A general and efficient CuBr2-catalyzed N-arylation of secondary acyclic amides

Article abstract of DOI:10.1002/cjoc.201200701

A general and efficient Cu(II)-catalyzed cross-coupling method is reported for the preparation of acyclic tertiary amides. Generally moderate to excellent yields and functional group tolerance were obtained with secondary acyclic amides and aryl halides as substrates in toluene. A general and efficient Cu(II)-catalyzed cross-coupling method is reported for the preparation of acyclic tertiary amides. Generally moderate to excellent yields and functional group tolerance were obtained with secondary acyclic amides and aryl halides as substrates in toluene. Copyright

Full text of DOI:10.1002/cjoc.201200701

FULL PAPER
DOI: 10.1002/cjoc.201200701
A General and Efficient CuBr2-Catalyzed N-Arylation of Sec-
ondary Acyclic Amides
Wang, Mangang(王满刚)
Wu, Jun*(吴军)
Yu, Hua(于华)
You, Xinwen(尤心稳)
Shang, Zhicai*(商志才)
Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027, China
A general and efficient Cu(II)-catalyzed cross-coupling method is reported for the preparation of acyclic tertiary
amides. Generally moderate to excellent yields and functional group tolerance were obtained with secondary acyclic
amides and aryl halides as substrates in toluene.
Keywords copper, N-arylation, cross-coupling, amides, aryl halides
Introduction
though, general methods are still needed for the prepa-
ration of tertiary amides, particularly because tertiary
aryl amides, the primary products described in this pa-
per, are found in a variety of biologically active mole-
cules and intermediates in total synthesis.[10] In addition,
access to tertiary amides via intermolecular N-arylation
of secondary amides under mild and efficient conditions
would not only allow the transformation in an eco-
nomical and ecological way, but also facilitate the
structure-activity relationship studies of these important
targets in life sciences. Herein, we reported a copper(II)-
catalyzed general method for access to tertiary amides
via intermolecular N-arylation of acyclic secondary
amides.
Transition-metal-catalyzed cross-coupling reactions
of aryl halides with various nucleophilic compounds are
now among the most prominent synthetic methods for
the formation of C—N, C—O, and C—S bonds in the
preparation of numerous important products in the fields
of biological, pharmaceutical, and material sciences.[1]
However, the Goldberg reaction,[2] the copper-catalyzed
N-arylation of amides, usually requires drastic reaction
conditions, for example, stoichiometric amounts of
copper salts, high temperatures (＞150 ℃), and polar
solvents such as DMF, collidine, and pyridine. In the
past few years, a wide range of ligands,[3] including
diamines,[4] diimines,[5] amino acids,[6] β-keto esters,[7]
and ethylene glycol,[8] have been exploited for these
catalytic processes in the presence of catalytic amounts
of the palladium or copper catalyst. Although these
processes display increased activity and substrate scope
relative to their predecessors, a significant limitation to
this process is that they are mostly restricted to primary
amides or lactams. The large size of acyclic secondary
amides,[9] combined with their relatively low nucleo-
philicity (compared to amines), has made secondary
amides a particularly challenging substrate class for
cross-coupling.[10] For secondary acyclic amides, only
few isolated examples involving either palladium or
copper as catalysts have been described until re-
cently.[3d,9,11] In an important advance, Buchwald et
al.[10] developed the Pd-catalyzed coupling of secondary
acyclic amides with aryl halides and related electro-
philes Another modern variant of the Goldberg reaction
for the coupling of acyclic secondary amides has been
recently developed with CuI and 2,2,6,6-tetramethyl-
3,5-heptadione (TMHD) as catalysis system.[12] Even
Results and Discussion
Initially, N-p-tolylbenzamide (1a) and iodobenzene
(2a) were selected as the model substrates in search of a
better protocol. After many trials and errors, we were
pleased to find that the reaction of N-p-tolylbenzamide
1a with iodobenzene 2a in xylene at 130 ℃ afforded
the desired product, N-phenyl-N-p-tolylbenzamide (3a),
in 75% yield with CuI as the catalyst (Entry 4, Table 1).
However, we found that CuBr2 was more effective than
CuI when xylene was used as solvent. The better yield
(96%) of 3a was obtained when toluene was used as
solvent rather than xylene. After screening the amounts
of base and CuBr2, it was observed that 2 equiv. of base
and 0.1 equiv. of CuBr2 are the best (Entries 6—10, Ta-
ble 1). Other bases or ligands led to a low yield or no
reaction at all (Entries 12—14, Table 1). The reaction
was not sensitive to aerobic conditions, conducting the
reaction under air atmosphere (94% yield, Entry 11,
Table 1) maintaining the same level of efficiency; CuBr2
*
E-mail: shangzc@zju.edu.cn; Fax: 0086-0571-87951895
Received July 9, 2012; accepted August 28, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200701 or from the author.
2356
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A General and Efficient CuBr2-Catalyzed N-Arylation of Secondary Acyclic Amides
exhibited superior catalytical efficiency over all other
examined Cu catalysts (Entries 15, 16, Table 1). Thus, we
defined the reaction of secondary amides with 1.2 equiv.
of aryl halides in the presence of 10 mol% of CuBr2 and
20 mol% DMEDA in toluene at 130 ℃ for 24 h as the
standard reaction conditions (Entry 8, Table 1).
N-arylation of N-p-tolylbenzamide (Entry 1, Table 2)
was observed by using our protocol, whereas N-alkyl-
benzamide (Entry 10, Table 2) gives a poor yield. By
using the optimized conditions, the simplest benzamide
can be converted into the corresponding N,N-disubsti-
tuted benzamide under a one-pot way with 2 equiv. of
2a (Entry 11, Table 2). However, the sterically hindered
coupling partners failed to give the desired products
(Entry 12, Table 2).
Table 1 Optimization of reaction conditionsa
Ph
O
NH
O
Ph
Cu , Ligand
Table 2 Amination of iodobenzenea
H3C
N
+
PhI
H3C
Base, solvent
Ph
2a
O
CuBr2 (10 mol%)
DMEDA (20 mol%)
3a
O
1a
R
R
+
PhI
Ph
N
Ph
N
Entry Catalyst (mol%) Ligandb Base
Solvent Yieldc/%
H
Toluene, Cs2CO3
130 oC
2a
Ph
3
1
1
2
CuI (10)
CuI (10)
TMEDA K3PO4
DMEDA KOH
DMEDA KOH
DMEDA Cs2CO3
DMEDA Cs2CO3
DMEDA Cs2CO3
DMEDA Cs2CO3
DMF
DMF
0
0
Entry
R
Product
3a
Yieldb/%
91 (52)[12]
96 (95)[12]
42 (48)[12]
51 (82)[12]
88 (92)[12]
86 (76)[12]
33 (23)[12]
98
3
CuI (10)
Xylene
Xylene
Xylene
Xylene
Xylene
0
1
2
4-MeC6H4
C6H5
4
CuI (10)
75
80
80d
91
96
78e
69
94
71
0
3b
3c
5
CuBr2 (10)
CuBr2 (20)
CuBr2 (20)
CuBr2 (10)
CuBr2 (10)
CuBr2 (5)
CuBr2 (10)
CuBr2 (10)
6
3
4-MeOC6H4
4-BrC6H4
4-NO2C6H4
4-FC6H4
2-ClC6H4
2-Naphthyl
4-ClC6H4
PhCH2
7
4
3d
3e
8
DMEDA Cs2CO3 Toluene
DMEDA Cs2CO3 Toluene
DMEDA Cs2CO3 Toluene
DMEDA Cs2CO3 Toluene (air)
5
9
6
3f
10
11
12
13
14
15
16
7
3g
8
3h
3i
DMEDA K3PO4
Toluene
9
80
CuBr2 (10) L-proline Cs2CO3 Toluene
10
11c
12d
38 (71)[12]
3j
CuBr2 (10)
CuO (10)
CuCl (10)
TMEDA Cs2CO3 Toluene
DMEDA Cs2CO3 Toluene
DMEDA Cs2CO3 Toluene
0
H
79
3a
19
77
H
—
0
a
a 1 (0.5 mmol), 2a (0.6 mmol), Cs2CO3 (2 equiv.) and catalyst (10
mol%) in 2 mL of solvent at 130 ℃ for 24 h under N2. b Isolated
yields. Using 1.2 mmol of 2a for 30 h. Using 1.2 mmol of
methyl 2-iodobenzoate as electrophiles for 30 h, and the main
product is methyl 2-(benzamido)benzoate.
1a (0.5 mmol), 2a (0.6 mmol), base (2 equiv.) and catalyst in 2
mL of solvent at 130 ℃ for 24 h under N2. b n(Cu)∶n(ligand)＝
1 ∶ 2; TMEDA ＝ N,N,N',N'-tetramethylethylenediamine;
DMEDA＝N,N'-dimethylethanediamine. Isolated yields. At
120 ℃ for 24 h. e Reaction was carried out at 130 ℃ in the
presence of 1 equiv. of base for 12 h.
c
d
c
d
The coupling of electrophiles bearing different sub-
stituents with various secondary acyclic amides 2 was
investigated next under the optimized reaction condi-
tions (Table 3). In general, the substituted iodobenzene
and secondary acyclic amides could be successfully
used in this copper-mediated cross-coupling reaction to
give the desired products (Entries 1—10, Table 3).
Good isolated yields were obtained, except with starting
compounds derived from 4-chlorobenzoic acid (Entry 7,
Table 3). The steric ortho-substituted coupling parter
was also tolerated although with a lower yield compared
with para- and meta-substituted aryl halides (Entry 11,
Table 3). The cross-coupling reaction was also extended
to bromobenzene with secondary acyclic amides (En-
tries 12—16, Table 3). In contrast to the iodobenzene,
the coupling reaction of bromobenzene derivatives af-
forded corresponding tertiary amides with lower yields
under the same reaction conditions. Generally, electro-
philes with an election-withdrawing group showed
The scope of the copper-catalyzed amination was
examined by reacting iodobenzene (2a) with a variety of
N-arylbenzamide 1. As shown in Table 2, under the op-
timized conditions (10 mol% of CuBr2, 20 mol%
N,N'-dimethylethanediamine), the coupling of 2a with
secondary acyclic amides 1 appeared to be quite general
with respect to the substituents. Thus, N-arylbenzamides
bearing electron-donating and electron-withdrawing
groups were smoothly arylated to give N,N-disubstituted
benzamides 3a—3j in moderate to good yields. Elec-
tron-deficient substrates gave better yields. In the case
of the N-(2-chlorophenyl)benzamide, the low yield of
object product could be explained by the steric hin-
drance effect (Entry 7, Table 2). In general, compared to
the reported results (Entries 1—7, 10, Table 2), two
catalytic system maintaining the same level of effi-
ciency with various sources of N-substituted benzamide.
It is worth noting that a synthetically useful yield for the
Chin. J. Chem. 2012, 30, 2356—2362
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Wang et al.
FULL PAPER
Table 3 N-Arylation of secondary acyclic amidesa
O
CuBr2 (10 mol%)
DMEDA (20 mol%)
O
Ar
Ar
R'
N
+
Ar'X
R'
N
Toluene, Cs2CO3
130 oC
H
2
Ar'
1
3
Entry
Product
Yieldb/%
1
2
O
O
I
N
1
88
N
H
H3C
H3C
3k
CH3
O
CH3
I
O
N
2
96
81
42
82
59
N
H
H3C
H3C
3l
Br
O
Br
I
I
O
N
3
N
H
H3C
H3C
3m
F
O
F
O
N
4
5
N
H
Br
I
Br
3n
OCH3
O
OCH3
O
N
N
H
CH3
3o
CH3
OCH3
O
OCH3
I
O
N
6
N
H
Br
CH3
Br
CH3
3p
O
I
N
O
7
Cl
37
94
N
H
Cl
Br
I
Br
3q
O
CH3
O
N
8
N
H
CH3
Br
3r
Br
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Chin. J. Chem. 2012, 30, 2356—2362

A General and Efficient CuBr2-Catalyzed N-Arylation of Secondary Acyclic Amides
Continued
Yieldb/%
Entry
9
1
2
Product
O
N
I
O
O
O
64
90
N
H
Br
Br
3d
O
N
I
10
N
H
F
F
3s
O
I
COOCH3
N
11c
36
31
COOCH3
CH3
N
H
3t
O
CH3
Br
O
N
O
12
N
H
3a
Br
O
O
O
N
13
14
15
37
22
50
N
H
3b
H3C
Br
3a
N
H
O
Br
N
N
H
Cl
Cl
N
3i
O
Br
Cl
O
O
16
17
61
N
H
Cl
Cl
Cl
N
3u
O
Cl
n.r.d
N
H
a 1 (0.5 mmol), 2 (0.6 mmol), Cs2CO3 (2 equiv.) and catalyst (10 mol%) in 2 mL of solvent at 130 ℃ for 24 h under N2. b Isolated yields.
c Under air atmosphere at 130 ℃ for 24 h. d No reaction.
Chin. J. Chem. 2012, 30, 2356—2362
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Wang et al.
FULL PAPER
higher reactivity than those with electron-donating
groups. It is worth noting that the corresponding product
was not observed when chlorobenzene was employed
(Entry 17, Table 3).
NMR (CDCl3, 500 MHz) δ: 7.04 (d, J＝8.6 Hz, 2H);
7.10 (d, J＝7.6 Hz, 2H), 7.20 (dt, J＝17.8, 7.6 Hz, 3H),
7.24—7.33 (m, 3H), 7.41 (d, J＝8.7 Hz, 2H), 7.42—
7.47 (m, 2H); 13C NMR (CDCl3, 126 MHz) δ: 126.2,
127.5, 128.5, 129.1, 129.4, 133.1, 140.5, 144.2, 170.7;
HRMS calcd for C19H14BrNO 351.0259, found
351.0264.
Conclusions
N-(4-Nitrophenyl)-N-phenylbenzamide (3e): 1H
NMR (CDCl3, 500 MHz) δ: 7.10 (d, J＝7.8 Hz, 2H),
7.20—7.28 (m, 3H), 7.32 (td, J＝9.4, 4.9 Hz, 5H), 7.46
(d, J＝7.5 Hz, 2H), 8.16 (d, J＝9.0 Hz, 2H); 13C NMR
(CDCl3, 126 MHz) δ: 124.5, 126.6, 127.5, 128.2, 128.3,
129.2, 129.7, 131.0, 135.1, 142.9, 144.8, 149.6, 170.7;
HRMS calcd for C19H14N2O3 318.1004, found
318.1001.
In conclusion, we have developed a general and ef-
fective way to prepare acyclic tertiary amides, which
can be found in numerous biologically active com-
pounds, by a copper(II)-catalyzed cross-coupling reac-
tion of aryl halides with secondary acyclic amides and
the corresponding target products were obtained in
moderate to good yields. Thus, this copper(II)-catalyzed
protocol is potentially useful in the synthesis of some
biologically active molecules. Further investigations in
this direction are in progress.
N-(4-Fluorophenyl)-N-phenylbenzamide (3f): 1H
NMR (CDCl3, 500 MHz) δ: 6.99 (t, J＝8.5 Hz, 2H),
7.09—7.24 (m, 7H), 7.27 (dd, J＝13.8, 5.6 Hz, 3H),
7.44 (d, J＝7.4 Hz, 2H); 13C NMR (CDCl3, 126 MHz) δ:
115.9, 116.1, 126.5, 127.4, 127.9, 128.9, 129.0, 129.1,
129.2, 130.3, 135.9, 139.9, 140.0, 143.8, 159.8, 161.7,
170.6; HRMS calcd for C19H14FNO 291.1059, found
291.1064.
Experimental
General procedure for the N-arylation of secondary
acyclic amides
To a mixture of the amide (0.5 mmol), CuBr2 (12 mg,
0.05 mmol), Cs2CO3 (0.33 g, 1 mmol) and DMEDA
(0.1 mmol) in dry toluene (2 mL) in a sealed tube was
added the aryl halide (0.6 mmol, 1.2 equiv.) under a
nitrogen atmosphere or air atmosphere. The mixture was
allowed to stir electromagnetically in an oil bath at 130
℃ for 24 h. After cooling to room temperature, 10 mL
of H2O were added and extracted with ethyl acetate (20
mL×3). The combined organic phases were dried over
anhydrous sodium sulfate, filtered and concentrated.
The residue was purified by flash column chromatogra-
phy with ethyl acetate (EA) and petroleum ether (Pet) as
eluent to afford the corresponding products.
N-(2-Chlorophenyl)-N-phenylbenzamide (3g): 1H
NMR (CDCl3, 500 MHz) δ: 7.13 (t, J＝7.1 Hz, 3H),
7.17—7.34 (m, 8H), 7.40—7.47 (m, 1H), 7.52 (d, J＝
7.7 Hz, 2H); 13C NMR (CDCl3, 126 MHz) δ: 126.2,
126.3, 126.6, 127.9, 128.8, 129.0, 129.1, 129.2, 130.4,
130.6, 130.7, 132.7, 135.6, 141.1, 170.4; HRMS calcd
for C19H14ClNO 307.0764, found 307.0770.
N-(Naphthalen-1-yl)-N-phenylbenzamide (3h): 1H
NMR (CDCl3, 500 MHz) δ: 7.03—7.16 (m, 3H), 7.21 (d,
J＝4.1 Hz, 5H), 7.28 (d, J＝7.2 Hz, 1H), 7.34 (t, J＝7.6
Hz, 1H), 7.40—7.55 (m, 4H), 7.74 (d, J＝8.1 Hz, 1H),
7.83 (d, J＝7.8 Hz, 1H), 8.08 (d, J＝8.1 Hz, 1H); 13C
NMR (CDCl3, 126 MHz) δ: 123.1, 125.6, 125.9, 126.0,
126.3, 127.2, 127.8, 128.2, 128.6, 128.9, 130.2, 130.3,
134.7, 136.1, 139.9, 144.0, 171.2; HRMS calcd for
C23H17NO 323.1310, found 323.1316.
N-Phenyl-N-p-tolylbenzamide (3a): 1H NMR
(CDCl3, 500 MHz) δ: 2.32 (s, 3H), 7.06 (d, J＝8.2 Hz,
2H), 7.10 (d, J＝8.2 Hz, 2H), 7.15—7.25 (m, 5H),
7.26—7.32 (m, 3H), 7.45—7.51 (m, 2H); 13C NMR
(CDCl3, 126 MHz) δ: 21.0, 126.2, 127.3, 127.8, 129.0,
129.1, 129.8, 130.1, 136.2, 141.3, 144.0, 170.7; HRMS
calcd for C20H17NO 287.1310, found 287.1313.
N-(4-Chlorophenyl)-N-phenylbenzamide (3i): 1H
NMR (CDCl3, 400 MHz) δ: 7.06—7.14 (m, 4H), 7.15—
7.34 (m, 8H), 7.42—7.48 (m, 2H); 13C NMR (CDCl3,
100 MHz) δ: 126.5, 127.5, 127.9, 128.4, 129.0, 129.1,
129.2, 130.3, 131.7, 135.6, 142.3, 143.4, 170.5; HRMS
calcd for C19H14ClNO 307.0764, found 307.0766.
N-Benzyl-N-phenylbenzamide (3j): 1H NMR
(CDCl3, 500 MHz) δ: 5.13 (s, 2H), 6.88—6.93 (m, 2H),
7.05—7.10 (m, 1H), 7.10—7.18 (m, 4H), 7.18—7.36
(m, 8H); 13C NMR (CDCl3, 126 MHz) δ: 53.8, 126.6,
127.3, 127.6, 127.7, 128.4, 128.5, 128.8, 129.0, 129.1,
129.6, 136.0, 137.6, 143.6, 170.5; HRMS calcd for
C20H17NO 287.1310, found 287.1306.
N,N-Diphenylbenzamide (3b): 1H NMR (CDCl3, 500
MHz) δ: 7.12—7.23 (m, 8H), 7.28 (t, J＝7.9 Hz, 5H),
7.45 (dd, J＝5.2, 3.3 Hz, 2H); 13C NMR (CDCl3, 126
MHz) δ: 126.3, 127.5, 127.9, 129.1, 129.2, 130.2, 136.1,
143.9, 170.6; HRMS calcd for C19H15NO 273.1154,
found 273.1151.
1
N-(4-Methoxyphenyl)-N-phenylbenzamide (3c): H
NMR (CDCl3, 500 MHz) δ: 3.76 (s, 3H), 6.80 (d, J＝
8.8 Hz, 2H), 7.07 (d, J＝8.7 Hz, 2H), 7.15 (t, J＝7.4 Hz,
3H), 7.20 (dd, J＝10.4, 4.6 Hz, 2H), 7.26 (dd, J＝12.0,
4.5 Hz, 3H), 7.44 (dd, J＝5.2, 3.4 Hz, 2H); 13C NMR
(CDCl3, 126 MHz) δ: 55.4, 114.4, 126.1, 127.2, 127.9,
128.7, 129.0, 129.1, 130.0, 136.3, 136.8, 144.1, 157.9,
170.6; HRMS calcd for C20H17NO2 303.1259, found
303.1256.
4-Methyl-N,N-diphenylbenzamide (3k): 1H NMR
(CDCl3, 500 MHz) δ: 2.28 (s, 3H), 7.00 (d, J＝8.0 Hz,
2H), 7.12—7.20 (m, 6H), 7.28 (t, J＝7.8 Hz, 4H), 7.35
(d, J＝8.1 Hz, 2H); 13C NMR (CDCl3, 126 MHz) δ:
26.9, 119.8, 126.7, 127.6, 128.0, 128.8, 129.2, 129.3,
130.4, 132.2, 135.7, 143.0, 143.6, 170.5; HRMS calcd
N-(4-Bromophenyl)-N-phenylbenzamide (3d): 1H
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Chin. J. Chem. 2012, 30, 2356—2362

A General and Efficient CuBr2-Catalyzed N-Arylation of Secondary Acyclic Amides
for C20H17NO 287.1310, found 287.1320.
N-(3-Fluorophenyl)-N-phenylbenzamide (3s): 1H
4-Methyl-N-phenyl-N-p-tolylbenzamide (3l): 1H
NMR (CDCl3, 500 MHz) δ: 2.28 (s, 3H), 2.30 (s, 3H),
6.98—7.05 (m, 4H), 7.08 (d, J＝8.1 Hz, 2H), 7.15 (dd,
J＝15.9, 7.7 Hz, 3H), 7.27 (d, J＝8.1 Hz, 2H), 7.35 (d,
J＝8.1 Hz, 2H); 13C NMR (CDCl3, 126 MHz) δ: 21.0,
21.4, 126.0, 127.3, 128.5, 129.0, 129.3, 129.7, 133.2,
136.1, 140.4, 141.6, 144.3, 170.7; HRMS calcd for
C21H19NO 301.1467, found 301.1466.
NMR (CDCl3, 400 MHz) δ: 6.87—7.02 (m, 3H), 7.16 (d,
J＝7.6 Hz, 2H), 7.19—7.27 (m, 4H), 7.28—7.38 (m,
3H), 7.50 (d, J＝7.5 Hz, 2H); 13C NMR (CDCl3, 100
MHz) δ: 113.1, 113.3, 114.4, 114.6, 122.9, 126.7, 127.6,
127.9, 129.1, 129.3, 130.0, 130.1, 130.4, 135.6, 143.4,
145.2, 145.3, 161.5, 164.0, 170.5; HRMS calcd for
C19H14FNO 291.1059, found 291.1058.
Methyl 2-(N-phenylbenzamido)benzoate (3t): 1H
NMR (CDCl3, 500 MHz) δ: 3.80 (s, 3H), 7.02—7.36 (m,
10H), 7.47 (dd, J＝18.3, 7.4 Hz, 3H), 7.93 (s, 1H); 13C
NMR (CDCl3, 126 MHz) δ: 52.4, 126.2, 126.8, 127.5,
127.8, 128.9, 129.1, 130.1, 131.1, 132.9, 135.9, 143.2,
143.8, 166.4, 170.6; HRMS calcd for C21H17NO3
331.1208, found 331.1205.
N-(4-Bromophenyl)-4-methyl-N-phenylbenzamide
1
(3m): H NMR (CDCl3, 500 MHz) δ: 2.29 (s, 3H),
7.00—7.04 (m, 4H), 7.10 (d, J＝7.5 Hz, 2H), 7.18 (t,
J＝7.4 Hz, 1H), 7.28 (t, J＝7.7 Hz, 2H), 7.34 (d, J＝8.2
Hz, 2H), 7.38—7.43 (m, 2H); 13C NMR (CDCl3, 126
MHz) δ: 21.5, 119.6, 126.5, 127.6, 128.7, 128.8, 129.3,
129.4, 132.2, 132.7, 140.9, 143.2, 143.8, 170.6; HRMS
calcd for C20H16BrNO 365.0415, found 365.0415.
N-(3,4-Dichlorophenyl)-N-phenylbenzamide (3u):
1H NMR (CDCl3, 500 MHz) δ: 7.04 (dd, J＝8.6, 2.2 Hz,
1H), 7.08 (d, J＝7.7 Hz, 2H), 7.18—7.34 (m, 7H), 7.36
(d, J＝8.6 Hz, 1H), 7.44 (d, J＝7.3 Hz, 2H); 13C NMR
(CDCl3, 126 MHz) δ: 126.4, 127.0, 127.8, 128.1, 128.8,
129.2, 129.5, 130.2, 130.6, 130.7, 132.9, 135.3, 143.0,
143.2, 170.6; HRMS calcd for C19H13Cl2NO 341.0374,
found 341.0369.
N-(4-Bromophenyl)-N-(4-fluorophenyl)benzamide
1
(3n): H NMR (CDCl3, 400 MHz) δ: 6.96—7.06 (m,
4H), 7.11 (dd, J＝13.0, 8.3 Hz, 2H), 7.27 (d, J＝7.3 Hz,
2H), 7.34 (t, J＝7.4 Hz, 1H), 7.44 (t, J＝8.1 Hz, 4H);
13C NMR (CDCl3, 100 MHz) δ: 116.1, 116.3, 119.8,
128.0, 128.6, 128.8, 128.9, 129.0, 129.1, 130.5, 132.2,
135.3, 138.2, 139.3, 139.4, 142.7, 159.6, 162.0, 170.4;
HRMS calcd for C19H13BrFNO 369.0165, found
369.0162.
Acknowledgement
1
We gratefully thank the National Natural Science
Foundation of China (No. 31071720) for generous fi-
nancial support.
N-(4-Methoxyphenyl)-N-p-tolylbenzamide (3o): H
NMR (CDCl3, 400 MHz) δ: 2.31 (d, J＝4.0 Hz, 3H),
3.77 (s, 3H), 6.80 (d, J＝8.6 Hz, 2H), 7.06 (dd, J＝18.1,
7.9 Hz, 6H), 7.21 (dd, J＝8.0, 6.7 Hz, 2H), 7.24—7.31
(m, 1H), 7.45 (dd, J＝8.2, 1.1 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 20.9, 55.3, 114.2, 126.9, 127.7,
128.4, 128.8, 129.0, 129.6, 129.8, 135.9, 136.2, 136.8,
141.4, 157.6, 170.5; HRMS calcd for C21H19NO2
317.1416, found 317.1418.
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4-Bromo-N-(4-methoxyphenyl)-N-m-tolylbenzamide
1
(3p): H NMR (CDCl3, 500 MHz) δ: 2.27 (s, 3H), 3.76
(s, 3H), 6.80 (d, J＝8.5 Hz, 2H), 6.92 (d, J＝6.1 Hz,
1H), 6.95—7.02 (m, 2H), 7.05 (d, J＝8.4 Hz, 2H), 7.16
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127.7, 128.6, 129.0, 130.8, 131.1, 135.2, 136.6, 139.2,
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N-(4-Bromophenyl)-4-chloro-N-phenylbenzamide
(3q): 1H NMR (CDCl3, 500 MHz) δ: 7.03 (d, J＝8.4 Hz,
2H), 7.09 (d, J＝7.7 Hz, 2H), 7.21 (t, J＝8.1 Hz, 3H),
7.30 (t, J＝7.7 Hz, 2H), 7.38 (d, J＝8.5 Hz, 2H), 7.43 (d,
J＝8.6 Hz, 2H); 13C NMR (CDCl3, 126 MHz) δ: 120.0,
126.9, 127.5, 128.3, 128.7, 129.4, 130.6, 132.3, 134.0,
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NMR (CDCl3, 500 MHz) δ: 2.05 (s, 3H), 2.36 (s, 3H),
7.10 (ddd, J＝52.7, 31.4, 17.2 Hz, 6H), 7.52 (d, J＝99.2
Hz, 2H); 13C NMR (CDCl3, 126 MHz) δ: 21.1, 23.9,
127.7, 128.3, 130.6, 131.9, 137.9, 140.3, 170.5; HRMS
calcd for C15H14BrNO 303.0259, found 303.0263.
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2356—2362