If your product is not too sensitive to oxidation I would add few drops of hydrogen peroxide to the reaction mix, that should promptly oxidize all phosphines to phosphine oxides and Pd to Pd(II). Pd(II) should wash away during aqueous workup (you can add some EDTA or cyanide during the extraction if you need really low levels of Pd) and phosphinoxides should stay on the start of the column, they are quite polar.
In that case I would use a aqueous sodium cyanide or sodium sulfide to complex out Pd – once I had a problem like this before (my diaminopyrimidine compounds were strong chelators and acrried metals with them, I added TMSCN during the workup to get Pd and Cu out)
Pd has only negligible toxicity (even nickel is lot more toxic than Pd) but unfortunately Pd can be detected in extremely low traces in the product and since it is classified as a “heavy metal”, a carry-over of Pd-related cotaminants into the final product is a serious complication in manufacturing active drug substances. As far as you dying of Pd poisoning I think you are safe unless you drink gram quantities of the stuff.
Okey Dokey Milkshake! Let’s hope those triphenylphospine ligands aren’t too toxic! 😉
I read about a chemist in the states some years ago who got a few drops of dimethyl mercury on her gloves and died some months later :O
Fortunately, I only got a few drops of this stuff on my gloves, and I was wearing two paris (nitrile 2x 0.11 mm) and took them off after contamination I’d say in <30 seconds. But dam, DCM eats nitrile!
does here anybody know how to make acrylamide of poor nuclophile nitrogen atom, such as pyrrole, indole etc!acyl chloride and mixed carbonate (acrylic acid and isobutylchloroformate with NMM in THF)did not work well..
yah, this is a serious problem with acryloyl chloride and other activated forms of acrylic acid – they crap up very easily, for example by conjugate addition.
I would try an experiment with a weak base like pyridine (or 2,6-lutidine) and acryloyl chloride. If this does not work I would suggest the N-silylation trick with acryloyl chloride and CuCl2 as a catalyst, as described in: Catriona Thom and Philip Kocienski: Synthesis (1991 or 1992, I am not sure) page 582-586
Is it possible to use a rotevap to seperate DCM and toluene, I mean, if the pressure is redued enough, somtimes the DCM misses the first trap, and goes straight into the second trap at the back…and the toluene goes into the first trap.
sorry i don’t understand what you mean, most lab-scale rotovaps that I saw had only one condenser (unless you use oil pump as a vacuum source – a pump which should be protected with additional cold trap – but highvac would be totally inappropriate for evaporating DCM).
Any distillation setup should be able to reasonably separate DCM and toluene because their boiling points are far apart and they probably do not form an azeotrope – but the purity of the recovered solvents would not be sufficient to put them back in the bottle (unless you are using these solvents only for a non-demanding application like solvent extraction). I would be very reluctant about using recycled solvents as a reaction media. Besides, these solvents are cheap enough to buy. The only concern is that DCM is somewhat expensive to dispose as a halogenated waste on large scale, and there are OSHA-mandated exposure limits, so thats why process chemists do not like to use it.
If you are concerned with a process-related question “how to recycle your solvent mix” I may not be the best person to ask because I never worked on process reactor scale.
Sorry James but you need to look up the basics for your silicone chemistry: 1) silanols are not water soluble at all: they are quite greasy in fact 2) Me3SiOH is unstable in free form and quickly dehydrates to Me3SiOSiMe3 on its own. (Hexamethyldisiloxan is a reasonably volatile liquid, with boiling 101C). 3) fluoride quickly transforms silyl ethers and silanols to silyl fluorides (compounds which are volatile and very greasy). Why don’t you find some organic textbook with a chapter on organosilicone chemistry and read it before posting even more comments?
I should see soon – Right now I am still setting up my lab space, learning the way around the institute and getting known the people, and bringing up some building blocks (I am still quite far from making anything that would be worth testing.)
You can use excess of triethylsilane in DCM at 0C to room temperature with your substrate and add TFA slowly, to saturate tetrasubst C=C in the presence of disubst C=C (but disubst C=C will be left alone only if the disubst C=C is not conjugated with anything). Ketones will be likely reduced to alcohols by the system. It proceeds by C=C protonation and the formed stabilized carbocation abstracts hydride from the silane. In rigid polycyclic systems like terpenoids the tetrasubst C=C between rings that gets saturated often ends as a trans ring junction – the thermodynamically more stable product is the main one.
Thank you very much, milkshake. I am impressed by how much you know! I am planning on reducing a tetrasubstituted olefin which sits a the ring junction in a 6,5-fused ring system, and I want the cis-fused stereochemistry in the product. This should (by far) be the most thermodynamically stable product, and I will thus try this methodology that you kindly mentioned.
I remember vaguely that delta G energy difference between the cis and trans isomer in hydrindane systems is not as great (but the cis should be still favored by something like 1 kcal/mol). I think you may end up with a mixture of both. Maybe you could try at first to run it at 0C – and if you get a poor cis/trans ratio you could try again at -78C and use triethylsilane with some stronger acid like TfOH in DCM for protonation (or better yet, TFA with added BF3.Et2O for extra kick)
Is there any electron-withdrawing group attached to that tetra-substituted olefin? In which case then you might be able to use dissolving metal single-electron reductions, such as Li or Na in NH3(l) with a proton source, such as tBuOH. Sometimes, there are run in a proton source, such as EtOH… In these cases, I seem to remember that protonation of the forming carbanion is thermodynamically driven… Something to consider, provided, of course, that your olefin is electron-poorer than your disusbstituted one that you want to avoid harming.
No, there is not. What I am planning to do is a Birch reduction of 2-indanol, then selectively saturate only the tetrasubstituted olefin and finally oxidizing the secondary alcohol to the corresponding ketone. As mentioned, I want the cis-fused stereochemistry in the product and this is now my only worry.
Can we use Et3B as a radical initiator instead of conventional AIBN/benzoyl peroxide for radical mediated side cahin bromination of alkyl benzenes. I end up in monobrominated, dibrominated and unreacted starting materials with either NBS OR dimethyldibromohydantoin using AIBN/benzoyl peroxide. Are there any ways to control the dibromnation. Because Et3B is known to initiate reactions even at -78 deg cel, will it be worth running bromination at lower temp using Et3B as initiator. Your expert comments are appreciated.