Iodination using ICl?

[Bandil]

Hi!

I've searched this site quite some time now without any conclusive answer. Will iodination of 2CH and DMA proceed as presumed (which means putting some iodine on the 4 position and not everywhere else) using iodinechloride? I would assume that the reaction should be run in GAA as the solvent? Would the iodination require that the amine group is protected by forming the phthalimide, using phthalic anhydride first?

If it works as easy as presumed, it would sure be a nice way to form DOI and 2CI without much fuzz. The chlorides of boths compounds would be formed directly and isolation should be as easy as with 2CB.HBr.

Thanks!

Regards
Bandil

[slappy]

ICl reacts almost the same as I2. Only it is just a little more reactive.

[Bandil]

*buuuhuuuu*

According to:
Sargent III, T.; Shulgin, A.T.; Mathis, C.A. J. Med. Chem., 1984, 27, 1071-1077.

and:
Braun, U.; Shulgin, A.T.; Braun, G.; Sargent III, T. J. Med. Chem., 1977, 20, 1543-1546.

the direct use of iodinechloride will result in an oxidative attack on the amine group - so protection is reuqired.

Guess iodine and some alkali nitrate will have to do...

Regards
Bandil

[Bandil]

Hmmm... seems that iodination of 2CH / DMA is quite tedious.

The only confirmed route i could find (that does not protect the amine first) is the Ag₂SO₄ / I₂ reaction. Anyone knows if alkalinitrate / I₂ will work at all, without protection?

Regards
Bandil

[Rhodium]

If I remember correctly, Barium performed some successful Oxone/KX halogenations last year on unprotected 2C-H...

[Prometheuz]

It sure would be a nifty iodation-procedure, but iodine-monochloride is one of the most tricky and obnoxious compounds I have ever worked with.
You know how both I₂ and Br₂ behaves; iodine is solid, doesn't have too high vapor-pressure, and isn't a serious hazard handling. Bromine IS pure liquid evil, but at least you know what to expect, such as lots of corrosive and toxic brown fumes if you haven't cooled it to exactly the right temperature before measuring the needed amount.
ICl is a strange sort of semi-solid at 20° C; it fumes almost as much as Br₂, and is QUITE hard to weigh off in this state. The normal procedure is to gently heat the container 'till it is all liquid, and measure the amount needed this way. But better cap those containers fast, cause at elevated temperature it of course vaporises faster. Handle with a fuckin' lot of care! 
Unfortunately I think there's no way around protecting the amine if trying this route. Should I shuffle through my old papers trying to find a suitable protective group for this particular reaction, or do you think the entire procedure would end up being too tedious?