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Article

Synthesis of Bis-ureas from Bis(o-nitrophenyl) Carbonate

by
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.
Molecules 2008, 13(12), 3192-3197; https://doi.org/10.3390/molecules13123192
Submission received: 18 November 2008 / Revised: 28 November 2008 / Accepted: 3 December 2008 / Published: 15 December 2008
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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.

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 [1,2,3,4,5], 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, 9,10,11] 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 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).
Molecules 13 03192 g001 550
Scheme 1. Synthesis of N-benzyl-o-nitrophenyl carbamate from bis(o-nitrophenyl) carbonate.
Scheme 1. Synthesis of N-benzyl-o-nitrophenyl carbamate from bis(o-nitrophenyl) carbonate.
Molecules 13 03192 g001
Molecules 13 03192 g002 550
Scheme 2. Synthesis of bis-ureas from N-benzyl-o-nitrophenyl carbamate
Scheme 2. Synthesis of bis-ureas from N-benzyl-o-nitrophenyl carbamate
Molecules 13 03192 g002
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.
Table
Table 1. Preparation of bis-ureas from different diamines.
Table 1. Preparation of bis-ureas from different diamines.
DiamineYield (%)mp (°C)ν C=O (cm-1)Bis-urea 3
Molecules 13 03192 i00186240-24216213a
Molecules 13 03192 i00295228-23016233b
Molecules 13 03192 i00386217-21916213c
Molecules 13 03192 i00492245-24716183d
Molecules 13 03192 i00590224-22616183e
Molecules 13 03192 i00691255-25716183f
Molecules 13 03192 i00776197-19916293g
Molecules 13 03192 i00895190-19216203h

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 and heating of the dried plates. The 1H-NMR and 13C-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 couplings (CH-CH, CH-NH): 6.5 -7 Hz. Detailed IR, 1H-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 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.
Bis(benzylcarbamoyl)-ethylenediamine (3a). 73.6 mg ( 86%); mp: 240-242 oC; IR (KBr, cm-1): 3330, 3031, 1621, 1575, 1264, 697. 1H-NMR δ 3.11 (t, 4H), 4.29 (d, 4H), 5.98 (NH, 2H), 6.39 (NH, 2H), 7.29 (m, 10H); 13C-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).
Bis(benzylcarbamoyl)-1,2-propylenediamine (3b). 84.2 mg (95%); mp: 228-230 oC; 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).
Bis(benzylcarbamoyl)-1,3-propylenediamine (3c). 76.2 mg (86%); mp: 217-219 oC; IR (KBr, cm-1): 3355, 3031, 2919, 2870,1621, 1578, 1287, 695; 1H-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).
Bis(benzylcarbamoyl)-1,4-butylenediamine (3d). 85.3 mg (92%); mp 245-247 oC; 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. 1H-NMR δ 1.30 (m, 4H), 1.39 (m, 4H), 3.01 (q, 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).
Bis(benzylcarbamoyl)-1,2-cyclohexylenediamine (3f). 90.9 mg (91%); mp: 255-257 oC;IR (KBr, cm-1): 3346, 3031, 2932, 2856, 1618, 1576, 1254, 695; 1H-NMR δ 1.27 (m, 4H), 1.41 (m, 4H), 3.31 (m, 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).
Bis(benzylcarbamoyl)-1,2-phenylenediamine (3g). 74.6 mg (76%); mp: 197-199 oC; IR (KBr, cm-1): 3294, 3030, 1686, 1629, 1247, 696; 1H-NMR δ 4.28 (d, 4H), 7.30 (m, 12H) 7.55 (d, 2H), 6.96 (NH, 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).
Bis(benzylcarbamoyl)-piperazine (3h). 92.5 mg (95%); mp: 190-192 oC; IR (KBr, cm-1): 3302, 3023, 1320, 1620, 1554, 1262, 694; 1H-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).

References

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  • Sample Availability: Samples of the compounds 1, 2, 3a-h, are available from the authors.

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MDPI and ACS Style

Turoczi, M.-C.; Simon, M.; Badea, V.; Csunderlik, C. Synthesis of Bis-ureas from Bis(o-nitrophenyl) Carbonate. Molecules 2008, 13, 3192-3197. https://doi.org/10.3390/molecules13123192

AMA Style

Turoczi M-C, Simon M, Badea V, Csunderlik C. Synthesis of Bis-ureas from Bis(o-nitrophenyl) Carbonate. Molecules. 2008; 13(12):3192-3197. https://doi.org/10.3390/molecules13123192

Chicago/Turabian Style

Turoczi, Maria-Cristina, Monika Simon, Valentin Badea, and Carol Csunderlik. 2008. "Synthesis of Bis-ureas from Bis(o-nitrophenyl) Carbonate" Molecules 13, no. 12: 3192-3197. https://doi.org/10.3390/molecules13123192

APA Style

Turoczi, M. -C., Simon, M., Badea, V., & Csunderlik, C. (2008). Synthesis of Bis-ureas from Bis(o-nitrophenyl) Carbonate. Molecules, 13(12), 3192-3197. https://doi.org/10.3390/molecules13123192

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