PAPER
Synthesis of Pyrrolo[2,1-b]thiazoles
2635
2-{3-[2-(4-Chlorophenyl)-2-oxoethyl]-4-oxo-2-thiazolidinyli-
dene}acetic Acid Methyl Ester (2b)
2-(2-Benzothiazolylmethylidene)-3-[2-(4-chlorophenyl)-2-oxo-
ethyl]thiazolidin-4-one (2d)
Mp 163 °C (DMF–H2O); yield: 1.5 g (77%).
Mp 256 °C (DMF); yield: 2.0 g (83%).
1H NMR: = 3.58 (s, 3 H, CH3), 4.01 (s, 2 H, SCH2), 5.36 (s, 2 H,
NCH2), 5.66 (s, 1 H, CH), 7.67 (d, 2 H, J = 8.0 Hz, Ar), 8.07 (d, 2
H, J = 8.0 Hz, Ar).
13C NMR: = 33.5 (5-C), 51.4 (CH3), 53.3 (NCH2), 90.8 (CHX),
129.1 (3,5-CAr), 133.6 (2,6-CAr), 134.2 (1-CAr), 138.3 (4-CAr), 152.2
(2-C), 166.1 (COO), 174.7 (4-C), 192.9 (COAr).
1H NMR: = 4.03 (s, 2 H, SCH2), 5.39 (s, 2 H, NCH2), 6.62 (s, 1 H,
CH), 7.28 (t, 1 H, J = 7.8 Hz, X), 7.42 (t, 1 H, J = 7.8 Hz, X), 7.63
(d, 2 H, J = 9.0 Hz, Ar), 7.83 (d, 1 H, J = 7.8 Hz, X), 7.89 (d, 1 H,
J = 7.8 Hz, X), 8.12 (d, 2 H, J = 9.0 Hz, Ar).
13C NMR: = 33.0 (5-C), 52.1 (NCH2), 92.5 (CHX), 121.2 (7-CX),
121.9 (4-CX), 123.9 (6-CX), 126.3 (5-CX), 128.8 (3,5-CAr), 131.7
(7a-CX), 133.6 (2,6-CAr), 135.5 (1-CAr), 138.2 (4-CAr), 152.9 (2-C),
153.5 (3a-CX), 163.8 (2-CX), 173.2 (4-C), 191.9 (COAr).
Anal. Calcd for C14H12ClNO4S: C, 51.62; H, 3.71; N, 4.30; S, 9.84;
Cl, 10.88. Found: C, 51.55; H, 3.89; N, 4.36; S, 9.77; Cl, 10.94.
Anal. Calcd for C19H13ClN2O2S2: C, 56.92; H, 3.27; N, 6.99; S,
16.00; Cl, 8.84. Found: C, 56.88; H, 3.32; N, 7.06; S, 15.87; Cl,
8.79.
2-[4-Oxo-3-(2-oxo-2-phenylethyl)-2-thiazolidinylidene]acetic
Acid Methyl Ester (5b)
Mp 149 °C (dioxane); yield: 1.3 g (75%).
3-[2-(4-Chlorophenyl)-2-oxoethyl]-2-[4-(4-methylphenyl)-2-
thiazolyl]methylidenethiazolidin-4-one (2e)
Mp 279 °C (DMF); yield: 2.1 g (81%).
1H NMR: = 2.34 (s, 3 H, CH3), 4.06 (s, 2 H, SCH2), 5.39 (s, 2 H,
NCH2), 6.67 (s, 1 H, CH), 7.26 (d, 2 H, J = 9.0 Hz, X), 7.68 (d, 2
H, J = 9.0 Hz, Ar), 7.79 (s, 1 H, 5-HX), 7.91 (d, 2 H, J = 9.0 Hz,
Ar), 8.11 (d, 2 H, J = 9.0 Hz, X).
13C NMR: = 21.1 (CH3), 32.5 (5-C), 52.1 (NCH2), 91.8 (CHX),
125.2 (2,6-Ctol), 129.1 (3,5-CAr), 130.2 (3,5-Ctol), 131.0 (4-Ctol),
133.5 (1-Ctol), 133.6 (2,6-CAr), 135.3 (1-CAr), 137.9 (4-CAr), 140.8
(5-CX), 153.5 (2-C), 166.4 (4-CX), 166.8 (2-CX), 173.4 (4-C), 191.2
(COAr).
1H NMR: = 3.58 (s, 3 H, CH3), 4.00 (s, 2 H, SCH2), 5.36 (s, 2 H,
NCH2), 5.63 (s, 1 H, CH), 7.59 (t, 2 H, J = 10.0 Hz, Ar), 7.72 (t, 1
H, J = 10.0 Hz, Ar), 8.06 (d, 2 H, J = 10.0 Hz, Ar).
13C NMR: = 32.6 (5-C), 51.4 (CH3), 52.5 (NCH2), 92.7 (CHX),
128.2 (3,5-CAr), 133.4 (2,6-CAr), 134.5 (4-CAr), 136.6 (1-CAr), 158.6
(2-C), 170.8 (COO), 173.7 (4-C), 193.2 (COAr).
Anal. Calcd for C14H13NO4S: C, 57.72:, H, 4.50; N, 4.81; S, 11.01.
Found: C, 57.65:, H, 4.39; N, 4.88; S, 11.12.
2-{3-[2-[4-(Isopropyl)phenyl]amino-2-oxoethyl]-4-oxo-2-thia-
zolidinylidene}acetic Acid Methyl Ester (10b)
Mp 125 °C (MeOH); yield: 1.9 g (91%).
Anal. Calcd for C22H17ClN2O2S2: C, 59.92; H, 3.89; N, 6.35; S,
14.54; Cl, 8.04. Found: C, 60.02; H, 3.84; N, 6.21; S, 14.67; Cl,
8.12.
1H NMR: = 1.17 [d, 6 H, J = 6.0 Hz, CH(CH3)2], 2.83 [1 H, m,
CH(CH3)2], 3.60 (s, 3 H, OCH3), 3.95 (s, 2 H, SCH2), 4.50 (s, 2 H,
NCH2), 5.55 (s, 1 H, CH), 7.17 (d, 2 H, J = 9.0 Hz, R), 7.45 (d, 2
H, J = 9.0 Hz, R), 10.19 (s, 1 H, NH).
13C NMR: = 23.4 [CH(CH3)2], 31.0 (5-C), 33.8 [CH(CH3)2], 50.8
(CH3), 54.3 (NCH2), 91.3 (CHX), 119.7 (2,6-CR), 129.7 (3,5-CR),
138.5 (4-CR), 139.9 (1-CR), 162.0 (2-C), 169.1 (COO), 171.4 (4-C),
176.7 (COR).
2-{3-[2-(4-Bromophenyl)-2-oxoethyl]-4-oxo-2-thiazolidinyli-
dene}acetonitrile (3c)
Mp 185 °C (DMF–H2O); yield: 1.8 g (89%).
1H NMR: = 4.26 (s, 2 H, SCH2), 5.28 (s, 2 H, NCH2), 5.38 (s, 1 H,
CH), 7.80 (d, 2 H, J = 8.4 Hz, Ar), 7.97 (d, 2 H, J = 8.4 Hz, Ar).
13C NMR: = 31.6 (5-C), 51.8 (NCH2), 65.6 (CHX), 119.6 (CN),
130.3 (4-CAr), 130.5 (3,5-CAr), 132.3 (2,6-CAr), 140.1 (1-CAr), 162.6
(2-C), 169.6 (4-C), 192.9 (COAr).
Anal. Calcd for C17H20N2O4S: C, 58.60; H, 5.79; N, 8.04; S, 9.20.
Found: C, 58.74; H, 5.71; N, 7.95; S, 9.11.
2-Thiazolidinylideneacetonitriles 2c, 3c, 4c, 7c, 9c and 2-Het-
arylmethylidene-4-thiazolidinones 2d,e, 3d, 4d,e, 7d; General
Procedure
Anal. Calcd for C13H9BrN2O2S: C, 46.31; H, 2.69; N, 8.31; S, 9.51;
Br, 23.70. Found: C, 46.32; H, 2.74; N, 8.23; S, 9.58; Br, 23.79.
Powdered K2CO3 (1.0 g, 7.2 mmol) was added to a solution of 1c–
e (6 mmol) and the corresponding alkylating agent (6 mmol) in
DMF (5 mL) and the resulting mixture was heated at 120–130 °C
for 1.5–2 h. When the derivative 1c was used as starting material,
the cooled mixture was poured into H2O, the precipitated solid was
filtered, dried and recrystallized from aq DMF yielding nitriles 2c,
3c, 4c, 7c, 9c. When the alkylation was carried out for compounds
1d,e, the mixture was cooled, the precipitate formed was filtered,
thoroughly washed with H2O to remove inorganic materials and re-
crystallized (if necessary) from DMF or aq DMF to give 2d,e, 3d,
4d,e, 7d.
2-(2-Benzothiazolylmethylidene)-3-[2-(4-bromophenyl)-2-oxo-
ethyl]thiazolidin-4-one (3d)
Mp 289 °C (DMF); yield: 2.3 g (86%).
1H NMR: = 4.08 (s, 2 H, SCH2), 5.41 (s, 2 H, NCH2), 6.70 (s, 1 H,
CH), 7.31 (t, 1 H, J = 7.8 Hz, X), 7.45 (t, 1 H, J = 7.8 Hz, X), 7.85
(m, 3 H, X, Ar), 7.97 (d, 1 H, J = 7.8 Hz, X), 8.03 (d, 2 H, J = 8.4
Hz, Ar).
13C NMR: = 33.6 (5-C), 52.1 (NCH2), 92.7 (CHX), 122.7 (7-CX),
122.9 (4-CX), 124.9 (6-CX), 125.8 (5-CX), 127.3 (4-CAr), 130.1 (3,5-
CAr), 131.8 (7a-CX), 135.9 (2,6-CAr), 136.8 (1-CAr), 151.8 (3a-CX),
156.1 (2-C), 161.8 (2-CX), 171.9 (4-C), 193.1 (COAr).
2-{3-[2-(4-Chlorophenyl)-2-oxoethyl]-4-oxo-2-thiazolidinyli-
dene}acetonitrile (2c)
Mp 137 °C (DMF–H2O); yield: 1.2 g (68%).
1H NMR: = 4.26 (s, 2H, SCH2), 5.28 (s, 2 H, NCH2), 5.38 (s, 1 H,
Anal. Calcd for C19H13BrN2O2S2: C, 51.24; H, 2.94; N, 6.29; S,
14.40; Br, 17.94. Found: C, 51.19; H, 2.99; N, 6.32; S, 14.28; Br,
18.01.
CH), 7.66 (d, 2 H, J = 9.0 Hz, Ar), 8.05 (d, 2 H, J = 9.0 Hz, Ar).
2-{3-[2-(4-Nitrophenyl)-2-oxoethyl]-4-oxo-2-thiazolidinyli-
dene}acetonitrile (4c)
Mp 196 °C (DMF–H2O); yield: 1.4 g (77%).
1H NMR: = 4.28 (s, 2 H, SCH2), 5.38 (s, 2 H, NCH2), 5.44 (s, 1 H,
CH), 8.28 (d, 2 H, J = 9.0 Hz, Ar), 8.39 (d, 2 H, J = 9.0 Hz, Ar).
13C NMR: = 32.7 (5-C), 51.8 (NCH2), 65.7 (CHX), 116.5 (CN),
129.0 (3,5-CAr), 133.5 (2,6-CAr), 135.9 (1-CAr), 138.4 (4-CAr), 156.5
(2-C), 172.8 (4-C), 192.5 (COAr).
Anal. Calcd for C13H9ClN2O2S: C, 53.34; H, 3.10; N, 9.57; S, 10.95;
Cl, 12.11. Found: C, 53.29; H, 3.21; N, 9.41; S, 11.03; Cl, 12.02.
Synthesis 2003, No. 17, 2632–2638 © Thieme Stuttgart · New York