METHOD FOR PREPARING IMIDAZOLINE-2 KETONE COMPOUND

Abstract

A method of preparing an imidazolin-2-tones compound includes: dissolving a cycloheptatrienone and an aromatic isocyanate in a solvent; and reacting the cycloheptatrienone and the aromatic isocyanate in the solvent without an oxidant and a catalyst to obtain the imidazolin-2-tone compound.

Claims

1. A method of preparing an imidazolin-2-tones compound, comprising the following steps: dissolving a cycloheptatrienone and an aromatic isocyanate in a solvent; and reacting the cycloheptatrienone and the aromatic isocyanate in the solvent without an oxidant or a catalyst to obtain the imidazolin-2-tones compound.

2. The method of according to claim 1, wherein the chemical formula of the aromatic isocyanate is ArNCO, and Ar is an aryl group or a substituted aryl group.

3. The method according to claim 1, wherein the solvent is triglyme, dimethyl sulfoxide, DMI, tetraglyme or bis(2-ethyl-hexyl)adipate.

4. The method of according to claim 1, wherein a molar ratio of the cycloheptatrienone and the aromatic isocyanate was 1:(2 to 6).

5. The method according to claim 4, wherein the molar ratio of the cycloheptatrienone and the aromatic isocyanate was 1:(3 to 5).

6. The method according to claim 1, wherein a reaction temperature is 100 C. to 250 C. and a reaction time is 0.5 to 5 hours.

7. The method according to claim 6, wherein the reaction temperature is 120 C. to 200 C. and the reaction time is 0.5 to 2 hours.

8. The method according to claim 2, wherein the aromatic isocyanate is ##STR00018##

Description

INVENTION EMBODIMENT

Embodiments of the Invention

EXAMPLE 1

[0018] ##STR00003##

[0019] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 2 (187 mg, 1 mmol, 2 equiv) into the tetraglyme, was heating at 250 C. for half an hour. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. And after that spun steam to dry, column chromatography, to obtain product 4 with a yield of 20%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.65 (s, 2H), 7.56 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 6.23 (d, J=9.4 Hz, 2H), 5.34 (dd, J=14.9, 6.9 Hz, 2H), 2.58 (t, J=6.3 Hz, 2H). .sup.13CNMR (151 MHz, CDCl.sub.3): 150.38, 134.11, 133.36, 131.55, 131.02, 127.65, 125.09, 124.43, 116.78, 116.75, 28.22. LR-MS (ESI): m/z 436.9 [M+H]+.

[0020] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 2 (280 mg, 1.5 mmol, 3 equiv.) into the bis(2-ethyl-hexyl)adipate , was heating at 230 C. for 2 hours. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography, to obtain product 4 with a yield of 23%.

[0021] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 2 (467 mg, 2.5 mmol, 5 equiv) into the DMI, was heating at 210 C. for 3 hours. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 4 with a yield of 63%.

[0022] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 2 (374 mg, 2 mmol, 4 equiv) into the triglyme, was heating at 180 C. for 1 hour. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 4 with a yield of 95%.

[0023] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 2 (561 mg, 3 mmol, 6 equiv) into the DMSO , was heating at 140 C. for 4 hours. When the solvent is cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 4 with a yield of 19%.

EXAMPLE 2

[0024] ##STR00004##

[0025] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 2 (374 mg, 2 mmol, 4 equiv) into the DMI , was heating at 120 C. for 1.5 hours. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 3 with a yield of 74%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.84 (s, 1H), 7.53-7.60 (m, 2H), 7.41-7.53 (m, 2H), 7.30 (s, 1H), 6.59 (dd, J=11.0, 6.8 Hz, 1H), 6.47 (dd, J=11.0, 5.8 Hz, 1H), 6.37-6.24 (m, 1H), 5.65 (d, J=6.2 Hz, 1H), 5.00 (dd, J=9.5, 2.8 Hz, 1H), 4.37 (s, 1H). .sup.13C NMR (151 MHz, CDCl.sub.3) 153.44, 137.02, 133.61, 133.55, 133.29, 132.41, 131.45, 131.28, 130.81, 129.31, 128.80, 127.37, 126.49, 126.19, 125.56, 120.43, 117.94, 116.06, 96.78, 56.96. LR-MS (ESI): m/z 436.9 [M+H]+.

EXAMPLE 3

[0026] ##STR00005##

[0027] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 2 (288 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 1 hour. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 6 with a yield of 89%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.82 (d, J=9.3 Hz, 4H), 7.68-7.58 (m, 4H), 6.22 (d, J=9.4 Hz, 2H), 5.38 (dd, J=15.6, 7.2 Hz, 2H), 2.62 (t, J=6.7 Hz, 2H). .sub.13C NMR (151 MHz, CDCl.sub.3): 150.39, 135.64, 130.86, 130.42, 130.04, 128.89, 124.37, 117.98, 117.34, 116.63, 113.63, 28.20. LR-MS (ESI): m/z 351.1.

EXAMPLE 4

[0028] ##STR00006##

[0029] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 7 (310 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 1 hour. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 8 with a yield of 86%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.12 (d, J=6.1 Hz, 4H), 6.82 (t, J=8.7 Hz, 2H), 6.28 (d, J=9.5 Hz, 2H), 5.36 (dd, J=16.3, 7.1 Hz, 2H), 2.58 (t, J=6.9 Hz, 2H). .sup.13C NMR (151 MHz, CDCl.sub.3): 163.22 (dd, J=249.0, 14.2 Hz), 150.13 (s), 136.84 (t, J=12.8 Hz), 124.40 (s), 116.92 (s), 116.88 (s), 109.13 (dd, J=22.4, 6.4 Hz), 103.08 (t, J=25.3 Hz), 28.21 (s). LR-MS (ESI): m/z 373.0.

EXAMPLE 5

[0030] ##STR00007##

[0031] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 9 (342 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 1 hour. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 10 with a yield of 91%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.54-7.63 (m, 2H), 7.36-7.38 (m, 2H), 7.23 (d, J=8.8 Hz, 2H), 6.19 (d, J=9.5 Hz, 2H), 5.30 (dd, J=16.0, 7.0 Hz, 2H), 2.55 (t, J=6.8 Hz, 2H). .sup.13C NMR (151 MHz, CDCl.sub.3): 157.22 (d, J=250.3 Hz), 150.74 (s), 131.31 (d, J=3.5 Hz), 128.37 (s), 125.93 (d, J=7.4 Hz), 124.52 (s), 121.92 (d, J=18.9 Hz), 117.23 (d, J=22.4 Hz), 116.73 (s), 116.59 (s), 28.20 (s). LR-MS (ESI): m/z 405.1.

EXAMPLE 6

[0032] ##STR00008##

[0033] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 11 (306 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 1 hour. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 12 with a yield of 96%. .sup.1H NMR (400 MHz, CDCl3): 7.54 (s, 2H), 7.42 (d, J=4.5 Hz, 4H), 7.34 (d, J=3.7 Hz, 2H), 6.24 (d, J=9.5 Hz, 2H), 5.31 (dd, J=16.1, 7.1 Hz, 2H), 2.57 (t, J=6.9 Hz, 2H). .sup.13C NMR (151 MHz, CDCl.sub.3): 150.63, 136.03, 134.96, 130.33, 127.67, 126.18, 124.59, 124.17, 117.08, 116.19, 28.22. LR-MS (ESI): m/z 369.1.

EXAMPLE 7

[0034] ##STR00009##

[0035] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 13 (306 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 50 min. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography, to obtain product 14 with a yield of 89%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.45 (s, 8H), 6.22 (s, 2H), 5.29 (s, 2H), 2.56 (s, 2H). .sup.13C NMR (151 MHz, CDCl.sub.3): 150.75, 133.44, 133.10, 129.56, 127.26, 124.59, 117.08, 115.96, 28.17. LR-MS (ESI): m/z 369.1.

EXAMPLE 8

[0036] ##STR00010##

[0037] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 15 (392 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 1H. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 16 with a yield of 87%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.60 (d, J=8.2 Hz, 4H), 7.40 (d, J=8.3 Hz, 4H), 6.22 (d, J=9.5 Hz, 2H), 5.29 (dd, J=14.5, 8.3 Hz, 2H), 2.56 (t, J=6.7 Hz, 2H). .sup.13C NMR (151 MHz, CDCl.sub.3): 150.60, 133.93, 132.53, 127.53, 124.55, 121.02, 117.07, 116.01, 28.17. LR-MS (ESI): m/z 458.9.

EXAMPLE 9

[0038] ##STR00011##

[0039] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 17 (406 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 1H. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography to obtain product 18 with a yield of 98%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.56 (d, J=8.7 Hz, 4H), 7.34 (d, J=8.4 Hz, 4H), 6.25 (d, J=9.5 Hz, 2H), 5.31 (dd, J=16.1, 7.0 Hz, 2H), 2.58 (t, J=6.8 Hz, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3): 150.87 (s), 148.01 (s), 133.40 (s), 127.39 (s), 124.62 (s), 121.95 (s), 120.57 (q, J=257.7 Hz), 117.04 (s), 116.20 (s), 28.17 (s). LR-MS (ESI): m/z 469.1.

EXAMPLE 10

[0040] ##STR00012##

[0041] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 19 (266 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 2H. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography, to obtain product 20 with a yield of 89%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.39 (d, J=8.0 Hz, 4H), 7.28 (d, J=8.2 Hz, 4H), 6.24 (d, J=9.5 Hz, 2H), 5.24 (dd, J=16.1, 7.0 Hz, 2H), 2.55 (t, J=6.8 Hz, 2H), 2.40 (s, 6H). .sup.13C NMR (101 MHz, CDCl.sub.3): 151.23, 137.31, 132.44, 129.93, 126.15, 124.79, 117.39, 114.93, 28.13, 21.28. LR-MS (ESI): m/z 329.0.

EXAMPLE 11

[0042] ##STR00013##

[0043] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 21 (274 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 50 min. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography, to obtain product 22 with a yield of 93%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.45 (dd, J=14.5, 7.3 Hz, 2H), 7.36-7.27 (m, 4H), 7.07 (t, J=7.8 Hz, 2H), 6.27 (d, J=9.4 Hz, 2H), 5.31 (dd, J=15.6, 7.2 Hz, 2H), 2.58 (t, J=6.6 Hz, 2H). .sup.13C NMR (151 MHz, CDCl.sub.3): 162.98 (d, J=247.1 Hz), 150.60 (s), 136.30 (d, J=10.2 Hz), 130.47 (d, J=9.1 Hz), 124.58 (s), 121.55 (d, J=3.0 Hz), 117.14 (s), 116.05 (s), 114.44 (d, J=21.0 Hz), 113.46 (d, J=24.3 Hz), 28.16 (s). LR-MS (ESI): m/z 337.0.

EXAMPLE 12

[0044] ##STR00014##

[0045] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 23 (442 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 1H. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography, to obtain product 24 with a yield of 96%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.87 (s, 2H), 7.60-7.72 (m, 4H), 6.22 (d, J=9.5 Hz, 2H), 5.38 (dd, J=16.0, 7.1 Hz, 2H), 2.62 (t, J=6.8 Hz, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3): 150.44 (s), 133.55 (s), 132.59 (s), 131.10 (s), 129.94 (s), 129.61 (q, J=32.0 Hz), 124.90 (q, J=5.2 Hz), 124.43 (s), 122.46 (q, J=273.6 Hz), 117.29 (s), 116.54 (s), 28.27 (s). LR-MS (ESI): m/z 505.1.

EXAMPLE 13

[0046] ##STR00015##

[0047] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 25 (266 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 2H. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography, to obtain product 26 with a yield of 97%. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.33-7.40 (m, 4H), 7.28 (d, J=9.1 Hz, 2H), 7.17 (d, J=7.4 Hz, 2H), 6.25 (d, J=9.5 Hz, 2H), 5.25 (dd, J=16.0, 7.1 Hz, 2H), 2.57 (t, J=6.8 Hz, 2H), 2.42 (s, 6H). .sup.13C NMR (151 MHz, CDCl.sub.3): 151.13, 139.32, 134.93, 129.05, 128.25, 126.95, 124.80, 123.29, 117.45, 114.98, 28.15, 21.52. LR-MS (ESI): m/z 329.0.

EXAMPLE 14

[0048] ##STR00016##

[0049] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 27 (322 mg, 2 mmol, 4 equiv) into the anhydrous triglyme, was heating at 180 C. for 70 min. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography, to obtain product 28 with a yield of 95%. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.08 (d, J=8.1 Hz, 4H), 7.66 (d, J=8.1 Hz, 4H), 6.27 (d, J=9.4 Hz, 2H), 5.34 (dd, J=15.6, 7.1 Hz, 2H), 2.63 (s, 8H). .sup.13C NMR (101 MHz, CDCl.sub.3): 197.14, 150.43, 138.97, 135.59, 129.55, 125.38, 124.63, 117.23, 116.45, 28.20, 26.79. LR-MS (ESI): m/z 385.1.

EXAMPLE 15

[0050] ##STR00017##

[0051] Dissolving compound 1 (53 mg, 0.5 mmol) and compound 29 (328 mg, 2 mmol, 4 equiv) into the anhydrous triglyme , was heating at 180 C. for 60 min. When the solvent was cooled, added ethyl acetate, and then washed the organic layer by water for three times. After that merged the water layer, and washed the water layer by ethyl acetate layer once, and then merged the organic layer, washed the organic layer by saturated salt water, and dried it with anhydrous sodium sulfate. Column chromatography, to obtain product 30 with a yield of 99%. .sup.1H NMR (400 MHz, CDCl.sub.3): 8.42 (s, 2H), 8.23 (d, J=8.1 Hz, 2H), 7.95 (d, J=7.9 Hz, 2H), 7.70 (t, J=8.1 Hz, 2H), 6.27 (d, J=9.5 Hz, 2H), 5.41 (dd, J=16.1, 7.1 Hz, 2H), 2.66 (t, J=6.9 Hz, 2H). .sup.13C NMR (151 MHz, CDCl.sub.3): 150.47, 148.88, 135.89, 131.57, 130.34, 124.46, 122.17, 120.64, 117.57, 116.55, 28.31. LR-MS (ESI): m/z 391.0.