[ketus]

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

[Babcock_Hall]

Are you following a specific literature protocol for this reaction?  I work with Dibal-H occasionally, but I don't have personal experience with the Rochelle salt procedure (I understand that it is well regarded).  One possibility is loss of a proton vicinal to the aldehyde group, leading to polymerization.

[rolnor]

Yes, I agree, if you are careful keeping pH at 7 you probably could get rid of the problem. A good way to make sensitive aldehydes is to cleave, 1,2-diols with sodium metaperiodate, then you have a clean neutral workup at neutral pH. So, 1,6,7,12-tetrahydroxy dodecane and 1,1 eqv. NaIO4 in water at 10 degrees Celsius for 10 minutes, then extract with Et2O, dry and evaporate. You can use the 6,7-alkene also and add some Osmium tetroxide but its toxic, nasty.