Potassium Carbonate Promoted C-N Coupling Reaction between Benzamides and Aryl Iodides

Article abstract of DOI:10.1055/s-0036-1591843

A practical and efficient method for N-arylation of benz-amides promoted by potassium carbonate in the presence of DMEDA was developed. The reaction was carried out without addition of any transition-metal catalyst to afford a variety of N-arylated products in moderate to good yields (up to 97%).

Full text of DOI:10.1055/s-0036-1591843

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–G
paper
A
en
F. Huang et al.
Paper
Synthesis
Potassium Carbonate Promoted C–N Coupling Reaction between
Benzamides and Aryl Iodides
Fei Huang
San Wu
transition-metal-free
base-promoted
O
O
R2
I
N
R2
NH2
+
Weiye Hu
H
one-pot reaction
up to 97% yield
R1
R1
Songlin Zhang*
Key Laboratory of Organic Synthesis of Jiangsu Province,
College of Chemistry, Chemical Engineering and Materials
Science, Dushu Lake Campus, Soochow University, Suzhou
215123, P. R. of China
zhangsl@suda.edu.cn
Received: 01.09.2017
Accepted after revision: 03.11.2017
Published online: 23.11.2017
Despite notable advances, the application of these tran-
sition-metal-catalyzed C–N couplings is still limited due to
the exorbitant price and toxicity of the transition-metal
catalyst. To meet the demand for environment benign and
economic efficient, developing a transition-metal-free pro-
tocol to construct N-arylated benzamides is highly signifi-
cant. Although various remarkable progresses were made
in transition-metal-free coupling reactions,7 only a few C–N
couplings promoted by base without addition of any transi-
tion metals were reported.8 Bolm et al. reported the first
base-promoted intermolecular C–N coupling reaction in
the absence of any transition metals in 2010. The reaction
of nitrogen-based nucleophiles with aryl iodides was pro-
moted by potassium hydroxide in DMSO in low to moderat-
ed yields. In the next year, Ramón and co-workers reported
a similar reaction condition for C–N, C–S, and C–O cou-
plings. However, the protocol is not suitable for the reaction
of amides and aryl halides because of low yields or long re-
action time. Herein, we describe an efficient base promoted
N-arylation of aryl amides in the absence of transition-
metal catalyst (Scheme 1).
The reaction between benzamide (1a) and aryl iodide
2a was selected as a model reaction to screen down the ide-
al reaction conditions (Table 1, entries 1–20). First, various
bases were screened in the presence of DMEDA (N,N′-di-
methylethylenediamine) in anhydrous toluene and the re-
sults are summarized in Table 1 (entries 1–7). To our de-
light, the N-arylated 4-chlorobenzamide was obtained in
37% yield in the presence of K2CO3. When the reaction time
was prolonged to 48 hours, the yield was improved to 87%
(entry 8). Then several nitrogen-contained ligands were ex-
amined and the results indicated that DMEDA was the most
suitable ligand for this reaction (entries 9–12). Next MeCN,
DMSO, DMF, DME, and PhCl were employed, respectively, as
the solvent; the product was formed only in the case of
PhCl, however, in a decreased yield of 56% (entries 13–16).
DOI: 10.1055/s-0036-1591843; Art ID: ss-2017-h0566-op
Abstract A practical and efficient method for N-arylation of benz-
amides promoted by potassium carbonate in the presence of DMEDA
was developed. The reaction was carried out without addition of any
transition-metal catalyst to afford a variety of N-arylated products in
moderate to good yields (up to 97%).
Key words coupling reaction, potassium carbonate, N-arylation,
N-arylbenzamides
N-Arylbenzamides are important building blocks in the
synthesis of many pharmaceutical and biologically active
molecules.1 Developing new methods to prepare this class
of valuable molecules is always a focus of organic chemists.
The straightforward methods to obtain the N-arylated ben-
zamides was transition-metal-catalyzed C–N coupling reac-
tion of benzamides with aryl halides. Since Ullmann,
Buchwald, and co-workers reported the copper-catalyzed
N-arylation of benzamides,2 the other transition metals
such as Pd,3 Fe,4 Ag,5 and Co6 catalyzed C–N coupling reac-
tions have been extensively developed (Scheme 1).
Previous work
O
O
Pd
Cu
Co
I
R2
NH2
N
H
+
R2
R1
R1
This work
O
O
I
base-promoted
R2
NH2
N
+
R2
R1
H
R1
Scheme 1 Strategies for N-arylation of benzamides
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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F. Huang et al.
Paper
Synthesis
When undistilled toluene was used instead of anhydrous
toluene, the yield decreased significantly (entry 18). Con-
sidering that a trace amount of transition metals remaining
in the base fundamentally affected the exact reaction path-
way in some cases,9 high-purity K2CO3 (99.995%) from Al-
drich was employed (entry 19), which gave the title prod-
uct in 84% yield. It is worth mentioning that the reaction
did not take place without the use of ligand DMEDA (entry
20). Based on the results observed in the current study and
the relevant literature,9d it could be concluded that the roles
of potassium carbonate, DMEDA, and toluene were indis-
pensable in the reaction. Potassium carbonate as a base, not
only neutralizes the acid (HI) produced in the coupling re-
action, but also interacts with DMEDA to produce free-radi-
cal anions. Then these free-radical anions activate aryl io-
dides to form aryl radical anions, which react further with
amides.
Table 1 Optimization of Reaction Conditionsa
Cl
O
O
base
I
ligand
NH2
N
+
H
solvent
Cl
2a
1a
3a
Entry
Base
KOt-Bu
Ligandb
Solvent
Yield (%)c
1
2
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L1
L1
L1
L1
L1
L1
L1
–
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
MeCN
0
0
LiOt-Bu
3
NaOt-Bu
K3PO4
0
4
0
5
KOH
0
6
K2CO3 (24 h)
Li2CO3
37
0
7
8
K2CO3 (48 h)
K2CO3
87
trace
0
Taken together, the results of these screening experi-
ments revealed that the optimal conditions for the reaction
were 3.0 equivalents K2CO3 as the base in the presence of
0.4 equivalent DMEDA and anhydrous toluene as the sol-
vent.
9
10
11
12
13
14
15
16
17
18d
19e
20
K2CO3
K2CO3
0
K2CO3
0
With the optimized reaction conditions in hand, the
substrate scope of the reaction was explored and the results
are summarized in Table 2. First a series of benzamides
were employed to react with 1-chloro-4-iodobenzene (Ta-
ble 2, entries 1–6). As shown in Table 2, benzamides with
an electron-withdrawing group on the aryl ring gave high
yields, such as 4-fluoro-, 4-chloro-, 3-chloro-, and 4-nitro-
benzamide (entries 2–5). For benzamide bearing an elec-
tron-donating group such as 4-methylbenzamide, the prod-
uct was obtained in moderate yield (entry 6). The results
indicated that electron-withdrawing groups on the aryl
ring were favored for the reaction than electron-donating
groups. Then various aryl iodides were examined and the
results showed that the corresponding N-arylated ben-
zamides were obtained in moderate to good yields when 2-
chloro-, 3-chloro-1-iodobenzene, and methyl 2-iodobenzo-
ate were employed (entries 7–12, 20).
K2CO3
0
K2CO3
DMSO
0
K2CO3
DMF
0
K2CO3
DME
0
K2CO3 (48 h)
K2CO3 (48 h)
K2C O3 (48 h)
K2CO3 (48 h)
PhCl
56
31
84
NR
toluene
toluene
toluene
a Reaction conditions: 1-chloro-4-iodobenzene (1.0 mmol), benzamide (0.5
mmol), base (1.5 mmol) were added to a solvent (5 mL) under N2, and the
resulting mixture warmed at 110 °C for 48 h.
b L1: N,N′-Dimethylethylenediamine; L2: N,N,N′,N′-Tetramethylethylenedi-
amine; L3: 2,2′-Bipyridine; L4: 1,10-Phenanthroline; L5: 2,6-Di-tert-bu-
tylpyridine.
c Isolated yield based on benzamide after silica gel chromatography. NR: No
reaction.
d Undistilled toluene was used instead of anhyd toluene.
e High purity K2CO3 (99.995%) from Aldrich was used.
Unfortunately, when 1-iodo-4-methoxybenzene, aryl
bromide, and other functionalized iodobenzene were em-
ployed as substrates, no corresponding products were ob-
tained (Table 2, entries 13, 21, 22–24). To highlight the utili-
zation of this reaction, the use of heterocyclic compounds
as substrates for this reaction was also investigated, which
to our delight, furnished the corresponding N-arylated am-
ides in moderate yields as well (entries 14–19).
In summary, we have documented a base promoted N-
arylation of benzamides. An efficient protocol has been de-
veloped for the synthesis of N-arylated benzamides using
potassium carbonate as a mediated agent in the presence of
DMEDA. This method has been successfully applied to the
C–N coupling of aryl amides with aryl halides without addi-
tion of any transition-metal catalysts.
All chemicals were purchased from J & K, Aldrich, Adamas, Acros, En-
ergy Chemical, and Alfa Asia company and used without further puri-
fication. Solvents were purchased from commercial sources and used
without further purification. Petroleum ether (PE) used refers to the
fraction boiling at 60–90 °C. All reactions were conducted under a N2
atmosphere. Flash column chromatography was carried out on Merck
1
silica gel (200–300 mesh). H and 13C NMR spectra were recorded in
DMSO-d6 or CDCl3 on a Bruker 400 MHz spectrometer. Chemical
shifts in 1H NMR spectra are reported in parts per million (ppm, δ)
downfield from the internal standard Me4Si (δ = 0.00) or DMSO (δ =
2.50). Chemical shifts in 13C NMR spectra are reported relative to the
central line of the CHCl3 signal (δ = 77.00) or DMSO signal (δ = 40.00).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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Synthesis
Table 2 Reactions of Aryl Amides with Aryl Iodides Promoted by Potassium Carbonatea
O
O
I
K2CO3, DMEDA
R2
NH2
N
+
R2
R1
H
toluene
R1
1
2
3
Entry
1
1
2
3
Yield (%)b
87
Cl
O
O
I
Cl
Cl
2a
1a
3aa
Cl
O
O
I
2
3
4
5
6
92
78
93
95
61
2a
F
1b
F
3ba
Cl
O
O
I
Cl
Cl
2a
Cl
1c
Cl
3ca
Cl
Cl
O
Cl
O
I
2a
1d
3da
Cl
O
O
NH2
I
Cl
Cl
N
H
2a
O2N
O2N
3ea
1e
Cl
O
O
I
2a
1f
3fa
O
O
O
O
O
O
Cl
7
8
9
81
72
59
I
Cl
2b
1a
1a
1a
3ab
3ac
3ad
Cl
I
Cl
2c
I
2d
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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F. Huang et al.
Paper
Synthesis
Table 2 (continued)
Entry
1
2
3
Yield (%)b
88
O
O
O
O
O
O
Cl
I
10
Cl
F
F
2b
1b
3bb
Cl
I
Cl
11
12
73
65
F
2c
F
1b
3bc
I
F
1b
F
3bd
2d
O
O
O
I
13
14
NR
80
O
2e
F
1b
F
3be
Cl
Cl
O
O
O
S
I
Cl
Cl
NH2
N
H
2a
S
1g
3ga
O
O
O
O
I
NH2
15
16
17
78
53
45
N
H
2a
O
S
S
1h
3ha
3gb
O
O
Cl
I
S
NH2
N
H
Cl
2b
1g
Cl
I
S
NH2
N
H
Cl
2c
2f
1g
1d
1a
3gc
Cl
O
Cl
O
N
N
I
I
N
18
19
73
51
N
N
H
3df
3af
O
O
N
H
2f
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F. Huang et al.
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Synthesis
Table 2 (continued)
Entry
1
2
3
Yield (%)b
O
O
O
O
I
N
H
O
20
54
O
O
1a
1a
2g
3ag
Cl
O
O
Br
Cl
21
22
23
NR
NR
NR
2h
3ah
O
O
O
O
N
H
I
2i
1a
1a
3ai
3aj
NO2
O
NO2
N
H
I
2j
O
O
O
O
H
H
24
NR
N
H
I
F
1b
2k
F
3bk
a Reaction conditions: aryl iodide (1.0 mmol), benzamide (0.5 mmol), K2CO3 (1.5 mmol), and DMEDA (0.2 mmol) were added to anhyd toluene (5.0
mL) under N2, and the resulting mixture warmed at 110 °C for 48 h.
b Isolated yield based on benzamide after silica gel chromatography. NR: No reaction.
N-Arylated Benzamides 3; General Procedure
N-(4-Chlorophenyl)-4-fluorobenzamide (3ba)11
An oven-dried Schlenk tube was charged with benzamide 1 (0.5
mmol), K2CO3 (207 mg, 1.5 mmol) and aryl iodide 2 (1.0 mol). The
tube was evacuated and backfilled with N2 (3 ×), and then DMEDA
(0.2 mmol) and anhyd toluene (5.0 mL) were added. The reaction
mixture was stirred at 110 ° C for 48 h. H2O was added and the crude
product was extracted with EtOAc. The combined organic phases
were washed with brine and H2O, dried (Na2SO4), and concentrated
under reduced pressure. The product was purified by silica gel chro-
matography to give the desired N-arylated benzamides (Table 2).
White solid; yield: 0.115 g (92%); mp 171–172 °C.
1H NMR (400 MHz, CDCl3): δ = 10.39 (s, 1 H), 8.06–8.02 (m, 2 H),
7.83–7.81 (m, 2 H), 7.41–7.33 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 165.01, 164.65 (1JC,F = 247.88 Hz),
138.56, 131.61 (4JC,F = 2.91 Hz), 130.93 (3JC,F = 9.03 Hz), 128.99, 127.86,
122.38, 115.83 (2JC,F = 21.78 Hz).
LC-MS: m/z = 250.0 [M + H]+.
4-Chloro-N-(4-chlorophenyl)benzamide (3ca)12
N-(4-Chlorophenyl)benzamide (3aa)10
White solid; yield: 0.1037 g (78%); mp 212–212.5 °C.
1H NMR (400 MHz, CDCl3): δ = 10.45 (s, 1 H), 7.98 (d, J = 8.4Hz, 2 H),
7.82 (d, J = 8.8 Hz, 2 H), 7.58 (d, J = 8.4 Hz, 2 H), 7.39 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 164.97, 138.45, 137.08, 133.83,
White solid; yield: 0.1009 g (87%); mp 199–201 °C.
1H NMR (400 MHz, CDCl3): δ = 10.38 (s, 1 H), 7.97–7.94 (m, 2 H),
7.85–7.82 (d, J = 12.0 Hz, 2 H), 7.60–7.51 (m, 3 H), 7.42–7.40 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 166.15, 138.65, 135.21, 132.18,
130.11, 128.99, 128.93, 127.96, 122.38.
LC-MS: m/z = 266.0 [M + H]+.
129.00, 128.90, 128.17, 127.76, 122.33.
LC-MS: m/z = 232.0 [M + H]+.
2-Chloro-N-(4-chlorophenyl)benzamide (3da)13
White solid; yield: 0.1237 g (93%); mp 121 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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F. Huang et al.
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1H NMR (400 MHz, CDCl3): δ = 10.68 (s, 1 H), 7.81–7.78 (m, 2 H),
LC-MS: m/z = 250.0 [M + H]+.
7.62–7.56 (m, 2 H), 7.53–7.41 (m, 4 H).
N-(3-Chlorophenyl)-4-fluorobenzamide (3bc)20
13C NMR (100 MHz, CDCl3): δ = 165.51, 138.37, 137.22, 131.67,
130.47, 130.17, 129.42, 129.19, 127.99, 127.73, 121.62.
White solid; yield: 0.0913 g (73%); mp 125–126 °C.
LC-MS: m/z = 266.0 [M + H]+.
1H NMR (400 MHz, CDCl3): δ = 10.42 (s, 1 H), 8.06–8.03 (m, 2 H),
7.98–7.97 (m, 1 H), 7.71–7.70 (m, 1 H), 7.39–7.34 (m, 3 H), 7.16–7.13
(m, 1 H).
N-(4-Chlorophenyl)-4-nitrobenzamide (3ea)14
White solid; yield: 0.1316 g (95%); mp 231 °C.
1H NMR (400 MHz, CDCl3): δ = 10.64 (s, 1 H), 8.33 (d, J = 7.6 Hz, 2 H),
8.16 (d, J = 8.4 Hz, 2 H), 7.81 (d, J = 8.4 Hz, 2 H), 7.39 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 165.18, 164.73 (1JC,F = 248.13 Hz),
141.10, 133.50, 131.49 (4JC,F = 2.90 Hz), 131.00 (3JC,F = 8.98 Hz), 130.77,
123.88, 120.28, 119.15, 115.89 (2JC,F = 21.63 Hz).
LC-MS: m/z = 250.0 [M + H]+.
13C NMR (100 MHz, CDCl3): δ = 164.34, 149.65, 140.74, 138.18,
129.69, 129.06, 128.35, 123.97, 122.46.
LC-MS: m/z = 277.0 [M + H]+.
4-Fluoro-N-phenylbenzamide (3bd)21
White solid; yield: 0.0702 g (65%); mp 182–184 °C.
1H NMR (400 MHz, CDCl3): δ = 10.27 (s, 1 H), 8.07–8.04 (m, 2 H), 7.79
(d, J = 8.0 Hz, 2 H), 7.35 (t, J = 8.0 Hz, 4 H), 7.10 (t, J = 7.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 164.96, 164.58 (1JC,F = 247.46 Hz),
139.59, 131.91 (4JC,F = 2.43 Hz), 130.89 (3JC,F = 9.09 Hz), 129.10, 124.23,
120.95, 115.79 (2JC,F = 21.50 Hz).
N-(4-Chlorophenyl)-4-methylbenzamide (3fa)15
White solid; yield: 0.075 g (61%); mp 210 °C.
1H NMR (400 MHz, CDCl3): δ = 10.29 (s, 1 H), 7.89–7.82 (m, 4 H),
7.41–7.31 (m, 4 H), 2.37 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 165.95, 142.22, 138.75, 132.32,
LC-MS: m/z = 216.1 [M + H]+.
129.41, 128.95, 128.22, 127.66, 122.32.
LC-MS: m/z = 246.0 [M + H]+.
N-(4-Chlorophenyl)thiophene-2-carboxamide (3ga)22
White solid; yield: 0.0952 g (80%); mp 142–143 °C.
N-(2-Chlorophenyl)benzamide (3ab)16
1H NMR (400 MHz, CDCl3): δ = 10.35 (s, 1 H), 8.03 (d, J = 4.0 Hz, 1 H),
7.84 (d, J = 4.8 Hz, 1 H), 7.78 (d, J = 8.8 Hz, 2 H), 7.39 (d, J = 8.8 Hz, 2 H),
7.22 (t, J = 4.4 Hz, 1 H).
13C NMR (101 MHz, DMSO-d6): δ = 160.47, 140.23, 138.22, 132.53,
129.83, 129.07, 128.56, 127.93, 122.36.
White solid; yield: 0.094 g (81%); mp 96–97 °C.
1H NMR (400 MHz, CDCl3): δ = 10.08 (s, 1 H), 8.03 (d, J = 7.6 Hz, 2 H),
7.64–7.53 (m, 5 H), 7.41–7.38 (m, 1 H), 7.30–7.28 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 165.88, 135.58, 134.46, 132.33,
130.03, 130.00, 128.98, 128.91, 128.19, 127.94, 127.92.
LC-MS: m/z = 232.0 [M + H]+.
LC-MS: m/z = 238.0 [M + H]+.
N-(4-Chlorophenyl)furan-2-carboxamide (3ha)22
N-(3-Chlorophenyl)benzamide (3ac)17
White solid; yield: 0.0866 g (78%); mp 142–143 °C.
White solid; yield: 0.0835 g (72%); mp 120–121 °C.
1H NMR (400 MHz, DMSO-d6): δ = 10.32 (s, 1 H), 7.92 (dd, J = 2.0, 0.8
Hz, 1 H), 7.82–7.80 (m, 2 H), 7.39–7.34 (m, 3 H), 6.68 (dd, J = 3.6, 2.0
Hz, 1 H).
13C NMR (101 MHz, DMSO-d6): δ = 156.76, 147.84, 146.28, 138.03,
129.02, 127.95, 122.38, 115.53, 112.69.
1H NMR (400 MHz, CDCl3): δ = 10.41 (s, 1 H), 8.00–7.95 (m, 3 H),
7.74–7.72 (m, 1 H), 7.62–7.58 (m, 1 H), 7.56–7.52 (m, 2 H), 7.38 (t, J =
7.6 Hz, 1 H), 7.17–7.14 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 166.30, 141.16, 135.07, 133.44,
132.27, 130.76, 128.91, 128.19, 123.79, 120.19, 119.09.
LC-MS: m/z = 222.0 [M + H]+.
LC-MS: m/z = 232.0 [M + H]+.
N-(2-Chlorophenyl)thiophene-2-carboxamide (3gb)19
N-Phenylbenzamide (3ad)18
White solid; yield: 0.0630 g (53%); mp 118–121 °C.
White solid; yield: 0.058 g (59%); mp 163 °C.
1H NMR (400 MHz, DMSO-d6): δ = 10.11 (s, 1 H), 8.02 (dd, J = 4.0, 1.2
Hz, 1 H), 7.87 (dd, J = 5.2, 1.2 Hz, 1 H), 7.57–7.54 (m, 2 H), 7.39–7.38
(m, 1 H), 7.32–7.30 (m, 1 H), 7.24–7.22 (m, 1 H).
13C NMR (101 MHz, DMSO-d6): δ = 160.51, 139.59, 135.04, 132.47,
130.17, 130.10, 129.97, 129.21, 128.66, 128.17, 128.01.
1H NMR (400 MHz, CDCl3): δ = 10.30 (s, 1 H), 8.02–7.99 (m, 2 H),
7.86–7.84 (m, 2 H), 7.61–7.51 (m, 3 H), 7.39–7.35 (m, 2 H), 7.12 (t, J =
7.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 166.14, 139.74, 135.56, 132.02,
129.11, 128.87, 128.19, 124.18, 120.94.
LC-MS: m/z = 238.0 [M + H]+.
LC-MS: m/z = 198.0 [M + H]+.
N-(3-Chlorophenyl)thiophene-2-carboxamide (3gc)22
N-(2-Chlorophenyl)-4-fluorobenzamide (3bb)19
White solid; yield: 0.0528 g (45%); mp 191 °C.
White solid; yield: 0.11 g (88%); mp 109–110 °C.
1H NMR (400 MHz, CDCl3): δ = 10.11 (s, 1 H), 8.10–8.07 (m, 2 H),
7.60–7.55 (m, 2 H), 7.41–7.28 (m, 4 H).
1H NMR (400 MHz, DMSO-d6): δ = 10.36 (s, 1 H), 8.03–8.02 (m, 1 H),
7.92–7.87 (m, 2 H), 7.68–7.62 (m, 1 H), 7.38 (t, J = 8.0 Hz, 1 H), 7.24–
7.22 (m, 1 H), 7.17–7.14 (m, 1 H).
13C NMR (101 MHz, DMSO-d6): δ = 160.56, 140.72, 139.99, 133.48,
132.79, 130.85, 129.98, 128.61, 123.87, 120.18, 119.06.
13C NMR (100 MHz, CDCl3): δ = 164.83, 164.73 (1JC,F = 247.89 Hz),
135.47, 130.97, 130.92, 130.88, 130.11, 130.04, 129.06, 128.01 (3JC,F
9.28 Hz), 115.95 (2JC,F = 21.62 Hz).
=
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

G
F. Huang et al.
Paper
Synthesis
LC-MS: m/z = 238.0 [M + H]+.
116, 7901. (d) Klapars, A.; Antilla, J. C.; Huang, X. H.; Buchwald,
S. L. J. Am. Chem. Soc. 2001, 123, 7729. (e) Klapars, A.; Huang, X.
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Chem. 2009, 74, 7514.
2-Chloro-N-(pyridin-2-yl)benzamide (3df)23
White solid; yield: 0.085 g (73%); mp 275.1 °C.
1H NMR (400 MHz, DMSO-d6): δ = 11.06 (s, 1 H), 8.33–8.21 (m, 2 H),
7.85 (t, J = 8.0 Hz, 1 H), 7.59–7.40 (m, 4 H), 7.15 (t, J = 7.6 Hz, 1 H).
13C NMR (101 MHz, DMSO-d6): δ = 166.29, 152.29, 148.58, 138.78,
136.97, 131.66, 130.46, 130.06, 129.52, 127.61, 120.51, 114.73.
LC-MS: m/z = 233.0 [M + H]+.
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2010, 2, 1044. (g) Shirakawa, E.; Zhang, X.; Hayashi, T. Angew.
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N-(Pyridin-2-yl)benzamide (3af)24
White solid; yield: 0.0508 g (51%); mp 87 °C.
1H NMR (400 MHz, DMSO-d6): δ = 10.78 (s, 1 H), 8.37 (d, J = 4.8 Hz, 1
H), 8.24 (d, J = 8.4 Hz, 1 H), 8.06 (d, J = 7.6 Hz, 2 H), 7.83 (t, J = 7.6 Hz, 1
H), 7.60–7.48 (m, 3 H), 7.16–7.13 (m, 1 H).
13C NMR (101 MHz, DMSO-d6): δ = 166.52, 152.73, 148.41, 138.58,
134.63, 132.40, 128.85, 128.51, 120.28, 115.25.
LC-MS: m/z = 199.1 [M + H]+.
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16737. (e) Shirakawa, E.; Itoh, K.; Higashino, T.; Hayashi, T.
J. Am. Chem. Soc. 2010, 132, 15537. (f) Huang, P.; He, B. Y.;
Wang, H. M.; Lu, J. M. Synthesis 2015, 47, 221. (g) Yang, S.; Wu,
C.; Ruan, M.; Yang, Y.; Zhao, Y.; Niu, J.; Yang, W.; Xu, J. Tetrahe-
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H.; He, C.; Wang, H. B.; Kwong, F. Y.; Lei, A. J. Am. Chem. Soc.
2010, 132, 16737.
Methyl 2-Benzamidobenzoate (3ag)25
White solid; yield: 0.0677 g (54%); mp 101 °C.
1H NMR (400 MHz, CDCl3): δ = 12.04 (s, 1 H), 12.04 (s, 1 H), 8.94 (dd,
J = 8.5, 1.0 Hz, 1 H), 8.94 (dd, J = 8.5, 1.0 Hz, 1 H), 8.07 (ddd, J = 12.2,
8.1, 1.7 Hz, 3 H), 8.07 (ddd, J = 12.2, 8.1, 1.7 Hz, 3 H), 7.68–7.47 (m, 4
H), 7.72–7.40 (m, 4 H), 7.13 (ddd, J = 8.4, 7.3, 1.2 Hz, 1 H), 7.13 (ddd,
J = 8.4, 7.3, 1.2 Hz, 1 H), 3.97 (s, 3 H), 3.97 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 169.22, 165.87, 142.02, 134.98,
132.08, 131.09, 128.95, 127.52, 122.75, 120.61, 115.30, 52.63.
LC-MS: m/z = 256.1 [M + H]+.
Funding Information
We would like to gratefully acknowledge financial support from the A
Project Funded by the Priority Academic Program for the Develop-
ment of Jiangsu Higher Education Institutions and the National Natu-
(10) Wagner, P.; Bollenbach, M.; Doebelin, C.; Bihel, F.; Bourguignon,
J.-J.; Salomé, C.; Schmitt, M. Green Chem. 2014, 16, 4170.
(11) Cheng, C.; Sun, G.; Wan, J.; Sun, C. Synlett 2009, 2663.
(12) Mieko, A.; Masahiko, Y. Org. Lett. 2001, 3, 311.
ral Science Foundation of China (No. 21072143).
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(13) Zhang, G.; Zhao, X.; Yan, Y.; Ding, C. Eur. J. Org. Chem. 2012, 669.
(14) Liley, M. J.; Johnson, T.; Gibson, S. E. J. Org. Chem. 2006, 71, 1322.
(15) Teo, Y. C.; Yong, F. F.; Ithnin, I. K.; Yio, S.-H. T.; Lin, Z. Eur. J. Org.
Chem. 2013, 515.
(16) Ghotas, E.; Robert, A. B. J. Org. Chem. 2006, 71, 1802.
(17) Satoshi, U.; Hideko, N. J. Org. Chem. 2009, 74, 4272.
(18) Crawford, S. M.; Lavery, C. B.; Stradiotto, M. Chem. Eur. J. 2013,
19, 16760.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591843. 1H and 13C NMR spectra for
all compounds are included.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G