2.2 General procedure for synthesis of substituted dual thiazole derivatives (4a-4h)
As described in scheme, in 50 ml single neck round bottom flask, phenacyl bromide derivative (3) refluxed with 0.1 gm of thiosemicarbazide (1) and 0.139 gm of 4-methylthiazole-5-carboxaldehyde (2) in the presence of 5ml ethanol and 2–3 drops of acetic acid at 70-80oC to obtain final substituted dual thiazole derivatives 4 (a-h). Reaction progress was monitored on TLC after 3–4 hours. Filtered the reaction mass and washed with 1 ml ethanol. Dry the material in oven at 40–45°C. The structures of the synthesized compounds were confirmed by 1 H-NMR, 13C-NMR and mass spectrometry.
2.2.1 (E)-4-methyl-5-((2-(4-(p-tolyl)thiazol-2-yl)hydrazineylidene)methyl)thiazole (4a)
Cream yellow solid; Yield: 90%; FTIR (KBr, υ cm− 1): 3060 (N-H stretch), 1611 (C = N stretch), 1498 (C = C stretch), 1316 (C–N stretch thiazole), 1197, 1117, 1015 (C-N, C-S stretch); 1H NMR (DMSO-d6, 500 MHz): δ 11.99 (bs, 1H), 9.03 (s, 1H), 8.28 (s, 1H), 7.73 (d, J = 8.1 Hz, 2H), 7.24 (s, 1H), 7.21 (d, J = 8.1 Hz, 2H), 2.47 (s, 3H), 2.31 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): δ 167.68, 154.22, 151.73, 137.12, 134.66, 131.38, 129.23, 128.91, 127.91, 127.79, 125.57, 103.09, 20.85, 15.18; HRMS Calcd. for C15H14N4S2 m/z 315.0660, Found 315.0472 [M + H]+
2.2.2 (E)-4-(4-chlorophenyl)-2-(2-((4-methylthiazol-5-yl)methylene)hydrazineyl)thiazole (4b)
Light-yellow solid; Yield: 86%; FTIR (KBr, υ cm− 1): 3063 (N-H stretch), 1614 (C = N stretch), 1484 (C = C stretch), 1311 (C–N stretch thiazole), 1270 (C-H bend), 1151, 1093 (C-N, C-S stretch), 825 (C-Cl stretch); 1H NMR (DMSO-d6, 500 MHz): δ 12.23 (bs, 1H), 9.03 (s, 1H), 8.27 (s, 1H), 7.87–7.85 (m, 2H), 7.47–7.45 (m, 2H), 7.39 (s, 1H), 2.47 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): δ 167.77, 154.09, 134.33, 133.23, 132.27, 129.53, 128.63, 128.40, 127.85, 127.25, 104.72, 15.17; HRMS Calcd. for C14H11ClN4S2 m/z 335.0114 [M + H]+; Found 335.0185.
2.2.3 (E)-4-methyl-5-((2-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)hydrazineylidene)methyl)thiazole (4c)
Yellow solid; Yield: 93%; FTIR (KBr, υ cm− 1): 3066 (N-H stretch), 1612 (C = N stretch), 1490 (C = C stretch), 1322 (C–N stretch thiazole), 1174, 1115, 1069 (C-N, C-S stretch), 948 (C-F stretch); 1H NMR (DMSO-d6, 500 MHz): δ 12.26 (bs, 1H), 9.04 (s, 1H), 8.29 (s, 1H), 8.07 (d, J = 8.1 Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H), 7.58 (s, 1H), 2.48 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): δ 167.91, 154.07, 151.79, 138.16, 135.45, 134.38, 128.45, 127.80, 126.06, 125.58, 125.31, 123.16, 106.70, 15.19; HRMS Calcd. for C15H11F3N4S2 m/z 369.0377 [M + H]+; Found 369.0449.
2.2.4 (E)-4-methyl-5-((2-(4-(4-nitrophenyl)thiazol-2-yl)hydrazineylidene)methyl)thiazole (4d)
Dark-yellow solid; Yield: 85%; FTIR (KBr, υ cm− 1): 3101 (N-H stretch), 1594 (C = N stretch), 1562 & 1280 (-NO2 stretch), 1500 (C = C stretch), 1330 (C–N stretch thiazole), 1106, 1053 (C-N, C-S stretch); 1H NMR (DMSO-d6, 500 MHz): δ 12.31 (bs, 1H), 9.03 (s, 1H), 8.28–8.27 (m, 2H), 8.26 (s, 1H), 8.11–8.09 (m, 2H), 7.72 (s, 1H), 2.47 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): δ 168.02, 154.12, 151.92, 148.45, 140.49, 134.54, 128.75, 127.72, 126.35, 124.09, 123.67, 108.77, 15.21; HRMS Calcd. for C14H11N5O2S2 m/z 346.0354 [M + H]+; Found 346.0431
2.2.5 (E)-4-(2-(2-((4-methylthiazol-5-yl)methylene)hydrazineyl)thiazol-4-yl)benzonitrile (4e)
Dark-yellow solid; Yield: 91%; FTIR (KBr, υ cm− 1): 3060 (N-H stretch), 2223 (-CN gr stretch), 1601 (C = N stretch), 1561 (C = C stretch), 1342 (C–N stretch thiazole), 1150, 1046 (C-N, C-S stretch); 1H NMR (DMSO-d6, 500 MHz): δ 12.27 (bs, 1H), 9.03 (s, 1H), 8.28 (s, 1H), 8.03–8.02 (m, 2H), 7.87–7.85 (m, 2H), 7.64 (s, 1H), 2.47 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): δ 167.92, 154.10, 151.83, 138.57, 134.46, 132.67, 132.37, 128.38, 127.79, 126.12, 118.70, 109.62, 107.75, 15.19; HRMS Calcd. for C15H11N5S2 m/z 326.0529 [M + H]+; Found 326.0456.
2.2.6 (E)-4-(2-(2-((4-methylthiazol-5-yl)methylene)hydrazineyl)thiazol-4-yl)phenol (4f)
Dark-yellow solid; Yield: 95%; FTIR (KBr, υ cm− 1): 3026 (N-H stretch), 2923 (C-H stretch), 1606 (C = N stretch), 1488 (C = C stretch), 1380 (C–N stretch thiazole), 1107, 1023 (C-N, C-S stretch); 1H NMR (DMSO-d6, 500 MHz): δ 11.80 (s, 1H), 9.03 (s, 1H), 8.28 (s, 1H), 7.66–7.63 (m, 2H), 7.04 (s, 1H), 6.80–6.77 (m, 2H), 5.85 (bs, 1H), 5.85 (bs, 1H), 2.47 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): δ 167.61, 157.37, 154.29, 151.93, 135.09, 129.02, 127.80, 127.75, 127.10, 124.83, 115.38, 115.18, 108.43, 15.18; HRMS Calcd. for C14H12N4OS2 m/z 317.0528 [M + H]+; Found 317.0453
2.2.7 (E)-4-(4-methoxyphenyl)-2-(2-((4-methylthiazol-5-yl)methylene)hydrazineyl)thiazole (4g)
Light-yellow solid; Yield: 82%; FTIR (KBr, υ cm− 1): 3061(N-H stretch), 1607 (C = N stretch), 1494 (C = C stretch), 1315 (C–N stretch thiazole), 1250 (C-O stretch), 1186, 1026 (C-N, C-S stretch); 1H NMR (DMSO-d6, 500 MHz): δ 12.10 (bs, 1H), 9.03 (s, 1H), 8.28 (s, 1H), 7.79–7.76 (m, 2H), 7.16 (s, 1H), 6.99–6.96 (m, 2H), 3.79 (s, 3H), 2.48 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): δ 167.95, 158.99, 154.29, 151.75, 134.80, 129.67, 128.83, 127.75, 126.98, 114.01, 113.85, 109.02, 55.09, 15.18; HRMS Calcd. for C15H14N4OS2 m/z 331.0609 [M + H]+; Found 331.0685
2.2.8 (E)-4-([1,1'-biphenyl]-4-yl)-2-(2-((4-methylthiazol-5-yl)methylene)hydrazineyl)thiazole (4h)
Brown solid; Yield: 85%; FTIR (KBr, υ cm− 1): 3044 (N-H stretch), 1606 (C = N stretch), 1561, 1480 (C = C stretch), 1403 (C–N stretch thiazole), 1188, 1101 (C-N, C-S stretch); 1H NMR (DMSO-d6, 500 MHz): δ 11.79 (s, 1H), 9.05 (s, 1H), 8.31 (s, 1H), 7.95–7.94 (s, 1H), 7.71–7.74 (m, 2H), 7.57–7.55 (m, 2H), 7.51–7.40 (m, 3H), 7.38–7.35 (m, 2H), 2.49 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): δ 167.66, 154.33, 150.93, 139.75, 138.80, 135.27, 129.10, 129.02, 128.92, 127.64, 127.16, 126.82, 126.62, 107.89, 15.27; HRMS Calcd. for C15H11F3N4S2 m/z 369.0377 [M + H]+; Found 369.0449.