Reaction between thiocarbamidoalkyl naphthols and acetylenic esters: An interesting cyclocondensation reaction for the synthesis of new thiazolidin-4-one derivatives

Article abstract of DOI:10.1007/s12039-015-0944-5

This investigation was set to provide derivatives of thiazolidin-4-ones incorporated with aminoalkyl naphthols in a molecular frame work. For this purpose, a series of 1-thiocarbamidoalkyl-2-naphthols was prepared by the three component condensation of aromatic aldehydes, phenylthiourea and 2-naphthol. In the next step, these compounds underwent reaction with dialkyl acetylenedicarboxylates at ambient temperature in ethanol to afford the corresponding 4-thiazolidinones in high yields. Following the completion of the reaction, the products were solidified and isolated by filtration. The method is easy, inexpensive, chemoselective and environmentally benign and illustrates an interesting instance of click chemistry.

Full text of DOI:10.1007/s12039-015-0944-5

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J. Chem. Sci. Vol. 127, No. 10, October 2015, pp. 1795–1800. ꢀ Indian Academy of Sciences.
DOI 10.1007/s12039-015-0944-5
Reaction between thiocarbamidoalkyl naphthols and acetylenic esters:
An interesting cyclocondensation reaction for the synthesis of new
thiazolidin-4-one derivatives
SAKINEH AMINI∗, AHMAD MOMENI TIKDARI and HOJATOLLAH KHABAZZADEH
Department of Chemistry, Shahid Bahonar University of Kerman, Kerman 7616914111, Iran
e-mail: h-amini@sci.uk.ac.ir
MS received 8 February 2015; revised 5 May 2015; accepted 20 May 2015
Abstract. This investigation was set to provide derivatives of thiazolidin-4-ones incorporated with amino-
alkyl naphthols in a molecular frame work. For this purpose, a series of 1-thiocarbamidoalkyl-2-naphthols was
prepared by the three component condensation of aromatic aldehydes, phenylthiourea and 2-naphthol. In the
next step, these compounds underwent reaction with dialkyl acetylenedicarboxylates at ambient temperature in
ethanol to afford the corresponding 4-thiazolidinones in high yields. Following the completion of the reaction,
the products were solidified and isolated by filtration. The method is easy, inexpensive, chemoselective and
environmentally benign and illustrates an interesting instance of click chemistry.
Keywords. Multi component reaction; cyclocondensation; 1-thiocarbamidoalkyl-2-naphthols; acetylenic
esters; thiazolidin-4-ones.
anti-inflammatory,11,12 anti-cancer,13–15 antihistaminic,16
anti-fungal,17 anti-HIV18 and anti-hypertensive19 agents.
Due to the biological importance of these com-
pounds, the development of efficient protocols for
their preparation has received significant attention
and several improved procedures have recently been
reported. One of the most convenient and effective
methods that has ever been designed is the reaction
between thioamides and thiosemicarbazide derivatives
with dialkyl acetylenedicarboxylates which provides
2-imino-5-alkoxycarbonyl-thiazolidin-4-ones.20–22
The current study was designed to afford derivatives
of thiazolidin-4-ones incorporated with aminoalkyl
naphthols in a molecular frame work.
1. Introduction
During the last two centuries, multicomponent reac-
tions have been considered as a unique and versatile
tool for the creation of diverse chemical libraries of
pharmaceutical agents.1 One instance of the MCRs is
the synthesis of 1-amidoalkyl-2-naphthol derivatives.
These compounds are a versatile class of intermedi-
ates in the synthesis of biologically active reagents
such as 1, 3-oxazines and aminoalkyl naphthols. It is,
therefore, not surprising that a considerable number
of protocols for the synthesis of these compounds
by three-component condensation of aldehydes, β-
naphthol and acetonitrile or amides/carbamates or
urea in the presence of different catalysts have been
reported.2–5 However, in consequence of the lower reac-
tivity of the thio analogues of amide and urea, only lim-
ited published information regarding the replacement of
amide with thioamide or thiourea are available in the
literature.6–9 The thioamido- and thiocarbamidoalkyl
naphthols which were produced by these methods can
be used as convenient building blocks in the synthesis of
sulfur and nitrogen containing heterocyclic compounds.
Thiazolidinones are an important group of five
membered heterocyclic rings. The 4-thiazolidinone
scaffold has featured in a number of clinically pre-
scribed drugs. They can be used as antibacterial,10
2. Experimental
2.1 Materials and Methods
All chemicals were purchased from Merck and Fluka
Chemical Companies and were used without further
purification. Melting points were determined using an
Electrothermal-9100 melting point apparatus and were
uncorrected. IR spectra were run on a Bruker Tensor-27
FT-IR spectrometer. NMR spectra were recorded on a
Bruker 400-MHz spectrometer using CDCl3 as solvent.
Carbon assignments for some of products were made
based on DEPT 135 spectroscopy. Elemental analyses
∗For correspondence
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Sakineh Amini et al.
were performed on a Vario Macro CHNS Element J = 9.2 Hz, 1H), 6.54 (s, 1H), 3.94 (s, 3H, OCH3) ppm;
Analyzer.
13C NMR (100 MHz, CDCl3) δ: 166.4, 163.9, 154.7,
154.0, 139.4, 139.1, 133.8, 133.4, 131.4, 130.2, 129.9,
129.1, 128.9, 128.8, 128.7, 127.7, 127.1, 123.1, 121.2,
120.3, 117.8, 115.3, 65.3, 53.0 ppm. Anal. Calc. for
C29H21ClN2O4S: C 65.84, H 4.00, N 5.30, S 6.06%.
Found: C 66.30, H 3.90, N 4.88, S 6.51%.
2.2 General procedure for the preparation
of thiazolidin-4-ones
To a magnetically well stirred solution of 1-
thiocarbamido-2-naphthol (1 mmol) in EtOH (5 mL),
dimethyl acetylenedicarboxylate (DMAD) or diethyl
acetylenedicarboxylate (DEAD), (1.2 mmol) was added
at ambient temperature. The reaction mixture was then
allowed to stir for an appropriate time. After the com-
pletion of reaction (as indicated by TLC, ethyl acetate:
n-hexane, 30:70), the solid product was filtered off and
washed thoroughly with cold ethanol.
2d: IR (KBr): νmax = 3477, 3145, 3062, 2949, 1726,
1709, 1631 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.35
(s, 1H, OH), 7.88 (d, J = 8.4 Hz, 1H), 7.77-7.72 (m,
2H), 7.59-7.42 (m, 5H), 7.34-7.31 (m, 3H), 7.25 ( dd,
J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.18 (dt, J1 = 8.0 Hz,
J2 = 1.6 Hz, 1H), 7.11 (d, J = 8.8 Hz, 1H), 7.07 (d, J
= 6.8 Hz, 1H), 7.05 (s, 1H), 6.92 (s, 1H), 3.90 (s, 3H,
OCH3) ppm; 13C NMR+DEPT (100 MHz, CDCl3) δ:
166.3 (C), 164.2 (C), 154.9 (C), 154.7 (C), 140.0 (C),
137.4 (C), 133.5 (C), 133.2 (C), 131.6 (C), 130.3 (CH),
130.2 (CH), 129.9 (CH), 129.8 (CH), 129.7 (CH), 129.4
(CH), 128.8 (CH), 128.7 (C), 127.9 (CH), 127.7 (CH),
127.3 (CH), 123.2 (CH), 121.4 (CH), 120.0 (CH), 117.3
(CH), 115.7 (C), 63.3 (CH), 52.8 (CH3) ppm. Anal.
Calc. for: C29H21ClN2O4S: C 65.84, H 4.00, N 5.30, S
6.06%. Found: C 65.75, H 4.10, N 5.32, S 6.56%.
2.3 Characterization data
2a: IR (KBr): νmax = 3430, 3062, 2955, 1731, 1684,
1644 cm−1; H NMR (400 MHz, CDCl3) δ: 9.81 (s,
1
1H, OH), 7.95 (d, J = 8.4 Hz, 1H), 7.75 (d, J =
7.6 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.64-7.54 (m,
3H), 7.50-7.46 (m, 1H), 7.43-7.40 (m, 2H), 7.36-7.21
(m, 6H), 7.09 (s, 1H), 7.08 (d, J = 9.2 Hz, 1H), 6.58
(s, 1H), 3.94 (s, 3H, OCH3) ppm; 13C NMR+DEPT
(100 MHz, CDCl3) δ: 166.4 (C), 164.0 (C), 154.7 (C),
153.6 (C), 140.6 (C), 139.7 (C), 133.5 (C), 131.6 (C),
130.0 (CH), 129.9 (CH), 129.8 (CH), 128.9 (CH), 128.8
(CH), 128.7 (C), 127.9 (CH), 127.8 (CH), 127.5 (CH),
127.0 (CH), 122.9 (CH), 121.4 (CH), 120.3 (CH), 117.6
(CH), 115.8 (C), 66.1 (CH), 52.9 (CH3) ppm. Anal.
Calc. for C29H22N2O4S: C 70.43, H 4.48, N 5.66, S
6.48%. Found: C 70.83, H 4.55, N 5.41, S 6.53%.
2e: IR (KBr): νmax = 3473, 3193, 3071, 2972, 1724,
1707, 1688, 1648 cm−1; 1H NMR (400 MHz, CDCl3) δ:
9.36 (s, 1H, OH), 8.25 (d, J = 2.0 Hz, 1H), 8.09 (dd,
J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.93 (d, J = 8.4 Hz,
1H), 7.79 (d, J = 7.6 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H),
7.66-7.51 (m, 5H), 7.41 (t, J = 8.0 Hz, 1H), 7.38-7.34
(m, 3H), 7.11 (s, 1H), 7.09 (d, J = 8.8 Hz, 1H), 6.67
(s, 1H), 3.93 (s, 3H, OCH3) ppm; 13C NMR (100 MHz,
CDCl3) δ: 166.3, 163.9, 154.7, 148.4, 142.8, 133.4,
131.4, 130.6, 130.0, 129.9, 129.1, 128.8, 127.7, 127.5,
123.3, 122.9, 122.1, 120.3, 118.2, 65.9, 53.0 ppm. Anal.
Calc. for C29H21N3O6S; C 64.55, H 3.92, N 7.79, S
5.94%. Found: C 64.03, H 4.21, N 7.54, S 5.66 %.
2b: IR (KBr): νmax = 3439, 3072, 3007, 1725, 1705,
1649 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.15 (s, 1H,
OH), 7.71 (d, J = 8.4 Hz, 1H), 7.65 (dd, J1 = 11.6 Hz,
J2 = 8.8 Hz, 2H), 7.50-7.34 (m, 5H), 7.25-7.19 (m,
3H), 7.06 (d, J = 8.4 Hz, 1H), 7.00 (d, J = 8.8 Hz,
1H), 6.96 (s, 1H), 6.93 (dd, J1 = 8.4 Hz, J2 = 2 Hz,
1H), 6.75 (s, 1H), 3.79 (s, 3H, OCH3) ppm; 13C NMR
(100 MHz, CDCl3) δ: 166.3, 164.2, 155.1, 154.9, 139.8,
136.1, 134.6, 133.9, 133.4, 131.4, 131.2, 130.6, 129.9,
129.8, 129.6, 128.8, 128.7, 128.0, 127.9, 127.5, 123.3,
121.1, 120.0, 117.5, 115.2, 62.7, 52.9 ppm. Anal. Calc.
for C29H20Cl2N2O4S: C 61.82, H 3.58, N 4.97, S 5.69%.
Found: C 61.99, H 3.55, N 4.69, S 6.69%.
2f: IR (KBr): νmax = 3480, 3062, 2953, 1715, 1691,
1642 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.51 (s, 1H,
OH), 8.12 (td, J1 = 9.2 Hz, J2 = 2.0 Hz, 2H), 7.89
(d, J = 8.4 Hz, 1H), 7.78 (d, J = 7.2 Hz, 1H), 7.73 (d,
J = 8.8 Hz, 1H), 7.65-7.49 (m, 7H), 7.36- 7.33 (m, 3H),
7.11 (s, 1H), 7.08 (d, J = 8.8 Hz, 1H), 6.66 (s, 1H), 3.93
(s, 3H, OCH3) ppm; 13C NMR (100 MHz, CDCl3) δ:
166.3, 163.8, 154.7, 154.6, 147.8, 147.7, 147.3, 139.2,
133.3, 131.3, 130.6, 130.0, 129.9, 129.1, 128.8, 128.2,
127.7, 127.4, 124.1, 123.3, 121.0, 120.3, 118.2, 64.6,
53.0 ppm. Anal. Calc. for C29H21N3O6S; C 64.55, H
3.92, N 7.79, S 5.94%. Found: C 64.55, H 4.40, N 7.39,
S 5.55%.
2c: IR (KBr): νmax = 3483, 3062, 2949, 1730, 1691,
1646 cm−1; H NMR (400 MHz, CDCl3) δ: 9.72 (s,
1
1H, OH), 7.88 (d, J = 8.4 Hz, 1H), 7.76 (d, J =
7.6 Hz, 1H), 7.70 (d, J = 9.2 Hz, 1H), 7.64-7.54 (m,
3H), 7.51-7.46 (m, 1H), 7.34-7.30 (m, 5H), 7.24 (td,
J1 = 8.4 Hz, J2 = 2 Hz, 2H), 7.10 (s, 1H), 7.07 (d,
2g: IR (KBr): νmax = 3386, 3061, 2949, 1730, 1690,
1643 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.87 (s, 1H,

Synthesis of substituted thiazolidin-4-one derivatives
1797
OH), 7.91 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 7.6 Hz, CDCl3) δ: 165.8, 164.2, 155.3, 154.9, 139.4, 136.1,
1H), 7.68 (d, J = 8.8 Hz, 1H), 7.63-7.53 (m, 3H), 7.49- 134.6, 133.9, 133.5, 131.4, 131.2, 130.6, 129.9, 129.8,
7.45 (m, 1H), 7.35-7.30 (m, 5H), 7.09 (s, 1H), 7.07 (d, 129.6, 128.8, 128.7, 128.0, 127.9, 127.5, 123.3, 121.1,
J = 8.8 Hz, 1H), 6. 80 (td, J1 = 8.8 Hz, J2 = 2 Hz, 120.0, 118.1, 115.3, 62.7, 62.1, 14.2 ppm; Anal. Calc.
2H), 6.53 (s, 1H), 3.94 (s, 3H, OCH3), 3.74 (s, 3H, for C30H22Cl2N2O4S; C 62.40, H 3.84, N 4.85, S 5.55.
OCH3) ppm; 13C NMR+DEPT (100 MHz, CDCl3) δ: Found: C 62.74, H 3.77, N 4.48, S 5.35%.
166.4 (C), 163.9 (C), 159.1 (C), 154.6 (C), 153.2 (C),
2k: IR (KBr): νmax = 3434, 3068, 2985, 1726, 1699,
139.7 (C), 133.5 (C), 132.8 (C), 131.5 (C), 129.9 (CH),
129.8 (CH), 128.9, 128.8 (CH), 128.7 (CH), 127.8
(CH), 127.0 (CH), 122.9 (CH), 121.4 (CH), 120.3 (CH),
117.5 (CH), 115.9 (C), 114.2 (CH), 65.7 (CH), 55.2
(CH3), 52.9 (CH3) ppm. Anal. Calc. for C30H24N2O5S:
C 68.69, H 4.61, N 5.34, S 6.11%. Found: C 68.36, H
4.99, N 5.70, S 6.27%.
1652 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.74 (s, 1H,
OH), 7.88 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H),
7.70 (d, J = 8.8 Hz, 1H), 7.64-7.54 (m, 3H), 7.50-7.46
(m, 1H), 7.35-7.30 (m, 5H), 7.25 (td, J1 = 8.4 Hz, J2 =
2.4 Hz, 2H), 7.10 (s, 1H), 7.07 (d, J = 8.8 Hz, 1H), 6.55
(s, 1H), 4.39 (q, J = 7.2 Hz, 2H, OCH2CH3), 1.41(t,
J = 7.2 Hz, 3H, OCH2CH3) ppm; 13C NMR+DEPT
2h: IR (KBr): νmax = 3374, 3061, 2949, 1731, 1690, (100 MHz, CDCl3) δ: 166.0 (C), 164.0 (C), 154.7 (C),
1644 cm−1; 1H NMR (400 MHz, CDCl3) δ: 10.0 (s, 1H, 154.2 (C), 139.2 (C), 139.1 (C), 133.7 (C), 133.4 (C),
OH), 7.90 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 7.2 Hz, 1H), 131.4 (C), 130.2 (CH), 129.9 (CH), 129.1 (CH), 128.9
7.68 (d, J = 8.8 Hz, 1H), 7.57-7.44 (m, 4H), 7.32-7.29 (CH), 128.8 (CH), 128.7 (C), 127.7 (CH), 127.1 (CH),
(m, 3H), 7.25 (td, J1 = 8.8 Hz, J2 = 2.8 Hz, 2H), 7.09 123.1 (CH), 121.2 (CH), 120.3 (CH), 118.3 (CH), 115.4
(s, 1H), 7.06 (d, J = 8.8 Hz, 1H), 6.69 (td, J1 = 8.8 Hz, (C), 65.3 (CH), 62.2 (CH2), 14.2 (CH3) ppm; Anal.
J2 = 2.8 Hz, 2H), 6.51 (s, 1H), 5.68 (s, 1H, OH), 3.94 Calc. for C30H23ClN2O4S; C 66.35, H 4.27, N 5.16, S
(s, 3H, OCH3) ppm; 13C NMR (100 MHz, CDCl3) δ: 5.90%. Found: C 66.55, H 4.15, N 5.03, S 5.61%.
166.5, 164.0, 155.5, 154.4, 153.3, 139.8, 133.4, 132.6,
2l: IR (KBr): νmax = 3430, 3065, 2983, 1726, 1697,
131.5, 129.9, 128.9, 128.8, 128.7, 127.7, 127.0, 123.0,
121.5, 120.2, 117.6, 115.9, 115.7, 65.7, 53.0 ppm. Anal.
Calc. for C29H22N2O5S: C 68.22, H 4.34, N 5.49, S
6.28%. Found: C 68.11, H 4.18, N 5.47, S 5.56%.
1637 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.36 (s, 1H,
OH), 7.88 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.4 Hz,
1H), 7.73 (d, J = 8.8 Hz, 1H), 7.59-7.46 (m, 4H), 7.42
(dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H), 7.34-7.30 (m, 3H),
2i: IR (KBr): νmax = 3456, 3141, 3071, 1726, 1680, 7.25 (dd, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H), 7.18 (dt,
1639 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.84 (s, 1H, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 7.11 (d, J = 8.8 Hz,
OH), 7.94 (d, J = 8.8 Hz, 1H), 7.75 (d, J = 7.2 Hz, 1H), 7.07 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.04 (s,
1H), 7.69 (d, J = 9.2 Hz, 1H), 7.63-7.54 (m, 3H), 1H), 6.91 (s, 1H), 4.34 (q, J = 7.2 Hz, 2H, OCH2CH3),
7.50-7.40 (m, 3H), 7.35-7.30 (m, 4H), 7.27-7.21 (m, 1.37 (t, J = 7.2 Hz, 3H, OCH2CH3) ppm; 13C NMR
2H), 7.09 (s, 1H), 7.07 (s, 1H), 6.58 (s, 1H), 4.39 (q, (100 MHz, CDCl3) δ: 165.8, 164.3, 154.9, 154.8, 139.7,
J = 7.2 Hz, 2H, OCH2CH3), 1.41 (t, J = 7.2 Hz, 3H, 137.5, 133.5, 133.2, 131.6, 130.3, 130.2, 129.9, 129.8,
OCH2CH3) ppm; 13C NMR+DEPT (100 MHz, CDCl3) 129.7, 129.4, 128.8, 128.7, 127.9, 127.7, 127.3, 123.2,
δ: 166.0 (C), 164.0 (C), 154.7 (C), 153.8 (C), 140.6 121.4, 120.0, 117.9, 115.7, 63.3, 62.0, 14.2 ppm; Anal.
(C), 139.4 (C), 133.5 (C), 131.6 (C), 130.0 (CH), 129.9 Calc. for C30H23ClN2O4S: C 66.35, H 4.27, N 5.16, S
(CH), 129.8 (CH), 128.9 (CH), 128.8 (CH), 128.7 (C), 5.90%. Found: C 66.88, H 4.27, N 5.03, S 5.75%.
127.9(CH), 127.8 (CH), 127.5 (CH), 127.0 (CH), 122.9
2m: IR (KBr): νmax = 3516, 3078, 2978, 1732, 1697,
(CH), 121.4 (CH), 120.3 (CH), 118.1 (CH), 115.8 (C),
1
1652 cm−1; H NMR (400 MHz, CDCl3) δ: 9.39 (s,
66.1 (CH), 62.2 (CH2), 14.2 (CH3) ppm; Anal. Calc.
for C30H24N2O4S: C 70.85, H 4.76, N 5.51, S 6.30%.
Found: C 70.37, H 4.87, N 5.42, S 6.58%
1H, OH), 8.25 (t, J = 2.0 Hz, 1H), 8.11-8.08 (m, 1H),
7.93 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H),
7.74 (d, J = 8.8 Hz, 1H), 7.66-7.51 (m, 5H), 7.41
2j: IR (KBr): νmax = 3437, 3070, 2993, 1727, 1698, (t, J = 8.0 Hz, 1H) 7.38-7.34 (m, 3H), 7.11 (s, 1H),
1651 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.28 (s, 1H, 7.09 (d, J = 8.8 Hz, 1H), 6.67 (s, 1H), 4.39 (q, J =
OH), 7.82 (d, J = 8.8 Hz, 1H), 7.78-7.73 (m, 2H), 7.2 Hz, 2H, OCH2CH3), 1.40 (t, J = 7.2 Hz, 3H,
7.60-7.44 (m, 5H), 7.35-7.30 (m, 3H), 7.16 (d, J = OCH2CH3) ppm; 13C NMR+DEPT (100 MHz, CDCl3)
8.4 Hz, 1H), 7.11 (d, J = 8.8 Hz, 1H), 7.05 (s, 1H), δ: 165.8 (C), 164.0 (C), 155.3 (C), 154.8 (C), 154.7
7.03 (dd, J1 = 8.8 Hz, J2 = 2.0 Hz, 1H), 6.86 (s, (C), 148.4 (C), 142.8 (C), 138.8 (C), 133.4 (CH), 131.4
1H), 4.34 (q, J = 7.2 Hz, 2H, OCH2CH3), 1.37 (t, J = (C), 130.6 (CH), 130.0 (CH), 129.9 (CH), 129.1 (CH),
7.2 Hz, 3H, OCH2CH3) ppm.; 13C NMR (100 MHz, 128.8 (C), 127.7 (CH), 127.5 (CH), 123.3 (CH), 122.9

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Sakineh Amini et al.
(CH), 122.1 (CH), 120.9 (CH), 120.3 (CH), 118.8 8.4 Hz, J2 = 2.8 Hz, 2H), 6.51 (s, 1H), 5.54 (s, 1H,
(CH), 64.2 (CH), 62.3 (CH2), 14.2 (CH3) ppm; Anal. OH), 4.39 (q, J = 7.2 Hz, 2H, OCH2CH3), 1.41 (t,
Calc. for C30H23N3O6S; C 65.09, H 4.19, N 7.59, S J = 7.2 Hz, 3H, OCH2CH3) ppm; 13C NMR+DEPT
5.79%.Found: C 65.16, H 4.38, N 7.52, S 5.43%.
(100 MHz, CDCl3) δ: 166.1 (C), 164.0 (C), 155.5 (C),
154.3 (C), 153.5 (C), 139.5 (C), 133.4 (C), 132.6 (C),
2n: IR (KBr): νmax = 3434, 3069, 2981, 1728, 1698, 131.5 (C), 129.9 (CH), 128.9 (CH), 128.8 (CH), 128.7
1649 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.54 (s, 1H, (C), 127.7 (CH), 127.0 (CH), 123.0 (CH), 121.5 (CH),
OH), 8.14-8.10 (m, 2H), 7.90 (d, J = 8.4 Hz, 1H), 7.78 120.2 (CH), 118.1 (CH), 116.0 (C), 115.7 (CH), 65.7
(d, J = 7.6 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.65- (CH), 62.3 (CH2), 14.2 (CH3) ppm; Anal. Calc. for
7.50 (m, 6H), 7.37-7.32 (m, 3H), 7.11 (s, 1H), 7.08 C30H24N2O5S; C 68.69, H 4.61, N 5.34, S 6.11%.
(d, J = 8.8 Hz, 1H), 6.66 (s, 1H), 4.39 (q, J = 7.2 Hz, Found: C 68.81, H 4.66, N 5.48, S 6.41%.
2H, OCH2CH3), 1.40 (t, J = 7.2 Hz, 3H, OCH2CH3)
ppm; 13C NMR+DEPT (100 MHz, CDCl3) δ: 165.9
3. Results and Discussion
(C), 163.9 (C), 155.3 (C), 154.7 (C), 147.7 (C), 147.4
(C), 138.8 (C), 133.3 (C), 131.3 (C), 130.6 (CH),
130.1 (CH), 130.0 (CH), 129.1 (CH), 128.8, 128.2
(CH), 127.7 (CH), 127.4 (CH), 124.1 (CH), 123.3
(CH), 120.9 (CH), 120.3 (CH), 118.7 (CH), 115.0 (C),
64.6 (CH), 62.3 (CH2), 14.2 (CH3) ppm; Anal. Calc.
for C30H23N3O6S: C 65.09, H 4.19, N 7.59, S 5.79%.
Found: C 65.25, H 4.28, N 7.59, S 5.74%.
In this research work, the use of 1-thiocarbamidoalkyl-
2-naphthol derivatives 1 as precursors in the synthe-
sis of new 4-thiazolidinones is described. The eight
required substrates (1a-1h) were synthesized according
to a previously reported method8 via three component
reaction of 2-naphthol, phenylthiourea and aromatic
aldehydes, containing electron-donating and electron-
withdrawing groups at various positions of aromatic
ring, in the presence of p-TSA (10 mol %) as catalyst
at ambient temperature in dichloromethane (scheme 1).
After synthesizing a series of 1-thiocarbamidoalkyl-
2-naphthols, we turned our attention on the synthesis
of thiazolidin-4-one derivatives via reaction of thio-
carbamidoalkyl naphthols with acetylenic esters. In an
initial study, the reaction of 1-((2-hydroxynaphthalen-
1-yl) (phenyl) methyl)-3-phenylthiourea (1a) with
DMAD was examined in different solvents. As table 1
shows, using of ethanol as solvent gave best results, so
ethanol was chosen as the solvent for this reaction.
In the first experiment, the reaction of 1-((2-hydroxy-
naphthalen-1-yl) (phenyl) methyl)-3-phenylthiourea
(1a, 1 mmol) with dimethyl acetylenedicarboxylate
(1.2 mmol) as representative, was performed at room
temperature with reaction time 1 h. After completion of
the reaction, the mixture was filtered and the precipitate
washed thoroughly with cold ethanol. The pure solid
product was isolated without need to further purifica-
tion, because the excess of unreacted DMAD is soluble
in EtOH and could easily be removed from the reac-
tion mixture. In addition, the reaction profile is very
2o: IR (KBr): νmax = 3437, 3066, 2998, 1729, 1691,
1646 cm−1; 1H NMR (400 MHz, CDCl3) δ: 9.89 (s, 1H,
OH), 7.91 (d, J = 8.8 Hz, 1H), 7.74 (d, J = 7.6 Hz,
1H), 7.68 (d, J = 8.8 Hz, 1H), 7.63-7.54 (m, 3H), 7.49-
7.44 (m, 1H), 7.35-7.30 (m, 5H), 7.09 (s, 1H), 7.07 (d, J
= 8.8 Hz, 1H), 6.80 (dt, J1 = 8.8 Hz, J2 = 2.8 Hz, 2H),
6.54 (s, 1H), 4.40 (q, J = 7.2 Hz, 2H, OCH2CH3), 3.75
(s, 3H, OCH3), 1.41 (t, J = 7.2 Hz, 3H, OCH2CH3)
ppm; 13C NMR (100 MHz, CDCl3) δ: 166.0, 164.0,
159.1, 154.6, 153.4, 139.4, 133.5, 132.8, 131.5, 129.9,
129.8, 129.7, 128.9, 128.8, 128.7, 127.8, 126.9, 122.9,
121.4, 120.3, 118.0, 115.9, 114.2, 65.7, 62.1, 55.2,
14.2 ppm; Anal. Calc. for C31H26N2O5S: C 69.13, H
4.87, N 5.20, S 5.95%. Found: C 69.62, H 4.95, N 5.22,
S 6.35%.
2p: IR (KBr): νmax = 3418, 3067, 2983, 1733, 1689,
1
1642 cm−1; H NMR (400 MHz, CDCl3) δ: 10.07 (s,
1H, OH), 7.89 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 7.6 Hz,
1H), 7.68 (d, J = 8.8 Hz, 1H), 7.56-7.43 (m, 4H), 7.32-
7.29 (m, 3H), 7.24 (td, J1 = 8.4 Hz, J2 = 2.8 Hz, 2H),
7.08 (s, 1H), 7.06 (d, J = 8.8 Hz, 1H), 6.67 (td, J1 =
Scheme 1. Preparation of 1-thiocarbamidoalkyl-2-naphthols.

Synthesis of substituted thiazolidin-4-one derivatives
Table 1. Effect of solvents on product formation.
1799
Entry
Solvent
Time (min)
Yield (%)
1
2
3
4
5
6
CH2Cl2
CHCl3
THF
180
180
180
60
180
120
0
0
80
90
60
75
EtOH
1, 4-Dioxane
CH3CN
Table 2. Synthesis of thiazolidin-4- ones from thiocarbamidoalkyl naphthols.
Product
R1
R2
Yield (%)
Time (min)
M.p.(◦C)
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
H
2,4-dichloro
4-Chloro
2-Chloro
3-NO2
4-NO2
4-OCH3
4-OH
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
90
85
91
92
86
93
89
90
81
82
86
84
80
85
86
81
60
60
90
243–245
212–213
187–189
146–148
132–133
143–145
203–204
224–226
171–172
210–211
189–190
121–122
201–202
229–231
203–205
223–225
75
120
120
75
60
H
180
170
180
165
180
180
165
150
2,4-dichloro
4-Chloro
2-Chloro
3-NO2
4-NO2
4-OCH3
4-OH
Scheme 2. Reaction of thiocarbamidoalkyl naphthols with DMAD and DEAD.
clean and no by product is formed. Encouraged by have been investigated. It was found that these reac-
these excellent results, we examined the scope of this tions gave lower yields of products and needed longer
method for reactions of the other synthesized thiocar- times to completion (2–3 h) due to the low reactivity
bamidoalkyl naphthols with DMAD. In every case, the of DEAD compared to DMAD. The results are summa-
reaction was accomplished in a short time and the cor- rized in table 2 (scheme 2).
responding product was obtained in high yield. It is
A plausible mechanism for the synthesis of
pertinent to note, since some of the compounds such thiazolidin-4-one derivatives has been proposed in
as 1e and 1f are less soluble in ethanol, longer reac- scheme 3. This reaction begins by addition of the sulfur
tion time (about 2 h) was needed for the reaction to atom onto the acetylene triple bond which is suscepti-
be completed. The difference in the product yields ble to nucleophilic attack. Subsequently the intermedi-
is mainly due to the different solubility of thiocar- ate (A) undergoes intramolecular cyclization to afford
bamidoalkyl naphthols in ethanol which is a result of deliberated thiazolidin-4-one.
different substituents on the phenyl ring.
All the synthesized thiazolidin-4-ones have been
In a similar fashion, the reactions of thiocarbami- characterized on the basis of elemental and spectral
doalkyl naphthols with diethyl acetylenedicarboxylate studies.

1800
Sakineh Amini et al.
Scheme 3. A plausible mechanism for the formation of thiazolidin-4- ones.
The FT-IR spectrum of 2a revealed a broad band at References
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In conclusion, an efficient, facile and environ-
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acetylenedicarboxylates in ethanol. The attractive fea-
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short reaction times, absence of any catalyst, high yields
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Supplementary Information
Supplementary Information associated with this article
is available at www.ias.ac.in/chemsci.
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We gratefully acknowledge the financial support from
the Research Council of Shahid Bahonar University of
Kerman.