Author Topic: vanillin -> TMA-2  (Read 2277 times)

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phenethyl_man

  • Guest
vanillin -> TMA-2
« on: October 04, 2004, 08:50:00 PM »
I don't believe I have seen this reaction scheme discussed on here before, but it seems like an easy route to TMA-2 using an easily accessible precursor.

Search for "2-methoxyhydroquinone" gave one article posted by Rhodium that follows a similar route, however the hydroquinone rather than an aldehyde is dimethylated and it is never formylated.

a. Dakin reaction on vanillin yields 2-methoxyhydroquinone.  I believe H2O2 under alkaline conditions will accomplish this.

b. Your choice of a phenolic ortho-formylation on 2-methoxyhydroquinone yields 2,5-dihydroxy-4-methoxybenzaldehyde.

c. Dimethylation w/DMS yields Asaronaldehyde [2,4,5-trimethoxybenzaldehyde];  plenty of representative procedures of this on rhodium.ws.

I shouldn't have to explain how to get to the target compound from there.  Anyone see any potential problems here?


Saddam_Hussein

  • Guest
asaraldehyde
« Reply #1 on: October 04, 2004, 10:55:00 PM »
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%.

You could also use TFSE.


Captain_America

  • Guest
For TMA-2 and sisters
« Reply #2 on: October 05, 2004, 01:41:00 AM »
Nah, simply methylate vanillin, brominate and do a methoxid swap and you'll have the asaraldehyde...

Post 214369 (missing)

(foxy2: "2 Bromination of 3,4-dimethoxybenzaldehyde", Chemistry Discourse)
in methanol

Post 214376 (missing)

(foxy2: "Re: 2 Bromination of 3,4-dimethoxybenzaldehyde", Chemistry Discourse)
in chloroform

For 2C-T and Alephs from vanillin it might bee better to make the 6-bromovanillin a la

Post 529398

(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

(Kinetic: "Iodination of arenes with KI and H2O2", Chemistry Discourse)
very simple, high-yielding and perfectly OTC, good find Kinetic.  :)

phenethyl_man

  • Guest
Re: First, you have to subject vanillin to a...
« Reply #3 on: October 05, 2004, 05:26:00 PM »

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.