A friend of mine told me this interesting story the other night.. Apparently he accidently broke his only condenser while disconnecting one of the
hoses. Angered but not defeated he eyed the limited supply of chemicals at his disposal and here is what happenend:
In a round-bottomed flask equipped with magnetic stirring was added 250 mL of H2O, and 45 mL of 25% NaOH. 15 grams of hydroquinone was then added
followed by 26mL of dimethyl sulfate. The flask was stirred at room temperature and after 15 minutes it was obviously no longer basic judging from
the light color and flakes of hydroquinone floating around. At this point more 25% NaOH soln was added. In fact, he admits that too much base was
added at this point which really hurt the yield in this reaction by slowing it down considerably. Anyhow, after another hour white crystals began to
form out of the dark mixture and it took on the familiar smell of p-dimethoxybenzene. Stirring was continued for another 6 hrs, after which he became
impatient and proceeded to vacuum filter the crystals on a buchner funnel and wash them with H2O. Yield: 11 grams (58%)
A solution of 10 g of potassium bromide in 250mL acetic acid was stirred on a ice/salt bath. When the solution was sufficiently cold, 5mL of 91%
sulfuric acid was added slowly and the solution took on a light brown color. Over the course of the next 30 minutes, while maintaining the
temperature at 5 degC, 8mL of 35% hydrogen peroxide was slowly added dropwise and subsequently the solution was allowed to stir for another 2 hrs.
The soln was extracted w/2x75mL toluene and the extracts were washed w/50mL 5% NaOH, and then 50mL brine. The toluene was then removed in vacuo
yielding a brown oil of presumably 1,4-dimethoxy-2-bromobenzene, which was used directly in the following reaction. Yield was not determined but
appeared to him to be very good.
To an unknown amount of 1,4-dimethoxy-2-bromobenzene was added a soln. of 5 grams of glyoxylic acid monohydrate and 12 mL H2O. The solution was
stirred vigorously on a ice/salt bath until a temperature of 5 degC was obtained and it was maintained at this temp throughout the subsequent
reaction. Over the course of the next 30 minutes, 30mL 91% sulfuric acid was added dropwise; at this point the solution took on a dark black. The
stirring was continued for the next 6 hours, the solution gradually taking on a light pink color with off-white crystals floating in the mixture.
After completion of the reaction, the mixture was so viscous it could hardly be stirred. 100mL of cold water was then added, the mixture stirred for
a short time longer and the crystals were vacuum filtered. The crystals were suspended in 100mL water and sufficent 25% aqueous NaOH was added until
all of them dissolved into a dark brown solution. The solution was then extracted w/75mL toluene. The aqueous solution was once again cooled in an
ice bath and ice-cold conc. HCl was added which cleared the solution and caused the crystals to precipitate back out and they were once again vacuum
filtered and washed w/water. Yield: 20g of 4-bromo-2,5-dimethoxymandelic acid (86% from p-dimethoxybenzene)
To a solution of 40mL distilled water, and 20mL of 31.25% HCl was added a suspension of 20 grams of 4-bromo-2,5-dimethoxymandelic acid. The soln was
cooled on an ice/salt bath to 5 degC and stirring was commenced. Into an addition funnel was added 4mL 70% nitric acid and 10mL water. The dilute
HNO3 was added dropwise over about 15 minutes. The flask was removed from the ice bath and placed into a water bath maintained at 50 degC. It was
heated and stirred at this temperature for about 1 hr. The flask was cooled to room temperature and an ice-cold solution of 60mL 25% NaOH was added
which caused the unreacted acid to dissolve into the mixture. The remaining crystals were vacuum filtered and recrystallized from methanol. Yield
12.5g (74%).
Overall yield: 12.5g 4-bromo-2,5-dimethoxybenzaldehyde from 15g hydroquinone (37.5%)
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