I posted a thread on DF a while ago regarding the virtues of Vanilin chemistry. It received minimal attention. Im pretty sure you guys already heard of Vanilin potential but I thought this thread could spark some ideas-QD

While browsing through some papers (what else?), I stumbled on a remarkable procedure regarding the iodination of vanillin. This beautiful, OTC and quite efficient procedure enables one to synthesize 5-hydroxyvanillin, from vanillin, in very high yields (and large scale) from the treatment of an aqueous solution of iodine and potassium iodide followed by hydroxylation catalyzed by a copper(I) compound or simply copper dust (see scheme provided below).

Now what Im really excited about is that 5-hydroxyvanillin is a powerful precursor to not one, not two, but 4 different PEA derivatives: MMDA, Lophophine, TMA and Mescaline.

As it can be seen on the scheme, once 5-hydroxyvanillin is in one’s hands one has two major options. Generate the methylenedioxy derivative or methylate the two hydroxy group in meta and para position. The latter substituted benzaldehydes are then treated with standards means of producing PEA or amphetamine derivatives.




1 Methylenation of catechols using dichloromethane and dimethylsulfoxide
Methylenation of catechols using dibromomethane and a PTC

2 Synthesis of 3,4,5-Trimethoxybenzaldehyde
EFFICIENT METHYLATION OF CARBOXYLIC ACIDS WITH POTASSIUM HYDROXIDE/METHYL SULFOXIDE AND IODOMETHANE
METHYL IODIDE preparation

3 and 4: Standard nitroaldol condensation to the corresponding substituted phenyl-2-nitropropene, with nitroethane and catalyst, followed by catalytic hydrogenation.
5 and 6: Standard nitroaldol condensation to the corresponding substituted nitrostyrene, with nitromethane and catalyst, followed by catalytic hydrogenation.

I'm pretty sure that the rhodium archives contain something to this effect. Actually, here it is.

http://www.erowid.org/archive/rhodium/chemistry/mmda.mescaline.html

Good thinking though, if you thought of that by yourself.

Actually I linked this already, look at the blue fonts on my post.

I2 is a bit of a turn off in todays weather. Would Cl2 be a suitable substitute in the hydroxylation of the vanillin or would its reactivity interfere with the reaction?

Im woundering if MEK condensation with the Methyl Piperonal would end in a product of 3-4MD-2 MeO-P2P. I hear that there is issues with this reaction using substituted benzaldahydes but nothing conclusive.

What is the consensus on the ethylated product here? Or brominated product for that matter?

I recently ordered some vanillin so expect at least a report to hydroxyvanillin soon enough, once it arrives.  I don't have any toluenesulfonyl chloride yet, but once I get that I will attempt trimethoxybenzaldehyde (and subsequently mescaline). 

Would trimethyl phosphate be possible to prepare from MeOH + phosphoric acid(H3PO4) under reflux?

I highly doubt it since reagent-grade H3PO4 is an 85 % aqueous  solution. All that water will gladly hydrolyze any phosphate ester present.

Heres a link that you may want to see. Its nothing special but it compliments this threed nicely. Its a synthesis of vanillin.

http://valhalla.chem.udel.edu/vanillin.html

I also noticed Quantum that you left out Demethylation of the Vanillin and ring formation to piperonyl. Everyone knows what happens after that but that is just one more product that someone could make from Vanillin.

Uhm, i'm not sure what industrial route you want, but if you want the aldehyde, here's an interesting procedure that I posted a while back.

https://www.sciencemadness.org/whisper/viewthread.php?tid=10132#pid120381

To avoid the use of elemental Iodine or Bromine one could proceed in a manner stated below.



Both reactions stated start with the mixture above the arrow with the slow addition of the materials below. I will search for some references to back up my claims also.

How do you feel the yeilds would compair against the means you proposed Quantum for the iodonation seeing as NaBr is easier to aquire then I2 and NaI?

[edit]

Here is a decent link of someone documenting the whole synthesis to (MeO)3BnO
http://www.hiwe.info/index.php/drill/comments/synthesis_of_mmda_and_mescaline_from_vanillin/

Synthesis of vanillin and Syringaldehyde from maple syrup. If someone has access to this paper please post.

A sugar-free maple flavor concentrate made by extracting maple sirup with chloroform has been found to contain vanillin, syringaldehyde, and dihydroconiferyl alcohol, aromatic compounds related to lignin. When a chloroform extract of the sap of the maple tree is subjected to alkaline hydrolysis and nitrobenzene oxidation, the amounts of vanillin and syringaldehyde increase. The amount of dihydroconiferyl alcohol in this sap extract increases upon alkaline hydrolysis and then decreases upon subsequent nitrobenzene oxidation. Nitrobenzene oxidation of lignin-like material in the sap yields vanillin as the chief reaction product.

Reference: http://www3.interscience.wiley.com/journal/119736318/abstract?CRETRY=1&SRETRY=0#ss1


Also a text from the old Rhodium archives,
http://www.erowid.org/archive/rhodium/chemistry/syringaldehyde.spruce-maple.html

I just bought 500g of synthetic vanillin, the msds isnt so clear nor if the CofA however I believe it to be, any one think of a quick indicator?

But myself and lab partner plan on a few little adventures of course only whilst dreaming and asleep

vanillin thiourea/AlCl3 demethylation http://www.sciencemadness.org/talk/viewthread.php?tid=11607

"A solution of 212g (1.6 M) AlCl3 (anhydrous) and 63.28g (0.8 M) Thiourea in 1L of DCM was made and let stir for 30 mins at room temperature, protected from atmospheric moisture. To this a solution of 60.86g (0.4 M) of Vanillin in 300 ml DCM was added. The solution was brought to reflux left with good stirring for 5 hours. During which time the mixture had turned turned slightly darker. The reaction was cooled to room temperature and made acidic with 15% HCL. The HCL was added slowly and in small amounts. The resulting solution had a yellowish clear upper layer, a red middle layer, and small brown oilly bottom layer.

The aqueous layer as removed. The red DCM layer was washed with 2 x 300 ml of H20, and the H20 added to the removed aqueous layer. The brown layer was washed with dissolved in 300 ml ethyl acetate and filtered. The aqueous layer was extracted with 3 x 300 ml ethyl acetate. All the ethyl acetate was combined and the solvent was removed over low heat. A large yellow precipitate with a melting point of 157C and weighting 49.6g (81.4% yield) was left.

Then treat the demethylated vanillin (3,4-DIHYDROXYBENZALDEHYDE) as a cathechol and methylate it with DCM

A solution of 110 g of catechol, 120 ml of 50% aqueous sodium hydroxide and 200 ml of DMSO was heated to 98°C and stirred at that temperature for 30 minutes. This solution at 98°C. was added over a 30 minute period to a refluxing solution of 120 ml of methylene dichloride in 300 ml of DMSO. Thereafter, the reaction mixture was stirred at reflux for 1.5 hours. Steam was then passed into the mixture to achieve steam distillation of the product. The distillate (600 ml) was extracted with 100 ml of methylene dichloride, which extract was washed once with 50 ml of water. The methylene dichloride solution was then concentrated in vacuo at 40°C. to yield 119.4 g. of a colorless oil. Gas chromatographic analysis showed 97.5 percent methylenedioxybenzene. Yield 116.4g (95.4%).

This yeilds piperonal, then this can be reacted with EtNO2 to yeild MDP-2-NP
http://www.erowid.org/archive/rhodium/chemistry/mdp2np.html

15g of piperonal was dissolved in 40ml of methanol under stirring in a 250ml Erlenmeyer flask. When all of the piperonal had dissolved, 7.1g nitroethane was added to the solution. The flask was put in a ice/salt-bath with magnetic stirring, and when the temperature of the solution had dropped to 0°C, an ice-cold solution of 4g of NaOH in 20ml H2O was added at such a rate that the temperature never rose above 10°C. A white precipitate formed at the bottom of the flask during this addition, which was broken up with a glass rod. The stirring was continued for another hour, while the temperature of the solution was never allowed to rise above 5°C, and at the end of this time, 100 ml of ice-cold H2O was added to the solution, which caused even more precipitation of white solid. The whole slurry was poured into 100 ml of ice-cold 2M HCl solution in a 500ml Erlenmeyer flask, which was gently swirled, and there was a slight bubbling and fizzing, with the color of the solution shifting from white to blue to green to yellow in under a minute. Quite spectacular! When the fizzing had subsided, the solution was once again placed in in an ice-bath with magnetic stirring. When the temperature had dropped to about 5°C, the solution was clear with yellow granules of crude product at the bottom. The granules were filtered with suction, and recrystallized from IPA. After air-drying, the canary-yellow crystals amounted to a yield of 65-70% of theory.

The MDP-2-NP can be reduced to MDA with Zn/HCL Al/Hg or  Ni urishubara!


Glorious! The only hard part about this process is obtaining EtNO2 but I have found  an australian supplier of this, or just make it from diethyl sulfate (120g) and sodium nitrite..........

I love vanillin! now to TMA and some more psyfun!

I agree with Enkidu - from what I've heard, mescaline is a much better phenethylamine as far as visuals go. 

Formula 409 - I would recommend a different dihalomethane than methylene chloride.  I have attempted methyleneation with dichloromethane, and yields are always low.  The problem being the low reflux temperature (and thus slow progression of the reaction).  Use methylene bromide, or methylene iodide - methylene iodide being produced with sodium iodide/acetone/methylene chloride under pressure.