Synthesis, characterization and crystal structure of 2-nitro-n-[2,4- dichlorophenyl]-N-(2-methylbenzoyl)benzamide

Article abstract of DOI:10.1007/s10870-010-9763-1

The title benzamide was synthesized in two steps by refluxing N-(2,4-dichlorophenyl)-2-nitrobenzamide with thionyl chloride in dry toluene to afford 2,4-dichloro-N-[chloro(2-nitrophenyl]methylene)benzenamine intermediate followed by treatment with 2-methyl benzoic acid in presence of triethyl amine. The structure was confirmed by spectroscopic and elemental analysis. The crystal structure was determined from single crystal X-ray diffraction data. It crystallizes in the monoclinic space group P 21/c with unit cell dimensions a = 10.4122(7), b = 12.9613(7) and c = 15.5518(10) A. The dihedral angle between the two aromatic rings is 82.32(4)°. The N2 and N3 nitro groups are oriented with respect to their attached phenyl rings at dihedral angles of 1.97(3)° and 15.73(3)°, respectively. Graphical Abstract: The title benzamide was synthesized in two steps from N-(2,4-dichlorophenyl)-2- nitrobenzamide. It crystallized in the monoclinic space group P 21/c. The dihedral angle between the two aromatic rings is 82.32(4)°. The N2 and N3 nitro groups are oriented with respect to their attached phenyl rings at dihedral angles of 1.97(3)° and 15.73(3)°, respectively.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-010-9763-1

J Chem Crystallogr (2010) 40:919–923
DOI 10.1007/s10870-010-9763-1
ORIGINAL PAPER
Synthesis, Characterization and Crystal Structure
of 2-Nitro-N-[2,4-dichlorophenyl]-N-(2-methylbenzoyl)benzamide
•
•
•
Aamer Saeed Shahid Hussain Naeem Abbas
Michael Bolte
Received: 28 July 2008 / Accepted: 7 May 2010 / Published online: 19 May 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The title benzamide was synthesized in two
steps by refluxing N-(2,4-dichlorophenyl)-2-nitrobenza-
mide with thionyl chloride in dry toluene to afford
2,4-dichloro-N-[chloro(2-nitrophenyl]methylene)benzen-
amine intermediate followed by treatment with 2-methyl
benzoic acid in presence of triethyl amine. The structure
was confirmed by spectroscopic and elemental analysis.
The crystal structure was determined from single crystal X-
ray diffraction data. It crystallizes in the monoclinic space
group P 21/c with unit cell dimensions a = 10.4122(7),
studied, using declopramide as a lead compound [1]. N-
substituted benzamides inhibit nuclear factor-B and nuclear
factor of activated T cells activity while inducing activator
protein 1 activity in T lymphocytes [2]. Various N-substi-
tuted benzamides exhibit potent antiemetic activity [3]. O-
Aryloxylation of N-substituted benzamides induced by the
copper(II)/trimethylamine N-oxide system has been studied
[4]. N,N-Disubstituted amides constitute an extremely
important and rare subclass of amides which are versatile
building blocks for the synthesis of a variety of heterocy-
cles as well as exhibit a wide spectrum of bioactivities. N-
Alkylated 2-nitrobenzamides are intermediates toward
dibenzo[b,e][1,4]diazepines [5]. N-Acyl-2-nitrobenzamides
are precursors towards 2,3-disubstitued 3H-quinazoline-4-
ones. Thus, reaction of 2-nitrobenzamides with thionyl
chloride affords the imidoyl chloride as an unstable inter-
mediate which is treated directly with Boc-protected amino
acids to afford the corresponding chiral N-acyl-2-nitroben-
zamide. Reductive cyclization of the latter lead to quinaz-
oline-4-ones without any racemization [6].
˚
b = 12.9613(7) and c = 15.5518(10) A. The dihedral
angle between the two aromatic rings is 82.32(4)°. The N2
and N3 nitro groups are oriented with respect to their
attached phenyl rings at dihedral angles of 1.97(3)° and
15.73(3)°, respectively.
Keywords X-ray crystallography ꢀ
2-Nitro-N-aroylbenzamide ꢀ Synthesis
Introduction
The title compound was synthesized in continuation of
our interest in the synthesis of novel heterocycles and for
the systematic study of its complexation behavior.
The benzanilide core is present in compounds with such a
wide range of biological activities that it has been called a
privileged structure. N-substituted benzamides are well
known anticancer compounds and the mechanism of action
for N-substituted benzamide-induced apoptosis has been
Results and Discussion
The synthesis started with N-(2,4-dichlorophenyl)-2-ni-
trobenzamide prepared according to procedure reported
earlier. It was refluxed with thionyl chloride in dry toluene
to afford 2,4-dichloro-N-[chloro(2-nitrophenyl)methylene]
benzenamine as air sensitive intermediate which was used
as such in the nest step involving treatment with 2-meth-
ylbenzoic acid in presence of base to afford in high yield
(Scheme 1).
A. Saeed (&) ꢀ S. Hussain ꢀ N. Abbas
Department of Chemistry, Quaid-I-Azam University,
Islamabad 45320, Pakistan
e-mail: aamersaeed@yahoo.com
M. Bolte
Institut fu¨r Anorganische Chemie, J.-W.-Goethe-Universitat,
Max-von-Laue-Str.7, 60438 Frankfurt, Germany
¨
123

920
J Chem Crystallogr (2010) 40:919–923
Scheme 1 Synthesis of 2-nitro-
N-[2,4-dichlorophenyl]-N-(2-
methylbenzoyl)benzamide
Cl
Cl
H
SOCl2
N
N
dry Toluene/ reflux
NO2
Cl
NO2
O
Cl
Cl
CH3
dry CH2Cl2 / Et3N
(under N2)
O
Cl
CH3
O
N
O2N
Cl
(I)
COOH
Absence of IR absorptions for free NH, and absorptions
1
for two carbonyls at 1678 and 1644 was noticed. H and
Table 1 Crystal data and structure refinement
Empirical formula
Formula weight
Temperature
C21H14Cl2N2O4
429.24
13C-NMR spectra supported the structure.
173(2) K
X-Ray Data Collection and Structure Refinement
˚
0.71073 A
Wavelength
Crystal system
Space group
Monoclinic
P21/c
Experimental data are listed in Table 1. The atomic coor-
dinates and equivalent isotropic displacement parameters
for non-hydrogen atoms are reported in Table 2. The
selected bond lengths and angles and hydrogen-bond
geometry are given in Tables 3 and 4, respectively. Crys-
tallographic data were recorded on a STOE IPDS-II dif-
Unit cell dimensions
˚
a = 10.4122(7) A, a = 90°
b = 12.9613(7) A, b = 106.986(5)°
˚
˚
c = 15.5518(10) A, c = 90°
3
˚
Volume
2007.2(2) A
˚
fractometer [7] using Mo Ka radiation (k = 0.71073 A) at
Z
4
T = 173 K. An absorption correction was applied using the
MULABS [8] option in PLATON [9]. The structure was
solved by direct methods and refined by full-matrix least-
squares using SHELXL-97 against F2 using all data [10].
All non-H atoms were refined anisotropically. H atoms
Density (calculated)
Absorption coefficient
F(000)
1.420 Mg/m3
0.354 mm-1
880
Crystal size
0.49 9 0.47 9 0.47 mm3
˚
were positioned geometrically at distances of 0.95 A
˚
(aromatic CH) and 0.98 A (methyl groups) from the parent
Theta range for data
collection
3.75–25.61°
Index ranges
-9 B h B 12, -15 B k B 15,
-18 B l B 18
C atoms; a riding model was used during the refinement
process and the Uiso(H) values were constrained to be
1.2 Ueq(aromatic C) or 1.5 Ueq(methyl C).
Reflections collected
22,101
Independent reflections
3,749 [R(int) = 0.0492]
99.6%
The X-ray structural determination of the title com-
pound 1 confirms the assignment of its structure from
spectroscopic data. The molecular structure of the title
compound 1 along with the atom-numbering scheme is
depicted in Fig. 1.
Completeness to
h = 25.00°
Absorption correction
Semi-empirical from equivalents
0.8513 and 0.8457
Max. and min.
transmission
Geometric parameters are in the usual ranges. The
central N atom is in a trigonal planar environment. The
sum of its bond angles is 359.5°. The nitrophenyl ring
makes dihedral angles of 48.9° and 12.8° with the meth-
ylphenyl and dichlorophenyl ring. The dihedral angles
between the methylphenyl ring and the dichlorophenyl ring
is 61.4°. A packing diagram is shown in Fig. 2.
Refinement method
Full-matrix least-squares on F2
3749/0/263
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2r(I)]
R indices (all data)
1.060
R1 = 0.0416, wR2 = 0.1053
R1 = 0.0465, wR2 = 0.1089
-3
˚
0.435 and -0.482 e A
Largest diff. peak and hole
123

J Chem Crystallogr (2010) 40:919–923
921
Table 2 Atomic coordinates (9104) and equivalent isotropic dis-
Table 3 Bond lengths (A) and angles (°)
˚
2
placement parameters (A 9 10 )
3
˚
Cl(1)–C(32)
Cl(2)–C(34)
N(1)–C(2)
1.7362(18)
1.7425(19)
1.412(2)
1.417(2)
1.446(2)
1.211(2)
1.508(2)
1.215(2)
1.499(3)
1.222(3)
1.224(3)
1.469(3)
1.389(3)
1.391(3)
1.388(3)
1.371(4)
0.9500
x
y
z
U(eq)
Cl(1)
Cl(2)
N(1)
2605(1)
4465(1)
7849(1)
5778(1)
5790(1)
5442(1)
6795(2)
6154(1)
5101(1)
7264(1)
7130(2)
5278(1)
5767(2)
5302(2)
4325(2)
3811(2)
4289(2)
5551(1)
6272(1)
6326(2)
5680(2)
4963(2)
4895(2)
6964(2)
6274(1)
5746(1)
6230(2)
7252(2)
7803(2)
7306(1)
818(1)
571(1)
39(1)
71(1)
25(1)
27(1)
28(1)
57(1)
38(1)
50(1)
55(1)
129(1)
27(1)
38(1)
52(1)
51(1)
44(1)
35(1)
26(1)
29(1)
40(1)
47(1)
45(1)
36(1)
44(1)
24(1)
27(1)
34(1)
36(1)
33(1)
28(1)
N(1)–C(1)
-451(1)
4856(1)
5623(2)
5354(2)
8147(2)
5148(1)
6485(2)
7083(2)
9182(3)
6982(2)
8181(2)
9423(2)
9476(2)
8304(2)
7056(2)
4427(2)
4740(2)
3898(2)
2801(2)
2517(2)
3328(2)
5959(2)
3560(2)
2458(2)
1222(2)
1105(2)
2183(2)
3413(2)
N(1)–C(31)
1971(1)
1354(1)
2872(1)
2427(2)
612(1)
C(1)–O(1)
C(1)
C(1)–C(11)
C(2)
C(2)–O(2)
N(2)
C(2)–C(21)
O(1)
N(2)–O(3)
O(2)
3165(1)
2239(1)
2948(3)
1591(1)
2036(2)
2158(2)
1833(2)
1395(1)
1265(1)
3445(1)
4150(1)
4701(1)
4573(2)
3886(2)
3315(1)
4315(2)
1650(1)
1102(1)
769(1)
N(2)–O(4)
O(3)
N(2)–C(12)
O(4)
C(11)–C(16)
C(11)–C(12)
C(12)–C(13)
C(13)–C(14)
C(13)–H(13)
C(14)–C(15)
C(14)–H(14)
C(15)–C(16)
C(15)–H(15)
C(16)–H(16)
C(21)–C(26)
C(21)–C(22)
C(22)–C(23)
C(22)–C(27)
C(23)–C(24)
C(23)–H(23)
C(24)–C(25)
C(24)–H(24)
C(25)–C(26)
C(25)–H(25)
C(26)–H(26)
C(27)–H(27A)
C(27)–H(27B)
C(27)–H(27C)
C(31)–C(32)
C(31)–C(36)
C(32)–C(33)
C(33)–C(34)
C(33)–H(33)
C(34)–C(35)
C(35)–C(36)
C(35)–H(35)
C(36)–H(36)
C(2)–N(1)–C(1)
C(2)–N(1)–C(31)
C(1)–N(1)–C(31)
O(1)–C(1)–N(1)
O(1)–C(1)–C(11)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(21)
C(22)
C(23)
C(24)
C(25)
C(26)
C(27)
C(31)
C(32)
C(33)
C(34)
C(35)
C(36)
1.383(4)
0.9500
1.400(3)
0.9500
0.9500
1.392(3)
1.405(3)
1.395(3)
1.514(3)
1.383(3)
0.9500
1.381(4)
0.9500
995(1)
1533(1)
1855(1)
1.395(3)
0.9500
U(eq) is defined as one-third of the trace of the orthogonalized Uij
tensor
0.9500
0.9800
0.9800
Experimental
0.9800
1.392(2)
1.393(2)
1.388(3)
1.385(3)
0.9500
Melting points were recorded using a digital Gallenkamp
(SANYO) model MPD.BM 3.5 apparatus and are uncor-
1
rected. H-NMR (300 MHz) spectra were determined in
CDCl3 at 300 MHz using a Bruker machine. FTIR spectra
were recorded on an FTS 3000 MX spectrophotometer.
Mass Spectra (EI, 70 eV) on a MAT 312 instrument, and
elemental analyses were conducted using a LECO-183
CHNS analyzer.
1.387(3)
1.390(3)
0.9500
0.9500
123.97(15)
121.00(14)
114.51(14)
119.73(16)
119.82(16)
Synthesis of 2-Nitro-N-(2,4-dichlorophenyl)-N-(2-
methylbenzoyl)benzamide
Thionyl chloride (0.12 mol) was added dropwise to a stirred
solution of 2-nitro-N-(2, 4-dichlorophenyl)benzamide
123

922
J Chem Crystallogr (2010) 40:919–923
˚
Table 3 Bond lengths (A) and angles (°)
Table 3 continued
N(1)–C(1)–C(11)
120.27(15)
121.28(16)
122.19(16)
116.52(15)
122.9(2)
118.85(19)
118.2(2)
117.68(18)
117.75(17)
124.24(17)
122.3(2)
118.1(2)
119.48(18)
119.2(2)
120.4
C(32)–C(31)–C(36)
C(32)–C(31)–N(1)
C(36)–C(31)–N(1)
C(33)–C(32)–C(31)
C(33)–C(32)–Cl(1)
C(31)–C(32)–Cl(1)
C(34)–C(33)–C(32)
C(34)–C(33)–H(33)
C(32)–C(33)–H(33)
C(33)–C(34)–C(35)
C(33)–C(34)–Cl(2)
C(35)–C(34)–Cl(2)
C(34)–C(35)–C(36)
C(34)–C(35)–H(35)
C(36)–C(35)–H(35)
C(35)–C(36)–C(31)
C(35)–C(36)–H(36)
C(31)–C(36)–H(36)
119.09(16)
120.78(15)
120.07(16)
120.95(17)
118.56(14)
120.50(13)
118.55(18)
120.7
O(2)–C(2)–N(1)
O(2)–C(2)–C(21)
N(1)–C(2)–C(21)
O(3)–N(2)–O(4)
O(3)–N(2)–C(12)
O(4)–N(2)–C(12)
C(16)–C(11)–C(12)
C(16)–C(11)–C(1)
C(12)–C(11)–C(1)
C(13)–C(12)–C(11)
C(13)–C(12)–N(2)
C(11)–C(12)–N(2)
C(14)–C(13)–C(12)
C(14)–C(13)–H(13)
C(12)–C(13)–H(13)
C(13)–C(14)–C(15)
C(13)–C(14)–H(14)
C(15)–C(14)–H(14)
C(14)–C(15)–C(16)
C(14)–C(15)–H(15)
C(16)–C(15)–H(15)
C(11)–C(16)–C(15)
C(11)–C(16)–H(16)
C(15)–C(16)–H(16)
C(26)–C(21)–C(22)
C(26)–C(21)–C(2)
C(22)–C(21)–C(2)
C(23)–C(22)–C(21)
C(23)–C(22)–C(27)
C(21)–C(22)–C(27)
C(24)–C(23)–C(22)
C(24)–C(23)–H(23)
C(22)–C(23)–H(23)
C(25)–C(24)–C(23)
C(25)–C(24)–H(24)
C(23)–C(24)–H(24)
C(24)–C(25)–C(26)
C(24)–C(25)–H(25)
C(26)–C(25)–H(25)
C(21)–C(26)–C(25)
C(21)–C(26)–H(26)
C(25)–C(26)–H(26)
C(22)–C(27)–H(27A)
C(22)–C(27)–H(27B)
H(27A)–C(27)–H(27B)
C(22)–C(27)–H(27C)
H(27A)–C(27)–H(27C)
H(27B)–C(27)–H(27C)
120.7
122.03(18)
118.06(15)
119.91(15)
118.46(17)
120.8
120.8
120.4
120.91(17)
119.5
120.1(2)
119.9
11
119.9
120.4(2)
119.8
Table 4 Hydrogen coordinates (9104) and isotropic displacement
˚
parameters (A2 9 103) for (1)
119.8
x
y
z
U(eq)
120.3(2)
119.9
H(13)
H(14)
H(15)
H(16)
H(23)
H(24)
H(25)
H(26)
H(27A)
H(27B)
H(27C)
H(33)
H(35)
H(36)
10,225
10,321
8,346
6,257
4,081
2,243
1,768
3,132
5,961
5,928
6,776
473
5,657
4,001
3,130
3,935
6,819
5,729
4,515
4,405
7,460
7,337
6,544
5,867
8,504
7,674
2,464
1,909
1,180
954
62
61
53
42
48
56
54
43
65
65
65
41
39
34
119.9
120.81(17)
120.09(17)
118.94(16)
117.98(18)
120.84(18)
121.19(17)
121.4(2)
119.3
5,174
4,957
3,801
2,841
4,791
3,761
4,499
396
119.3
120.0(2)
120.0
2,083
4,165
1,679
2,220
120.0
120.1(2)
120.0
(0.1 mol) in toluene (10 mL) and the reaction mixture
refluxed for 4 h. After completion of reaction the contents
were concentrated in vacuo and the residue was taken up in
dichloromethane (5 mL). The latter was added drop-wise
with continuous stirring to a solution of 2-methyl benzoic
acid in dichloromethane at 0–5 °C. The reaction mixture
was stirred overnight at room temperature. The reaction
mixture was quenched and diluted with distilled water,
washed with 10% aqueous citric acid followed by NaHCO3,
dried over anhydrous sodium sulfate and concentrated in
vacuo. The residue was recrystallized from ethanol. Yield
120.0
119.65(19)
120.2
120.2
109.5
109.5
109.5
109.5
109.5
109.5
123

J Chem Crystallogr (2010) 40:919–923
923
Fig. 1 The molecular structure
of the title molecule, with the
atom-numbering scheme.
Displacement ellipsoids are
drawn at the 50% probability
level
Supplementary Material
Crystallographic data for the structure reported in this
paper have been deposited with the Cambridge Crystallo-
graphic Data Centre (deposition number: CCDC 691753).
Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [e-mail: deposit@ccdc.cam.ac.uk].
Acknowledgments Naeem Abbas gratefully acknowledges
a
research scholarship from HEC Islamabad under HEC Indigenous
Ph.D Scholarship 5000 Scheme.
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123