反应详情

温度

5 °C

3,4,5-Trimethoxybenzaldehyde (5, 54.7 g), (4-methoxy-3-nitrobenzyl)triphenylphosphonium bromide (4, 148.6 g) and 1300 ml of toluene are charged, at 20° C. and under nitrogen, into a 2 litre three-necked flask equipped with a mechanical stirrer, a thermometer, a T piece, a dropping funnel and a reflux condenser surmounted by a bubble counter. The stirred suspension is cooled to 5° C. using an ice bath and then 63.2 g of a 25% w/w solution of sodium methoxide in methanol are added at 5° C. over 40 minutes. As the addition progresses, the suspension color changes from off-white to yellow and then to brown. The mixture is stirred for 1 hour at 5° C. and the end of the reaction is monitored by HPLC (complete consumption of the aldehyde). Acetic acid (3 g, 0.05 mol) is then added. The suspension is heated to 40° C. and is maintained at 40° C. for 30 minutes. At this temperature, only the salts remain insoluble. The mixture is filtered at 40° C. through a sintered glass filter (No. 3) and the salts are washed on the filter 3 times with 100 ml portions of toluene. The filtrate is returned to a round-bottomed flask with 250 ml of distilled water, and the two-phase mixture is stirred for 20 minutes at 40° C. and then the phases are separated. The toluene phase is washed twice with 250 ml portions of distilled water and then concentrated to dryness on a rotary evaporator. The residue is taken up in 600 ml of isopropanol and 12 ml of toluene at 40° C. The expected product begins to crystallize and the temperature is allowed to return to ambient temperature overnight with slow stirring. The stirred suspension is cooled to and maintained for 1 hour at 5° C., then filtered through a sintered glass filter, and the filter cake is washed twice with 125 ml portions of isopropanol, sucked dry and dried in an oven under vacuum (35° C./30 mmHg/18 hours). A mixture of Z and E isomers (6) and (7) (91.7 g) is obtained with a Z/E ratio of 75/25 (IS IPLC) and a yield of 95%.

1. customequipped with a mechanical stirrer
2. additionAs the addition progresses
3. customcomplete consumption of the aldehyde)
4. temperatureThe suspension is heated to 40° C.
5. temperatureis maintained at 40° C. for 30 minutes
6. filtrationThe mixture is filtered at 40° C. through a sintered glass
7. filtrationfilter (No
8. wash3) and the salts are washed on the
9. filtrationfilter 3 times with 100 ml portions of toluene
10. customThe filtrate is returned to a round-bottomed flask with 250 ml of distilled water
11. stirringthe two-phase mixture is stirred for 20 minutes at 40° C.
12. customthe phases are separated
13. washThe toluene phase is washed twice with 250 ml portions of distilled water
14. concentrationconcentrated to dryness on a rotary evaporator
15. customat 40° C
16. customto crystallize
17. waitto return to ambient temperature overnight with slow stirring
18. temperatureThe stirred suspension is cooled to and
19. temperaturemaintained for 1 hour at 5° C.
20. filtrationfiltered through a sintered glass
21. filtrationfilter
22. washthe filter cake is washed twice with 125 ml portions of isopropanol
23. customsucked dry
24. customdried in an oven under vacuum (35° C./30 mmHg/18 hours)
25. additionA mixture of Z and E isomers (6)