[joc]

Please help.

Pls refer to the attached file for the structure of caffeine.

The question is which N atom in caffeine is the least basic.

I think the N_gamma is the least basic because the electron pair is involved in an aromatic ring system (Huckel's rule).  However, some suggest that it is the N_beta is the least basic because the lone pair is delocalized to the two neighbouring strongly electron withdrawing C=O groups.  Which one is more likely to be true?

Thanks a million!

joc

[Doc Oc]

I would also wager on beta, but I'm not an expert with nucleotide chemistry.

[Schrödinger]

Something tells me it is N_beta.

When you try to draw some of its resonance structures, you can come up with the following(see figure attached) :

In addition to the stabilization due to aromaticity in the figure, the beta N is attached to 2 C=O groups.

I'm definitely not sure, but I thought I'd give it a shot


Oh...and one more thing. How do I attach a figure without having to attach a file?
I mean can I copy a picture from Chemdraw and just paste it here?

[nj_bartel]

My guess would be beta too.

[joc]

Thanks for your input. 

By the way, is there any source on the internet on the data of pK_b values or pK_a values of the common natural organic compounds such as caffeine.  What I mean is for all the N atoms or OH groups.  I have tried to search but can only get the values for the most basic one or the most acidic one.

Thanks again.

[MissPhosgene]

Hello,

   I doubt you will find tables for that specifically. However, you could look at  pka tables and try to deduce..

I have to use this one in class and it's really really good...

http://evans.harvard.edu/pdf/evans_pKa_table.pdf

[demoninatutu]

This one turns out to be a little trickier than I expected. I'm going with the gamma nitrogen for the same reason you suggested, it's aromatic. Aromaticity trumps conjugation.

[toddwick]

I would say that depending on the aromatic nature of the entire molecule, which I'm sure has been explored (didn't do a literature search myself so that may not be true), both beta and gamma could be argued as the least basic.  I would suggest trying to find some sort of modeling program and seeing what happens.  I'm not exactly sure how one would come up with an approximation on the lone pairs relative basicities, but I am positive that you could find some protocol that could give you at least a qualitative (which is stronger) judgment.

If you have access to Gaussian thats a great start.