Metal-free synthesis of amides by oxidative amidation of aldehydes with amines in PEG/oxidant system

Article abstract of DOI:10.1016/j.tet.2011.08.091

A simple, inexpensive, and efficient one-pot synthesis of amide derivatives were achieved in good to excellent yields via the directly oxidative amidation of aldehydes with amines under PEG/Oxidant system.

Full text of DOI:10.1016/j.tet.2011.08.091

Tetrahedron 67 (2011) 8532e8535
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Metal-free synthesis of amides by oxidative amidation of aldehydes with amines
in PEG/oxidant system
Jun Liang, Jing Lv, Zhi-cai Shang *
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 April 2011
Received in revised form 26 August 2011
Accepted 30 August 2011
Available online 3 September 2011
A simple, inexpensive, and efficient one-pot synthesis of amide derivatives were achieved in good to
excellent yields via the directly oxidative amidation of aldehydes with amines under PEG/Oxidant
system.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Aldehyde
Amine
PEG
Oxidant
Amides
1. Introduction
ruthenium under the assistance of oxidant like iodine and H
2 2
O ,
lanthanide and lithium metals as the catalyst for amidation of al-
1
2
The amides are one class of most common intermediates in
synthetic organic chemistry and biological chemistry. One of the
dehydes with amines, radical mediated oxidant NBS/AIBN or
1
13
oxone, etc., Metal-free oxidative protocol has been recently
14
most traditional methods for the preparation of amides is con-
densation of activated carboxylic acids with amines. However, the
application scope of this method is still limited by some flaws, such
as the demand on activated carboxylic acids, harsh conditions, and
tedious workup, etc.2 Therefore, development of facile, effective
and more economical methods for the synthesis of amide has been
attracting a great deal of attention. Various unconventional strat-
egies have been devised and displayed practical utilities in syn-
thesizing diverse amides. Typical examples including transition
achieved.
Poly(ethylene glycol) (PEG) and its monomethyl ethers are in-
expensive, thermally stable, recoverable and nontoxic media fre-
quently used in phase transfer catalysis. Developing efficient
catalyst systems, which utilizing PEG as reaction medium is highly
desirable in terms of environmental friendliness as well as atom
economics due to the unique advantages of PEG. As our continuous
endeavor in exploring practical PEG mediated synthesis, we wish
to describe herein the reaction of aldehydes with amines for direct
synthesis of amides in PEG/oxidant system. To the best of our
knowledge, there are no examples using PEG/oxidant system for
the direct oxidative amidation of aldehydes with amines is pres-
ently available (Scheme 1).
15
16
3
4
metal-catalyzed aminocarbonylation of aryl halides, nitriles, al-
dehydes,5 aldoximes,6 alcohols, alkenes, alkynes as well as the
Staudinger reaction using thioacids in the presence of azides. The
acid-promoted Schmidt reaction between ketones and alkyl azides
or hydrazoic acids have been also reported. Although effective
and significant results were obtained, the high cost of transition
metals greatly restricted the large scale application of these kinds of
methodologies.
7
8
9
1
0
11
O
O
Oxidant
PEG
R' NH2
+
R'
R
H
R
N
H
Considering the atom economics, a promising access to amides
is employing aldehyde and amine as starting materials via direct
oxidative amidation. Although this reaction was early declared to
proceed in the presence of transition metals such as palladium and
R, R'=Alkyl, Aryl
Scheme 1.
2
. Results and discussion
In our initial attempt, we chose the reaction of benzaldehyde
with aniline as the model reaction. Generally, a mixture of
*
Corresponding author. Fax: þ86 571 87951895; e-mail address: lxj2001101@
yahoo.com.cn (Z.-cai Shang).
0
040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.091

J. Liang et al. / Tetrahedron 67 (2011) 8532e8535
8533
benzaldehyde (1 mmol), aniline (1 mmol) has been vigorously
stirred at 120 C for 12 h in the presence of oxidant in different
Table 2 (continued )
ꢀ
Yieldb (%)
Entry
Aldehydes
Amines
media. The results on reaction condition optimization were shown
in Table 1, it can be found in these data that NaOCl is favored as the
best oxidant for this reaction by providing a yield of 90% 3a with the
6
7
8
9
CHO
Cl
NH2
NH2
70 (3f)
52 (3g)
83 (3h)
66 (3i)
4 4
assistance of Bu NHSO (entry 5, Table 1). The results obtained in
other conditions, such as different oxidants (entries 1e4 and 10e12,
Table 1) as well as other solvents (entries 6e9, Table 1) were all
evidently poorer. Further investigation on the effect of catalyst
CHO
CHO
CHO
O N
2
N
H
loading implied that 1.5 equiv of NaOCl/Bu
for optimal results.
4
NHSO
4
is most proper
NH2
Table 1
a
Oxidative amidation of benzaldehyde with aniline under different conditions
H N
CHO
NH2
2
10
11
CHO
45 (3j)
HN
oxidant
+
PEG-400
O
o
1
20 C, 12 h
77 (3k)
81 (3l)
CHO
CHO
CHO
HN
HN
1
a
2a
3a
Entry
Oxidant
SeO
MnO
Solvent
Yieldb (%)
1
1
2
3
1
2
3
4
5
6
7
8
9
2
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
55
46
0
2
I
Al
2
80 (3m)
2
O
3
/KF
12
90
68
49
42
31
57
61
39
NH2
NaOCl/Bu
NaOCl/Bu
NaOCl/Bu
NaOCl/Bu
NaOCl/Bu
4
4
4
4
4
NHSO
NHSO
NHSO
NHSO
NHSO
4
4
4
4
4
No
c
CH
CHCl
Toluene
3
CN
14
H3C
CHO
NH2
NH2
88 (3n)
74 (3o)
c
3
c
10
11
12
K
K
2
S
2
O
8
/Bu
4
NHSO
NHSO
4
4
PEG-400
PEG-400
PEG-400
15
H CO
CHO
3
2
SO
5
/Bu
4
2 2
H O /NBS
H3C
N
H3C
a
Reaction conditions: (1 mmol) benzaldehyde, (1 mmol) aniline, (1.5 equiv)
oxidants in 2g PEG-400 at 120 C.
16
CHO
76 (3p)
69 (3q)
NH2
NH2
ꢀ
b
Isolated yields after column chromatography.
Reaction in corresponding solvents (3 ml).
CH3
CHO
CH3
c
17
H C
3
Based on the optimized reaction conditions in hand, the scope
and generality of this PEG-400/NaOCl/Bu NHSO promoted ami-
4 4
dation was subsequently examined. A wide range of substituted
aromatic aldehydes with various amines were subjected for re-
action. The amidation results were shown in Table 2. In general,
1
8
9
Cl
CHO
NH2
NH2
93 (3r)
94 (3s)
1
O N
CHO
2
Table 2
Synthesis of various aldehydes and amines in PEG-400/NaOCl/Bu
4
NHSO
4
systema
Cl
O
20
21
NH2
93 (3t)
H
R1
R2
PEG-400
Cl
CHO
+
H
N
R3
N R1
R3
NaOCl / Bu NHSO
4 4
O
R2
NH2
N.R
CHO
Entry
Aldehydes
Amines
Yieldb (%)
OHC
2
2
NH2
Trace
1
2
CHO
CHO
NH2
90 (3a)
a
Reaction perform with (1 mmol) aldehydes, (1 mmol) amines, (1.5 equiv)
in 2 g PEG-400 at 120 C.
Isolated yields after column chromatography.
H3C
NH2
91 (3b)
89 (3c)
ꢀ
NaOCl/Bu
4
NHSO
4
b
CH3
3
4
CHO
CHO
aromatic aldehydes and aromatic/aliphatic were well tolerated in
this reaction system, while aliphatic aldehydes didn’t provide cor-
responding products under present conditions (entries 21 and 22,
Table 2). Based on the obtained results, the electronic effects and
the steric effects of the substituents both in amines and aldehydes
played significant role in the yields of products. Electron donating
group such as CH on the amine was able to facilitate the trans-
3
formation by giving evidently higher yield of products than the
entries using electron withdrawing groups functionalized anilines
NH2
CH3
NH2
81 (3d)
63 (3e)
CH3
NH2
5
CHO
NH2

8534
J. Liang et al. / Tetrahedron 67 (2011) 8532e8535
(
entries 2, 6, and 7, Table 2), while electron donating effect in ar-
2 4
dried over anhydrous Na SO , and filtered. After the solvents were
omatic aldehydes displayed remarkable hindering effect by leading
to lower yields of products than equivalent entries using electron
withdrawing aldehydes (entries 14e16 and 19, Table 2). One the
other hand, steric effects from both amines and aldehydes under-
mined the efficiency of corresponding reactions (entries 1, 3e5 and
evaporated, the crude product was purified by column chroma-
tography on silica gel using ethyl acetate/petroleum ether (9:1) as
the eluent to give corresponding amides in analytical purity.
ꢀ
1
4.2.1. Compound 3a: N-phenylbenzamide. Mp 164e165 C; H NMR
(CDCl , 500 MHz)
7.24 (t, J¼14.2 Hz, 2H), 7.53e7.59 (m, 3H),
7.66e7.71 (m, 3H), 7.98 (d, J¼7.2 Hz, 2H); C NMR (CDCl
120.2, 124.6, 126.7, 128.4, 128.8, 132.1, 134.6, 137.9, 165.4; IR (KBr)
1, 17, Table 2). Finally, in order to further demonstrate the wide
3
d
13
application scope of the present methodology, we investigated the
reactions using both aliphatic aldehydes and amines as starting
materials. While aliphatic aldehydes could not undergo the ami-
dation transformation as mentioned above, aliphatic amines of
different frameworks were successfully converted to corresponding
amides in moderate to good yields (entries 8e13, Table 2), and the
yields provided by aliphatic amines were generally inferior to their
aromatic counterparts.
According to the known literature and results obtained in our
experiments, a mechanism is proposed for this amidation reaction
as shown in Scheme 2. First, the imine intermediates 4 were formed
via the condensation of the aldehydes and amines. Subsequently, 4
was oxidized to give oxaziridine intermediates 5 in the presence of
oxidant. The tautomerization of 5 led to the final formation of
amide products.
3
, 125 MHz)
d
ꢂ1
3301, 1645, 1552, 1492, 1452, 1415, 727, 695 cm ; GCeMS: m/z, 197.
ꢀ
1
4.2.2. Compound 3b: N-p-tolylbenzamide. Mp 156e157 C. H NMR
(CDCl , 500 MHz)
2.35 (s, 3H), 7.20 (d, J¼8.7 Hz, 2H), 7.56e7.67 (m,
3
d
13
5H), 8.03 (d, J¼7.1 Hz, 2H); C NMR (CDCl
3
, 125 MHz) d 21.2, 121.5,
128.6, 128.8, 129.4, 132.2, 134.4, 135.3, 137.1, 165.2; IR (KBr) 3335,
ꢂ1
1652 cm ; GCeMS: m/z, 211.
ꢀ
1
4.2.3. Compound 3c: N-o-tolylbenzamide. Mp 143e145 C; H NMR
(CDCl , 500 MHz) 2.42 (s, 3H), 7.16e7.21 (m, 1H), 7.25e7.38 (m,
3
d
13
2H), 7.63e7.71 (m, 3H), 7.92 (d, J¼7.4 Hz, 2H), 10.04 (s, 1H); C NMR
(CDCl
3
,125 MHz)
d
17.6, 126.4, 126.2,126.8, 127.6, 128.8,130.7, 132.2,
ꢂ1
134.7, 134.9, 136.6, 164.9; IR (KBr) 3296, 1644 cm ; GCeMS: m/z,
211.
O
O
R'
R' NH2
R
N
4.2.4. Compound 3d: N-(2,6-dimethylphenyl)benzamide. Mp 157e
+
PEG
H
ꢀ
1
R
H
1
58 C; H NMR (CDCl
3
, 500 MHz)
d
2.29 (d, J¼7.5 Hz, 6H),
13
7.20e7.36 (m, 3H), 7.63e7.70 (m, 3H), 7.98 (m, 2H); C NMR (CDCl
3
,
[O]
125 MHz)
d
131.2,132.4,133.2,134.0, 137.2,139.7,140.6, 142.3, 165.7;
H
N
R
O
R'
R'
H
ꢂ1
N
IR (KBr) 3271, 1654 cm ; GCeMS: m/z, 225.
R
4
5
ꢀ
.2.5. Compound3e: N-(2-aminophenyl)benzamide. Mp 154e155 C;
4
1
Scheme 2. Proposed mechanism for the reaction oxidized by PEG/NaOCl/Bu
4
NHSO
4
3
H NMR (CDCl , 500 MHz) d 5.08 (s, 2H), 6.85e6.89 (m, 2H), 7.21 (t,
system.
J¼12.5 Hz, 1H), 7.36 (d, J¼9.5 Hz, 1H), 7.6e7.68 (m, 3H), 7.99 (s, 1H),
1
3
8
.12 (d, J¼9.5 Hz, 2H); C NMR (CDCl
3
,125 MHz) d 115.6,117.8,124.6,
3
. Conclusion
In summary, we have developed a green and efficient new ap-
proach for the synthesis of amides via direct oxidative amidation of
aldehydes and amines. The features of environmentally benign
solvent, cheap oxidant, wide range of reactant tolerance and sat-
isfactory product yields of our method should reasonably make it
a useful supplement for those known strategies.
127.7, 127.7, 128.4, 128.9, 132.1, 134.7, 145.6, 170.9; IR (KBr) 3271,
643 cm ; GCeMS: m/z, 212.
ꢂ1
1
ꢀ
4.2.6. Compound 3f: N-(4-chlorophenyl)benzamide. Mp 199e200 C;
1
H NMR (CDCl
J¼11.2 Hz, 2H), 7.85e7.48 (m, 5H); C NMR (CDCl
122.4, 127.8, 128.2, 128.8, 129.0, 133.2, 135.1, 137.9, 166.8; IR (KBr)
3
, 500 MHz)
d
7.45 (d, J¼11.2 Hz, 2H), 7.83 (d,
13
3
, 125 MHz)
d
ꢂ1
3348, 1654 cm ; GCeMS: m/z, 231.
ꢀ
4
.2.7. Compound 3g: N-(4-nitrophenyl)benzamide. Mp 198e199 C;
4
4
. Experimental
1
H NMR (CDCl
.24 (d, J¼15.0 Hz, 2H); C NMR (CDCl
27.9, 129.1, 132.7, 134.6, 143.9, 145.8, 167.2; IR (KBr) 3336,
3
, 500 MHz)
d
7.63e7.52 (m, 4H), 7.84e8.03 (m, 3H),
13
8
1
3
, 125 MHz) 120.2, 124.6,
d
.1. General
ꢂ1
1658 cm ; GCeMS: m/z, 242.
All chemicals were purchased from Aldrich. Mps were de-
termined on a WRR/X-4 digital mp apparatus and were not cor-
rected, NMR spectra were recorded on a Bruker Avance DMX
.2.8. Compound 3h: N, N-diethylbenzamide. Colorless, liquid; 1
4
H
NMR (CDCl
3
, 500 MHz)
d 1.29 (t, 3H), 1.34 (t, 3H), 3.35 (q, 2H), 3.57
1
13
5
00 MHz ( H, 500 MHz; C, 125 MHz) spectrometer in CDCl
3
using
13
(
q, 2H), 7.67e7.87 (m, 5H); C NMR (CDCl , 125 MHz) d 12.9, 13.9,
3
TMS as internal standard. Chemical shifts ( ) are reported in parts
d
3
9.2, 43.2, 127.2, 128.5, 128.8, 129.7, 137.1, 170.2; IR (KBr) 2974, 2935,
per million. IR spectra were obtained with a NICOLET 560 type FT-IR
spectrometer, GCeMS spectra were recorded on HP6890. All data
are in full agreement with those previously reported in the
literature.1
ꢂ1
1627,1427,1381,1288,1219,1099, 786, 736, 705 cm ; GCeMS: m/z,
177.
2,14
ꢀ
4
.2.9. Compound 3i: N-isopropylbenzamide. Mp 99e101 C; 1H
NMR (CDCl , 500 MHz)
1.27 (d, J¼9.6 Hz, 6H), 4.25e4.31 (m, 1H),
5.83 (br, 1H), 7.53e7.61 (m, 3H), 7.84 (d, J¼9.6 Hz, 2H); C NMR
(CDCl , 125 MHz) 23.2, 41.5, 127.9, 128.5, 132.3, 134.9, 167.8; IR
KBr) 3298, 2970, 2874, 1631, 1535, 1489, 1458, 1346, 1288,
3
d
13
4
.2. General procedure for the synthesis of amides from the
reaction of aldehydes with amines
3
d
(
ꢂ1
698 cm ; GCeMS: m/z, 163.
Typically reactions were carried out as follows: A mixture of
aldehydes (1 mmol), amines (1 mmol), NaOCl/Bu
4 4
NHSO
4.2.10. Compound 3j: N-tert-butylbenzamide. Mp 135e136 C; 1
NMR (CDCl , 500 MHz) 1.48 (s, 9H), 7.54e7.61 (m, 3H), 7.78 (d,
J¼12 Hz, 2H); C NMR (CDCl , 125 MHz) 29.2, 51.7, 126.8, 128.2,
ꢀ
H
(
1.5 equiv), and PEG (2 g) was placed in a 15 mL round-bottomed
ꢀ
flask, stirring at 120 C for 12 h. After the reaction was com-
pleted, the mixture was extracted with ethyl acetate (3ꢁ10 mL),
3
d
13
3
d

J. Liang et al. / Tetrahedron 67 (2011) 8532e8535
8535
1
31.7, 135.6, 169.4; IR (KBr) 3325, 2966, 2928, 1635, 1532, 1492,
2H), 7.65 (d, J¼13.2 Hz, 2H), 8.11 (d, J¼13.8 Hz, 2H), 8.43 (d,
13
ꢂ1
1458, 1278, 692 cm ; GCeMS: m/z, 177.
J¼14 Hz, 2H); C NMR (CDCl
3
, 125 MHz)
d
121.5, 124.0, 124.7,
ꢂ1
1
28.2, 138.1, 141.1, 151.6, 164.4; IR (KBr) 3321, 1651 cm ; GCeMS:
4
.2.11. Compound 3k: phenyl(pyrrolidin-1-yl)methanone. Colorless,
m/z, 242.
4.2.20. Compound 3t: 2,4-dichloro-N-phenylbenzamide. Mp 153e
1
3
liquid; H NMR (CDCl , 500 MHz) d 1.62 (t, 2H), 1.71 (t, 2H), 3.43 (t,
2
4
13
3
H), 3.50 (t, 2H), 7.63e7.84 (m, 5H); C NMR(CDCl ,125 MHz)d 25.5.
ꢀ
1
5.4,127.8,128.6,129.4,129.8,135.2,170.1; IR (KBr) 2936, 2856,1643,
154 C; H NMR (CDCl , 500 MHz) d 7.19 (t, 1H), 7.43e7.48(m, 4H),
3
ꢂ1
13
1578, 1492, 1429, 1273, 781, 722, 710 cm ; GCeMS: m/z, 175.
7.63(d, J¼13 Hz, 2H), 7.73(d, J¼13.8 Hz, 1H), 7.90(s, 1H); C NMR
(
CDCl
3
, 125 MHz)
d
122.3, 125.1, 127.6, 129.2, 130.1, 131.2, 131.5,
ꢂ1
4.2.12. Compound 3l: phenyl(piperidin-1-yl)methanone. Colorless,
133.6, 137.1, 137.9, 164.7; IR (KBr) 3344, 1659 cm ; GCeMS: m/z,
1
liquid; H NMR (CDCl
3
, 500 MHz)
d
1.53e1.59 (m, 6H), 3.53 (t, 2H),
265.
13
3
2
2
.70(t, 2H), 7.64e7.85 (m, 5H); C NMR (CDCl ,125MHz) 24.2, 25.6,
3
d
6.5, 43.1, 48.7, 126.8, 128.4, 128.5, 129.3, 136.5, 170.3; IR (KBr) 2939,
ꢂ1
Supplementary data
861, 1642,1579, 1492, 1437, 1281, 786, 732, 709 cm ; GCeMS: m/z,
1
89.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.08.091.
.2.13. Compound 3m: N-benzylbenzamide. Mp 105e106 C; 1
NMR (CDCl , 500 MHz)
4.65 (d, J¼9.4 Hz, 2H) 6.40 (s, 1H),
.23e7.26 (m, 5H), 7.63e7.69 (m, 3H), 7.86 (d, J¼11.2 Hz, 2H);
NMR (CDCl , 125 MHz) 44.8, 126.7, 127.2127.5, 128.3, 128.5, 135.2,
34.1, 137.9, 167.8; IR (KBr) 3313, 1649, 1598, 1525, 1515, 1491, 1475,
ꢀ
H
4
3
d
1
3
7
C
References and notes
3
d
1
6
1. (a) Humphrey, J. M.; Chamberlin, A. R. Chem. Rev. 1997, 97, 2243e2266.
2. (a) Kang, Y.; Chung, H.; Kim, J.; Yoon, Y. Synthesis 2002, 733e738; (b) Azumaya,
I.; Okamoto, T.; Imabeppu, F.; Takayanagi, H. Tetrahedron 2003, 59, 2325e2331;
ꢂ1
98, 675 cm ; GCeMS: m/z, 211.
(c) Wu, X.; Hu, L. J. Org. Chem. 2007, 72, 765e774; (d) Daniel, G.; David, B.;
4
.2.14. Compound 3n: 4-methyl-N-phenylbenzamide. Mp 145e
Simon, W. Tetrahedron Lett. 2008, 49, 5687e5688; (e) Teichert, A.; Jantos, K.;
Harms, K.; Studer, A. Org. Lett. 2004, 6, 3477e3480; (f) Naik, S.; Bhattacharjya,
G.; Talukdar, B.; Patel, B. K. Eur. J. Org. Chem. 2004, 1254e1260; (g) Shendage, D.
M.; Froehlich, R.; Haufe, G. Org. Lett. 2004, 6, 3675e3678; (h) Black, D. A.;
Arndtsen, B. A. Org. Lett. 2006, 8, 1991e1993; (i) Katritzky, A. R.; Cai, C.; Singh,
S. K. J. Org. Chem. 2006, 71, 3375e3380.
. (a) Fukuoka, S.; Ryang, M.; Tsutsumi, S. J. Org. Chem. 1971, 36, pp 2721e2721; (b)
Uozumi, Y.; Arii, T.; Watanabe, T. J. Org. Chem. 2001, 66, 5272e5274; (c) Na-
mayakkara, P.; Alper, H. Chem. Commun. 2003, 2384e2385; (d) Lin, Y. S.; Alper,
H. Angew. Chem., Int. Ed. 2001, 40, 779e781.
ꢀ
1
146 C; H NMR (CDCl , 500 MHz) d 2.37 (s, 3H), 7.22e7.27 (m, 3H),
3
7
.38 (t, J¼13.2 Hz, 2H), 7.64 (d, J¼13.2 Hz, 2H), 7.89 (d, J¼13.5 Hz, 2H),
1
3
3
C NMR (CDCl , 125 MHz)
d
21.3, 121.2, 124.4, 126.8, 127.1, 129.1,
ꢂ1
129.4, 132.1, 138.2, 142.4, 165.8; IR (KBr) 3348, 1651 cm ; GCeMS:
3
m/z, 211.
4.2.15. Compound 3o: 4-methoxy-N-phenylbenzamide. Mp 174e
1
4
. (a) Murahashi, S. I.; Naota, T.; Saito, E. J. Am. Chem. Soc. 1986, 108, 7846e7847;
ꢀ
175 C; H NMR (CDCl
3
, 500 MHz)
d
3.83 (s, 3H), 7.15 (d, J¼14.5 Hz,
(b) Cobley, C. J.; van den Heuvel, M.; Abbadi, A.; de Vries, J. G. Tetrahedron Lett.
2
H), 7.21 (t, 1H), 7.37 (t, 2H), 7.63 (d, J¼13.1 Hz, 2H), 7.88 (d,
2000, 41, 2467e2470.
. Tillack, A.; Rudloff, I.; Beller, M. Eur. J. Org. Chem. 2001, 523e528.
13
5
J¼14.5 Hz, 2H); C NMR (CDCl
3
, 125 MHz)
d
55.8, 114.4, 121.6, 123.9,
ꢂ1
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127.4, 129.0, 130.0, 139.7, 163.4, 165.5; IR (KBr) 3329, 1654 cm
;
1
GCeMS: m/z, 227.
8
9
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4
.2.16. Compound 3p: 4-(dimethylamino)-N-phenylbenzamide. Mp
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1
182e183 C; H NMR (CDCl
3
, 500 MHz) d 3.06 (s, 6H), 7.19 (t, 1H),
7
.43e7.56 (m, 3H), 7.36 (t, J¼12.8 Hz, 2H), 7.63 (d, J¼13.3 Hz, 2H), 7.78
13
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(
1
d, J¼14.5 Hz, 2H); C NMR (CDCl
3
, 125 MHz) d 41.6, 112.3, 124.5,
25.2,127.3,127.6,132.7,133.4,143.9,155.6,168.7;IR(KBr)3267,1643,
ꢂ1
1604, 1519, 1489, 1435, 1323, 759 cm ; GCeMS: m/z, 240.
1
1. (a) Schmidt, R. F. Ber. Dtsch. Chem. Ges. 1924, 57, 704e706; (b) Yao, L.; Aube, J. J.
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4
.2.17. Compound 3q: 2,4,6-trimethyl-N-phenylbenzamide. Mp
ꢀ
1
156e157 C; H NMR (CDCl
3
, 500 MHz)
d 2.34e2.46 (m, 9H), 6.89 (s,
12. (a) Qian, C. W.; Zhang, X. M.; Zhang, Y.; Shen, Q. J. Organomet. Chem. 2010, 695,
2
2
H), 7.31 (br, 1H), 7.38e7.43 (m, J¼7.7 Hz, 3H), 7.62 (d, J¼12.8 Hz,
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10022e10024; (c) Seo, S. Y.; Marks, T. J. Org. Lett. 2008, 10, 317e319; (d) Wang,
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ꢂ1
1543, 1492, 1442, 1323, 756 cm ; GCeMS: m/z, 239.
1
3. (a) Annegret, T.; Ivo, R.; Matthias, B. Eur. J. Org. Chem. 2001, 523e528; (b) Shie,
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.2.18. Compound 3r: 4-chloro-N-phenylbenzamide. Mp 199e200 C;
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7.19 (t, 1H), 7.43e7.57 (m, 4H), 7.75 (d,
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13
J¼13.6 Hz, 2H), 7.91 (d, J¼14 Hz, 2H); C NMR (CDCl
3
, 125 MHz)
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121.6, 124.3, 128.9, 129.1, 131.1, 134.5, 137.4, 139.7, 164.7; IR (KBr)
1
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3
351, 1654 cm ; GCeMS: m/z, 231.
1
997; (c) Kochi, M. Green Reaction Media for Organic Synthesis; Blackwell: Ox-
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4
.2.19. Compound 3s: 4-nitro-N-phenylbenzamide. Mp 214e216 C;
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H NMR (CDCl
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7.17e7.27 (t, 1H), 7.43 (t, J¼12.6 Hz,
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