Objective

Welcome! In this guide, you'll learn how to identify the most acidic proton in a molecule, a fundamental skill in organic chemistry.

Let's begin with a simple example.

Challenge 1

Question:

Identify the most acidic proton in acetic acid

Here’s how we’ll do it

Step 1: Draw the corresponding conjugate base for each proton

First, let’s label the protons.

Next, draw the corresponding conjugate base for each labeled proton.

• Conjugate base a

• Conjugate base b

Step 2: Evaluate and rank the stability of the conjugate bases

Next, we need to figure out how stable each conjugate base is. Remember, the stronger the acid, the more stable its conjugate base. By figuring out which conjugate base is more stable, we can identify the most acidic proton.

To evaluate stability, consider these five factors in this order: Charge, Atom, Resonance, Induction, Orbitals, taking into account any exceptions to the order of priority.

Charge

What is the charge on each conjugate base?

Each base carries a negative one (-1) charge.

Conclusion: The charge factor doesn’t help us here since all the bases have the same charge.

Atom

Which atom is holding the negative charge?

• In conjugate base a, the negative charge is on carbon.

• In conjugate base b, the negative charge is on oxygen.

There are two trends to consider: electronegativity and size.

• Across a row on the periodic table: We consider electronegativity.

• Down a column on the periodic table: We consider size.

Carbon and oxygen are in the same row of the periodic table, so we consider electronegativity.

Oxygen is more electronegative than carbon, making it better at stabilizing the negative charge. Therefore, conjugate base B is more stable than conjugate base A.

Since we’ve determined the acid based on this factor, there’s no need to consider the remaining factors.

Step 3: The more stable conjugate base corresponds with the more acidic proton

Since conjugate base B is more stable, the proton B is the most acidic proton in acetic acid.

We can also confirm our results with the actual pK_a values for each proton.

The pK_a value is a measure of the acidity of a proton. A lower pK_a value indicates a stronger acid (more acidic proton). Let's look at the pK_a values for the protons in acetic acid:

• Proton A (C-H): The pK_a is around 20.

• Proton B (O-H): The pK_a is around 4-5.

The much lower pKa of proton B confirms that it is significantly more acidic than proton A. This aligns with our earlier analysis based on the stability of the conjugate bases.

Let's take it up a notch with this next example

Challenge 2

Question:

In the following molecule, which of the labeled protons is the most acidic?

We'll follow the same steps we used before.

Step 1: Draw the corresponding conjugate base for each proton

Let’s draw the conjugate base for each labeled proton.

• Conjugate base a

• Conjugate base b

• Conjugate base c

Step 2: Evaluate and rank the stability of the conjugate bases

Next, we need to figure out how stable each conjugate base is. Remember, the stronger the acid, the more stable its conjugate base. By figuring out which conjugate base is more stable, we can identify the most acidic proton.

To do this, we’ll look at five factors: Charge, Atom, Resonance, Induction, and Orbitals.

Charge

What is the charge on each conjugate base?

Each base carries a negative one (-1) charge.

Conclusion: The charge factor doesn’t help us here since all the bases have the same charge.

Atom

Which atom is holding the negative charge?

In conjugate bases a, b, and c, the negative charge is on carbon.

Conclusion: The atom factor doesn’t help us here either since the negative charge is on the same atom in all bases.

Resonance

Is the negative charge delocalized over multiple atoms?

• Conjugate base a

The negative charge is ‘stuck’ on the carbon atom (localized).

• Conjugate base b

The negative charge is spread out over two carbon atoms and one oxygen atom.

• Conjugate base c

The negative charge is spread out over one carbon atom and one oxygen atom.

Conjugate bases b and c are stabilized by resonance, while a is not. This makes a the least stable conjugate base and proton a the least acidic of the three protons.

🤔 But, between b and c, which is more stable?

• Conjugate base b

The negative charge is spread out over three atoms (two carbon atoms and one oxygen atom).

• Conjugate base c

The negative charge is spread out over two atoms (one carbon atom and one oxygen atom).

This makes conjugate base b more stable and the most stable of all three conjugate bases.

Step 3: The more stable conjugate base corresponds with the more acidic proton

Since conjugate base b is the most stable conjugate base, proton B is the most acidic of the three highlighted protons.

By following these steps, we see that proton b is the most acidic because its conjugate base is the most stable. Keep practicing with different molecules to get the hang of identifying the most acidic proton!