Ultrasonics promoted synthesis of thiazolidinones from 2-aminopyridine and 2-picolilamine

Article abstract of DOI:10.1016/j.ultsonch.2012.03.004

The efficient multicomponent synthesis of thiazolidinones from the reaction of arenealdehydes, mercaptoacetic acid and 2-picolilamine or 2-aminopyridine under ultrasound irradiation are reported. The reaction with 2-aminopyridine needs a Lewis acid cataly

Full text of DOI:10.1016/j.ultsonch.2012.03.004

Ultrasonics Sonochemistry 19 (2012) 1127–1131
Contents lists available at SciVerse ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultson
Short Communication
Ultrasonics promoted synthesis of thiazolidinones from 2-aminopyridine
and 2-picolilamine
Daniela P. Gouvêa, Valéria D.O. Bareño, Juliano Bosenbecker, Bruna B. Drawanz, Patrícia D. Neuenfeldt,
⇑
Geonir M. Siqueira, Wilson Cunico
Núcleo de Química Aplicada (NuQuiA), Universidade Federal de Pelotas - UFPel, Campus Universitário, s/n°, 96010-900 Pelotas, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
The efficient multicomponent synthesis of thiazolidinones from the reaction of arenealdehydes, mercap-
toacetic acid and 2-picolilamine or 2-aminopyridine under ultrasound irradiation are reported. The
reaction with 2-aminopyridine needs a Lewis acid catalysis to afford the corresponding 2-aryl-3-(pyridin-
2-yl)-1,3-thiazolidin-4-ones. All novel compounds were identified and characterized by 1H and 13C NMR
spectra. Applying the sonochemical methodology, two series of heterocyclic thiazolidinones were synthe-
sized in good yields after short reaction times.
Received 10 November 2011
Received in revised form 16 December 2011
Accepted 13 March 2012
Available online 21 March 2012
Keywords:
Ó 2012 Elsevier B.V. All rights reserved.
Thiazolidinones
Ultrasound irradiation
One-pot synthesis
1. Introduction
2-picolilamine) as precursor to the thiazolidinones by sonochemi-
cal synthesis.
Ultrasound irradiation has been utilized to accelerate a number
of synthetically useful reactions during the last few years. Cavita-
tion is the formation, growth and collapse of bubbles in an irradi-
ated liquid. This effect induces very high local pressure and
temperatures inside the bubbles and enhances mass transfer and
turbulent flow in the liquid [1]. Ultrasound has been utilized to
accelerate a number of synthetically useful reactions, especially
in heterocyclic chemistry. The literature reports the sonochemistry
synthesis of 1,2,4-oxadiazoles [2], benzoxazoles [3], pyrazoles [4],
thiazoles [5], isoxazoles [6], imidazolines [7], thiazolidinones [8],
triazoles [9], pyrimidines [10], pyrazolopyridines [11], thiazina-
nones [12].
For the past five years, our research program has extensively
studied the formation five-membered heterocyclic thiazolidinones
[13]. Thiazolidinones have valuable biological activities as antitumor
[14], antidiabetes [15], antioxidant [16], anti-hepatitis C virus [17],
antiinflamatory [18], antimicrobial [19], antitubercular [20], and
anti-HIV agents [21]. More recently, we also showed the tubercu-
lostatic activity of such heterocycles [22] and improved the meth-
odologies to synthesis thiazolidinones under solvent-free [13d]
and using ultrasound irradiation [13e]. Now, we aim to explore
the potential synthetic of different amines (2-aminopyridine and
2. Results and discussion
The study of reaction conditions to afford the thiazolidinone 5k
using ultrasound irradiation was summarized in Table 1. The pro-
gresses of reactions were monitored by TLC and GC analysis. It can
see clearly that the best condition were achieved when the mer-
captoacetic acid were added after the reaction of 3-methoxybenz-
aldehyde 1k with 2-aminopyridine 3 (entry 4, 5 and 6). Due the
low nucleophilic reactivity of 2-aminopyridine 3, the presence of
a Lewis acid (BF3:MeOH 50%) was necessary and 10 min in ultra-
sound irradiation to complete the formation of the imine. When
the reaction was carried out in a one-pot methodology, low con-
centration of the desire thiazolidinone 5k was identified due the
formation of the common by-product 2-(3-methoxyphenyl)-1,3-
oxathiolan-5-one (entry 1, 3 and 7) [13c]. The complete imine for-
mation decreases the concentration of aldehyde and avoids the
formation of by-product.
All (pyridin-2-yl)thiazolidinones 5a–o were synthesized from
the reaction of intermediate imines (formed in situ from areneal-
dehyde 1a–o and 2-aminopyridine 3 with a 50% solution of boron
trifluoride in methanol for 10 min) with mercaptoacetic acid 2
using ultrasound irradiation for 25 min in good yields (Scheme 1
and Table 2). In this condition, the compounds 5a, 5b, 5c, 5e, 5g
and 5h showed low yields due the formation of by-product oxa-
thiolane. The thiazolidinones 5a–o were also obtained via conven-
tional methodology after 16 h of reaction using catalytic BF3 to
⇑
Corresponding author.
E-mail addresses: wjcunico@yahoo.com.br, wilson.cunico@ufpel.edu.br (W. Cunico).
1350-4177/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ultsonch.2012.03.004

1128
D.P. Gouvêa et al. / Ultrasonics Sonochemistry 19 (2012) 1127–1131
Table 1
Optimization of reaction medium for the synthesis of thiazolidinone 5k under ultrasonic irradiation.
Entry
Equimolar proportion
Amine
Reaction time (min)
BF3:MeOH
GC-Analyses (%)
Aldehyde
Acid
5k
1
2
3
4
5
6
7
1
1
1
1
1
1
1
1
1
1
1
1
1
2
3
3
3
3
3
1
3
25
No
No
46
52
45
67
98
94
30
5 + 20a
25
10 drops
10 drops
10 drops
10 drops
10 drops
5 + 20a
10 + 25a
10 + 25a
10 + 25a
a
Mercaptoacetic acid added after.
O
N
purification. The reactions were carried out with a microtip probe
(3 mm) connected to a 500 Watt Sonics Vibra-cell ultrasonic pro-
cessor operating at 20 kHz at 25% of the maximum power output.
The progress of reactions and the purity of compounds were mon-
itored by thin layer chromatography (TLC, using silica gel 60F253
aluminum sheets; visualization by ultraviolet light 254 nm) and
i
ii
53-90%
S
N
N
R
N
O
H
R
5a-o
R
O
by
a Shimadzu Gas Chromatograph GC-2010, Column I.D.,
1a-o
N
S
0.25 mm; Column length, 30 m; Column Head Pressure, 14 psi,
program: T0 = 50 °C; t0 = 2.0 min; rate 16.0 °C/min; Tf = 250 °C;
tf = 10.0 min; Inj. = 250 °C; Det. = 270 °C. Melting points were deter-
mined using open capillaries on a Fisatom model 430 apparatus
and are uncorrected. GC–MS analyses were performed on a GC
2010-plus GC–MS-QP2010SE System AOC-20i – auto injector. 1H
and 13C NMR spectra were recorded using a Bruker DRX 400 spec-
trometer (1H at 400.14 MHz and 13C at 100.61 MHz) or a Bruker
Avance 500 spectrometer (1H at 500.13 MHz and 13C at
125.75 MHz) in CDCl3 containing TMS as in internal standard. Ele-
mental analysis was carried out using a CHN EA 1110; percentages
of C, H and N agreed with the product formula (within 0.4% of the-
oretical values for elements).
N
iii
6a-o
R
Scheme 1. (i) 2-Aminopyridine 3, toluene, BF3:MeOH, ultrasonic irradiation,
10 min. (ii) HSCH2COOH 2, ultrasonic irradiation, 25 min. (iii) 2-Picolilamine 4,
toluene, HSCH2COOH 2, ultrasonic irradiation, 10 min.
better yields (Table 2). The compounds were confirmed by GC–MS
and by melting points and are in agreement with literature data
[23–27]. The novel compounds 5d, 5j and 5n were also fully char-
acterized by 1H and 13C NMR (see experimental part).
As expected, the (pyridin-2-ylmethyl)thiazolidinones 6a–o
required less time for complete consumption of the starting materials
due the more reactivity of the aliphatic nitrogen of 2-picolilamine
4. So, those one-pot reactions were carried out in toluene using
ultrasound irradiation for 10 min in good yields without any fur-
ther purification (Scheme 1 and Table 2). Only a few amount of
by-product was observed in GC (up to 5%). The heterocycles 6a–o
were confirmed and characterized by 1H and 13C NMR (see exper-
imental part).
3.1. Conventional synthesis of 2-aryl-3-(pyridin-2-yl)-1,3-thiazolidin-
4-ones 5a-o
A mixture of 2-aminopyridine 3 (1 mmol), BF3:MeOH 50% (10
drops) and corresponding arenaldehyde 1a–o (1 mmol) in toluene
(30 mL) was heated at 110 °C with a Dean–Stark trap for 3 h. After-
ward, the mercaptoacetic acid 2 (1 mmol) was added and the
mixture was heated until the reaction was complete, as shown
by TLC (about 16 h). The organic layer was washed with a saturated
solution of NaHCO3 (3 x 30 mL), dried with MgSO4 and concen-
trated to give the products. When necessary, the compounds were
washed with a hot solution of hexane:ethyl acetate (9:1) to fur-
nished the pure products.
3. Experimental
Unless otherwise indicated, all common reagents and solvents
were used as obtained from commercial suppliers without further
Table 2
Yields and melting points of 3-(pyridin-2-yl)thiazolidinones 5a–o and 3-(pyridin-2-ylmethyl)thiazolidinones 6a–o.
Product
R
m.p.(°C)a Ultrasound yield (%)b Conventional yield (%)b Product
R
m.p.(°C)a Ultrasound yield (%)b Conventional yield (%)b
5a [23]
5b [23,24] 3-NO2
5c [23]
5d
2-NO2
162–164 61
153–155 54
152–154 57
81
74
89
75
50
59
88
83
87
64
72
64
59
50
62
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
2-NO2
3-NO2
4-NO2
2-F
3-F
4-F
2-Cl
3-Cl
4-Cl
2-OCH3 73–74
3-OCH3 Oil
4-OCH3 Oil
2-OH
3-OH
4-CH3
109–112 95
74
58
88
70
75
43
98
98
59
83
90
99
91
89
93
Oil
79
54
52
83
58
52
62
72
70
70
59
89
63
90
4-NO2
2-F
3-F
Oil
Oil
78–80
Oil
79–82
59
45
62
5e [23]
5f [24,17]
5g [25]
5h [24]
5i [24]
5j
5k [24]
5l [26]
5m [27]
5n
78–80
Oil
4-F
2-Cl
3-Cl
4-Cl
108–111 29
53–55
Oil
Oil
Oil
30
50
88–90
2-OCH3 112–115 55
3-OCH3 129–131 69
4-OCH3 102–105 74
2-OH
3-OH
4-CH3
118–120 57
Oil 53
128–130 73
Oil
Oil
Oil
5o [24]
a
Melting points are uncorrected.
Yields of pure compounds.
b

D.P. Gouvêa et al. / Ultrasonics Sonochemistry 19 (2012) 1127–1131
1129
3.2. Ultrasonics synthesis of 2-aryl-3-(pyridin-2-yl)-1,3-thiazolidin-4-
ones 5a-o
3.4. Ultrasonics synthesis of 2-aryl-3-(pyridin-2-ylmethyl)-1,3-
thiazolidin-4-ones 6a–o
In a 25 mL beaker was added a mixture of 2-aminopyridine 3
In a 25 mL beaker was added a mixture of 2-picolilamine 4
(1 mmol) the corresponding arenaldehyde 1a–o (1 mmol) and
the mercaptoacetic acid 2 (3 mmol) in toluene (10 mL). The
reaction mixture was sonicated by an ultrasonic probe with a fre-
quency of 20 kHz at room temperature for 10 min (until complete
consumption of starting materials, as monitored by TLC and GC).
The solution was washed with saturated solution of NaHCO3
(3 x 10 mL), dried with MgSO4 and concentrated to give the pure
products without any further purification.
(1 mmol), BF3:MeOH 50% (10 drops), and the corresponding aren-
aldehyde 1a–o (1 mmol) in toluene (10 mL). The mixture was then
sonicated by an ultrasonic probe with a frequency of 20 kHz at
room temperature for 10 min. The mercaptoacetic acid 2 (1 mmol)
was added and the mixture was sonicated for 25 more minutes un-
til the complete consumption of reagents, as monitored by TLC and
GC. The solution was washed with saturated solution of NaHCO3
(3 x 10 mL), dried with MgSO4 and concentrated to give the pure
products without any further purification. For thiazolidinones 5a,
5b, 5c, 5e, 5g and 5h the pure product were obtained after washed
with hot hexane / ethyl acetate 9:1 (3 x 10 mL).
3.4.1. Selected data for 2-(2-nitrophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6a
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.49 (d, 1H, py, 3J = 5.1);
8.19 (m, 1H, aryl); 8.14 (t, 1H, py, 4J = 2.0); 7.65 (m, 2H, py and
aryl); 7.56 (t, 1H, aryl, 3J = 8.2); 7.22 (m, 2H, aryl); 5.89 (d, 1H,
H2, 4J = 2.0); 5.02 (d, 1H, CH2a, 2J = 15.2); 3.96 (d, 1H, CH2b,
2J = 15.2); 3.93 (dd, 1H, H5a, 2J = 15.6, 4J = 2.0); 3.82 (d, 1H, H5b,
2J = 15.6). 13C NMR d (100 MHz, ppm): 171.4 (C4); 154.9; 149.4;
141.6; 137.1; 133.4; 130.0; 124.0; 122.9; 122.6; 62.7 (C2); 48.1
(CH2); 32.7 (C5).
3.2.1. Selected data for 2-(2-fluorophenyl)-3-(pyridin-2-yl)1,3-
thiazolidin-4-one 5d
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.22 (d, 2H, py and Ph,
3J = 7.4); 7.70 (dt, 1H, py, 3J = 8.6, 4J = 1.8); 7.22 (m, 1H, py); 7.13
(td, 1H, aryl, 3J = 7.8, 4J = 1.5); 7.07 (s, 1H, H2); 7.02 (m, 3H, aryl);
4.05 (dd, 1H, H5a, 2J = 16.0, 4J = 1.2); 3.78 (d, 1H, H5b, 2J = 16.0).
13C NMR
d (100 MHz, ppm, JC–F = Hz): 171.5 (C4); 159.9 (d,
1JC–F = 248.4); 150.6; 147.7; 137.8; 129.5 (d, 3J = 8,8); 126.4;
124.1; 120.6; 116.0 (d, 2J = 28.0); 57.6 (C2); 34.1 (C5). GC–MS m/
z (%): 274 (M, 38); 232 (37), 181 (28), 125 (55), 79 (100).
3.4.2. Selected data for 2-(3-nitrophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6b
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.47 (m, 1H, py); 8.11 (dd,
1H, aryl, 3J = 8.2, 4J = 1.8); 7.70 (dd, 1H, py, 3J = 7.6, 4J = 1.8); 7.49
(m, 2H, py and aryl); 7.24 (m, 2H, aryl); 7.19 (m, 1H, aryl); 6.28
(d, 1H, H2, 4J = 1.2); 5.24 (d, 1H, CH2a, 2J = 15.0); 3.86 (d, 1H, H5a,
2J = 14.6); 3.75 (d, 2H, CH2b and H5b, 2J = 15.0 Hz). 13C NMR d
(100 MHz, ppm): 171.0 (C4); 163.9; 154.5; 148.1; 142.3; 135.9;
132.0; 123.3; 121.8; 121.5; 117.5; 114.9; 62.9 (C2); 47.8 (CH2);
32.6 (C5).
3.2.2. Selected data for 2-(2-methoxyphenyl)-3-(pyridin-2-yl)1,3-
thiazolidin-4-one 5j
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.27 (d, 1H, aryl, 3J = 7.8);
8.23 (dd, 1H, py, 3J = 5.1, 4J = 1.9); 7.70 (dt, 1H, py, 3J = 7.4, 4J = 1.9);
7.22 (td, 1H, py, 3J = 7.9, 4J = 1.5); 7.10 (s, 1H, H2); 6.99 (m, 2H,
aryl); 6.90 (d, 1H, aryl, 3J = 7.8); 6.80 (t, 1H, aryl, 3J = 7.4); 3.95 (d,
1H, H5a, 2J = 16.0); 3.92 (s, 3H, OCH3); 3.70 (d, 1H, H5b,
2J = 16.0). 13C NMR d (100 MHz, ppm): 172.1 (C4); 156.3; 150.9;
147.8; 137.7; 129.3; 128.9; 124.8; 120.3; 116.1; 110.9; 58.6 (C2);
55.6 (OCH3); 34.0 (C5). GC–MS m/z (%): 286 (M, 60); 211 (66),
181 (32), 125 (75), 105 (31), 79 (100).
3.4.3. Selected data for 2-(4-nitrophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6c
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.48 (d, 1H, py, 3J = 4.2);
7.63 (dd, 1H, py, 3J = 7.8, 4J = 2.0); 7.28 (d, 2H, aryl, 3J = 7.8); 7.20
(m, 1H, py); 7.15 (m, 1H, aryl); 6.92 (d, 2H, aryl, 3J = 8.0); 5.88 (s,
1H, H2); 5.12 (d, 1H, CH2a, 2J = 14.6); 3.91 (d, 2H, CH2b and H5a,
2J = 14.8); 3.81 (d, 1H, H5b, 2J = 15.2). 13C NMR d (100 MHz, ppm):
169.9 (C4); 161.4; 154.6; 149.8; 141.8; 136.6; 130.1; 123.5; 123.0;
122.1; 116.9; 115.4; 62.5 (C2); 49.1 (CH2); 33.0 (C5).
3.2.3. Selected data for 2-(3-hydroxyphenyl)-3-(pyridin-2-yl)1,3-
thiazolidin-4-one 5n
1H NMR d (400 MHz, ppm, JH–H = Hz):8.24 (m, 1H, py); 8.06 (d,
1H, py, 3J = 8.3); 7.70 (td, 1H, py, 3J = 7.4 Hz, 4J = 1.9); 7.13 (t, 1H,
aryl, 3J = 7.8); 7.00 (ddd, 1H, aryl, 3J = 7.4, 3J = 5.1, 4J = 1.2); 6.84
(d, 1H, aryl, 3J = 7.8); 6.81 (s, 1H, H2); 6.76 (t, 1H, aryl, 4J = 1.9);
6.68 (ddd, 1H, aryl, 3J = 5.5, 4J = 2.5, 4J = 1.2); 4.02 (dd, 1H, H5a,
3.4.4. Selected data for 2-(2-fluorophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6d
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.51 (d, 1H, py, 3J = 4.0);
7.66 (dd, 1H, py, 3J = 8.0, 4J = 1.9); 7.37 (dd, 1H, py, 3J = 8.0,
4J = 2.0); 7.25 (dd, 1H, aryl, 3J = 7.8, 4J = 1.8); 7.25 (m, 2H, aryl);
7.10 (m, 1H, aryl); 5.79 (s, 1H, H2); 5.08 (d, 1H, CH2a, 2J = 14.8);
2J = 16.4, 4J = 1.2); 3.79 (d, 1H, H5b, 2J = 16.0). 13C NMR
d
(100 MHz, ppm): 171.5 (C4); 156.1; 150.6; 147.8; 142.8; 137.8;
130.0; 120.9; 118.1; 115,3; 112.7; 62.7 (C2); 34.1 (C5).
GC–MS m/z (%): 272 (M, 47); 230 (35), 197 (55), 125 (52), 105
(20), 79 (100).
3.86 (d, 2H, CH2b and H5a, 2J = 14.8); 3.71 (d, 1H, H5b, 2J = 15.0).
1
13C NMR d (100 MHz, ppm, JC–F = Hz): 170.4 (C4); 163.4 (d, JC–F
=
4
3
248.4); 156.0; 149.1; 144.1 (d, JC–F = 5.8); 135.1; 130.2 (d, JC–F = 9.4);
2
2
122.9; 122.0; 121.2; 117.3 (d, JC–F = 22.4); 115.6 (d, JC–F = 22.0);
62.7 (C2); 48.3 (CH2); 33.0 (C5). Anal. Calcd for C15H13FN2OS: C,
62.48; H, 4.54; N, 9.72. Found: C, 62.40; H, 4.79; N, 9.81.
3.3. Conventional synthesis of 2-aryl-3-(pyridin-2-ylmethyl)-1,3-
thiazolidin-4-ones 6a–o
A mixture of 2-picolilamine 4 (1 mmol), corresponding arenal-
dehyde 1a–o (1 mmol) and mercaptoacetic acid 2 (3 mmol) in tol-
uene (30 mL) was heated at 110 °C with a Dean–Stark trap for 16 h.
The organic layer was washed with saturated solution of NaHCO3
(3 x 30 mL), dried with MgSO4 and concentrated to give the prod-
ucts. When necessary, the compounds were washed with a hot
solution of hexane:ethyl acetate (9:1) to furnished the pure
products.
3.4.5. Selected data for 2-(3-fluorophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6e
1H NMR d (500 MHz, ppm, JH–H = Hz): 8.53 (d, 1H, py, 3J = 3.9);
7.63 (dd, 1H, py, 3J = 7.8, 4J = 1.9); 7.33 (dd, 1H, py, 3J = 7.8,
4J = 1.9); 7.18 (m, 2H, aryl); 7.00 (m, 2H, aryl); 7.07 (d, 1H, aryl,
3J = 7.8 Hz); 7.02 (m, 1H, aryl); 5.75 (s, 1H, H2); 5.06 (d, 1H,
CH2a, 2J = 14.6); 3.88 (d, 2H, CH2b and H5a, 2J = 14.6); 3.79 (d, 1H,
H5b, 2J = 15.6). 13C NMR d (125 MHz, ppm, JC–F = Hz): 171.6 (C4);

1130
D.P. Gouvêa et al. / Ultrasonics Sonochemistry 19 (2012) 1127–1131
1
4
163.2 (d, JC–F = 249.2); 155.5; 149.7; 142.0 (d, JC–F = 5.5); 136.9;
127.0; 122.7; 120.8; 111.1; 58.5 (C2); 55.5 (OMe); 48.0 (CH2);
32.5 (C5). Anal. Calcd for C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33.
Found: C, 64.05; H, 5.21; N, 9.57.
3
2
130.8 (d, JC–F = 9.1); 123.1; 122.8; 122.6; 116.3 (d, JC–F = 22.0);
2
114.4 (d, JC–F = 22.0); 63.0 (C2); 48.1 (CH2); 32.8 (C5). Anal. Calcd
for C15H13FN2OS: C, 62.48; H, 4.54; N, 9.72. Found: C, 62.46; H,
4.89; N, 9.80.
3.4.11. Selected data for 2-(3-methoxyphenyl)-3-(pyridin-2-ylmethyl)
1,3-thiazolidin-4-one 6k
3.4.6. Selected data for 2-(4-fluorophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6f
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.53 (d, 1H, py, 3J = 4.0);
7.63 (dd, 1H, py, 3J = 8.0, 4J = 1.9); 7.32 (dd, 1H, py, 3J = 7.8,
4J = 1.9); 7.20 (m, 2H, aryl); 7.01 (m, 2H, aryl); 6.89 (d, 1H, aryl,
3J = 8.0); 7.02 (m, 1H, aryl); 5.78 (s, 1H, H2); 5.03 (d, 1H, CH2a,
2J = 15.0); 3.93 (d, 2H, CH2b and H5a, 2J = 14.8); 3.81 (s, 3H,
OCH3); 3.77 (d, 1H, H5b, 2J = 15.6). 13C NMR d (100 MHz, ppm):
170.6 (C4); 163.2; 155.4; 149.6; 139.9; 136.4; 130.2; 124.6;
122.5; 121.9; 117.3; 114.4; 62.3 (C2); 55.9 (OCH3); 48.6 (CH2);
32.5 (C5). Anal. Calcd for C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33.
Found: C, 64.25; H, 5.55; N, 9.45.
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.49 (d, 1H, py, 3J = 3.8);
7.60 (dd, 1H, py, 3J = 7.8, 4J = 2.2); 7.29 (d, 2H, aryl, 3J = 7.8); 7.18
(m, 1H, py); 7.13 (m, 1H, aryl); 6.89 (d, 2H, aryl, 3J = 7.8); 5.85 (s,
1H, H2); 5.15 (d, 1H, CH2a, 2J = 14.8); 3.88 (d, 2H, CH2b and H5a,
2J = 14.8); 3.74 (d, 1H, H5b, 2J = 15.2). 13C NMR d (100 MHz, ppm,
1
JC–F = Hz): 169.9 (C4); 164.6 (d, JC–F = 247.8); 157.0; 149.1; 141.8
4
3
(d, JC–F = 6.0); 136.7; 131.2 (d, JC–F = 9.4); 123.1; 122.7; 122.6;
2
2
117.5 (d, JC–F = 21.8); 115.4 (d, JC–F = 22.0); 64.1 (C2); 49.3
(CH2); 32.5 (C5). Anal. Calcd for C15H13FN2OS: C, 62.48; H, 4.54;
N, 9.72. Found: C, 62.53; H, 4.62; N, 9.88.
3.4.12. Selected data for 2-(4-methoxyphenyl)-3-(pyridin-2-ylmethyl)
1,3-thiazolidin-4-one 6l
3.4.7. Selected data for 2-(2-chlorophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6g
1H NMR d (500 MHz, ppm, JH–H = Hz): 8.52 (d, 1H, py, 3J = 4.9);
7.62 (td, 1H, py, 3J = 7.8, 4J = 1.9); 7.22 (d, 2H, aryl, 3J = 8.8); 7.18
(m, 1H, py); 7.15 (m, 1H, aryl); 6.87 (d, 2H, aryl, 3J = 8.8); 5.71 (s,
1H, H2); 5.02 (d, 1H, CH2a, 2J = 15.6); 3.88 (m, 2H, CH2b and
H5a); 3.81 (s, 3H, OCH3); 3.79 (d, 1H, H5b, 2J = 14.6). 13C NMR d
(125 MHz, ppm): 171.6 (C4); 160.4; 155.8; 149.7; 130.8; 129.1;
128.0; 122.6; 122.5; 114.5; 63.4 (C2); 55.5 (OCH3); 47.9 (CH2);
33.2 (C5). Anal. Calcd for C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33.
Found: C, 63.87; H, 5.31; N, 9.20.
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.55 (d, 1H, py, 3J = 3.8);
7.62 (dd, 1H, py, 3J = 8.0, 4J = 2.0); 7.30 (dd, 1H, py, 3J = 8.0,
4J = 2.0); 7.20 (dd, 1H, aryl, 3J = 7.8, 4J = 2.0); 7.16 (m, 2H, aryl);
7.08 (dd, 1H, aryl, 3J = 8.0, 4J = 2.0); 5.71 (s, 1H, H2); 5.11 (d, 1H,
CH2a, 2J = 14.8); 3.89 (d, 2H, CH2b and H5a, 2J = 14.6); 3.69 (d, 1H,
H5b, 2J = 15.0). 13C NMR d (100 MHz, ppm): 170.0 (C4); 164.1;
155.1; 149.6; 141.5; 136.0; 130.1; 122.9; 122.4; 120.6; 118.4;
115.5; 63.1 (C2); 48.1 (CH2); 33.1 (C5). Anal. Calcd for
C15H13ClN2OS: C, 59.11; H, 4.30; N, 9.19. Found: C, 59.00; H,
4.41; N, 9.12.
3.4.13. Selected data for 2-(2-hydroxyphenyl)-3-(pyridin-2-ylmethyl)
1,3-thiazolidin-4-one 6m
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.51 (d, 1H, py, 3J = 3.5);
7.68 (dt, 1H, py, 3J = 7.4, 4J = 1.9); 7.24 (m, 2H, py and aryl); 7.13
(t, 1H, aryl, 3J = 7.8); 6.73 (m, 3H, aryl); 5.63 (d, 1H, H2, 4J = 1.9);
5.07 (d, 1H, CH2a, 2J = 15.7); 3.96 (d, 1H, CH2b, 2J = 15.6); 3.87
(dd, 1H, H5a, 2J = 15.6, 4J = 1.6); 3.76 (d, 1H, H5b, 2J = 15.6). 13C
NMR d (100 MHz, ppm): 172.0 (C4); 157.5; 155.3; 148.9; 140.4;
137.4; 130.2; 122.9; 122.8; 118.4; 116.5; 113.9; 63.5 (C2); 47.7
(CH2); 32.7 (C5). Anal. Calcd for C15H14N2O2S: C, 62.92; H, 4.93;
N, 9.78. Found: C, 62.89; H, 5.11; N, 9.53.
3.4.8. Selected data for 2-(3-chlorophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6h
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.39 (d, 1H, py, 3J = 4.2);
7.66 (m, 1H, py); 7.27 (dd, 1H, py, 3J = 8.0, 4J = 2.0); 7.15 (m, 2H,
aryl); 7.01 (m, 2H, aryl); 6.96 (d, 1H, aryl, 3J = 8.0); 6.90 (m, 1H,
aryl); 5.62 (s, 1H, H2); 5.06 (d, 1H, CH2a, 2J = 14.0); 4.01 (d, 2H,
CH2b and H5a, 2J = 14.8); 3.77 (d, 1H, H5b, 2J = 15.0). 13C NMR d
(100 MHz, ppm): 171.4 (C4); 162.4; 152.9; 148.2; 142.2; 138.5;
130.0; 123.4; 122.6; 121.9; 116.3; 114.5; 59.9 (C2); 47.5 (CH2);
32.9 (C5). Anal. Calcd for C15H13ClN2OS: C, 59.11; H, 4.30; N,
9.19. Found: C, 59.20; H, 4.39; N, 9.22.
3.4.14. Selected data for 2-(3-hydroxyphenyl)-3-(pyridin-2-ylmethyl)
1,3-thiazolidin-4-one 6n
3.4.9. Selected data for 2-(4-chlorophenyl)-3-(pyridin-2-ylmethyl)1,3-
thiazolidin-4-one 6i
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.57 (m, 1H, py); 7.63 (m,
1H, py); 7.28 (dd, 1H, py, 3J = 8.2, 4J = 1.9); 7.14 (m, 2H, aryl); 7.01
(m, 2H, aryl); 6.94 (d, 1H, aryl, 3J = 8.0); 7.02 (m, 1H, aryl); 5.89 (d,
1H, H2, 4J = 1.0); 5.10 (d, 1H, CH2a, 2J = 14.8); 3.88 (d, 2H, CH2b and
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.53 (d, 1H, py, 3J = 4.2);
7.64 (td, 1H, py, 3J = 7.4, 4J = 1.5); 7.33 (d, 2H, aryl, 3J = 8.2); 7.21
(m, 4H, py and aryl); 5.74 (br, 1H, H2); 5.04 (d, 1H, CH2a,
2J = 15.2); 3.88 (dd, 1H, H5a, 2J = 15.6, 4J = 1.9); 3.85 (d, 1H, CH2b,
2J = 15.2); 3.79 (d, 1H, H5b, 2J = 15.6). 13C NMR d (100 MHz, ppm,
JC–F = Hz): 171.4 (C4); 155.3; 149.5; 137.5; 136.8; 129.2; 128.8;
122.6; 122.5; 62.8 (C2); 47.8 (CH2); 32.8 (C5). Anal. Calcd for
H5a, 2J = 14.6); 3.72 (d, 1H, H5b, 2J = 15.0). 13C NMR
d
(100 MHz, ppm): 172.9 (C4); 162.8; 155.9; 148.2; 141.9; 132.1;
129.4; 124.4; 121.9; 116.3; 113.9; 59.9 (C2); 49.9 (CH2); 32.9
(C5). Anal. Calcd for C15H14N2O2S: C, 62.92; H, 4.93; N, 9.78. Found:
C, 63.07; H, 5.15; N, 9.97.
C15H13ClN2OS: C, 59.11; H, 4.30; N, 9.19. Found: C, 58.98; H,
4.21; N, 9.33.
3.4.15. Selected data for 2-(4-methylphenyl)-3-(pyridin-2-ylmethyl)
1,3-thiazolidin-4-one 6o
3.4.10. Selected data for 2-(2-methoxyphenyl)-3-(pyridin-2-ylmethyl)
1,3-thiazolidin-4-one 6j
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.50 (d, 1H, py, 3J = 4.0);
7.65 (td, 1H, py, 3J = 8.0, 4J = 1.9); 7.18 (d, 2H, aryl, 3J = 8.2); 7.17
(m, 1H, py); 7.12 (m, 1H, aryl); 6.89 (d, 2H, aryl, 3J = 8.2); 5.88 (s,
1H, H2); 5.02 (d, 1H, CH2a, 2J = 15.0); 3.88 (m, 2H, CH2b and
H5a); 3.76 (d, 1H, H5b, 2J = 14.6); 2.31 (s, 3H, CH3). 13C NMR d
(100 MHz, ppm): 170.9 (C4); 163.8; 155.3; 150.7; 131.8; 129.6;
128.3; 123.0; 122.6; 115.1; 63.4 (C2); 47.9 (CH2); 33.5 (C5); 20.8
(CH3). Anal. Calcd for C16H16N2OS: C, 67.58; H, 5.67; N, 9.85. Found:
C, 67.76; H, 5.88; N, 9.91.
1H NMR d (400 MHz, ppm, JH–H = Hz): 8.51 (d, 1H, py, 3J = 3.9);
7.67 (td, 1H, py, 3J = 7.8, 4J = 2.0); 7.29 (dd, 1H, py, 3J = 8.2,
4J = 1.5); 7.21 (m, 2H, py and aryl); 7.11 (dd, 1H, aryl 3J = .7.9,
4J = 1.6); 6.93 (td, 1H, aryl, 3J = 7.4, 4J = 1.1); 6.86 (d, 1H, aryl,
3J = 7.8); 5.95 (d, 1H, H2, 4J = 1.6); 5.13 (d, 1H, CH2a, 2J = 15.7);
3.97 (d, 1H, CH2b, 2J = 15.7); 3.83 (dd, 1H, H5a, 2J = 15.6, 4J = 1.6);
3.77 (s, 3H, OMe); 3.70 (d, 1H, H5b, 2J = 15.6). 13C NMR d
(100 MHz, ppm): 172.5 (C4); 157.0; 155.5; 149.0; 137.2; 129.9;

D.P. Gouvêa et al. / Ultrasonics Sonochemistry 19 (2012) 1127–1131
1131
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[13] a) W. Cunico, C.R.B. Gomes, M.L.G. Ferreira, L.R. Capri, M. Soares, S.M.S.V.
Wardell, Tetrahedron Lett. 48 (2007) 6217;
4. Conclusion
In summary, we applied the ultrasound methodology to pro-
mote the synthesis of heterocyclic thiazolidinones in good yields
and good purities. The reaction times were lower than conven-
tional synthetic methodology, however, even using ultrasound
irradiation, the 3-(pyridin-2-yl) thiazolidinones 5a–o needed a Le-
wis acid catalysis.
b) W. Cunico, L.R. Capri, C.R.B. Gomes, R.H. Sizilio, S.M.S.V. Wardell, Synthesis
(2006) 3405;
c) W. Cunico, W.T. Vellasco Junior, M. Moreth, C.R.B. Gomes, Lett. Org. Chem. 5
(2008) 349;
d) P.D. Neuenfeldt, B.B. Drawanz, G.M. Siqueira, C.R.B. Gomes, S.M.S.V.
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The authors gratefully acknowledge UFPel and CNPq (Proc.
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