Efficient method of synthesis of N,N′-disubstituted ureas/thioureas by a Zinc chloride catalyzed thermal reaction

Article abstract of DOI:10.1080/00397910802697467

Symmetrically N,N'-disubstituted ureas/thioureas were synthesized by heating amines or phenyl hydrazine and urea/thiourea on a preheated hot plate at 80-85C under solvent-free conditions in the presence of a catalytic amount of ZnCl₂ as a catalyst. The protocol has the advantages of not using toxic phosgene and other hazardous substrates or organic solvents. Increased reaction rate, good yield, and a simple workup procedure are involved.

Full text of DOI:10.1080/00397910802697467

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Efficient Method of Synthesis
of N,N′-Disubstituted Ureas/
Thioureas by a Zinc Chloride
Catalyzed Thermal Reaction
M. A. Pasha a & M. B. Madhusudana Reddy a
a Department of Studies in Chemistry, Central
College Campus, Bangalore University, Bangalore,
India
Version of record first published: 14 Jul 2009.
To cite this article: M. A. Pasha & M. B. Madhusudana Reddy (2009): Efficient Method
of Synthesis of N,N′-Disubstituted Ureas/Thioureas by a Zinc Chloride Catalyzed
Thermal Reaction, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 39:16, 2928-2934
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Synthetic Communications1, 39: 2928–2934, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802697467
Efficient Method of Synthesis of
N,N0-Disubstituted Ureas/Thioureas by a
Zinc Chloride Catalyzed Thermal Reaction
M. A. Pasha and M. B. Madhusudana Reddy
Department of Studies in Chemistry, Central College Campus,
Bangalore University, Bangalore, India
Abstract: Symmetrically N,N0-disubstituted ureas=thioureas were synthesized by
heating amines or phenyl hydrazine and urea=thiourea on a preheated hot plate
at 80–85ꢀC under solvent-free conditions in the presence of a catalytic amount
of ZnCl2 as a catalyst. The protocol has the advantages of not using toxic phos-
gene and other hazardous substrates or organic solvents. Increased reaction rate,
good yield, and a simple workup procedure are involved.
Keywords: Disubstituted ureas=thioureas, solvent-free reaction, thermal condi-
tion, ZnCl2
INTRODUCTION
The synthesis of substituted ureas and thioureas involves reaction of
amines with urea and thiourea,[1] phosgenation,[2] and reductive[3] or
oxidative carbonylation of amines.[4] Use of microwave irradiation in
the presence of CeCl3 ꢁ 7H2O-KI and polyethylene glycol (PEG)-400 (a
phase-transfer catalyst, PTC) as catalyst have also been reported.[5]
In continuation of our work on solvent-free organic transforma-
tions,[6] we have recently reported an efficient synthesis of N,N0-disubsti-
tuted ureas=thioureas catalyzed by iodine.[7] In the present article, ZnCl2
is used as a catalyst for a similar transformation.
Received October 6, 2008.
Address correspondence to M. A. Pasha, Department of Studies in Chemistry,
Central College Campus, Bangalore University, Bangalore 560001, India. E-mail:
m_af_pasha@ymail.com
2928

N,N0-Disubstituted Ureas/Thioureas
2929
RESULTS AND DISCUSSION
An aromatic amine (1) or phenylhydrazine was heated with urea or
thiourea (2) in the presence of a catalytic amount of ZnCl2 to get sym-
metric N,N0-disubstituted urea=thiourea (3) in good yields (Scheme 1).
The reaction was rapid and afforded excellent yields of the products with
good purity.
In a typical reaction, p-anisidine (20 mmol) was heated with urea=
thiourea (10 mmol) in the presence of ZnCl2 (0.5 mmol) at 80ꢀC to give
the desired N,N0-bis(4-methoxyphenyl) urea within 5 min (98%).
The reaction was extended to get different N,N0-disubstituted ureas
from a variety of aryl and alkyl amines, and the results are summarized
in Tables 1 and 2. It is interesting to note that substituents on aryl amines
such as ꢂOCH3, ꢂCl, ꢂBr, and ꢂNO2 are unaffected under the present
reaction conditions.
In the absence of any catalyst, N,N0-disubstituted urea was obtained
in very trace amounts even after 30 min at 80ꢀC. The other Lewis acids
(such as CuCl2, FeCl3, NiCl2, CoCl2, MnCl2 and AlCl3) had poor effects.
EXPERIMENTAL
Chemicals are commercial products and were used without further
purification. The products were characterized by comparison of their
physical data with those of known samples or by comparison of their
1
infrared (IR), H NMR, and liquid chromatography (LC)–mass spectra
(MS) data.
General Procedure for N,N0-Disubstituted Urea/Thiourea
p-Anisidine (2.46 g, 20 mmol), urea (0.60 g, 10 mmol), and ZnCl2 (0.068 g,
0.5 mmol) were taken in a 50-ml, flat-bottomed flask, mixed well, and
heated on a preheated hot plate at 80ꢀC for 5 min. After completion of
Scheme 1. Zinc chloride catalyzed synthesis of N,N0-disubstituted ureas=thioureas.

2930

2931

2932

N,N0-Disubstituted Ureas/Thioureas
2933
the reaction, contents were cooled to room temperature and poured
onto crushed ice, and the solid was washed with water to give N,N0-bis
(4-methoxyphenyl)urea (5.32 g, 98%) as a white solid. An analytical-
grade sample was obtained by recrystallization from methanol.
CONCLUSION
In conclusion, another reliable, practical procedure and an alternative
method for the preparation of symmetrically substituted ureas=thioureas
oureas has been developed. The method involves the use of inexpensive
readily available zinc chloride as a catalyst and a simple workup proce-
dure. In our opinion this method is superior to previous methods of
synthesizing N,N0-disubstituted ureas=thioureas[2–4] and is equally
efficient as our previous method.[7]
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M. A. Pasha and M. B. M. Reddy
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