CHM1321

Module 5 – Practice Problem Set - Solutions

1. What is a conjugate acid/base pair? Give some examples.

A conjugate acid/base pair consists of two species that differ by a single proton (H+). In the
pair, the protonated species is the acid, and the other is the conjugate base, or vice versa.

General form:

lose H gain H
HA A B HB
acid conjugate base conjugate
base acid

Some examples:

• CH3COOH/CH3COO–: acetate ion is the conjugate base of acetic acid (alternatively,

we could say that acetic acid is the conjugate acid of the acetate ion).
• NH3/NH4+ : ammonium ion is the conjugate acid of ammonia
• H2CO3/HCO3– : bicarbonate ion is the conjugate base of carbonic acid
• HCO3–/CO32– : carbonate ion is the conjugate base of the bicarbonate ion

2. How can acidity be quantified? In other words, what makes one acid stronger or weaker
than another? Explain.

The acidity of a compound is measured by the equilibrium constant for the ionization of the
acid, i.e.:

[H 3 O+ ][A – ]
Ka =
HA + H2O D H3O+ + A– [HA]

The stronger the acid, the greater the dissociation and the larger the value of Ka. Therefore,
strong acids have large values of Ka (>1), weak acids have small values of Ka (<1). We can also
represent these equilibrium constants as pKa’s, where strong acids have low or even negative
values of pKa and weak acids have large values of pKa.
3. Trimethylamine reacts with BF3 to give the adduct Me3NBF3. Is this an acid-base reaction?
If so, which is the base and which the acid? Show the electron-pushing arrows for this
reaction.

This is an example of a Lewis acid-base reaction: the trimethylamine is the Lewis base (electron
pair donor, or nucleophile) and the BF3 is the Lewis acid (electron pair acceptor, or electrophile).
BF3 is able to accept a pair of electrons because the B atom has an incomplete octet and is thus
electron deficient. It is sp2-hybridized, with an empty unhybridized p orbital. Below is the
mechanism:
F
F N B F
N F B
F F
empty
p orbital

Note that the hybridization at the B atom changes from sp2 to sp3.

4. The reaction profile of a Brønsted acid-base reaction is shown below.

a. Which is the stronger acid, HA or HB+? HB+
b. Does the equilibrium favour the reactants or products? REACTANTS
ENERGY

A– + HB+

HA + B

rxn coord.

5. Complete the following statement: the acidity of a compound can be increased by

___RAISING____ the free energy of the acid form and/or _____LOWERING_____ the free
energy of its conjugate base.
6. Identify the stronger acid in the following pairs of molecules. Justify your choice, using
pKa values.

General procedure: First, identify the most acidic proton in each compound. Recall that the
lower the pKa value, the stronger the acid. Next, compare the acidities of the two identified
protons to determine the more acidic compound overall. The answers below show the results
of the second step:

OH OH
vs

pKa ≈ 17
a. pKa ≈ 10

The phenol proton (pKa = 9.9) has a lower pKa than the alcohol (~17), therefore phenol is
the stronger acid. This makes sense, due to the resonance effect: the conjugate base of phenol
(phenoxide, C6H5O–), is stabilized by the delocalization of the negative charge over 4
different atoms:

O O O O

Since this is a more stable conjugate base, phenol is a better proton donor than cyclohexanol
(which has no such delocalization).

H
vs H2

pKa ≈ 25 pKa ≈ 36
b.
Using pKa’s: the alkyne proton is more acidic.

H vs H
N N

pKa ≈ 40
c. pKa ≈ 10.6

Using pKa’s: a protonated amine (ammonium cation) is more acidic than a neutral amine.
This also makes sense when examining the corresponding conjugate bases: a neutral amine
(R3N) versus an anionic amide (R2N–).
 HCl vs H2SO4

d. pKa ≈ -8 pKa ≈ -3

Using pKa’s: hydrochloric acid is more acidic (however, note that these are both strong
acids!)

H2 vs H 2O

e. pKa ≈ 36 pKa ≈ 15.7

Using pKa’s: water is more acidic. This makes sense: the O–H is much more polar than H-
H!

H
vs
H

pKa ≈ 25

f. pKa ≈ 51

Using pKa’s: an alkyne proton is more acidic than an alkane. This is due to increasing s-
character (sp is 50% s whereas sp3 is only 25% s).
7. The reaction profiles below shows the free-energy changes for the ionization of three
different acids, A, B, and C. Use the relative energies of the curves to match the compound
number (compound 1, compound 2, compound 3) with the acids in the diagram (A, B, C).

Ranking the relative acidities of the three compounds: RS–H > R2P–H > R2N–H

Since acidity is correlated to the stability of the conjugate base, we can rank the relative
stabilities of the three conjugate bases: RS– > R2P– > R2N–

Therefore, A = 2, B = 3, C = 1.
8. Draw the conjugate bases of the following molecules. For each pair of compounds, identify
the stronger acid. Justify your choice, using qualitative factors (i.e. not just pKa values).

NH2 – H+ NH OH – H+ O

a.
Comparing the conjugate bases: O and N are in the same row of the periodic table; moving
horizontally, we should examine the electronegativity of the deprotonated atom (the location
of the negative charge). Since oxygen is more electronegative than nitrogen, that means the
alkoxide anion (RO–) is more stable (lower energy) than the amide anion (RNH–). Therefore,
the alcohol must be the stronger acid (this is confirmed with general pKa values for alcohols
versus amines).

OH – H+ O – H+
OH O
O O
b.
Comparing the conjugate bases: here, the deprotonated atom (the location of the negative
charge) is identical in both cases (an oxygen atom). The difference between the two
conjugate bases is the presence of the resonance effect: a second, equivalent resonance
structure exists for the carboxylate anion (RCO2–); this delocalization of the negative charge
makes this conjugate base lower energy (more stable); in the alkoxide, no such
delocalization exists. Therefore, the carboxylic acid must be the stronger acid (this is
confirmed with general pKa values for carboxylic acids versus alcohols).

F F Br Br
– H+
OH – H+ O OH O
O O O O
c.
Comparing the conjugate bases: here, the deprotonated functional group is identical in both
cases (a carboxylic acid). The difference between the two conjugate bases is the presence of
the inductive effect: the presence of an electronegative atom elsewhere on the molecule
creates a dipole that helps draw electron density away from the site of deprotonation. Since
fluorine is more electronegative than bromine, this effect is more pronounced, and so the
conjugate base on the left is more stable (lower energy). Therefore, 2-fluoro-propanoic acid
must be the stronger acid.
 O O O O

N N – H+ N N N N – H+ N N

OH O SH S

d.
Comparing the conjugate bases: O and S are in the same column of the periodic table; moving
vertically, we should examine the size of the deprotonated atom (the location of the negative
charge). Since sulfur is larger than oxygen, that means the thiolate anion (RS–) is more stable
(lower energy) than the alkoxide anion (RO–). Therefore, the thiol must be the stronger acid
(this is confirmed with general pKa values for thiols versus alcohols).

H H
– H+ – H+
N N CH3 N N H
CH3 H

e.
In this case, we are starting with charged acids, and so we must instead compare the relative
stability of the acids: the less stable the acid, the more likely it will donate a proton (to
become neutral and thus lower energy). As shown in class, adding alkyl substituents
increases electron density and thus lowers the energy of charged molecules. Therefore, the
tertiary ammonium cation (R3NH+) is more stable than the secondary ammonium cation
(R2NH2+), which means the latter is the stronger acid.
9. Each of the following molecules has two possible basic sites (i.e. atoms which can be
protonated). Draw the two possible conjugate acids for each molecule. Identify the most
basic site and justify your answer.

O OH O
+ H+
H H OR H
O O O
a. H

The two protonation sites are the two oxygen atoms. The carbonyl oxygen is the more basic
site, since it leads to a lower energy, resonance-stabilized cation:

OH OH
H H
O O

+ H+
S O HS O OR S OH
b.

The two protonation sites are the oxygen atom and sulfur atom, which are found in the
same column of the periodic table. The sulfur atom is larger than oxygen, and larger atoms
are not as easily protonated as smaller atoms (the positive charge is less stable on a larger
atom). Therefore, the oxygen atom is the more basic site.

+ H+ H
N O N O OR N O
c. H

The two protonation sites are the oxygen atom and nitrogen atom, which are found in the
same period of the periodic table. The nitrogen atom is less electronegative than the oxygen
atom, so the positive charge will be more stable on N, making it the more basic site.
10. Draw the conjugate base of each of the following molecules (i.e. where would each
compound be deprotonated first?). Briefly justify your answer.

O O O
HO HO HO
OH O O
a.
Carboxylic acids are more acidic than alcohols due to resonance stabilization of their
conjugate bases.

O O O

H H
b.
While C-H bonds are not at all acidic, protons on carbons adjacent to p bonds (like
carbonyls), are slightly more acidic due to resonance stabilization of their conjugate bases.

H H H
H
Br Br
c. Br

While sp2 C-H bonds are slightly more acidic than sp3 C-H bonds, in this example,
deprotonation of the sp3 carbon adjacent to the carbocation allows for the formation of an
extremely stable resonance structure with no formal charges.
11. What is the speciation of phenol…

a. …at pH = 7

b. …at pH = 2

c. …at pH = 12

There are three possible species for phenol: neutral (PhOH), deprotonated (PhO–), and
protonated (PhOH2+), which produces the following two conjugate pairs:

Pair 1 : Pair 2 :

O H O H O H O
H

pKa ~ –2 pKa = 10

According to these pKa values, we can construct the pH scale below:

–2 10

O H O H O
H

From this scale, we can now determine the predominant form (>50%) of phenol at each pH:

• neutral at pH = 7
• neutral at pH = 2
• deprotonated at pH = 12
12. Draw the mechanism and the products of the following Brønsted acid-base reactions.
Identify the acid, base, conjugate acid, and conjugate base. Does the equilibrium favour the
reactants or products? Justify your choice.

O O O O
H + H
+

ACID BASE CONJ. BASE CONJ. ACID

a. 9.9 ~17
The equilibrium favours the products since phenol is a stronger acid than cyclohexanol (it
has a resonance-stabilized conjugate base).

H
C + H
H + H

BASE ACID CONJ. ACID CONJ. BASE

b. 36 ~25
The equilibrium favours the reactants since the conjugate acid (an alkyne) is a stronger acid
than molecular hydrogen.

H
N + N N + NH

ACID BASE CONJ. BASE CONJ. ACID

c. ~11 ~40
The equilibrium favours the products since a protonated amine is a stronger acid than a
neutral amine.

H + O H + OH
H H H
BASE ACID CONJ. ACID CONJ. BASE
d. 14 36
The equilibrium favours the products because water is a stronger acid than molecular
hydrogen.
 H
CH2 + C CH3 + C

BASE ACID CONJ. ACID CONJ. BASE

e. ~25 51
The equilibrium favours the products because alkynes are stronger acids than alkanes (due
to the increased s character of the sp hybridized C atom).

O + H F H
O + F
H H
BASE ACID CONJ. BASE
CONJ. ACID
3.2
f. ~ - 2.2
The equilibrium favours the reactants since the conjugate acid (a protonated alcohol, or
oxonium ion) is a stronger acid than hydrofluoric acid.

O + H Cl H
O + Cl
H H
BASE ACID CONJ. BASE
CONJ. ACID
-8
g. ~ - 2.2
By switching to HCl, now the equilibrium favours the products since hydrochloric acid is a
stronger acid than the oxonium ion.

CF3O + CF3CH2O H CF3O H + CF3CH2O

h. BASE ACID CONJ. ACID CONJ. BASE

The equilibrium favours the reactants: while the inductive effect (created by the presence of
three fluorine atoms) is present in both anions, the fluorine atoms are closer to the
deprotonated site in the reactant. This makes the CF3O– ion more stable (lower energy) than
CF3CH2O–. Therefore, CF3OH is the stronger acid and the equilibrium tends to go towards
reactants.
 H
N N + N N H N N H + H N N H
H

i. ACID BASE CONJ. BASE CONJ. ACID

This equilibrium favours the products: in both cases, a doubly-substituted ammonium

cation is formed. However, in the products, the ammonium cation is resonance-stabilized:

H N N H H N N H

Therefore, this cation is more stable (lower energy) and is the weaker acid of the two.

13. Which would be the more appropriate solvent choice for the acid-base reaction below:
cyclohexane or ethanol? The pKa of NH3 is 38; you may ignore any potential solubility
issues.

For the desired reaction to occur, the base must deprotonate the reactant (cyclohexylethyne),
NOT the solvent. Therefore, we need to determine whether the base (the amide anion) will
favourably deprotonate cyclohexane or ethanol - if so, the solvent won’t be a good choice.

H
N H H H N H
H + +
H H
cyclohexane ammonia
pKa ~ 51 pKa ~ 38

Here, the equilibrium will favour the reactants, and so NH2– will not react appreciably with
cyclohexane. Conclusion : cyclohexane is an appropriate solvent for the desired reaction (it
won’t compete with it).

H
O N H H N H
+ O +
H H
ethanol ammonia
pKa ~ 17 pKa ~ 38

Here, the equilibrium will favour the products; in other words, the NH2– ion will react
preferentially with the solvent! Conclusion : ethanol is not an appropriate choice for the desired
reaction.