Methylating Eugenol -Lone Ranger

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dormouse
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04-20-00 22:41
No 108467




Methylating Eugenol -Lone Ranger
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Methylating Eugenol

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Author Topic:   Methylating Eugenol
Lone Ranger
unregistered   posted 08-09-98 08:54 PM
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I know that many people would want to demethylate their Eugenol - and Strike covers this subject very well. How about methylating it? What is a good way to do this?

Rhodium
Administrator   posted 08-09-98 10:26 PM
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Nothing would be easier. Just dissolve your eugenol in aqueous sodium hydroxide/carbonate, and add a small excess of MeI or Me2SO4, stir for 24 hours... But your product is pretty useless - or do you have a great idea on how to make anything useful from the methyleugenol?

Lone Ranger
unregistered   posted 08-10-98 04:17 PM
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The trimethoxy substituted benzine compounds can be quite useful, but one would be hesitant to order such a compound. But ordering a dimethoxy or methoxy benzine with hydroxy where methoxy "should be" would not be such an "eyebrow raiser", and if the methylating procedure is general (I think it should be), they are very valuble starting materials.
Thaanks

Ritter
Member   posted 08-11-98 01:10 PM
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The tri-MeO substituted amphetamines could be made from eugenol very easily. I suppose the best way would be to run eugenol through that patent procedure for 3,4,5 tri-MeO benzaldehyde from vanilla everyone was ranting about a few months ago. A few modifications would have to be made. First the Eugenol could be demethylated and halogenated to 1-(3,4 dihydroxy phenyl)-2-bromopropane with aq. HBr and a PTC catalyst (Aliquat 336 is king). Bromination of ring w/ Br2/HOAc followed by the copper powder -Br-->-OH conversion will result in 1-(3,4,5 tri hydroxyphenyl)-2-bromo propane. Methylate all those -OH groups and run an azide swap with the 2-bromo group in carbitol/NaN3 and reduce Azide to amine using NaBH4, Al/Hg, or whatever you name it reduction and voila, TMA. Wow, thats a hell of a lot more complicated in writing than in my mind!

Rhodium
Administrator   posted 08-11-98 01:47 PM
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Yes, but nobody wants TMA. Perhaps making MMDA would be better, by hydroxylating the 5-bromo, followed by methylenation.

neocelsis
unregistered   posted 08-12-98 01:49 PM
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Ethylation of the 4 hydroxyl would probably be more interesting.

nubee · Master Archiver

what would this give...??

fogged · Tue May 03, 2005 2:03 pm

This post actually gave me something of an idea...

Consider the following scheme.
1 - Treat eugenol with HBr to form bromoeugenol. This may demethylate, I'm not certain, but anyway...
2 - Treat bromoeugenol with DMS, MeI or any other methylating agent to form methylbromoeugenol (if eugenol was demethylated by HBr this would require 2 eq. methyalting agent; if not, just the one).
3 - Ring-brominate the methylbromoeugenol. As I recall, simple AcOH/Br₂ bromination of 3,4-dimethoxybenzenes leads to 2-bromo-4,5-dimethoxybenzenes.
4 - Methoxylate this (2-bromo-4,5-dimethoxyphenyl)-isopropylbromide compound with sodium methoxide (and whatever the catalyst is, I cant remember, just look for a synth of syringaldehyde, that's certain to have it)
5 - Reaction of the resulting (2,4,5-trimethoxyphenyl)-isopropylbromide with sodium azide and reduction as discussed in the original post. Unless I'm quite mistaken, this should lead to TMA-2, in semi-decent yields.

The only query I have with this is that the bromination was noted from a post using veratraldehyde. The question is whether the bromination is predominantly directed by the methoxy groups, or if the aldehyde in that example was the key factor. If so, the bromination may not work as I've suggested above on this molecule. Does anyone have the post from the Hive that I'm referring to? Maybe I should put in a second request in the Hive files thread...

Be interesting to find out one way or the other, though! It seems to be a relatively straightforward synthesis, from all OTC materials. Be a bit of work, but potentially worth it!

If nobody's keen on searching for empirical evidence, I'd be interested in a critique of the proposed method from someone more knowledgeble than myself... Also, please nobody quote me on the above, particularly on the ring-bromination step. As i've just mentioned, I dont have any actual evidence to support it working on this molecule (hell, I can only vaguely remember it for the veratraldehyde!)