Microwave Promoted Efficient Synthesis of N-Aryl-N′-aroyl Thioureas under Solvent-Free and Phase Transfer Catalysis Conditions

Article abstract of DOI:10.1081/SCC-120027251

A simple, rapid and efficient method for the synthesis of N-aryl-N′-aroyl thioureas under phase transfer catalysis, microwave irradiation and solvent-free conditions is reported.

Full text of DOI:10.1081/SCC-120027251

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Microwave Promoted Efficient Synthesis of
N‐Aryl‐N′‐aroyl Thioureas Under Solvent‐Free and
Phase Transfer Catalysis Conditions
Tai‐Bao Wei a , Qi Lin a , You‐Ming Zhang a & Wei Wei a
a Department of Chemistry, Northwest Normal University, Lanzhou, Gansu, 730070, P.R.
China
Version of record first published: 16 Aug 2006.
To cite this article: Tai‐Bao Wei , Qi Lin , You‐Ming Zhang & Wei Wei (2004): Microwave Promoted Efficient Synthesis of
N‐Aryl‐N′‐aroyl Thioureas Under Solvent‐Free and Phase Transfer Catalysis Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:1, 181-186
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 1, pp. 181–186, 2004
Microwave Promoted Efficient Synthesis
of N-Aryl-N0-aroyl Thioureas Under
Solvent-Free and Phase Transfer
Catalysis Conditions
*
Tai-Bao Wei, Qi Lin, You-Ming Zhang, and Wei Wei
Department of Chemistry, Northwest Normal University, Lanzhou,
Gansu, P.R. China
ABSTRACT
A simple, rapid and efficient method for the synthesis of N-aryl-N0-aroyl
thioureas under phase transfer catalysis, microwave irradiation and
solvent-free conditions is reported.
Key Words: N-aryl-N0-aroyl thioureas; Microwave irradiation; Solvent
free organic synthesis.
Thiourea derivatives have been found to possess many important bio-
logical activites.[1] Some thioureas are useful as heribicides,[2] insecticides[3]
*
Correspondence: You-Ming Zhang, Department of Chemistry, Northwest Normal
University, Aning East Road 805, Lanzhou, Gansu 730070, P.R. China.
181
DOI: 10.1081/SCC-120027251
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

182
Wei et al.
and plant-growth regulators.[4] Many methods have been described for the
preparation of isothiocyanates,[5–9] which are important for the synthesis of
thiourea derivatives. The reaction of acyl chloride with ammonium
thiocyanate under phase transfer catalysis is a good method for the preparation
of acyl isothiocyanates, which react with aniline to afford the acyl phenyl
thioureas. In our earlier work, we have reported the use of this method in the
synthesis of a series of thiourea derivatives.[4,9–15]
In recent years the use of microwave technology in organic synthesis has
received considerable attention, this technology can increase the purity of the
resulting products, enhance the chemical yield and shorten the reaction
time.[16–19] In addition, most of MWI assisted reaction use solvents,[16–18]
which often lead to a need of specialized sealed vessel for this highly pressure
reaction.
Moreover, as we know, solvent-free organic synthesis has great applied
value and expansive prospects. It has many advantages such as high efficiency
and selectivity, easy separation and purification and environmental
acceptability.[19–22] All these merits are in accord with the green chemistry’s
requests of energy-saving, high efficiency and environmentally benign.
In view of these and in continuation of our earlier work on the synthesis
and activity of thiourea derivatives, we decided to try to synthesis the title
compounds under solvent-free and microwave irradiation conditions. The
reactions are shown in Sch. 1 below. At first, we estimated the reactivity of the
model reacting between benzoyl chloride (11 mmol) and potassium
isothiocyanate (12 mmol) under solvent-free and microwave irradiation
conditions. These steps are solid-liquid phase reactions though they do not use
any solvents. So, we carried out two experiments under the condition as
mentioned above. In the first experiment, we did not use phase transfer
catalyst and in the second one we used PEG-400 (0.1 mL) as the phase transfer
catalyst. The reaction mixture of two experiments were subjected to
microwave irradiation (500 W) intermittently at 0.5 min intervals, after 5 min
the reaction of second experiment was completed but the first one almost
Scheme 1.

N-Aryl-N0-Aroyl Thioureas
183
didn’t take place. Then irradiation the first one at the same condition for 5 min
again, the reaction almost did not take place yet. Cooled the reaction mixture
of the second one to room temperature, the phenylamine (10 mmol) was
slowly added to the reaction mixture with constant stirring. Then, the reaction
mixture was subjected to microwave irradiation (500 W) for 5 min
intermittently at 0.5 min intervals again. When the reaction completed, the
reaction mixture was washed with 8 mL 75% ethanol three times and 10 mL
H2O three times, then, the product was obtained. Recrystallization from
ethanol gave the pure product 2a in 98.0% yield. According to these
experiments, the first steps of these reactions do need phase transfer catalysis.
The catalysis procedure is carried out at the interface between the solid phase
and liquid phase. In this procedure, potassium ion is complexed by PEG-400
forming a large organic soluble cation, which is paired with isothiocyanate
ion; this ionic pair is soluble in benzoyl chloride. After isothiocyanate ion
reacted with benzoyl chloride, the large organic soluble cation pairs with
isothiocyanate ion again. So the reaction is catalyzed. It must be emphasized
that the first step almost can’t carry out if without phase transfer catalyst. In
addition, it’s a solvent-free reaction in spite of use liquid PEG-400 as the
phase transfer catalyst because we used only 0.1 mL PEG-400. In a second
series of experiments we explored the general validity of the present
methodology; different N-aryl-N0-aroyl thioureas 2b-2m were synthesized in
80.0–98.1% yield. The results for the compounds prepared are listed in
Table 1. All products were characterized by 1HNMR, IR spectra and
Elemental analysis.
Table 1. N-aryl-N0-aroyl thioureas 2a ꢀ m prepared.
Entry
R
M.P./8C
Lit. M.P./8C
Yield/%
2a
2b
2c
2d
2e
2f
C6H5
147 ꢀ 148
127 ꢀ 128
158 ꢀ 159
140 ꢀ 141
164 ꢀ 165
143 ꢀ 144
139 ꢀ 140
149 ꢀ 150
127 ꢀ 128
168 ꢀ 170
171 ꢀ 172
116 ꢀ 117
154 ꢀ 155
1488
1288
98.0
95.9
91.9
89.4
86.1
95.0
98.1
95.8
97.1
94.8
85.1
95.6
94.9
3-CH3C6H4
4-CH3C6H4
2-NO2C6H4
3-NO2C6H4
2-ClC6H4
1578
1399
1649
1448
2g
2h
2i
4-ClC6H4
4-BrC6H4
4-FC6H4
140.58
1508
128 ꢀ 129.58
2j
1-Nephthyl
2-Nephthyl
2-CH3C6H4
4-CH3OC6H4
17123
2k
2l
17323
1178
2m
154.4 ꢀ 1558

184
Wei et al.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
IR spectra were recorded in KBr on an Alpha Centauri FT-IR
spectrophotometer and 1HNMR spectra on an FT-80A instrument using
CDCl3 as solvent and TMS as internal reference. Elemental analysis was
determined on PE-2400 CHN instrument. Microwave irradiation was carried
out with a WP 750B commercial microwave oven at 2450 MHz.
General Procedure
The synthesis of N-aryl-N0-aroyl thioureas was carried out by adding
powered KSCN (12 mmol), benzoyl chloride (11 mmol) and PEG-400
(0.1 mL) in a dried test tube. The reaction mixture was subjected to microwave
irradiation (500 W) for 5 min intermittently at 0.5 min intervals. On
completion of the reaction the mixture was cooled to room temperature, the
aromatic amine (10 mmol) was slowly added to the reaction mixture with
constant stirring. Then, the reaction mixture was subjected to microwave
irradiation (500 W) for 5 min intermittently at 0.5 min intervals again. When
the reaction completed, the reaction mixture was washed with 8 mL 75%
ethanol three times and 10 mL H2O three times. By this treatment the product
was obtained. Recrystallization from ethanol gave the pure product.
ACKNOWLEDGMENT
This work was supported by Natural Science Foundation (No. 20371040)
of China, the Foundation (GS022-A52-069) of Gansu province and the
Foundation (No. 02-18) of Northwest Normal University, which are gratefully
acknowledged.
REFERENCES
1. Schroeder, D.C. Thioureas. Chem. Rev. 1955, 50, 185–228.
2. Zhonghua, Li; Yan, Zhang; Zhihong, Peng; Yangang, Wang. Synthesis
and herbicidal activity of N-ethoxyformyl-N0-aryl substituted thioureas.
Huaxue Shiji 2002, 24 (214–215), 218.
3. Madan, V.K.; Taneja, A.D.; Kudesia, V.P. Preparation and spectral
studies of some carboxyalkyl substituted thiouras as potential fungicides
and nematicides. J. Indian Chem. Soc. 1991, 68, 162–163.

N-Aryl-N0-Aroyl Thioureas
185
4. Taibao, Wei; Jichou, Chen; Xiuchun, Wang; Suyou, Yang. Studies on the
synthesis and biological activity of N-aryl-N0-(5-aryl-2-fouroyl) thiourea
derivatives. Chem. J. Chinese Univ. 1992, 13, 1217–1221.
5. Reeves, W.P.; Simmons, A.J.; Keller, K. Phase transfer catalysis
preparation of aryl thiocyanates. Synth. Commun. 1980, 10 (8), 633.
6. Smith, P.A.S.; Kan, R.O. Cyclizaton of isothiocyanates as a route to
phthalic and homophthalic acid derivatives. J. Org. Chem. 1964, 29,
2261–2265.
7. Cainelli, G.; Manescalchi, F.; Panunzio, M. Polymer supported reagents.
Synthesis of N,N0-alkylurethanes and thiocyanates from alkyl halides
under mild conditions. Synthesis 1979, 141–144.
8. Rasmassen, R.; Villani, F.J.; Weaner, L.E.; Reynolds, B.E.; Hood, A.R.;
Hecker, L.R.; Nortey, S.O.; Hanslin, A.; Costanzo, J.; Powell, E.T.;
Molinari, A.J. Improved procedures for the preparation of cycloalkyl-,
arylalkyl-, and arylthioureas. Synthesis 1988, 456–459.
9. Jichou, Cheng; Taibao, Wei; Suyou, Yang. Studies on the synthesis and
biological activity of N-aryl-N0-benzoylthioureas. NONGYAO 1991,
30 (2), 8–9.
10. Youming, Zhang; Taibao, Wei; Liming, Gao. Synthesis and biological
activity of N-aroyl-N0-substituted thiourea derivatives. Synth. Commun.
2001, 31 (20), 3099–3105.
11. Youming, Zhang; Taibao, Wei; Lailai, Wang. Phase transfer catalyzed
synthesis of N-aryl-N0-(2-chlorobenzoyl)-thiourea derivatives. Synth.
Commun. 1997, 27 (5), 1088–1090.
12. Taibao, Wei; Jichou, Chen; Xicun, Wang; Youming, Zhang. Phase
transfer catalyzed synthesis of 1-aryloxyacetyl-4-(2-furoyl) thiosemicar-
bazide derivatives. J. Chem. Research (S) 1995, 1, 138–139.
13. Youming, Zhang; Taibao, Wei; Liming, Gao. Phase transfer catalyzed
synthesis of arene-bis-aroyl thiourea derivatives. Indian J. Chem. 2000,
39B, 700–702.
14. Youming, Zhang; Taibao, Wei. Synthesis and biological activity of N-
aroyl-N0-carboxyalkyl thiourea derivatives. Indian J. Chem. 1998, 37B,
604–606.
15. Youming, Zhang; Taibao, Wei; Liming, Gao. Synthesis and biological
activity of N-aroyl-N0-substituted thiourea derivatives. Sythn. Commun.
2001, 31 (20), 3099–3105.
16. Galema, S.A. Microwave chemistry. Chem. Soc. Rev. 1997, 26 (3),
223–232.
17. Caddick, S. Microwave assisted organic reaction. Tetrhedron 1995, 51,
10403–10432.

186
Wei et al.
18. Gedye, R.J.; Smith, F.; Westaway, K.C.; Baldisera, L.; Laberge, L.;
Rousell, J. The use of microwave ovens for rapid organic synthesis.
Tetrahedron Lett. 1986, 27, 279–282.
19. Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault, P.;
Mathe, D. New solvent-free organic synthesis using focused microvaves.
Synthesis 1998, 1213–1234.
20. Goff, D.A.; Zuckermann, R.N. Solide-phase synthesis of defined 1,4-
benzodiazepine-2,5-dione mixtures. J. Org. Chem. 1995, 60, 5744–5745.
21. Jianping, Li; Qianfu, Luo; Yulu, Wang; Hong, Wang. An efficient solid-
state method for the preparation of acyl thiosemicarbazides. Synth.
Commun. 2001, 31 (12), 1793–1797.
22. Abenhaim, D.; Son, C.P.N.; Loupy, A.; Hiep, N.B. Synthesis of
jasminaldehyde by solid-liquid phase transfer catalysis without solvent,
under microwave irradiation. Synth. Commun. 1994, 24 (9), 1199–1205.
23. Nair, G.V. Interaction of benzoyl isothiocyanate and primary and
secondary amines: Formation of the related benzoylthiocarbamides and
thiocarbamides. J. Indian Chem. Soc. 1963, 40 (11), 953–956.
Received in Japan June 2, 2003