A facile one-pot synthesis of substituted N-{[2-(aminocarbonyl)phenylamino]thioxomethyl}benzamides and 2-aryl-quinazolin-4(3H)-ones

Article abstract of DOI:10.1134/S1070363215100278

The substituted N-{[2-(aminocarbonyl)phenylamino]thioxomethyl}benzamides and 2-arylquinazolin-4(3H)-ones are synthesized by the reaction of ammonium thiocyanate and aroyl chlorides with 2-amino-benzamide under solvent-free conditions or under reflux in MeCN.

Full text of DOI:10.1134/S1070363215100278

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 10, pp. 2395–2398. © Pleiades Publishing, Ltd., 2015.
A Facile One-Pot Synthesis of Substituted
N-{[2-(Aminocarbonyl)phenylamino]thioxomethyl}benzamides
and 2-Aryl-quinazolin-4(3H)-ones1
R. Mohebat, M. Raja, and Gh. Mohammadian
Department of Chemistry, Islamic Azad University, Yazd Branch, Yazd, P.O. Box 89195-155, Iran
e-mail: mohebat@iauyazd.ac.ir
Received July 21, 2015
Abstract—The substituted N-{[2-(aminocarbonyl)phenylamino]thioxomethyl}benzamides and 2-arylquinazolin-
4(3H)-ones are synthesized by the reaction of ammonium thiocyanate and aroyl chlorides with 2-amino-
benzamide under solvent-free conditions or under reflux in MeCN.
Keywords: 2-aminobenzamide, aroyl chlorides, ammonium thiocyanate, N-{[2-(aminocarbonyl)phenylamino]-
thioxomethyl}benzamides, 2-aryl-quinazolin-4(3H)-ones
DOI: 10.1134/S1070363215100278
INTRODUCTION
100 Hz) in DMSO-d6 using TMS as internal standard.
Melting points were determined with an Electro-
thermal 9100 apparatus. Elemental analyses were per-
formed with a Costech ECS 4010 CHNS-O analyzer at
the analytical laboratory of the Islamic Azad University,
Yazd branch. IR spectra were recorded on a Shimadzu
IR-470 spectrometer. Mass spectra were measured on a
FINNIGAN-MAT 8430 mass spectrometer (ionization
potential 70 eV). The chemicals for this study were
purchased from Fluka (Buchs, Switzerland) and used
without further purification.
Many acyl thiourea derivatives are well known in
agriculture as fungicidal, antiviral, and regulating
agents for plant protection [1–5]. Also, they are
commercial insecticides [6] and herbicides [7, 8] and
chelating agents in transition metal complexes [9]. The
complexes of thiourea derivatives also show a wide
range of biological activities [10]. Thioureas and their
substituted analogues are epoxy resin curing agents [9]
and intermediates in synthesis of N-aroyl, N'-aryl-
thioureas [9, 11, 12].
General procedure. In a 50-mL round bottom
flask, ammonium thiocyanate (2 mmol) and aroyl
chloride 1 (2 mmol) were added, the mixture was
heated at about 80°C for 5 min and. then cooled to
room temperature. a. 2-aminobenzamide 2 (2 mmol) in
MeCN (5 mL) was then added and the mixture was
refluxed for 30 min. The solvent was removed in
vacuum and then the reaction mixture was treated with
20 mL water. The precipitate was filtered off and
dried. The residue was then purified by a column
chromatography [silica gel (60, 230–400 mesh),
hexane–ethyl acetate (3 : 1)]. Fractions containing 3
and 4 were evaporated to obtain pure compounds. Com-
pounds 3c–3e and 4c–4e obtained by Method A can be
also simply separated by filtration and recrystallized
from EtOH.
Quinazolin-4(3H)-ones are important precursors for
the synthesis of natural and pharmacological com-
pounds, including febrifugine and isofebrifugine [13].
They can also be obtained by the cyclization of
anthranilamides with aldehydes and by other similar
methods [14–22]. In the study, N-{[2-(aminocarbonyl)-
phenylamino]thioxomethyl}benzamides and 2-aryl-
quinazolin-4(3H)-ones were synthesized by the
reaction of ammonium thiocyanate and aroyl chlorides
with 2-aminobenzamide under solvent-free conditions
or under reflux in MeCN.
EXPERIMENTAL
NMR spectra were measured on a Bruker DRX-400
Avance spectrometer (1H NMR at 400 Hz, 13C NMR at
Method b. 2-aminobenzamide 2 (2 mmol) was then
added slowly and the mixture was stirred for 3 h at
1 The text was submitted by the authors in English.
2395

2396
MOHEBAT et al.
Yield by N-{[2-(aminocarbonyl)phenylamino]thioxomethyl}benzamides (3a–3e) and 2-aryl-quinazolin-4(3H)-ones (4a–4e)
from the reaction between 2-aminobenzamide and aroyl chlorides in the presence of ammonium thiocyanate (see Scheme 1,
methods a and b)
Yielda, %
mp, °C
calculated, %
Comp. no.
Ar
method a
method b
found, %
180–190
193–195
213–215
226–228
198–200
235–237
219–221
314–315
348–249
360–262
3a
3b
3c
3d
3e
4a
4b
4c
4d
4e
C6H5
37
43
12
6
87
93
77
55
34
8
188–190 [23]
194–195 [23]
–
3-MeC6H4
4-BrC6H4
3-NO2C6H4
4-NO2C6H4
C6H5
–
–
–
46
44
73
76
84
235–237 [24]
219–220 [25]
314–316 [26]
351–353 [27]
363–364 [27]
3-MeC6H4
4-BrC6H4
3-NO2C6H4
4-NO2C6H4
5
16
36
55
a Yields refer to the pure isolated products.
room temperature under solvent-free conditions. Then,
the reaction mixture was treated with a 20 mL of
water. The following procedure was the same as in
method a.
N-{([2-(Aminocarbonyl)phenyl]amino)thioxo-
methyl}-3-nitrobenzamide (3d). Cream powder, mp
226–228°C. IR spectrum, ν, cm–1: 3465, 3305, 3200,
3060, 1676, 1646, 1608, 1576, 1525, 1499, 1347,
1
1243, 1144. H NMR spectrum, (J, Hz): 7.33 t (1H,
General procedure for conversion of 3 to 4 by
NaOH. A mixture of compound 3 (2 mmol) and 5 mL
of NaOH (10% w/v) was stirred at room temperature
for 1 h. The compound was extracted with ethyl
acetate (5 × 3 mL). The organic layer was washed with
brine, dried over Na2SO4, and concentrated in vacuum.
The crude product was ground to a fine powder with
diethyl ether to obtain a pure compound 4 as white
solid.
7.6 Hz, CHarom), 7.52 t (1H, 7.6 Hz, CHarom), 7.60 s
(1H, NH), 7.63 br.d (1H, 8.0 Hz, CHarom), 7.82 t (1H,
8.0 Hz, CHarom), 8.12 s (1H, NH), 8.16 br.d (1H,
7.6 Hz, CHarom), 8.36 d (1H, 7.4, CHarom), 8.47 d (1H,
7.6 Hz, CHarom), 8.76 s (1H, CHarom), 12.00 s (1H,
13
NH), 13.09 s (1H, NH). C NMR spectrum, δC, ppm:
123.6, 124.2, 126.3, 127.3, 128.4, 129.3, 129.7, 130.4,
131.2, 136.5, 140.2, 148.5 (carbons of aromatics),
165.8, 169.4 (2C=O), 179.6 (C=S). Found, %: C 52.12;
H 3.62; N 16.20; S 9.27. C15H12N4O4S. Calculated, %:
C 52.32; H 3.51; N 16.27; S 9.31. M 344.
N-{[(2-(Aminocarbonyl)phenyl]amino)thioxo-
methyl}-4-bromobenzamide (3c). Cream powder, mp
213–215°C. IR spectrum, ν, cm–1: 3480, 3315, 3205,
3045, 1675, 1644, 1609, 1585, 1514, 1475, 1326,
N-{([2-(Aminocarbonyl)phenyl]amino)thioxo-
methyl}-4-nitrobenzamide (3e). Cream powder, mp
198–200°C. IR spectrum, ν, cm–1: 3520, 3365, 3245,
3055, 1683, 1644, 1609, 1579, 1520, 1482, 1329, 1244,
1
1250, 1147. H NMR spectrum, δ, ppm (J, Hz): 7.30 t
(1H, 7.6 Hz, CHarom), 7.49 t (1H, 7.6 Hz, CHarom), 7.57
s (1H, NH), 7.60 br.d (1H, 7.2 Hz, 1CHarom), 7.73 d
(2H, 8.8 Hz, 2CHarom), 7.88 d (2H, 8.4 Hz, 2CHarom),
8.09 s (1H, NH), 8.12 br.d (1H, 8 Hz, CHarom), 11.63 s
1
1139. H NMR spectrum, (J, Hz): 7.32 t (1H, 7.6 Hz,
CHarom), 7.51 t (1H, 7.2 Hz, CHarom), 7.58 s (1H, NH),
7.62 br.d (1H, 8.0 Hz, CHarom), 8.11 s (1H, NH), 8.15 d
(2H, 8.8 Hz, 2CHarom), 8.19 br.d (1H, 7.6 Hz, CHarom),
8.33 d (2H, 8.8 Hz, 2CHarom ), 11.92 s (1H, NH), 13.07
s (1H, NH). 13C NMR spectrum, δC, ppm: 123.8, 126.4,
127.3, 128.4, 129.7, 130.4, 130.8, 136.9, 138.6, 150.3
(carbons of aromatics), 166.3, 169.4 (2C=O), 179.5
13
(1H, NH), 13.08 s (1H, NH). C NMR spectrum, δC,
ppm: 126.2, 126.3, 127.4, 127.5, 128.3, 129.9, 130.3,
131.3, 131.9, 136.9 (carbons of aromatics), 166.9,
169.4 (2C=O), 179.7 (C=S). Found, %: C 47.50; H
3.28; N 11.07, S 8.45. C15H12BrN3O2S. Calculated, %:
C 47.63; H 3.20; N 11.11; S 8.48. M 379.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 10 2015

A FACILE ONE-POT SYNTHESIS
H
2397
O
NH2
+
O
N
O
H
O
N
N
Ar
NH
Ar
NH2
method a or b
NH4SCN
+
+
Cl
Ar
O
S
NH2
3
1
2
4
Fig. 1. The reaction between 2-aminobenzamide and aroyl chlorides in the presence of ammonium. thiocyanate. Method a: CH3CN,
teflux; method b: solvent-free.
(C=S). Found, %: C 52.22; H 3.59; N 16.25, S 9.27.
C15H12N4O4S. Calculated, %: C 52.32; H 3.51; N
16.27; S 9.31. M 344.
NH proton. Multiplets between 7.50 and 8.23 ppm are
due to aromatic protons. The 13C NMR spectrum of
compound 4a shows 12 signals, in agreement with the
proposed structure. The IR spectrum of compound 4a
also supports the suggested structure. The mass
spectrum of compound 3c has a molecular ion peak at
m/z = 379. The 1H NMR spectrum of the compound 3c
in DMSO exhibits four single signals at 7.57, 8.09,
11.63, and 13.08 ppm, which disappear after addition
of a few drops of D2O. These signals are attributed to
NH protons. Multiplets between 7.30 and 8.12 ppm are
due to aromatic protons. The 13C NMR spectrum of the
compound 3c shows 13 signals, in agreement with the
proposed structure. The suggested structure of this
compound is also supported by the IR spectrum.
RESULTS AND DISCUSSION
The reaction of aroyl chlorides 1 and 2-amino-
benzamide 2 in the presence of ammonium thiocyanate
gives products 3 and 4 under solvent-free conditions or
under reflux in MeCN (Fig 1).
The results are listed in the table.
Compounds 3a, 3b, 4a–4e are known and their
structures were deduced from the comparison of
melting points and spectral data with authentic samples
[20].
A tentative mechanism of this transformation is
proposed in Fig. 2.
Compounds 3c–3e are new and their structures
were deduced by the elemental and spectral analyses.
For example, the mass spectrum of the compound 4a
Probably, aroyl chloride 1 easily reacts with
ammonium thiocyanate to form aroyl thiocyanate 5,
then a compound 3 is generated in the presence of 2-
aminobenzamide 2 and is converted to a compound 4
by elimination of HSCN and H2O.
1
has a molecular ion peak at m/z = 222. The H NMR
spectrum of this compound in DMSO has a single
signal at δ = 12.59 ppm that disappears after addition
of a few drops of D2O. This signal is attributed to the
O
O
O
S
2
+ NH4SCN
Ar
N C
S
Ar
Cl
Ar
N
N
H
H
5
1
H2N
O
3
O
S
O
O
O
−HSCN
Ar
N
−H2O
4
Ar
N
or −COS
H
N
H
H2N
NH3 or OH
7
6
Fig. 2. The suggested mechanism for the formation of compounds 3 and 4.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 10 2015

2398
MOHEBAT et al.
O
N
O
NH2
H
H
N
N
Ar
NaOH (10% w/v)
NH
Ar
room temperature, 1 h
O
S
3
4
Fig. 3. The compounds 3 are converted to compounds 4 in the presence of NaOH.
1964, vol. 53, pp. 40–42.
In some experiments, we found that compounds 3
are converted to compounds 4 in the presence of
triethylamine (Fig. 3).
11. Saeed, S., Bhatti, M. H., Tahir, M.K., and Jones, P.G.,
Acta Crystallogr. E, 2008, vol. 64, p. o1369.
12. Saeed, S., Bhatti, M.H., Yunus, U., and Jones, P.G.,
In conclusion, we have developed a straightforward
protocol for the synthesis of acyl thiourea derivatives
and quinazoline-4(3H)-ones under solvent-free
conditions or under reflux in MeCN. This procedure
has several advantages, including clean reactions and
lower reaction time.
Acta Crystallogr. E, 2008, vol. 64, p. o1566.
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ACKNOWLEDGMENTS
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16. Salehi, P., Dabiri, M., Zolfigol, M.A., and
The study was financially supported by the
Research Council of the Islamic Azad University
(Yazd, Iran).
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