Rapid synthesis of N-acyl ureas from their thio analogues using wet silica-supported permanganate under solvent-free conditions

Article abstract of DOI:10.1080/10426500500272343

A rapid method to N-acyl ureas from corresponding N-acyl thioureas is described. N-coumaroyl-N′-arylthioureas, which are easily prepared by the reaction of coumarin-3-carboxylic acid chloride with potassium thiocyanate and arylamines, can be expeditiously

Full text of DOI:10.1080/10426500500272343

This article was downloaded by: [McMaster University]
On: 06 April 2015, At: 10:44
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Rapid Synthesis of N-Acyl Ureas
from Their Thio Analogues
Using Wet Silica-Supported
Permanganate Under Solvent-
Free Conditions
Zheng Li a , Jin-Lan Yu a , Sheng-Yi Shi a & Wei Zhu a
a Gansu Key Laboratory of Polymer Materials ,
College of Chemistry and Chemical Engineering,
Northwest Normal University , Lanzhou, Gansu, P.R.
China
Published online: 01 Feb 2007.
To cite this article: Zheng Li , Jin-Lan Yu , Sheng-Yi Shi & Wei Zhu (2006) Rapid
Synthesis of N-Acyl Ureas from Their Thio Analogues Using Wet Silica-Supported
Permanganate Under Solvent-Free Conditions, Phosphorus, Sulfur, and Silicon and the
Related Elements, 181:5, 1031-1037, DOI: 10.1080/10426500500272343
To link to this article: http://dx.doi.org/10.1080/10426500500272343
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with

primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 181:1031–1037, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500272343
Rapid Synthesis of N-Acyl Ureas from Their Thio
Analogues Using Wet Silica-Supported Permanganate
Under Solvent-Free Conditions
Zheng Li
Jin-Lan Yu
Sheng-Yi Shi
Wei Zhu
Gansu Key Laboratory of Polymer Materials, College of Chemistry
and Chemical Engineering, Northwest Normal University, Lanzhou,
Gansu, P.R. China
A rapid method to N-acyl ureas from corresponding N-acyl thioureas is de-
scribed. N-coumaroyl-Nꢀ-arylthioureas, which are easily prepared by the reaction of
coumarin-3-carboxylic acid chloride with potassium thiocyanate and arylamines,
can be expeditiously transformed into corresponding N-acyl ureas via r.t. grinding
with wet silica supported potassium permanganate under solvent-free conditions
in an excellent yield.
Keywords N-acyl urea; N-acyl thiourea; potassium permanganate; solvent-free
INTRODUCTION
N-acyl ureas are compounds of great interest because of their important
biological activities1 and their applications as intermediates for the
synthesis of many important heterocyclic compounds.2
The general synthesis of N-acyl ureas involves the reactions of sub-
stituted ureas with acyl chlorides at elevated temperatures3 the rather
the slow reaction of amides with isocyanates4 and the reaction of amines
with unstable N-acyl isocyanates.5 Recently, methods by the reaction
of S-allyl N-acylmonothiocarbamates with amines6 and the rearrange-
ment of O-acyl isoureas7 have also been reported. Very recently, we
Received April 28, 2005; accepted April 28, 2005.
The authors thank the Chun-Hui Project of the Minister of Education of China (Z2004-
1-62034) for the financial support of this work.
Address correspondence to Zheng Li, Gansu Key Laboratory of Polymer Materials,
College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou,
Gansu, 730070, P.R. China. E-mail: lizheng@nwnu.edu.cn
1031

1032
Z. Li et al.
have found that N-acyl ureas can be generated from corresponding N-
acyl thioureas by refluxing a suspension of the substrate in an aqueous
solution of potassium iodate for several hours.8 This new route thor-
oughly eliminated the employment of very toxic phosgene, which was
the starting material of isocyanates, and therefore represented a good
alternative to N-acyl ureas. As a part of our ongoing studies, herein we
report a more expeditious solvent-free strategy for N-acyl ureas from
their thio analogues by r.t. grinding with wet silica supported potassium
permanganate.
In a typical investigation, we selected ureas containing a coumaroyl
moiety as target products, which might be good candidates for biologi-
cally active9 or optically active10 compounds.
RESULTS AND DISCUSSION
The required N-coumaroyl-Nꢀ-arylthioureas (1a–k) were easily pre-
pared by solvent-free grinding of coumarin-3-formyl chloride with
potassium thiocyanate in the presence of a catalytic amount of
poly(ethylene glycol)-400 (PEG-400) followed by further grinding with
arylamines at r.t. in a high yield. Compounds 1a–k were further ground
with an equivalent of wet silica supported potassium permanganate in
a mortar under a solvent-free condition at r.t. to afford N-coumaroyl-
Nꢀ-arylureas (2a–k) in an excellent yield (Scheme 1). The overall reac-
tions studied were complete within 14–16 minutes with slightly quicker
rate for aryl rings bearing electron-donating groups and slightly slower
for those bearing electron-withdrawing groups. The products could be
readily obtained by extracting the resulting mixture with DMF.
SCHEME 1 a: Ar C6H5; b: Ar O2NC6H4; c: Ar 3-O2NC6H4; d: Ar 4-
O2NC6H4; e: Ar 3-BrC6H4; f: Ar 4-BrC6H4; g: Ar 2-ClC6H4; h: Ar 4-ClC6H4;
i: Ar 4-CH3OC6H4; j: Ar 1-Naphthyl; k: Ar 2-Naphthyl.
The reagent, potassium iodate, used in the literature8 also was
tested for the solvent-free reaction; however, no products were observed

Rapid Synthesis of N-Acyl Ureas
1033
although it gave good yields in aqueous solution after a long period of
refluxing.
In conclusion, N-acyl ureas could be easily generated from the cor-
responding N-acyl thioureas. The features of expeditiousness, the ease
of handling, the high yield, and the solvent-free and phosgene-free pro-
cedure allow this protocol to be well suitable to the synthesis of ureas
bearing various N-acyl substituents.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on an Alpha Centauri FTIR
1
spectrophotometer and H NMR spectra on a FT-80A instrument us-
ing (CD3)2SO as solvent and Me4Si as internal standard. Elemental
analyses were performed on a Carlo-Erba 1106 Elemental Analysis in-
strument. Mass spectra were recorded on a QP-1000A GC-MS using
the impact mode (70 eV). Melting points were observed in a melting
point apparatus and are uncorrected. Coumarin-3-formyl chloride was
prepared by refluxing coumarin-3-carboxylic acid with thionyl chloride.
General Procedure for the Preparation of Compounds 1a–k
To 3 mmol of coumarin-3-formyl chloride, 4.5 mmol of potassium thio-
cyanate and 0.1 mmol of PEG-400 were added. The mixture was ground
in a mortar with a pestle for 5 min at r.t., then 2.95 mmol of arylamine
was added, and the reaction mixture was ground for additional 2 min
at r.t. until TLC indicated the completion of the reaction. To the result-
ing mixture, 20 mL of distilled water was added, then the slurry was
filtered, and the solid was washed with 3 × 5 mL of water and recrys-
tallized from DMF-EtOH-H2O (6:3:1) to give the products. The physical
and spectral data of compounds 1a–k follow.
1
1a: Yellow solid. yield: 89%. m.p: 218–220◦C. H NMR (200 MHz,
DMSO-d6) δ12.39 (s, 1H, NH), 11.77 (s, 1H, NH), 9.12 (s, 1H, CH),
7.33–8.06 (m, 9H, Ar-H). IR (KBr, ν, cm−1): 3201 (N H), 1717, 1663
(C O), 1153 (C S). MS (m/z): 324 (M+). Anal. calcd. for C17H12N2O3S:
C, 62.95; H, 3.73; N, 8.64%. Found: C, 62.86; H, 3.90; N, 8.51%.
1
1b: Yellow solid. yield: 93%. m.p: 232–233◦C. H NMR (200 MHz,
DMSO-d6) δ12.63 (s, 1H, NH), 11.93 (s, 1H, NH), 9.15 (s, 1H, CH),
7.52-8.11 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3216 (N H), 1722, 1676
(C O), 1158 (C S). MS (m/z): 369 (M+). Anal. calcd. for C17H11N3O5S:
C, 55.28; H, 3.00; N, 11.38%. Found: C, 55.19; H, 2.89; N, 11.52%.
1
1c: Yellow solid. yield: 92%. m.p: 239–241◦C. H NMR (200 MHz,
DMSO-d6) δ12.59 (s, 1H, NH), 11.92 (s, 1H, NH), 9.13 (s, 1H, CH),
7.53–8.12 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3217 (N H), 1724, 1675

1034
Z. Li et al.
(C O), 1157 (C S). MS (m/z): 369 (M+). Anal. calcd. for C17H11N3O5S:
C, 55.28; H, 3.00; N, 11.38. Found: C, 55.17; H, 2.92; N, 11.45.
1
1d: Yellow solid. yield: 95%. m.p: 262◦C (dec). H NMR (200 MHz,
DMSO-d6) δ12.60 (s, 1H, NH), 11.91 (s, 1H, NH), 9.14 (s, 1H, CH),
7.51–8.09 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3219 (N H), 1723, 1674
(C O), 1161(C S). MS (m/z): 369 (M+). Anal. calcd. for C17H11N3O5S:
C, 55.28; H, 2.98; N, 11.38%. Found: C, 55.36; H, 3.11; N, 11.20%.
1
1e: Yellow solid. yield: 90%. m.p: 249–251◦C. H NMR (200 MHz,
DMSO-d6) δ12.51 (s, 1H, NH), 11.82 (s, 1H, NH), 9.14 (s, 1H,
CH), 7.48–8.07 (m, 8H, Ar-H). IR (KBr,ν, cm−1): 3215 (N H), 1728,
1683 (C O), 1145 (C S). MS (m/z): 402 (M+). Anal. calcd. for
C17H11N2O3SBr: C, 50.63; H, 2.75; N, 6.95%. Found: C, 50.71; H, 2.63;
N, 7.04%.
1
1f: Yellow solid. yield: 95%. m.p: 238–240◦C. H NMR (200 MHz,
DMSO-d6) δ12.55 (s, 1H, NH), 11.84 (s, 1H, NH), 9.14 (s, 1H, CH), 7.49-
8.09 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3217 (N H), 1730, 1686 (C O),
1147 (C S). MS (m/z): 402 (M+). Anal. calcd. for C17H11N2O3SBr: C,
50.63; H, 2.75; N, 6.95%. Found: C, 50.74; H, 2.67; N, 6.86%.
1
1g: White solid. yield: 89%. m.p: 234–235◦C. H NMR (200 MHz,
DMSO-d6) δ12.45 (s, 1H, NH), 11.82 (s, 1H, NH), 9.13 (s, 1H,
CH), 7.44–8.06 (m, 8H, Ar-H). IR (KBr, v, cm−1): 3216 (N H),
1730, 1684 (C O), 1145 (C S). MS (m/z): 358 (M+). Anal. calcd. for
C17H11N2O3SCl: C, 56.91; H, 3.09; N, 7.81%. Found: C, 56.82; H, 2.99;
N, 7.89%.
1
1h: White solid. yield: 92%. m.p: 236–237◦C. H NMR (200 MHz,
DMSO-d6) δ12.46 (s, 1H, NH), 11.83 (s, 1H, NH), 9.13 (s, 1H,
CH), 7.44–8.05 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3218 (N H),
1716, 1682 (C O), 1144 (C S). MS (m/z): 358 (M+). Anal. calcd. for
C17H11N2O3SCl: C, 56.91; H, 3.09; N, 7.81%. Found: C, 56.98; H, 3.13;
N, 7.74%.
1i: White solid. yield: 95%. m.p: 252–253◦C. 1H NMR (200 MHz,
DMSO-d6) δ12.53 (s, 1H, NH), 11.80 (s, 1H, NH), 9.14 (s, 1H, CH), 7.47-
8.10 (m, 8H, Ar-H), 3.84 (s, 3H, OCH3). IR (KBr, ν, cm−1): 3214 (N H),
1713, 1668 (C O), 1157 (C S). MS (m/z): 354 (M+). Anal. calcd. for
C18H14N2O4S: C, 61.01; H, 3.98; N, 7.90%. Found: C, 60.93; H, 3.86; N,
8.04%.
1
1j: Yellow solid. yield: 94%. m.p: 234–235◦C. H NMR (200 MHz,
DMSO-d6)δ12.43 (s, 1H, NH), 11.79 (s, 1H, NH), 9.13 (s, 1H, CH),
7.51–8.09 (m, 11H, Ar-H). IR (KBr, ν, cm−1): 3213 (N H), 1718, 1665
(C O), 1154 (C S). MS (m/z): 374 (M+). Anal. calcd. for C21H14N2O3S:
C, 67.37; H, 3.77; N, 7.48%. Found: C, 67.28; H, 3.65; N, 7.40%.
1
1k: Yellow solid. yield: 88%. m.p: 243–244◦C. H NMR (200 MHz,
DMSO-d6)δ 12.44 (s, 1H, NH), 11.80 (s, 1H, NH), 9.13 (s, 1H, CH),

Rapid Synthesis of N-Acyl Ureas
1035
7.52–8.09 (m, 11H, Ar-H). IR (KBr, ν, cm−1): 3214 (N H), 1715, 1667
(C O), 1149 (C S). MS (m/z): 374 (M+). Anal. calcd. for C21H14N2O3S:
C, 67.37; H, 3.77; N, 7.48%. Found: C, 67.24; H, 3.90; N, 7.53%.
General Procedure for the Preparation of Compounds 2a–k
Wet silica gel was prepared by shaking silica gel (20 g, 200–400 mesh)
with distilled water (5 mL). The reagent was prepared by mixing
KMnO4 (1 mmol, 0.16 g) with wet silica gel (3 g) using a pestle and
mortar until a fine, homogeneous, and purple powder was obtained.
A mixture of N-acyl thioureas 1a–k (1 mmol) and KMnO4/wet SiO2
(1 mmol) was ground with a pestle in a mortar until a color change
from purple to black was observed, which required 7–9 min. Then DMF
(20 mL) was added to the reaction mixture. After vigorous stirring, the
solid was filtered and the filtrate was then evaporated under vacuum to
remove the solvent, and the residue was crystallized from DMF-EtOH
(2:1) to give the product. The physical and spectral data of compounds
2a–k follow.
1
2a: White solid. yield: 93%. m.p: 208–210◦C. H NMR (200 MHz,
DMSO-d6) δ 10.61 (s, 1H, NH), 10.29 (s, 1H, NH), 8.89 (s, 1H, CH),
7.32–7.93 (m, 9H, Ar-H). IR (KBr, ν, cm−1): 3187 (N H), 1690 (C O).
MS (m/z): 308 (M+). Anal. calcd. for C17H12N2O4: C, 66.23; H, 3.92; N,
9.09%. Found: C, 66.14; H, 4.02; N, 8.91%.
2b: Yellowish solid. yield: 90%. m.p: 240–242◦C. 1H NMR (200 MHz,
DMSO-d6) δ10.98 (s, 1H, NH), 10.55 (s, 1H, NH), 9.06 (s, 1H, CH),
7.51–8.09 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3265 (N H), 1705 (C O).
MS (m/z): 353 (M+). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14; N,
11.89%. Found: C, 57.76; H, 3.08; N, 11.72%.
2c: Yellowish solid. yield: 92%. m.p: 252–253◦C. 1H NMR (200 MHz,
DMSO-d6) δ 10.96 (s, 1H, NH), 10.51 (s, 1H, NH), 9.05 (s, 1H, CH),
7.42–8.03 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3263 (N H), 1704 (C O).
MS (m/z): 353 (M+). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14; N,
11.89%. Found: C, 57.92; H, 3.24; N, 11.75%.
2d: White solid. yield: 87%. m.p: > 300◦C. 1H NMR (200 MHz, DMSO-
d6) δ 10.97 (s, 1H, NH), 10.53 (s, 1H, NH), 9.04 (s, 1H, CH), 7.46–8.03
(m, 8H, Ar-H). IR (KBr, ν, cm−1): 3266 (N H), 1706 (C O). MS (m/z):
353 (M+). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14; N, 11.89%.
Found: C, 57.68; H, 3.11; N, 11.97%.
1
2e: Yellow solid. yield: 94%. m.p: 254◦C (dec.). H NMR (200 MHz,
DMSO-d6) δ10.80 (s, 1H, NH), 10.46 (s, 1H, NH), 8.99 (s, 1H, CH),
7.49–8.16 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3256 (N H), 1697 (C O).
MS (m/z): 386 (M+). Anal. calcd. for C17H11N2O4Br: C, 52.74; H, 2.86;
N, 7.24%. Found: C, 52.81; H, 2.71; N, 7.38%.

1036
Z. Li et al.
2f: White solid. yield: 93%. m.p: 256–257◦C. 1H NMR (200 MHz,
DMSO-d6) δ 10.82 (s, 1H, NH), 10.48 (s, 1H, NH), 9.00 (s, 1H, CH),
7.46–8.07 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3258, 3053 (N H), 1698
(C O). MS (m/z): 386 (M+). Anal. calcd. for C17H11N2O4Br: C, 52.74; H,
2.86; N, 7.24%. Found: C, 52.67; H, 2.92; N, 7.12%.
1
2g: White solid. yield: 93%. m.p: 248–249◦C. H NMR (200 MHz,
DMSO-d6) δ10.78 (s, 1H, NH), 10.42 (s, 1H, NH), 8.92 (s, 1H, CH),
7.39-8.02 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3252 (N H), 1692 (C O).
MS (m/z): 342 (M+). Anal. calcd. for C17H11N2O4Cl: C, 59.58; H, 3.24;
N, 8.17%. Found: C, 59.64; H, 3.18; N, 8.24%.
1
2h: Yellow solid. yield: 92%. m.p: 251–253◦C. H NMR (200 MHz,
DMSO-d6) δ10.79 (s, 1H, NH), 10.43 (s, 1H, NH), 8.93 (s, 1H, CH),
7.37–8.08 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3255 (N H), 1694 (C O).
MS (m/z): 342 (M+). Anal. calcd. for C17H11N2O4Cl: C, 59.58; H, 3.24;
N, 8.17%. Found: C, 59.44; H, 3.10; N, 8.11%.
2i: White solid. yield: 91%. m.p: 252–253◦C. 1H NMR (200 MHz,
DMSO-d6) δ 10.79 (s, 1H, NH), 11.46 (s, 1H, NH), 8.95 (s, 1H, CH),
7.30–7.90 (m, 8H, Ar-H), 3.82 (s, 3H, OCH3). IR (KBr, ν, cm−1): 3246
(N H), 1687 (C O). MS (m/z): 338 (M+). Anal. calcd. for C18H14N2O5:
C, 63.90; H, 4.17; N, 8.28%. Found: C, 63.81; H, 4.24; N, 8.19%.
2j: Orange solid. yield: 89%. m.p: >300◦C. 1H NMR (200 MHz,
DMSO-d6) 10.68 (s, 1H, NH), 10.32 (s, 1H, NH), 8.90 (s, 1H, CH),
7.52–8.16 (m, 11H, Ar-H). IR (KBr, ν, cm−1): 3190 (N H), 1688 (C O).
MS (m/z): 358 (M+). Anal. calcd. for C21H14N2O4: C, 70.39; H, 3.94; N,
7.82%. Found: C, 70.47; H, 3.78; N, 7.91%.
2k: Yellow solid. yield: 90%. m.p: >300◦C. 1H NMR (200 MHz, DMSO-
d6) 10.70 (s, 1H, NH), 10.31 (s, 1H, NH), 7.53–8.18 (m, 11H, Ar-H), 8.90
(s, 1H, CH). IR (KBr, ν, cm−1): 3186 (N H), 1686 (C O). MS (m/z): 358
(M+). Anal. calcd. for C21H14N2O4: C, 70.39; H, 3.94; N, 7.82%. Found:
C, 70.48; H, 4.05; N, 7.77%.
REFERENCES
[1] A. Ranise, S. Schenone, O. Bruno, F. Bondavalli, W. Filippelli, G. Falcone, and B.
Rivaldi, Farmaco, 56, 647 (2001).
[2] G. Heinicke, T. V. Hung, R. H. Prager, and A. D. Ward, Aust. J. Chem., 37, 831
(1984).
[3] (a) Y. Akcamur, A. Sener, A. M. Ipekoglu, and G. Kollenz, J. Heterocycl. Chem., 34,
221 (1997); (b) A. Padwa, J. P. Snyder, E. A. Curtis, S. M. Sheehan, K. J. Worsencroft,
and C. O. Kappe, J. Am. Chem. Soc., 122, 8155 (2000).
[4] (a) P. F. Wiley, J. Am. Chem. Soc., 71, 1310 (1949); (b) P. F. Wiley, J. Am. Chem. Soc.,
71, 3746 (1949).
[5] (a) X. L. Yang, Y. Ling, D. Q. Wang, and F. H. Chen, Chin. J. Org. Chem., 18, 54
(1998); (b) M. Z. Deng, J. P. Senet, and S. Lecolier, Tetrahedron, 44, 6079 (1988).

Rapid Synthesis of N-Acyl Ureas
1037
[6] P. Kutschy, M. Dzurilla, V. Ficeri, and D. Koscik, Collect. Czech. Chem. Commun.
58, 575 (1993).
[7] J. Ravn, M. Ankersen, M. Begtrup, and J. F. Lau, Tetrahedron Lett., 44, 6931 (2003).
[8] (a) Z. Li, X. Wang, Y. Da, and J. Chen, Synth. Commun., 30, 2635 (2000); (b) X.
Wang, Z. Li, and Z. Guo, Synth. Commun., 32, 3373 (2002).
[9] Y. Shikishima, Y. Takaishi, G. Honda, M. Ito, Y. Takeda, O. K. Kodzhimatov, O.
Ashurmetov, and K. H. Lee, Chem. Pharm. Bull., 49, 877 (2001).
[10] M. H. Elnagdi, S. O. Abdallah, K. M. Ghoneim, E. M. Ebied, and K. N. Kassab, J.
Chem. Res. (M), 375 (1997).