hello all,
After some experimentation with the rearrangement of an amide, I thought I might try my luck and see if I could get some guidance around increasing yields.
When I first attempted this reaction, yields were around 3-4% and the reaction did not run very clean at all and a lot of work up was required post reaction. After experimentation, I have finally ended up around the 25% mark with a much cleaner product, but this is still leaving me rather unsatisfied! Much amide is going to waste..
Anyway, the highest yielding reaction has been run something like this:
-add 1.2 molar excess of hypochlorite to an RB
-dissolve ~1 molar eq. of NaOH in RB
-Bring temperature down to 0-10ºc, then add all the amide
-add DH2O as required to allow good stirring
-maintian temp and stir for ~4hrs
-prepare a hot solution with 1 mole eq. of NaOH, and add to RB
-bring temp of reaction up to ~75ºc, maintain temp for ~20min
-extract with NP solvent, workup as usual
Now I recently tried to run it much like the below referenced patent, which basically encompassed 2 changes. One was to neutralise the excess hypochlorite with a 10% NaHSO3 solution, which actually gave a MUCH cleaner reaction (no polymerised looking goop to be seen) and the second change was dripping the reaction mixture onto a solution of hot NaOH. The latter change was not entirely possible, as the amide never fully dissolved like it does in the patent (even though I left it for 8hrs this time), so instead it was poured in portions from a beaker onto the hot NaOH solution. Now, whilst this was by far the cleanest reaction, the yield had in fact dropped from ~25% to ~10%. The other problem though, was that upon the completed reaction being let to stand, ~45% of the original amide crashed out and was recovered (some has always crashed out but I had not previously weighed it).
From this I concluded one of two things was happening, either the recovered amide had never been converted to the intermediate isocyanate, or alot of the formed isocyanate was reversing back to an amide during the rearrangement. I have no idea if the latter is even possible, but I made the assumption that the isocyanate was not forming explaining why it never completely dissolved in the solution.
So, can anyone provide some guiance on what could be done to bring up the yields . I have seen on other forums claims of 60% being made, though I was unable to replicate it by following their procedure.
Any help is appreciated.
Reference: US Patent 7205440
After some experimentation with the rearrangement of an amide, I thought I might try my luck and see if I could get some guidance around increasing yields.
When I first attempted this reaction, yields were around 3-4% and the reaction did not run very clean at all and a lot of work up was required post reaction. After experimentation, I have finally ended up around the 25% mark with a much cleaner product, but this is still leaving me rather unsatisfied! Much amide is going to waste..
Anyway, the highest yielding reaction has been run something like this:
-add 1.2 molar excess of hypochlorite to an RB
-dissolve ~1 molar eq. of NaOH in RB
-Bring temperature down to 0-10ºc, then add all the amide
-add DH2O as required to allow good stirring
-maintian temp and stir for ~4hrs
-prepare a hot solution with 1 mole eq. of NaOH, and add to RB
-bring temp of reaction up to ~75ºc, maintain temp for ~20min
-extract with NP solvent, workup as usual
Now I recently tried to run it much like the below referenced patent, which basically encompassed 2 changes. One was to neutralise the excess hypochlorite with a 10% NaHSO3 solution, which actually gave a MUCH cleaner reaction (no polymerised looking goop to be seen) and the second change was dripping the reaction mixture onto a solution of hot NaOH. The latter change was not entirely possible, as the amide never fully dissolved like it does in the patent (even though I left it for 8hrs this time), so instead it was poured in portions from a beaker onto the hot NaOH solution. Now, whilst this was by far the cleanest reaction, the yield had in fact dropped from ~25% to ~10%. The other problem though, was that upon the completed reaction being let to stand, ~45% of the original amide crashed out and was recovered (some has always crashed out but I had not previously weighed it).
From this I concluded one of two things was happening, either the recovered amide had never been converted to the intermediate isocyanate, or alot of the formed isocyanate was reversing back to an amide during the rearrangement. I have no idea if the latter is even possible, but I made the assumption that the isocyanate was not forming explaining why it never completely dissolved in the solution.
So, can anyone provide some guiance on what could be done to bring up the yields . I have seen on other forums claims of 60% being made, though I was unable to replicate it by following their procedure.
Any help is appreciated.
Reference: US Patent 7205440