Three tricyclic ring system, pyridazino[6,1-b]quinazolin-10-ones, benzimidazolo-pyridazine thione, and 1,2,4-benzotriazino-pyridazinethione along with imidazo-[1,2-b]-pyridazinethione, 1,2,4-triazolo[4,3-b]pyridazine-thione derivatives were synthesized starting from 6-chloropyridazin3-(2
The chemistry of pyridazines and their fused heterocyclic derivatives has received considerable attention owing to their synthetic and effective biological importance. Pyridazines have been reported to possess antimicrobial [
Uncorrected melting points were determined on Gallenkamp Electric Melting point Apparatus. IR spectra (KBr Disces) were recorded on a FT/IR-400 Spectrophotometer (Perkin Elmer). 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were recorded on a Varian instrument. Chemical shifts were reported as
To a solution of compound (
A mixture of
A solution of
A mixture of (
A mixture of compound (
Compound
A solution of (
A mixture of compound (
6-Chloropyridazin-3(2
Antimicrobial activity of synthetic compounds.
Compd. no. | Gram +ve Bacteria | Gram −ve bacteria | Fungi | |||
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24 | 30 | 22 | 20 | 19 | 14 |
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18 | 20 | 10 | 10 | 10 | 13 |
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18 | 10 | 11 | 10 | 16 | 12 |
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20 | 23 | 17 | 17 | 20 | 15 |
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25 | 27 | 11 | 12 | 19 | 14 |
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18 | 19 | 10 | 18 | 18 | 15 |
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21 | 23 | 16 | 12 | 18 | 14 |
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12 | 20 | 19 | 17 | 16 | 12 |
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11 | 16 | 11 | 18 | 19 | 13 |
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15 | 13 | 14 | 11 | 22 | 16 |
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19 | 22 | 10 | 12 | 19 | 15 |
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26 | 29 | 22 | 20 | 23 | 18 |
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17 | 16 | 15 | 13 | 18 | 12 |
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19 | 19 | 22 | 20 | 16 | 15 |
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14 | 19 | 18 | 17 | 24 | 17 |
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14 | 11 | 13 | 15 | 19 | 10 |
Ampicillin |
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Micostatin |
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Physical properties of the prepared compounds (
Compd. no. | m.p. °C | Yield (%) | Solvent of cryst. | Mol. formula (M.wt) | Elemental analysis | |||
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C | H | N | S | |||||
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182–184 |
37 |
Ethanol |
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57.61 | 3.10 | 18.35 | 13.99 |
229.26 | 57.63 | 3.08 | 18.33 | 13.98 | ||||
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255–257 |
41 | Methanol |
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34.16 | 1.33 | 10.89 | 8.30 |
387.05 | 34.14 | 1.30 | 10.86 | 8.28 | ||||
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232–234 |
45 |
Ethanol |
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42.91 | 1.98 | 13.68 | 10.42 |
308.15 | 42.88 | 1.96 | 13.64 | 10.40 | ||||
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168–170 |
49 |
Methanol |
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59.70 | 3.56 | 20.92 | 15.96 |
201.25 | 59.68 | 3.51 | 20.88 | 15.93 | ||||
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285–287 |
39 |
Acetic acid |
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55.56 | 3.92 | 25.95 | 14.92 |
216.26 | 55.54 | 3.73 | 25.91 | 14.82 | ||||
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282-283 |
61 |
Ethanol |
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60.58 | 4.78 | 16.38 | 12.49 |
257.06 | 60.68 | 4.31 | 16.33 | 12.46 | ||||
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279-280 |
58 |
Ethanol |
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35.94 | 3.07 | 41.92 | 19.20 |
167.19 | 35.92 | 3.01 | 41.89 | 19.18 | ||||
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261–263 |
52 |
Ethanol |
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50.33 | 2.71 | 21.37 | 12.24 |
262.72 | 50.29 | 2.69 | 21.33 | 12.20 | ||||
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242-243 |
63 |
Ethanol |
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57.85 | 3.55 | 24.56 | 14.07 |
228.27 | 57.88 | 3.53 | 24.54 | 14.04 | ||||
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271–273 |
35 |
Methanol |
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59.02 | 4.99 | 22.97 | 13.10 |
244.31 | 58.99 | 4.95 | 22.93 | 13.12 | ||||
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246–248 |
44 |
Methanol |
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49.78 | 3.86 | 24.23 | 11.12 |
289.31 | 49.82 | 3.83 | 24.21 | 11.08 | ||||
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205–207 |
49 |
Ethanol |
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47.52 | 3.57 | 20.17 | 23.09 |
278.35 | 47.47 | 3.62 | 20.13 | 23.04 | ||||
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239-240 |
73 |
Methanol |
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34.86 | 1.62 | 16.29 | 18.63 |
344.75 | 34.84 | 1.46 | 16.25 | 18.60 | ||||
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221–223 |
85 |
ether 60–80/Benzene |
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33.04 | 1.42 | 19.25 | 22.09 |
291.17 | 33.00 | 1.38 | 19.24 | 22.02 | ||||
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234–236 |
73 |
Ethanol |
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47.64 | 3.25 | 11.14 | 38.15 |
252.37 | 47.59 | 3.20 | 11.10 | 38.11 | ||||
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186–88 |
71 |
Methanol |
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37.10 | 1.59 | 21.65 | 12.40 |
259.11 | 37.08 | 1.56 | 21.62 | 12.37 |
Spectral data of compounds (
Comp. | IR cm−1 | 1H NMR ppm | 13C-NMR ppm |
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3380 (NH), 1750 (CO), 1610 (C=N), 1459 (N–C=S), 1405 (C=S). | 6.1 (s, 1H, NH, exchangeable with D2O), 6.9–7.6 (m, 6Ar H) | 126.72 (C6, C9), 127.45 (C8), 130.12 (C4), 130.48 (C3), 134.76 (C7), 154 (C2), 162 (C=O). |
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3410 (NH), 1620 (CO), 1595 (C=N), 1451 (N–C=S), 1411 (C=S). | 6.4 (s, 1H, NH, exchangeable with D2O), 7.4–7.9 (m, 4H Ar H) | 114 (C6), 123 (C8), 131.2 (C4), 131.6 (C3), 1349 (C9), 139.9 (C7), 154 (C2), 162 (C=O). |
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3385 (NH), 1616 (CO), 1580 (C=N), 1432 (N–C=S), 1418 (C=S). | 6.6 (s, 1H, NH, exchangeable with D2O), 7.1–7.8 (m, 5H, Ar H) | 122 (C8), 125 (C6), 131 (C4), 131.8 (C3), 133 (C9), 138 (C7), 153.4 (C2), |
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3370 (NH), 1610 (C=N), 1438 (N–C=S), 1401 (C=S). | 6.7 (s, 1H, NH, exchangeable with D2O), 6.8–7.6 (m, 6H, Ar H). | 110.3 (C7), 112.1 (C10), 121.2 (C4), 123 (C8), 123 (C9), 125.2 (C5), 180.6 (C3). |
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3420 (NH), 3390 (NH), 1610 (C=N), 1432 (N–C=S), 1416 (C=S). | 6.3 (s, 1H, NH, exchangeable with D2O), 6.8 (s, 1H, NH, exchangeable with D2O), 6.9–7.6 (m, 6H, Ar H). | 116.8 (C5 & C8 benzotriazine), 120.4 (C6 & C7, benzotriazine), 132.4 (C4, pyridazine), 134.1-(C5, pyridazine), 151 (C6), 154.1 (C3). |
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3310 (NH), 1660 (CO), 1605 (C=N), 1440 (N–C=S), 1413 (C=S). | 2.95 (d, 1H, −CH2), 3.15 (d, 1H, −CH2), 3.85 (d, 1H, −CH), 6.83 (s, 1H, NH, exchangeable with D2O), 7.41–7.96 (m, 7H, Ar H). | 40.1 (CH2), 72.4 (C4, imidazole), 125.1, 127.3, 128 (Ph–C), 130 (C5, pyridazine), 131.3 (C4, pyridazine), 152.3 (C6, pyridazine), 154.2 (C3, pyridazine), 174.2 (C=O). |
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3427-3409 (NH2), 3316 (NH), 1580 (C=N), 1444 (NC=S), 1408 (C=S). | 6.29 (s, 2H, NH2, exchangeable with D2O), 6.45 (s, 1H, NH), 6.81–6.93 (m, 2H, Ar H). | 122.1 (C4, pyridazine), 125.3 (C5, pyridazine), 137.9 (C3, triazole), 141.6 (C6, pyridazine), 179.3 (C3, p-yridazine). |
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3357 (NH), 1600 (C=N), 1425 (N–C=S), 1405 (C=S). | 6.52 (s, 1H, NH, exchangeable with D2O), 6.81–7.84 (m, 6H, Ar H). | 119.9 (C4, pyridazine), 122.2 (C5, pyridazine), 126.1 (C1, phenyl), 126.7 (C2 & C6, phenyl), 129.1 (C3 & C5, phenyl), 132.4 (C–Cl), 179.1 (C3, pyridazine). |
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3349 (NH), 1606 (C=N), 1432 (N–C=S), 1418 (C=S). | 6.48 (s, 1H, NH, exchangeable with D2O), 6.76–7.59 (m, 7H, Ar H). | 120.1 (C4, pyridazine), 122.5 (C5, pyridazine), 127.2 (C2 & C6, phenyl) 129.2 (C3 & C5, phenyl), 130.6 (C1, phenyl), 130.9 (C4, phenyl), 139.8 (C3, triazole), 180.1 (C3, pyridazine) |
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3420 (NH), 3391 (NH), 1610 (C=N), 1429 (N–C=S), 1408 (C=S). | 2.14 (s, 3H, CH3), 6.42 (s, 1H, NH, exchangeable with D2O), 6.9–7.7 (m, 7H, Ar H), 10.14 (s, 1H, NH, exchangeable with D2O). | 25.4 (CH3), 81.5 (C3, triazole), 126 (C4, phenyl), 126.9 (C2 & C6, phenyl), 128 (C3 & C5, phenyl), 129.8 (C4, pyridazine), 134.2 (C5, pyridazine), 141.2 (C1, phenyl), 150.1 (C3, pyridazine). |
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3406 (NH), 3360 (NH), 1590 (C=N), 1437 (N–C=S), 1410 (C=S). | 2.23 (s, 3H, CH3), 6.56 (s, 1H, NH, D2O-exchangeable), 6.8–7.7 (m, 6H, Ar H), 10.67 (s, 1H, NH, exchangeable with D2O). | 25.8 (CH3), 83.2 (C3, triazole), 122 (C4, phenyl), 123.5 (C2, phenyl), 129.1 (C5, phenyl), 129.8 (C4, pyridazine), 131.2 (C4, pyridazine), 133.2 (C6, phenyl), 136.2 (C5, pyridazine), 143.2 (C1, phenyl), 148.2 (C–NO2), 152.3 (C3, pyridazine). |
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3360 (NH), 1572 (C=N), 1417 (C=S), 1345 (S=O). | 2.99 (s, 3H, CH3), 6.5 (s, 1H, NH, exchangeable with D2O), 6.89–7.92 (m, 6H, Ar H). | 22.1 (CH3), 123.3 (C1, phenyl), 128.1 (C3 & C5, phenyl), 129.2 (C5, pyridazine), 129.8 (C4, pyridazine), 130.4 (C2 & C6, phenyl), 132.6 (C4, phenyl), 154.1 (C3, pyridazine). |
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1605 (C=N), 1530-1380 (NO2), 1340 (C–S–). | 7.9 (d, 1H, CH), 8.1 (d, 1H, CH), 8.58–8.62 (m, 2H, (NO2)2C6H3–), 9.08 (s, 1H, (NO2)2C6H3–), | 123.6 (C5, pyridazine), 124.8 (C3, phenyl), 129.1 (C5, phenyl), 129.3 (C4, pyridazine), 143.2 (C4, phenyl), 145.9 (C2, phenyl), 152.2 (C–Cl), 178.2 (C6, pyridazine). |
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1620 (C=N) | 7.9 (d, 2H, 2CH), 8.0 (d, 2H, 2CH) | 124.2 (2C5), 125.4 (2C4), 152.2 (2C–Cl), 178.1 (2C6). |
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3340 (NH), 1600 (C=N), 1273 (C–S–). | 6.35 (s, 1H, NH, exchangeable with D2O), 6.81–7.98 (m, 7H, Ar H). | 120.3 (C4 & C5, pyridazine), 122.5 (C4, phenyl), 127.1 (C2 & C6, phenyl), 128.2 (C3 & C5, phenyl), 134.2 (C1, phenyl), 177.2 (2C–S). |
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1580 (C=N). | 7.99 (d, 2H, 2CH), 8.87 (d, 2H, 2CH). | 122.1 (2C5), 126.3 (2C4), 152.6 (2C–Cl), 178 (2C–S). |
Imidazo[1,2-b]pyridazinethione derivative (
Treatment of 6-chloro-pyrizadinethione (
Finally, disulfide derivatives were prepared. Stirring a solution of pyridazine-3-thione (
The antimicrobial activity of the synthesized compounds has been evaluated by filter paper disc method [
6-Chloropyridazin-3(2
The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this paper through the research group Project no. RGP-VPP-133.