Synthesis of bis-ureas from Bis(o-nitrophenyl) carbonate

Article abstract of DOI:10.3390/molecules13123192

A general method for the preparation of bis-ureas from bis(o-nitrophenyl) carbonate has been developed. Directional urea synthesis is achieved by sequential amine addition to bis(o-nitrophenyl) carbonate in two steps: in the first step bis(o-nitrophenyl) carbonate is reacted with benzylamine to form benzyl-o-nitrophenyl carbamate; in the second step the carbamate is reacted with a variety of diamines in toluene to yield bis-ureas.

Full text of DOI:10.3390/molecules13123192

Molecules 2008, 13, 3192-3197; DOI: 10.3390/molecules13123192
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molecules
ISSN 1420-3049
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Article
Synthesis of Bis-ureas from Bis(o-nitrophenyl) Carbonate
Maria-Cristina Turoczi *, Monika Simon, Valentin Badea and Carol Csunderlik
“ POLITEHNICA” University of Timisoara, Department of Applied Chemistry and Engineering of
Organic and Natural Compounds, 300006 Timisoara, Piata Victoriei 2, Romania
* Author to whom correspondence should be addressed; E-mail: cristina_turoczi@yahoo.com; Tel:
+40-256-404233; Fax: +40-256-403060.
Received: 18 November 2008; in revised form: 28 November 2008 / Accepted: 3 December 2008 /
Published: 15 December 2008
Abstract: A general method for the preparation of bis-ureas from bis(o-nitrophenyl)
carbonate has been developed. Directional urea synthesis is achieved by sequential amine
addition to bis(o-nitrophenyl) carbonate in two steps: in the first step bis(o-nitrophenyl)
carbonate is reacted with benzylamine to form benzyl-o-nitrophenyl carbamate; in the
second step the carbamate is reacted with a variety of diamines in toluene to yield bis-ureas.
Keywords: Bis(o-nitrophenyl) carbonate; Carbamate, Bis-urea.
Introduction
Bis-urea compounds are well-suited for material science. Bis-urea grafted molecules or polymers
give rise to strong hydrogen bonding interactions that have been used to obtain gelling agents [1-5], to
structure inorganic materials [6] and also in polymeric assemblies [7, 8]. Also, it has been
demonstrated that bis-ureas are guest-host molecules that exhibits molecular recognition [7]. Recently,
it has been reported some chiral bis-ureas which can form microfibrillar foams [9] or lyotropic liquid
crystals [10].
The reaction of amines or diamines with isocyanates [1, 2, 6] or diisocyanate [4, 5, 9-11] is the key
step in the preparation of bis-urea. This method is very inconvenient because isocyanates and
diisocyanates are usually prepared from phosgene, a very dangerous reagent. Our attention was
therefore directed towards bis(o-nitrophenyl) carbonate (1), a mild reagent, that can be used in organic
synthesis instead of phosgene or its derivatives. We have already reported its reactivity in reaction

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with primary and secondary amines and have obtained successfully di- and trisubstituted ureas [12,
13]. In this paper we wish to report the use of bis(o-nitrophenyl) carbonate (1) in the synthesis of bis-
ureas 3.
Results and Discussion
An efficient and strainghtforward two-step synthetic route for bis-ureas 3 using bis(o-nitrophenyl)
carbonate (1) has been developed. In the first step, bis(o-nitrophenyl) carbonate (1) is reacted with
benzylamine to produce the intermediate, N-benzyl-o-nitrophenyl carbamate (2, Scheme 1). The
second step is the formation of bis-ureas 3 by treatment of this intermediate with various diamines
(Scheme 2).
Scheme 1. Synthesis of N-benzyl-o-nitrophenyl carbamate from bis(o-nitrophenyl) carbonate.
O
O
+
+
NH2
OH
O
N
O
O
H
NO2
NO2
NO2
NO2
1
2
Scheme 2. Synthesis of bis-ureas from N-benzyl-o-nitrophenyl carbamate
O
H
H
H
H
2
R
2
+
+
H2N
N
N
N
N
NH2
R
OH
O
N
H
O
O
NO2
NO2
3
2
The synthesis of N-benzyl-o-nitrophenyl carbamate (2) was based on the published procedure for
the preparation of o-nitrophenyl carbamates [14], but without the isolation of this intermediate. Thus to
obtain bis-ureas 3 a solution of carbamate 2 which also contains o-nitrophenol was treated with a
diamine in the molar ratio carbamate: diamine = 2.5:1. The reactions we carried out in toluene because
in the second step the transformation of carbamate occurs more slowly and it was necessary to increase
the reaction temperature to reflux.
Following our protocol with aliphatic diamine isolation of bis-ureas 3a-f was achieved, from the
reaction mixture by precipitation after one hour, in yields between 86-95% (Table 1). From o-
phenylenediamine, an aromatic diamine, using 0.1 equiv. of 4-dimethylaminopyridine,
bis(benzylcarbamoyl)-o-phenylenediamine (3g) was obtained in 76%, after two hours of heating.
We also were investigated the reactions with secondary diamines. The bis-urea
bis(benzylcarbamoyl)piperazine (3h) was easily prepared in high yield by reaction of piperazine with
N-benzyl-o-nitrophenyl carbamate.

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Table 1. Preparation of bis-ureas from different diamines.
Yield
Diamine
mp (°C)
ν
C=O (cm-1) Bis-urea 3
(%)
86
240-242
228-230
217-219
1621
1623
1621
3a
3b
3c
H2N
H2N
NH2
NH2
95
86
NH2
NH2
H2N
H2N
H2N
92
90
245-247
224-226
1618
1618
3d
3e
NH2
H2N
NH2
NH2
91
255-257
1618
3f
H2N
76
95
197-199
190-192
1629
1620
3g
3h
HN
NH
Conclusions
We have developed a convenient two-step synthesis procedure for the preparation of bis-ureas
using bis(o-nitrophenyl) carbonate as a starting material.
Experimental
General
Melting points were determined in a Boetius apparatus (Carl Zeiss Jena). The IR spectra were
recorded in KBr pellet for solid compounds and the reaction monitoring was carried out in
thermostated silicon cells of 0.137 mm thickness on a Jasco FT/IR-430 instrument. TLC analyses were
carried out on pre-coated plates silica gel 60 F254 (Merk). Spot visualization was achieved by exposing
the plates under a UV 254 lamp and by treatment with 5% ethanolic phosphomolybdenic acid solution
1
13
and heating of the dried plates. The H-NMR and C-NMR were recorded on a Bruker DPX at 200
MHz in DMSO-d6, with TMS as reference. The values of coupling constants are normal for vicinal
1
couplings (CH-CH, CH-NH): 6.5 -7 Hz. Detailed IR, H-NMR and 13C-NMR spectra are available
from the authors. Elemental analysis was carried out on a Vario EL instrument. Bis(o-nitrophenyl)
carbonate (1) was obtained by our published method [15, 16]. All reagents were purchased from
chemical suppliers and used without further purification.
General procedure for the preparation of bis-ureas
Compound 1 (200 mg, 0.657 mmol) was dissolved in toluene (10 mL) and benzylamine (1.2 equiv.)
was added. The reaction mixture was stirred at room temperature until no further carbonate could be

Molecules 2008, 13
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detected by TLC (eluent: dichloromethane). The reaction mixture was washed with 1M HCl solution
(5 mL), dried over anhydrous Na2SO4 and filtered. The diamine (2.5 equiv.) was then added to the
filtrate and the resulting reaction mixture was heated under reflux conditions until no diamine was
detectable by TLC (eluent: dichloromethane). The insoluble bis-urea 3 obtained was filtered off and
washed with cold toluene and a recrystalization from ethanol was performed.
o
Bis(benzylcarbamoyl)-ethylenediamine (3a). 73.6 mg ( 86%); mp: 240-242 C; IR (KBr, cm-1): 3330,
1
3031, 1621, 1575, 1264, 697. H-NMR δ 3.11 (t, 4H), 4.29 (d, 4H), 5.98 (NH, 2H), 6.39 (NH, 2H),
13
7.29 (m, 10H); C-NMR δ 40.31, 42.99, 126.39, 126.98, 128.04, 140.8, 158.21; Elemental Analysis
[Calculated (Found)] C18H22N4O2: C: 66.24 (66.29); H: 6.79 (6.50); N: 17.17 (16.90).
o
Bis(benzylcarbamoyl)-1,2-propylenediamine (3b). 84.2 mg (95%); mp: 228-230 C; IR (KBr, cm-1):
3330, 3031, 1623, 1568, 1260, 694; 1H-NMR δ 1.02 (d, 3H), 3.03 (t, 2H), 3.71 (m, 1H), 4.22 (d, 4H),
7.23 (m, 10H), 5.86 (NH, 1H), 6.03 (NH, 1H) 6.32 (NH, 1H), 6.42 (NH, 1H); 13C-NMR δ 18.97,
40.61, 45.16, 45.94, 126.42, 126.94, 128.08, 140.8, 158.29. Elemental Analysis [Calculated (Found)]
C19H24N4O2: C: 67.04 (66.62); H: 7.11 (6.73); N: 16.46 (16.14).
o
Bis(benzylcarbamoyl)-1,3-propylenediamine (3c). 76.2 mg (86%); mp: 217-219 C; IR (KBr, cm-1):
1
3355, 3031, 2919, 2870,1621, 1578, 1287, 695; H-NMR δ 1.48(m, 2H), 3.05 (q, 4H), 4.22 (d, 4H),
5.94 (NH, 2H), 6.34 (NH, 2H), 7.25 (m, 10H); 13C-NMR δ 31.03, 38.23, 42.86, 126.36, 126.87,
128.04, 140.87, 158.11; Elemental Analysis [Calculated (Found)] C19H24N4O2: C: 67.04 (66.50); H:
7.11 (7.08); N: 16.46 (16.30).
o
Bis(benzylcarbamoyl)-1,4-butylenediamine (3d). 85.3 mg (92%); mp 245-247 C; IR (KBr, cm-1):
3338, 3031, 2939, 2863, 1618, 1573, 1268, 695; 1H-NMR δ 1.39 (m, 4H), 3.05 (q, 4H), 4.23 (d, 4H),
5.86 (NH, 2H), 6.21 (NH, 2H), 7.25 (m, 10H); 13C-NMR δ 25.57, 40.03, 42.96, 126.38, 129.94,
128.04, 140.83, 158.1; Elemental Analysis [Calculated (Found)] C20H26N4O2: C: 67.77 (67.43); H:
7.39 (7.27); N: 15.81 (15.52).
Bis(benzylcarbamoyl)-1,6-hexamethylenediamine (3e). 90.2 mg (90%); mp: 224-226 oC; IR (KBr, cm-
1): 3346, 3031, 2932. 2856, 1618, 1576, 1254, 695. H-NMR δ 1.30 (m, 4H), 1.39 (m, 4H), 3.01 (q,
1
4H), 4.22 (d, 4H), 5.81 (NH, 2H), 6.18 (NH, 2H), 7.22 (m, 10H); Elemental Analysis [Calculated
(Found)] C22H30N4O2: C: 69.08 (68.74); H: 7.91 (7.50); N: 14.65 (14.40).
o
Bis(benzylcarbamoyl)-1,2-cyclohexylenediamine (3f). 90.9 mg (91%); mp: 255-257 C; IR (KBr, cm-
1): 3346, 3031, 2932, 2856, 1618, 1576, 1254, 695; H-NMR δ 1.27 (m, 4H), 1.41 (m, 4H), 3.31 (m,
1
2H), 4.21 (d, 4H), 5.78 (NH, 2H), 6.36 (NH, 2H), 7.25 (m, 10H); 13C-NMR δ 24.40, 33.03, 42.96,
53.10, 126.35, 126.46, 126.94, 140.83, 158.08; Elemental Analysis [Calculated (Found)] C22H28N4O2:
C: 69.45 (69.02); H: 7.42 (7.37); N: 14.73 (14.48).
o
Bis(benzylcarbamoyl)-1,2-phenylenediamine (3g). 74.6 mg (76%); mp: 197-199 C; IR (KBr, cm-1):
1
3294, 3030, 1686, 1629, 1247, 696; H-NMR δ 4.28 (d, 4H), 7.30 (m, 12H) 7.55 (d, 2H), 6.96 (NH,

Molecules 2008, 13
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2H), 7.90 (NH, 2H); 13C-NMR δ 42.97, 123.19, 123.43, 126.6, 127.16, 128.15, 140.17, 155.86;
Elemental Analysis [Calculated (Found)] C22H22N4O2: C: 70.57 (70.05); H: 5.92 (5.52); N: 14.96
(14.85).
o
Bis(benzylcarbamoyl)-piperazine (3h). 92.5 mg (95%); mp: 190-192 C; IR (KBr, cm-1): 3302, 3023,
1
1320, 1620, 1554, 1262, 694; H-NMR δ 3.37 (t, 8H), 4.27 (d, 4H), 7.09 (NH, 2H), 7.28 (m, 10H);
13C-NMR δ 43.23, 43.44, 126.31, 126.93, 127.97, 140.79, 157.37; Anal. Calc. (C20H24N4O2): C: 68.16
(67.88); H: 6.86 (6.59); N: 15.90 (15.72).
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Sample Availability: Samples of the compounds 1, 2, 3a-h, are available from the authors.
© 2008 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
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