Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents
Abstract
:Introduction
Results and Discussion
Compound | 1H-NMR (DMSO-d6) | 13 C-NMR (DMSO-d6) |
---|---|---|
1 | δ 2.96-3.17 (2H, m), 3.18-3.21 (2H, m), 3.28 (2H, t, J = 6.7 Hz), 3.55 (2H, t, J = 6.9 Hz), 7.22-7.34 (5H, m), 7.53-7.69 (3H, m), 7.96-7.98 (2H, m), 9.23 (1H, br s). | δ 32.2, 35.1, 42.4, 48.4, 127.4, 128.6, 129.31, 129.34, 129.5, 134.4, 136.5, 137.9, 197.6. |
2 | δ 2.37 (1H, s), 2.48-2.99 (2H, m), 3.18-3.37 (4H, m), 3.49 (2H, t, J = 6.9 Hz), 7.24-7.36 (7H, m), 7.87 (2H, d, J = 8.0 Hz ), 9.10 (1H, br s). | δ 21.8, 32.2, 34.9, 42.5, 48.4, 127.4, 128.7, 129.3, 129.4, 130.0, 134.1, 137.9, 144.8, 197.1. |
3 | δ 2.96-3.00 (2H, m), 3.16-3.20 (2H, m), 3.26 (2H, t, J = 6.9 Hz), 3.47 (2H, t, J = 6.7 Hz), 3.83 (3H, s), 7.94 (2H, d, J = 8.7 Hz ), 7.06 (2H, d, J = 8.7 Hz ), 7.22-7.34 (5H, m), 9.16 (1H, br s). | δ 32.2, 34.7, 42.6, 48.4, 56.3, 114.7, 127.4, 129.31, 129.33, 129.5, 131.0, 137.9, 164.2, 195.9. |
4 | δ 2.94-2.99 (2H, m), 3.17-3.21 (2H, m), 3.28 (2H, t, J = 6.5 Hz), 3.52 (2H, t, J = 6.7 Hz), 7.22-7.34 (5H, m), 7.63 (2H, d, J = 8.4 Hz ), 7.98 (2H, d, J = 8.7 Hz ), 9.10 (1H, br s). | δ 32.2, 35.1, 42.3, 48.4, 127.4, 129.3, 129.4, 129.6, 130.6, 135.3, 137.9, 139.2, 196.7. |
5 | δ 2.95-2.99 (2H, m), 3.16-3.20 (2H, m), 3.27 (2H, t, J = 6.7 Hz), 3.53 (2H, t, J = 6.9 Hz), 7.21-7.41 (7H, m), 8.05 (2H, dd, J = 8.7, 5.4 Hz ), 9.18 (1H, br s). | δ 32.2, 35.0, 42.4, 48.4, 116.5, 127.4, 129.3, 131.7, 133.3, 137.9, 164.7, 167.2, 196.2. |
6 | δ 2.95-3.00 (2H, m), 3.16-3.20 (2H, m), 3.27 (2H, t, J = 6.6 Hz), 3.52 (2H, t, J = 6.8 Hz), 7.22-7.34 (5H, m), 7.76 (2H, d, J = 8.4 Hz ), 7.90 (2H, d, J = 8.4 Hz ), 9.20 (1H, br s). | δ 32.2, 35.1, 42.3, 48.4, 127.4, 128.4, 129.31, 129.34, 130.6, 132.6, 135.6, 137.9, 196.9. |
7 | δ 2.96-3.00 (2H, m), 3.14-3.18 (2H, m), 3.26 (2H, t, J = 6.7 Hz), 3.50 (2H, t, J = 6.9 Hz), 7.20-7.33 (5H, m), 7.58 (1H, dd, J = 8.4, 2.4 Hz ), 7.73 (1H, d, J = 2.2 Hz), 7.82 (1H, d, J = 8.4 Hz ), 9.20 (1H, br s). | δ 32.2, 38.9, 42.1, 48.4, 127.4, 128.4, 129.30, 129.31, 130.9, 132.01, 132.05, 136.5, 137.4, 137.9, 198.4. |
8 | δ 3.12-3.16 (2H, m), 3.37-3.45 (2H, m), 3.57-3.61 (2H, m), 3.80 (2H, t, J = 6.7 Hz), 7.22-7.35 (5H, m), 8.24 (2H, d, J = 8.7 Hz), 8.37 (2H, d, J = 9.1 Hz), 11.09 (1H, br s). | δ 30.0, 33.8, 47.8, 54.3, 124.5, 127.4, 129.2, 129.5, 130.1, 137.7, 141.3, 150.8, 196.6. |
9 | δ 3.08-3.58 (8H, m), 6.88 (2H, d, J = 8.7 Hz), 7.21-7.34 (5H, m), 7.89 (2H, d, J = 8.7 Hz), 10.57(1H, s), 10.60 (1H, br s). | δ 30.0, 32.5, 48.3, 54.2, 115.9, 127.4, 128.3, 129.2, 129.5, 131.3, 137.7, 163.2, 195.4. |
10 | δ 2.95-2.99 (2H, m), 3.14-3.18 (2H, m), 3.26 (2H, t, J = 6.9 Hz), 3.48 (2H, t, J = 6.9 Hz), 7.22-7.34 (5H, m), 7.98 (2H, dd, J = 4.0, 1.1 Hz), 8.05 (2H, dd, J = 4.7, 1.1 Hz), 9.20 (1H, br s). | δ 32.2, 35.4, 42.3, 48.4, 127.4, 129.31, 129.33, 129.6, 134.5, 136.1, 137.9, 143.4, 190.5. |
Compound | MW | UV* | MS m/z M+ | IR (KBr, cm-1) | ||
---|---|---|---|---|---|---|
λmax | logε | C(M) | C=O stretching | |||
1 | 289.80 | 244 | 4.12 | 5.1x10-5 | 253.3 | 1678 |
2 | 303.83 | 255 | 4.2 | 6.58x10-5 | 267.7 | 1677 |
3 | 319.83 | 286 | 3.81 | 12.5x10-5 | 283.4 | 1655 |
4 | 324.24 | 253 | 4.21 | 3.8x10-5 | 287.7 | 1675 |
5 | 307.79 | 245 | 4.03 | 6.5x10-5 | 271.6 | 1671 |
6 | 368.70 | 258 | 4.28 | 5.4x10-5 | 331.0 | 1672 |
7 | 427.58 | 248 | 3.85 | 13.9x10-5 | 321.3 | 1701 |
8 | 334.80 | 262 | 4.33 | 4.48x10-5 | 298.5 | 1695 |
9 | 305.80 | 283 | 4.48 | 3.2x10-5 | 269.3 | 1666 |
10 | 295.83 | 262, 287 | 3.95, 3.86 | 13.5x10-5 | 259.4 | 1651 |
Product characterization
Synthetic condition optimization
Entry | Target compound | Reagent ratioa | Solvent | Acid | Time | Yield (%) |
---|---|---|---|---|---|---|
A | 1 | 1:1.2:1 | Ethanol | Yes | 7 hrs | 95 |
B | 10 | 1:1.2:1 | Ethanol | Yes | 7 hrs | 93 |
C | 1 | 1:1.2:1 | Ethanol | No | 13 hrs | 95 |
D | 10 | 1:1.2:1 | Ethanol | No | 19 hrs | 96 |
E | 1 | 2:2:1 | Ethanol | Yes | 8 hrs | 74 |
F | 10 | 2:2:1 | Ethanol | Yes | 14 hrs | 69 |
G | 1 | 2:2:1 | Ethanol | No | 7 hrs | 0 |
H | 10 | 2:2:1 | Ethanol | No | 16 hrs | 74 |
I | 1 | 2:2:1 | None | No | – b | 18c |
J | 10 | 2:2:1 | None | No | – b | 16d |
K | 1 | 1:1.2:1 | None | No | – b | 37 |
L | 10 | 1:1.2:1 | None | No | – b | 47 |
- a Ketone:paraformaldehyde:phenethylamine hydrochloride
- b Reaction mixture heated to 83-86°C (ca. 10 minutes); then an exothermic reaction ocurred (see text for details)
- c 15 % of 1-phenethyl-3-benzoyl-4-phenyl-4-piperidinol was also formed
- d 21 % of 1-phenethyl-3-(2-thienylcarbonyl)-4-(2-thienyl)-4-piperidinol was also formed
Conclusions
Experimental
General
Synthesis of 1-aryl-3-phenethylamino-1-propanone hydrochlorides 1-10
Compound | Ketone | Paraformaldehyde | Phenethylamine hydrochloride | Time (hours) | Crystallisation solvent | Yield % | Melting Point (°C) |
---|---|---|---|---|---|---|---|
1 | 8.3 | 9.9 | 8.3 | 7 | Ethyl acetate | 95 | 169-171 |
2 | 7.4 | 8.9 | 7.4 | 8 | Methanol | 97 | 163-165 |
3 | 6.6 | 7.9 | 6.6 | 13 | Ethanol | 94 | 164-165a |
4 | 6.4 | 7.7 | 6.4 | 16 | Ethanol | 96 | 195-197b |
5 | 7.2 | 8.6 | 7.2 | 12 | Ethanol | 87 | 192-194c |
6 | 5.0 | 6.0 | 5.0 | 14 | Methanol. | 97 | 205-207 |
7 | 5.2 | 6.3 | 5.2 | 26 | Methanol | 91 | 167-169 |
8 | 6.0 | 7.2 | 6.0 | 8 | Methanol | 98 | 194-195 |
9 | 7.3 | 8.8 | 7.3 | 19 | Methanol | 93 | 167-169 |
10 | 7.9 | 9.5 | 7.9 | 7 | Ethanol | 93 | 156-157 |
Acknowledgments
References
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Mete, E.; Gul, H.I.; Kazaz, C. Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents. Molecules 2007, 12, 2579-2588. https://doi.org/10.3390/12122579
Mete E, Gul HI, Kazaz C. Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents. Molecules. 2007; 12(12):2579-2588. https://doi.org/10.3390/12122579
Chicago/Turabian StyleMete, Ebru, Halise Inci Gul, and Cavit Kazaz. 2007. "Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents" Molecules 12, no. 12: 2579-2588. https://doi.org/10.3390/12122579