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Topic: Reduction of Lactams to amines  (Read 12570 times)

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Offline Nescafe

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Re: Reduction of Lactams to amines
« Reply #15 on: October 01, 2014, 03:18:28 PM »
I am trying out BH3THF, I dont think I can just vac off and column it as I will have the same issue as before. If it looks decent I am going to try an amberlite resin, rinse with Methanol:THF then ammonium hydroxide. vac off the ammonium hydroxide and purify it  What do you think?

Offline Nescafe

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Re: Reduction of Lactams to amines
« Reply #16 on: October 02, 2014, 01:29:27 PM »
Yeah BH3THF is a no go the major spot by MS is basically my SM - 2 protons which makes me speculate that I have made an alkene, although I am not sure where or how exactly so I will have to make the LAH work.

So can you please explain to me exactly what your suggestion  is post reaction. Qunch and then load onto an amberline column flush with ethanol/water and then 2M ammonium hydroxide to elute my amine out?

Offline Dan

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Re: Reduction of Lactams to amines
« Reply #17 on: October 02, 2014, 03:49:13 PM »
Yeah BH3THF is a no go the major spot by MS is basically my SM - 2 protons which makes me speculate that I have made an alkene, although I am not sure where or how exactly so I will have to make the LAH work.

Unlikely to be a dehydrogenation, this would be an oxidation using borane.

How many equivalents of BH3 did you use? Maybe it could be this aminoborane:

[*:1]CN([*:2])B

Not sure that would survive MS though. If it is, then it worked and just needs decomposing to the free amine.  Repeated concentration from methanol should do the job (trimethyl borate is volatile), but the acidification followed by ion exchange will also work if not.

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So can you please explain to me exactly what your suggestion  is post reaction. Qunch and then load onto an amberline column flush with ethanol/water and then 2M ammonium hydroxide to elute my amine out?

Yes, exactly.
My research: Google Scholar and Researchgate

Offline Nescafe

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Re: Reduction of Lactams to amines
« Reply #18 on: October 02, 2014, 04:43:03 PM »
I used 2.5 but after 24hrs at reflux I had 50:50 so added another eq.

Based on LCMS it could very well be it as the mass matches the specie you suggested perfectly.

I tried azeotroping with MeOH and no luck. I left it stirring in acetonitrile with a bit of sodium bicarbonate hoping that will free the amine. Not sure if it was a good idea but I was in a rush to leave.

Thanks for the advice, still surprised how MeOH did not help release it.

Offline Dan

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Re: Reduction of Lactams to amines
« Reply #19 on: October 02, 2014, 05:08:49 PM »
See how it looks after the bicarb, but maybe acidify it with a little bit of conc HCl to protonate off the amine, then resume concentration from MeOH. This will leave you with the ammonium salt of your product (and NaCl from bicarb/HCl), which you can freebase (and remove NaCl from the neutralised bicarb) by the ion exchange method.

This is all assuming that it is actually the aminoborane, it might not be.
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Offline Nescafe

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Re: Reduction of Lactams to amines
« Reply #20 on: October 02, 2014, 05:38:35 PM »
I will definitely try that.

I just cant see what else it could be, I have drawn out a number of other possibilities but the only thing that matches the mass is the borane specie you suggested. And like you said dehydrogenation is unlikely.

I like the idea of making the ammonium salt if the bicarb does not do it.

Adding a total of 3.5eq definitely moved the reaction along but made things difficult at the end.

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