(Hive Bee)
10-13-04 13:53
No 535646
(Rated as: good idea!)
Since the begining of The Hive there have been several attempts to synthesize this amazing psychedelic fom easily obtainable chemicals. Most of them strated by monomethylation of hydroquinone, followed by Reimer-Tiemann formylation of thus obtained p-methoxyphenol. The isolated 2-OH-5-MeO benzaldehyde is then methylated to get the much desired product, 2,5-dimethoxybenzaldehyde. The true pioneer of this method is Antoncho, who has made several attempts to prepare that damn aldehyde, bu AFAIK he wasn't very successful
(feel free to correct me if I'm wrong). The problem with this method is major tar formation during formylation if one does not follow the procedure correctly. Therefore I propose a new, kitchen (as Antoncho would say
) synthesis of 2,5-dimethoxybenzaldehyde.Step 1: Bromination of Salicylaldehyde
Lugh has posted an article in Post 511284 (lugh: "5-bromosalicylaldehyde", Chemistry Discourse), but "deutsche sprache" is kinda like ancient hieroglyphics for me. I briefly understand what they say and as far as I can see it is a standard Br2/GAA bromination. One could therefore easily use a procedure for brominating vanillin as an example. I believe (or should I say, hope) that hydroxyl group would push the bromine to the para position, so the main product would be 5-bromo-2-hydroxybenzaldehyde (5-Br salicylaldehyde).
Patent US4551558 - Bromination of substituted benzaldehydes
../rhodium /345-tmb
Step 2: Methoxylation of 5-bromosalicylaldehyde
../rhodium /arylhal
Post 503332 (Rhodium: "Methoxylation of Aryl bromides cat. by Cu(II)-CO2", Chemistry Discourse)
Post 511008 (demorol: "Methoxylation of various aryl bromides", Chemistry Discourse)
Post 477850 (Rhodium: "ArBr --NaOMe/Cu(I)--> ArOMe", Chemistry Discourse)
Preparation of alkali metal alkoxides:
Post 257912 (Antoncho: "Alkali metal alkoxides: finally, OTC!", Novel Discourse)
Post 512006 (Nicodem: "The patents work", Newbee Forum)
Step 3: Methylation of 2-OH-5-MeO benzaldehyde
This step is probably the one that is the most widely covered at The Hive. Here are some links, just to get the impression of what I am talking about.
Post 348592 (Antoncho: "Methyl iodide methylation of 2-OH-5-MeO-BA.", Chemistry Discourse)
Post 511704 (Aurelius: "O-Alkylation Agents: Synthesis and Use", Methods Discourse)
../rhodium /me3po4.
You all know how the things go from here. I wold be thankful if bees would now reply to this post and share their thoughts on this project.
(Hive Bee)
10-13-04 14:24
No 535649
Hey demorol,
That salicylaldehyde approach is very interesting, and has been the subject of some of my literature study a while ago. The project was put on hold, due to other, more interesting practical work. Very nice to see you bring the subject back again
.My reason of interest was not directly aimed at the synthesis of 2,5-dimethoxybenzaldehyde, and consequently 2C-B or other 2C-H derivatives. 2C-B is an illegal substance where Saddam resides, and he already is familiar with its effects anyway
. However, the 5-EtO looks very interesting from the pharmacological, chemical and legal point of view 
. Swap NaOMe for NaEtO and you've got your precursor benzaldehyde.For the bromination of salicylaldehyde, one might want to try MeOH/Br2. If the product does not precipitate from MeOH by itself, you might want to evaporate some of the solvent prior to addition of water.
Have fun with the project
President of the Iraqi Chemical Weapons of Mass Destruction Development Society
(Hive Bee)
10-13-04 18:12
No 535669
Here o-Anisaldehyde brominated however yields aren't high.
Post 532051 (Captain_America: "5-bromo-2-methoxybenzaldehyde", Methods Discourse)
and here you have 5-bromo-o-anisaldehyde prepared using oxone, yields are in the 70% range.
Post 532056 (amine: "Bromination of Electron Rich Benzaldehydes", Methods Discourse)
The ring seems slightly deactivated by the aldehyde group you could aways go ahead and use one of the more stronger bromination techiques using NBS and FeCl3 to get those 90%+ yields (which I am sure you know about...sine you found the article
) Post 459979 (demorol: "High-Yielding Halogenations using Halosuccinimides", Chemistry Discourse)
(Stranger)
10-13-04 22:42
No 535705
Since the begining of The Hive there have been several attempts to synthesize this amazing psychedelic fom easily obtainable chemicals. Most of them strated by monomethylation of hydroquinone, followed by Reimer-Tiemann formylation of thus obtained p-methoxyphenol. The isolated 2-OH-5-MeO benzaldehyde is then methylated to get the much desired product, 2,5-dimethoxybenzaldehyde. The true pioneer of this method is Antoncho, who has made several attempts to prepare that damn aldehyde, bu AFAIK he wasn't very successful (feel free to correct me if I'm wrong). The problem with this method is major tar formation during formylation if one does not follow the procedure correctly.
Tar production is always a considerable side-reaction (sometimes main reaction
) in the Reimer-Tiemann formylation. However, a bee with average chem skills should be able to pull at least 50% yield of the pure benzaldehyde if p-methoxyphenol is used as precursor. Admitted that the steam distillation is time consuming and should be followed by an additional distillation (Vigreux), the method is as OTC as you can get.Lenin has tried Reimer-Tiemann formylation of p-methoxyphenol several times, always in the 0.5-1 mole range, and always was succesful (except the first time
).