反应详情

温度

0 °C

A 1000 mL four-necked round-bottomed flask equipped with mechanical stirrer, reflux condenser, nitrogen inlet, constant pressure addition funnel and thermometer was charged with 3-(4-methylthiophenyl-2-(4-methylphenyl)propenoic acid from Step 1 (25 g, 87.91 mmol), triethylamine (12.9 mL, 92.31 mmol) and toluene (200 mL). The addition funnel was charged with diphenylphosphoryl azide (19 mL, 87.91 mmol) dissolved in toluene (100 mL), and the reaction vessel was cooled to 0° C. Over approximately ten minutes, the diphenylphosphoryl azide solution was added to the reaction flask, keeping the reaction temperature ≥10° C. After holding the reaction temperature at 0° C. for 30 minutes, water (100 mL) was added, and the biphasic solution was transferred to a separatory funnel and extracted with toluene (2×200 mL). The combined organic solution was dried over anhydrous MgSO4 and filtered. Over approximately thirty minutes, the solution was carefully warmed to reflux and held for one hour. Upon removing the heat source, tert-butanol (9 mL, 96.7 mmol) was added, and reflux was continued for an additional thirty minutes. Concentrated HCl (8 mL, 96.8 mmol) was added with extreme caution, producing copious evolution of gas. After continuing reflux for a final twenty minutes, the reaction was cooled to room temperature, and held for 16 hours. The solvent volume was reduced in vacuo, until crystals appeared. Diethyl ether (300 mL) was added, and the suspension was cooled to 0° C., held for 30 minutes, filtered and washed with diethyl ether to provide, after air-drying, pure 2-(4-methylthiophenyl)-1-(4-methylphenyl) ethanone (11.3 g, 50%): mp 120°-121° C. 1H NMR (CDCl3) 300MHz 7.89 (d, J=8.26 Hz, 2H), 7.23-7.15(m, 6H), 4.21(s, 2H), 2.45(s, 3H), 2.40(s, 3H).

1. customA 1000 mL four-necked round-bottomed flask equipped with mechanical stirrer
2. temperaturereflux
3. additioncondenser, nitrogen inlet, constant pressure addition funnel
4. waitOver approximately ten minutes
5. customthe reaction temperature ≥10° C
6. customat 0° C.
7. customfor 30 minutes
8. customthe biphasic solution was transferred to a separatory funnel
9. extractionextracted with toluene (2×200 mL)
10. dry with materialThe combined organic solution was dried over anhydrous MgSO4
11. filtrationfiltered
12. waitOver approximately thirty minutes
13. temperaturethe solution was carefully warmed
14. temperatureto reflux
15. additionwas added
16. temperaturereflux
17. waitwas continued for an additional thirty minutes
18. customproducing copious evolution of gas
19. temperatureAfter continuing reflux for a final twenty minutes
20. temperaturethe reaction was cooled to room temperature
21. waitheld for 16 hours
22. temperaturethe suspension was cooled to 0° C.
23. waitheld for 30 minutes
24. filtrationfiltered
25. washwashed with diethyl ether
26. customto provide
27. customafter air-drying