Author Topic: possible improvement on bromosafrole->MDMA -drone 342  (Read 5440 times)

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dormouse

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possible improvement on bromosafrole->MDMA -drone 342
« on: April 19, 2000, 11:52:00 AM »
Author    Topic:   possible improvement on bromosafrole->MDMA
drone 342
Member     posted 09-18-98 01:35 PM          
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Recently, I pose the question of the use of sodium methylamide as a potential nucleophile to react with bromosafrole to form MDMA. This idea didn't seem to get much of a response. I feel this method is worth further inquiry, and so I'll pose the question again -- why not? Methylamine is relatively easily isolatable as a liquid (its bp is around -5 deg C), and by simply adding a dash of sodium, you can make the sodamide. This, when added to bromosafrole would readily substitute, forming MDMA and NaBr.

So why not? True, the ring *might* not care for this treatment, but my suspiscion is that its more stable than people give it credit for. Any thoughts? Ideas regarding technique?

This really looks like it could be a nice method. Why isn't it used?

-drone #342


drone 342
Member     posted 09-20-98 03:21 PM          
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Hmmm. This would seem like the kind of thing people would get hot and bothered about, yet no response! Hmmm.

Well, I've been thinking, and I realized a few more things about this method:

1)Would happen very quickly, and provided there are no side reactions, there would be very high yields.

2)alkali alkylamides are actually quite stable and isolatable, so preparing and working with this starting material material (alkali methylamide) would be cake (relatively speaking; shit still has to be anhydrous.)

3)The temps would probobly have to be low.

4)If the methylenedioxy ring is too delicate, resoring to the use of another allyl benzene as a starting material might be fortuitous.

So any ideas, or shall I continue my speculative monologue sans critique/input?

-drone #342


Rhodium
Administrator     posted 09-20-98 05:44 PM          
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I think there is too much speculation and too little groundwork... You have known the halobenzene/enolate reaction for several months, and still you haven't posted any conclusive evidence if the reaction even works or not?

I there is too much talking and too little


drone 342
Member     posted 09-21-98 05:54 PM          
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I've known about the enolate/halobenzene reaction for YEARS, and gave a nice bibliography that shows several examples and variations on it; including the use of bromobenzene in DMSO.

I'm scratching my head here, Rho. I really can't think of any more ways to conclusively prove that it does indeed work. Geez, if peer-reviewed articles by respected members of the scientific community aren't enough to sway you on this one, then you're on your own. Have you taken a look at those articles?

-drone #342


Rhodium
Administrator     posted 09-21-98 08:14 PM          
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I've read one of them, the one posted at Optimus Prime's Journal site. I'm not saying that it won't work, I'm just curious why you aren't developing a nice DMSO/PhBr/acetone synth of your own, instead of citing a whole bunch of articles ONLY. Literature searches isn't the hard part if you've got the resources to do it, it is the development of a usable method.

Take a look at all your posts in this forum, they involve loose speculations all of them, and no real conclusions. And then you wonder why you get so little response?

Say, if you took all the many tens of refs on lignin oxidation/hydrolysis you've posted here, read them, went over to some kind of wood processing industry and got yourself 10 kilos of suitable lignosulfonates or whatever, and then played around with them for a while, and developed a way of making syringaldehyde and vanillin available cheap and easy for anyone.

It is a waste of your talent to just browse Beilstein Crossfire and the rest of the chem literature, when you can do so much more useful things in the lab! You have a much greater potential than you have been showing here lately.


drone 342
Member     posted 09-22-98 11:12 AM          
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I have many interests, and they cover many fields. I looked into lignosulfonate chemistry, came up with a lot of stuff, but my interest in it waned (I've secured a bulk supplier of 3,4,5-trimethoxybenzaldehyde, so the need for it seemed less important.) This was a file sitting in my cabinet for the last year or so, and I thought I'd share what I had along with a little bit of Beistein for those less fortunate.

Regarding the bromobenzene/DMSO/acetone enolate reaction, I felt no need to come up with developing a personal methods, since the kind scientists who published the articles I reviewed already came up with a practical method. In highly explicit terms, they described in full and complete detail their experimental methods for producing P2P. The method is there, and there's really not too much one could do for improvements.

I'm not sure what you're looking for on this one. Literature searching is a bit of an art, and few people have the resources that their disposal that I do. Until I came along, nobody even discussed this method, as well as a lot of other reactions on The Hive as well.

For that matter, regarding references and literature, I wouldn't be casting too many of the first stones if I were you. Looking at a few FAQ's you've put together, there seems to be *a lot* of verbatim quoting regarding experimental sections. Not to say that its a bad thing (Sasha does it throughout the second halves of PiHKAL and TiHKAL, and doesn't even footnote it), I just want to frame this critique in the aproppriate context. Refereing to the appropriate literature is crucial, and I don't think I deserve such criticism for it.

So what exactly do you want? Do you want personal lab notes on the reaction? What scrap of information haven't I covered regarding the enolates? I'm all ears.

There are millions of avenues that research may be lead down. Millions of quesitons, and some have been already ppartially answered. My mind is constantly active, asking these questions. So as to make it simpler for those that follw, I provide lists of information I've gathered along the way. I still have my pet projects that I devote real lab time to, but more on those prolects will follow later.

-drone #342


Rhodium
Administrator     posted 09-23-98 06:59 PM          
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I am not talking about my own findings, the FAQ's I've put together are merely compilations of information from numerous journal articles, where in each and every text one have what is necessary to synthesize the final product.

Before I put up my Quaalude FAQ, everything that could be found on the net was one wrongly translated copy of Klosa's synth, nothing else. Now we have at least four different methods to use, and when I've gone through the precursors chapter once more, it can be made from earth, fire and water.

How long would it take for you to write up something on acetone enolate/bromobenzene?

1) Prep of bromobenzene
2) Prep of acetone enolate w/ Na isopropxide
3) Synthesis of P2P w/ purification.

If you could go all the way making something like that, you are making yourself MUCH more useful than when pointing into a stack of journals saying "you may find what you are looking for there", as you are doing right now. Yes, I can go and extract the relevant info from those sources, but my spare time is unfortunately limited...

Look at my Pseudonitrosite FAQ for example. Not a single thing is discovered by me. I just went through all the literature I could find on the subject, sorted out the relevant info, translated the experimental procedures into english and wrote an illustrated explanation to the reaction and put it at the top. I think I made many people a much greater favor doing it like that, than just posting the reference section and telling people that pseudonitrosation can be done.

The truly original projects I work on, I don't feel I can divulge to the general public before they are completely finished...

I just want you to fulfill all your projects, I think it is better if you publish 5 complete reports on a few reactions, intead of 10 drafts... But again, this is just _my_ thoughts on it all...


drone 342
Member     posted 09-25-98 11:31 AM          
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Rhodium,

Hmmm. Well, I guess I can see that. The way I see it though, I want to share my ideas as much as possible, so as to catalyze more creative thought, and to get good input from others. Also, some of this is in hopes that perhaps somebody else has done similar work, and so I won't have to repeat myself -- this has rarely been the case, but who knows. The other hope is that other people will take greater interest in these ideas, and a discussion can start on them.

Anyways, I realize that some are less fortunate than I, and whereas I and others can head to the library and pick up copies of just about anything, others aren't so lucky. For those poor devils, I'm putting all the relevant data I have regarding enolate chemistry on my webpage. I'm currently editing the documents, putting in the tables, etc. Hopefully soon, even more of the good citizens of The Hive will truly reap the benefits of my 100% volunteer labor.

The one problem here is that I simply don't have time to put everything up on the net. I am constantly living and breathing chemistry, and new ideas and interests come to me quickly. Merely making photocopies of my collection of literature would cost several hundred dollars. Already, simply getting people the information I already do takes a great deal of resources; providing FAQ's on inorganic amide chemistry, Snr1 enolate reactions, the various alternative metal reagents for reductive amination, alternative sources for phenylacetic acid and phenylacetone, new methods for alkylating amines, new methods of adding halogen acids across double bonds, starting materials and synthetic methods for preparing exotic fentanyl analogs, new methods for producing benzaldehydes, and benzedrine from alanine is not feasible.

The reason I provide the information I do is not out of malice, or laziness, or personal gain. Far from it; the reason I do is because I think it will help.

-drone #342


drone 342
Member     posted 09-25-98 11:37 AM          
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On second thought, I better qualify those last couple of sentences. The reason I post is for discussion; I hope new ideas will come out of it. I hope that other people will take interest, and come up with independant input on these topics.

But lets try now to improve the signal-to-noise ratio in this section, and get back to the topic at hand. Why will or won't this work, and which conditions might be most desirable?

-drone #342


drone 342
Member     posted 09-27-98 05:44 PM          
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Examples abound of nucleophilic addition to methylenedioxybenzene-related compounds. This reaction should work. I'll do some extensive information strip-mining, and I'll come up with some proposals for conditions. Eairlier, there was discussion regarding the use of nitromethane with the Grignard reagent of halosafrole, but this was tossed out when people started thinking that suck Grignard reagents wouldn't be stable. With sability out of the picture as an issue, We're back in business.

This actually would be a pretty good way of doing it with methylamine of course. The beautious part is that there'd be no concern about side reactions -- there's no way that tertiary byproducts could form!

Ooooh, spicy!

-drone #342


Labrat
Member     posted 09-29-98 09:28 AM          
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Sorry to ruin the party, but something came to mind yesterday. You're proposing to use a stronger nucleophile then methylamine, c.q. a metal methylamide to displace the bromide group in bromosafrole.

But the metal methylamide is not only a strong nucleophile, but also a strong base. This strong base can very probably abstracts the benzylic proton from bromosafrole with elimination of the bromide group to give isosafrole. This could very well be the dominant reaction, since the amide is a strong base. Lr/


drone 342
Member     posted 09-29-98 01:41 PM          
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LR,

Though it is a strong base, Br- is an excellent leaving group. I think this, rather than the removal of HBr, would be the more dominant reaction. That secondary carbon in the chain is nice and electron-deficient, with a leaving group begging to be knocked off. That nucleophile is going to be a lot more attracted to that kind of electron deficiency than to any pesky benzylic proton. Its a classic Sn2 reaction.

-drone #342


Osmium
Member     posted 09-29-98 04:12 PM          
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Every Sn2 reaction at a secondary carbon has the alkene as a side product. Having a benzlic H next to the halogen doesn't help either. Even with MeNH2 (which is a much weaker base and a not the best nucleophile), considerable isosafrole is formed. I guess Labrat is right, your main product will be isosafrole.


Labrat
Member     posted 09-30-98 09:35 AM          
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Like Osmium mentioned, Sn2 reactions work best on primary halides, then secondary, then tertiary. With Sn1 reactions, it's just the other way around. But I do believe that the reason why the amide has never been used to displace the bromide is exactly what I mentioned: benzylic proton abstraction. Lr/

drone 342
Member     posted 09-30-98 05:03 PM          
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...But already we have successful examples of the Sn2 reaction working well in this arena; the classic methylamine with a halosafrole works like a charm; the only difference is a stronger base -- which, provided the temp is kept low, should work *better* (the stronger the nucleophile, the better Sn2 rxn's go.)

Does anybody have any numbers on how acidic the benzylic protons on a halosafrole would be? Though the amide hasn't been used before, I don't believe its because of this; my guess is that people simply haven't investigated this kind of chemistry before with MDMA.

Os, where did you get that information regarding the isosafrole production? I haven't seen it in the literature. You have a refrence I don't?


drone 342
Member     posted 09-30-98 06:49 PM          
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Lr, Os,

I saw/see your point regarding the reaction clearly, and its definately a consideration. After looking in the literature regarding Sn2 reactions and 2-halo(1-phenyl)-propanes, it looks like slim pickings. Seems like there's really no easy way to separate basicity from nucleophilicity in this case. Any ideas?

-drone #342


Labrat
Member     posted 10-01-98 09:13 AM          
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>Seems like there's really no easy way to separate basicity from nucleophilicity in this case.

That's right! There's no way to make methylamine more nucleophilic without making the basicity higher! With methylamine, the free electron pair on the nitrogen is pretty nucleophilic, but also basic. With the amide, the free electron pairs are both very basic and nucleophilic. This seems like a dead-end. Lr/