30 grams of vanillin (USP) were dissolved in 150ml GAA (homemade from vinegar). This process is endothermic, and it took ~10 min for the vanillin to finish dissolving, even with heavy magnetic stirring. The mixture turned slightly yellow. 48 grams NaBr (pool supply >99%) are dissolved in 75ml dH2O in another flask, and is then added to the GAA/vanillin flask. 11ml 95% H2SO4 is diluted with 20ml GAA in a beaker. The temperature quickly rises, and the beaker is placed in a refrigerator for 20 minutes until it is somewhat below room temperature. The GAA/H2SO4 and GAA/vanillin mixtures are then poured into a mason jar in a water bath with magnetic stirring, and allowed to sit for several minutes.
22ml 30% cold H2O2 is then measured out, and added in 1ml portions every 3 minutes. After each addition, a column of reddish-brown fluid formed in the vortex caused by the stirring, and it took a few seconds to dissolve. Ice was added to the water bath during the addition so as to keep the temperature between 15 and 25C. After approximately 30 minutes of the addition (~10ml H2O2), a yellow precipitate started to form. After the addition was finished, the mixture was stirred for 90 minutes, and then diluted with 400ml cold water. By this point, the mixture had become too thick to stir magnetically, and so was stirred manually at approximately 1 minute intervals for 20 minutes. The mixture was filtered, and the yellow filtrate washed with 100ml cold dH2O.
The liquid was placed in the refrigerator for 24 hours, but nothing else precipitated. The filtrate was dried over calcium chloride to constant
weight. Yield: 27.27g (60%)
A melting-point test was not performed.
This reaction was a precise halving of Uemura’s wonderful writeup Post 297806 (https://www.thevespiary.org/talk/index.php?topic=9683.msg29780600#msg29780600)
(uemura: "How to prepare hydroxyvanillin", Methods Discourse), with the exception of the NaBr. The experimenter spaced out whilst weighing the NaBr, by measuring precisely half of Uemura’s value for KBr. The substitution should have been equimolar, not equimassive. The H2O2 may have been added too quickly, since the color of the solution oscillated from brownish-red to yellow in between additions. The high bromine concentration (both from adding H2O2 too quickly and using too much NaBr) probably accounts for the lower yield.
Even with these mistakes, the reaction went very smoothly, and exactly as Uemura wrote--the Br-vanillin didn’t even gum the filter paper. If only everything was this easy.
Complete writeup on the rest of the mescaline synthesis to follow, probably next week.
- MethyMouse