Grimble_Gromble (Stranger)
12-08-01 17:50
No 245618
      Methylation with MeI  Bookmark   


I've looked for about methylation with methyl iodide to make trimethoxybenzaldehyde. I found somethings, but not exactly what I want.
What I found that's here:

* Quinacetophenona is converted into a monomethyl ether by cooling a solution in acetone to room temperature, adding potassium carbonate and methyl iodide, and refluxing for 6 hrs.
* Carbohydrates are methylated by combination of methyl iodide-silver oxide (barium oxide can replace Ag2O(1)).
Kuhn(2) found that carbohydrates can be completely methylated in a single step by silver oxide and methyl iodide if dimethylformamide is used as solvent. The carbohydrate is dissolved in 10-25 times its weight of DMF and treated at room temperature with MeI (3equiv. per OH group) and silver oxide (2 equiv. per OH group).

Have anybody ever maked trimethoxybenzalheyde form 5-hidroxy-vanillin using methyl iodide? And what were the conditions and the solvent used?

I would appreciate if you give me some information.


Reagents for Organic Synthesis
Louis F. Fieser and Mary Fieser., 682,683 - (1967)

(1) - R. Kuhn, H. Baer, and A. Seeliger. Ann, 611, 236 (1958)
(2) - R. Kuhn, H. Trischmann, and I. Lw, Angew. Chem., 67,32 (1955)crazy
(Chief Bee)
12-08-01 17:56
No 245622
      Re: Methylation with MeI  Bookmark   

Search for a methyl iodide methylation of a phenol in Pihkal, and then just double the amounts of base and methyl iodide, as there are two phenolic groups to methylate.
(Official Hive Translator)
04-29-02 18:10
No 303013
      Not that easy!  Bookmark   

Believe it or not, there isn't a single proc in PiHKAL that mentions aMeI alkylation of an ortho-substituted benzaldehyde!

This is rather important, since:

a) Benzaldehydes are less nucleophylic, so the conditions described for phenols shouldn't bee strictly adhered to (SWIA knows for a fact that methylation of vanillin w/NaMeSO4 proceeds much worse that HQ, e.g.)

b) Ortho-position is especially deactivated by the aldehyde group

c) Am i not correct to assume that simply inreasing the rxn time can bee insufficient,since MeI will hydrolyse (well, methanolyse) over time in alkaline solution??

d) Performing it in acetone DOES NOT seem to bee an option, since it is obviously for a reason that Shulgin never does it on aldehydes w/out a PTC, while w/phenols he always does it 'straight' (yes, i shuffled the whole PiHKAL back and forth ten times looking for an example!!!)

SWIVitsh did itlike this: stirred at RT for 24 hrs, then refluxed for an hour, and got a 31% yield, yuck. Obviously, 1hr doesn't sound right, but who will guarantee that at longer reaction times all MeI won't simply fall apart? Can anyone give a poor bee a clue, please?