Author Topic: Ring bromination in solvents other than GAA?  (Read 915 times)

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Antoncho

  • Guest
Ring bromination in solvents other than GAA?
« on: April 26, 2002, 11:01:00 AM »
It seemed highly unlikely to Antoncho that such an obvious idea has never been mentioned, so he UTFSE'd his ass off, but - to no avail.

Say, what do you think, is it possible to use anything else than GAA in bromination of a ring-substituted phenethylamine? (well, you guessed it right, i mean 2C-H, of course).

The point is: bromination the "usual way" gives a low yield, with the amt of the final product being roughly the same that the used freebase - the theoretical yield being twice as much!

So... Obviously, the bromination conditions are way too vigorous for the amine function. The most obvious solution for this would bee to carry out this rxn at a lower temp. And, indeed, Hest's recent account on chlorination of 2,5-DMA at -78 C, the yield being 70%+ , suggests that it can and should bee done.

Unfortunately, GAA solidifies at 16 C.

So, does anyone see any visible obstacles to performing the bromination of 2C-H in CHCl3 at a freezer temperature, for whatever time it will take? Has anybee, maybee, actually done this or something similar?

Another interesting possibility would bee to use dioxane dibromide, which is highly selective and mild brominaiton agent - see for example its use in bromination of benzenes ond acetone (BTW, can anyone explain me, why it's so selective? Is it only due to the fact of Br2 being unable to form free radicals or some other effect?)


Please, dear bees, share whatever you have in mind ;)


Antoncho

foxy2

  • Guest
See my post in DMF
« Reply #1 on: April 26, 2002, 11:07:00 AM »
Antoncho
Check out my post at the end of the DMF thread


Hey I have a reference here that gives highly selective bromination in trifluoroacetic acid.
Is that better?   :P

SpicyBrown

  • Guest
Re: Hey I have a reference here that gives highly ...
« Reply #2 on: April 26, 2002, 12:15:00 PM »

Hey I have a reference here that gives highly selective bromination in trifluoroacetic acid.
Is that better?




I for one am very interested in that!

SpicyBrown


Osmium

  • Guest
Vanillin ---> bromovanillin 98% in HBr.
« Reply #3 on: April 26, 2002, 12:41:00 PM »
Vanillin ---> bromovanillin 98% in HBr.
You can use all kinds of solvents for this reaction, it shouldn't matter much.

I'm not fat just horizontally disproportionate.

Antoncho

  • Guest
Yes,...
« Reply #4 on: April 26, 2002, 12:48:00 PM »
Yes, i know of several examples when aromatics are halogenated in other solvts - CHCl3, even water. But i was wondering specifically about amines....

You see, i was thinking like "well, bromination in different solvents is such a widely known, versatile reaction - and for 2C-H noone ever uses anything other that GAA. So there must bee a reason for that - that is, unless it is just the effect of traditional sticking to the known routes." So i thought i'd just ask.

Another thing that just occurred to me is :

When bromination is performed in GAA, the amine is kinda in form of acetate salt, isn't it? So the amine function is much less nucleophilic than in its freebase form - and it is thus less prone to react w/the electron-hungry bromine molecules? (Can anyone confirm or disapprove of this speculation, please?)

So it might bee a good idea to just add some, say, CHCl3 to the GAA to prevent it from freezing - OTOH, not too much so as not to crash out the acetate salt. Whaddayathink?

For that matter, bromination in aq. HBr also sounds very good.

Antoncho

Rhodium

  • Guest
Less nucleophilic acetate
« Reply #5 on: April 26, 2002, 01:22:00 PM »
The speculation above is fully correct.

hest

  • Guest
Solvent's
« Reply #6 on: April 26, 2002, 05:57:00 PM »
NBS in AcCN works greath
All the halogenated solvents works fine (Chlorofom, DCM, perchloroethylen, Carbontetrachlorid ect. (and the 'dry' cleaner use them all to clean you suit))

Antoncho

  • Guest
Hest, again a couple of questions for you:
« Reply #7 on: April 26, 2002, 06:33:00 PM »

All the halogenated solvents works fine


- you mean, with NBS or with bromine as well? What conditions - like temp?

Please, bee a little more specific! :-[  - ahh, why all you really cool chemists are so tough to get talking! :)

Sorry if i'm bugging you...

But, see, your experience is so important - noone else seems to have done it on this board...

Antoncho


hest

  • Guest
More solvents
« Reply #8 on: April 26, 2002, 07:50:00 PM »
The halogenated solvents is only for the bromination with bromine, usual at 0° to sub 0°C

The NBS thing is Acetonitrile at 25°C for 12 houers (I think there are something at Rhodiums page)

Sunlight

  • Guest
bromination on the amine group
« Reply #9 on: April 26, 2002, 09:01:00 PM »
It could be interesting a direct bromination in DCM, but the question is if the amine group would be affected and/or bromination occurs exclusively in 4 position.

uemura

  • Guest
Useful elsewhere as well---
« Reply #10 on: April 27, 2002, 07:12:00 AM »

highly selective bromination in trifluoroacetic acid.



trifluoroacetic acid usage as catalysator in epoxidation. It's a bit expensive to bee used as a sovesnt, isn't it?


Carpe Diem

hest

  • Guest
Bromination
« Reply #11 on: April 27, 2002, 01:16:00 PM »

It could be interesting a direct bromination in DCM, but the question is if the amine group would be affected and/or bromination occurs exclusively in 4 position.




Well, haven' t done it but I'm damm sure it will brominate solo in the 4 potition, and the amine will not affect it.


slappy

  • Guest
MeCN works well...
« Reply #12 on: April 29, 2002, 02:07:00 AM »
Acetonitrile works very well. Best way, like Hest said, is NBS in MeCN 25°C for like 6 hours. You can also substitute N,N'-Dibromo-2,2-dimethylhydantoin (DBDMH) avantageously.

You wouldn't want to use something like DCM, because you want a polar aprotic solvent to stabilize the carbocation intermediate formed during electrophilic aromatic substitution.

Osmium

  • Guest
> You wouldn't want to use something like DCM, ...
« Reply #13 on: April 29, 2002, 09:53:00 AM »
> You wouldn't want to use something like DCM, because you
> want a polar aprotic solvent to stabilize the carbocation
> intermediate formed during electrophilic aromatic
> substitution.

It really shouldn't matter much what solvent you use. I have used DCM in Friedel Crafts acylations and it worked well. Brominations of less activated aromatics like toluene and benzene works too, the solvent really doesn't matter much.

I'm not fat just horizontally disproportionate.