Solid-state synthesis of 1-ethoxycarbonyl-4-substituted-semicarbazides

Article abstract of DOI:10.3390/80400359

A rapid and simple method for the preparation of 1-ethoxycarbonyl-4- substituted-semicarbazides has been developed. As examples the reaction of six different isocyanates with ethyl carbazate under solvent-free conditions are reported.

Full text of DOI:10.3390/80400359

Molecules 2003, 8, 359-362
molecules
ISSN 1420-3049
http://www.mdpi.org/
Solid-state Synthesis of 1-Ethoxycarbonyl-4-substituted-
semicarbazides
Shadpour Mallakpour *,† Abdol Reza Hajipour and Hedayat A. Taghizadeh
Organic Polymer Chemistry Research Laboratory, College of Chemistry, Isfahan University of
Technology, Isfahan 84156, IR Iran
†
Former name: Shadpour E. Mallakpour
*
Author to whom correspondence should be addressed; e-mail: mallak@cc.iut.ac.ir
Received: 29 November 2002; in revised form: 25 March 2003 / Accepted: 1 April 2003 / Published:
0 April 2003
3
Abstract: A rapid and simple method for the preparation of 1-ethoxycarbonyl-4-
substituted-semicarbazides has been developed. As examples the reaction of six different
isocyanates with ethyl carbazate under solvent-free conditions are reported.
Keywords: Solid state, Semicarbazide, Ethyl carbazate.
Introduction
1
-Ethoxycarbonyl-4-substituted-semicarbazides are important organic intermediates for the
synthesis of 4-substituted-urazoles, which have usually been prepared by the reaction of the
corresponding isocyanates with ethyl carbazate in benzene or toluene solution [1]. The reported
methods, however, invariably require long reaction times, low temperatures, and involve large amount
of solvents, all of which increase the costs of production. Therefore, the aim of this work was to
prepare a wide variety of the semicarbazides under solvent-free conditions.
In recent years, there has been increasing interest in reactions that proceed in the absence of
solvents due to reduced pollution, lower costs and simplicity in processing and handling [2]. In
continuation of our ongoing program to develop such solvent-free reactions [3], we wish to report here

Molecules 2003, 8
360
the preparation of semicarbazides from ethyl carbazate and isocyanates under solvent-free conditions.
As a model reaction we first decided to investigate the preparation of 1-ethoxycarbonyl-4-phenyl-
semicarbazide (2) from ethyl carbazide and phenylisocyanate (1) under solvent-free conditions. The
progress of the reaction was monitored by TLC and it was observed that the reaction was complete in a
short period of time (ca. 20 min.). A variety of semicarbazides (both aliphatic and aromatic) were then
prepared upon simple mixing of ethyl carbazate and the corresponding aliphatic and aromatic
isocyanates in a mortar and grinding the mixture with a pestle at room temperature for the time
specified in Table 1 (Scheme 1). The reaction yields are high and the reaction times are exceedingly
short (20-30 min). The products were isolated by washing the reaction mixtures with small amounts of
solvents like n-hexane or toluene followed by filtration. In this method, the optimum molar ratio of
ethyl carbazate to isocyanate for complete preparation of semicarbazides was determined to be 1:1.
Scheme 1
R-N=C=O + H NNHCOOEt
R-NH-CO-NHNH-COOEt
2
Compound
R
Ph
4-Cl-C
3,4-Cl
1
3
5
7
9
1
,2
,4
,6
,8
,10
1,12
6
H
4
2
C
6
H
3
C
6
H
4
11
n-C
n-C
H
H
9
3
7
Table 1. Solid-state synthesis of 1-ethoxycarbonyl-4-substituted-semicarbazides
o
Substrate
1
Product
2
Time (min)
Yield (%)a
mp ( C)/(Lit)
20
95
144-145 ([1a]: 146-147)
3
5
7
9
4
6
30
30
20
20
20
87
96
95
94
88
193-195 ([1d]: 202-204)
206-208 ([1e]: 212-213.5)
115-117 ([1d]: 116-118)
96-98 ([1d]: 108-109)
94-96 ([1d]: 110)
8
10
12
1
1
aYields of isolated pure products after purification.

Molecules 2003, 8
361
Conclusions
In this study we have presented a simple method for the preparation of different types of
-ethoxycarbonyl-4-substituted-semicarbazides from ethyl carbazate and the corresponding
1
isocyanates under solvent-free conditions. This method is superior to previously reported ones in terms
of high yields, facile work-up, short reaction times, and the cost of the solvents have been minimized.
Acknowledgments
We are thankful to the Isfahan University of Technology (IUT) Research Council for the partial
support of this work. Further financial support from Center of Excellency in Chemistry Research (IUT)
is gratefully acknowledged.
Experimental
General
Yields refer to isolated products after purification. All reactions were carried out under solvent-free
conditions in a hood with strong ventilation. Ethyl carbazate and isocyanates were purchased from
Merck Co. Reactions were followed using silica gel 60 F254 aluminium TLC plates and ethyl
acetate/cyclohexane (50:50) as solvent mixture. The products were characterized by comparison of
1
1
their spectral (IR, UV, H-NMR) and physical data with that of authentic samples [1]. All H-NMR
spectra were recorded at 90 MHz in DMSO-d relative using TMS as an internal standard. IR spectra
were recorded on Shimadzu 435 IR spectrometer.
6
Typical Procedure: Preparation of 1-Ethoxycarbonyl-4-phenyl Semicarbazide (2) from Ethyl
Carbazate and Phenyl Isocyanate (1)
A mixture of ethyl carbazate (0.104 g, 1 mmol) and phenyl isocyanate (1, 0.119 g, 1 mmol) placed
in a mortar was ground with a pestle for the time specified in Table 1. When TLC showed complete
disappearance of starting material, the mixture was washed with dry toluene or n-hexane and the solids
were filtered off and dried to give 1-ethoxycarbonyl-4-phenyl semicarbazide (2). The yield was 0.212
o
o
g (95%) of crystalline white solid, mp 144-145 C (lit. [1a] mp 146-147 C). IR (KBr): 3360 (s), 3200
(
(
3
s), 3050 (m), 2980 (m), 1710 (s), 1665 (s), 1600 (s), 1545 (s), 1500 (m), 1475 (m), 1440 (m), 1370
w), 1310 (s), 1130 (s), 1050 (m), 1010 (m), 890 (m), 750 (m), 630 (m, br) cm . H-NMR: δ 1.19 (t,
H, J = 7.0 Hz), 4.07 (q, 2H, J = 7.0 Hz), 7.19 (m, 5H), 8.01 (s, 1H), 8.73 (s, 1H), 8.93 (s, 1H) ppm.
-1 1

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362
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1
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Sample availability: Samples of compounds 2, 4, 6, 8, 10 and 12 are available from MDPI.
2003 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.
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