3.2. Synthesis of 5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-thiazolidinone derivatives (2a-l)

A mixture of (2Z)-2-chloro-3-(4-nitrophenyl)prop-2-enal (0.01 mol) and appropriate 4-thiazolidinone (0.01 mol) in the medium of acetic acid (20 mL) and the presence of sodium acetate (0.01 mol) was refluxed for 3 h. Obtained solid product was collected after cooling by filtration and recrystallized from the mixture DMF-ethanol (1:2).

5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-2,4-thiazolidinedione (2a). Yield: 78%, mp >270 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 7.70 (s, 1H, CH=), 7.88 (s, 1H, CH=), 8.00 (d, 2H, J = 7.5 Hz, arom.), 8.31 (d, 2H, J = 8.0 Hz, arom.), 12.70 (br.s, 1H, NH). LCMS (ESI): m/z 309.9/312.0 (95.58%, [M + H]⁺). Anal. Calc. for C₁₂H₇ClN₂O₄S: C 46.39%; H 2.27%; N 9.02%. Found: C 46.50%; H 2.40%; N 8.90%.

5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-2-thioxo-4-thiazolidinone (2b). Yield: 81%, mp 251–253 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 7.55 (s, 1H, CH=), 7.94 (s, 1H, CH=), 8.01 (d, 2H, J = 8.5 Hz, arom.), 8.31 (d, 2H, J = 8.2 Hz, arom.), 13.91 (br.s, 1H, NH). LCMS (ESI): m/z 324.9/326.9 (100%, [M + H]⁺). Anal. Calc. for C₁₂H₇ClN₂O₃S₂: C 44.11%; H 2.16%; N 8.57%. Found: C 44.00%; H 2.25%; N 8.70%.

5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-3-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylideneamino]-2-thioxo-4-thiazolidinone (2c). Yield: 74%, mp >260 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 7.79 (s, 1H, =CH), 8.01 (s, 1H, =CH), 8.06 (d, 2H, J = 8.1 Hz, arom.), 8.06 (s, 1H, =CH), 8.07 (s, 1H, =CH), 8.18 (d, 2H, J = 8.8 Hz, arom.), 8.33 (d, 2H, J = 8.8 Hz, arom.), 8.37 (d, 2H, J = 8.1 Hz, arom.), 8.98 (s, 1H, CH=N). LCMS (ESI): m/z 535.0 (95.05%, [M + H]⁺). Anal. Calc. for C₂₁H₁₂Cl₂N₄O₅S₂: C 47.11%; H 2.26%; N 10.46%. Found: C 47.00%; H 2.15%; N 10.65%.

5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-3-(4,5,6,7-tetrahydrobenzo[b]thiophen-3-ylcarboxamido)-2-thioxo-4-thiazolidinone (2d). Yield: 80%, mp >230 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 1.68–1.74 (m, 4H, 2*CH₂), 2.67–2.78 (m, 4H, 2*CH₂), 7.87 (s, 1H, s, 1H, CH=), 8.03–8.09 (m, 3H, arom., CH=), 8.10 (s, 1H, s, 1H, thiophene), 8.33 (d, 2H, J = 8.3 Hz, arom.), 11.46 (s, 1H, NH). ¹³C-NMR (100 MHz, DMSO-d₆): δ (ppm) 27.2, 27.8, 29.8, 30.4, 128.2, 129.1, 134.8, 136.2, 137.9, 140.3, 142.5, 144.3, 144.8, 145.0, 152.7, 168.7 (C=O), 177.9 (C=O), 196.4 (C=S). LCMS (ESI): m/z 504.0/506.0 (100%, [M-H]⁺). Anal. Calc. for C₂₁H₁₆ClN₃O₄S₃: C 49.85%; H 3.19%; N 8.30%. Found: C 50.00%; H 3.15%; N 8.35%.

N¹-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}-2-[2-(2,6-dichloroanilino)phenyl]acetamide (2e). Yield: 74%, mp 257–258 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 3.85 (d, 1H, J = 14.8 Hz, CH₂), 3.90 (d, 1H, J = 14.8 Hz, CH₂), 6.30 (d, 1H, J = 7.6 Hz, arom.), 7.08 (t, 1H, J = 7.5 Hz, arom.), 7.19 (t, 1H, J = 8.0 Hz, arom.) 7.29 (s, 1H, NH), 7.34 (d, 1H, J = 7.3 Hz, arom.), 7.53 (d, 2H, J = 8.0 Hz, arom.), 7.83 (s, 1H, =CH), 8.05 (d, 2H, J = 7.7 Hz, arom.), 8.06 (s, 1H, =CH), 8.33 (2H, arom., J = 8.4 Hz, arom.), 11.68 (s, 1H, NH). ¹³C-NMR (100 MHz, DMSO-d₆): δ (ppm) 41.6 (CH₂), 121.4, 121.5, 126.1, 126.2, 129.1, 129.2, 130.8, 132.9, 134.4, 134.8, 135.3, 135.6, 136.2, 137.7, 142.3, 144.8, 152.7, 168.3 (C=O), 177.0 (C=O), 195.9 (C=S). LCMS (ESI): m/z 618.8/621.6 (96.2%, [M - H]⁺). Anal. Calc. for C₂₇H₁₆Cl₃N₄O₄S₂: C 50.37%; H 2.76%; N 9.04%. Found: C 50.20%; H 2.85%; N 9.15%.

5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-3-(4-hydroxyphenyl)-2-thioxo-4-thiazolidinone (2f). Yield: 76%, mp >260 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 6.89 (d, 2H, J = 8.4 Hz, arom.), 7.16 (d, 2H, J = 8.4 Hz, arom.), 7.72 (s, 1H, =CH), 8.02 (s, 1H, =CH), 8.05 (d, 2H, J = 8.5 Hz, arom.), 8.32 (d, 2H, J = 8.5 Hz, arom.), 9.89 (s, 1H, OH). ¹³C-NMR (100 MHz, DMSO-d₆): δ (ppm) 116.3, 119.5, 122.9, 124.4, 127.8, 130.2, 130.4, 131.37, 131.4, 138.2, 149.2, 152.9, 158.7 (C=O), 199.3 (C=S). LCMS (ESI): m/z 419.0/421.0 (97.1%, [M + H]⁺). Anal. Calc. for C₁₈H₁₁ClN₂O₄S₂: C 51.61%; H 2.65%; N 6.69%. Found: C 51.80%; H 2.85%; N 6.80%.

2-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}-1-ethanesulfonic acid (2g). Yield: 83%, mp >260 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 1.95 (t, 2H, J = 7.9 Hz, CH₂), 3.47 (t, 2H, J = 7.9 Hz, CH₂), 6.89 (s, 1H, CH=), 7.19 (s, 1H, CH=), 7.23 (d, 2H, J = 8.9 Hz, arom.), 7.51 (d, 2H, J = 8.8 Hz, arom.). ¹³C-NMR (100 MHz, DMSO-d₆): δ (ppm) 41.7 (CH₂), 47.6 (CH₂), 124.3, 127.1, 130.3, 130.9, 131.3, 138.2, 140.3, 147.7, 167.1 (C=O), 194.3 (C=S). LCMS (ESI): m/z 432.8/435.0 (100%, [M + H]⁺). Anal. Calc. for C₁₄H₁₁ClN₂O₆S₃: C 38.67%; H 2.55%; N 6.44%. Found: C 38.80%; H 2.45%; N 6.60%.

3-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (2h). Yield: 75%, mp 254–256 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 2.63 (t, 2H, J = 6.8 Hz, CH₂), 4.22 (t, 2H, J = 6.8 Hz, CH₂), 7.73 (s, 1H, CH=), 8.02 (s, 1H, CH=), 8.04 (d, 2H, J = 8.9 Hz, arom.), 8.32 (d, 2H, J = 8.9 Hz, arom.), 12.29 (br.s, 1H, COOH). LCMS (ESI): m/z 399.0/401.0/402.0 (100%, [M + H]⁺). Anal. Calc. for C₁₅H₁₁ClN₂O₅S₂: C 45.17%; H 2.78%; N 7.02%. Found: C 45.00%; H 2.65%; N 6.90%.

6-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}hexanoic acid (2i). Yield: 75%, mp >220 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 1.30 (quint, 2H, J = 6.7 Hz, CH₂), 1.52 (quint, 2H, J = 7.1 Hz, CH₂), 1.62 (quint, 2H, J = 6.7 Hz, CH₂), 2.20 (quint, 2H, J = 7.0 Hz, CH₂), 3.99 (quint, 2H, J = 6.9 Hz, CH₂), 7.69 (s, 1H, CH=), 7.98 (s, 1H, CH=), 8.02 (d, 2H, J = 8.5 Hz, arom.), 8.30 (d, 2H, J = 8.5 Hz, arom.), 12.00 (s, 1H, COOH). ¹³C-NMR (100 MHz, DMSO-d₆): δ (ppm) 24.5 (CH₂), 26.1 (CH₂), 26.5 (CH₂), 33.8 (CH₂), 44.5 (CH₂), 124.3, 126.8, 130.2, 131.2, 131.3, 138.4, 140.2, 147.8, 167.4, 174.7 (C=O), 194.6 (C=S). LCMS (ESI): m/z 441.0/443.1 (100%, [M + H]⁺). Anal. Calc. for C₁₈H₁₇ClN₂O₅S₂: C 49.03%; H 3.89%; N 6.35%. Found: C 49.10%; H 3.85%; N 6.40%.

2-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}-3-phenylpropanoic acid (2j). Yield: 70%, mp >220 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 3.49 (t, 2H, CH₂), 5.87 (br.s, 1H, CH), 7.10–7.25 (m, 5H, arom.), 7.71 (s, 1H, s, 1H, CH=), 8.00 (s, 1H, s, 1H, CH=), 8.02 (d, 2H, J = 8.0 Hz, arom.), 8.31 (d, 2H, J = 8.0 Hz, arom.), 13.59 (br.s, 1H, COOH). ¹³C-NMR (100 MHz, DMSO-d₆): δ (ppm) 38.2 (CH₂), 63.3 (CH), 129.1, 132.0, 133.5, 134.2, 134.7, 136.2, 137.1, 137.2, 141.6, 144.1, 152.6, 171.6 (C=O), 173.7 (C=O), 198.7 (C=S). LCMS (ESI): m/z 324.9/326.9 (100%, [M + H]⁺). Anal. Calc. for C₂₁H₁₅ClN₂O₅S₂: C 53.11%; H 3.18%; N 5.90%. Found: C 53.00%; H 3.15%; N 5.80%.

2-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}succinic acid (2k). Yield: 68%, mp 220–222 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 2.89 (d, 1H, J = 15.5 Hz, CH₂), 3.23 (dd, J = 7.6, 15.6 Hz, 1H, CH₂), 5.94 (br.s, 1H, CH), 7.75 (s, 1H, CH=), 8.02 (s, 1H, CH=), 8.04 (d, 2H, J = 8.9 Hz, arom.), 8.32 (d, 2H, J = 8.8 Hz, arom.), 12.68 (br.s, 2H, 2*COOH). ¹³C-NMR (100 MHz, DMSO-d₆): δ (ppm) 33.0 (CH₂), 53.2 (CH), 115.1 (C-Cl), 123.9, 129.6 (=CH), 131.0, 131.7 (=CH), 138.6, 139.7, 147.4, 166.5 (C=O), 168.6 (COOH), 171.2 (COOH), 193.5 (C=S). LCMS (ESI): m/z 442.8/444.7 (100%, [M + H]⁺). Anal. Calc. for C₁₆H₁₁ClN₂O₇S₂: C 43.40%; H 2.50%; N 6.33%. Found: C 43.54%; H 2.48%; N 6.45%.

2-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}pentanedioic acid (2l). Yield: 72%, mp 205–207 °C. ¹H-NMR (400 MHz, DMSO-d₆): δ (ppm) 2.25–2.45 (m, 4H, CH₂CH₂), 5.59 (br.s, 1H, CH), 7.72 (s, 1H, CH=), 8.01 (s, 1H, CH=), 8.04 (d, 2H, J = 8.9 Hz, arom.), 8.32 (d, 2H, J = 8.9 Hz, arom.), 12.59 (br.s, 2H, 2*COOH). ¹³C-NMR (100 MHz, DMSO-d₆): δ (ppm) 23.3 (CH₂), 30.7 (CH₂), 57.2 (CH), 119.3 (C-Cl), 124.3, 125.7 (=CH), 131.4, 131.8 (=CH), 138.8, 140.2, 147.8, 162.5 (C=O), 169.3 (COOH), 174.1 (COOH), 194.8 (C=S). LCMS (ESI): m/z 455.0/456.9 (100%, [M + H]⁺). Anal. Calc. for C₁₇H₁₃ClN₂O₇S₂: C 44.69%; H 2.87%; N 6.13%. Found: C 44.56%; H 2.78%; N 6.05%.