Synthesis and biological activity of N-aroyl-N′-substituted thiourea derivatives

Article abstract of DOI:10.1081/SCC-100105882

A series of N-aroyl-N′-substituted thiourea derivatives have been prepared in good to excellent yields under the condition of solid-liquid phase transfer catalysis using polyethylene glycol-400(PEG-400) as the catalyst. The products have been characterize

Full text of DOI:10.1081/SCC-100105882

This article was downloaded by: [Fordham University]
On: 10 April 2013, At: 11:03
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
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
SYNTHESIS AND BIOLOGICAL ACTIVITY OF N-AROYL-
N′-SUBSTITUTED THIOUREA DERIVATIVES
You-Ming Zhang a , Tai-Bao Wei b & Li-Ming Gao a
a Department of Chemistry, Northwest Normal University, Lanzhou, Gansu, 730 070, P. R.
China
b Department of Chemistry, Northwest Normal University, Lanzhou, Gansu, 730 070, P. R.
China
Version of record first published: 16 Aug 2006.
To cite this article: You-Ming Zhang , Tai-Bao Wei & Li-Ming Gao (2001): SYNTHESIS AND BIOLOGICAL ACTIVITY OF
N-AROYL-N′-SUBSTITUTED THIOUREA DERIVATIVES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:20, 3099-3105
To link to this article: http://dx.doi.org/10.1081/SCC-100105882
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
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.
The publisher does not give any warranty express or implied or make any representation that the contents
will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses
should be independently verified with primary sources. The publisher shall not be liable for any loss, actions,
claims, proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

SYNTHETIC COMMUNICATIONS, 31(20), 3099–3105 (2001)
SYNTHESIS AND BIOLOGICAL
ACTIVITY OF N-AROYL-N 0-SUBSTITUTED
THIOUREA DERIVATIVES
You-Ming Zhang, Tai-Bao Wei,* andLi-Ming Gao
Department of Chemistry, Northwest Normal
University, Lanzhou, Gansu, 730 070, P. R. China
ABSTRACT
A series of N-aroyl-N 0-substituted thiourea derivatives have
been prepared in good to excellent yields under the condition
of solid–liquid phase transfer catalysis using polyethylene
glycol-400(PEG-400) as the catalyst. The products have
been characterized on the basis of analytical and spectral
(IRand 1H NMR) data. The promoting effects of some com-
pounds on wheat growth have been tested preliminary.
Thioureas and their derivatives have found extensive applications in
the field of medicine, agriculture and analytical chemistry, and the wide
spectrum of biological activities associated with such compounds have
been fully reviewed.1 In view of these observations and in continuation of
*Corresponding author.
3099
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

ORDER
REPRINTS
3100
ZHANG, WEI, AND GAO
our earlier work on the synthesis and biological activity of thiourea deriva-
tives,2–5 the present work was undertaken to prepare a series of N-aroyl-N 0-
substituted thiourea derivatives under the condition of solid-liquid phase
transfer catalysis using PEG-400 as PTC and tested them as plant-growth
regulators on wheat seeds (Gansu 1106).
Aroyl chloride (1) obtained by the reaction of aromatic acid with
thionyl chloride was treated with ammonium thiocyanate under the con-
dition of solid–liquid phase transfer catalysis using 3% PEG-400 as the
catalyst to give the corresponding aroyl isothiocyanate (2) in quantitative
yield. Compound 2 does not need to be isolated and reacts immediately with
aminophenol, aminobenzoic acid and glycylglycine to give the correspond-
ing thiourea derivatives 3, 4 and 5 in good to excellent yield (Scheme 1 and
Table 1).
Scheme 1.
Acyl isothiocyanate is known to condence with amines, alcohols,
amino acid, hydrazine, phenols and thiols. However the reaction of acyl
isothiocyanates are complex, since addition to the –N¼C¼S system and
nucleophilic substitution at carbonyl-carbon atom may compete with one
another.6–7 We have found that aroyl isothiocyanate reacts additively with
aminophenol to give the corresponding thiourea derivatives 3, the formation
of the corresponding esters of N-aroyl thiocarbamic acids was not observed.
Aminobenzoic acid and glycylglycine also react additively with aroyl

ORDER
REPRINTS
N-AROYL-N 0-SUBSTITUTED THIOUREA DERIVATIVES
Table 1. Preparation of N-Aroyl-N 0-Substituted Thioureas
3101
Found (%) (Calcd)
Yield
m. p.
Compd
3a
RAr
(%)
Mol. Formula
C
H
N
4-NO2 1,2-C6H4
4-NO2 1,3-C6H4
4-NO2 1,4-C6H4
95
88
88
72
83
91
97
92
93
88
87
88
85
85
87
87
75
63
172–173 C14H11N3O4S
211–213 C14H11N3O4S
143–145 C14H11N3O4S
208–210 C14H10N4O6S
198–200 C14H12N2O2S
171–172 C14H12N2O2S
217–219 C15H11N3O5S
189–191 C15H11N3O5S
52.87
3.50
13.14
(52.99) (3.49) (13.24)
52.91 3.38 13.37
(52.99) (3.49) (13.24)
52.85 3.32 13.48
(52.99) (3.49) (13.24)
46.53 2.91 15.49
(46.41) (2.78) (15.46)
61.66 4.34 10.27
(61.75) (4.44) (10.29)
61.83 4.36 10.28
(61.75) (4.44) (10.29)
52.35 3.37 12.29
(52.17) (3.21) (12.17)
52.26 3.41 12.09
(52.17) (3.21) (12.17)
232–234 C15H11CIN2O3S 53.92 3.46 8.30
(53.89) (3.32) (8.38)
200–201 C15H11ClN2O3S 53.76 3.39 8.43
(53.89) (3.32) (8.38)
52.33 3.17 12.24
(52.17) (3.21) (12.17)
52.29 3.13 12.36
(52.17) (3.21) (12.17)
59.86 4.24 9.27
(59.99) (4.03) (9.33)
59.74 4.07 9.42
(59.99) (4.03) (9.33)
205–207 C15H11BrN2O3S 47.61 2.99 7.45
(47.51) (2.92) (7.39)
205–207 C15H11BrN2O3S 47.49 2.86 7.52
(47.51) (2.92) (7.39)
48.74 4.35 14.11
(48.80) (4.44) (14.2)
42.41 3.21 16.88
(42.35) (3.55) (16.46)
3b
3c
3d
3e
3f
4-NO2 4-NO2-1,
2-C6H3
H
1,2-C6H4
H
1,4-C6H4
4a
4b
4c
4d
4e
4f
2-NO2 1,4-C6H4
2-NO2 1,2-C6H4
4-CI 1,4-C6H4
4-CI 1,2-C6H4
4-NO2 1,2-C6H4
4-NO2 1,4-C6H4
216–218 C15H11N3O5S
272–274 C15H11N3O5S
160–161 C15H12N2O3S
221–222 C15H12N2O3S
4g
4h
4i
H
H
1,2-C6H4
1,4-C6H4
1,2-C6H4
4Br
4j
4-Br 1,4-C6H4
5a
5b
H
–
–
220–221
C12H13N3O4S
4-NO2
196–198 C12H12N4O6S

ORDER
REPRINTS
3102
ZHANG, WEI, AND GAO
isothiocyanate to give the title compounds 4 and 5 respectively. All the title
compounds were characterised by elemental and spectral data. The charac-
terisation data of these compounds are given in Tables 1 and 2.
As a representative case the reaction of o-amino phenol with benzoyl
chloride and ammonium thiocyanate was carried out at room temperature
in dichloromethane under the condition of solid–liquid phase transfer catal-
ysis using PEG-400 as the PTC. The crude product obtained was recrystal-
lised from ethanol to obtain a pure compound, m.p. 198–200ꢀC. The
IR(KBr) spectrum displayed absorptions at 3394 and 3303 cmꢁ1, due to
NH and OH, at 1657 and 1197 cmꢁ1 due to C¼O and C¼S functions,
respectively. The 1H-NMR(DMSO-d 6) spectrum revealed signals at d
12.95 (s, 1H, NH, D2O exchangeable), d 11.45 (s, 1H, NH, D2O exchange-
able), d 10.34 (s, 1H, OH, D2O exchangeable), d 6.84–8.59 (m, 9H, C6H5 and
C6H4). Based on the foregoing spectral data, the compound was assigned N-
benzoyl-N 0-(o-hydroxyphenyl) thiourea structure (3e).
Some selected compounds were tested on wheat seeds (Gansu 1106)
and average length of seedings and roots were recorded. The concentrations
chosen were 0.001–100 ppm. The results showed that compound 3a, 3e, 3f
and 5a have good promoting effects on wheat growth.
EXPERIMENTAL SECTION
IRspectra were recorded using KBr pellets on an Alpha Centauri
FT-IRspectrophotometer and 1H NMRspectra on FT-80 instrument
DMSO-d6 was as solvent and Me4Si as internal standard. Elemental analy-
sis were performed on a PE-2400 CHN instrument. Mps were observed in an
open capillary tube and are uncorrected. Aroyl chloride was prepared in
85–96% yield by refluxing aromatic acids and an excess of thionyl chloride.
General Procedure for the Preparation of Compound3 and4
Powdered ammonium thiocyanate (15 mmol), aroyl chloride
(10 mmol), PEG-400 (0.18 g, 3% with respect to ammonium thiocyanate)
and methylene dichloride (25 mL) were placed in a dried round-bottomed
flask containing a magnetic stirrer bar and stirred at room temperature for
1 h, then aminophenol (9.5 mol) or aminobenzoic acid (9.5 mmol) was
added, and the mixture was stirred for 2 h. The product was washed with
water to remove inorganic salts and the solvent distilled off. The resulting
solid was filtered, dried and recrystallised from anhydrous ethanol or DMF-
EtOH to give compound 3 or 4.

ORDER
REPRINTS
N-AROYL-N 0-SUBSTITUTED THIOUREA DERIVATIVES
3103
Table 2. IRand 1H NMRSpectral Data of N-Aroyl-N 0-Substituted Thioureas
Compd
3a
IR( vmax, cmꢁ1
)
1H NMR( d, ppm)
3328, 3111 (N–H, O–H), 1742
(C¼O), 1529, 1335 (NO2), 1254,
1173 (C¼S), 1598, 1501, 1473
(C¼C)
12.80 (s, 1H, NH), 11.98 (s, 1H, NH),
10.40 (s, 1H, OH), 6.84–8.60 (m, 8H,
Ar–H)
3b
3c
3d
3378, 3173 (N–H, O–H), 1679
(C¼O), 1284, 1146 (C¼S),
1547, 1343 (NO2), 1602, 1547,
1489 (C¼C)
12.33 (s, 1H, NH), 11.83 (s, 1H, NH),
9.61 (s, 1H, OH), 6.64–7.27 (m, 8H,
Ar–H), 8.09–8.40 (m, 8H, Ar–H)
3208, 3167 (N–H, O–H), 1670
(C¼O), 1268, 1153 (C¼S),
1529, 1347 (NO2), 1600, 1529,
1452 (C¼C)
12.32 (s, 1H, NH), 11.85 (s, 1H, NH),
9.63 (s, 1H, OH), 6.77–7.91 (m, 8H,
Ar–H), 8.23–8.71 (m, 8H, Ar–H)
3415, 3373, 3220, 3106 (N–H, O–H), 12.34 (s, 1H, NH), 11.85 (s, 1H, NH),
1679 (C¼O), 1284, 1146 (C¼S),
1547, 1343 (NO2), 1602, 1547,
1489 (C¼C)
10.01 (s, 1H, OH), 7.04–7.15 (d,
J ¼ 8.8 Hz, 1H, Ar–H), 7.94–7.97
(d, J ¼ 2.4 Hz, 1H, Ar–H), 8.05–8.42
(m, 4H, Ar–H), 8.70 (s, 1H, Ar–H)
12.95 (s, 1H, NH), 11.45 (s, 1H, NH),
10.21 (s, 1H, OH), 6.84–8.59 (m, 9H,
Ar–H)
3e
3f
3394, 3303 (N–H, O–H), 1657
(C¼O), 1254, 1197 (C¼S),
1601, 1510, 1447 (C¼C)
3358, 3216, 3173 (N–H, O–H), 1658
(C¼O), 1256, 1178 (C¼S), 1598,
1514, 1472 (C¼C)
12.16 (s, 1H, NH), 11.81 (s, 1H, NH),
9.52 (s, 1H, OH), 6.87–8.51 (m, 9H,
Ar–H)
4a
4b
3416, 3327, 3161 (N–H, O–H), 1695
(C¼O), 1253, 1168 (C¼S), 1527,
1342 (NO2), 1603, 1509, 1475 (C¼C)
3443, 3330, 3162 (N–H, O–H), 1692
(C¼O), 1250, 1169 (C¼S), 1529,
1343 (NO2), 1603, 1586, 1472
(C¼C)
12.43 (s, 1H, NH), 12.19 (s, 1H, NH),
7.62–8.30 (m, 8H, Ar–H)
13.09 (s, 1H, NH), 12.12 (s, 1H, NH),
11.74 (s, 1H, COOH), 7.28–8.33
(m, 8H, Ar–H)
4c
4d
4e
3319, 3272 (N–H, O–H), 1676, 1688
(C¼O), 1264, 1154 (C¼S), 1592,
1485, 1529 (C¼C)
12.74 (s, 1H, NH), 11.68 (s, 1H, NH),
7.25–8.17 (m, 8H, Ar–H)
3339, 3151 (N–H, O–H), 1684
(C¼O), 1257, 1177 (C¼S),
1607, 1594, 1582, 1485 (C¼O)
3347, 3216, 3135 (N–H, O–H), 1687
(C¼O), 1253, 1171 (C¼S), 1534,
1332 (NO2), 1601, 1583, 1486
(C¼C)
12.83 (s, 1H, NH), 11.57 (s, 1H, NH),
7.22–8.31 (m, 8H, Ar–H)
12.62 (s, 1H, NH), 11.41 (s, 1H, NH),
7.35–8.37 (m, 8H, Ar–H)
(continued )

ORDER
REPRINTS
3104
ZHANG, WEI, AND GAO
Table 2. Continued
Compd
4f
IR( vmax, cmꢁ1
)
1H NMR( d, ppm)
3352, 3208, 3147 (N–H, O–H),
1689 (C¼O), 1261, 1158
12.88 (s, 1H, NH), 11.59 (s, 1H, NH),
7.38–8.42 (m, 8H, Ar–H)
(C¼S), 1535, 1338 (NO2), 1596,
1588, 1479 (C¼C)
4g
4h
4i
3347, 3256 (N–H, O–H), 1692
(C¼O), 1255, 1164 (C¼S),
1601, 1587, 1481 (C¼C)
12.81 (s, 1H, NH), 11.67 (s, 1H, NH),
7.35–8.46 (m, 8H, Ar–H)
3328, 3165 (N–H, O–H), 1690
(C¼O), 1264, 1173 (C¼S),
1592, 1578, 1473 (C¼C)
12.83 (s, 1H, NH), 11.74 (s, 1H, NH),
7.12–8.16 (m, 8H, Ar–H)
3317, 3251, 3133 (N–H, O–H), 1689 12.75 (s, 1H, NH), 11.58
(C¼O), 1268, 1159 (C¼S), 1603,
1589, 1481 (C¼C)
(s, 1H, NH), 7.21–8.19 (m, 8H, Ar–H)
4j
3348, 3169 (N–H, O–H), 1670
(C¼O), 1256, 1167 (C¼S),
1599, 1581, 1475 (C¼C)
12.81 (s, 1H, NH), 11.67 (s, 1H, NH),
7.17–8.25 (m, 8H, Ar–H)
5a
3251, 3167 (N–H, O–H), 1672, 1685 11.89 (s, 1H, NH), 11.03 (s, 1H, NH),
(C¼O), 1262, 1171 (C¼S), 1600,
1511, 1467 (C¼C)
8.92 (s, 1H, NH), 4.37 (s, 2H, CH2),
4.39 (s, 2H, CH2),7.31–7.69 (m, 5H,
Ar–H)
5b
3328, 3216, 3133 (N–H, O–H), 1668, 11.91 (s, 1H, NH), 11.05 (s, 1H, NH),
1683 (C¼O), 1258, 1167 (C¼S),
1534, 1350 (NO2), 1592, 1583,
1479 (C¼C)
8.90 (s, 1H, NH), 8.08–8.39 (m, 4H,
Ar–H), 4.40 (s, 2H, CH2), 4.39 (s, 2H,
CH2O)
General Procedure for the Preparation of Compound 5
A mixture of 2 (10 mmol) and glycylglycine (9 mmol) in anhydrous
acetone (25 ml) was refluxed on a steam-bath for 3 h and excess of acetone
distilled off. The solid mass thus obtained was recrystallized from DMF-
EtOH-H2O to give compound 5.
ACKNOWLEDGMENT
The authors are thankful to Natural Science Foundation of China –
29971026 and Gansu Province – YS991-A25-005 for financial support.

ORDER
REPRINTS
N-AROYL-N 0-SUBSTITUTED THIOUREA DERIVATIVES
REFERENCES
3105
1. Schroeder, D.C. Chem. Rev. 1955, 181.
2. Wei, T.B.; Chen, J.C.; Wang, X.C.; Zhang, Y.M. J. Chem. Res.(S)
1955, 138.
3. Wei, T.B.; Chen, J.C.; Wang, X.C.; Yang, S.Y. Gaodeng Xuexiao
Huaxue Xuebao, 1992, 13, 1217; Chem. Abstr. 1993, 118, 1914479.
4. Zhang, Y.M.; Wei, T.B. Indian J. Chem. 1996, 35B, 1088.
5. Zhang, Y.M.; Wei, T.B.; Wang, X.C.; Yang, S.Y. Indian J. Chem. 1998,
37B, 604.
6. Schroepl, E.; Pohlondek-Fabin, R. Pharmazie, 23, 1968, 484; Chem.
Abstr. 1969, 70, 317.
7. Hoggarth, E. J. Chem. Soc. 1949, 1160.
Received in the USA December 4, 2000

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request
Permission/Reprints Here" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
(AAP) website for guidelines on Fair Use in the Classroom.
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our Website
User Agreement for more details.
Order now!
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC100105882