Synthesis, Antitubercular and Antimicrobial Potential of Some New Thiazole Substituted

Synthesis, Antitubercular and Antimicrobial Potential of Some New Thiazole Substituted

Synthesis, antitubercular and antimicrobial potential of some new thiazole substituted thiosemicarbazide derivatives

Yogita K. Abhale1 . Abhijit Shinde2.Keshav K. Deshmukh1 .Laxman Nawale3 . Dhiman Sarkar3 . Pravin C. Mhaske2

✉ Pravin C. Mhaske

1 Post-Graduate Department of Chemistry and Research Centre, S. N. Arts, D. J. M. Commerce and B. N. S. Science College, College Road, Sangamner, District Ahmednagar, India 422 605, (Affiliated to Savitribai Phule Pune University)

2 Post Graduate Department of Chemistry, S. P. Mandali’s Sir Parashurambhau College, Tilak Road, Pune, India 411 030, (Affiliated to Savitribai PhulePune University)

3 CombiChemBio Resource Centre, CSIR-National Chemical Laboratory, Pune 411 008, India

Spectral Data of Intermediate Compounds

Ethyl 2-phenylthiazole-4-carboxylate (2a) Yield 70 %; IR (KBr) : 3132, 2993, 1728, 1456, 1334, 1209, 1089, 833 cm-1; 1H NMR (400 MHz, DMSO-d6) δ: 1.36 (t, J = 5.6 Hz, 3H), 4.30 (q, J = 5.6 Hz, 2H), 7.31-7.40 (m, 3H), 7.89 (d, J = 7.6 Hz, 2H), 8.60 (s, 1H); LC-MS m/z : 234.1 (M+H)+.

Ethyl 2-(4-chlorophenyl)thiazole-4-carboxylate(2b) Yield 68 %; IR (KBr) : 3130, 2993, 1725, 1460, 1338, 1210, 1092, 833 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 1.33 (t, J = 5.6 Hz, 3H), 4.33 (q, J = 5.6 Hz, 2H), 7.73 (d, J = 7.6 Hz, 2H), 7.94 (d, J = 7.6 Hz, 2H), 8.61 (s, 1H); LC-MS m/z: 268.0 (M+H)+, 270.0 (M+H+2)+.

Ethyl 2-(4-fluorophenyl)thiazole-4-carboxylate(2c) Yield 74 %; IR (KBr) : 3130, 2989, 1727, 1458, 1339, 1208, 1092, 835 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 1.33 (t, J = 5.6 Hz, 3H), 4.33 (q, J = 5.6 Hz, 2H), 7.37 (t, J = 6.8 Hz, 2H), 7.94 (m, 2H), 8.56 (s, 1H); LC-MS, m/z: 252.1 (M+H)+.

Ethyl 2-(p-tolyl)thiazole-4-carboxylate (2d) Yield 71 %; IR (KBr) : 3128, 2997, 1728, 1464, 1341, 1212, 1088, 830 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 1.33 (t, J = 5.6 Hz, 3H), 2.38 (s, 3H), 4.34 (q, J = 5.6 Hz, 2H), 7.35 (d, J = 7.6 Hz, 2H), 8.54 (s, 1H), 7.87 (d, J = 7.6 Hz, 2H); LC-MS m/z: 268.0 (M+H)+.

(2-Phenylthiazol-4-yl)methanol(3a) Yield 94 %; IR (KBr) : 3281, 1602, 1462, 1230, 839 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 4.62 (d, J = 3.2 Hz, 2H), 5.41 (t, J = 3.2 Hz, 1H), 7.48-7.50 (m, 3H), 7.51 (s, 1H), 7.86 (d, J = 7.6 Hz, 2H); LC-MS m/z: 192.1 (M+H)+.

(2-(4-Chlorophenyl)thiazol-4-yl)methanol(3b) Yield 90 %; IR (KBr) : 3289, 1600, 1465, 1232, 836 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 4.62 (d, J = 3.2 Hz, 2H), 5.41 (t, J = 3.2 Hz, 1H), 7.51 (s, 1H), 7.57 (d, J = 7.6 Hz, 2H), 7.95 (d, J = 7.6 Hz, 2H); LC-MS m/z: 226.0 (M+H)+, 228.0 (M+H+2)+.

(2-(4-Fluorophenyl)thiazol-4-yl)methanol(3c) Yield 95 %; IR (KBr) : 3285, 1602, 1466, 1230, 830 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 4.62 (d, J = 3.2 Hz, 2H), 5.41 (t, J = 3.2 Hz, 1H), 7.33 (t, J = 6.8 Hz, 2H), 7.47 (s,1H), 7.95-7.98 (m, 2H); LC-MS m/z: 210.0 (M+H)+.

(2-(p-Tolyl)thiazol-4-yl)methanol(3d) Yield 91 %; IR (KBr) : 3279, 1601, 1468, 1230, 832 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 2.35 (s, 3H), 4.61 (d, J = 3.2 Hz, 2H), 5.39 (t, J = 3.2 Hz, 1H), 7.30 (d, J = 7.6 Hz, 2H), 7.43 (s, 1H), 7.81 (d, J = 7.6 Hz, 2H); LC-MS m/z: 206.1 (M+H)+.

2-Phenylthiazole-4-carbaldehyde(4a) Yield 90 %, m.p. 90-91 ºC; IR (KBr) : 2752, 1693, 1450, 1330, 833 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 7.38-7.42 (m, 3H), 7.97 (d, J = 7.6 Hz, 2H), 8.80 (s, 1H), 9.98 (s, 1H); LC-MS m/z: 190.0 (M+H)+.

2-(4-Chlorophenyl)thiazole-4-carbaldehyde (4b) Yield 88 %, m.p. 104-106 ºC; IR (KBr) : 2749, 1697, 1455, 1332, 836 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 7.52 (d, J = 6.8 Hz, 2H), 7.96 (d, J = 7.6 Hz, 2H), 8.79(s,1H), 9.99 (s,1H); LC-MS m/z: 224.0 (M+H)+, 226.0 (M+H+2)+.

2-(4-Fluorophenyl)thiazole-4-carbaldehyde(4c) Yield 90 %, m.p. 78-80 ºC; IR (KBr) : 2754, 1696, 1452, 1334, 833 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 7.37 (t, J = 6.8 Hz, 2H), 7.94-7.97 (m, 2H), 8.76 (s, 1H), 9.97 (s, 1H); LC-MS m/z : 208.0 (M+H)+.

2-(p-Tolyl)thiazole-4-carbaldehyde(4d) Yield 92 %, m.p. 96-98 ºC; I.R (KBr) : 2752, 1693, 1452, 1330, 832 cm-1; 1H NMR (400 MHz, DMSO-d6) δ : 2.38 (s, 3H), 7.36 (d, J = 6.8 Hz, 2H), 7.91 (d, J = 7.6 Hz, 2H), 8.74 (s, 1H), 9.97 (s, 1H); LC-MS m/z: 204.0 (M+H)+.

(4-methyl-2-phenylthiazol-5-yl) methanol(3e) Yield 84 %, m.p. 94-95 °C; IR (KBr) : 3295, 1597 1494, 1437, 1091 cm-1; 1H NMR (400 MHz, CDCl3) δ : 2.45 (s, 3H), 4.82 (s, 2H), 7.38-7.41 (m, 3H), 7.87-7.90 (m, 2H); 13C NMR (100 MHz, CDCl3) δ : 15.1, 55.2, 127.2, 129.3, 129.8, 130.6, 133.4, 154.2, 168.1; HRMS m/z: 206.0646 (M+H)+.

(2-(4-chlorophenyl)-4-methylthiazol-5-yl) methanol(3f) Yield 90 %, m.p. 134-136 °C; IR (KBr): 3279, 1593, 1496, 1437, 1091, 1014, 831 cm-1; 1H NMR (400 MHz, CDCl3) δ : 2.45 (s, 3H), 4.82 (s, 2H), 7.38 (d, 7.8 Hz, 2H), 7.83 (d, 7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ : 15.5, 55.1, 127.2, 128.7, 129.7, 131.9, 134.4, 158.0, 169.5; HRMS m/z : 240.0254 (M+H)+.

(2-(4-fluorophenyl)-4-methylthiazol-5-yl) methanol(3g) Yield 93 %, m.p. 88-90 °C; IR (KBr): 3285, 1578, 1489, 1436, 1088, 1080, 835 cm-1; 1H NMR (400 MHz, CDCl3) δ : 2.42 (s, 3H), 4.80 (s, 2H), 7.15 (t, 8.1 Hz, 2H), 7.83 (m, 2H); 13C NMR (100 MHz, CDCl3) δ : 15.4, 55.0, 115.5, 128.8, 130.1, 134.4, 158.0, 162.8, 169.5; HRMS m/z : 224.0554 (M+H)+.

(4-methyl-2-(p-tolyl) thiazol-5-yl) methanol(3h) Yield 85 %, m.p. 128-130 °C; IR (KBr): 3275, 1591, 1492, 1432, 1088, 1015, 825 cm-1; 1H NMR (400 MHz, CDCl3) δ : 2.39 (s, 3H), 2.47 (s, 3H), 4.78 (s, 2H), 7.32 (d, 7.8 Hz, 2H), 7.82 (d, 7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ : 15.4, 21.0, 55.2, 127.8, 128.6, 129.8, 131.7, 137.5, 157.8, 169.2; HRMS m/z : 220.0812 (M+H)+.

4-Methyl-2-phenylthiazole-5-carbaldehyde(4e) Yield 95 %, m.p. 110-112 °C; IR (KBr) : 2730, 1690, 1605 cm-1; 1H NMR (400 MHz, CDCl3) δ : 2.78 (s, 3H), 7.49 (m, 3H), 7.99 (m, 2H), 10.10 (s, 1H); 13C NMR (100 MHz, CDCl3) δ : 16.2, 127.1, 128.9, 129.6, 131.6, 132.5, 162.4, 173.7, 182.0; HRMS m/z : 236.0756 (M+MeOH+H)+.

2-(4-chlorophenyl)-4-methylthiazole-5-carbaldehyde (4f) Yield 90 %, m.p. 144-146 °C; IR (KBr): 2732, 1695, 1608 cm-1; 1H NMR (400 MHz, CDCl3) δ : 2.77 (s, 3H), 7.32 (d, J = 7.8 Hz, 2H), 7.93 (d, J = 7.8 Hz, 2H), 10.08 (s, 1H); 13C NMR (100 MHz, CDCl3) δ : 16.1, 127.6, 128.8, 129.9, 131.8, 134.6, 162.0, 171.8, 184.0; HRMS m/z : 270.0369 (M+MeOH+H)+.

2-(4-fluorophenyl)-4-methylthiazole-5-carbaldehyde (4g) Yield 92 %, m.p. 121-122 °C; IR (KBr): 2724, 1699, 1608 cm-1; 1H NMR (400 MHz, CDCl3) δ : 2.72 (s, 3H), 7.10 (t, J = 7.8 Hz, 2H), 7.84 (m, 2H), 10.04 (s, 1H); 13C NMR (100 MHz, CDCl3) δ : 16.0, 116.1, 128.8, 133.2, 140.5, 162.9, 163.5, 171.2, 182.6; HRMS m/z : 254.0657 (M+ MeOH+H)+.

4-methyl-2-(p-tolyl)thiazole-5-carbaldehyde (4h) Yield 90 %, m.p. 138-140 °C; IR (KBr) : 2735, 1698, 1605 cm-1; 1H NMR (400 MHz, CDCl3) δ : 2.41 (s, 3H), 2.76 (s, 3H), 7.36 (d, J = 7.8 Hz, 2H), 7.91 (d, J = 7.8 Hz, 2H), 9.97 (s, 1H); 13C NMR (100 MHz, CDCl3) δ : 16.1, 21.3, 127.6, 128.8, 129.9, 131.8, 134.6, 162.0, 171.8, 184.0; HRMS m/z : 218.0655 (M+MeOH+H)+.

Representative spectral Data of Synthesized Compounds

1H NMR spectrum (DMSO-d6, 400 MHz) of Ethyl 2-(4-chlorophenyl)thiazole-4-carboxylate (2b)

1H NMR spectrum (DMSO-d6, 400 MHz) of (2-(4-Chlorophenyl)thiazol-4-yl)methanol(3b)

1H NMR spectrum (DMSO-d6, 400 MHz) of2-(4-Chlorophenyl)thiazole-4-carbaldehyde (4b)

13C NMR spectrum (CDCl3, 126 MHz) of 2-(4-Chlorophenyl)thiazole-4-carbaldehyde (4b)

1H NMR spectrum (DMSO-d6, 400 MHz) of Ethyl 2-(4-fluorophenyl)thiazole-4-carboxylate(2c)

1H NMR spectrum (DMSO-d6, 400 MHz) of (2-(4-Fluorophenyl)thiazol-4-yl)methanol(3c)

1H NMR spectrum (DMSO-d6, 400 MHz) of 2-(4-Fluorophenyl)thiazole-4-carbaldehyde(4c)

1H NMR spectrum (DMSO-d6, 400 MHz) of Ethyl 2-(p-tolyl)thiazole-4-carboxylate (2d)

1H NMR spectrum (DMSO-d6, 400 MHz) of (2-(p-Tolyl)thiazol-4-yl)methanol(3d)

1H NMR spectrum (CDCl3, 500 MHz) of 2-(p-Tolyl)thiazole-4-carbaldehyde (4d)

13C NMR spectrum (CDCl3, 126 MHz) of 2-(p-Tolyl)thiazole-4-carbaldehyde (4d)

1H NMR spectrum (CDCl3, 400 MHz) of (4-methyl-2-phenylthiazol-5-yl) methanol(3e)

1H NMR spectrum (CDCl3, 400 MHz) of 4 Spectrum of 4-Methyl-2-phenylthiazole-5-carbaldehyde (4e)

13C NMR spectrum (CDCl3, 75 MHz) of 4 Spectrum of 4-Methyl-2-phenylthiazole-5-carbaldehyde (4e)

HRMS Spectrum of 4-Methyl-2-phenylthiazole-5-carbaldehyde (4e)

1H NMR spectrum (CDCl3, 400 MHz) of 2-(4-chlorophenyl)-4-methylthiazole-5-carbaldehyde (4f)

HRMS Spectrum of 2-(4-chlorophenyl)-4-methylthiazole-5-carbaldehyde(4f)

1H NMR spectrum (DMSO-d6, 400 MHz) of 4-methyl-2-(p-tolyl)thiazole-5-carbaldehyde (4h)

1H NMR spectrum (500 MHz, DMSO-d6) of 1-((2-phenylthiazol-4-yl)methylene)thiosemicarbazide (5a)

13C NMR spectrum (125 MHz, DMSO-d6) of 1-((2-phenylthiazol-4-yl)methylene)thiosemicarbazide (5a)

1H NMR spectrum (500 MHz, DMSO-d6) of 1-((2-(4-chlorophenyl)thiazol-4-yl)methylene)thiosemicarbazide (5b)

13C NMR spectrum (125 MHz, DMSO-d6) of 1-((2-(4-chlorophenyl)thiazol-4-yl)methylene)thiosemicarbazide (5b)

1H NMR Spectrum (500 MHz, DMSO-d6) of 1-((2-(4-fluorophenyl)thiazol-4-yl)methylene)thiosemicarbazide (5c)

13C NMR Spectrum (125 MHz, DMSO-d6) of 1-((2-(4-fluorophenyl)thiazol-4-yl)methylene)thiosemicarbazide (5c)

1H NMR Spectrum (500 MHz, DMSO-d6) of 1-((2-p-tolylthiazol-4-yl)methylene)thiosemicarbazide (5d)

13C NMR Spectrum (500 MHz, DMSO-d6) of 1-((2-p-tolylthiazol-4-yl)methylene)thiosemicarbazide (5d)

1H NMR Spectrum (500 MHz, DMSO-d6) of 1-((4-methyl-2-phenylthiazol-5-yl)methylene)thiosemicarbazide (5e)

13C NMR spectrum (DMSO-d6, 100 MHz) of 1-((4-methyl-2-phenylthiazol-5-yl)methylene)thiosemicarbazide (5e)

Mass Spectrum of 1-((2-phenyl)-4-methylthiazol-5-yl)methylene) thiosemicarbazide (5e)

1H NMR Spectrum (500 MHz, DMSO-d6) of 1-((2-(4-chlorophenyl)-4-methylthiazol-5-yl)methylene)thiosemicarbazide (5f)

13C NMR Spectrum (125 MHz, DMSO-d6) of 1-((2-(4-chlorophenyl)-4-methylthiazol-5-yl)methylene)thiosemicarbazide (5f)

1H NMR Spectrum (500 MHz, DMSO-d6) of 1-((2-(4-fluorophenyl)-4-methylthiazol-5-yl)methylene)thiosemicarbazide (5g)

13C NMR Spectrum (125 MHz, DMSO-d6) of 1-((2-(4-fluorophenyl)-4-methylthiazol-5-yl)methylene)thiosemicarbazide (5g)

1H NMR Spectrum (500 MHz, DMSO-d6) of 1-((4-methyl-2-p-tolylthiazol-5-yl)methylene)thiosemicarbazide (5h)

13C NMR Spectrum (125 MHz, DMSO-d6) of 1-((4-methyl-2-p-tolylthiazol-5-yl)methylene)thiosemicarbazide (5h)

1H NMR Spectrum (500 MHz, DMSO-d6) of 1-(1-(2-(4-chlorophenyl)-4-methylthiazol-5-yl)ethylidene)thiosemicarbazide (5j)

13C NMR Spectrum (125 MHz, DMSO-d6) of 1-(1-(2-(4-chlorophenyl)-4-methylthiazol-5-yl)ethylidene)thiosemicarbazide (5j)

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