Author Topic: 'Novel' elemicin--> mescaline routes sans ozone  (Read 2069 times)

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  • Guest
'Novel' elemicin--> mescaline routes sans ozone
« on: February 07, 2003, 10:09:00 PM »
These routes are mainly 'novel' in that they are not in _PiHKAL_.  They are also 'novel' in that they may or may not (i.e., as of February 7, 2003, have been successfully applied to elemicin yet).  However, synthetically the following reactions are well-established in general.

Ozonolysis requires the use of an ozonator to generate ozone and is a fairly dangerous reaction due to its extreme reactivity.  The following synthetic outline(s) uses either KMnO4 or OsO4 and HIO4 (wet chemistry) to achieve the same end products.

From a book:

"The dihydroxylation of an alkene occurs by adding one OH group to each of the 2 alkene carbon atoms.  Because 2 oxygen atoms are incorporated into the product, the net effect is oxidation.  The products of dihydroxylation are vicinal diols, commonly called glycols.  They are made either with potassium permanganate (KMnO4) or with osmium tetraoxide (OsO4) as the oxidizing agent."

Dihydroxylation with KMnO4:

"KMnO4 is a readily available and inexpensive reagent.  It reacts with alkenes in slightly alkaline conditions [that us, where the pH is between around 7.0 and 7.5] to produce vicinal diols.  The reaction also gives manganese dioxide (MnO2), a brown insoluble product, as a by-product.  KMnO4 is purple in aqueous solution.  Manganese dioxide (MnO2), the product of the reaction, is a brown solid that precipitates from the solution.  Since there is a color change, oxidation with potassium permanganate can be used to test visually for the presence of a double bond.  Alkanes and cycloalkanes are not oxidized by KMnO4, so the purple color remains [if they are treated with KMnO4]."

Dihydroxylation with OsO4:

"The oxidation of alkenes with osmium tetraoxide (OsO4) gives excellent yields of vicinal diols.  However, this reagent is both expensive and highly toxic.  Therefore, it is used only in small scale laboratory synthesis, not in industrial processes.  OsO4 can, however, be used in a catalytic process in which the oxidizing agent is recycled.  Hydrogen peroxide (H2O2) is used to oxidize the reduced osmium back to osmium tetraoxide, which continues to oxidize the alkene to a diol.  This process allows the reaction to be carried out with only a small amount of the toxic OsO4."

Note:  under vigorous reaction conditions (high temperature, extremes of pH, long reflux times), KMnO4 would oxidize the elemicin all the way to gallic acid (3,4,5-trimethoxybenzoic acid).


"Vicinal diols are cleaved by periodic acid (HIO4) to yield aldehydes or ketones, depending on the number or substituents on the carbon atoms bearing the hydroxyl groups.  The periodic acid is reduced to iodic acid (HIO3) plus water.  Because vicinal diols are obtained from alkenes, the combination of dihyrdoxylation followed by oxidative cleavage of the diol provides an alternative to ozonolysis of alkenes to yield the same products."

3,4,5-trimethoxyphenylacetaldehyde (unstable in solution, use quickly after its preparation) is easily reductively aminated at pH 7 with ammonium acetate in MeOH and NaBH3CN (sodium cyanoborohydride) under an inert N2 or He atmosphere overnight to yield mescaline.  See _TS2_ under MDA via MDP2P.  Substitute 3,4,5-trimethoxyacetaldehyde for MDP2P.

Alternatively, using vigorous reaction conditions, KMnO4 can be used to make gallic acid from elemicin, which can then be converted to the aldehyde either through reduction of the gallic acid with LAH followed by oxidation with PCC (pyridinium chlorochromate) in methylene chloride (CH2Cl2) or by conversion of the gallic acid to the acid chloride with thionyl chloride followed by reduction with lithium aluminum tri-tert-butoxy hydride in dry ether to yield the 
3,4,5-trimethoxybenzaldehyde.  See _PiHKAL_ entry #96 from there. 

3,4,5-trimethoxyacetaldehyde can also be reduced with NaBH4 in water or alcohol at pH 7 followed by the primary alcohol's reaction with PBr3 and finally the Sn2 reaction of the bromoalkane with NaN3 in DMF followed by reduction again with NaBH4 to give mescaline.  Excess anhydrous ammonia can be used in place of NaN3 if either acetonitrile (ACN; CH3CN), dimethylsulfoxide (DMSO) or dimethylformamide (DMF) are used as the solvents.  The advantage of the latter is that the final reduction with NaBH4 or LAH is no longer necessary, though overall yields may suffer because ammonia is a much weaker nucleophile than is the azide anion (N3-).

* * *

"Jesus, how can shit be so easy?
How can one Chandra be so Levy?"-Eminem


  • Guest
You don't have any more precise experimental...
« Reply #1 on: February 07, 2003, 10:11:00 PM »
You don't have any more precise experimental suggestions to share?


  • Guest
No, sorry.
« Reply #2 on: February 07, 2003, 10:15:00 PM »
No, sorry, that is as much information as I can muster at the present time.


  • Guest
« Reply #3 on: February 08, 2003, 10:51:00 AM »
The KMnO4 reaction is also known as the Baeyer reaction, applied to detect C=C bonds. A brown precipitate (MnO2) demonstrates the presence of compounds with C=C bonds in your testing solution.
OsO4 is quite nice if you run a legal company, but for clandestine laboratories, it is as good as inapplicable. Maybe you could check out its $$$.


  • Guest
would isoElemicin be a propenylbenzenes?
« Reply #4 on: February 09, 2003, 10:23:00 AM »
would isoElemicin be a propenylbenzenes? and if that is the case would one be able to perform the oxidative cleavage @

so elemicin ---> isoelemicin via KOH
isoelemicin ---> 3,4,5tmba  via KMnO4

I know there are several posts on this topic, but there is no report on any actual attemps. (from the isoelemicin---> 3,4,5 tmba).


  • Guest
Beside the high price OsO 4 is extremely ...
« Reply #5 on: February 09, 2003, 01:02:00 PM »
Beside the high price OsO4 is extremely toxic, so even in a professional lab you usually don't want to use that chemical if you can avoid it.


  • Guest
a few questions
« Reply #6 on: February 18, 2003, 12:46:00 AM »
In Benzaldehydes from Propenylbenzenes and Cinnamic Acids.
It looks as if you can use,isosafrole, asarone. And for the solid supports if one uses Al2O3, how does one make alumina acidic, or if one uses Amberlite IR-120, I noitced that there are 2 diffrent kinds, one looks like ph normal, and one acidic, which one sould i use?


  • Guest
Alumina can be bought in acidic, neutral and...
« Reply #7 on: February 18, 2003, 01:48:00 AM »
Alumina can be bought in acidic, neutral and basic versions. Buy the cheapest Amberlite of the two, the difference is only which ion they have preloaded the resin with (H+ or Na+).


  • Guest
sorry, that wasnt clear
« Reply #8 on: February 18, 2003, 02:57:00 AM »
Im sorry I didnt make myself clear enough. The method calls for acidic alumina, I have access to normal alumina from my supplier, but not acidic alumina, can i make normal alumina, acidic.