Microwave Assisted Synthesis of 4-Substituted 1-Ethoxycarbonyl Semicarbazides from Ethyl Carbazate and Isocyanates

Article abstract of DOI:10.1007/s00706-003-0012-6

A rapid and simple method for the preparation of 4-substituted 1-ethoxycarbonyl semi[0-9] carbazide is reported. The reaction is carried out under microwave irradiation by the reaction of five different isocyanates with ethyl carbazate.

Full text of DOI:10.1007/s00706-003-0012-6

Monatshefte f €u r Chemie 134, 1015–1017 (2003)
DOI 10.1007/s00706-003-0012-6
Microwave Assisted Synthesis of 4-Substituted
1-Ethoxycarbonyl Semicarbazides from Ethyl
Carbazate and Isocyanates
Ã; a
and Hedayat A. Taghizadeh
Shadpour Mallakpour , Abdol Reza Hajipour,
Organic Polymer Chemistry Research Laboratory, College of Chemistry,
Isfahan University of Technology, Isfahan 84156, Iran
Received October 28, 2002; accepted October 31, 2002
Published online May 15, 2003 # Springer-Verlag 2003
Summary. A rapid and simple method for the preparation of 4-substituted 1-ethoxycarbonyl semi-
carbazide is reported. The reaction is carried out under microwave irradiation by the reaction of five
different isocyanates with ethyl carbazate.
Keywords. Microwave irradiation; Solid-state; Semicarbazide.
Introduction
4-Substituted 1-ethoxycarbonyl semicarbazides are important organic intermediates
for the synthesis of 4-substituted urazoles and they are prepared by reaction of the
corresponding isocyanates with ethyl carbazate in toluene solution [1]. However,
some of the mentioned methods invariably require lower temperatures, long reaction
times, and involve solvents which are toxic and detrimental to the environment.
Therefore, there is a need for a simple, less expensive, and safer method for synthesis
of semicarbazides. In recent years, there has been a growing interest in the applica-
tion of microwave irradiation in chemical reaction enhancement, because of cleaner
reactions, decreased reaction times, and easier work-up [2]. In continuation of our
program [3] we now report a facile preparation of semicarbazides from ethyl carba-
zate and isocyanates accelerated under microwave irradiation.
Results and Discussion
One equivalent of ethyl carbazate and phenyl isocyanate were ground in a mortar until
a homogeneous mixture is formed (1 min). Then, the reaction mixture was transferred
Ã
Corresponding author. E-mail: mallak@cc.iut.ac.ir
a
Previous name. Shadpour E. Mallakpour

1
016
S. Mallakpour et al.
Table 1. Microwave-assisted synthesis of 1-ethoxycarbonyl-4-substituted-semicarbazides (micro-
wave oven was used at 70% of it’s power)
Educt
Product
t=min
Yield=%
Ref.
1
3
5
7
9
2
4
2
2
2
2
2
95
95
96
81
94
[1a]
[1d]
[1e]
[1d]
[1d]
6
8
10
Formula 1
to an Erlenmeyer flask and irradiated in a microwave oven (2 min; after this time the
ꢀ
temperature had risen to 80 C). The optimum molar ratio of ethyl carbazate and
phenyl isocyanate was found to be 1:1. A variety of semicarbazides (aliphatic and
aromatic) were prepared (Table 1). The yields of the reactions are high. The products
were isolated by washing the reaction mixture with solvent followed by filtration of
the mixture, which often produced pure product without any purification.
For comparison, according to the conventional method 2 has been prepared as follows: ethyl
ꢀ
carbazate dissolved in toluene is cooled in an ice-water bath to about 10 C. To this solution 1 is
added dropwise over a period of 75min. The mixture is then stirred at room temperature for 2.5 h and
heated under reflux for additional 2 h. After cooling to room temperature 2 is separated by filtration,
washed with toluene, and dried for 24h to provide a yield of 96% [1a].
In conclusion, we reported a new and efficient methodology for the synthesis of
semicarbazides from ethyl carbazate and isocyanates under microwave irradiation.
This method is superior to previously reported methods in terms of high yields,
purity of products, facile work-up, short reaction time, and the cost of the solvent.
Experimental
All of the yields refer to isolated products after purification. All of the products were characterized by
1
comparison of their spectral (IR, H NMR) and physical data (melting and boiling points) with those of
1
authentic samples [1]. All H NMR spectra were recorded at 90 MHz in DMSO-d relative to TMS as
6
internal standard and IR spectra were recorded on a Shimadzu 435 IR spectrometer. A Samsung

Microwave Assisted Synthesis
1017
domestic microwave oven (2450 MHz, 900 W) was used without any modification, but all of the
reactions were carried out in a hood with strong ventilation.
Typical Procedure for the Preparation of Semicarbazides from Ethyl Carbazate
and Isocyanates Under Microwave Irradiation
A mixture of 1 mmol ethyl carbazate (0.104g) and 1 mmol phenyl isocyanate (0.11 g) was prepared
and irradiated for the time specified in Table 1. When TLC showed complete disappearance of starting
material, the mixture was treated with toluene, and pure 1-ethoxycarbonyl-4-phenyl semicarbazide was
ꢀ
isolated by filtration. The yield was 0.20 g (95%) of a crystalline white solid, mp 141–143 C (Ref. [1a]
ꢀ
1
46–147 C).
Acknowledgement
We are thankful to the Isfahan University of Technology (IUT) Research Council for financial support.
Further financial support from Center of Excellency in Chemistry Research (IUT) is gratefully
acknowledged.
References
[1] a) Mallakpour SE (1992) J Chem Edu 69: 238; b) Mallakpour SE, Butler GB, Aghabozorg H,
Plenik GJ (1985) Macromolecules 18: 342; c) Mallakpour SE, Zolfigol MA (1993) J Sci I R Iran 4:
1
99; d) Arya VP, Shenoy SJ (1976) Indian J Chem 14B: 883; e) Raheno H (2002) MSc Thesis,
Isfahan University of Technology, P29
[
2] For recent reviews on microwave-assisted chemical reactions see: a) Abramovich RA (1991) Org
Prep Proced Int 23: 683; b) Caddick S (1995) Tetrahedron 51: 10403; c) Mingos DMP, Baghurst
DR (1991) Chem Soc Rev 20: 1; d) Raner KD, Strauss CR, Trainor RW, Thorn JS (1995) J Org
Chem 60: 2456; e) Strauss CR, Trainor RW (1995) Aust J Chem 48: 1665; f) Lidstrom P, Tierney J,
Wathey B, Westman J (2001) Tetrahedron 57: 9225
[
3] a) Hajipour AR, Mallakpour SE, Khoee S (2000) Chem Lett 120; b) Hajipour AR, Mallakpour SE,
Khoee S (2000) Synlett 740; c) Hajipour AR, Mallakpour SE, Imanzadeh Gh (2001) Indian J
Chem 40B: 237; d) Hajipour AR, Mallakpour SE, Imanzadeh Gh (2001) Indian J Chem 40B: 250;
e) Hajipour AR, Islami F (1999) Indian J Chem 38B: 461; f) Hajipour AR, Mallakpour SE, Baltork
IM, Khoee S (2001) Synth Commun 31: 1187; g) Hajipour AR, Ghasemi M (2001) Indian J Chem
4
0B: 504