Author Topic: 4-MMC Proposed synthesis  (Read 151 times)

solidstone

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4-MMC Proposed synthesis
« on: October 20, 2010, 04:09:56 AM »
I've been staring at 4-MMC good and long and think I have a viable synthetic route.

From Propylene glycol or Tartaric acid it is an easy step to pyruvic acid.

The acid chloride can be prepared using phosgene (it's over the counter, despite its danger... it's convenient)

There is a patent that shows the friedel craft will happen para and outlines the preparation of cathinones via Friedel craft.

So, in the presence of AlCl3 A friedel craft is performed utilizing toluene.

The last step would be to form the amino group.  I am uncertain whether this would be best accomplished before or after the craft addition.  In the patent I found it is done prior however they utilize a protecting group, I'm reading up more on alternative protecting groups, but think it could be easier to just worry about forming the amine after.

This looks to be very straightforward.  Anyone see any complications?

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6THT-48MY1K8-D&_user=10&_coverDate=06%2F06%2F2003&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1505333638&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=bfad1815454112ec57f6a71e77cb5b86&searchtype=a

"Pyruvic acid is easily prepared in 50+% yield from tartaric acid (over the counter in grocery stores) and potassium bisulfate." - Sauron (science madness)


akcom

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Re: 4-MMC Proposed synthesis
« Reply #1 on: October 20, 2010, 01:25:50 PM »
Just curious, how are you getting phosgene?

solidstone

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Re: 4-MMC Proposed synthesis
« Reply #2 on: October 20, 2010, 04:07:06 PM »
The way I see it you could go about it a few ways.  One could make chloroform out of bleach and acetone then subject it to heat and UV to get phosgene.

Or the simple reaction CO +Cl2 seems viable.  powdered zinc and some calcium carbonate heat to liberate CO.  Gas with Cl2 gas generated from TCCA or from MnO2 and HCl.

for dealing with phosgene I've heard the best approach is to gas the solution your working with.  Keep the solution on a scale and measure the progress of the reaction by weight difference.  Phosgene is also soluble in toluene, benzene and acetic acid, so it is possible to use a trap to dissolve any excess phosgene you would not want in your immediate environment.

Vesp

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Re: 4-MMC Proposed synthesis
« Reply #3 on: October 20, 2010, 05:18:22 PM »
The CO and Cl2 than must be passed through activated carbon - possibly as it is heated? I don't think it is a friendly or convenient  reaction but generally dealing with three toxic gases implies that it is not a friendly reaction.
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solidstone

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Re: 4-MMC Proposed synthesis
« Reply #4 on: October 20, 2010, 05:33:42 PM »
yeah...  I would vote for decomposing chloroform by heating.  More or less thionyl chloride of phosphoryl chloride could be used as well, but I saw phosgene as the easiest to produce and actually handle.  Mostly since it can be generated in a closed system and dissolved in a trap, limiting its exposure to your environment.

I think there might be better production of phosgene from CCl4 which could be prepared from gassing chloroform with Cl2. 
« Last Edit: October 20, 2010, 05:49:50 PM by solidstone »

Tsathoggua

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Re: 4-MMC Proposed synthesis
« Reply #5 on: October 20, 2010, 05:53:39 PM »
How practical would it be to liquify phosgene or its brominated equivalent, as I just bet carbonyl bromide as a higher BP than C=OCl.

Been thinking of a way to the bloody expensive and nigh on unobtanium oxalyl chloride starting with propylene glycol via the carbonate, a lab scale bottle of phosgene would be pretty handy for that sort of thing.
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solidstone

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Re: 4-MMC Proposed synthesis
« Reply #6 on: October 20, 2010, 05:58:40 PM »
you could just make thionyl chloride from phosgene if you needed a higher bp.

solidstone

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Re: 4-MMC Proposed synthesis
« Reply #7 on: October 21, 2010, 02:12:05 AM »
Heres and idea for a super simple over the counter method perhaps best suited for smaller scale (unless you have a bulk source for ephedrine or pseudo-ephedrine)

Methanol+ HCL ---> methyl chloride
CH3Cl + ephedrine friedel craft should yield both the ortho and para products, which can of course be oxidized easily to 2 and 4-MMC.

I think 4-MMC is a far more acceptable product than meth in todays culture (I'm from the east coast, we don't really do meth...).  Ephedrine could be got from the obvious plant sources and corresponding supplements.  Given how cheap 4-MMC is I do not see a huge economic incentive however I think it is a neat experiment in the friedel craft reaction.

Sedit

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Re: 4-MMC Proposed synthesis
« Reply #8 on: October 21, 2010, 02:28:32 AM »
HCl + MeOH does not make MeCl very well and even with a catalyst the yeilds where reported around 30% IIRC from someone over at sciencemadness.

Better to use HBr or NaBr + H+ else you will have troubles.
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solidstone

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Re: 4-MMC Proposed synthesis
« Reply #9 on: October 21, 2010, 02:47:28 AM »
good to know.  I am curious if the alkyl chloride will attack the amino group rather then attach via friedel craft...  perhaps a protecting group is needed or perhaps it will go once the amino group is saturated.  I'll do some looking.