[Organiker 8]

Hello all,

     I am new to this forum. I have just completed my second semester of Organic Chemistry and have taken a real interest in the subject. Although I just completed my second semester of organic chemistry I have been confused on the reactivity of nucleophiles and electrophiles. The mechanisms I've learned generally go over simple molecules to get the mechanism across to the student. My question is... How do I know which atom in a molecule a nucleophile will attack? Is there a systematic way knowing which atom in a molecule will attract the nucleophile specifically? I have been given a plethora of mechanisms I have memorized and understand, but I do not understand why a certain nucleophile in a certain mechanism will attack a certain atom in a molecule? I don't know if I am asking this question clearly, but can anyone help me on this?

[TwistedConf]

It sounds like you've memorized a lot, and were tested on exactly what you memorized- but actually learned very little about organic chemistry.

You are correct the that simple molecules that are (unfortunately) always used in average introductory courses don't do much to answer your question.

In molecules with more than one functional group there are ways to anticipate the most likely reaction site---  perhaps the MOST electrophilic or the MOST nucleophilic atom among several choices. Other times, reaction at multiple sites is competitive. In such cases the reaction is not selective and probably not part of a useful synthetic strategy.

How do you know? Time and experience play a big role. But it all starts with understanding the WHY of these mechanisms you've learned rather than just memorizing a bunch of curved arrows to draw.

[Organiker 8]

It sounds like you've memorized a lot, and were tested on exactly what you memorized- but actually learned very little about organic chemistry.

Please don't take advantage of the fact I am asking a question to assume that I don't know anything about organic chemistry. I did not JUST learned curved arrows to draw. I understand the mechanism, my teacher made it very clear by the depth of our tests.

That being said, you, yourself, have not answered my question. If you do not know the answer that is fine, but if you're going to insult someone's intelligence at least show a bit of yours. To rephrase, my question is what determines the the reactivity of the atoms in a molecule? Obviously polarity, but how do you measure that polarity to compare to other atoms in the molecule? Also, as the case for nitration of benzene, a nitronium ion is formed by reaction of HNO3 and H2SO4.... The HNO3 is protonated by the H2SO4 but at H-O-N oxygen, rather than the (-)O-N oxygen. It would make sense for the protonation to occur at the negative charged oxygen rather than form another plus charge. What dictates this protonation?

[orgopete]

It is difficult to answer these general questions. It would be better if you gave an example of a problem that displayed the difficulty being asked about.

[magician4]

IMHO, there is no such thing as "the one and only principle" which allows for the decision where and why for example a nucleophile will attack a molecule with a multitude of potential sites that might be available.

"polarity" is one of the aspects to consider, yes, but besides that a lot of other aspects might come into play: solvent matrix, steric aspects, ΔG of total reaction, kinetics...

... and sometimes even (by equilibrium) unfavoured initial intermediates might become  relevant, as only their successors are the stable products (or the most stable products) in town.

... as is the case with the protonation of nitiric acid with subsequent water elimination, leading to NO₂⁺ - if we're talking aromatic electrophilic substitution , that is ( in other circumstances, this particle would be completely irrelevant, as it will vanish in a New York minute )

in this case, however, this particle is being discussed, not because it is "likely", but because , by the end of the day , it's the only game in town.


regards

Ingo

[salteen]

As others have mentioned, there is no systematic way to definitively predict what will happen in a reaction - sometimes even the brightest chemist is surprised by a particular mechanism.  This is what makes organic chemistry so intriguing (at least for me).   There are indeed lots of factors which determine reaction outcome, but with practice you can sometimes narrow down what's happening.

To answer your question about what determines the reactivity of an atom, you have to first identify the role it plays in the reaction - let's limit it to nucleophile or electrophile for this discussion.  You probably know that nucleophiles possess negative or partial negative charge, and electrophiles have positive or partial positive charge.  Things that affect an atom's charge character can include:

1)  Acid/base reactions the atom is involved in (these are fast and therefore happen first)
2)  The inherent properties of the atom such as its electronegativity and atomic radius
3)  Any resonance structures the atom participates in. 

I usually suggest to students to go through that list (in that order) when trying to figure out a mechanism they haven't seen before.  It is by no means exhaustive, but for 1st and 2nd year-level reactions it often helps in identifying your nucleophile and electrophile, which are present in the majority of reactions taught at the introductory level.  I recommend you keep those concepts in mind when looking for enlightenment on a particular problem.

Regarding your question about the nitronium ion formation: You're right, the negatively-charged oxygen on nitric acid is more basic and more likely to get protonated.  In reality, it does get protonated.  However, it doesn't lead to the formation of the nitronium ion like protonation of the other oxygen does, and it's an equilibrium process. So once it happens, it will eventually be deprotonated since it doesn't accomplish anything.  For this reason it isn't traditionally shown in the mechanism.