Post 214369 (missing)
(foxy2: "2 Bromination of 3,4-dimethoxybenzaldehyde", Chemistry Discourse) in methanolPost 214376 (missing)
(foxy2: "Re: 2 Bromination of 3,4-dimethoxybenzaldehyde", Chemistry Discourse) in chloroformPost 529398 (https://www.thevespiary.org/talk/index.php?topic=12056.msg52939800#msg52939800)
(Captain_America: "5-Bromo-4-formyl-2-methoxyphenol", Novel Discourse) then swap with the methoxid and transform the -OH on para to S-R by tosylation/mesylation followed by mercaptan swap... It would of bee a nice shortcut to make the 4-alkylthio vanillin following the same strategy and then go from there, but I don't know if it would give good yields in bromination step to come, if so, then good - there is no reason going via acetoxy ester. Alternative solution would bee using a nice oxidative iodination method found by Kinetic that works on less activated substrates (maybee on 4-alkylthio-vanillin),Post 518568 (https://www.thevespiary.org/talk/index.php?topic=7492.msg51856800#msg51856800)
(Kinetic: "Iodination of arenes with KI and H2O2", Chemistry Discourse) very simple, high-yielding and perfectly OTC, good find Kinetic. :)First, you have to subject vanillin to a Dakin reaction (H2O2/NaOH), followed by methylation of the resulting phenol. 1,2,4-Trimethoxybenzene is extracted and subsequently purified by distillation, followed by Vilmeier-Haack formylation (DMF). Total yield from vanillin is 40-50%.
Yes, I know about the Vilsmeier-Haack formylation. The idea was to be able to use a phenolic formylation by methylating last since I don't have any POCl3 or other toxic alternative, and the Gattermann formylation seems like a nice way to poison myself. The cost to have DMS shipped by truck freight already has SWIM's funding for this project running quite low.
The route suggested by Captain_America which I had forgotten about seems viable although I guess I will have to synth some NaOMe.