Improved preparation of 2,4-thiazolidinedione

Full text of DOI:10.1080/00304948.2011.582008

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Improved Preparation of 2,4-
Thiazolidinedione
a
a
a
Ge Meng , Yang Gao & Mei-Lin Zheng
a
Faculty of Pharmacy, School of Medicine, Xi'an Jiaotong University,
Xi'an, P. R. China
Version of record first published: 09 Jun 2011.
To cite this article: Ge Meng, Yang Gao & Mei-Lin Zheng (2011): Improved Preparation of 2,4-
Thiazolidinedione, Organic Preparations and Procedures International: The New Journal for Organic
Synthesis, 43:3, 312-313
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Organic Preparations and Procedures International, 43:312–313, 2011
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2011.582008
Improved Preparation of 2,4-Thiazolidinedione
Ge Meng, Yang Gao, and Mei-Lin Zheng
Faculty of Pharmacy, School of Medicine, Xi’an Jiaotong University,
Xi’an, P. R. China
The widely utilized industrial product 2,4-thiazolidinedione (3) has been chosen as the
1
starting material for our ongoing research on rosiglitazone, which is a selective PPAR-γ
2
3
receptor inhibitor for the treatment of type-II diabetes. Based on the literature and our own
experience, we developed an efficient one-step method to obtain 3 using conc. hydrochloric
4
3
acid. This improved synthesis seemed to be much better than the previous methods, all of
which shared the disadvantage that the strongly acidic waste from the reaction and solvents
from the recrystallization process have to be disposed of without harm to the environment.
In order to alleviate these problems, we decreased the amount of hydrochloric acid
and our results show that the yield of 3 is still acceptable while the concentration of HCl
has been decreased by more than one half (Table 1). This result encouraged us to do further
5
research, which resulted in a green and inexpensive method to prepare 3. Herein, we report
this economic and environmentally friendly synthesis of 3, starting from chloroacetic
acid (1) and thiourea (2) using water as the solvent for the preparation as well as the
recrystallization process.
O
S
OH
H O, ∆
Cl
2
+
NH
O
H N NH2
2
O
S
1
2
3
Experimental Section
Melting points were taken on a WRS-1 digital melting point apparatus and are uncorrected.
1
IR spectra were recorded on a Nicolet FI-IR 360 Spectrophotometer. H NMR spectra were
obtained on a Bruker AM 400 (400 MHz) spectrometer with TMS as an internal standard.
Chemical shifts were reported in δ. Mass Spetra were measured on a HP5988A instrument
Submitted September 11, 2010.
Address correspondence to Ge Meng, Faculty of Pharmacy, School of Medicine, Xi’an Jiaotong
University, Xi’an, 710061, P. R. China. E-mail: mengge@mail.xjtu.edu.cn
312

Improved Synthesis of 2,4-Thiazolidinedione
313
Table 1
Concentration of HCl versus the yield
No.
1
2
3
4
5
CHCl (%)
Yield (%)
36
84
18
83
12
67
9
78
0
79
by direct inlet at 70ev. All materials were obtained from commercial suppliers and used as
received.
2,4-Thiazolinedione (3)
To a 100 mL three neck flask equipped with a thermometer, a stirrer and a condenser were
added 2-chloroacetic acid (1, 18.9 g, 0.2 mol), thiourea (2, 15.2 g, 0.2 mol) and water
(50 mL). This mixture was stirred at room temperature for at least 1 h, and then was heated
to reflux. The process of the reaction was monitored by TLC (silica gel, Rf = 0.5, elution:
chloroform-methanol: 20:1) until the reaction was complete (3 h). Then the solution was
allowed to cool down gradually to room temperature while still being stirred. The large
amount of pale yellow crystalline solid was collected, washed with small amount of water
to give the crude product as pale yellow crystals, recrystallized from water (decolorized
◦
with active carbon) to give pure white crystals (3, 18.3 g, 79%), mp. 124–125 C, lit.
◦
4
1
25–1126 C.
IR(KBr): 3398, 2800, 1731, 1677 cm ; H NMR (CDCl3): δ 3.75(s, 2H, -CH2); 9.9(s,
−1 1
+
46
1
H, -NH); MS(m/z,%): 118 (M ). All the analytical data were agreed the literature data.
Acknowledgment
The authors are grateful to the Doctor Initiating Research Foundation of Xi’an Jiaotong
University for the financial support (2007).
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