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6-hydroxyhexanal degradation product

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RickMonnink1234:
Hi,

I am a Master student in chemistry and I am currently working on the synthesis of lipid nanoparticles. One step involves the DIBAL-H reduction of caprolactone in DCM at -80 C, followed by an aqueous work-up with Rochelle's salt. After concentrating my crude and at some time at the bench my 6-hydroxyhexanal (oil) spontaneously degrades and forms a solid goo. We suspect a kind of polymerization/oligomerization as the goo is insoluble in any NMR solvent, and extra spots are observed over time on TLC when the 6-hydroxyhexanal as diluted prior. We cannot figure out by what kind of mechanism, as hemiacetal formation would not be favourable, right? Nonetheless, I am very curious about the mechanism. Does someone has experience or has any idea what the degradation product might be?

Kind regards,

Rico

Babcock_Hall:
There are more experienced synthetic chemists here than I am, but I am happy to throw out some ideas. If the aldehyde loses an α-H to base, the carbanion could attack the carbonyl group of a different molecule.  One, have you demonstrated that you made the desired crude product prior to work-up?  In discussions with a more experienced synthetic chemist, I became convinced that isolating the steps (synthesis, work-up, purification) was a good strategy.  Two, are you following a literature protocol?  If so, you might email the authors; in my experience, they usually reply, but they do not always know what the problem is.  Three, my experience with DIBAL-H is limited to using it to reduce Weinreb amides to aldehydes.  In that application, I have used either NaHSO4 or KHSO4 to work up the reaction.  However, I would be hesitant to suggest this protocol unless it has been shown to work in the reduction of another lactone.

RickMonnink1234:
Dear Babcock_Hall,

Thank you for your reply. I will investigate this stepswise further. Yes, the NMR confirmed we synthesized the target compound, but the NMR shows a decreasing purity over several minutes.

Kind regards,

Rico

rolnor:
I agree, it can be polymer formation. You may have trace of base in the sample. If you cleave a diol with NaIO4 to get the hydroxyaldehyde you will have a completely neutral sample, this way you can even make the sensitive glyceraldehyde. You would start with 6,7,12-tetrahydroxydodecan-1-ol

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