Hello all,
First of all, I would like to take a moment to say that Rhodium's chemistry page is one of the most comprehensive archives that I have ever seen on any subject. I have always been staunchly anti-drug, but I admit that I have begun rethinking my stance after carefully reviewing current medical literature pertaining to entactogens, hallucinogens, etc.
I have attempted the demethylation of eugenol many times, although not for the purpose of MDP2P synthesis. (My purpose is to obtain the anti-oxidant 4-allylcatechol, but one of the ways of proving it is to methylate the product to safrole). This is not a straight-forward task; as Startinout/wacko-reaco stated earlier, the synthesis of 4-allylcatechol has not been well-studied in open literature.
I have a few comments regarding the properties of 4-allylcatechol and various methods that have been attempted:
1. 4-allylcatechol properties:
In response to Pyschokitty, 4-allylcatechol is indeed unstable under RT/exposure to light and air. I have a dish of 4-allylcatechol sitting in the lab that has turned from a light clear-yellow color to a dark red over the course of three days.
However, it must be noted that 4-allylcatechol does not decompose very quickly, provided that Lewis acids are not used in the demethylation process. Moreover, the "smokey" demethylated smell is due, in some part, to the interaction of AlCl3 with eugenol rather than some intrisinic property of 4-allylcatechol itself. I believe this to be the case because the demethylated product from pyridine hydrochloride does not particularly smell like smoke.
2. Pyridine hydrochloride
This method does work (I have never had problems obtaining 4-allylcatechol from pyridine hydrochloride) but the construction of a microwave reflux apparatus is probably necessary. I believe that this method is the best way of obtaining a sample of 4-allylcatechol for analysis, since the catechol spontaneously recrystallizes in high purity in situ following hydrolysis in an ice-bath.
3. Triethylamine hydrochloride
Triethylamine hydrochloride, by itself, does not work as a demethylating agent under microwave radiation. I suspect that the main reason is the high melting temperature (~260 C), but in the many trials that I have performed, the amine salt actually decomposes, leaving a polymerized tar substance.
4. Triethylamine hydrochloride and aluminum chloride under microwave irradiation:
I actually succeeded in a one-pot synthesis of safrole from this combination, although the yield was so low that I didn't bother isolating the product (most likely < 5% yield of a clear oil with a candy-shop odour).
5. Aluminum Chloride
Literature states that o-methoxy groups may be demethylated by the cleavage agent NaI/AlCl3, but I highly doubt that this will work, given the sensitivity of the double-bond to iodination. Nevertheless I have not tried this, and experimentation is king.
I have attempted cleaving the ether using AlCl3 independently in both solvent and solvent-free conditions. However, this does not seem to work, since product was not obtained after hydrolysis of the oxonium complex.
Thoughts:
Given that I have not tried SIBX, LiCl, AlI3, or other classical reagents such as BBr3, I cannot really say that (reasonable) demethylation of eugenol is impossible. It is possible, but to obtain it in large quantities will require a lot more research.
If anyone has any suggestions (Psychokitty and wacko_reaco, you guys/gals seem to know quite a bit about o-ether cleavage, do you have any ideas?)