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June 25, 2012
The Good Ol' Friedel-Crafts
Posted by Derek
It's not anything to shake the earth, but I'm actually happy to see new variations being discovered for ancient reactions like the Friedel-Crafts. It makes sense that an activated amide could participate in the reaction, but it looks like no one's ever quite explored the idea like this.
And yes, I know that a large Friedel-Crafts can be a pain, what with all that aluminum gunk. The biggest one I ever ran used protic conditions (methanesulfonic acid), so I haven't had the complete experience, but I've still managed to work my way through some gooey aluminum milkshakes. But it's still a useful reaction on the bench scale.
And somehow, I can read a paper like this one and be pleased, while a paper on yet another way to dehydrate an oxime to a nitrile makes me roll my eyes. I'm still trying to work out why that might be - a bit broader scope? More possible utility? Just the fact that this was something that no one had quite thought of, as opposed to another way to take the same starting material to the same product? I should figure out what my boundaries are.
Comments (8)
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1. okemist on June 25, 2012 10:01 AM writes...
I have done FC reactions on 10-20 kilo scale without problem. Like most procedures, planning and familiarity are key.
Permalink to Comment2. johan on June 25, 2012 11:22 AM writes...
No access to full text, so this might be addressed in the paper, but I really don't see how a bis-protonated species like that in the TOC can be an intermediate or even a TS. Single protonation of the nitro will result in net positive charge mainly on the amide nitrogen, and looks like enough activation and "diminished C-N resonance" to me.
Permalink to Comment3. Organometallica on June 25, 2012 2:22 PM writes...
I've thought about how I judge papers too. It's sometimes very difficult to define your own aesthetics.
Permalink to CommentI found this particular paper interesting because the conditions are almost like umpoled reactivity for the normal, electron rich amide carbon. Also, I tend to think of amides as being one of the more relatively inert functional groups, so any transformation involving an amide as a substrate is interesting to me.
4. Hap on June 25, 2012 5:18 PM writes...
The first protonation should be at the amide oxygen, most likely (the amide O should be more basic than the nitro O). Once that happens, you need to activate the nitro to generate something electrophilic enough to yank the lone pair on N away from the amide and into the aromatic ring so that the amide N-C bond order drops, making it easier for the aniline to act as a leaving group.
Using a nitro-substituted amide as reactant might make it easier to FC away starting material and leaving group from the product, or to monitor the reaction by TLC (without having to stain).
Permalink to Comment5. LMBass on June 25, 2012 6:57 PM writes...
The chemistry is fairly characteristic for superelectrophiles (diprotonated structures). It has been known for quite some time that multiply charged ions exhibit unusual reactivities.
Permalink to Comment6. freezedream on June 25, 2012 8:54 PM writes...
Nice! Now I know something to try if I ever need to make an indanone.
Permalink to Comment7. Secondaire on June 25, 2012 10:23 PM writes...
Wow, it's pretty cool. Can't access full text, but I'd bet the nitrogen probably plays some role in complexing the aluminum too - I wonder what would happen with an activated (e.g, p-nitrophenyl) ester? There are indium-catalyzed variants of that...
Permalink to Comment8. barry on June 26, 2012 12:55 PM writes...
"all that aluminum gunk" can often be rendered tractable by Yamamoto's trick. Add four equivalents of NaF and one of water for the quench. Na(AlF4) is easily filtered away
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