rf = 0.56 (9% EtOAc in n-Hexane) 1H NMR (500 MHz,
CDCl3) δ 7.95 (d, J = 7.4 Hz, 1 H), 7.76 (d, J = 7.4 Hz, 1 H), 7.37-
7.34 (m, 1 H), 7.12-7.09 (m, 1 H), 3.89 (s, 3 H) 13C{1H} NMR (125
MHz, CDCl3) δ 167.0, 141.4, 135.1, 132.8, 131.0, 128.0, 94.2, 52.6.
Data in accordance with the literature.[15]
Methyl 4’-(tert butyl)-[1,1’-biphenyl]-2-carboxylate (4n): Methyl 2-
iodobenzoate (299.5 µL, 2.0 mmol) gave Methyl 4’-(tert butyl)-[1,1’-
biphenyl]-2-carboxylate (90%, 482.7 mg) as a white solid. Rf = 0.24
General procedure for the synthesis of methyl 2-iodobenzoate
2-iodobenzoic acid (6.2 g, 25.0 mmol, 1.0 equiv) was taken up in
concentrated H2SO4 (50 mL), and heated to 60 °C (oil bath). The
solid NBS (5.34 g, 30.0 mmol, 1.2 equiv) was added a small amount
to the reaction mixture during 15 minutes and stirred for 2 hours. The
reaction was monitored by TLC. After the reaction was completed, a
1
(5% EtOAc in n-Hexane) H NMR (500 MHz, CDCl3) δ 7.81 (d, J =
8.6 Hz, 1 H), 7.52 (td, J = 1.1, 8.0 Hz, 1 H), 7.44-7.37 (m, 4 H), 7.37-
7.25 (m, 2 H), 3.65 (s, 3 H), 1.37 (s, 9 H) 13C{1H} NMR (125 MHz,
CDCl3) δ 169.5, 150.2, 142.4, 138.3, 131.3, 131.0, 130.9, 129.8,
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10.1002/ejoc.201900536
European Journal of Organic Chemistry
FULL PAPER
128.1, 127.0, 125.1, 52.0, 34.7, 31.5. Data in accordance with the
literature.[16]
4’-(tert Butyl)-[1,1’-biphenyl]-2-carboxylic acid (5n): Methyl 4’-
(tert butyl)-[1,1’-biphenyl]-2-carboxylate (456.2 mg, 1.7 mmol) gave
4’-(tert butyl)-[1,1’-biphenyl]-2-carboxylic acid (85%, 366.8 mg) as a
white solid. Rf = 0.56 (10% MeOH in CHCl3). 1H NMR (500 MHz,
CDCl3) δ 7.96 (dd, J = 1.1, 8.0 Hz, 1 H), 7.56 (td, J = 1.7, 6.3 Hz, 1
H), 7.44-7.38 (m, 4 H), 7.31-7.29 (m, 2 H), 1.38 (s, 9 H). 13C{1H} NMR
(125 MHz, CDCl3) δ 174.1, 150.3, 143.3, 138.0, 132.2, 131.5, 130.8,
129.4, 128.3, 127.1, 125.2, 34.7, 31.5. Data in accordance with the
literature.[16]
Methyl 4’-phenyl-[1,1’-biphenyl]-2-carboxylate (4o): Methyl 2-
iodobenzoate (299.5 µL, 2.0 mmol) gave Methyl 4’-phenyl-[1,1’-
biphenyl]-2-carboxylate (91%, 524.2 mg) as a white solid. m.p. = 106-
107 ºC. Rf = 0.15 (5% EtOAc in n-Hexane) 1H NMR (500 MHz, CDCl3)
δ 7.85 (dd, J = 1.2, 8.0 Hz, 1 H), 7.67-7.64 (m, 4 H), 7.55 (td, J = 1.2,
7.4 Hz, 1 H), 7.48-7.38 (m, 6 H), 7.37 (t, J = 7.4 Hz, 1 H), 3.68 (s, 3
H) 13C{1H} NMR (125 MHz, CDCl3) δ 169.3, 142.2, 140.8, 140.4,
140.1, 131.4, 130.9, 130.9, 130.0, 128.9, 127.5, 127.3, 127.2, 126.9,
52.1. IR (ATR) 3032, 1724, 1572, 1086 cm-1. HRMS (DART) Found
289.1232, Calcd. for C20H17O2, [M + H]+ 289.1229.
4’-Phenyl-[1,1’-biphenyl]-2-carboxylic acid (5o): Methyl 4’-phenyl-
[1,1’-biphenyl]-2-carboxylate (490.2 mg, 1.7 mmol) gave 4’-phenyl-
[1,1’-biphenyl]-2-carboxylic acid (86%, 402.6 mg) as a white solid. Rf
= 0.49 (10% MeOH in CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.97 (d,
J = 8.0 Hz, 1 H), 7.64-7.62 (m, 4 H), 7.58 (td, J = 1.7, 8.0 Hz, 1 H),
7.46-7.41 (m, 6 H), 7.35 (t, J = 7.5 Hz, 1 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 172.8, 143.1, 140.8, 140.3, 140.1, 132.3, 131.3, 130.9,
129.2, 129.0, 128.9, 127.4, 127.4, 127.2, 126.9. Data in accordance
with the literature.[18]
Methyl 4’-chloro-[1,1’-biphenyl]-2-carboxylate (4p): Methyl 2-
iodobenzoate (299.5 µL, 2.0 mmol) gave Methyl 4’-chloro-[1,1’-
biphenyl]-2-carboxylate (79%, 391.5 mg) as a colorless oil. Rf = 0.24
(5% EtOAc in n-Hexane). 1H NMR (500 MHz, CDCl3) δ 7.86 (dd, J =
1.1, 7.4 Hz, 1 H), 7.53 (td, J = 1.1, 7.4 Hz, 1 H), 7.42 (td, J = 1.1, 7.4
Hz, 1 H), 7.37 (d, J = 8.6 Hz, 2 H), 7.35-7.32 (m, 1 H), 7.24 (d, J =
8.6 Hz, 2 H), 3.67 (s, 3 H) 13C{1H} NMR (125 MHz, CDCl3) δ 168.8,
141.5, 139.9, 133.5, 131.6, 130.8, 130.6, 130.2, 129.8, 128.3, 127.6,
52.1. Data in accordance with the literature.[17]
4’-Chloro-[1,1’-biphenyl]-2-carboxylic acid (5p): Methyl 4’-chloro-
[1,1’-biphenyl]-2-carboxylate (370.0 mg, 1.5 mmol) gave 4’-chloro-
[1,1’-biphenyl]-2-carboxylic acid (83%, 290.7 mg) as a white solid. Rf
= 0.50 (10% MeOH in CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.98 (d,
J = 8.1 Hz, 1 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 1 H),
7.36 (d, J = 8.6 Hz, 2 H), 7.32 (d, J = 8.6 Hz, 2 H), 7.26-7.24 (m, 2
H). 13C{1H} NMR (125 MHz, CDCl3) δ 173.1, 142.4, 139.6, 133.6,
132.4, 131.3, 131.1, 129.9, 129.0, 128.3, 127.7. Data in accordance
with the literature.[19]
Methyl 4-phenyl-[1,1’-biphenyl]-2-carboxylate (4r): Methyl 5-
bromo-2-iodobenzoate (681.5 mg, 2.0 mmol) gave Methyl 4-phenyl-
[1,1’-biphenyl]-2-carboxylate (87%, 503.4 mg) as a white solid. Rf =
0.17 (5% EtOAc in n-Hexane). 1H NMR (500 MHz, CDCl3) δ 8.07 (t,
J = 2.3 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.66 (dd, J = 1.7, 8.0 Hz,
2 H), 7.50-7.46 (m, 3 H), 7.43-7.36 (m, 6 H), 3.67 (s, 3 H). 13C{1H}
NMR (125 MHz, CDCl3) δ 169.3, 141.4, 141.0, 140.3, 139.8, 131.4,
131.3, 129.9, 129.0, 128.6, 128.4, 128.2, 127.9, 127.4, 52.1. Data in
accordance with the literature.[16]
4’-Trifluoromethyl-[1,1’-biphenyl]-2-carboxylic acid (5q): Methyl
2-iodobenzoate (299.5 µL, 2.0 mmol) gave 4’-trifluoromethyl-[1,1’-
biphenyl]-2-carboxylic acid (85%, 451.1 mg, 2 steps) as a white solid.
Rf = 0.44 (10% MeOH in CHCl3). 1H NMR (500 MHz, CDCl3) δ 8.03
(dd, J = 1.1, 8.0 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 2 H), 7.60 (td, J = 1.1,
7.5 Hz, 1 H), 7.48 (td, J = 1.1, 6.8 Hz, 1 H), 7.42 (d, J = 8.0 Hz, 2 H),
7.33 (d, J = 6.9 Hz, 1 H). 13C{1H} NMR (125 MHz, CDCl3) δ 173.0,
144.9, 142.4, 132.6, 131.3, 129.9, 129.7, 129.4, 129.2, 128.9, 128.9,
128.7, 128.1, 127.6, 125.4, 125.0, 125.0, 123.3, 121.1. 19F NMR (470
MHz, CDCl3) δ -62.3. Data in accordance with the literature.[16]
General procedure for the saponification of methyl biphenyl-2-
carboxylates
Methyl biphenyl-2-carboxylates was dissolved in MeOH (0.25 M) and
aq. NaOH (1 M, 4.0 equiv) was added. The mixture was warmed up
to 50 °C (oil bath) and stirred overnight. After the reaction was
completed, the reaction mixture was cooled dawn to room
temperature. Then the mixture was concentrated in vacuo until
MeOH was removed. Aq. HCl (2 M) and Et2O were added in the
residue and extracted with Et2O. The combined organic layers were
dried over MgSO4, filtered and concentrated in vacuo to give
biphenyl-2-carboxylic acids.
General procedure for the synthesis of N-arylamides from carbonic
acids
General procedure for the preparation of acyl chlorides from
carbonic acids
A dry flask was refilled with argon. The solution of the carbonic acid
and DMF (1 drop) in CH2Cl2 (1.25 M) was added. Then thionyl
chloride (1.2 equiv) was added in the solution at 0 ºC. The reaction
mixture was stirred for 30 min at 0 ºC and then stirred at room
temperature for 3 h. After the reaction was completed, the solvent
was removed under reduced pressure to give acyl chlorides.
4’-Methoxy-[1,1’-biphenyl]-2-carboxylic acid (5m): Methyl 4’-
methoxy-[1,1’-biphenyl]-2-carboxylate (460.3 mg, 1.9 mmol) gave 4’-
methoxy-[1,1’-biphenyl]-2-carboxylic acid (83%, 358.3 mg) as a white
solid. Rf = 0.49 (10% MeOH in CHCl3). 1H NMR (500 MHz, CDCl3) δ
7.93 (d, J = 7.4 Hz, 1 H), 7.54 (td, J = 1.1, 7.4 Hz, 1 H), 7.39 (t, J =
7.4 Hz, 1 H), 7.36 (d, J = 7.5 Hz, 1 H), 7.27 (d, J = 8.6 Hz, 2 H), 6.93
(d, J = 8.6 Hz, 2 H), 3.84 (s, 3 H). 13C{1H} NMR (125 MHz, CDCl3) δ
174.0, 159.2, 143.0, 133.4, 132.2, 131.3, 130.8, 129.7, 129.4, 126.9,
113.7, 55.4. Data in accordance with the literature.[16]
General procedure for the synthesis of N-arylamides from acyl
chlorides
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900536
European Journal of Organic Chemistry
FULL PAPER
A dry flask was refilled with argon. The solution of the anilines (1.0
equiv) and triethylamine in CH2Cl2 (0.625 M) was added. Then the
acyl chlorides in CH2Cl2 (0.5 M) was added dropwise in the solution
at 0 ºC. The reaction mixture was stirred for 30 min at 0 ºC and then
stirred at room temperature overnight. After the reaction was
completed, aqueous NH4Cl was added to the reaction mixture. The
mixture was extracted with CH2Cl2. The combined organic layers
were washed with brine, dried over Na2SO4, filtered and
concentrated in vacuo. Purification of the crude product by column
chromatography on silica gel provided the N-arylamides.
N-4-Chlorophenyl biphenyl-2-carboxamide (1e): 2-Phenyl-
benzoic acid (396.2 mg, 2.0 mmol) gave N-4-chlorophenyl biphenyl-
2-carboxamide (22%, 136.6 mg) as a pale yellow solid. m.p. = 166-
168 ºC. Rf = 0.43 (20% EtOAc in n-Hexane). 1H NMR (500 MHz,
CDCl3) δ 7.87 (d, J = 7.5 Hz, 1 H), 7.55 (t, J = 7.5 Hz, 1 H), 7.49-7.39
(m, 7 H), 7.17 (d, J = 8.5 Hz, 2 H), 7.03 (d, J = 8.6 Hz, 2 H), 6.89 (brs,
1 H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.2, 140.0, 139.7, 136.2,
135.0, 131.0, 130.5, 129.8, 129.5, 129.1, 128.9, 128.9, 128.3, 128.1,
121.1. IR (ATR) 3273, 3020, 1653, 1536, 1091 cm-1. HRMS (DART)
Found 308.0832, Calcd. for C19H15ClNO, [M + H]+ 308.0842.
N-Phenyl biphenyl-2-carboxamide (1a): 2-Phenyl-benzoic acid
(1.0 g, 5.0 mmol) gave N-phenyl biphenyl-2-carboxamide (81%, 1.1
g) as a white solid. Rf = 0.41 (25% EtOAc in n-Hexane). 1H NMR (500
MHz, CDCl3) δ 7.88 (d, J = 7.4 Hz, 1 H), 7.54 (td, J = 1.1, 7.4 Hz, 1
H), 7.49-7.38 (m, 7 H), 7.22 (t, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.0 Hz,
2 H), 7.05 (t, J = 7.4 Hz, 1 H), 6.94 (brs, 1 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 167.2, 140.0, 139.7, 137.6, 135.4, 130.8, 130.5, 129.7,
129.1, 128.9, 128.2, 128.0, 124.5, 120.0. Data in accordance with the
literature.[20]
N-4-Bromophenyl biphenyl-2-carboxamide (1f): 2-Phenyl-
benzoic acid (396.2 mg, 2.0 mmol) gave N-4-bromophenyl biphenyl-
2-carboxamide (45%, 314.6 mg) as a pale yellow solid. m.p. = 172-
173 ºC. Rf = 0.43 (20% EtOAc in n-Hexane). 1H NMR (500 MHz,
CDCl3) δ 7.87 (d, J = 7.4 Hz, 1 H), 7.55 (t, J = 7.4 Hz, 1 H), 7.49-7.40
(m, 7 H), 7.31 (d, J = 8.6 Hz, 2 H), 6.98 (d, J = 8.6 Hz, 2 H), 6.88 (brs,
1 H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.2, 140.0, 139.7, 136.7,
134.9, 131.9, 131.0, 130.5, 129.8, 129.1, 128.9, 128.3, 128.1, 121.5,
117.1. IR (ATR) 3279, 3105, 1653, 1537, 1072 cm-1. HRMS (DART)
Found 352.0340, Calcd. for C19H15BrNO, [M + H]+ 352.0337.
N-4-Methoxyphenyl biphenyl-2-carboxamide (1b): 2-Phenyl-
benzoic acid (396.4 mg, 2.0 mmol) gave N-4-methoxyphenyl
biphenyl-2-carboxamide (32%, 191.2 mg) as a pale yellow solid. m.p.
= 159-160 ºC. Rf = 0.31 (25% EtOAc in n-Hexane). 1H NMR (500
MHz, CDCl3) δ 7.86 (d, J = 6.8 Hz, 1 H), 7.53 (t, J = 6.8 Hz, 1 H),
7.48-7.40 (m, 7 H), 7.00 (d, J = 8.6 Hz, 2 H), 6.81 (brs, 1 H), 6.75 (d,
J = 8.0 Hz, 2 H), 3.74 (s, 3 H). 13C{1H} NMR (125 MHz, CDCl3) δ
167.2, 156.6, 140.1, 139.6, 135.5, 130.7, 130.4, 129.6, 129.0, 128.9,
128.1, 128.0, 122.0, 114.1, 55.5. IR (ATR) 3213, 3028, 1640, 1509,
1028 cm-1. HRMS (DART) Found 304.1322, Calcd. for C20H18NO2,
[M + H]+ 304.1338.
N-3-Bromophenyl biphenyl-2-carboxamide (1g): 2-Phenyl-
benzoic acid (396.2 mg, 2.0 mmol) gave N-3-bromophenyl biphenyl-
2-carboxamide (81%, 573.0 mg) as a white solid. m.p. = 141-142 ºC.
1
Rf = 0.45 (20% EtOAc in n-Hexane). H NMR (500 MHz, CDCl3) δ
7.84 (t, J = 7.5 Hz, 1 H), 7.54 (t, J = 7.5 Hz, 1 H), 7.49-7.42 (m, 8 H),
7.16 (d, J = 8.0 Hz, 1 H), 7.05 (t, J = 8.0 Hz, 1 H), 6.99 (brs, 1 H),
6.91 (d, J = 8.0 Hz, 1 H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.3,
139.9, 139.7, 138.9, 134.9, 131.0, 130.5, 130.2, 129.7, 129.2, 128.9,
128.3, 128.1, 127.4, 122.9, 122.6, 118.4. IR (ATR) 3216, 3056, 1656,
1596, 1046 cm-1. HRMS (DART) Found 352.0344, Calcd. for
C19H15BrNO, [M + H]+ 352.0337.
N-4-Methylphenyl biphenyl-2-carboxamide (1c): 2-Phenyl-
benzoic acid (396.2 mg, 2.0 mmol) gave N-4-methylphenyl biphenyl-
2-carboxamide (45%, 260.2 mg) as a white solid. m.p. = 146-148 ºC.
N-2-Bromophenyl biphenyl-2-carboxamide (1h): 2-Phenyl-
benzoic acid (396.2 mg, 2.0 mmol) gave N-2-bromophenyl biphenyl-
2-carboxamide (33%, 229.7 mg) as a white solid. m.p. = 88-89 ºC. Rf
= 0.58 (20% EtOAc in n-Hexane). 1H NMR (500 MHz, CDCl3) δ 8.46
(d, J = 8.0 Hz, 1 H), 7.84 (d, J = 7.5 Hz, 1 H), 7.55 (dd, J = 1.2, 7.5
Hz, 2 H), 7.50-7.45 (m, 4 H), 7.40-7.36 (m, 3 H), 7.35-7.33 (m, 1 H),
7.29 (t, J = 8.0 Hz, 1 H), 6.91 (td, J = 1.1, 8.0 Hz, 1 H). 13C{1H} NMR
(125 MHz, CDCl3) δ 167.8, 139.8, 139.7, 135.8, 135.6, 132.3, 131.0,
130.8, 129.5, 129.1, 129.0, 128.7, 128.3, 127.9, 125.1, 121.5, 113.0.
IR (ATR) 3209, 3026, 1656, 1522, 1028 cm-1. HRMS (DART) Found
352.0348, Calcd. for C19H15BrNO, [M + H]+ 352.0337.
1
Rf = 0.36 (25% EtOAc in n-Hexane). H NMR (500 MHz, CDCl3) δ
7.88 (d, J = 7.5 Hz, 1 H), 7.55-7.52 (m, 1 H), 7.49-7.39 (m, 7 H), 7.02
(d, J = 8.6 Hz, 2 H), 6.98 (d, J = 8.6 Hz, 2 H), 6.83 (brs, 1 H), 2.26 (s,
3 H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.1, 140.1, 139.6, 135.0,
134.2, 130.7, 130.4, 129.7, 129.4, 129.0, 128.9, 128.2, 128.0, 120.1,
21.0. IR (ATR) 3233, 3054, 1600, 1511 cm-1. HRMS (DART) Found
288.1382, Calcd. for C20H18NO, [M + H]+ 288.1388.
N-4-Fluorophenyl biphenyl-2-carboxamide (1d): 2-Phenyl-
benzoic acid (396.2 mg, 2.0 mmol) gave N-4-fluorophenyl biphenyl-
2-carboxamide (46%, 266.8 mg) as a white solid. m.p. = 145-147 ºC.
N-4-Trifluoromethylphenyl biphenyl-2-carboxamide (1i): 2-
Phenyl-benzoic acid (396.2 mg, 2.0 mmol) gave N-4-
trifluoromethylphenyl biphenyl-2-carboxamide (61%, 413.1 mg) as a
white solid. m.p. = 138-140 ºC. Rf = 0.29 (CHCl3). 1H NMR (500 MHz,
CDCl3) δ 7.81 (d, J = 7.4 Hz, 1 H), 7.55 (t, J = 8.0 Hz, 1 H), 7.47-7.40
(m, 9 H), 7.26 (d, J = 7.5 Hz, 1 H), 7.21 (d, J = 8.0 Hz, 2 H). 13C{1H}
NMR (125 MHz, CDCl3) δ 167.5, 140.7, 140.1, 139.9, 139.8, 134.7,
131.7, 131.2, 130.5, 129.7, 129.1, 128.9, 128.5, 128.4, 128.2, 128.1,
127.4, 126.3, 126.2, 126.2, 126.1, 126.0, 125.2, 123.1, 119.9, 119.5.
19F NMR (470 MHz, CDCl3) δ -62.0. IR (ATR) 3250, 3065, 1666, 1543,
1
Rf = 0.32 (20% EtOAc in n-Hexane). H NMR (500 MHz, CDCl3) δ
7.87 (d, J = 7.5 Hz, 1 H), 7.54 (td, J = 1.1, 7.5 Hz, 1 H), 7.49-7.39 (m,
7 H), 7.05-7.02 (m, 2 H), 6.90 (t, J = 8.6 Hz, 2 H), 6.85 (brs, 1 H).
13C{1H} NMR (125 MHz, CDCl3) δ 167.2, 160.5, 158.6, 140.1, 139.6,
135.1, 133.6, 130.9, 130.4, 129.7, 129.1, 128.9, 128.2, 128.0, 121.9,
121.8, 115.7, 115.5. 19F NMR (470 MHz, CDCl3) δ -117.7. IR (ATR)
3249, 3059, 1652, 1504, 1206 cm-1. HRMS (DART) Found 292.1136,
Calcd. for C19H15FNO, [M + H]+ 292.1138.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900536
European Journal of Organic Chemistry
FULL PAPER
1320 cm-1. HRMS (DART) Found 342.1117, Calcd. for C20H15F3NO,
[M + H]+ 342.1106.
1526 cm-1. HRMS (DART) Found 330.1873, Calcd. for C23H24NO, [M
+ H]+ 330.1858.
N-2-benzothiazolyl biphenyl-2-carboxamide (1j): 2-Phenyl-
benzoic acid (396.2 mg, 2.0 mmol) gave N-2-benzothiazolyl
biphenyl-2-carboxamide (40%, 266 mg) as a pale brown solid. m.p.
N-Phenyl 4’-phenyl-biphenyl-2-carboxamide (1o): 4’-Phenyl-[1,1’-
biphenyl]-2-carboxylic acid (384.1 mg, 1.4 mmol) gave N-phenyl 4’-
phenyl-biphenyl-2-carboxamide (36%, 177.6 mg) as a white solid.
1
1
= 207-209 ºC. Rf = 0.28 (20% EtOAc in n-Hexane). H NMR (500
m.p. = 236-238 ºC. Rf = 0.34 (20% EtOAc in n-Hexane). H NMR
MHz, CDCl3) δ 7.76 (d, J = 8.0 Hz, 1 H), 7.46 (d, J = 7.4 Hz, 1 H),
7.39 (td, J = 1.5, 7.4 Hz, 1 H), 7.34-7.15 (m, 8 H), 7.01 (t, J = 7.4 Hz,
1 H), 6.53 (brs, 1 H). 13C{1H} NMR (125 MHz, CDCl3) δ 168.4, 160.1,
147.3, 141.0, 139.6, 133.4, 131.5, 131.3, 130.8, 129.1, 128.7, 128.6,
127.9, 127.5, 126.1, 123.8, 121.2, 119.7. IR (ATR) 3123, 3058, 1683,
1599, 1544 cm-1. HRMS (DART) Found 331.0902, Calcd. for
C20H15N2OS, [M + H]+ 331.0905.
(500 MHz, CDCl3) δ 7.90 (d, J = 8.0 Hz, 1 H), 7.67 (d, J = 8.0 Hz, 2
H), 7.60 (dd, J = 1.2, 7.4 Hz, 2 H), 7.56 (d, J = 8.1 Hz, 3 H), 7.51-7.45
(m, 4 H), 7.39-7.36 (m, 1 H), 7.21 (t, J = 7.5 Hz, 2 H), 7.12 (d, J = 8.0
Hz, 2 H), 7.04 (t, J = 7.4 Hz, 1 H), 6.93 (brs, 1 H). 13C{1H} NMR (125
MHz, CDCl3) δ 167.3, 141.1, 140.5, 139.2, 138.9, 137.6, 135.5, 130.9,
130.4, 129.7, 129.4, 129.0, 128.1, 127.8, 127.7, 127.2, 124.6, 120.0.
IR (ATR) 3294, 3024, 1659, 1543 cm-1. HRMS (DART) Found
350.1559, Calcd. for C25H20NO, [M + H]+ 350.1545.
N-Methyl biphenyl-2-carboxamide (1k): 2-Phenyl-benzoic acid
(500 mg, 2.5 mmol) gave N-methyl biphenyl-2-carboxamide (63%,
331.4 mg) as a white solid. Rf = 0.38 (67% EtOAc in n-Hexane). 1H
NMR (500 MHz, CDCl3) δ 7.67 (d, J = 7.4 Hz, 1 H), 7.47 (td, J = 1.1,
7.4 Hz, 1 H), 7.41-7.31 (m, 7 H), 5.23 (brs, 1 H), 2.66 (d, J = 5.1 Hz,
3 H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.4, 140.2, 139.4, 135.7,
130.2, 128.9, 128.7, 128.7, 128.6, 127.9, 127.7, 26.8. Data in
accordance with the literature.[20]
N-Phenyl 4’-chloro-biphenyl-2-carboxamide (1p): 4’-Chloro-[1,1’-
biphenyl]-2-carboxylic acid (279.2 mg, 1.2 mmol) gave N-phenyl 4’-
chloro-biphenyl-2-carboxamide (20%, 75.2 mg) as a white solid. m.p.
1
= 199-201 ºC. Rf = 0.26 (20% EtOAc in n-Hexane). H NMR (500
MHz, CDCl3) δ 7.80 (d, J = 8.0 Hz, 1 H), 7.53 (td, J = 1.2, 7.5 Hz, 1
H), 7.48 (t, J = 7.5 Hz, 1 H), 7.43-7.38 (m, 5 H), 7.29-7.25 (m, 1 H),
7.21 (d, J = 7.4 Hz, 2 H), 7.09 (t, J = 7.4 Hz, 1 H), 6.94 (brs, 1 H).
13C{1H} NMR (125 MHz, CDCl3) δ 167.3, 138.4, 137.5, 135.7, 134.3,
130.8, 130.4, 130.1, 129.3, 129.2, 129.1, 128.3, 124.8, 120.0. IR
(ATR) 3225, 3026, 1649, 1592, 1087 cm-1. HRMS (DART) Found
308.0835, Calcd. for C19H15ClNO, [M + H]+ 308.0842.
N-tert Butyl biphenyl-2-carboxamide (1l): 2-Phenyl-benzoic acid
(396.2 mg, 2.0 mmol) gave N-tert butyl biphenyl-2-carboxamide
(53%, 270.2 mg) as a white solid. 1H NMR (500 MHz, CDCl3) δ 7.72
(dd, J = 1.2, 7.5 Hz, 1 H), 7.46-7.37 (m, 7 H), 7.33 (dd, J = 1.2, 7.5
Hz, 1 H), 4.98 (brs, 1 H), 1.10 (s, 9 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 168.4, 140.6, 139.4, 136.9, 130.1, 129.9, 129.1, 129.0,
128.7, 127.8, 127.7, 51.4, 28.3. Data in accordance with the
literature.[20]
N-Phenyl 4’-trifluoromethyl-biphenyl-2-carboxamide (1q): 4’-
trifluromethyl-[1,1’-biphenyl]-2-carboxylic acid (452.6 mg, 1.7 mmol)
gave N-phenyl 4’-trifluoromethyl-biphenyl-2-carboxamide (58%,
337.7 mg) as a white solid. m.p. = 198-200 ºC. Rf = 0.29 (20% EtOAc
in n-Hexane). 1H NMR (500 MHz, CDCl3) δ 7.79 (d, J = 7.4 Hz, 1 H),
7.67 (d, J = 8.6 Hz, 2 H), 7.60-7.56 (m, 3 H), 7.51 (td, J = 1.1, 7.4 Hz,
1 H), 7.43 (d, J = 8.1 Hz, 1 H), 7.27-7.24 (m, 2 H), 7.18 (d, J = 8.1 Hz,
2 H), 7.09 (t, J = 7.4 Hz, 1 H), 6.97 (brs, 1 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 167.1, 143.7, 140.2, 138.4, 137.4, 135.9, 131.6, 130.9,
130.4, 130.3, 129.3, 129.2, 129.1, 128.6, 128.5, 125.9, 125.8, 125.0,
124.9, 120.2, 120.0. 19F NMR (470 MHz, CDCl3) δ -62.5. IR (ATR)
3229, 3063, 1648, 1548, 1323 cm-1. HRMS (DART) Found 342.1103,
Calcd. for C20H15F3NO, [M + H]+ 342.1106.
N-Phenyl 4’-methoxy-biphenyl-2-carboxamide (1m): 4’-Methoxy-
[1,1’-biphenyl]-2-carboxylic acid (342.4 mg, 2.0 mmol) gave N-phenyl
4’-methoxy-biphenyl-2-carboxamide (92%, 416.4 mg) as a white
1
solid. m.p. = 130-132 ºC. Rf = 0.30 (20% EtOAc in n-Hexane). H
NMR (500 MHz, CDCl3) δ 7.86 (d, J = 7.4 Hz, 1 H), 7.52 (td, J = 1.2,
7.5 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 1 H), 7.42-7.39 (m, 3 H), 7.24 (t, J =
7.4 Hz, 2 H), 7.16 (d, J = 7.5 Hz, 2 H), 7.06 (t, J = 7.4 Hz, 1 H), 6.96
(d, J = 8.6 Hz, 3 H), 3.82 (s, 3 H). 13C{1H} NMR (125 MHz, CDCl3) δ
159.7, 139.2, 137.7, 135.2, 132.2, 130.8, 130.5, 130.2, 129.7, 129.0,
127.6, 124.5, 120.0, 114.5, 55.5. IR (ATR) 3238, 3003, 1653, 1531,
1178 cm-1. HRMS (DART) Found 304.1333, Calcd. for C20H18NO2,
[M + H]+ 304.1338.
N-Phenyl 4-phenyl-biphenyl-2-carboxamide (1r): 4-Phenyl-[1,1’-
biphenyl]-2-carboxylic acid (384.4 mg, 1.1 mmol) gave N-phenyl 4-
phenyl-biphenyl-2-carboxamide (17%, 65.3 mg) as a white solid. m.p.
1
= 183-185 ºC. Rf = 0.50 (20% EtOAc in n-Hexane). H NMR (500
N-Phenyl 4’-tert butyl-biphenyl-2-carboxamide (1n): 4’-tert Butyl-
[1,1’-biphenyl]-2-carboxylic acid (330.6 mg, 1.3 mmol) gave N-phenyl
4’-tert butyl-biphenyl-2-carboxamide (80%, 342.7 mg) as a white
MHz, CDCl3) δ 8.12 (d, J = 1.7 Hz, 1 H), 7.77 (dd, J = 1.7, 8.0 Hz, 1
H), 7.68 (d, J = 7.5 Hz, 2 H), 7.52-7.38 (m, 9 H), 7.24 (t, J = 7.5 Hz,
2 H), 7.14 (d, J = 7.5 Hz, 2 H), 7.06 (t, J = 7.5 Hz, 1 H), 7.00 (brs, 1
H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.2, 140.9, 139.7, 139.7,
138.4, 137.6, 135.8, 131.0, 129.3, 129.1, 129.1, 129.0, 128.3, 128.0,
127.2, 124.6, 120.1. IR (ATR) 3186, 3028, 1644, 1544 cm-1. HRMS
(DART) Found 350.1545, Calcd. for C25H20NO, [M + H]+ 350.1545.
1
solid. m.p. = 136-138 ºC. Rf = 0.32 (20% EtOAc in n-Hexane). H
NMR (500 MHz, CDCl3) δ 7.89 (d, J = 7.5 Hz, 1 H), 7.53 (td, J = 1.1,
7.5 Hz, 1 H), 7.48-7.39 (m, 6 H), 7.20 (t, J = 8.0 Hz, 2 H), 7.04 (t, J =
8.0 Hz, 4 H), 1.37 (s, 9 H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.2,
151.3, 139.7, 137.8, 137.2, 135.3, 130.8, 130.3, 129.9, 128.8, 128.8,
127.9, 126.1, 124.4, 120.2, 34.8, 31.4. IR (ATR) 3241, 3029, 1656,
N-Phenyl 4-bromo-biphenyl-2-carboxamide (1s): 4-bromo-[1,1’-
biphenyl]-2-carboxylic acid (332.5 mg, 1.2 mmol) gave N-phenyl 4-
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10.1002/ejoc.201900536
European Journal of Organic Chemistry
FULL PAPER
bromo-biphenyl-2-carboxamide (18%, 78.1 mg) as a white solid. m.p.
pale yellow solid. Rf = 0.24 (16% EtOAc in n-Hexane). 1H NMR (500
MHz, CDCl3) δ 8.57 (d, J = 8.0 Hz, 1 H), 8.33 (d, J = 8.6 Hz, 1 H),
8.30 (dd, J = 1.8, 8.6 Hz, 1 H), 7.80 (t, J = 7.5 Hz, 1 H), 7.61 (t, J =
7.5 Hz, 1 H), 7.41 (d, J = 8.0 Hz, 2 H), 7.29 (td, J = 1.7, 8.0 Hz, 2 H),
7.21 (d, J = 8.0 Hz, 2 H), 6.74 (d, J = 8.5 Hz, 1 H), 2.48 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3) δ 161.9, 139.4, 138.8, 135.7, 134.1,
1
= 131-133 ºC. Rf = 0.53 (20% EtOAc in n-Hexane). H NMR (500
MHz, CDCl3) δ 7.98 (d, J = 1.2 Hz, 1 H), 7.64 (dd, J = 1.2, 8.1 Hz, 1
H), 7.43-7.41 (m, 4 H), 7.28 (d, J = 8.0 Hz, 1 H), 7.22 (t, J = 8.0 Hz,
3 H), 7.09-7.05 (m, 3 H), 7.00 (brs, 1 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 165.7, 138.9, 138.5, 137.3, 136.9, 133.8, 132.5, 132.0,
129.2, 129.0, 128.8, 128.6, 124.8, 122.1, 120.2. IR (ATR) 3292, 3060, 132.9, 131.0, 129.2, 128.8, 128.2, 126.0, 123.1, 122.7, 121.9, 119.1,
1652, 1522, 1078 cm-1. HRMS (DART) Found 352.0328, Calcd. for
C19H15BrNO, [M + H]+ 352.0337.
117.2, 21.4. Data in accordance with the literature.[9]
5-(4-Fluorophenyl)phenanthridin-6(5H)-one
(2d):
N-(4-
Intramolecular C–H amidation of N-aryl biphenyl-2-carboxamide
Fluorophenyl) biphenyl-2-carboxamide (43.7 mg, 0.15 mmol) gave 5-
(4-fluorophenyl)phenanthridin-6(5H)-one (92%, 40.0 mg) as a white
solid. Rf = 0.33 (20% EtOAc in n-Hexane). 1H NMR (500 MHz, CDCl3)
δ 8.55 (dd, J = 1.2, 8.0 Hz, 1 H), 8.34 (d, J = 8.0 Hz, 1 H), 8.31 (dd,
J = 1.7, 7.4 Hz, 1 H), 7.82 (td, J = 1.2, 8.0 Hz, 1 H), 7.62 (t, J = 7.4
Hz, 1 H), 7.34-7.28 (m, 6 H), 6.69 (dd, J = 1.7, 7.4 Hz, 1 H). 13C{1H}
NMR (125 MHz, CDCl3) δ 163.6, 161.9, 161.6, 139.2, 134.2, 134.1,
133.1, 131.0, 129.3, 129.1, 128.3, 125.8, 123.2, 122.9, 121.9, 119.2,
117.4, 117.3, 116.9. 19F NMR (470 MHz, CDCl3) δ -112.5. Data in
accordance with the literature.[9]
A solution of N-aryl biphenyl-2-carboxamide (0.15 mmol), 1-Cl-AQN
(0.4 mg, 0.0015 mmol) and K2CO3 (2.1 mg, 0.015 mmol) in CHCl3 (2
mL) was irradiated with fluorescent lamp (23W x 4) at approximately
6 cm away from the light source and stirred for 20 h. The reaction
mixture was concentrated in vacuo. Purification of the crude product
by flash chromatography on silica gel provided desired product.
1 mmol scale procedure
The reaction was conducted in round-bottom-flask (30 ml). A solution
of N-3-bromophenyl biphenyl-2-carboxamide (1g) (352.2 mg, 1
mmol), 1-Cl-AQN (2.4 mg, 0.01 mmol) and K2CO3 (41.5 mg, 0.3
mmol) in CHCl3 (13 mL) was irradiated with fluorescent lamp (23W x
4) at approximately 6 cm away from the light source and stirred for
20 h. The reaction mixture was concentrated in vacuo. Purification of
the crude product by flash chromatography on silica gel provided
desired product (2g) (93%, 326.4 mg).
5-(4-Chlorophenyl)phenanthridin-6(5H)-one
(2e):
N-(4-
Chlorophenyl) biphenyl-2-carboxamide (46.2 mg, 0.15 mmol) gave
5-(4-chlorophenyl)phenanthridin-6(5H)-one (89%, 40.6 mg) as a
white solid. Rf = 0.25 (CHCl3). 1H NMR (500 MHz, CDCl3) δ 8.54 (dd,
J = 1.2, 8.0 Hz, 1 H), 8.34 (d, J = 8.6 Hz, 1 H), 8.31 (dd, J = 1.7, 7.5
Hz, 1 H), 7.82 (td, J = 1.2, 8.0 Hz, 1 H), 7.64-7.58 (m, 3 H), 7.34-7.27
(m, 4 H), 6.69 (dd, J = 1.2, 8.0 Hz, 1 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 161.8, 139.0, 136.8, 134.9, 134.1, 133.1, 130.7, 130.6,
129.3, 129.1, 128.4, 125.8, 123.2, 123.0, 121.9, 119.2, 116.9. Data
in accordance with the literature.[9]
5-Phenylphenanthridin-6(5H)-one (2a): N-Phenyl biphenyl-2-
carboxamide (41.0 mg, 0.15 mmol) gave 5-phenylphenanthridin-
6(5H)-one (96%, 38.9 mg) as a pale yellow solid. Rf = 0.28 (20%
EtOAc in n-Hexane). 1H NMR (500 MHz, CDCl3) δ 8.56 (dd, J = 1.2,
8.1 Hz, 1 H), 8.33 (d, J = 8.1 Hz, 1 H), 8.30 (dd, J = 1.2, 8.0 Hz, 1 H),
7.81 (td, J = 1.1, 8.0 Hz, 1 H), 7.61 (t, J = 8.0 Hz, 1 H), 7.54 (t, J =
7.5 Hz, 1 H), 7.34 (d, J = 7.5 Hz, 2 H), 7.32-7.26 (m, 2 H), 7.24 (d, J
= 8.6 Hz, 2 H), 6.70 (dd, J = 1.7, 8.0 Hz, 1 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 161.8, 139.3, 138.4, 134.1, 132.9, 130.3, 129.2, 129.1,
128.9, 128.3, 126.0, 123.1, 122.7, 121.9, 119.1, 117.1. Data in
accordance with the literature.[9]
5-(4-Bromophenyl)phenanthridin-6(5H)-one
(2f):
N-(4-
Bromophenyl) biphenyl-2-carboxamide (52.8 mg, 0.15 mmol) gave
5-(4-bromophenyl)phenanthridin-6(5H)-one (88%, 46.2 mg) as a
white solid. Rf = 0.27 (20% EtOAc in n-Hexane). 1H NMR (500 MHz,
CDCl3) δ 8.54 (d, J = 8.0 Hz, 1 H), 8.34 (d, J = 8.6 Hz, 1 H), 8.31 (dd,
J = 1.7, 7.5 Hz, 1 H), 7.82 (t, J = 8.0 Hz, 1 H), 7.74 (d, J = 8.6 Hz, 2
H), 7.62 (t, J = 8.1 Hz, 1 H), 7.34-7.25 (m, 2 H), 7.22 (d, J = 8.6 Hz,
2 H), 6.69 (dd, J = 1.7, 7.4 Hz, 1 H). 13C{1H} NMR (125 MHz, CDCl3)
δ 161.7, 138.9, 137.4, 134.1, 133.6, 133.1, 131.0, 129.3, 129.1,
128.4, 125.8, 123.3, 123.0, 123.0, 122.0, 119.2, 116.9. Data in
accordance with the literature.[9]
5-(4-Methoxyphenyl)phenanthridin-6(5H)-one
(2b):
N-(4-
Methoxyphenyl) biphenyl-2-carboxamide (45.5 mg, 0.15 mmol) gave
5-(4-methoxyphenyl)phenanthridin-6(5H)-one (92%, 41.5 mg) as an
1
orange solid. Rf = 0.29 (1% MeOH in CHCl3). H NMR (500 MHz,
5-(3-Bromophenyl)phenanthridin-6(5H)-one
(2g):
N-(3-
CDCl3) δ 8.56 (dd, J = 1.2, 8.1 Hz, 1 H), 8.33 (d, J = 8.1 Hz, 1 H),
8.30 (dd, J = 1.2, 8.0 Hz, 1 H), 7.81 (td, J = 1.1, 8.0 Hz, 1 H), 7.61 (t,
J = 8.0 Hz, 1 H), 7.33-7.26 (m, 2 H), 7.24 (d, J = 8.6 Hz, 2 H), 7.12
(d, J = 9.1 Hz, 2 H), 6.76 (dd, J = 1.7, 8.0 Hz, 1 H), 3.90 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3) δ 162.1, 159.7, 139.6, 134.1, 132.9,
130.9, 130.1, 129.2, 128.2, 126.0, 123.1, 122.7, 121.9, 119.2, 117.2,
115.6, 55.7. Data in accordance with the literature.[9]
Bromophenyl) biphenyl-2-carboxamide (52.8 mg, 0.15 mmol) gave
5-(3-bromophenyl)phenanthridin-6(5H)-one (93%, 48.8 mg) as a
pale yellow solid. Rf = 0.28 (CHCl3). m.p. = 192-194 ºC. 1H NMR (500
MHz, CDCl3) δ 8.54 (d, J = 8.1 Hz, 1 H), 8.34-8.28 (m, 2 H), 7.84-
7.80 (m, 1 H), 7.68 (dd, J = 1.1, 8.1 Hz, 1 H), 7.52 (t, J = 1.7 Hz, 1
H), 7.50 (t, J = 8.1 Hz, 1 H), 7.35-7.28 (m, 3 H), 6.68 (dd, J = 1.2, 8.0
Hz, 1 H). 13C{1H} NMR (125 MHz, CDCl3) δ 161.7, 139.6, 138.8,
134.1, 133.2, 132.5, 132.2, 131.5, 129.4, 129.1, 128.4, 128.2, 125.7,
123.6, 123.3, 123.1, 122.0, 119.1, 116.9. IR (ATR) 3061, 1649, 1575,
1061 cm-1. HRMS (DART) Found 350.0177, Calcd. for C19H13BrNO,
[M + H]+ 350.0181.
5-(4-Methylphenyl)phenanthridin-6(5H)-one
(2c):
N-(4-
Methylphenyl) biphenyl-2-carboxamide (43.1 mg, 0.15 mmol) gave
5-(4-methylphenyl)phenanthridin-6(5H)-one (94%, 40.2 mg) as a
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10.1002/ejoc.201900536
European Journal of Organic Chemistry
FULL PAPER
5-(2-Bromophenyl)phenanthridin-6(5H)-one
(2h):
N-(2-
solid. Rf = 0.13 (CHCl3). m.p. = 216-218 ºC. 1H NMR (500 MHz,
CDCl3) δ 8.56 (d, J = 8.0 Hz, 1 H), 8.31 (d, J = 8.6 Hz, 1 H), 8.22 (d,
J = 8.6 Hz, 1 H), 7.79 (td, J = 1.1, 8.1 Hz, 1 H), 7.65-7.62 (m, 2 H),
7.60-7.53 (m, 2 H), 7.37-7.33 (m, 3 H), 6.69 (d, J = 1.8 Hz, 1 H), 1.19
(s, 9 H). 13C{1H} NMR (125 MHz, CDCl3) δ 162.0, 152.8, 139.1, 138.5,
134.1, 132.9, 130.2, 129.2, 129.1, 128.9, 127.8, 125.7, 122.8, 121.7,
120.4, 116.7, 113.9, 35.0, 31.1. IR (ATR) 3071, 1652, 1597 cm-1.
HRMS (DART) Found 328.1714, Calcd. for C23H22NO, [M + H]+
328.1701.
Bromophenyl) biphenyl-2-carboxamide (52.8 mg, 0.15 mmol) gave
5-(2-bromophenyl)phenanthridin-6(5H)-one (71%, 37.1 mg) as a
1
yellow viscous oil. Rf = 0.28 (CHCl3). H NMR (500 MHz, CDCl3) δ
8.58 (dd, J = 1.1, 8.0 Hz, 1 H), 8.35 (d, J = 8.6 Hz, 1 H), 8.33 (dd, J
= 1.7, 8.1 Hz, 1 H), 7.86-7.81 (m, 2 H), 7.62 (td, J = 1.1, 8.0 Hz, 2 H),
7.56 (td, J = 1.1, 8.0 Hz, 2 H), 7.44-7.39 (m, 2 H), 7.35-7.29 (m, 2 H),
6.57 (dd, J = 1.7, 8.0 Hz, 1 H). 13C{1H} NMR (125 MHz, CDCl3) δ
161.1, 138.1, 137.6, 134.3, 134.3, 133.2, 131.1, 130.6, 129.5, 129.4,
129.3, 128.3, 125.8, 123.8, 123.3, 123.1, 122.0, 119.2, 116.3. IR
(ATR) 3074, 1655, 1590, 1041 cm-1. HRMS (DART) Found 350.0196,
Calcd. for C19H13BrNO, [M + H]+ 350.0181.
3,5-Diphenylphenanthridin-6(5H)-one (2o): N-Phenyl 4’-phenyl-
biphenyl-2-carboxamide (52.4 mg, 0.15 mmol) gave 3,5-diphenyl
phenanthridin-6(5H)-one (90%, 47.1 mg) as a yellow solid. Rf = 0.20
(CHCl3). m.p. = 223-225 ºC. 1H NMR (500 MHz, CDCl3) δ 8.57 (d, J
= 7.4 Hz, 1 H), 8.36 (d, J = 8.0 Hz, 2 H), 7.83 (td, J = 1.7, 7.4 Hz, 1
H), 7.65-7.61 (m, 3 H), 7.56-7.52 (m, 2 H), 7.44-7.37 (m, 4 H), 7.35-
7.31 (m, 1 H), 6.90 (d, J = 1.7 Hz, 1 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 162.0, 142.1, 140.2, 139.7, 138.3, 133.9, 133.0, 130.4,
129.2, 129.0, 129.0, 128.2, 128.0, 127.2, 125.9, 123.6, 121.9, 121.8,
118.2, 115.4. IR (ATR) 3053, 1660, 1587 cm-1. HRMS (DART) Found
348.1387, Calcd. for C25H18NO, [M + H]+ 348.1388.
5-(4-Trifluoromethylphenyl)phenanthridin-6(5H)-one (2i): N-(4-
Trifluoromethylphenyl) biphenyl-2-carboxamide (51.2 mg, 0.15
mmol) gave 5-(4-trifluoromethylphenyl)phenanthridin-6(5H)-one
1
(86%, 43.9 mg) as a white solid. Rf = 0.31 (CHCl3). H NMR (500
MHz, CDCl3) δ 8.54 (dd, J = 1.2, 7.5 Hz, 1 H), 8.35 (d, J = 8.6 Hz, 1
H), 8.34-8.32 (m, 1 H), 7.89 (d, J = 8.6 Hz, 2 H), 7.85-7.82 (m, 1 H),
7.63 (t, J = 7.5 Hz, 1 H), 7.49 (d, J = 8.6 Hz, 2 H), 7.34-7.30 (m, 2 H),
6.64-6.62 (m, 1 H). 13C{1H} NMR (125 MHz, CDCl3) δ 161.7, 147.7,
141.7, 138.7, 134.1, 133.3, 131.3, 131.0, 130.1, 129.4, 129.1, 128.4,
127.5, 127.5, 127.2, 127.2, 125.7, 125.0, 123.3, 123.1, 122.8, 122.0,
119.2, 116.7. 19F NMR (470 MHz, CDCl3) δ -62.4. Data in accordance
with the literature.[9]
3-Chloro-5-phenylphenanthridin-6(5H)-one (2p): N-Phenyl 4’-
chloro-biphenyl-2-carboxamide (46.2 mg, 0.15 mmol) gave 3-chloro-
5-phenyl phenanthridin-6(5H)-one (89%, 40.8 mg) as a white solid.
Rf = 0.17 (CHCl3). m.p. = 200-201 ºC. 1H NMR (500 MHz, CDCl3) δ
8.54 (dd, J = 1.2, 8.0 Hz, 1 H), 8.26 (d, J = 8.0 Hz, 1 H), 8.20 (d, J =
8.6 Hz, 1 H), 7.81 (td, J = 1.1, 8.0 Hz, 1 H), 7.65-7.61 (m, 3 H), 7.58-
7.55 (m, 1 H), 7.33-7.31 (m, 2 H), 7.24 (dd, J = 2.3, 8.6 Hz, 1 H), 6.68
(d, J = 2.3 Hz, 1 H). 13C{1H} NMR (125 MHz, CDCl3) δ 161.7, 140.1,
137.8, 135.1, 133.4, 133.2, 130.5, 129.3, 129.2, 129.0, 128.5, 125.7,
124.4, 123.0, 121.9, 117.7, 116.9. IR (ATR) 3061, 1659, 1582, 1104
cm-1. HRMS (DART) Found 306.0673, Calcd. for C19H13ClNO, [M +
H]+ 306.0686.
5-(2-benzothiazolyl)phenanthridin-6(5H)-one
(2j):
N-(2-
Benzothiazolyl) biphenyl-2-carboxamide (49.6 mg, 0.15 mmol) gave
5-(2-benzothuazolyl)phenanthridin-6(5H)-one (84%, 41.6 mg) as a
white solid. Rf = 0.28 (CHCl3). m.p. = 196-198 ºC. 1H NMR (500 MHz,
CDCl3) δ 8.55 (dd, J = 1.2, 8.0 Hz, 1 H), 8.33 (d, J = 8.0 Hz, 1 H),
8.30 (dd, J = 1.7, 8.0 Hz, 1 H), 8.15 (d, J = 8.6 Hz, 1 H), 7.99 (d, J =
8.0 Hz, 1 H), 7.85 (td, J = 1.2, 8.0 Hz, 1 H), 7.64-7.57 (m, 2 H), 7.55-
7.52 (m, 1 H), 7.38-7.33 (m, 2 H), 6.92 (dd, J = 1.7, 8.0 Hz, 1 H).
13C{1H} NMR (125 MHz, CDCl3) δ 161.9, 158.6, 150.5, 137.9, 136.8,
134.3, 133.8, 129.7, 129.2, 128.5, 126.6, 126.5, 125.2, 124.4, 123.9,
123.3, 122.2, 122.2, 119.2, 116.5. IR (ATR) 3060, 1664, 1591 cm-1.
HRMS (DART) Found 329.0759, Calcd. for C20H13N2OS, [M + H]+
329.0749.
5-Phenyl-3-trifluoromethyl-phenanthridin-6(5H)-one (2q): N-
Phenyl 4’-trifluoromethyl-biphenyl-2-carboxamide (51.2 mg, 0.15
mmol) gave 5-phenyl-3-trifluoromethyl-phenanthridin-6(5H)-one
(69%, 35.2 mg) as a white solid. Rf = 0.25 (CHCl3). m.p. = 157-159
ºC. 1H NMR (500 MHz, CDCl3) δ 8.57 (dd, J = 1.1, 8.0 Hz, 1 H), 8.40
(d, J = 8.6 Hz, 1 H), 8.36 (d, J = 8.0 Hz, 1 H), 7.86 (td, J = 1.1, 8.0
Hz, 1 H), 7.71-7.63 (m, 3 H), 7.59-7.56 (m, 1 H), 7.51 (dd, J = 1.2,
8.6 Hz, 1 H), 7.34-7.32 (m, 2 H), 6.93 (s, 1 H). 13C{1H} NMR (125
3-Methoxy-5-phenylphenanthridin-6(5H)-one (2m): N-Phenyl 4’-
methoxy-biphenyl-2-carboxamide (45.5 mg, 0.15 mmol) gave 3-
methoxy-5-phenyl phenanthridin-6(5H)-one (99%, 44.7 mg) as a
yellow solid. Rf = 0.16 (CHCl3). m.p. = 161-163 ºC. 1H NMR (500 MHz, MHz, CDCl3) δ 161.6, 140.1, 139.3, 137.5, 133.3, 132.9, 131.1, 130.8,
CDCl3) δ 8.51 (d, J = 8.0 Hz, 1 H), 8.20 (dd, J = 6.3, 8.0 Hz, 2 H),
7.77 (td, J = 1.2, 8.0 Hz, 1 H), 7.61 (t, J = 7.5 Hz, 2 H), 7.55-7.51 (m,
2 H), 7.33 (dd, J = 1.7, 9.2 Hz, 2 H), 6.86 (dd, J = 2.3, 9.2 Hz, 1 H),
6.17 (d, J = 2.8 Hz, 1 H), 3.68 (s, 3 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 162.2, 160.4, 140.7, 138.4, 134.3, 132.9, 130.3, 129.1,
128.9, 127.1, 124.8, 124.5, 121.3, 112.8, 109.4, 102.1, 55.4. IR
(ATR) 3054, 1651, 1583, 1046 cm-1. HRMS (DART) Found 302.1177,
Calcd. for C20H16NO2, [M + H]+ 302.1181.
130.6, 129.4, 129.3, 129.2, 129.0, 128.6, 128.3, 126.5, 124.9, 124.8,
123.9, 122.6, 122.4, 121.8, 120.2, 119.1, 119.1, 114.0, 114.0. 19F
NMR (470 MHz, CDCl3) δ -62.6. IR (ATR) 3062, 1665, 1519, 1330
cm-1. HRMS (DART) Found 340.0958, Calcd. for C20H13F3NO, [M +
H]+ 340.0949.
5,8-Diphenylphenanthridin-6(5H)-one (2r): N-Phenyl 4-phenyl-
biphenyl-2-carboxamide (52.4 mg, 0.15 mmol) gave 5,8-diphenyl
phenanthridin-6(5H)-one (83%, 43.0 mg) as a white solid. Rf = 0.28
(CHCl3). m.p. = 205-207 ºC. 1H NMR (500 MHz, CDCl3) δ 8.80 (d, J
= 1.8 Hz, 1 H), 8.41 (d, J = 8.1 Hz, 1 H), 8.33 (dd, J = 1.7, 6.3 Hz, 1
H), 8.07 (dd, J = 1.7, 8.0 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 2 H), 7.64 (t,
3-tert Butyl-5-phenylphenanthridin-6(5H)-one (2n): N-Phenyl 4’-
tert butyl-biphenyl-2-carboxamide (49.4 mg, 0.15 mmol) gave 3-tert
butyl-5-phenyl phenanthridin-6(5H)-one (>99%, 49.1 mg) as a white
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10.1002/ejoc.201900536
European Journal of Organic Chemistry
FULL PAPER
[3]
[4]
a) P. Y. S. Lam, G. Vincent, C. G. Clark, S. Deudon, P. K. Jadhav,
Tetrahedron Lett., 2001, 42, 3415-3418; b) K. S. Rao, T. Wu,
Tetrahedron, 2012, 68, 7735-7754.
J = 8.6 Hz, 2 H), 7.56 (dd, J = 1.1, 7.4 Hz, 1 H), 7.50 (t, J = 8.6 Hz, 2
H), 7.40 (td, J = 1.1, 7.4 Hz, 1 H), 7.36 (d, J = 8.0 Hz, 2 H), 7.33-7.28
(m, 2 H), 6.71 (dd, J = 1.7, 7.5 Hz, 1 H). 13C{1H} NMR (125 MHz,
CDCl3) δ 161.9, 140.9, 139.8, 139.3, 138.4, 133.0, 131.7, 130.3,
129.2, 129.2, 129.1, 128.9, 128.0, 127.3, 127.1, 126.3, 123.1, 122.8,
122.6, 119.0, 117.2. IR (ATR) 3057, 1648, 1588 cm-1. HRMS (DART)
Found 348.1395, Calcd. for C25H18NO, [M + H]+ 348.1388.
a) H. C. Van der Plas, H. C. Acc. Chem. Res., 1978, 11, 462-468; b)
M. Makosza, J. Winiarski, Acc. Chem. Res., 1987, 20, 282-289; c) A.
Kaga, H. Hayashi, H. Hakamata, M. Oi, M. Uchiyama, R. Takita, S.
Chiba, Angew. Chem. Int. Ed., 2017, 56, 11807-11811; d) N. E. S.
Tay, D. A. Nicewicz, J. Am. Chem. Soc., 2017, 139, 16100-16104.
[5] a) D. E. Ames, A. Opalko, Tetrahedron, 1984, 40, 1919-1925; b) M. A.
Siddiqui, V. Snieckus, Tetrahedron Lett., 1988, 29, 5463-5466; c) T.
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Acknowledgments
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Keywords: C-H amidation • visible-light • transition-metal-free •
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900536
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
FULL PAPER
C–H amidation, organophotocatalyst
Kaoru Usami, Eiji Yamaguchi, Norihiro
Tada and Akichika Itoh *
Page No. – Page No.
We have developed a method to construct a phenanthridinone skeleton frequently
found in bioactive substances without using transition metals. This reaction proceeds
photooxidative C–H amidation with the visible light irradiation and the commercially
available organophotocatalyst. Phenanthridinones are afforded under mild conditions
at low cost in this synthetic method.
Transition-Metal-Free Synthesis of
Phenanthridinones through Visible-
Light-Driven Oxidative C–H
Amidation
This article is protected by copyright. All rights reserved.