There should be no issue with drying the AMS since water destroys it. I wish I could give you experimental data on how its used but I have never done it. I know there is a reference around here in a thread on methylating reagents. Due to the fact that it rearranges into Methylamine Bisulfate when heated there is a good possibility it is a radical reaction similar to the rearrangement reaction.

Like I said your best bet is to research it, use the search engine here and the web because I can not remember the details for the life of me only the fact that it can be used as a methylating reagent.

The synthesis is a Solvolysis reaction. As the Sulfamic acid is dissolved into the MeOH it is converted into AMS. When all of the Sulfamic acid is dissolved the reaction is complete. Use 3 times molar excess of MeOH and distill off 1/2 of the post reaction fluid and on cooling long needles will crystallize out. Make sure you stir it as refluxing because if not there is some kind of decomposition reaction that will taint the reaction brown. It also will cut down a normal 6 hour for one mol reaction down to only an hour or so.

     This is not true, There is a reference posted somewhere on this site here that speaks of using Ammonium Methylsulfate to Methylate Phenols. This should apply fine here as well even though I have never heard first hand home chemist use of it.

     AMS can be made very simply by refluxing Sulfamic acid in Methyl alcohol in dry condition and good stirring. On cooling large pure crystals of AMS can be filtered off and stored in a dry environment to prevent hydrolysis. The synthesis can be performed in an afternoon and a pound could be made cheep as chips. Its also much less toxic then MeI and many other methylation reagents.

I can't seem to find that reference through the search engine. Any idea which thread it might be lurking in? Do you remember whether the AMS was applied directly to our mono or dihydroxy aldehyde, or was it on something else which should behave similarly?


Besides the AMS, there are two interesting threads (1) and (2) on Sciencemadness regarding trimethylsulfonium bromide. The synthesis is OTC and simple, although the dimethyl sulfide byproduct will not be ideal for clandestine labs. I'll personally get around to this one some day.


MeBr would be easy on the acquisition front but not so home friendly for those who can't engineer an appropriate apparatus.

http://www.sciencemadness.org/talk/viewthread.php?tid=1261&page=4#pid157397

US patent 2490842 Anisole manufacture
Column 2 lines 6+
The methyl sulfate may also contain a metal substituent on the sulfate radical, as in the case of sodium methyl sulfate or potassium methyl sulfate, it may contain an ammonium substituent as in the case of ammonium methyl sulfate, or it may contain a hydrogen substituent as in the case of methyl acid sulfate.

US patent 2529887 Process for the preparation of anisole
Column 5 lines 30+
Suitable methylating agents for phenol include, for example, a methyl sulfate having the methyl group directly attached to the sulfate radical such as dimethyl sulfate, sodium methyl sulfate, potassium methyl sulfate, ammonium methyl sulfate, or methyl acid sulfate; also methyl halides such as methyl chloride, methyl iodide, and methyl bromide; and organic methyl esters such as methyl acetate.

Source: http://127.0.0.1/talk/index.php/topic,187.40.html

There is also further mention somewhere around here about it but atlest this provides a patent number so that you can go further with research by following the trail of references in the patents.

To make Syringaldehyde from 5-bromovanillin, DMF  is probably not necessary.

Very nice information. This method will probably be applicable to bromovanilin. MeOLi can be made by dissolving Li into anhydrous MeOH. CuBr and Cu(AcO)2 can be used instead of CuI. CuBr can be made by treating a CuSO4 solution with sodium sulfite in the presence of Bromide ions. The white precipitate (CuBr) is insoluble and can be filtered and washed with water before drying in a dessicator. For this reaction an inert atmosphere is compulsory because in basic condition the bromovaniline phenolate rapidely oxidises and the end product would be only tar.

I will follow the pyramid' idea about making the bromovaniline instead of the iodo one : Bromide salts are easiers to find and cost less. Bromine is more reactive than iodine and would give better yield eaven on high-activated rings like vaniline.

I would not choose neither the MeONa/DMF/Cu(I) nor the AcOEt catalysed methoxylation because I've read and eaven done some of these reaction and it always gave poor yield or black gunk. These methods only worked on paper. The main problem can be the miss of the inert atmosphere, but i didn't remerber the exact condition of theses reactions.

EtOLi/EtOH can lead to Escaline wich is legal and according to shulgin lacks some of the side effects of the mescaline.

The O-Alkylation can be performed with MeI or Me2SO4 but this latter can (and MUST) be replaced with Me3PO4 or Me2CO3. Both of theses give acceptable yields and are much less toxic and dangerous to use than Me2SO4 and MeI. Some forgotten methylating agent such as Methl mesylate or tosylate can be made from MsCl or TsCl and are very efficient. Tetramethylammonium salt do the job, too. Trimethylsulfonium is a very interesting alternative I've never seen as alkylating agent but I bet it would give acceptable yield and can be easily made.

The cold condensation at 0°C in MeOH with 3 eq. of MeNO2 give very high yield (above 95%) of nitrostyrene. All other hot amino-catalysed gave lass than 60% yield.

The reduction can be performed by Zn/HCl but it apparently worked only on small scales. This reduction method can be replaced by the well-known Al/Hg.

On the nitrostyrene, my favorite potential route is SnCl2 / Zn + NH4Cl. SnCl2 reduces nitrostyrenes to oximes, and Zn / NH4Cl reduces oximes to amines.

First reaction:

http://www.erowid.org/archive/rhodium/pdf/nitroalkene-stannite-2.pdf

Second reaction:

http://www.erowid.org/archive/rhodium/chemistry/oxime2amine.zn-af.html

NH4CO2H gives around 5% better yields than NH4Cl, but the latter is significantly easier to obtain. This is a two-step reaction, but it doesn't require any expensive or dangerous reagents, and both steps have nice yields. It remains to be seen if both can be carried out in one pot.

On the nitrostyrene, my favorite potential route is SnCl2 / Zn + NH4Cl. SnCl2 reduces nitrostyrenes to oximes, and Zn / NH4Cl reduces oximes to amines.

First reaction:

http://www.erowid.org/archive/rhodium/pdf/nitroalkene-stannite-2.pdf

Second reaction:

http://www.erowid.org/archive/rhodium/chemistry/oxime2amine.zn-af.html

NH4CO2H gives around 5% better yields than NH4Cl, but the latter is significantly easier to obtain. This is a two-step reaction, but it doesn't require any expensive or dangerous reagents, and both steps have nice yields. It remains to be seen if both can be carried out in one pot.

Hi,

could you give more information about the yield ? The NaBH4 followed by Zn/HCOONH4 give poor yield in my case. NaBH4 reduction of the double bond in AcOEt worked well but the nitro reduction failed in case of 2c-c, 2c-g-t-3 and allyescaline preparation. Gave only 20% yield...

The best yield and simple method is still the use of LAH in my opinion. Always acceptable yield (~60%) and easy work up. LAH give better yield on 3C and 4C compound.

Make a solution of 500g concentrated aq. HCl and 500ml methanol (5:4 weight ratio). Chill it to ~15C. Start mechanical stirring (400rpm is the minimum required, 500rpm is ideal). Add 50g of the nitrostyrene. Let it dissolve. Place in a water bath maintained at ~10C.
Weigh out 140g Zinc metal in powder form. Add half a teaspoon of zinc every 5-10 minutes. Reaction is exothermic and produces lots of bubbling. Keep reaction between 10-20C by varying the addition time. When all the zinc has been added, stir the reaction for a further 20 hours. In total the reaction took ~24 hours.
Workup as usual (evaporate all methanol, basify, extract with toluene, evaporate and distill under high vac.). amine distilled over at ~130C @ ~300-400micron. Yield is ~80%. (Sulfate salt is easy to make)

The method was tested on 4-allyloxy-3,5-dimethoxy-b-nitrostyrene and the first test gave 75% yield but when it has been tried to scale it up (30g nitrostyrene reduction) it failed and gave minimal yield. The main problem was the solubility of the nitrostyrene in the solvent . (conc HCl, iPrOH) was used. How did you solubilise you nitrostyrene in the mixture ? Is MeOH a better solvent than iPrOH ? Perhaps the allyloxydimethoxy was more tricky to get into solution than the trimethoxy. Next time, THF will be used as co-colvent.

could you give more information about the yield ? The NaBH4 followed by Zn/HCOONH4 give poor yield in my case. NaBH4 reduction of the double bond in AcOEt worked well but the nitro reduction failed in case of 2c-c, 2c-g-t-3 and allyescaline preparation. Gave only 20% yield..

The method is not analogous to the NaBH4 method and does not use a nitroalkane intermediate; rather, it uses an oxime. The yields reported in literature for CTH oxime reduction are more promising than those for CTH nitro reduction. The reaction you had trouble with isn't the one I was proposing, which is partially why I wasn't proposing it: CTH on nitroalkanes is a pain, and we're all aware of this.

If you look at the original paper which introduced CTH of nitroalkanes, you'll note that the only high yield reactions were the ones done on aromatic nitro compounds; the aliphatic reactions had lower yields. The paper on oximes describes only aliphatic reactions, with a wider variety of reagents, and higher yields across the board. Some other reductions of oximes have also been described and might be better than the method I suggested -- SnCl2 appears to be the real trick here, since it saves us from having to reduce a nitro. Oximes are easier to reduce in general, it would seem.

I agree that LAH is generally a superior alternative, but it is really goddamn hard to get hold of.

you can get online very very easy elemicin extract from elemi oil.

just use google first page and a few after.

isomerise with KOH
crack that alkene with dichromate too the aldehyde.

henry with nitromethane then reduce in acetic acid amalgum.

done home made mescaline and very very easy

the extract is quite expensive though

about $4 a gram on the site I saw but thats ok if your just making some for your self.

What reaction did you mean by henry?


I thought the most OTC would be (not my idea):

Vanillin + NaOH(aq) + NaI3.NaI + H2SO4 -> 5-iodovanillin (99% yield * (http://www.erowid.org/archive/rhodium/chemistry/iodovanillin.html))

5-iodovanillin + NaOH + Cu -> 5-hydroxyvanillin (99% yield, iodine can be recovered * (http://www.erowid.org/archive/rhodium/chemistry/iodovanillin.html))

5-hydroxyvanillin + acetone + dimethylsulfate + Na2CO3.H2O + KOH -> 3,4,5-trimethoxybenzaldehyde (94% yield * (http://www.erowid.org/archive/rhodium/chemistry/mmda.mescaline.html))

3,4,5-trimethoxybenzaldehyde + nitromethane + ammonium acetate -> 3,4,5-trimethoxynitrostyrene (* (http://www.erowid.org/archive/rhodium/chemistry/mescaline.cathyd.html))

3,4,5-trimethoxynitrostyrene + Pd/C + EtOH + HCl -> mescaline (* (http://www.erowid.org/archive/rhodium/chemistry/mescaline.cathyd.html))


Not sure if it'd be better to start from elemicin or vanillin though.

you can get online very very easy elemicin extract from elemi oil.

just use google first page and a few after.

isomerise with KOH
crack that alkene with dichromate too the aldehyde.

henry with nitromethane then reduce in acetic acid amalgum.

Why not ozonolysis? Reductive workup to the phenylacetaldehyde, reductive amination with ammonia, bam, mescaline.

Shroomedalice I am not clear on how exactly you are proposing to go from elemicin to 3,4,5-TMB utilizing KOH and dichromate. Would you mind elaborating?

A member that's now a guest isn't likely to answer in timely manner  You should probably register at Hyperlab since the citation of the article about this particular synthesis is:

Shamshurin, A A Journal of General Chemistry USSR 14, 211 (1944)

and you can probably get some help in translating since they have discussed it already  It's mentioned in this particular Hyperlab translation at the Collective:

https://the-collective.ws/forum/index.php?topic=20022