[arooga]

I am having trouble discerning and explaining the least basic nitrogen in the structure of caffeine (image attached).

I know that the most basic nitrogen is Ndelta because it is double-bonded to one carbon and single-bonded to another carbon and there's the least steric hinderance from other groups and the positive charge can be distributed over the ring structure due to the conjugation of the double bonds.

The other 3 nitrogens are not basic at all, but how would I determine and explain the least basic nitrogen?

Thank you

[Schrödinger]

Please see http://www.chemicalforums.com/index.php?topic=41147.0

[arooga]

Based on that thread, could either Nbeta or Ngamma be argued as the least basic nitrogen? I am not sure if there is a way to find the exact pKb values of each specific nitrogen atom.

[stevieG22]

..

[adianadiadi]

No doubt it is beta nitrogen, which is less basic since it is involved in aromaticity and its contribution is even more alleviated by two electron withdrawing carbonyl oxygens and more hindered sterically.

No conclusive argument found in case of gamma.

[spirochete]

Also alpha is directly conjugated with the electron donating gamma nitrogen.  In contrast, Beta is only cross conjugated with this electron donating group.  This makes it relatively more basic, all other things equal.