Sciencemadness Discussion Board

hydrohalogenation of safrole

jwarr - 28-2-2010 at 20:55

I'm interested in the hydrohalogenation of safrole, placing an iodine on the beta carbon specifically. This is all hypothetical, but I'd like to hear from some more experienced people why this may or may not work.

Working with HI is not something I really have any interest in, so I was thinking of ways to try to avoid its use. Could one use a mixture of NaI, H2SO4, and safrole?

My thinking is that the sulfuric acid will donate a proton to the C/C double bond in safrole, after which a nucleophile will add onto the resulting carbocation in a markovnikov fashion. But is it possible the HSO4- would attack, as opposed to the iodide?

Comments, suggestions, flames all welcome.

turd - 1-3-2010 at 10:51

I have never done this so I cannot be of much help, but I faintly remember from discussions on Usenet that this looks only good on paper.

Some remarks: You will probably want to do this in a solvent like DMSO. Phosphoric acid may be better than sulfuric acid, since the latter oxidizes HI to I2. It will be much more economical to make the bromide and then generate the iodide in-situ with catalytic amounts of iodide during the next step. The Delepine reaction will NOT work on this substrate. And last but not least: if your goal is MDA or MDMA, stick to proven procedures, even if they have more steps. Unless you provide some references: this is not one of them.

nyll - 20-4-2012 at 09:16

Quote: Originally posted by turd  
I have never done this so I cannot be of much help, but I faintly remember from discussions on Usenet that this looks only good on paper.

Some remarks: You will probably want to do this in a solvent like DMSO. Phosphoric acid may be better than sulfuric acid, since the latter oxidizes HI to I2. It will be much more economical to make the bromide and then generate the iodide in-situ with catalytic amounts of iodide during the next step. The Delepine reaction will NOT work on this substrate. And last but not least: if your goal is MDA or MDMA, stick to proven procedures, even if they have more steps. Unless you provide some references: this is not one of them.


I think the Delepine reaction may work for making MDA in fact. There are even a couple of successful reports on erowid on the subject, though it is still quite poorly documented.

Some of these reports claim to have achieved good yields after refluxing bromo or iodo compound in hexamine for a few hours, while others say letting the mixture sit at room temperature for a couple of weeks also works.

http://www.erowid.org/archive/rhodium/chemistry/dmmda-2.html
http://www.erowid.org/archive/rhodium/chemistry/halosafrole....

GreenD - 20-4-2012 at 11:30

I've heard, from a variety of sources, that halogenation isn't worth it, unless the oxidation method is really impossible for you.

nyll - 20-4-2012 at 16:48

I've heard that from many sources also, but some still say otherwise. Most negative reports' workup involved bromosafrole in ammonia or methylamine solutions, while positive ones said iodosafrole (or even bromo) + delepine gave great results.

Maybe iodosafrole (or bromo also) in liquid ammonia/methylamine could be the way to go? Although, this would be super nasty and dangerous, and not something one should do at home. It also overcomes the main reason of attractiveness of the halogenation procedures, which are their sheer simplicity.

Anyway, I'm quite convinced the delepine actually works, the problem is the whole reaction period which remains unclear. Since safrole is now so hard to buy, and since I don't enjoy MDA/MDMA as I used to, we may never know afterall.

Nicodem - 21-4-2012 at 00:56

Please read the forum guidelines for posting! Using phrases like "I've heard..." without providing the source equals misinformation.

In regard to the Delepine reaction, even a superficial literature search would have told you that secondary alkyl halides do not react with hexamine (only a few alpha-haloketones are exceptions to this). That Hive post by Egotrip is the only one claiming such success, but the minimum critical review of what he wrote shows that his experimental lacks many details, including also the most essential data, such as the product analysis. He provides no references whatsoever, which in the view of the uniqueness of his claims raises serious concerns about the authenticity of his work.

The standard N-nucleophile commonly used for the reaction with secondary alkyl halides is the azide. There are many literature reports of successful use for the SN2 reaction of 1-aryl-2-bromopropanes with NaN3 in the literature. There are some reports at the Hyperlab forum as well (with references and analytical data), if for whatever perverted reason you prefer forum posts.

There is an abundance of people who post "reports" about their breakthrough syntheses in all kind of forums, but do not provide proper experimental data and most commonly no references whatsoever. Blindly believing such posts even when they are contrary to the science of synthesis is pretty much naive. The least one should do is demand the references.

simba - 22-4-2012 at 17:24

The use of liquid ammonia or methylamine will likely greatly lower your yields since the alkylation of the amine is unselective, and by using a large excess of concentrated reactant, you will privilege the formation of higher amines instead of the desired primary amine.