How Protonation and Deprotonation Affect Reactivity

Protonation and Deprotonation: How They Affect Reactivity

One thing has been missing from our discussion of acid-base reactions.

Who cares?

What does it matter that we understand acid base reactions? Why is it important?

Today, I hope to show that it matters a lot, not only for its own sake, but for topics that concern the rest of the course, because acid-base reactions can have a drastic effect on the reactivity of molecules.

Table of Contents

1. Acid Base Reactions Dramatically Affect The Reactivity Of A Molecule
2. Deprotonation Of A Molecule Makes It More Electron Rich (And More Nucleophilic)
3. Protonation Of A Molecule Makes It More Electron-Poor (Electrophilic)
4. Through Resonance, Acid-Base Reactions Can Affect The Electron-Density Of Neighboring Atoms
5. Notes

1. Acid Base Reactions Dramatically Affect The Reactivity Of A Molecule

Let’s review one last time what happens in acid-base reactions.

• When a molecule acts as an acid, it loses a proton (H+) to become its conjugate base. The conjugate base is always more negative (by 1 charge unit) than the acid.
• When a molecule acts as a base, it gains a proton (H+) to become its conjugate acid. The conjugate acid is always more positive (by 1 charge) than the base.

Okay. So why bring up the charges here?

Because, as I’ve said many times before, the “one sentence summary of chemistry” is the following: opposite charges attract, and like charges repel.
The second part to this is that chemical reactions are transactions of electrons between atoms – from areas of high electron density, to areas of low electron density.

So….

• When a molecule is deprotonated to become its conjugate base, it gains negative charge – and therefore becomes more electron-rich. 
• And when a molecule is protonated to become its conjugate acid, it loses a unit of negative charge – and therefore becomes more electron – poor.

Electrons are the “currency” of chemistry. So acid base reactions – by increasing or decreasing electron density – drastically affect the reactivity of a molecule.

In chemical reactions, electron rich areas are likely to be the source of electrons in chemical reactions, and electron-poor areas are likely to be the eventual destination of electrons.

2. Deprotonation Of A Molecule Makes It More Electron Rich (And More Nucleophilic)

When a neutral molecule is deprotonated, it becomes more electron-rich.  To continue with the currency analogy, it’s a little bit someone who suddenly finds themselves with more money than they know what to do with,  and starts to contemplate philanthropic endeavors.

And when a neutral molecule is protonated, it becomes more electron-poor,  if someone who suddenly found themselves wiped out in a stock market crash and in need of social assistance.

Chemistry operates a little bit like Marx’s idealized version of Communism: “from those of greatest number, to those of greatest need.”

Let’s illustrate this with some examples.

Here’s three compounds that react with base.

Note how deprotonation has charged the formal charge on each of these molecules; they’ve gone from neutral to negatively charged – and therefore, more electron rich. [I just used a generic “base” here, so we could just focus on what happens to one component of the reaction].
That’s the bottom line here: removal of a proton makes any molecule more electron rich.

3. Protonation Of A Molecule Makes It More Electron-Poor (Electrophilic)

The opposite applies for molecules that are protonated. In the example of the alcohol and the amine below, for instance, addition of acid removes electron density from the oxygen and nitrogen respectively.

One common pitfall, however: recall that “formal charge” can mislead sometimes! Since oxygen (and nitrogen) are more electronegative than hydrogen and carbon, the positive charge (i.e. low electron density) is actually distributed among these atoms!

[Another important consequence of this, as we’ll see, is that protonation will also weaken the carbon-oxygen bond (i.e. make it much more likely to break). ]

4. Through Resonance, Acid-Base Reactions Can Affect The Electron-Density Of Neighboring Atoms

It’s also important not to forget about resonance. When the oxygen of a ketone is protonated, for instance, it can distribute a significant portion of the positive charge to the adjacent carbon through resonance!

This leads to what might seem like a counter-intuitive result. Protonation of the oxygen makes the carbon more electron poor!!!

Bottom line here (again) – addition of a proton  to a molecule makes it more electron poor. [Note 1]

This post does it for our series on acid-base reactions.

But like I said before, acid-base reactions will have tremendous consequences for chemical reactivity in some of the subsequent classes of reactions that will get covered… so you haven’t seen the last of them!

In the next series, we’ll cover another important class of reaction called substitution reactions, that have several important similarities (and differences) to acid-base reactions.

Notes

Note 1: This holds not just hold for protons, but for any type of Lewis acid (such as BF₃, AlCl₃, etc.)

Note 2. We have specialized words that we use to describe the properties of “electron rich” and “electron poor” without using those words exactly. Those words are, respectively, nucleophilic and electrophilic.