[Breakerofglassware97]

Hey!


So in the lab I deprotonated adenine using sodium hydride in DMF and then reacted it with an alkyl group. The proton NMR showed that adenine was deprotonated at N9 (the secondary amine).

I'm trying to figure out why N9 was deprotonated over the primary amine (on C6)... The pKa of N9 is 4.15 and the NH2 is 9.15, so am I correct in saying that N9 is deprotonated over NH2 due to the pKa difference?


Secondly, I added a benzoyl protecting group to thymine with the aim of forming 3-benzoylthymine. However, this typically formed the 1,3-disubstituted byproduct. When deprotecting 1,3-product, the N1 position is selectively deprotected over the N3 position.

I want to find out what the reason for this selectivity is? I think it is to do with the stability of the anionic intermediates. If I'm correct in drawing my resonance structures (apologies, I've attached a hand-drawn diagram rather than chemdraw), both intermediates have the same number of resonance forms, but the N1-deprotected product is more stable because it delocalised the negative charge over a greater number of atoms. Therefore, it is selectively unprotected.


I've attached the structures of adenine and thymine just for reference!


Thanks,

Breakerofglassware97

P.S. I hope everyone is keeping safe!

[kriggy]

Hey!


So in the lab I deprotonated adenine using sodium hydride in DMF and then reacted it with an alkyl group. The proton NMR showed that adenine was deprotonated at N9 (the secondary amine).

I'm trying to figure out why N9 was deprotonated over the primary amine (on C6)... The pKa of N9 is 4.15 and the NH2 is 9.15, so am I correct in saying that N9 is deprotonated over NH2 due to the pKa difference?

Well the pKa is measure of the acidity of the proton so it is the reason somehow. btw are you sure the NH2 pka is 9.15? That is fairly low compared to other amines which are around 30. Are you sure you werent looking at pKa of protonated species?

Im not sure about the thymine deprotection but the N1 position seems more stericaly accesible than the N3