So I have this ridiculous problem which has eaten up my last few days. I have a caffeine like molecule and I need to cleave the two amides on the 6 membered ring to liberate the amine. Conditions that I have found suggested in the literature include:
1) NaBH4 in 6:1 ipro/H20 for 4 hours, then reflux overnight at pH 5 (AcOH)
2) Hydrazine, methyl hydrazine, hydrazine monohydrate, etc. all excess, in MeOH, or in THF, or neat, ON @ RT
3) TFA in both MeOH and neat, ON @ RT
4) LAH in THF, ON @ RT
5) Excess n-BuLi in THF, ON @ RT
6) Excess LiOH with iodine, 4 hours @ RT, then acidify with AcOH
7) 6% HCl/H2O2, in H20, ON @ RT
Excess NBS in THF, ON @ RT
9) Excess NaOH, ON @ RT
As you can see, I have been using some pretty forcing conditions. I get a lot of new spots on TLC (4:3:1 CHCl3/MeOH/NH4OH) but nothing that corresponds with the liberated amine (I have am authentic standard).
Next step is to prep TLC all of this garbage and do the NMR and MS one by one. This could take weeks.
If anyone could suggest a set of conditions to cleave this type of amide, I would be forever grateful. I suppose that this amide is so robust compared to others because to cleave it, you have to disrupt the aromaticity of the entire ring system.
One thing that I thought about doing was using Pd on C and H2 to reduce the ring and then the amide will be easier to cleave... the only problem being that I have a olefin elsewhere in the molecule that I can't sacrifice.
Thanks in advance.