Sciencemadness Discussion Board

Do stronger bases create stronger nucleophiles?

JefferyH - 8-5-2014 at 18:55

Very nooby question... I know....

If there is a compound that can be deprotonated by a base to give a nucleophilic enolate. Does a stronger base create a stronger nucleophile? Versus, if a weaker base was able to deprotonate the same compound? Or does the strength of the nucleophile depend on the molecule itself and not the base use to deprotonate it?


thesmug - 8-5-2014 at 18:56

I think it's a combination of both. Please correct me if I'm wrong

DraconicAcid - 8-5-2014 at 19:47

If you're deprotonating HX to give X-, the nucleophilicity of X- will not depend on the strength of the base you're using to deprotonate HX, although a stronger base may give you a higher concentration of X- at equilibrium.

JefferyH - 8-5-2014 at 19:50

That's what I assumed but I wasn't entirely sure. That helps a lot! Thanks!

Nicodem - 9-5-2014 at 07:35

Quote: Originally posted by JefferyH  
If there is a compound that can be deprotonated by a base to give a nucleophilic enolate. Does a stronger base create a stronger nucleophile? Versus, if a weaker base was able to deprotonate the same compound? Or does the strength of the nucleophile depend on the molecule itself and not the base use to deprotonate it?

The type of the base can have a strong influence on the nucleophilicity of anions, particularly of the ambiphilic nucleophiles. This is not due to the base itself, but due to its counter-ion. This effect can be either irrelevant in highly polar protic solvents (such as water, lower alcohols, etc.), or it can have an extremely strong effect in non-polar solvents.
See this thread for more info.

Obviously though, this has nothing to do with the strength of the base. The pKa of the base influences the proton transfer equilibrium point (and trough this it affects the rate of the reaction), but the strength itself it has no effect on the nucleophilicity (counter-ion effects and possible effects from the coordination with the base protonation product are not necessarily related to the "strength").

madscientist - 14-5-2014 at 20:58

Basicity is thermodynamic, nucleophilicity is kinetic. Strong bases can be poor nucleophiles, and vice versa. For example, Hunig's base isn't much of a nucleophile, but it's a hell of a lot more basic than CN-, and will deprotonate HCN easily. Steric hinderance and delocalization of charge are the most common ways to increase the strength of a base while diminishing nucleophilicity. On the other end of the spectrum, things like the alpha effect become important - hydroxylamine is more nucleophilic than ammonia, and yet, it is less basic.

JefferyH - 14-5-2014 at 22:04

Here's a question. I was going to make a new thread for this but realized it could be tied into this one.

I was reading over a paper where the authors claimed the [totally deprotonated] potassium tert-butoxide enolate of a dicarbonyl was not reacting with the electrophile at any appreciable speed (less than 1% after 5 hours). The authors switched to potassium metal to deprotonate the substrate (forming the dipotassium salt), and it reacted to over 80% in an hour. There were no further comments made on this. The authors do make causual remarks about the reaction being effected by steric hindrance, but they make no specific reference to the butoxide ions. Out of 30 different substrates tested, only one of them (which didn't react at all as a butoxide enolate) was tested with potassium. So I am not sure if this specific case is included when they remark about steric hindrance effecting the reaction, or if there is another mechansm unbeknownst to me.

I realize tert-butoxide is more sterically hindered than a lone potassium atom, and this decreases its nucleophiliticity, but does this also mean that enolates of tert-butoxide are more sterically hindered and this itself can limit the reaction? As I understand it, the strength of the nucleophile doesn't always depend on the base that deprotonates it as said above.

Is this an explanation for why this reaction did/did not occur, the base was adding too much steric hindrance for the nucleophile to attack the electrophile?

[Edited on 15-5-2014 by JefferyH]

Nicodem - 15-5-2014 at 05:43

You forgot to add the reference.
Surely you don't believe anyone can answer that without knowing what you talk about or before reading the article?

PS: An enolate is an anion, so there is no such thing as a "butoxide enolate". Utmost you can have a potassium enolate (and the tert-butanol residue from the consumed base).

JefferyH - 15-5-2014 at 10:25

Sorry I don't have a digital copy. I have in front of me a brief physical copy of a paper we were given.

What I was asking is whether or not the carbons on the tert butyl are capable of blocking the site of deprotonation to an appreciable extent if the molecule (being deprotonated) is already sterically hindered. The question applies to any molecule. I am asking about the behavior of how these bases deprotonate.

These molecules on this paper are not named either, there are just pictures of them, at least on these pages I have. Being dicarbonyls, a good majority of them, it seems the potassium portion would be much more free to move, as opposed to the tert butyl. Do the bases stick around nearby to these molecules while the molecule is deprotonated? Allowing steric factors to influence the molecules nucleophilicity when trying to attack an electrophile?

DraconicAcid - 15-5-2014 at 10:29

You have a physical copy- does it give the authors? Title? Publication date? Page number?

If the t-butoxide deprotonates the diketone, then the t-butanol formed really has no reason to hang around the enolate formed, so why would it sterically hinder it?