Acetic Acid → 2-Methoxy-5-[2-(3,4,5-trimethoxyphenyl)vinyl]nitrobenzene
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH:6]=O.[Br-].[N+:16]([C:19]1[CH:20]=[C:21]([CH:42]=[CH:43][C:44]=1[O:45][CH3:46])[CH2:22][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O-:18])=[O:17].C[O-].[Na+].C(O)(=O)C>CO.C1(C)C=CC=CC=1>[CH3:46][O:45][C:44]1[CH:43]=[CH:42][C:21]([CH:22]=[CH:6][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:10]([O:11][CH3:12])=[C:9]([O:13][CH3:14])[CH:8]=2)=[CH:20][C:19]=1[N+:16]([O-:18])=[O:17]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 5 °C
Procedure
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%.
Workup
- customequipped with a mechanical stirrer
- additionAs the addition progresses
- customcomplete consumption of the aldehyde)
- temperatureThe suspension is heated to 40° C.
- temperatureis maintained at 40° C. for 30 minutes
- filtrationThe mixture is filtered at 40° C. through a sintered glass
- filtrationfilter (No
- wash3) and the salts are washed on the
- filtrationfilter 3 times with 100 ml portions of toluene
- customThe filtrate is returned to a round-bottomed flask with 250 ml of distilled water
- stirringthe two-phase mixture is stirred for 20 minutes at 40° C.
- customthe phases are separated
- washThe toluene phase is washed twice with 250 ml portions of distilled water
- concentrationconcentrated to dryness on a rotary evaporator
- customat 40° C
- customto crystallize
- waitto return to ambient temperature overnight with slow stirring
- temperatureThe stirred suspension is cooled to and
- temperaturemaintained for 1 hour at 5° C.
- filtrationfiltered through a sintered glass
- filtrationfilter
- washthe filter cake is washed twice with 125 ml portions of isopropanol
- customsucked dry
- customdried in an oven under vacuum (35° C./30 mmHg/18 hours)
- additionA mixture of Z and E isomers (6)
Sources & evidence
- ORD record
- ord-ef69a0b5b5e24d3e999af2b076b77429
- Source dataset
- uspto-grants-2004_07
- Patent number
- US06759555B2
Reaction notes
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