During oxime synthesis using C12 MNA with hydroxylamine.HCl left ~5% aldehyde. Does there have
Addition of excess NH2OH.HCl and NaOAc will help completing your reaction
Thank you for the reply. I had tried with NH2OH.HCl and Na2CO3. Added in excess 1.1 ~ 1.3 times. But still about 3 % aldehyde remained. Let me try one with NaOAc instead of sodium carbonate.
For my part, I use a ketone (1 part) poured on a mixture of hydroxylamine hydrochloride (1.26 part) and pyridin (1.8 part) in absolute ethanol. Then remove under vacuo the ethanol and the bruto is taken by dichloromethane, washed by an aqueous solution of HCl (6 M), an aqueous solution saturated by NaHCO3, twice by water and one time by brine. The product is pure.
If you cannot improve the conversion by increasing the amount of hydroxylamine, maybe the issue is not the reaction be rather the caracterization. Some oxime hydrolyse back to the corresponding aldehyde rather easily, so you might see residual aldehyde present in LCMS or in NMR if your solvents are not dry.
If the aldehyde present is real and you cannot push the reaction, I would carry on to the next step (except in GMP context...). 3-5% is not that much and I presume the aldehyde will not interfere in the next reaction. Once you reacted the oxime you will be able to purify the more stable product without hydrolysis issues.
yes, i used this oxime to synthesize nitrile. the reaction undergoes without any problem to nitrile. the problem is that as the product is of perfumery importance, the presence of aldehyde (even after distillation) comes up as top note on blotter. Let me try for a perfect distillation.
With the nitrile / aldehyde mixture, you can probably react the remaining aldehyde with NaOCl and tBuOH (lingrend type oxidation) to oxidize the remaining aldehyde to the corresponding carboxylic acid. Might even be able to do this in the extraction funnel as this oxidation is quite fast. The acid should be removable by NaHCO3 wash. I suggest you have a look into it is it causes issue in your distillation.
For my case, I used 3 eq. of NH2OH.HCl and 3 eq. NaOAc for the protection of Ketone (1 eq.). 95% EtOH was used as a solvent. The reaction was refluxed for 10h or 48h at room temp. The reaction mixture was poured into crash ice with constant stirring and kept for overnight in refrigerator. Next day, crystalline product was filtered. There was no ketone was observed after reaction. I think it may be applicable for aldehyde also.
I have seen mention of pyridin as a driving force for equilibration toward complete oxime synthesis.