[johnpinecone]

Hi Everyone, hoping I can get some help on a fairly simple but still frustrating problem I'm having,

I'm currently working on a fragment for my synthesis and have hit a problem at my crimmins aldol stage, the problem being the purity of the aldehyde used (4-Pentenal) which is really reducing the yields to below 30%

The problem is the volatility of 4-Pentenal which comes off on the rotovap meaning flash chromatography is not really an option. I have been making the aldehyde by oxidising 4-penten-1-ol using IBX in DCM, which is relatively clean as i can just filter off the solid residue and remove some solvent by distillation (though i always lose a little aldehyde by doing this). I have tried distilling the aldehyde out but the amount of product compared to the amount of solvent means I never really can isolate just the aldehyde,

any help would be greatly appreciated,

Johnpinecone

[cpncoop]

If you don't want to switch oxidation conditions (which I would suggest - either TEMPO/NaOCl or something analagous), just drop the amount of solvent being used for your oxidation.  Distillation is going to be your best bet for purification.  The starting material is cheap enough such that you should just make a large amount of it and go from there.

[stewie griffin]

I have made this aldehyde very successfully on several occasions using Crimmins' actual prep (see JACS 2005, 127, 17200-17201 SI for the exact info). Basically you first make hex-5-ene-1,2-diol using allyl magnesium bromide and glycidol (yields around 85-90%) instead of oxidizing the alcohol. You can just do a quick silica plug on that to clean it up. Then from there you do an oxidative diol cleavage with NaIO₄ in water/DCM. Once that reaction is finished, I just pour the quenched water/DCM mixture into a sep funnel and separate. Wash the desired DCM layer with some sodium thiosulfate, dry over Na₂SO₄, filter, and concentrate down most of the DCM.
The concentration part can be tricky. I rotavap without any heat and I let it take it's time. At most I use a room temp water bath to help nudge the DCM into the vapor phase. Once I feel like I've gotten most of the DCM off, I transfer the remaining solution into a shortpath distillation setup. Distill with a heatgun (I have written that it should distill at around 96 degrees) to get a clear colorless liquid.
Personally I then take an NMR of the stuff and integrate the DCM peaks and product peaks. I usually have something that's 90% or more of 4-pentenal by weight in DCM. Since the Crimmins aldols are run in DCM anyway it's really not an issue... at least the one I do I've gotten yields in the 85%+ range this way.
The first time I made this aldehyde I only got a 46% yield, but after several goes I've been able to get it up to 90%. Guess it just depends on how much your rotavap. So yeah it comes off on the rotavap, but it doesn't all have to if you're careful.

[johnpinecone]

Thanks  alot for the help,

Got nice amounts of the aldehyde for my crimmins!