[wildfyr]

Just want to say I'm excited by all the support and advice . I guess I gave our organic crew a juicy problem to chew on.


I'm trying the white light today, I don't expect success. If that doesn't work I ordered DBU and NaH already to see if I can coax some R₂N^- formation and attack. In the meantime while they get here I will try reactions with adding KI, and also heating the christ out of it with a few eq's of diphenylamine. I might as well try Na₂CO₃ too since its technically a weaker base than the potassium version.



I have this strange lab setup where I am the only chemist at this site, but I have a huge space, lots of glassware and hoods, a poor stock of chemicals when I arrived, but a chemical budget where I have yet to hear "No." So all suggestions are welcome haha.

[pgk]

1). Using 1.1 eq. diphenylamine and 2 eq. TEA sounds smart and promising.
2). I read this article and it is really interesting. Nevertheless, radical conditions must be inhibited during the preparation of tertiary amines, in order to avoid the formation of N-oxide side products (among other measures, vacuum must be broken with nitrogen, remember?).
A good trick is adding a little amount of BHT (say 0.5-1.0 % w/w per amine) and removing it after the end of the reaction, by alkaline washing.
3). Don’t worry so much, about fluorescence because radical initiation demands UV light energy ≈ 100 kcal/mol, which corresponds to a wavelength < 300 nm that is rarely achieved by fluorescence/luminescence, whose energy is lower than the one of the initial irradiation. Anyway, it is safer to work in the dark, at the beginning.
4). TEA is a cheap and effective, basic catalyst that is easily removed. On the other hand, tertiary amines that have nitrogen at the bridge-edge of bridged rings, such as DBU and BABCO are more basic and more effective catalysts because the high bridged-ring tension, consists the nitrogens electron pair, somehow more “approachable”. In other words, DBU and BABCO can catalyze reactions that might not be catalyzed by TEA.
5). I am wondering whether DMAP could simultaneously play both the roles of a catalyst and a leaving group.
Good luck, again.

[wildfyr]

Heating the christ out of it overnight did not work. Surprisingly the dye didnt degrade, just no conversion.

I've ordered DBU and NaH to look further down the amide attack route. I hope DBU works, because working with NaH is more sensitive and will require a more complex setup. For NaH, likely would deprotonate the DPA in one flask cold, then slowly add it to the dye flask via cannula to reduce the chance of the amide chewing up other parts of the dye. DBU should be just mix and stir.

P.S. Who decided that amide (the RCONR₂ compound) and amide (R₂N^-) would have the same dang name!

[clarkstill]

Heating the christ out of it overnight did not work. Surprisingly the dye didnt degrade, just no conversion.

I've ordered DBU and NaH to look further down the amide attack route. I hope DBU works, because working with NaH is more sensitive and will require a more complex setup. For NaH, likely would deprotonate the DPA in one flask cold, then slowly add it to the dye flask via cannula to reduce the chance of the amide chewing up other parts of the dye. DBU should be just mix and stir.

Bad luck so far. I'm not sure about the NaH route - the amide* you generate is pretty damn basic (and hindered so non-nucleophilic) - I'd expect it to behave more much like LDA, and you'll deprotonate your cyanine dye before any nucleophilic attack happens. Hopefully i'm wrong though. No enthusiasm for Pd-catalysis?

* I agree wholeheartedly regarding the word "amide", it's always bothered me. Much like the absence of any fluorine in fluorenone.

[pgk]

Meanwhile, please take a look at the patents below, describing the preparation of dimethylallylamine from allyl chloride + dimethylamine + NaOH:
US Patent 2923701, (1960)
US Patent 4946996, (1990)

But take care about any potential allylic rearrangement. It is not clarified therein.

[clarkstill]

Meanwhile, please take a look at the patents below, describing the preparation of dimethylallylamine from allyl chloride + dimethylamine + NaOH:
US Patent 2923701, (1960)
US Patent 4946996, (1990)

But take care about any potential allylic rearrangement. It is not clarified therein.

I fear dimethylamine is rather a different beast from diphenylamine...

[pgk]

Yes, but the main problem hereby, is forming the diphenylimide anion without deteriorating the rest of the cyanine molecule. Therefore, any relevant information is useful.
Please, note that allylamine synthesis by amination of allyl chloride is not an easy task and thus, various methods adopting organometallic catalysis are proposed. Indicatively, see:
Allylic Aminations with Hindered Secondary Amine Nucleophiles Catalyzed by Heterobimetallic Pd–Ti Complexes, Organic Letters, (2015), 17(3), 752-755, DOI: 10.1021/acs.orglett.5b00058
https://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b00058
However, it is doubtful if the rest of the cyanine molecule will stay quite in the presence of such an exotic organometallic catalyst.

[wildfyr]

I have no experience with Pd catalyzed aminations. I'm going to set up the iodide containing reaction today. Or maybe just dump KI into the reaction I already had going with 2 eq DPA and 2 eq TEA (but at 120°C all night I think its fair assume all the TEA has boiled out and left via the bubbler)

[kriggy]

I think you could you convert your halide into boronic acid and run chan-lam coupling. (if nothing else works )

[wildfyr]

Oy, I would rather do the Buchwald Hartwig and deal with Pd. The point is to make sure this is 1 step so I can cycle through a bunch of variations. If I have to do more than one step I'll go earlier in the synthesis when the chloro spot is more reactive and make many variations there.

Right now I'm working with an off the shelf dye with the chloro in it.