Permethylation of pyrogallol with DMS

[GC_MS]

The following procedure was developed after some tweaking here and there. Pyrogallol trimethylether may be a useful precursor for several PEAs for some bees buzzing around the forum.

Substances: 150 ml DMS (dimethyl sulfate); 300 mL 20% aq NaOH; 50.8 g pyrogallol; 100 mL acetone

Method: Pyrogallol was dissolved in 100 mL acetone. The aqueous NaOH solution and DMS were added portionwise with stirring: 20 ml aq NaOH + 10 mL DMS every 5 min. The reaction mixture was allowed to return to ambient temperature and the reaction continued overnight. It might be necessary to add a little bit of aq NaOH (pH should be neutral to slightly alkaline). Subsequently, the reaction mixture was acidified (HCl) and extracted with ether. The combined organic phases were washed with aq NaOH (until the aqueous phases became colourless) and the solvent removed via distillation. This resulted in a red oil, which after distillation under reduced pressure yielded 61.7 g (91%) of a yellow oil that solidified (white needles) on standing. GC was clean.

Note: take the necessary precautions for distilling the product. It easily solidifies in the condenser.

[heavenadisaster]

could this method be adapted using methyl iodide?

[GC_MS]

I have tried a similar method for p-methoxyphenol

Substances: 1 mol p-methoxyphenol, 1.1 mol DMS, 800 mL 20% aq NaOH, 2 mL acetone per gram phenol.

Method: 4-Methoxyphenol was introduced into a 3 L erlenmeyer flask equipped with a stir-bar and dissolved in acetone. The mixture was gently stirred (yellowish colour). The aqueous NaOH and DMS were added in portions: 75-100 mL aq NaOH + 15-20 mL DMS. The reaction was rather exothermic. When all DMS was added, the reaction mixture was gently heated (35-40°C) overnight (ca 6 hours). Acidification of the reaction mixture (concentrated HCl) and extraction with ether gave a dark burgundy mixture, which was washed with aq NaOH till the aqueous phase became colourless. Removing the solvent under reduced pressure yielded 133.4 g of a yellow oil that crystallized upon standing. GC is pretty OK (97%).

Purification via distillation may be necessary, depending on the use of the p-dimethoxybenzene.

Substituting DMS for MeI: buy PiHKAL. It's full with MeI methylation examples. Or UTFSE. Plenty of examples. However, ring methylation side reactions might occurr.

Acetone: the use of acetone as co-solvent helps preventing the saponification side-reaction of DMS, hereby increasing the yield and the amount of reagent. Substituting DMS for DES has been proven to work as well, though yields are about 5% lower.