[Aromic_Me]

Hello everyone. So, I just found this forum and I’m overwhelmed by the many intriguing topics being discussed here. Keep it up!

I have three seperate questions, and would be eternally grateful someone could nudge me in the right directions.

    1)   I have problems finding a commercial source for “JJ-TPP”-polymer (JandaJel triphenylphosphine). It was earlier sold by Sigma-Aldrich, but has now been discontinued - worst case I’ll have to synthesize it myself. https://www.sigmaaldrich.com/catalog/product/aldrich/533416
   
    2)   I’m trying to add an acetylide to a quite sterically demanding nitrile (dietoksyacetonitrile) to furnish the imine, which in turn shall be hydrolyzed to the corresponding ketone. Firstly, I’ve generated the acetylide with BuLi or EtMgBr, but upon addition of the nitrile rapid polymerization occurs. Is there some way to avoid this side reaction? My next tries will be: Slower dropping of the nitrile and/or adding catalytic amounts of CuBr to the mixture. I’m also considering dropping the acetylide in solution into a round bottom flask loaded with the nitrile.
   
    3)   I’m also facing a problem with polymerization of 2,3-dimethylbutadiene during an attempted Diels-Alder reaction. When stirring at elevated temperatures no Diels-Alder adduct is formed. The enone dienophile is recovered in almost quantitative yield, while the diene polymerizes to a tarry residue. Picture: https://imgur.com/a/Zle0cK8
My next tries will be to run the reaction in aqueous media, with a Lewis acid catalyst, and with Nafion-H.

So if you have any input on my next attempts or some useful information I would love to hear it!
Thanks in advance

[pgk]

1). You can try to “google”, for alternative suppliers.
2). a). CuBr might lead to acetylide dimerization.
b). Slowly (dropwise) dropping the acetylide in solution into a round bottom flask loaded with the nitrile (and not the inverse), is the best because imine formation is exothermic and thus, the so generated heat accelerates the acetylide dimerization.
3). a). Diels-Alder reactions are sensible to steric hindrance and thus, they may not be favored by high temperatures that lead to trans-cis isomerizations and consequently, to possible steric hindrance.
b). Try the desired Diels-Alder reaction at lower temperatures, under Lewis acid catalysis (e.g. AlCl3) but do not use water as a solvent, in order to avoid any acid-catalyzed, hydrolysis of the acetal group.

[Enthalpy]

1) Is it very different from the similar items still available from Sigma Aldrich?
https://www.sigmaaldrich.com/catalog/product/aldrich/14664
https://www.sigmaaldrich.com/catalog/product/aldrich/93093
https://www.sigmaaldrich.com/catalog/product/aldrich/366455
https://www.sigmaaldrich.com/catalog/product/aldrich/14664

[wildfyr]

pgk, for the Diels-Alder' I'd like to point out that water has been found to be an excellent solvent for Diels-Alder, even when reagents aren't very soluble in it. I'd say doing the Diels-Alder in water (or even "on-water" stirring the hell out of it since those materials won't be soluble) is an intriguing idea. The aldol acetal can always be regenerated after the Diels-Alder. Or rather, do the Diels-Alder before the acetal formation in the first place.

Edit: Whoopsies on aldol vs acetal

[pgk]

1). Indeed, water may be the best solvent for Diels-Alder reactions.
2). This is not a typical acetal but it is the mono-acetal of a monoalkylene-glyoxal derivative that seems difficult to regenerate.
3). Thus, “Aromic_Me” (the OP) has to choose, either an aqueous medium or an (Lewis) acid catalysis. Both of them simultaneously, are incompatible in this case.

[Aromic_Me]

...

1) Oh believe me, I’ve tried googling. Was wondering what other resources you guys would turn to next!

2) a) I got the idea of CuBr from this article: https://pubs.acs.org/doi/abs/10.1021/jo00226a033?journalCode=joceah
When you say acetylide dimerization you’re referring to the Glaser coupling, right?
b) Okey, so I should slowly drop the lithiated acetylide/Grignard reagent into a solution with nitrile. I’ve seen both ways done in the literature, so was curious about this. Thanks!

3) a) Thanks for your suggestions here! I first saw no trace of the TM at r.t., and neither when increasing the temperature even after several days when running the reaction in a great excess of diene, but I saw some signs of polymerization. I then added AlCl3 which basicly polymerized all the diene in a heartbeat, but no traces of Diels-Alder adduct could be seen on NMR.
b) That acetal group is surprisingly compatible with water, we’ve have actually yet to find a method of deprotection to the aldehyde! All sorts of acidic media have been tried.

1) Is it very different from the similar items still available from Sigma Aldrich?

Thanks, but PS-TPP is the catalyst I'm using now, it's giving very low yields and the resulting mixture of configurational isomers are nearly impossible to separate. JJ-TPP gives a lot better yields for the reaction I'm running according to the litterature: https://www.sciencedirect.com/science/article/pii/S0040403907018680

And thanks for the input wildfyr, but as earlier mentioned, the acetal functionality is fully compatible with water

[pgk]

1). Alky(aryl) Grignard reagents are somehow different than acetylidemagnesium halides towards dimerization. But you can always try CuBr a in little amount, in order to see if this helps.
2). If the aldol group is compatible with water, then try the Diels-Alder reaction in aqueous medium and a little amount of Lewis acid catalyst, as Wildfyr suggests.
3). The hydrolytic stability of this aldol may be related to its lipophilicity. So, if you want to hydrolyze it, you need an organometallic Lewis acid as a catalyst (e.g. dibutyltin diacetate or something similar).
Good Luck.

[wildfyr]

3. There's always warm aqueous sulfuric acid. If that can't hydrolyze something, then extreme measures can be taken (like dibutyltin, ugh).

[Aromic_Me]

1). Alky(aryl) Grignard reagents are somehow different than acetylidemagnesium halides towards dimerization. But you can always try CuBr a in little amount, in order to see if this helps.

Yes, I was afraid of alkyl/aryl grignards being to different from their acetylenic counterparts, thanks for pointing this out. If anyone know of any literature describing addition of metallated terminal acetylides to nitriles I'd love to read it I've had trouble finding much.

2). If the aldol group is compatible with water, then try the Diels-Alder reaction in aqueous medium and a little amount of Lewis acid catalyst, as Wildfyr suggests.

Okey, I will and I will surely report back Would you guys have used mechanical stirring or would a magnet be enough?

dibutyltin

Yeeee, I'm good..! In my case the stability of the acetal actually works in my favor, since I want to keep it intact for the moment being.

And thanks again to both of you. Really appreciate the help

[wildfyr]

Whatever it takes it get it very agitated. It should look like an emulsion, even if its not really stable once you stop stirring. Usually in a 10-250 mL rbf this is easily obtained with a magnetic stir bar.

[pgk]

1). Glaser coupling:
https://en.wikipedia.org/wiki/Glaser_coupling
2). Copper (I) acetylide is highly explosive, if dry:
HAZARDS  IN  HANDLING  ACETYLENE  IN  CHEMICAL  PROCESSES   PARTICULARLY   UNDER   PRESSURE  SYMPOSIUM ON CHEMICAL PROCESS HAZARDS, INSTN CHEM. ENGRS, 87-94, 1960
http://www.whynotchemeng.com/communities/subject_groups/safety%20and%20loss%20prevention/resources/hazards%20archive/~/media/Documents/Subject%20Groups/Safety_Loss_Prevention/Hazards%20Archive/I/I-Paper-13.pdf
3). If well understood, metal acetylides tend to form complexes with nitriles; whatever this means about their reactivity:
Synthesis and Nonlinear Optical Properties of n-5-Monocyclopentadienyliron(II) Acetylide Derivatives.
X-ray Crystal Structures of[Fe(n5-C5H5)(DPPE)(p-CΞCC6H4NO2)] and
[Fe(n5-C5H5)(DPPE)((E)-p-CΞCC6H4C(H)=C(H)C6H4NO2), Organometallics, 21, 2107-211, (2002)
http://www.physics.ua.ac.be/~wwens/reprints/OM2002.pdf