[Big-Daddy]

What are the guidelines to working out which atom, in a large organic molecule, is the most likely to become protonated in an acidic or salt solution?
 
In one of the examples I have seen, it was the lone N atom (not attached to any H atoms, but connected to 3 C atoms which formed parts of a long chain). What is the general method for deducing which atoms are more likely than others to be protonated in a salt solution (with an acidic salt)?

[Dan]

This is a broad question. There are many factors affecting the basicity of organic molecules, such as induction, resonance and hydrogen bonding. Acid-base behavior is a fundamental topic in organic chemistry, and there is a chapter on acids and bases in most organic chemistry textbooks. I would recommend you do some background reading and then post more specific questions if there are any points you don't understand.

[Big-Daddy]

With a look at my Organic Chemistry book I've been able to come up with some general guidelines on how to work out how acidic (how likely to be the proton dissociated, or removed in the presence of a base) a H proton is based on the atom (let it be X) to which it is attached, the atoms to which X is attached, etc.

However, I'm not entirely confident on how to translate this to figuring out which atoms in the large organic molecule are most likely to be protonated in an acidic solution.

[Dan]

Can you give an example, then we can work through it with you?

[Big-Daddy]

Can you give an example, then we can work through it with you?

I don't think so, because with specific examples it's always easy simply to apply one of the rules and that answers the question, but what I'm looking to do is understand all the rules rather than how they apply, because I just don't know them yet.

OK, I can show what I've got when it comes to the acidity of H atoms (i.e. a more acidic H atom is one that is likeliest to dissociate or be removed by the base in solution). Please correct me on anything that is wrong:

1. Which atom is the H attached to? Let this atom be called X. Then in order of decreasing acidity of the H atoms attached to X, we have X=I, Br, Cl, S, P, F, O, N and C (I'm not entirely sure about the order of the "S, P, F, O" block).
2. If X is attached to the C from C=O, or C from C=C, the acidity is increased (C=O > C=C). In the general case where X is attached to the M₁ from M₁=M₂ (where M1 and M2 are two atoms), the more electronegative M₁ and M₂ are the more acidic the protons on X will be.
3. The presence of electronegative atoms near X increases acidity of protons on X. The closer they are the more acidic; the greater their electronegativity, the more acidic; the greater their number, the more acidic. (I think that's the rough order of precedence as well - the closeness is the most important factor, followed by their place in the electronegativity series, followed by how many of them there are.)
4. If X is attached to one of the C atoms from C≡C, the protons on it will be more acidic than if X were simply attached to C atoms single bonded. (The same applies even if, instead of C carbon, we have something like N nitrogen instead.)

There must be a few inaccuracies which I would appreciate if you could correct, but on the whole this is what I can glean from the textbook.

If you could help me with that first, we can move on later to how this relates to the opposite, which is likelihood of protonation rather than likelihood of dissociation.