U. Bhanushali et al. / Bioorganic Chemistry 67 (2016) 139–147
141
2.3. Synthesis of 2-[4-(2,4-dioxothiazolidin-5-ylidenemethyl)
phenoxy]-N-arylacetamide (3a-3j)
bon), 160.78, 134.57, 133.21, 129.28, 127.75, 124.23, 121.20,
116.92, 116.75, 44.40 (methylene carbon). Anal. Calcd. for C18
13ClN2O4S: C, 55.59; H, 3.34; N, 7.20. Found: C, 55.55; H,
-
H
The mixture of 5-(4-hydroxybenzylidene)-2,4-thiazolidene
dione (1) (1.0 mol) and 1.5 mol of substituted aryl/heteroaryl chlo-
racetamides (2a-2j) was dissolved in dimethyl formamide (DMF).
The solution was stirred overnight with 1.5 mol of potassium car-
bonate at room temperature. The reaction was monitored by TLC.
After completion of reaction, ice cold water was added to precipi-
tate crude product (3a-3j). The compounds were the purified by
recrystallization from absolute ethanol.
3.28; N, 7.12.
2.3.5. N-(5-chloropyridin-2-yl)-2-[4-(2,4-dioxothiazolidin-5-
ylidenemethyl)phenoxy]acetamide (3e)
Yield 58%, Pale Yellow Solid, mp 238–240 °C. IR [KBr cmꢀ1]:
3365 (NAH), 1788 (C@O, of 2,4-TZD), 1683 (C@O of amide). 1H
NMR [300 MHz, d, ppm, DMSO-d6]: 11.17 (bs, 1H, NH), 8.40 (d,
J = 2.7 Hz, 1H, pyridine proton), 8.00 (d, J = 9.3 Hz, 1H, pyridine pro-
ton), 7.91 (dd, J = 8.8 & 2.7 Hz, 1H, pyridine proton), 7.86 (s, 1H,
benzylidene proton), 7.50 (d, J = 8.4 Hz, 2H, Ar-protons), 6.90 (d,
J = 8.7 Hz, 2H, Ar-protons), 4.50 (s, 2H, ACH2A). 13C NMR
[100 MHz, d, ppm, DMSO-d6]: 167.73 (C@O), 165.33 (C@O),
164.57 (C@O), 134.09 (benzylidene carbon), 160.48, 132.49,
123.56, 116.36, 116.06, 150.00, 146.21, 137.62, 125.54, 114.52
(pyridine carbon). Anal. Calcd. for C17H12ClN3O4S: C, 52.37; H,
3.08; N, 10.78. Found: C, 52.35; H, 3.00; N, 10.69.
2.3.1. 2-[4-(2,4-Dioxothiazolidin-5-ylidenemethyl)phenoxy]-N-
phenylacetamide (3a)
Yield 58%, Yellow colored solid, mp 285 °C. IR [KBr cmꢀ1]: 3306
(NAH), 1788 (C@O, of 2,4-TZD), 1666 (C@O of amide). 1H NMR
[300 MHz, d, ppm, DMSO-d6]: 10.39 (s, 2H, TZD-NH & amide NH),
7.88 (s, 1H, benzylidene proton), 7.56–7.51 (m, 4H, Ar-protons),
7.32 (t, J = 7.2 Hz, 2H, Ar-protons), 7.07 (t, 1H, J = 7.5 Hz, Ar-
proton), 6.94 (d, 2H, J = 8.7 Hz, Ar-protons), 4.49 (s, 2H, ACH2A).
13C NMR [100 MHz, d, ppm, DMSO-d6]: 167.14 (C@O), 165.40
(C@O), 163.64 (C@O), 138.35 (benzylidene carbon), 160.24,
133.95, 132.44, 128.60, 123.69, 123.48, 119.07, 116.30, 116.27,
43.77 (methylene carbon). Anal. Calcd. for C18H14N2O4S: C, 61.01;
H, 3.95; N, 7.90. Found: C, 59.96; H, 3.89; N, 7.85.
2.3.6. 2-[4-(2,4-Dioxothiazolidin-5-ylidenemethyl)-phenoxy]-N-
pyridin-2-yl-acetamide (3f)
Yield 88%, Pale Yellow Solid, mp 181–182 °C. IR [KBr cmꢀ1]:
3392 (NAH), 1797 (C@O, of 2,4-TZD), 1689 (C@O of amide). 1H
NMR [300 MHz, d, ppm, DMSO-d6]: 10.97 (s, 1H, NH), 10.41 (s,
1H, NH) 8.34 (d, J = 4.2 Hz, 1H, pyridine proton), 7.97 (d,
J = 6.9 Hz, 1H, pyridine proton), 7.88 (s, 1H, benzylidene proton),
7.78 (t, J = 7.2 Hz, 1H, pyridine proton), 7.52 (d, J = 8.7 Hz, 2H, Ar-
protons), 7.13 (t, J = 6.6 Hz, 1H, pyridine proton), 7.52 (d,
J = 8.7 Hz, 2H, Ar-protons), 4.57 (s, 2H, ACH2A). 13C NMR
[75 MHz, d, ppm, DMSO-d6]: 167.34 (C@O), 165.50 (C@O), 164.83
(C@O), 134.09 (benzylidene carbon), 160.32, 132.74, 123.80,
116.46, 116.35, 151.41, 148.12, 138.43, 132.74, 113.51, 43.92
(methylene carbon). Anal. Calcd. for C17H13N3O4S: C, 57.46; H,
3.66; N, 11.83. Found: C, 57.84; H, 3.89; N, 11.70.
2.3.2. 2-[4-(2,4-Dioxothiazolidin-5-ylidenemethyl)-phenoxy]-N-(3-
trifluoromethyl-phenyl) acetamide (3b)
Yield 88%, Pale Yellow Solid, mp 234–237 °C. IR [KBr cmꢀ1]:
3398 (NAH), 1788 (C@O, of 2,4-TZD), 1699 (C@O of amide). 1H
NMR [300 MHz, d, ppm, DMSO-d6]: 10.75 (s, 1H, NH), 10.41 (s,
1H, NH), 8.05 (s, 1H, Ar-proton), 7.89 (s, 1H, benzylidene proton),
7.73 (d, J = 8.7 Hz, 1H, Ar-proton), 7.51–7.60 (m, 3H, Ar-protons),
7.44 (d, J = 7.5 Hz, 1H, Ar-proton), 6.94 (d, J = 9 Hz, 2H,
Ar-protons), 4.54 (s, 2H, ACH2A). 13C NMR [75 MHz, d, ppm,
DMSO-d6]: 167.34 (C@O), 165.48 (C@O), 164.67 (C@O), 139.14
(benzylidene carbon), 160.35, 134.18, 132.77, 130.22, 129.80,
125.83, 123.78, 122.76, 116.48, 115.22, 120.09, 44.39 (methylene
carbon). Anal. Calcd. for C19H13F3N2O4S: C, 54.02; H, 3.08; N,
6.63. Found: C, 53.60; H, 3.02; N, 6.59.
2.3.7. 2-[4-(2,4-Dioxothiazolidin-5-ylidenemethyl)phenoxy]-N-(5-
methylisoxazol-3-yl) acetamide (3g)
Yield 75%, Pale Yellow Solid, mp 244–246 °C. IR [KBr cmꢀ1]:
3400 (NAH), 1788 (C@O, of 2,4-TZD), 1697 (C@O of amide). 1H
NMR [300 MHz, d, ppm, DMSO-d6]: 11.40 (s, 1H, NH), 10.40 (s,
1H, NH), 7.88 (s, 1H, benzylidene proton), 7.52 (d, J = 8.7 Hz, 2H,
Ar-protons), 6.93 (d, J = 8.4 Hz, 2H, Ar-protons), 6.56 (s, 1H, isoxa-
zole proton), 4.51 (s, 2H, ACH2A), 2.37 (s, 3H, CH3). 13C NMR
[75 MHz, d, ppm, DMSO-d6]: 167.30 (C@O), 165.41 (C@O), 164.52
(C@O), 134.14 (benzylidene carbon), 160.33, 132.76, 123.78,
116.46, 116.29, 169.94, 157.63, 96.16, 43.66 (methylene carbon),
12.14 (methyl carbon). Anal. Calcd. for C16H13N3O5S: C, 53.48; H,
3.62; N, 11.69. Found: C, 53.40; H, 3.57; N, 3.51.
2.3.3. N-(3-chlorophenyl)-2-[4-(2,4-dioxothiazolidin-5-
ylidenemethyl) phenoxy] acetamide (3c)
Yield 64%, pale yellow solid, mp 250–251 °C. IR [KBr cmꢀ1]:
3377 (NAH), 1788 (C@O, of 2,4-TZD), 1695 (C@O of amide). 1H
NMR [400 MHz, d, ppm, DMSO-d6]: 10.63 (s, 1H, NH), 7.89 (s, 1H,
benzylidene proton), 7.74 (t, J = 2 Hz, 1H, Ar-proton), 7.53 (d,
J = 8.8 Hz, 2H, Ar-protons), 7.41 (d, J = 2 Hz, 1H, Ar-proton), 7.38–
7.34 (m, 1H, Ar-proton), 7.15 (d, J = 8.8 Hz, 1H, Ar-proton), 6.94
(d, J = 8.8 Hz, 2H, Ar-protons), 4.51 (s, 2H, ACH2A). 13C NMR
[100 MHz, d, ppm, DMSO-d6]: 167.81 (C@O), 165.93 (C@O),
163.85 (C@O), 140.21 (benzylidene carbon), 160.78, 134.60,
133.64, 133.21, 131.12, 124.20, 119.13, 188.04, 116.93, 116.71,
44.39 (methylene carbon). Anal. Calcd. for C18H13ClN2O4S: C,
55.59; H, 3.34; N, 7.20. Found: C, 55.63; H, 3.26; N, 7.10.
2.3.8. 2-[4-(2,4-Dioxothiazolidin-5-ylidenemethyl) phenoxy]-N-(5-
methylthiazol-2-yl) acetamide (3h)
Yield 88%, Pale Yellow Solid, mp 230–235 °C. IR [KBr cmꢀ1]:
3315 (NAH), 1790 (C@O, of 2,4-TZD), 1660 (C@O of amide). 1H
NMR [300 MHz, d, ppm, DMSO-d6]: 12.40 (bs, 1H, NH), 10.40 (s,
1H, NH), 7.90 (s, 1H, benzylidene proton), 7.52 (d, J = 9.0 Hz, 2H,
Ar-protons), 7.16 (s, 1H, thiazole proton), 6.94 (d, J = 8.4 Hz, 2H,
Ar-proton), 4.88 (s, 2H, ACH2A), 2.40 (s, 3H, CH3). 13C NMR
[100 MHz, d, ppm, DMSO-d6]: 167.17 (C@O), 165.31 (C@O),
164.11 (C@O), 134.09 (benzylidene carbon), 160.54, 132.62,
123.55, 116.46, 116.44, 116.23, 155.82, 134.18, 126.58, 43.17
(methylene carbon), 12.07 (methyl carbon). Anal. Calcd. for
2.3.4. N-(4-chlorophenyl)-2-[4-(2,4-dioxothiazolidin-5-
ylidenemethyl)phenoxy] acetamide (3d)
Yield 42%, Pale Yellow Solid, mp 242–243 °C. IR [KBr cmꢀ1]:
3416 (NAH), 1790 (C@O, of 2,4-TZD), 1701 (C@O of amide). 1H
NMR [400 MHz, d, ppm, DMSO-d6]: 10.54 (s, 2H, TZD-NH &
amide NH), 7.89 (s, 1H, benzylidene proton), 7.59 (d, J = 8 Hz,
2H, Ar-protons), 7.53 (d, J = 8.4 Hz, 2H, Ar-protons) 7.38 (d,
J = 8 Hz, 2H, Ar-proton), 6.95 (d, J = 8.4 Hz, 2H, Ar-proton), 4.50
(s, 2H, ACH2A). 13C NMR [100 MHz, d, ppm, DMSO-d6]: 167.78
(C@O), 165.94 (C@O), 164.58 (C@O), 137.81 (benzylidene car-
C16H13N3O4S2: C, 55.97; H, 3.79; N, 12.24. Found: C, 55.92; H,
3.72; N, 12.19.