A: The Brønsted-Lowry definition of acidity and basicity

We’ll begin our discussion of acid-base chemistry with a couple of essential definitions. The
first of these was proposed in 1923 by the Danish chemist Johannes Brønsted and the English
chemist Thomas Lowry, and has come to be known as the Brønsted-Lowry definition of acidity
and basicity. An acid, by the Brønsted-Lowry definition, is a species which acts as a proton
donor, while a base is a proton acceptor. We have already discussed in the previous chapter one
of the most familiar examples of a Brønsted-Lowry acid-base reaction, between hydrochloric
acid and hydroxide ion:

In this reaction, a proton is transferred from HCl (the acid, or proton donor) to hydroxide ion
(the base, or proton acceptor). As we learned in the previous chapter, curved arrows depict the
movement of electrons in this bond-breaking and bond-forming process.
After a Brønsted-Lowry acid donates a proton, what remains is called the conjugate base.
Chloride ion is thus the conjugate base of hydrochloric acid. Conversely, when a Brønsted-Lowry
base accepts a proton it is converted into its conjugate acid form: water is thus the conjugate
acid of hydroxide ion.
Here is an organic acid-base reaction between acetic acid and methylamine:

In the reverse of this reaction, acetate ion is the base and methylammonium ion (protonated
methylamine) is the acid.

What makes a compound acidic (likely to donate a proton) or basic (likely to accept a proton)?
Answering that question is one of our main jobs in this chapter, and will require us to put to use
much of what we learned about organic structure in the first two chapters, as well as the ideas
about thermodynamics that we reviewed in chapter 6.
For now, let's just consider one common property of bases: in order to act as a base, a molecule
must have a reactive pair of electrons. In all of the acid-base reactions we'll see in this chapter,
the basic species has an atom with a lone pair of electrons. When methylamine acts as a base,
for example, the lone pair of electrons on the nitrogen atom is used to form a new bond to a
proton.
Clearly, methylammonium ion cannot act as a base – it does not have a reactive pair of electrons
with which to accept a proton.

Later, in chapter 14, we will study reactions in which a pair of electrons in a pi bond of an alkene
or aromatic ring act in a basic fashion - but for now, will concentrate on the basicity of non-
bonding (lone pair) electrons.
EXERCISE 7.1.1

Complete the reactions below - in other words, draw structures for the missing conjugate acids
and conjugate bases that result from the curved arrows provided.

Solutions

B: The Lewis definition of acidity and basicity

The Brønsted-Lowry picture of acids and bases as proton donors and acceptors is not the only
definition in common use. A broader definition is provided by the Lewis definition of acidity
and basicity, in which a Lewis acid is an electron-pair acceptor and a Lewis base is an electron-
pair donor. This definition covers Brønsted-Lowry proton transfer reactions, but also includes
reactions in which no proton transfer is involved. The interaction between a magnesium cation
(Mg+2) and a carbonyl oxygen is a common example of a Lewis acid-base reaction in enzyme-
catalyzed biological reactions. The carbonyl oxygen (the Lewis base) donates a pair of electrons
to the magnesium cation (the Lewis acid).
While it is important to be familiar with the Lewis definition of acidity, the focus throughout
the remainder of this chapter will be on acid-base reactions of the (proton-transferring)
Brønsted-Lowry type.

A: Defining the acidity constant

You are no doubt aware that some acids are stronger than others. The relative acidity of
different compounds or functional groups – in other words, their relative capacity to donate a
proton to a common base under identical conditions – is quantified by a number called the acidity
constant, abbreviated Ka. The common base chosen for comparison is water.
We will consider acetic acid as our first example. If we make a dilute solution of acetic acid in
water, an acid-base reaction occurs between the acid (proton donor) and water (proton
acceptor).

Acetic acid is a weak acid, so the equilibrium favors reactants over products - it is
thermodynamically 'uphill', as indicated in the figure above by the relative length of the
forward and reverse reaction arrows, and in the reaction coordinate diagram below in which
products are higher energy than reactants.

As you know, the equilibrium constant Keq is defined as:

In more general terms, the dissociation constant for a given acid HA or HB + is expressed as:

The value of Ka for acetic acid is 1.75 x 10-5 - much less than 1, indicating there is much more
acetic acid in solution at equilibrium than acetate and hydronium ions.
Conversely, sulfuric acid, with a Ka of approximately 109, or hydrochloric acid, with a Ka of
approximately 107, both undergo essentially complete dissociation in water: they are very strong
acids.
A number like 1.75 x 10- 5 is not very easy either to say, remember, or visualize, so chemists
usually use a more convenient term to express relative acidity. The pKa value of an acid is simply
the log (base 10) of its Ka value.
pKa = -log Ka Ka = 10-pKa
Doing the math, we find that the pKa of acetic acid is 4.8. The pKa of sulfuric acid is -10, and of
hydrochloric acid is -7. The use of pKa values allows us to express the relative acidity of common
compounds and functional groups on a numerical scale of about –10 (for a very strong acid) to 50
(for a compound that is not acidic at all). The lower the pKa value, the stronger the acid.
The ionizable (proton donating or accepting) functional groups relevant to biological organic
chemistry generally have pKa values ranging from about 5 to about 20. The most important of
these are summarized below, with very rough pKa values for the conjugate acid forms. More
acidic groups with pKa values near zero are also included for reference.
Approximate pKa values to know
hydronium ion (H3O+) : 0
protonated alcohol: 0
protonated carbonyl: 0
carboxylic acids: 5
protonated imines: 7
protonated amines: 10
phenols: 10
thiols: 10
alcohols, water: 15-18 (water is 15.7)
 alpha-carbon acids*: 20
*alpha-carbon acids will be discussed later in this chapter
You are strongly recommended to commit these rough values to memory now - then if you need a
more precise value, you can always look it up in a pKa table.
Caution! pKa is not the same as pH!
It is important to realize that pKa is not the same thing as pH: the former is an inherent
property of a compound or functional group, while the latter is a measure of hydronium ion
concentration in a given aqueous solution:
pH = -log [H3O+]
Knowing pKa values not only allows us to compare acid strength, it also allows us to compare base
strength. The key idea to remember is this: the stronger the conjugate acid, the weaker the
conjugate base. We can determine that hydroxide ion is a stronger base than ammonia (NH3),
because ammonium ion (NH4+, pKa = 9.2) is a stronger acid than water (pKa = 15.7).
EXERCISE 7.2.1

Which is the stronger base, CH3O- or CH3S-? Acetate ion or ammonia? Hydroxide ion or acetate
ion?
Solution
Let's put our understanding of the pKa concept to use in the context of a more complex molecule.
For example, what is the pKa of the compound below?

We need to evaluate the potential acidity of four different types of protons on the molecule,
and find the most acidic one. The aromatic protons are not all acidic - their pKa is about 45. The
amine group is also not acidic, its pKa is about 35. (Remember, uncharged amines are basic: it is
positively-charged protonated amines, with pKa values around 10, that are weakly acidic.) The
alcohol proton has a pKa of about 15, and the phenol proton has a pKa of about 10: thus, the most
acidic group on the molecule above is the phenol. (Be sure that you can recognize the difference
between a phenol and an alcohol - remember, in a phenol the OH group is bound directly to the
aromatic ring). If this molecule were to react with one molar equivalent of a strong base such as
sodium hydroxide, it is the phenol proton which would be donated to form a phenolate anion.
EXERCISE 7.2.2

Identify the most acidic functional group on each of the molecules below, and give its
approximate pKa.
Solution

B: Using pKa values to predict reaction equilibria

By definition, the pKa value tells us the extent to which an acid will react with water as the base,
but by extension we can also calculate the equilibrium constant for a reaction between any acid-
base pair. Mathematically, it can be shown that:
Keq = 10ΔpKa
. . . where ΔpKa = (pKa of product acid minus pKa of reactant acid).
Consider a reaction between methylamine and acetic acid:

The first step is to identify the acid species on either side of the equation, and look up or
estimate their pKa values. On the left side, the acid is of course acetic acid while on the right
side the acid is methyl ammonium ion (in other words, methyl ammonium ion is the acid in the
reaction going from right to left). We can look up the precise pK a values in table 7 (at the back
of the book), but we already know (because we have this information memorized, right?!) that
the pKa of acetic acids is about 5, and methyl ammonium is about 10. More precise values are 4.8
and 10.6, respectively.
Without performing any calculations at all, you should be able to see that this equilibrium lies
far to the right-hand side: acetic acid has a lower pKa, meaning it is a stronger acid than methyl
ammonium, and thus it wants to give up its proton more than methyl ammonium does. Doing the
math, we see that
Keq = 10ΔpKa = 10(10.6 – 4.8) = 105.8 = 6.3 x 105
So Keq is a very large number (much greater than 1) and the equilibrium for the reaction between
acetic acid and methylamine lies far to the right-hand side of the equation, just as we had
predicted. This also tells us that the reaction has a negative Gibbs free energy change, and is
thermodynamically favorable.
If you had just wanted to quickly approximate the value of Keq without benefit of precise
pKa information or a calculator, you could have approximated pK a ~ 5 (for the carboxylic acid)
and pKa ~10 (for the ammonium ion) and calculated in your head that the equilibrium constant
should be somewhere in the order of 105.