Synthesis of N -Aryl Amides by Ligand-Free Copper-Catalyzed ipso -Amidation of Arylboronic Acids with Nitriles

Article abstract of DOI:10.1055/s-0036-1588373

A facile copper-catalyzed ipso-amidation of arylboronic acids with nitriles has been developed. The method provides a highly efficient and economical synthesis of N-aryl amides with a broad substrate scope.

Full text of DOI:10.1055/s-0036-1588373

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–E
paper
A
Y. Qiao et al.
Paper
Synthesis
Synthesis of N-Aryl Amides by Ligand-Free Copper-Catalyzed ipso-
Amidation of Arylboronic Acids with Nitriles
Yan Qiao
Gaoqiang Li*
Sha Liu
Yujie Yangkai
Jingxuan Tu
Feng Xu*
Key Laboratory of Macromolecular Science of Shaanxi Province,
School of Chemistry and Chemical Engineering, Shaanxi Normal
University, Xi’an, Shaanxi 710062, P. R. of China
gqli@snnu.edu.cn
fengxu@snnu.edu.cn
Received: 13.09.2016
Accepted after revision: 21.11.2016
Published online: 16.12.2016
per-catalyzed sequential hydrolysis/coupling reactions of
nitriles with aryl halides to give N-aryl amide motifs have
been reported.3,5–7 Furthermore, Jamieson and co-workers
developed an efficient synthesis of N-aryl amides by a sila-
noate-mediated combination of hydrolysis of nitriles and
palladium-catalyzed coupling with aryl bromides.8 Never-
theless, most of these synthetic procedures require the as-
sistance of expensive nongeneralized ligands, and the reac-
tions must be performed under an inert atmosphere.
DOI: 10.1055/s-0036-1588373; Art ID: ss-2016-f0622-op
Abstract A facile copper-catalyzed ipso-amidation of arylboronic acids
with nitriles has been developed. The method provides a highly effi-
cient and economical synthesis of N-aryl amides with a broad substrate
scope.
Key words amides, nitriles, amination, copper catalysis, arylboronic
acids, tandem reactions
Chan–Lam coupling9 is a popular C–N or C–O bond-
forming reaction of organoboryl reagents with amines or
alcohols, respectively. This reaction is catalyzed by cop-
per(II) species and can be conducted in air using oxygen as
an oxidant. Therefore, a combination of the hydrolysis of ni-
triles and a Chan–Lam reaction should significantly expand
the substrate scope for N-aryl amide synthesis, avoid the
use of ligands, and permit the synthetic operations to be
conducted in air. In 2009, Prakash et al. reported a XeF2-me-
diated synthesis of anilides from arylboronic acids and ni-
triles.10 The reactions reach completion in a short time and
generate anilides in moderate to high yields. However, it is
disappointing that electron-deficient arylboronic acids give
no or low yields of the desired products. Recently, Xiang et
al. developed a copper-catalyzed amidation of arylboronic
acids with nitriles.11 The reactions showed a broad sub-
strate scope and gave N-aryl amides in up to 87% yield. Nev-
ertheless, these transformations required the use of
MesI(OAc)2 as an oxidant, BF3·OEt2 and TMSOTf as additives,
and proceeded under argon, making the method uneco-
nomical. In 2015, Dash and co-workers reported the hydro-
lysis of nitriles to the corresponding amides by using potas-
sium tert-butoxide in tert-butanol under nitrogen.12 The
hydrolysis proceeded smoothly for a broad range of nitriles
under mild conditions, using the potassium tert-butoxide
as an oxygen source, and it provided the amides in excellent
yields without over-hydrolysis.
N-Aryl amides are valuable compounds that are widely
present in proteins, bioactive molecules, organic functional
materials, and drugs.1,2 Various approaches to N-aryl am-
ides have been well documented in the literature. Access to
N-aryl amides is mainly through coupling reactions of pre-
formed amides with aryl halides. Amides can also be ac-
cessed through hydrolysis of nitriles; consequently, nitriles,
as excellent precursors of amides with wide availability and
low cost, have aroused great interest among organic chem-
ists. Classical procedures for nitrile hydrolysis generally in-
volve treatment with a strong inorganic acid or base in wa-
ter. However, the formation of carboxylic acids through fur-
ther hydrolysis of the amide is a serious problem that limits
the application of such procedures. Recently, a copper-
assisted hydrolysis of nitriles to give the corresponding am-
ides was developed by Zhou et al.3 This strategy, using 2.5
mol% of Cu4I4(H2O)4 complex in pure water, showed high ef-
ficiency and afforded the amides in high yields of up to 98%.
Copper metal is also an active catalytic species in coupling
reactions of amides with aryl halides.4 Therefore, a combi-
nation of the copper-catalyzed hydrolysis of a nitrile to an
amide and subsequent copper-catalyzed coupling of the re-
sulting amide with an aryl halide in situ would be expected
to provide an efficient approach to N-aryl amides from sim-
ple reactants. Accordingly, several excellent studies on cop-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–E

B
Y. Qiao et al.
Paper
Synthesis
We set out to develop an efficient, air-tolerant, and eco-
nomical copper-catalyzed procedure for the preparation of
N-aryl amides by a combination of potassium tert-butoxide
mediated hydrolysis of nitriles and subsequent coupling
with arylboronic acids. In this sequential hydrolysis/cou-
pling method, a wide variety of arylboronic acids and ni-
triles were well tolerated and successfully afforded the cor-
responding N-aryl amides in good to excellent yields in air.
Initially, we chose phenylboronic acid (1a) and benzoni-
trile (2a) as model substrates to investigate the reaction pa-
rameters. As shown in Table 1, we first performed the reac-
tion in the presence of Cu(OAc)2 and t-BuOK in tert-butyl
alcohol in air at room temperature. Gratifyingly, the desired
N-phenylbenzamide (3aa) was successfully isolated in 61%
yield (entry 1). Further screening of the solvents indicated
that THF, DMSO, and DMF were completely ineffective for
this transformation (entries 2–4). When the solvent was
changed to i-PrOH, a decreased yield (42%) was obtained
(entry 5). To our surprise, none of the desired product was
formed in EtOH (entry 6). However, when bulky neopentyl
alcohol was used as a solvent, a 49% yield of N-phenyl-
benzamide (3aa) was isolated (entry 7). This indicated that
steric hindrance of the alkyl group in the alcohol has a
marked effect on the formation of the desired product and
that t-BuOH is the optimal solvent. Next, we examined the
catalytic performance of various copper species, including
CuI, CuBr, CuCl, Cu powder, CuO, CuBr2, CuCl2, and Cu(OTf)2
(entries 8–15). CuBr2 showed the best catalytic ability and
finally improved the yield to 90%. When the reaction was
performed under the optimal conditions in argon, only
benzamide was formed and no N-phenylbenzamide was
produced, confirming that oxygen in air as an oxidant was
essential for the Chan–Lam process in the current strategy.
Having identified the optimal reaction conditions (Table
1, entry 13), we next investigated the substrate scope of the
copper-catalyzed tandem hydrolysis/coupling reaction.
First, the reactions of various arylboronic acids with benzo-
nitrile were examined, and the results are summarized in
Table 2. Arylboronic acids bearing either electron-with-
drawing or electron-donating groups smoothly underwent
the sequential transformation to give the corresponding N-
aryl amides in moderate to excellent yields. Arylboronic
acids with ortho-substituents showed a lower reactivity
than the corresponding para-substituted compounds (Table
2; entry 2 versus entry 3; entry 5 versus entry 7). Further-
more, when the sterically hindered arylboronic acids 1-
naphthylboronic acid, 9-phenanthrylboronic acid, and mes-
itylboronic acid were subjected to this transformation, all
successfully gave the corresponding products (entries 11,
12 , and 4); however, the most hindered reactant, mesityl-
boronic acid, gave the corresponding product 3da in only
25% yield, indicating that steric hindrance has a marked ef-
fect on this reaction. For the halo-substituted arylboronic
acids (4-chlorophenyl)boronic acid and (4-fluorophe-
nyl)boronic acid, the corresponding products 3ia and 3ja
Table 1 Optimization of the Reaction Conditionsa
O
[Cu], KOtBu
CN
B(OH)2
+
NH
solvent, r.t., 20 h
1a
2a
3aa
Entry
[Cu]
Solvent
Yieldb (%)
1
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
CuI
t-BuOH
THF
61
2
n.r.c
n.r.c
n.r.c
42
3
DMSO
4
DMF
5
i-PrOH
EtOH
6
n.d.d
49
7
t-BuCH2OH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
8
51
9
CuBr
73
10
11
12
13
14
15
16e
CuCl
69
Cu powder
CuO
50
30
CuBr2
90
CuCl2
76
Cu(OTf)2
CuBr2
68
n.d.d
a Reaction conditions: 1a (0.6 mmol), 2a (0.5 mmol), [Cu] (5.0 mol%),
t-BuOK (3.0 equiv), solvent (3 mL), 20 h, r.t., air.
b Isolated yield.
c No reaction.
d Not determined.
e The reaction was performed under argon.
were obtained in excellent yields of 88% and 85%, respec-
tively (entries 8 and 9). Note that the incorporation of halo
substituents in N-aryl amides has great significance be-
cause the products can be easily derivatized by means of
simple coupling strategies or the like.
Phenylboronic acid was next selected as a coupling part-
ner to react with various nitriles to examine the reaction
scope (Table 3). Substituted benzonitriles with either elec-
tron-withdrawing or electron-donating groups successfully
underwent the transformation to give the corresponding N-
aryl amides in moderate to excellent yields. Benzonitriles
with para-substituents such as methyl, methoxy, fluoro,
bromo, or iodo were well tolerated, and all smoothly fur-
nished the desired products (Table 3, entries 1–5). Sterically
hindered 2-bromobenzonitrile and 2,6-dimethylbenzoni-
trile afforded the corresponding amides 3ag and 3ah in
yields of 83% and 30%, respectively (entries 6 and 7). The
heteroaromatic nitriles 4-cyanopyridine and 2-cyanopyra-
zine also underwent the transformation, affording the cor-
responding N-substituted amides 3aj and 3ak in good
yields (entries 9 and 10). When isophthalonitrile was used,
the monohydrolysis/coupling product 3al was obtained in
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–E

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Y. Qiao et al.
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Synthesis
Table 2 Reactions of Arylboronic Acids with Benzonitrile
ciency and a wide functional-group tolerance. All halo sub-
stituents are well tolerated. The transformations is also
highly economical, as it can be carried out effectively in air
at room temperature in the presence of only catalytic
amounts of CuBr2 and t-BuOK, without the use of expensive
ligands, oxidants, or other additives.
O
CuBr2, KOtBu
tBuOH, r.t.
CN
Ar B(OH)2
+
Ar NH
1
3
2a
Entry
Ar
Ph
Product
Time (h)
Yield (%)
1
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
20
20
20
38
20
20
20
20
20
26
26
20
90
84
59
25
75
72
52
88
85
65
45
40
Commercially available reagents were used directly without further
purification. t-BuOH was freshly distilled before use. Melting points
were recorded on a Beijing Tech X-5 instrument and are uncorrected.
Column chromatography was performed on silica gel (particle size
2
4-MeC6H4
2-MeC6H4
Mes
3
1
4
10–40 μm; Ocean Chemical Factory, Qingdao). H NMR spectra were
recorded on Bruker 300M and 400M instruments at r.t. with CDCl3 or
DMSO-d6 as the solvent.
5
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
4-ClC6H4
4-FC6H4
6
7
Amides 3aa–la and 3ab–am; General Procedure
8
A 10 mL round-bottomed flask was charged with the appropriate ni-
trile 2 (0.50 mmol), arylboronic acid 1 (0.60 mmol), CuBr2 (6 mg, 5
mol%), t-BuOK (168 mg, 1.50 mmol), and t-BuOH (3.0 mL), and the
mixture was stirred at r.t. until the reaction was complete (TLC). H2O
(4.0 mL) was added, and the mixture was extracted with EtOAc (3 ×
10 mL). The combined organic layers were washed twice with H2O,
dried (Na2SO4), and concentrated to give a residue that was purified
by column chromatography (silica gel, PE–EtOAc).
9
10
11
12
4-F3CC6H4
1-naphthyl
3ja
3ka
3la
9-phenanthryl
N-Phenylbenzamide (3aa)11
White solid; yield: 89 mg (90%); mp 159.2–160.9 °C (Lit.24 159–161 °C).
Table 3 Reactions of Nitriles with Phenylboronic Acid
O
NH
3
1H NMR (400 MHz, CDCl3): δ = 7.88–7.85 (m, 3 H), 7.64 (d, J = 7.6 Hz, 2
H), 7.58–7.50 (m, 1 H), 7.49–7.46 (m, 2 H), 7.38 (t, J = 7.6 Hz, 2 H), 7.15
(t, J = 7.4 Hz, 1 H).
CuBr2, KOtBu
R
B(OH)2
R
CN
+
tBuOH, r.t.
2
1a
N-(4-Tolyl)benzamide (3ba)13
White solid; yield: 89 mg (84%); mp 155.0–156.2 °C (Lit.25 155–156 °C).
Entry
R
Product
Time (h)
Yield (%)
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 7.6 Hz, 3 H), 7.52 (d, J = 7.9
Hz, 3 H), 7.49–7.46 (m, 2 H), 7.16 (d, J = 8.1 Hz, 2 H), 2.30 (s, 3 H).
1
4-MeC6H4
4-MeOC6H4
4-FC6H4
3ab
3ac
3ad
3ae
3af
24
24
28
28
28
35
30
28
37
37
24
35
81
82
64
65
61
83
30
72
73
56
69
79
2
3
N-(2-Tolyl)benzamide (3ca)14
White solid; yield: 62 mg (59%); mp 142.1–143.5 °C (Lit.26 142–144 °C).
1H NMR (400 MHz, CDCl3): δ = 7.97 (s, 1 H), 7.85 (d, J = 7.3 Hz, 2 H),
7.54–7.50 (m, 3 H), 7.44 (t, J = 7.5 Hz, 2 H), 7.15 (d, J = 8.3 Hz, 2 H),
2.34 (s, 3 H).
4
4-BrC6H4
4-IC6H4
5
6
2-BrC6H4
3ag
3ah
3ai
7
2,6-Me2C6H3
3-F3CC6H4
4-pyridyl
pyrazin-2-yl
3-NCC6H4
Me
8
N-Mesitylbenzamide (3da)15
White solid; yield: 30 mg (25%); mp 198.8–200.2 °C (Lit.27 202–204 °C).
1H NMR (400 MHz, CDCl3): δ = 7.94–7.90 (m, 2 H), 7.57–7.54 (m, 1 H),
7.52–7.49 (m, 2 H), 7.31 (s, 1 H), 6.94 (s, 2 H), 2.30 (s, 3 H), 2.25 (s, 6 H).
9
3aj
10
11
12
3ak
3al
3am
N-(4-Methoxyphenyl)benzamide (3ea)11
White solid; yield: 85 mg (75%); mp 151.5–152.3 °C (Lit.28 153–154 °C).
1H NMR (400 MHz, CDCl3): δ = 7.87–7.82 (m, 3 H), 7.55–7.52 (m, 3 H),
7.49–7.46 (m, 2 H), 6.90 (d, J = 8.6 Hz, 2 H), 3.81 (s, 3 H).
69% yield, and no dihydrolysis/coupling product was
formed (entry 11). The aliphatic nitrile acetonitrile reacted
smoothly with phenylboronic acid to give N-phenylacet-
amide (3am) in 79% yield.
In summary, we have developed a facile copper-cata-
lyzed ipso-amidation of arylboronic acids with nitriles to
give N-aryl amides. The current strategy shows a high effi-
N-(3-Methoxyphenyl)benzamide (3fa)16
White solid; yield: 82 mg (72%); mp 105.3–106.1 °C (Lit.29 103–104 °C).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–E

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Y. Qiao et al.
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Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.98 (s, 1 H), 7.84 (dd, J = 1.48, 3.2 Hz, 2
H), 7.53–7.48 (m, 1 H), 7.48–7.43 (m, 3 H), 7.24–7.21 (m, 1 H), 6.72–
6.71 (m, 1 H), 6.47–6.42 (m, 1 H), 3.80 (s, 3 H).
1H NMR (400 MHz, DMSO-d6): δ = 10.26 (s, 1 H), 8.05–8.01 (m, 2 H),
7.76 (d, J = 7.9 Hz, 2 H), 7.39–7.32 (m, 4 H), 7.10 (t, J = 7.4 Hz, 1 H).
4-Bromo-N-phenylbenzamide (3ae)17
White solid; yield: 89 mg (65%); mp 202.5–203.5 °C (Lit.19 202–204 °C).
1H NMR (400 MHz, CDCl3): δ = 7.80 (s, 1 H), 7.74 (d, J = 8.5 Hz, 2 H),
7.62 (d, J = 8.4 Hz, 4 H), 7.38 (t, J = 8.3 Hz, 2 H), 7.19–7.15 (m, 1 H).
N-(2-Methoxyphenyl)benzamide (3ga)16
White solid; yield: 59 mg (52%); mp 59.5–60.1 °C (Lit.29 60–61 °C).
1H NMR (400 MHz, DMSO-d6): δ = 9.43 (s, 1 H), 7.97 (d, J = 7.4 Hz, 2
H), 7.79 (d, J = 7.7 Hz, 1 H), 7.60–7.57 (m, 1 H), 7.55–7.50 (m, 2 H),
7.19 (t, J = 7.5 Hz, 1 H), 7.10 (d, J = 8.0 Hz, 1 H), 6.97 (t, J = 7.5 Hz, 1 H),
3.84 (s, 3 H).
4-Iodo-N-phenylbenzamide (3af)11
White solid; yield: 99 mg (61%); mp 205.5–207.0 °C.
1H NMR (400 MHz, DMSO-d6): δ = 10.29 (s, 1 H), 7.94–7.90 (m, 2 H),
7.77–7.73 (m, 4 H), 7.35 (t, J = 7.9 Hz, 2 H), 7.10 (t, J = 7.4 Hz, 1 H).
N-(4-Chlorophenyl)benzamide (3ha)17
White solid; yield: 102 mg (88%); mp 192.8–193.4 °C (Lit.30 192–193
°C).
2-Bromo-N-phenylbenzamide (3ag)19
White solid; yield: 114 mg (83%); mp 120.4–121.0 °C (Lit.19 122–123
1H NMR (400 MHz, DMSO-d6): δ = 10.38 (s, 1 H), 7.94 (d, J = 7.4 Hz, 2
H), 7.82 (d, J = 8.7 Hz, 2 H), 7.61–7.58 (m, 1 H), 7.56–7.51 (m, 2 H),
7.41 (d, J = 8.7 Hz, 2 H).
°C).
1H NMR (400 MHz, CDCl3): δ = 10.47 (s, 1 H), 7.72 (d, J = 8.2 Hz, 3 H),
7.57–7.54 (m, 1 H), 7.52–7.47 (m, 1 H), 7.44– 7.40 (m, 1 H), 7.37–7.32
(m, 2 H), 7.10 (t, J = 7.4 Hz, 1 H).
N-(4-Fluorophenyl)benzamide (3ia)11
White solid; yield: 91 mg (85%); mp 184.6–185.6 °C (Lit.31 184–185 °C).
1H NMR (400 MHz, CDCl3): δ = 7.90–7.86 (m, 2 H), 7.80 (s, 1 H), 7.64–
7.58 (m, 2 H), 7.56 (d, J = 7.3 Hz, 1 H), 7.52–7.49 (m, 2 H), 7.09 (t, J =
8.6 Hz, 2 H).
2,6-Dimethyl-N-phenylbenzamide (3ah)20
White solid; yield: 34 mg (30%); mp 127.4–128.2 °C.
1H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 7.6 Hz, 2 H), 7.39 (t, J = 7.9
Hz, 2 H), 7.32 (s, 1 H), 7.24–7.15 (m, 2 H), 7.08 (d, J = 7.6 Hz, 2 H), 2.40
(s, 6 H).
N-[(4-Trifluoromethyl)phenyl]benzamide (3ja)16
White solid; yield: 86 mg (65%); mp 204.5–205.5 °C (Lit.32 205–206 °C).
1H NMR (400 MHz, CDCl3): δ = 8.18 (s, 1 H), 8.13 (d, J = 7.9 Hz, 1 H),
8.04 (s, 1 H), 7.82 (d, J = 7.6 Hz, 1 H), 7.65–7.60 (m, 3 H), 7.38 (t, J = 7.4
Hz, 2 H), 7.19 (t, J = 7.4 Hz, 1 H).
N-Phenyl-3-(trifluoromethyl)benzamide (3ai)21
White solid; yield: 95 mg (72%); mp 149.7–150.5 °C.
1H NMR (400 MHz, DMSO-d6): δ = 10.48 (s, 1 H), 8.29–8.25 (m, 2 H),
7.96 (d, J = 7.8 Hz, 1 H), 7.79–7.76 (m, 3 H), 7.37 (t, J = 7.9 Hz, 2 H),
7.13 (t, J = 7.4 Hz, 1 H).
N-1-Naphthylbenzamide (3ka)13
White solid; yield: 56 mg (45%); mp 157.2–158.7 °C Lit.4b 159–160 °C.
1H NMR (400 MHz, DMSO-d6): δ = 10.46 (s, 1 H), 8.10 (d, J = 7.2 Hz, 2
H), 8.01–7.97 (m, 2 H), 7.88 (d, J = 7.9 Hz, 1 H), 7.64–7.54 (m, 7 H).
N-Phenylisonicotinamide (3aj)22
White solid; yield: 72 mg (73%); mp 169.5–170.5 °C (Lit.35 169–171 °C).
1H NMR (400 MHz, CDCl3): δ = 8.76 (s, 2 H), 8.18–8.07 (m, 1 H), 7.70
(s, 2 H), 7.63 (d, J = 8.0 Hz, 2 H), 7.41–7.35 (m, 2 H), 7.19 (t, J = 7.5 Hz,
1 H).
N-9-Phenanthrylbenzamide (3la)18
White solid; yield: 59 mg (40%); mp 197.5–198.6 °C (Lit.33 199–201 °C).
1H NMR (400 MHz, DMSO-d6): δ = 10.52 (s, 1 H), 8.92 (d, J = 8.1 Hz, 1
H), 8.86 (d, J = 7.9 Hz, 1 H), 8.15–8.08 (m, 3 H), 8.02 (d, J = 7.6 Hz, 1 H),
7.97 (s, 1 H), 7.78–7.57 (m, 7 H).
N-Phenylpyrazine-2-carboxamide (3ak)23
White solid; yield: 56 mg (56%); mp 127.5–128.0 °C (Lit.36 128–130 °C).
1H NMR (400 MHz, CDCl3): δ = 9.67 (s, 1 H), 9.52 (d, J = 1.4 Hz, 1 H),
8.81 (d, J = 2.5 Hz, 1 H), 8.60–8.58 (m, 1 H), 7.76 (d, J = 7.9 Hz, 2 H),
7.40 (t, J = 7.9 Hz, 2 H), 7.19 (t, J = 7.5 Hz, 1 H).
4-Methyl-N-phenylbenzamide (3ab)13
White solid; yield: 85 mg (81%); mp 143.5–144.5 °C (Lit.19 143–144 °C).
1H NMR (400 MHz, CDCl3): δ = 7.88 (s, 1 H), 7.77 (d, J = 8.2 Hz, 2 H),
7.64 (d, J = 7.9 Hz, 2 H), 7.36 (t, J = 7.9 Hz, 2 H), 7.28–7.25 (m, 2 H),
7.14 (t, J = 7.4 Hz, 1 H), 2.42 (s, 3 H).
3-Cyano-N-phenylbenzamide (3al)21
White solid; yield: 77 mg (69%); mp 172.5–173.4 °C.
1H NMR (400 MHz, DMSO-d6): δ = 10.42 (s, 1 H), 8.40 (s, 1 H), 8.25 (d,
J = 7.9 Hz, 1 H), 8.07 (d, J = 7.7 Hz, 1 H), 7.78–7.73 (m, 3 H), 7.38 (t, J =
7.9 Hz, 2 H), 7.13 (t, J = 7.4 Hz, 1 H).
4-Methoxy-N-phenylbenzamide (3ac)11
White solid; yield: 93 mg (82%); mp 165.8–166.4 °C (Lit.34 168–170 °C).
1H NMR (400 MHz, CDCl3): δ = 7.84 (d, J = 8.7 Hz, 2 H), 7.77 (s, 1 H),
7.63 (d, J = 7.8 Hz, 2 H), 7.36 (t, J = 7.8 Hz, 2 H), 7.14 (t, J = 7.4 Hz, 1 H),
6.97 (d, J = 8.5 Hz, 2 H), 3.87 (s, 3 H).
N-Phenylacetamide (3am)11
White solid; yield: 53 mg (79%); mp 113.8–114.6 °C (Lit.37 113–114 °C).
1H NMR (300 MHz, CDCl3): δ = 7.49 (d, J = 7.9 Hz, 2 H), 7.34–7.28 (m, 3
H), 7.09 (t, J = 7.3 Hz, 1 H), 2.17 (s, 3 H).
4-Fluoro-N-phenylbenzamide (3ad)11
White solid; yield: 69 mg (64%); mp 179.2–180.1 °C (Lit.19 180–181 °C).
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Synthesis
Acknowledgment
(9) (a) Chan, D. M. T.; Kevin, L. M.; Wang, R.-P.; Michael, P. W. Tetra-
hedron Lett. 1998, 39, 2933. (b) Evans, D. A.; Katz, J. L.; West, T. R.
Tetrahedron Lett. 1998, 39, 2937. (c) Lam, P. Y. S.; Charles, C. G.;
Saubern, S.; Adams, J.; Winters, M. P. W.; Chan, D. M. T.; Combs,
A. Tetrahedron Lett. 1998, 39, 2941.
We are grateful for financial support from the National Natural Sci-
ence Foundation of China (21302117 and 21572123) and from Funda-
mental Research Funds for the Central Universities (GK201603047
and GK201601003).
(10) Prakash, G. K. S.; Moran, M. D.; Mathew, T.; Olah, G. A. J. Fluorine
Chem. 2009, 130, 806.
(11) Huang, H.; Jiang, Z.-T.; Wu, Y.; Gan, C.-Y.; Li, J.-M.; Xiang, S.-K.;
Feng, C.; Wang, B.-Q.; Tang, W.-T. Synlett 2016, 27, 951.
(12) Midya, G. C.; Kapat, A.; Maiti, S.; Dash, J. J. Org. Chem. 2015, 80,
4148.
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(15) Liu, Z.; Zhang, X.; Li, J.; Li, F.; Li, F.; Jia, X.; Li, J. Org. Lett. 2016, 18,
4052.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588373.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–E