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The Conjugate Base is Always a Stronger Nucleophile

Let’s say you get asked this exam question:

All else being equal, what’s a better nucleophile: water or OH(-) ? Acetic acid or OAc(-)? HF or F(-)? [Let’s agree to leave out the counterion for the moment: it isn’t  crucial for this discussion]. Butane or Bu(-) ? NH3 or NH2(-)? Hydrogen peroxide or HOO(-) ? Given an acid and its conjugate base, which will have the highest affinity for a given electrophile?

Recall that nucleophilicity refers to the “nucleus-seeking” (i.e. positive charge seeking) ability of a species, which is proportional to its electron density. When a proton is stripped from an acid, the electron pair that was previously shared with hydrogen is completely handed over to the conjugate base, which becomes negatively charged. Opposite charges attract, and the strength of the interaction is proportional to the magnitude of the respective positive and negative charges. [Tying it back to physics, this is Coulomb’s law in action]. Therefore, the affinity of this species for a given electrophile will always be higher than that of the acid due to the greater electrostatic attraction between opposite charges.

So given identical reactlon conditions (e.g. temperature, solvent, and electrophile) the conjugate base is always a better nucleophile. And when I say “always” I don’t mean “always*” with fingers crossed behind my back because you may subsequently discover that I only told you part of the truth (a common pedagogical necessity, I am sorry to say). I mean always –  as in, I cannot think of an exception to this.

N.B. Don’t forget that when we talk about the “strength” of nucleophiles, we are talking about reaction rate. This is the key difference between nucleophilicity and acidity. The strength of an acid – its pKa – is measured by the position of the equilibrium between an acid and its conjugate base, which is a function of their relative thermodynamic stability. Not so with nucleophilicty, which is all about speed, or “kinetics” as we like to say.

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