反应详情

温度

-3 °C

A 250 mL of 4-neck flask equipped with an internal thermometer and a condenser were added anisole (5.7 g, 52.0 mmol) and dichloromethane (17 mL) and the mixture was cooled to −3° C. Aluminum (III) chloride (7.4 g, 55.0 mmol) was added to the above solution over 1 h while maintaining the internal temperature below 5° C. After the addition was completed, the mixture was stirred for 30 min at 0˜5° C., and a solution of 2-chloro-5-iodobenzoyl chloride (15.0 g, 0.05 mol) in dichloromethane (15 mL) was added dropwise over 1 hour while maintaining the internal temperature below 5° C. The mixture was stirred for another 1 hour at 0˜5° C. and warmed to 10˜15° C. PMHS (15.0 g, 0.25 mol) was added dropwise while maintaining the internal temperature below 25° C. After stirring for 10 hours at 25° C., additional PMHS (9.0 g, 0.15 mol) was added to the above mixture. After stirring for another 16 hours at 30° C., the mixture was cooled to 5˜10° C. and ice water (100 mL) was added slowly dropwise over 1 hour with stirring. Note: A severe exotherm would occur upon addition of the first portion of water. The mixture was filtered and the filter cake was slurried with dichloromethane (100 mL) containing diatomite (30 g). The mixture was filtered and the filter cake was washed with dichloromethane (2×50 mL). The combined organic layers were washed with brine (100 mL). After removal of the volatiles, the residue was recrystallized from absolute ethanol (58 mL) to give 12.0 g of 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene as a white solid (yield, 67%, HPLC-0002: 98.7%). Note: The purity can be increased by doing a second recrystallization of 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene, HPLC purity could be up to 99.5% with 75˜80% yield. 1H NMR (CDCl3, 400 MHz): δ 7.50 (d, J=8.4 Hz, 2H), 7.10˜7.13 (m, 3H), 6.88 (d, J=8.4 Hz, 2H), 4.00 (s, 2H), 3.82 (s, 3H). MS ESI (m/z): 357 [M+1]+. 13C NMR (CDCl3, 100 MHz): δ 158.3, 141.5, 139.5, 136.6, 134.2, 131.2, 130.6, 129.9, 114.1, 91.71, 55.29, 38.09.

1. customA 250 mL of 4-neck flask equipped with an internal thermometer and a condenser
2. temperaturewhile maintaining the internal temperature below 5° C
3. additionAfter the addition
4. temperaturewhile maintaining the internal temperature below 5° C
5. stirringThe mixture was stirred for another 1 hour at 0˜5° C.
6. temperaturewarmed to 10˜15° C
7. temperaturewhile maintaining the internal temperature below 25° C
8. stirringAfter stirring for 10 hours at 25° C.
9. stirringAfter stirring for another 16 hours at 30° C.
10. temperaturethe mixture was cooled to 5˜10° C.
11. stirringwith stirring
12. filtrationThe mixture was filtered
13. additioncontaining diatomite (30 g)
14. filtrationThe mixture was filtered
15. washthe filter cake was washed with dichloromethane (2×50 mL)
16. washThe combined organic layers were washed with brine (100 mL)
17. customAfter removal of the volatiles
18. customthe residue was recrystallized from absolute ethanol (58 mL)
19. customto give