A facile synthesis of 5-arylidene-2-imino-4-thiazolidinones under microwave irradiation

Article abstract of DOI:10.1080/00397910802323072

A series of 5-arylidene-2-imino-4-thiazolidinone derivatives were synthesized by the cross-aldol condensation of aromatic aldehydes with 2-imino-4-thiazolidinone in sodium acetate/acetic acid under microwave irradiation. The reactions were completed in 10 min with 63-91% yields, were environmental benign, and had easy workup. Copyright Taylor & Francis Group, LLC.

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A Facile Synthesis of 5-
Arylidene-2-imino-4-
thiazolidinones Under
Microwave Irradiation
Jian-Feng Zhou a , Xiao-Jun Sun a , Feng-Xia Zhu a
Yan-Lun Li a & Gui-Xia Gong b
,
a Department of Chemistry, Huaiyin Teachers
College, Jiangsu Key Laboratory for Chemistry of
Low-Dimensional Materials, Huaian, China
b School of Chemistry and Chemical Engineering,
Suzhou University, Suzhou, China
Version of record first published: 31 Oct 2008.
To cite this article: Jian-Feng Zhou, Xiao-Jun Sun, Feng-Xia Zhu, Yan-Lun Li & Gui-
Xia Gong (2008): A Facile Synthesis of 5-Arylidene-2-imino-4-thiazolidinones Under
Microwave Irradiation, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 38:23, 4182-4187
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Synthetic Communications1, 38: 4182–4187, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802323072
A Facile Synthesis of 5-Arylidene-2-imino-4-
thiazolidinones Under Microwave Irradiation
Jian-Feng Zhou,1 Xiao-Jun Sun,1 Feng-Xia Zhu,1 Yan-Lun Li,1
and Gui-Xia Gong2
1Department of Chemistry, Huaiyin Teachers College, Jiangsu Key
Laboratory for Chemistry of Low-Dimensional Materials, Huaian, China
2School of Chemistry and Chemical Engineering, Suzhou University,
Suzhou, China
Abstract: A series of 5-arylidene-2-imino-4-thiazolidinone derivatives were
synthesized by the cross-aldol condensation of aromatic aldehydes with 2-imino-
4-thiazolidinone in sodium acetate=acetic acid under microwave irradiation. The
reactions were completed in 10 min with 63–91% yields, were environmental
benign, and had easy workup.
Keywords: Aromatic aldehyde, 2-imino-4-thiazolidinone, microwave irradiation
Thiazolidin-4-ones derivatives have been proven to be attractive com-
pounds because of their outstanding biological activities.[1–8] Therefore,
the syntheses of these compounds are of considerable interest. Continu-
ing our interest in the development of efficient reagents and simple pro-
cedures for the synthesis of organic compounds, we reported previously
an efficient synthesis of 5-benzylidenerhodamines.[9] Herein, we report
a facile synthesis of 5-arylidene-2-imino-4-thiazolidinone by the cross-
aldol condensation of aromatic aldehydes with 2-imino-4-thiazolidinone
using sodium acetate as catalyst in acetic acid under microwave irradia-
tion (Scheme 1). The reactions were completed in 10 min with 63–91%
yields, were environmentally benign, and had easy workup.
Received February 11, 2008.
Address correspondence to Jian-Feng Zhou, Department of Chemistry,
Huaiyin Teachers College, 223300 Huaian, China. E-mail: orgjfzhou@yahoo.com.cn
4182

5-Arylidene-2-imino-4-thiazolidinones
4183
Scheme 1. Synthesis of 5-arylidene-2-imino-4-thiazolidinone under microwave
irradiation.
RESULTS AND DISCUSSION
When a mixture of aromatic aldehyde 1, 2-imino-4-thiazolidinone 2, and
ammonium acetate was irradiated in a microwave (Scheme 1), the reac-
tions were completed in 10 min. The crude products were purified by
recrystallization from 95% ethanol to afford products with mild to good
yields (63–91%). However, conventional approaches for the synthesis of
these compounds often involve long reaction times, harsh reaction condi-
tions, unsatisfactory yields, and environmentally unfavorable solvents.
For example, the condensation of aromatic aldehyde with 2-imino-4-thia-
zolidinone has been performed using piperidine as catalyst in ethanol at
reflux for 20–24 h,[10] using sodium acetate in glacial acetic acid under
reflux for 0.5–12 h,[11] or using pyridine in xylene at 150–160 ꢀC for
3 h,[12] and so on. The results as summarized in Table 1 clearly reveal
the scope and generality of the reaction with respect to various substituted
Table 1. Microwave irradiation synthesis of 3a–i
Reaction
temperaturea (ꢀC) time (min)
Reaction Yieldsb
(%)
Mp
(ꢀC)
Compounds
X
3a
3b
3c
3d
3e
3f
H
4-Cl
4-NO2
3-NO2
4-HO
4-CH3
4-CH3O
4-(CH3)2N
3,4-(OCH2O)
170
160
150
150
140
170
170
170
170
10
10
10
10
10
10
10
10
10
77
77
74
79
63
78
91
83
78
275–276
>300
>300
292–293
295–297
281–283
257–258
276–278
287–288
3g
3h
3i
aMicrowave power: 150 W.
bYields of the isolated products.

4184
J.-F. Zhou et al.
aromatic aldehyde and that reasonable yields (63–94%) of the products
were achieved after only 10 min of microwave irradiation.
In conclusion, we have described a rapid and environmentally
friendly procedure for the synthesis of 5-arylidene-2-imino-4-thiazolidi-
none derivatives from the corresponding aromatic aldehyde with
2-imino-4-thiazolidinone under microwave irradiation.
EXPERIMENTAL
Melting points were determined in a WRS-1B digital melting-point instru-
ment and are uncorrected. IR spectra were recorded on a Nicolet Avatar
1
360 FT-IR instrument. H NMR were measured on a Burke 400-MHz
spectrometer in DMSO-d6 with TMS as internal standard. Mass spectra
(MS) were recorded on an LCQ Advantage instrument. Reactions under
microwaves were performed in a CEM Discover1 monomode microwave
reactor. All the reagents are commercially available.
General Procedure for 5-Arylidene-2-imino-4-thiazolidinones (3a–i)
A 10-mL process vial was charged with a mixture of the aromatic alde-
hyde (1 mmol), 2-imino-4-thiazolidinone (1 mmol), sodium acetic
(1.5 mmol), and acetic acid (5 mL) and sealed with a cap containing a sep-
tum. The loaded vial was then placed into the cavity of the microwave
reactor and heated at 150 W, 140–170 ꢀC for 10 min (as indicated by
thin-layer chromatography, TLC). The reaction mixture was allowed to
stand at room temperature to solidify. The crude product was collected,
washed with water, and recystallized from 95% ethanol.
Data
Compound 3a
1H NMR (400 MHz, DMSO-d6): d 9.44 (s, 1H, ¼NH), 9.17 (s, 1H, NH),
7.81 (s, 1H, CH¼), 7.54 (s, 5H, ArH); IR (KBr): 3184, 3018, 1673, 1508,
1278, 1143 cmꢁ1; MS: m=e (M þ H)þ 204.2. Anal. Calcd. for C10H8N2OS:
C, 58.81; H, 3.95; N, 13.72. Found: C, 59.06; H, 3.97; N, 13.79.
Compound 3b
1H NMR (400 MHz, DMSO-d6): d 9.54 (s, 1H, ¼NH), 9.27 (s, 1H, NH),
7.93 (s, 1H, CH¼), 7.62 (d, 2H, J ¼ 8.8 Hz, ArH), 7.51 (d, 2H, J ¼ 8.8 Hz,

5-Arylidene-2-imino-4-thiazolidinones
4185
ArH); IR (KBr): 3206, 3010, 1670, 1559, 1274, 1139 cmꢁ1; MS: m=e
(M þ H)þ 239.9. Anal. calcd. for C10H7ClN2OS: C, 50.32; H, 2.96; N,
11.74. Found: C, 50.55; H, 2.98; N, 11.80.
Compound 3c
1H NMR (400 MHz, DMSO-d6): d 9.63 (s, 1H, ¼NH), 9.35 (s, 1H, NH),
8.34 (d, 2H, J ¼ 8.8 Hz, ArH), 7.83 (d, 2H, J ¼ 8.8 Hz, ArH), 7.71 (s, 1H,
CH¼); IR (KBr): 3217, 3020, 1671, 1528, 1279, 1136 cmꢁ1; MS: m=e
(M þ H)þ 250.5. Anal. calcd. for C10H7N3O3S: C, 48.20; H, 2.83; N,
16.86. Found: C, 48.42; H, 2.85; N, 16.95.
Compound 3d
1H NMR (400 MHz, DMSO-d6): d 9.61 (s, 1H, ¼NH), 9.23 (s, 1H, NH),
8.42 (s, 1H, ArH), 8.26 (d, 1H, J ¼ 8.0 Hz, ArH), 8.04 (d, 1H, J ¼ 8.0 Hz,
ArH), 7.81 (s, 1H, CH¼); IR (KBr): 3228, 3011, 1689, 1530, 1268,
1141 cmꢁ1; MS: m=e (M þ H)þ 250.5. Anal. calcd. for C10H7N3O3S: C,
48.20; H, 2.83; N, 16.86. Found: C, 48.41; H, 2.85; N, 16.96.
Compound 3e
1H NMR (400 MHz, DMSO-d6) d 10.09 (s, 1H, OH), 9.29 (s, 1H, ¼NH),
9.04 (s, 1H, NH), 7.71 (s, 1H, CH¼), 7.42 (d, 2H, J ¼ 8.8 Hz, ArH), 6.90
(d, 2H, J ¼ 8.8 Hz, ArH); IR (KBr): 3207, 3010, 1648, 1588, 1260,
1143 cmꢁ1; MS: m=e (M þ H)þ 221.5. Anal. calcd. for C10H8N2O2S: C,
54.53; H, 3.66; N, 12.72. Found: C, 54.78; H, 3.68; N, 12.78.
Compound 3f
1H NMR (400 MHz, DMSO-d6) d 9.39 (s, 1H, ¼NH), 9.12 (s, 1H, NH), 7.76
(s, 1H, CH¼), 7.47 (d, 2H, J ¼ 8.0 Hz, ArH), 7.33 (d, 2H, J ¼ 8.0 Hz, ArH),
2.35 (s, 3H, CH3); IR (KBr): 3186, 3016, 1677, 1507, 1277, 1145 cmꢁ1; MS:
m=e (M þ H)þ 219.3. Anal. calcd for C11H10N2OS: C, 60.53; H, 4.62; N,
12.83. Found: C, 60.80; H, 4.65; N, 12.90.
Compound 3g
1H NMR (400 MHz, DMSO-d6) d 9.36 (s, 1H, ¼NH), 9.09 (s, 1H, NH),
7.76 (s, 1H, CH¼), 7.53 (d, 2H, J ¼ 8.8 Hz, ArH), 7.10 (d, 2H, J ¼ 8.8 Hz,
ArH), 3.32 (s, 3H, OCH3); IR (KBr): 3198, 3003, 1696, 1505, 1255,

4186
J.-F. Zhou et al.
1146 cmꢁ1; MS: m=e (M þ H)þ 235.6. Anal. calcd. for C11H10N2O2S: C,
56.40; H, 4.30; N, 11.96. Found: C, 56.65; H, 4.32; N, 12.02.
Compound 3h
1H NMR (400 MHz, DMSO-d6) d 9.18 (s, 1H, ¼ NH), 8.94 (s, 1H, NH),
7.67 (s, 1H, CH¼), 7.43 (d, 2H, J ¼ 8.8 Hz, ArH), 6.81 (d, 2H, J ¼ 8.8 Hz,
ArH), 3.32 [s, 3H, N(CH3)2]; IR (KBr): 3100, 3002, 1684, 1523, 1269,
1145 cmꢁ1; MS: m=e (M þ H)þ 248.6. Anal. calcd. for C12H13N3OS: C,
58.29; H, 5.30; N, 17.00. Found: C, 58.55; H, 5.33; N, 17.09.
Compound 3i
1H NMR (400 MHz, DMSO-d6): d 9.81 (s, 1H, ¼NH), 9.44 (s, 1H, NH),
7.76 (s, 1H, CH¼), 7.61 (s, 1H, ArH), 7.16 (d, 1H, J ¼ 8.0 Hz, ArH), 7.07
(d, 2H, J ¼ 8.0 Hz, ArH), 6.02 (s, 2H, OCH2O); IR (KBr): 3200, 3002,
1666, 1495, 1255, 1144 cmꢁ1; MS: m=e (M þ H)þ 249.5. Anal. calcd. for
C11H8N2O3S: C, 53.21; H, 3.25; N, 11.28. Found: C, 53.44; H, 3.27; N,
11.33.
ACKNOWLEDGMENT
We thank the Jiangsu Key Laboratory for Chemistry of Low-
Dimensional Materials for financial support.
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