A convenient and efficient protocol for the synthesis of symmetrical N,N'-alkylidine bisamides by sulfamic acid under solvent-free conditions

Article abstract of DOI:10.1139/V07-134

A simple and convenient approach to the synthesis of symmetrical N,N'-alkylidine bisamides is described. Aromatic and aliphatic nitriles react with aromatic aldehydes in the presence of sulfamic acid to give the corresponding bisamides in moderate yields.

Full text of DOI:10.1139/V07-134

32
A convenient and efficient protocol for the
synthesis of symmetrical N,N′-alkylidine bisamides
by sulfamic acid under solvent-free conditions
Nagarajan Panneer Selvam, Sundar Saranya, and Paramasivan T. Perumal
Abstract: A simple and convenient approach to the synthesis of symmetrical N,N′-alkylidine bisamides is described.
Aromatic and aliphatic nitriles react with aromatic aldehydes in the presence of sulfamic acid to give the corresponding
bisamides in moderate yields.
Key words: alkylidine bisamides, nitrile, sulfamic acid.
Résumé : On a mis au point une méthode simple et pratique de réaliser la synthèse de N,N′-alkylidinebisamides symé-
triques. Les nitriles aliphatiques et aromatiques réagissent avec les aldéhydes aromatiques, en présence d’acide sulfa-
mique, pour conduire à la formation des bisamides correspondants avec des rendements modérés.
Mots-clés : alkylidinebisamides, nitrile, acide sulfamique.
[Traduit par la Rédaction] Selvam et al. 38
Introduction
The increasing demands of environmental legislation have
been prompting the chemical industry to minimize or prefer-
ably eliminate waste production in chemical manufacture
(9). During the last few years, sulfamic acid has emerged as
a substitute for conventional acidic catalysts. Sulfamic acid
has been used as an efficient heterogeneous catalyst for acid-
catalyzed reactions (10), Biginelli condensation (11), Beck-
mann rearrangement (12), inter- and intra-molecular imino
Diels–Alder reactions (13), and Pechmann condensations
(14). The distinctive catalytic features and intrinsic Zwitter
ionic property of sulfamic acid are very different from con-
ventional acidic catalysts. This has encouraged us to investi-
gate further the application of sulfamic acid in carbon–
carbon and carbon–hetero atom bond-forming reactions.
Recently, we reported the synthesis of acetamidophenols
(15) from aldehydes, β-naphthols and acetonitrile via modi-
fied Ritter-type protocol catalyzed by anhyd. ceric sulphate.
Encouraged by these results, we also extented the protocol
by replacing β-naphthols with activated substituted benzenes,
like anisole, toluene, and so forth. Interestingly, we observed
that anisole or toluene was not involved in the reaction,
while the aldehyde reacted with acetonitrile in the presence
of anhyd. ceric sulfate, yielding symmetrical bisacetamides
as the major product (Scheme 1).
The amidation of organic compounds using nitriles is a
very useful tool in organic chemistry, as amide moieties are
important constituents of many biologically significant com-
pounds. In the last years, retro-amide links have successfully
been incorporated in the synthesis of retro-inverso peptide
analogues, such as enkephalinamide (1), substance P (2),
somatosatin (3), or gastrin (4). Residues with retro-amide
links are also the basic units of some aliphatic polyamides
(nylons) (5), which are closely related to fibrous proteins.
Specifically, bisamides are key fragments for the introduc-
tion of gem-iminoalkyl residues in retro-inverso pseudo pep-
tide derivatives (6) by treating the corresponding amide with
iodobenzene bistrifluoroacetate (7). In this regard, bisamides
are of considerable interest in the synthesis of pepti-
domimetic compounds (5).
Result and discussion
Magat et al. (8) reported the synthesis of bisamides using
sulfuric acid in good yields. However, this method suffers
from few disadvantages, such as the use of 85% sulphuric
acid (solvent) and the scope of the reaction was limited to
few aldehydes only. Hence, the development of highly expe-
dient protocol with wide applicability is necessary for their
syntheses.
However, this methodology suffers from few limitations;
the reaction was not complete even after refluxing for 24 h,
and it requires stoichiometric amount of catalyst. Hence, to
overcome these limitations, we focused on an efficient and
eco-benign protocol for the synthesis of bisamides.
In the present study, we report a highly efficient method
for the synthesis of biologically valuable bisamides from ar-
omatic aldehydes with a series of nitriles using sulfamic acid
in moderate yields (Scheme 2).
Received 18 October 2007. Accepted 7 November 2007.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 5 December 2008.
N.P. Selvam, S. Saranya, and P.T. Perumal.1 Organic
Chemistry Division, Central Leather Research Institute,
Chennai 600020, India.
Initially, we carried out the reaction of 4-nitrobenzalde-
hyde in acetonitrile using various catalysts for the synthesis
of bisacetamides (Scheme 3). After systematic screening
1Corresponding author (e-mail: ptperumal@gmail.com).
Can. J. Chem. 85: 32–38 (2008)
doi:10.1139/V07-134
© 2007 NRC Canada

Selvam et al.
33
Scheme 1.
Table 1. Screening of catalysts.
Yielda
(%)
Cl
Time
(h)
Cl
Entry
Catalyst (1 equiv.)
CH3CN
1
2
3
4
Anhyd. Ce(SO4)2
InCl3
24
48
48
48
48
0
R
+
O
O
Ce(SO4)2
85 °C
BiCl3
0
CHO
H3C
N
H
CH3
N
H
SnCl2·2H2O
0
5
6
7
Sulfamic acid
K10 montmorillonite
H3PW12O40
20
48
48
65
0
5
Scheme 2.
CHO
R
NH2SO3H
Neat
aIsolated yield.
R
2 R'
N
+
O
O
R'
N
H
R'
N
H
ther harsh conditions nor hazardous acids. The present pro-
tocol offers several advantages, including clean and simple
reaction procedure, isolation of products by crystallization
without employing purification methods like column chro-
matography, use of an eco-friendly catalyst, and solvent-free
conditions, which make it an attractive method for the syn-
thesis of N,N′-alkylidine symmetrical bisamides.
Scheme 3.
NO2
NO2
Catalyst
CH3CN
O
O
CH3
N
H
CH3
N
H
Experimental
CHO
General
Glassware was dried in a hot-air oven prior to use.
2-(Trifluoromethyl)benzonitrile and benzonitrile were pur-
chased from Lancaster Research Chemicals. All other re-
agents were purchased from S. D. Fine. Chem. Limited and
used as received. Acetonitrile was distilled from CaH2 under
nitrogen and stored over 4 Å molecular sieves. DMSO-d6
was purchased from Aldrich. IR measurements were done as
KBr pellets for solids using PerkinElmer Spectrum RXI
FTIR. The 1H and 13C NMR spectra were recorded in
DMSO-d6 with JEOL 500 MHz high-resolution NMR spec-
trometer. DMSO-d6 was used as the solvent for the NMR
spectral measurements, and the spectra were recorded in
ppm with TMS as internal standards. Multiplicities are ab-
breviated as follows: singlet (s), doublet (d), triplet (t),
multiplet (m), and broad (br). Mass spectra were recorded
by using an Electrospray Ionization Method with Thermo
Fennigan Mass spectrometer. Melting points were deter-
mined in capillary tubes and are uncorrected. Analytical
TLC was performed on precoated plastic sheets of silica gel
G/UV-254 of 0.2 mm thickness (Macherey–Nagel, Ger-
many). Elemental analysis data were recorded using Thermo
Finnigan FLASH EA 1112 CHN analyzer. Column Chroma-
tography was carried out using 100–200 mesh silica gel.
(Table 1), sulfamic acid was found to be the catalyst of
choice. Similarly, the mole ratio of sulfamic acid was stud-
ied and found 50 mol% of sulfamic acid to be optimum.
We extended our protocol with various substituted aro-
matic nitriles. In the course of our study, we investigated the
reaction of 3-nitrobenzaldehyde and 2-chlorobenzonitrile
with sulfamic acid using various solvents for the synthesis of
bisamides (Scheme 4), and found that solvent-free condition
was the best for the conversion. The results are listed in Ta-
ble 2.
The reaction was carried out with aldehyde (10 mmol)
and nitrile (22 mmol) in the presence of sulfamic acid (50
mol%) and heated at 125 °C under solvent-free condition.
This protocol is remarkably simple and requires non-
hazardous reagents or inert atmosphere.
A mechanistic rationale portraying the probable sequence
of events is given in Scheme 5. The substrate scope of the
reaction under the optimized condition was investigated, and
the results are summarized in Table 3. The reaction was
amenable to wide variations in nitriles. The reaction went
smoothly with aromatic aldehydes containing electron-
withdrawing groups, while no product formation was seen
with electron-rich aldehydes and aliphatic aldehydes. How-
ever, in the case of terephthalaldehyde, mono bis-amide was
formed, wherein only one aldehydic group was involved in
the reaction with nitrile (Table 3, entry 5).
Representative procedure for the synthesis of N,N′-
alkylidine bisamides
A mixture of aldehyde (10 mmol), nitrile (22 mmol), and
sulfamic acid (5 mmol) was stirred at 125 °C for the appro-
priate time as mentioned in Table 3. When acetonitrile
(taken in excess, 10 mL) was used, the reaction was carried
out at 85 °C. After the completion of the reaction (as moni-
tored by TLC), ethanol:water (8:2 mL) was added, and the
reaction mixture was refluxed for 20 min and allowed to
stay overnight. The solid obtained was filtered and dried.
Conclusion
Clearly, the results show that the sulfamic-acid-catalyzed
protocol provides an efficient tool for the synthesis of N,N′-
alkylidine symmetrical bisamides under relatively mild con-
ditions. In conclusion, we have developed a green approach
to the synthesis of symmetrical bisamides that requires nei-
© 2007 NRC Canada

34
Can. J. Chem. Vol. 85, 2008
Scheme 4.
NO2
Cl
NO2
CN
O
O
NH2SO3H
+
N
H
N
H
CHO
Different solvents
Cl
Cl
Scheme 5.
NH2SO3H
R
R
R
+
H
R'
N:
+
N
+
+
N
R'
OH
H
O
R'
OH2
R'
N:
H2O
R
R
R
O
O
+
+
N
H
N
H
R'
N
N
R'
R'
N
N
R'
R'
R'
OH
HO
(M+). Anal. calcd. for C11H13N2O2Cl: C 54.89, H 5.44, N
11.64. Found: C 54.86; H 5.42; N,11.62%.
Table 2. Solvent-effect study.
Entry
Solvent
Temperature
Yielda (%)
N-[acetylamino-(3-nitrophenyl)methyl]-acetamide
(Table 3, entry 3)
1
2
3
4
5
1,2-Dichloroethane
1,2-Dichlorobenzene
PhMe
Xylene
Neat
Reflux
Reflux
Reflux
Reflux
125 °C
34
Trace
22
48
68
White solid. Yield: 68%, mp: 256–257 °C (Lit 256–
257 °C) (18). IR νmax: 3275, 3118, 2369, 1665, 1561, 1529,
1
1350, 1272, 1095, 764 cm–1. H NMR (500 MHz, DMSO-
d6) δ: 1.86 (s, 6H), 6.53 (t, 1H, J = 7.45Hz), 7.62 (t, 1H, J =
8.05Hz), 7.74 (d, 1H, J = 7.45Hz), 8.14 (s, 2H, br), 8.71 (d,
2H, J = 7.45Hz, D2O exchangeable). 13C NMR (125 MHz,
DMSO-d6) δ: 98, 57.45, 121.47, 123.16, 130.50, 133.99,
143.22, 148.31, 169.49. MS (ESI): 251(M+). Anal. calcd. for
C11H13N3O4: C 52.59, H 5.22, N 16.73. Found: C 52.65, H
5.18, N 16.68%.
aIsolated yield.
N-[acetylamino-(4-nitrophenyl)methyl]-acetamide
(Table 3, entry 1)
Pale brownish yellow solid. Yield: 65%, mp: 270–272 °C
(Lit. 272 °C) (16). IR νmax: 3270, 3107, 1672, 1518, 1352,
1194, 1094, 824 cm–1. H NMR (500 MHz, DMSO-d6) δ:
1
N-[acetylamino-(2-nitrophenyl)methyl]-acetamide
(Table 3, entry 4)
1.85 (s, 6H), 6.53 (t, 1H, J = 7.65 Hz), 7.54 (d, 2H, J =
8.4 Hz), 8.17 (d, 2H, J = 9.15 Hz), 8.70 (d, 2H, J = 7.5 Hz,
D2O exchangeable). 13C NMR (125 MHz, DMSO-d6) δ:
22.94, 57.45, 123.99, 128.28, 147.41, 148.36, 169.53. MS
(ESI): 251 (M+). Anal. calcd. for C11H13N3O4: C 52.59, H
5.22, N 16.73. Found: C 52.68, H 5.15, N 16.67%.
Reddish brown solid. Yield: 60%, mp: 231–232 °C (Lit.
231–232 °C) (19). IR νmax: 3273, 1668, 1526, 1359, 1097,
1
776 cm–1. H NMR (500 MHz, DMSO-d6) δ: 1.79 (s, 6H),
6.82 (t, 1H, J = 7.65 Hz), 7.69 (t, 3H, J = 6.9 Hz), 7.88 (d,
1H, J = 8.4 Hz), 8.62 (d, 2H, J = 7.65 Hz, D2O
exchangeable).13C NMR (125 MHz, DMSO-d6) δ: 22.74,
54.83, 124.80, 128.92, 129.69, 133.60, 134.61, 148.81,
169.29. MS (ESI): 251 (M+). Anal. calcd. for C11H13N3O4:
C 52.59, H 5.22, N 16.73. Found: C 52.40, H 5.26, N
16.70%.
N-[acetylamino-(4-chlorophenyl)methyl]-acetamide
(Table 3, entry 2)
White solid. Yield: 60%, mp: 258–260 °C (Lit. 260–
261 °C) (17). IR ν
KBr: 3271, 3123, 1670, 1093, 1529,
max
1
1370 cm–1. H NMR (500 MHz, DMSO-d6) δ: 1.83 (s, 6H),
6.42 (t, 1H, J = 8.05 Hz), 7.28 (d, 2H, J = 8.6 Hz), 7.37 (d,
2H, J = 8.6 Hz), 8.52 (d, 2H, J = 8.05 Hz, D2O exchange-
able). 13C NMR (125 MHz, DMSO-d6) δ: 22.96, 57.33,
128.73, 128.80, 132.66, 139.87, 169.35. LR-MS (EI+): 240
N-[(acetylamino)(4-formylphenyl)methyl]acetamide
(Table 3, entry 5)
Off white solid. Yield: 40%, mp: 258–260 °C. IR νmax
:
1
3261, 3116, 1665, 1560, 1373, 1094, 802 cm–1. H NMR
© 2007 NRC Canada

Selvam et al.
35
Table 3. Results of the reactions under the optimized conditions.
Producta
NO2
Yield (%)b
Time (h)
Mp (Ref.)
Entry
Nitrile
Aldehyde
NO2
1
270–272 °C (Lit. 272 °C)(16)
20
CH3CN
65
O
O
CHO
Cl
CH3
N
H
N
H
CH3
Cl
258–260 °C (Lit. 260–261 °C)(17)
60
20
2
CH3CN
O
O
CHO
CH3
N
H
CH3
N
H
NO2
NO2
O
18
256–257 °C (Lit. 256–257 °C)(18) 68
3
CH3CN
CH3CN
O
CHO
CH3
N
H
CH3
N
H
231–232 °C (Lit. 231–232 °C)(19) 60
18
4
NO2
O
NO2
O
CHO
CHO
CH3
N
H
CH3
N
H
CHO
CH3CN
24
258–260 °C
40
5
O
O
CHO
CH3
N
H
CH3
N
H
CN
NO2
O
NO2
214–215 °C (Lit. 216 °C)(20)
65
5
6
O
N
H
N
H
CHO
NO2
O
Cl
NO2
CN
Cl
O
Cl
68
212–214 °C
6
7
N
H
N
H
CHO
Cl
Cl
Cl
Cl
O
CN
Cl
O
Cl
4
65
202–204 °C
8
N
H
N
H
Cl
CHO
© 2007 NRC Canada

36
Can. J. Chem. Vol. 85, 2008
Table 3 (concluded).
Producta
NO2
Yield (%)b
Mp (Ref.)
Time (h)
Entry
Nitrile
Aldehyde
NO2
Cl
CN
244–246 °C
60
8
9
Cl
O
O
O
Cl
Cl
N
H
N
H
CHO
Cl
Cl
O
CN
Cl
6
223–226 °C
63
10
N
H
N
H
Cl
CHO
Cl
Cl
Cl
Cl
Cl
CN
CN
CN
Cl
O
O
Cl
6
225–226 °C
68
11
N
H
N
H
CHO
OMe
–
–
24
No product
12
CHO
OMe
OMe
–
–
No product
Cl
24
13
CHO
Cl
CF3
Cl
O
CN
CF3
O
CF3
14
Cl
N
H
N
H
6
244–246 °C
45
CHO
NO2
NO2
CF3
CN
CF3
O
O
CF3
15
N
H
N
H
6
233–234 °C
60
CHO
Cl
Cl
CN
Cl
O
16
O
Cl
190–192 °C
42
8
N
H
N
H
CHO
CF3
CN
–
-
no product
24
17
CHO
aThe products were characterized by IR, NMR, mass spectroscopy, and combustion analyses and compared with authentic samples.
bIsolated yields
© 2007 NRC Canada

Selvam et al.
37
(500 MHz, DMSO-d6) δ: 1.84 (s, 6H), 6.51 (t, 1H, J =
7.65 Hz), 7.49 (d, 2H, J = 8.4Hz), 7.86 (d, 2H, J = 8.4 Hz),
8.71 (d, 2H, J = 7.65 Hz, D2O exchangeable), 9.96 (s,
1H).13C NMR (125 MHz, DMSO-d6) δ: 22.98, 57.69,
127.67, 130.12, 136.07, 147.56, 169.36, 193.33. MS (ESI):
234 (M+). Anal. calcd. for C12H14N2O3: C 61.53, H 6.02, N
11.96. Found: C 61.42, H 5.96, N 11.85%.
2-Chloro-N-[[(2-chlorobenzoyl)amino](2-
chlorophenyl)methyl]benzamide (Table 3, entry 10)
White solid. Yield: 63%, mp: 223–226 °C. IR νmax: 3264,
1
1667, 1507, 1548, 1074, 749 cm–1. H NMR (500 MHz,
DMSO-d6) δ: 7.06 (t, 1H, J = 7.65 Hz), 7.35 (m, 4H), 7.41
(t, 2H, J = 7.65 Hz), 7.45 (t, 5H, J = 7.65 Hz), 7.71 (d, 1H,
J = 6.9 Hz), 9.32 (d, 2H, J = 6.9 Hz, D2O exchangeable).
13C NMR (125 MHz, DMSO-d6) δ: 56.94, 127.44, 127.56,
128.91, 129.79, 129.94, 130.12, 130.24, 130.63, 131.49, 133.02,
136.77, 137.28, 166.14. MS (ESI): 455 (M + 23) – Na
adduct. Anal. calcd. for C21H15N2O3Cl3: C 58.16, H 3.49, N
6.46. Found: C 58.32, H 3.54, N 6.38%.
2-Phenyl-N-{(3-nitrophenyl)[(phenyl-
acetyl)amino]methyl}acetamide (Table 3, entry 6)
Pale yellow solid. Yield: 65%, mp: 214–215 °C (Lit
216 °C) (16). IR νmax: 3285, 3026, 1668, 1555, 1514, 1348,
1
704 cm–1. H NMR (500 MHz, DMSO-d6) δ: 3.49 (s, 4H),
2-Chloro-N-[[(2-chlorobenzoyl)amino](4-
6.54 (t, 1H, J = 7.8 Hz), 7.21 (m, 10H), 7.52 (d, 2H, J =
8.4 Hz), 8.17 (d, 2H, J = 8.4Hz), 8.97 (d, 2H, J = 7.95 Hz,
D2O exchangeable).13C NMR (125 MHz, DMSO-d6) δ:
42.39, 57.66, 124.02, 126.97, 128.16, 128.77, 129.60,
136.45, 147.46, 148.15, 170.35. MS (ESI): 403 (M+). Anal.
calcd. for C23H21N3O4: C 68.47, H 5.25, N 10.42. Found: C
68.30, H 5.20, N 10.38%.
chlorophenyl)methyl]benzamide (Table 3, entry 11)
White solid. Yield: 68%, mp: 225–226 °C. IR νmax: 3247,
1
1672, 1493, 1069, 742 cm–1. H NMR (500 MHz, DMSO-
d6) δ: 6.86 (t, 1H, J = 7.65Hz), 7.38 (t, 2H, J = 7.65Hz),
7.43 (m, 8H), 7.51 (d, 2H, J = 8.4Hz), 9.29 (d, 2H,
J = 7.65Hz, D2O exchangeable). 13C NMR (125 MHz,
DMSO-d6) δ: 58.17, 127.53, 128.81, 129.09, 129.73, 130.13,
130.57, 131.55, 132.97, 136.74, 138.84, 166.31. MS
(ESI): 455 (M + 23) – Na adduct. Anal. calcd. for
C21H15N2O3Cl3: C 58.16, H 3.49, N 6.46. Found: C 58.30, H
3.44, N 6.38%.
2-Chloro-N-[[(2-chlorobenzoyl)amino](3-
nitrophenyl)methyl]benzamide (Table 3, entry 7)
Off white solid. Yield: 68%, mp: 212–214 °C. IR νmax
:
3276, 1667, 1594, 1529, 1346, 1068, 738 cm–1. H NMR
(500 MHz, DMSO-d6 + acetone-d6) δ: 7.54 (t, 1H, J =
8.4 Hz), 7.84 (m, 6H), 8.00 (d, 2H, J = 7.6 Hz), 8.16 (t, 1H,
J = 8.4Hz), 8.48 (d, 1H, J = 7.6 Hz), 8.65 (d, 1H, J =
8.65 Hz), 8.99 (s, 1H), 9.75 (d, 2H, J = 7.65 Hz, D2O ex-
changeable).13C NMR (125 MHz, DMSO-d6) δ: 58.76,
122.30, 123.43, 127.69, 130.02, 130.43, 130.55, 131.16,
131.73, 134.24, 137.06, 142.83, 148.87, 166.83. MS (ESI):
466 (M + 23) – Na adduct. Anal. calcd. for C21H15N3O4Cl2:
C 56.77, H 3.40, N 9.46. Found: C 56.59, H 3.46, N 9.40%.
1
N-((2,4-dichlorophenyl){[2-(trifluoromethyl)benzoyl]-
amino}methyl)-2-(trifluoromethyl)benzamide (Table 3,
entry 14)
Off white solid. Yield: 45%, mp: 244–246 °C. IR νmax
:
3259, 1672, 1548, 1318, 1125, 766 cm–1. 1H NMR
(500 MHz, DMSO-d6) δ: 7.00 (t, 1H, J = 6.9 Hz), 7.49 (d,
1H, J = 8.4 Hz), 7.56 (d, 2H, J = 7.65 Hz),7.63 (m, 4H),
7.70 (t, 2H, J = 7.65 Hz), 7.76 (d, 2H, J = 7.65 Hz), 9.43 (d,
2H, J = 6.85 Hz, D2O exchangeable). 13C NMR (125 MHz,
DMSO-d6) δ: 56.56, 123.10, 125.27, 126.55, 126.79, 127.75,
129.45, 130.13, 130.57, 132.79, 133.97, 134.03, 136.08,
136.24, 166.94. MS (ESI): 557 (M + 23) – Na adduct. Anal.
calcd. for C23H14N2O2Cl2F6: C 51.61, H 2.62, N 5.23.
Found: C 51.75, H 2.56, N 5.17%.
2-Chloro-N-[[(2-chlorobenzoyl)amino](2,4-dichloro-
phenyl)methyl]benzamide (Table 3, entry 8)
White solid. Yield: 65%, mp: 202–204 °C. IR νmax: 3287,
1
3084, 2959, 1665, 1546, 745 cm–1. H NMR (500 MHz,
DMSO-d6) δ: 6.99 (t, 1H, J = 6.85 Hz), 7.35 (m, 11H), 9.33
(d, 2H, J = 7.65 Hz, D2O exchangeable proton). 13C NMR
(125 MHz, DMSO-d6) δ: 56.62, 127.48, 127.76, 128.68,
129.39, 129.74, 130.15, 130.27, 130.60, 131.11, 131.58,
133.95, 136.57, 166.22. MS (ESI): 489 (M + 23) – Na
adduct. Anal. calcd. for C21H14N2O2Cl4: C 53.88, H 3.01, N
5.98. Found: C 53.78, H 3.07, N 5.89%.
N-((4-nitrophenyl){[2-(trifluoromethyl)benzoyl]-
amino}methyl)-2-(trifluoromethyl)benzamide (Table 3,
entry 15)
Pale yellow solid. Yield: 60%, mp: 233–234 °C. IR νmax
:
3259, 1669, 1530, 1349, 1315, 1126, 731 cm–1. H NMR
(500 MHz, DMSO-d6) δ: 6.95 (t, 1H, J = 7.6 Hz), 7.59 (d,
2H, J = 7.65 Hz), 7.64 (t, 2H, J = 7.65 Hz), 7.69 (t, 1H, J =
7.6 Hz), 7.73 (t, 2H, J = 7.6 Hz), 7.78 (d, 2H, = 7.65 Hz),
7.91 (d, 1H, J = 7.6 Hz) 8.19 (d, 1H, J = 8.4 Hz), 8.34 (s,
1H), 9.59 (d, 2H, J = 7.65 Hz, D2O exchangeable). 13C
NMR (125 MHz, DMSO-d6) δ: 58.18, 121.81, 123.47,
126.78, 129.33, 130.55, 130.62, 132.91, 134.06, 136.05,
141.83, 148.33, 167.25. MS (ESI): 534 (M + 23) – Na
adduct. Anal. calcd. for C23H15N3O4F6: C 59.23, H 3.46, N
6.01. Found: C 59.14, H 3.42, N 5.98%.
1
.
2-Chloro-N-[[(2-chlorobenzoyl)amino](4-
nitrophenyl)methyl]-benzamide (Table 3, entry 9)
Yellow solid. Yield: 60%, mp: 244–246 °C. IR νmax: 3239,
1
1671, 1523, 1348, 1069, 743 cm–1. H NMR (500 MHz,
DMSO-d6) δ: 6.95 (t, 1H, J = 7.65 Hz), 7.38 (t, 2H, J =
7.65 Hz), 7.43 (t, 2H, J = 7.65 Hz), 7.48 (t, 4H, J = 7.6Hz),
7.77 (d, 2H, J = 9.2 Hz), 8.26 (d, 2H, J = 8.4 Hz), 9.47 (d,
2H, J = 8.45 Hz, D2O exchangeable). 13C NMR (125 MHz,
DMSO-d6) δ: 58.30, 124.09, 127.58, 128.58, 129.73, 130.16,
130.59, 131.67, 136.50, 147.12, 147.68, 166.53. MS (ESI):
466 (M + 23) – Na adduct. Anal. calcd. for C21H15N3O4Cl2:
C 56.77, H 3.40, N 9.46. Found: C 56.70, H 3.42, N 9.50%.
N-[(benzoylamino)(2,4-dichlorophenyl)methyl]benzamide
(Table 3, entry 16)
Off white solid. Yield: 42%, mp: 190–192 °C. IR νmax
:
3286, 1640, 1542, 1514, 1145, 696 cm–1. 1H NMR
© 2007 NRC Canada

38
Can. J. Chem. Vol. 85, 2008
8. (a) E.E. Magat, B.F. Faris, J.E. Reith, and L.F. Salibury. J.
Am. Chem. Soc. 73, 1028 (1951); (b) E.E. Magat, L.B. Chan-
dler, B.F. Faris, J.E. Reith, and L.F. Salisbury J. Am. Chem.
Soc. 73, 1031 (1951); (c) E.E. Magat and L.F. Salisbury. J.
Am. Chem. Soc. 73, 1035 (1951).
(500 MHz, DMSO-d6) δ: 7.00 (t, 1H, J = 7.6 Hz), 7.43 (m,
5H), 7.50 (m, 2H), 7.61 (m, 2H), 7.88 (d, 4H, J = 7.6 Hz),
9.09 (d, 2H, J = 6.8Hz, D2O exchangeable).13C NMR
(125 MHz, DMSO-d6) δ: 57.47, 127.73, 128.20, 128.77,
129.33, 130.36, 132.14, 133.74, 134.00, 134.16, 137.08,
166.34. MS (ESI): 399 (M+). Anal. calcd. for
C21H16N2O2Cl2: C 63.17, H 4.04, N 7.02. Found: C 63.42, H
3.95, N 6.94%.2
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Acknowledgement
N.P. thanks the Council of Scientific and Industrial Re-
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2 Supplementary data for this article are available on the journal Web site (canjchem.nrc.ca) or may be purchased from the Depository of Un-
published Data, Document Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0R6, Canada. DUD 5248. For more in-
formation on obtaining material, refer to cisti-icist.nrc-cnrc.gc.ca/irm/unpub_e.shtml.
© 2007 NRC Canada