nucleophilicity and atom size

[theonlytycrane]

I came across a question based on whether Se was a better nucleophile than S. Se is bigger so I figured it was a worse nucleophile (thinking of bulkier nucleophiles from organic).

Does nucleophilicity for atoms increase down the table?

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[salemstein]

I'd actually say its a better nucleophile because its got a wider valence electron orbital + more orbitals in between, shielding from the pull of the nucleus. Makes it easier to scoop up those electrons.

 

[7331poas]

It's more because the atom is large and has a lower charge density than the above to my knowledge.

 

[aalamruad]

I came across a question based on whether Se was a better nucleophile than S. Se is bigger so I figured it was a worse nucleophile (thinking of bulkier nucleophiles from organic).

Does nucleophilicity for atoms increase down the table?

Bulky organic molecules behave very differently that individual atoms in terms of nucleophilicity. When you get stuck on problems like this, just think of F-. Very small, very poor nucleophile. The elements directly below it in the periodic table are much better nucleophiles because they can more easily "squeeze" their electron clouds into tighter spaces that are farther away from their nuclei.

 

[7331poas]

Bulky organic molecules behave very differently that individual atoms in terms of nucleophilicity. When you get stuck on problems like this, just think of F-. Very small, very poor nucleophile. The elements directly below it in the periodic table are much better nucleophiles because they can more easily "squeeze" their electron clouds into tighter spaces that are farther away from their nuclei.

F is only a poor nucleophile in protic polar solvents. The reason large is better is because they can better perform with hydration layers on its surface.

If we were working in hexane I would be the worse nucleophile nucleophile

 

[BerkReviewTeach]

7331poas is spot on here. Nucleophilicity, at least in terms of traditional SN2 and SN1 reactions, varies with both the nucleophile and the solvent. In a portic solvent, fluoride is hindered by a solvent cage. because its ability to form hydrogen bonds and thus reduce the amount of electron density it can donate to an electrophile. In an aprotic solvent, where there is little to no solvent cage, fluorides are more mobile and can attack positively charged (or partially positively charged) sites readily, thus making it a better nucleophile than the other halides under those conditions.

In the case of S versus Se, there is no hydrogen bonding coming into play, but without knowing the solvent, it would be difficult to make a prediction, Was there a solvent specified in this question?

 

[aalamruad]

If we were working in hexane I would be the worse nucleophile nucleophile

I'm not sure about that, actually. You'd have a tough time getting the halides to dissolve in a solvent like hexane. And it's unlikely that you'd see something like that on the MCAT anyways, since most problems are viewed through a lens of human physiology, where we'll never have solvents like hexane. But what you say is certainly true for polar aprotic solvents, where nucleophilicity ends up correlating strongly with basicity due to the relative lack of h-bonding. That's a good point.

 

[7331poas]

I'm not sure about that, actually. You'd have a tough time getting the halides to dissolve in a solvent like hexane. And it's unlikely that you'd see something like that on the MCAT anyways, since most problems are viewed through a lens of human physiology, where we'll never have solvents like hexane. But what you say is certainly true for polar aprotic solvents, where nucleophilicity ends up correlating strongly with basicity due to the relative lack of h-bonding. That's a good point.

I would say its probably not a good policy to not learn things just because it probably wouldn't happen in the body. The principle of why nucleophilicity depends on solvent is pretty useful I think.

 

[aalamruad]

I would say its probably not a good policy to not learn things just because it probably wouldn't happen in the body. The principle of why nucleophilicity depends on solvent is pretty useful I think.

Agreed - I was just pointing out that hexane isn't a polar aprotic solvent, so using that as an example of F-'s variable nucleophilicity didn't quite make sense because F- wouldn't even dissolve in hexane.

 

[7331poas]

Agreed - I was just pointing out that hexane isn't a polar aprotic solvent, so using that as an example of F-'s variable nucleophilicity didn't quite make sense because F- wouldn't even dissolve in hexane.

I mean, there are ways to work a reaction in hexane with nucleophiles. This trend doesn't just apply to F and I, it applies to everything with lone pairs.

 

[BerkReviewTeach]

I mean, there are ways to work a reaction in hexane with nucleophiles. This trend doesn't just apply to F and I, it applies to everything with lone pairs.

This is a very good point. It's a reasonably common trick to use tetra-alkyl ammonium cations (which are nonpolar cations) to pull anions into aprotic, nonpolar solvents.

One point I'd love to add is that nucleophilicity correlates with basicity to some extent, but because basicity also competes with nucleophilicity, there are a good number of exceptions. A compound would much rather undergo a proton transfer reaction than a nucleophilic substitution, because of the smaller size of H versus an alkyl group. So strong bases make terrible nucleophiles, as they opt to deprotonate rather than substitute. However, once you get past a solvent-related threshold, the compound is too weak to act as a base, so it by default becomes a nucleophile. As a weak base gets stronger, it typically becomes a better nucleophile (with some deviation attributed to steric hindrance). This is why our best nucleophiles in aprotic solvents are things like CN-, RS-, and small amines. They are weak bases that are small and able to penetrate into the active carbon of an electrophile.

There are generalizations that apply to this topic, but because there are so many factors, it's hard to generate a one-size fits all rule for nucleophilicity. So for the original question, I would lean towards S2- being a better nucleophile than Se2-, because as a stronger weak base, S has concentrated charge that can be donated to an electrophile more readily than Se. The larger Se atom spreads its charge out more (is more diffuse), making it more stable and less reactive. Because neither species forms an H-bond, I would nervously ignore solvent effects for this question. I would conclude that the question writer wanted me to pick S over Se.

 

[theonlytycrane]

Here is the question and solution (from TPR):

Reaction 1 was a nucleophilic substitution with cysteine. Solvent effects were not taken into account and the answer choice given was A (I picked B thinking that S was a smaller ~ better nucleophile). Thoughts on their provided reasoning?

 

[7331poas]

Here is the question and solution (from TPR):

View attachment 203650 View attachment 203649

Reaction 1 was a nucleophilic substitution with cysteine. Solvent effects were not taken into account and the answer choice given was A (I picked B thinking that S was a smaller ~ better nucleophile). Thoughts on their provided reasoning?

What they said is correct and in line with what we are saying. Presumably this is a protic solvent when not specified and in that case the winner is Se which is the larger atom and better and attacking despite hydration layers.

 

[innominate18]

Here is the question and solution (from TPR):

View attachment 203650 View attachment 203649

Reaction 1 was a nucleophilic substitution with cysteine. Solvent effects were not taken into account and the answer choice given was A (I picked B thinking that S was a smaller ~ better nucleophile). Thoughts on their provided reasoning?

I believe everyone is hung up on size at the molecular level. This question specifically asks about two atoms: there is a direct relationship between ATOMIC size and nucleophilic strength. Atoms of larger sizes (example I-) serve as great nucleophiles. Valence electrons that are a distance away from the atom are more capable of being donated to an electrophile. At the molecular level is were nucleophiles run into steric issues. I hope this helps! If I'm wrong feel free to correct me.