C. Nitsche, C. D. Klein / Tetrahedron Letters 53 (2012) 5197–5201
5201
3
-Isopropyl-2-thioxo-1,3-thiazolidin-4-one (4): Pale yellow solid (69% yield). 55.2, 113.8, 127.0, 130.8, 159.5, 173.9, 201.0 ppm; MS (EI, 70 eV): m/z (%):
1
+
H NMR (300 MHz, CDCl
J = 6.9 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl
02.1 ppm; MS (EI, 70 eV): m/z (%): 175.0 (93) [M ]; Anal. Calcd for C
C, 41.12; H, 5.18; N, 7.99. Found: C, 41.26; H, 5.25; N, 7.99.
-Propyl-2-thioxo-1,3-thiazolidin-4-one (5): Yellow liquid (58% yield). 1H
NMR (300 MHz, CDCl ): d = 0.93 (t, J = 7.4 Hz, 3H), 1.66 (m, 2H), 3.93 (m, 2H),
.96 (s, 2H) ppm; 13C NMR (75 MHz, CDCl
): d = 11.2, 20.1, 35.3, 46.2, 173.9,
01.2 ppm; MS (EI, 70 eV): m/z (%): 175.0 (100) [M ]; Anal. Calcd for C
3
): d = 1.47 (d, J = 6.9 Hz, 6H), 3.82 (s, 2H), 5.22 (sept,
252.9 (81) [M ]; Anal. Calcd for C11
C, 53.78; H, 4.88; N, 5.04.
2 2
H11NO S : C, 52.15; H, 4.38; N, 5.53. Found:
3
): d = 18.2, 34.0, 50.4, 174.2,
+
2
6
H
9
NOS
2
:
25. General procedure for the synthesis of N-substituted rhodanines using the
bis(carboxymethyl)trithiocarbonate based method: A suspension of amine
(5 mmol) and bis(carboxymethyl)trithiocarbonate (5.5 mmol) in water was
reacted in a microwave reactor (Monowave 300, Anton Paar) at the different
described time and temperature conditions. After automated cooling to 40 °C
the crude product was extracted with ethyl acetate and purified by flash
3
3
3
2
3
+
6
H
9
NOS
2
:
C, 41.12; H, 5.18; N, 7.99. Found: C, 41.04; H, 5.22; N, 8.36.
3
chromatography (cyclohexane/ethyl acetate) using
system.
a Biotage Isolera One
-Butyl-2-thioxo-1,3-thiazolidin-4-one (6): Yellow liquid (58% yield). 1H NMR
(
2
4
for C
300 MHz, CDCl ): d = 0.94 (t, J = 7.3 Hz, 3H), 1.35 (m, 2H), 1.61 (m, 2H), 3.95 (s,
3
3-(4-Methylphenyl)-2-thioxo-1,3-thiazolidin-4-one (15): Pale yellow solid
1
3
(54% yield). 1H NMR (300 MHz, CDCl
H), 3.97 (m, 2H) ppm; C NMR (75 MHz, CDCl
4.6, 173.9, 201.2 ppm; MS (EI, 70 eV): m/z (%): 189.0 (100) [M ]; Anal. Calcd
11NOS : C, 44.41; H, 5.86; N, 7.40. Found: C, 44.59; H, 5.78; N, 8.05.
-Cyclopentyl-2-thioxo-1,3-thiazolidin-4-one (7): Colorless solid (59% yield).
3
): d = 13.6, 20.0, 28.8, 35.3,
3
): d = 2.41 (s, 3H), 4.17 (s, 2H), 7.07 (m,
): d = 21.4, 36.3, 128.0, 130.4,
132.2, 140.0, 173.5, 201.3 ppm; MS (EI, 70 eV): m/z (%): 223.1 (100) [M ]; Anal.
+
13
2H), 7.33 (m, 2H) ppm; C NMR (75 MHz, CDCl
3
+
7
H
2
3
Calcd for C10
6.84.
H
9
NOS
2
: C, 53.78; H, 4.06; N, 6.27. Found: C, 55.92; H, 4.28; N,
1
H NMR (300 MHz, CDCl
3
): d = 1.53–1.67 (m, 2H), 1.80–2.00 (m, 4H), 2.03–2.17
13
1
(
m, 2H), 3.81 (s, 2H), 5.31 (quint, J = 8.7 Hz, 1H) ppm; C NMR (75 MHz,
3-Phenyl-2-thioxo-1,3-thiazolidin-4-one (16): Pale yellow solid (32% yield).
NMR (300 MHz, CDCl
NMR (75 MHz, CDCl ): d = 36.3, 128.3, 129.6, 129.8, 134.9, 173.4, 201.1 ppm;
H
CDCl
3
): d = 25.5, 27.5, 34.2, 57.8, 173.8, 202.5 ppm; MS (EI, 70 eV): m/z (%):
): d = 4.18 (s, 2H), 7.19 (m, 2H), 7.52 (m, 3H) ppm; 13
C
3
+
2
4
3
01.0 (76) [M ]; Anal. Calcd for C
8
H
11NOS
2
: C, 47.73; H, 5.51; N, 6.96. Found: C,
3
+
7.73; H, 5.58; N, 6.97.
9 7 2
MS (EI, 70 eV): m/z (%): 208.9 (100) [M ]; Anal. Calcd for C H NOS : C, 51.65; H,
-(Tetrahydrofuran-2-ylmethyl)-2-thioxo-1,3-thiazolidin-4-one
(8):
): d = 1.65 (m, 1H), 1.80–
.07 (m, 3H), 3.72 (m, 1H), 3.82–3.95 (m, 2H), 3.98 (d, J = 3.8 Hz, 2H), 4.09 (m,
Pale
3.37; N, 6.69. Found: C, 50.51; H, 3.42; N, 6.33.
1
yellow solid (68% yield). H NMR (300 MHz, CDCl
3
3-(4-Methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one (17): Pale yellow solid
2
1
6
(39% yield). 1H NMR (300 MHz, CDCl
3
): d = 3.84 (s, 3H), 4.16 (s, 2H), 7.02 (m,
3
2H), 7.10 (m, 2H) ppm; C NMR (75 MHz, CDCl ): d = 36.2, 55.5, 114.9, 127.2,
1
3
13
H), 4.36 (m, 1H) ppm; C NMR (75 MHz, CDCl
7.9, 74.6, 173.9, 201.6 ppm; MS (EI, 70 eV): m/z (%): 217.0 (18) [M ]; Anal.
11NO : C, 44.22; H, 5.10; N, 6.45. Found: C, 44.53; H, 5.24; N,
3
): d = 25.2, 29.1, 35.3, 47.9,
+
+
129.4, 160.3, 173.5, 201.5 ppm; MS (EI, 70 eV): m/z (%): 238.9 (100) [M ]; Anal.
Calcd for C
6
3
8
H
S
2 2
Calcd for C10
5.82.
9 2 2
H NO S : C, 50.19; H, 3.79; N, 5.85. Found: C, 50.24; H, 3.73; N,
.39.
-Allyl-2-thioxo-1,3-thiazolidin-4-one (9): Pale yellow solid (77% yield). 1
H
3-(4-Fluorophenyl)-2-thioxo-1,3-thiazolidin-4-one (18): Pale yellow solid
1
NMR (300 MHz, CDCl
3
): d = 3.97 (s, 2H), 4.57 (dt, J = 6.0, 1.4 Hz, 2H), 5.18–5.28
(38% yield). H NMR (300 MHz, CDCl
3
): d = 4.18 (s, 2H), 7.15–7.25 (m, 4H)
): d = 36.2, 116.6 + 116.9 (d, CF = 23.3 Hz),
130.2 + 130.4 (d, JCF = 9.2 Hz), 130.5 + 130.6 (d, JCF = 3.2 Hz), 161.3 + 164.6 (d,
1
3
13
(
m, 2H), 5.77 (m, 1H) ppm; C NMR (75 MHz, CDCl
3
): d = 35.7, 46.4, 119.5,
ppm;
C
NMR (75 MHz, CDCl
3
J
+
1
for C
29.3, 173.3, 200.6 ppm; MS (EI, 70 eV): m/z (%): 173.1 (96) [M ]; Anal. Calcd
+
6
7
H NOS
2
: C, 41.59; H, 4.07; N, 8.08. Found: C, 41.66; H, 3.98; N, 8.05.
JCF = 250 Hz), 173.3, 201.0 ppm; MS (EI, 70 eV): m/z (%): 227.1 (100) [M ]; Anal.
3
-(2-Phenylethyl)-2-thioxo-1,3-thiazolidin-4-one (10): Pale yellow solid (65%
Calcd for C
6.17.
9 6 2
H FNOS : C, 47.56; H, 2.66; N, 6.16. Found: C, 47.68; H, 2.41; N,
1
yield). H NMR (300 MHz, CDCl
7
1
Anal. Calcd for C11
N, 5.88.
3
3
): d = 2.93 (m, 2H), 3.92 (s, 2H), 4.19 (m, 2H),
.20–7.33 (m, 5H) ppm; C NMR (75 MHz, CDCl ): d = 32.6, 35.2, 45.7, 126.8,
28.5, 128.9, 137.3, 173.4, 200.9 ppm; MS (EI, 70 eV): m/z (%): 236.9 (76) [M ];
1
3
3
3-(4-Chlorophenyl)-2-thioxo-1,3-thiazolidin-4-one (19): Pale yellow solid
+
1
(47% yield). H NMR (300 MHz, CDCl
(m, 2H) ppm; 13C NMR (75 MHz, CDCl
173.1, 200.7 ppm; MS (EI, 70 eV): m/z (%): 242.9 (100) [M ]; Anal. Calcd for
ClNOS : C, 44.35; H, 2.48; N, 5.75. Found: C, 45.76; H, 2.51; N, 6.23.
3
): d = 4.18 (s, 2H), 7.14 (m, 2H), 7.50
H11NOS
2
: C, 55.67; H, 4.67; N, 5.90. Found: C, 55.67; H, 4.82;
3
): d = 36.3, 129.7, 129.9, 133.1, 135.8,
+
-Benzyl-2-thioxo-1,3-thiazolidin-4-one (11): Pale yellow solid (81% yield). 1
H
C
9
H
6
2
NMR (300 MHz, CDCl
3
): d = 3.98 (s, 2H), 5.18 (s, 2H), 7.30 (m, 3H), 7.42 (m, 2H)
): d = 35.4, 47.6, 128.2, 128.6, 129.0, 134.7,
3-(4-Nitrophenyl)-2-thioxo-1,3-thiazolidin-4-one (20): Pale yellow solid (3%
ppm; 13C NMR (75 MHz, CDCl
yield). 1H NMR (300 MHz, CDCl
): d = 4.24 (s, 2H), 7.43 (m, 2H), 8.39 (m, 2H)
3
ppm; C NMR (125 MHz, CDCl ): d = 36.5, 124.8, 129.9, 140.1, 148.2, 172.7,
3
3
+
13
1
C
3
73.8, 201.0 ppm; MS (EI, 70 eV): m/z (%): 222.9 (88) [M ]; Anal. Calcd for
NOS : C, 53.78; H, 4.06; N, 6.27. Found: C, 53.92; H, 4.13; N, 6.23.
-(4-Chlorobenzyl)-2-thioxo-1,3-thiazolidin-4-one (12): Pale yellow solid
): d = 3.98 (s, 2H), 5.13 (s, 2H), 7.27 (m,
H), 7.38 (m, 2H) ppm; C NMR (75 MHz, CDCl ): d = 35.6, 46.9, 128.7, 130.6,
33.1, 134.2, 173.7, 200.8 ppm; MS (EI, 70 eV): m/z (%): 256.8 (85) [M ]; Anal.
ClNOS : C, 46.60; H, 3.13; N, 5.43. Found: C, 46.48; H, 3.43; N,
+
10
H
9
2
199.9 ppm; MS (EI, 70 eV): m/z (%): 253.9 (100) [M ]; Anal. Calcd for
: C, 42.51; H, 2.38; N, 11.02. Found: C, 40.82; H, 2.26; N, 10.45.
9 6 2 3 2
C H N O S
(
2
1
80% yield). 1H NMR (300 MHz, CDCl
3
3-(2-Hydroxyethyl)-2-thioxo-1,3-thiazolidin-4-one (21): Pale yellow oil (17%
1
3
yield). 1H NMR (300 MHz, CDCl
(t, J = 5.5 Hz, 2H) ppm; C NMR (75 MHz, CDCl
201.9 ppm; MS (EI, 70 eV): m/z (%): 177.0 (60) [M ]; Anal. Calcd for C H NO S :
5 7 2 2
3
3
): d = 3.90 (t, J = 5.5 Hz, 2H), 4.01 (s, 2H), 4.25
): d = 35.4, 46.6, 59.9, 174.6,
+
13
3
+
Calcd for C10
H
8
2
5
3
.23.
-(4-Fluorobenzyl)-2-thioxo-1,3-thiazolidin-4-one (13): Pale yellow solid (85%
C, 33.88; H, 3.98; N, 7.90. Found: C, 33.29; H, 4.12; N, 7.20.
Methyl 2-(4-oxo-2-thioxo-1,3-thiazolidin-3-yl)hexanoate (22): Pale yellow oil
(15% yield). 1H NMR (300 MHz, CDCl
): d = 0.87 (t, J = 7.1 Hz, 3H), 1.10–1.38 (m,
4H), 2.13–2.29 (m, 2H), 3.72 (s, 3H), 3.98 (s, 2H), 5.51 (dd, J = 9.3, 5.9 Hz, 1H)
ppm; 13C NMR (75 MHz, CDCl
): d = 13.8, 22.3, 27.6, 28.2, 34.6, 52.7, 57.6,
168.7, 173.3, 201.0 ppm; MS (EI, 70 eV): m/z (%): 261.0 (55) [M ]; Anal. Calcd
for C10 15NO : C, 45.95; H, 5.78; N, 5.36. Found: C, 47.24; H, 6.12; N, 5.84.
(4-Oxo-2-thioxo-1,3-thiazolidin-3-yl)acetic acid (23): Pale yellow solid (<5%
1
yield). H NMR (300 MHz, CDCl
.44 (m, 2H) ppm; 13C NMR (75 MHz, CDCl
CF = 21.6 Hz), 130.5 + 130.6 (d, CF = 3.5 Hz), 131.1 + 131.3 (d,
60.9 + 164.2 (d, JCF = 247 Hz), 173.8, 200.9 ppm; MS (EI, 70 eV): m/z (%):
3
): d = 3.97 (s, 2H), 5.14 (s, 2H), 6.98 (m, 2H),
): d = 35.4, 46.8, 115.3 + 115.6 (d,
CF = 8.1 Hz),
3
7
J
1
2
3
J
J
3
+
+
40.9 (84) [M ]; Anal. Calcd for C10
8
H FNOS
2
: C, 49.77; H, 3.34; N, 5.80. Found:
H
3 2
S
C, 50.30; H, 3.71; N, 5.38.
-(4-Methoxybenzyl)-2-thioxo-1,3-thiazolidin-4-one (14): Pale yellow solid
20% yield). 1H NMR (300 MHz, CDCl
): d = 3.77 (s, 3H), 3.95 (s, 2H), 5.11 (s,
1
3
(
2
yield, not isolated). H NMR (300 MHz, CDCl
3
): d = 4.08 (s, 2H), 4.77 (s, 2H)
)+: d = 35.6, 44.4, 171.0, 173.1, 200.2 ppm; MS (EI,
70 eV): m/z (%): 191.0 (94) [M ].
13
3
ppm; C NMR (75 MHz, CDCl
3
1
3
3
H), 6.83 (m, 2H), 7.41 (m, 2H) ppm; C NMR (75 MHz, CDCl ): d = 35.4, 47.1,