Source: CHM 255 PSO Exam 2 Practice Problems
Acid-base chemistry in organic molecules comes down to understanding pKa and pKb values, predicting which side of an equilibrium is favoured, and identifying the most acidic proton in a molecule. You need to know how structural features (electronegativity, resonance, induction, atom size) stabilise conjugate bases and shift equilibria. This material underpins every reaction mechanism you will see for the rest of the course.
Difficulty: Intermediate
Prerequisites: General chemistry acid-base concepts (Brønsted-Lowry theory), functional group identification, basic understanding of electronegativity and periodic trends.
Organic chemistry reactions are driven by acids giving up protons and bases accepting them. Before you can predict products or draw mechanisms for additions, substitutions, or eliminations, you need to know which proton leaves and which direction the equilibrium lies. This topic is the foundation for Exam 2 material on alkene reactions, where acid-catalysed hydration, HBr addition, and similar transformations all begin with a proton-transfer step. If you are coming in cold, revisit Brønsted-Lowry acid-base theory and the pKa table from general chemistry.
pKa
The negative logarithm of the acid dissociation constant (Ka). A lower pKa means a stronger acid. Think of it as a scoreboard: the smaller the number, the more willing the molecule is to give up its proton.
pKb
The negative logarithm of the base dissociation constant (Kb). A lower pKb means a stronger base. In simple terms, this tells you how eager a molecule is to grab a proton.
Conjugate acid (CA)
The species formed when a base accepts a proton. In simple terms, it is the "protonated version" of the base.
Conjugate base (CB)
The species formed when an acid donates a proton. Think of it as the "leftovers" after the acid gives up H+.
Brønsted-Lowry acid
A proton (H+) donor in a reaction.
Brønsted-Lowry base
A proton (H+) acceptor in a reaction.
Equilibrium
The state where the forward and reverse reaction rates are equal. In acid-base reactions, the equilibrium favours the side with the weaker acid and weaker base (the more stable pair).
Inductive effect
The electron-withdrawing or electron-donating effect transmitted through sigma bonds. Electronegative atoms (F, Cl, O) pull electron density away, stabilising nearby negative charges and making a conjugate base more stable.
Resonance stabilisation
Delocalisation of charge across multiple atoms through pi bonding. When a conjugate base can spread its negative charge over several atoms, the acid that produced it is stronger.
Phenols (ArOH): A phenol losing its O-H proton to form a phenoxide ion (ArO-) has a typical pKa around 10. Resonance with the aromatic ring stabilises the conjugate base.
Amines as bases: When an amine (e.g. a primary amine, -NH2) acts as a base and picks up a proton to form -NH3+, you describe that with pKb. A typical aliphatic amine pKb is around 3 to 4 (pKa of the conjugate acid is around 10 to 11). Amines attached to electron-withdrawing groups (carbonyl, aromatic ring) are weaker bases.
Thiols (R-SH): A thiol losing its S-H proton to form a thiolate (RS-) has a typical pKa around 10 to 11. Sulphur is larger and more polarisable than oxygen, so it stabilises the negative charge on the conjugate base more easily than you might expect from electronegativity alone.
The equilibrium in an acid-base reaction always favours the formation of the weaker acid and weaker base. The practical method:
Identify the acid on each side of the equation.
Look up or estimate each acid's pKa.
The equilibrium lies towards the side with the higher pKa (weaker acid, more stable products).
Example from the worksheet: a thiol (pKa ~10) reacting with an amine (conjugate acid pKa ~10 to 11). You compare the pKa of the thiol to the pKa of the ammonium ion. The side with the higher-pKa acid is favoured.
For any proton-transfer reaction:
Acid (A): The species that donates H+.
Base (B): The species that accepts H+.
Conjugate acid (CA): The protonated form of the base (on the product side).
Conjugate base (CB): The deprotonated form of the acid (on the product side).
Always pair them across the arrow: A with CB, B with CA.
When a molecule has several types of protons, rank them using these factors (in rough order of importance):
Atom identity: S-H is more acidic than O-H, which is more acidic than N-H, which is more acidic than C-H, all else being equal.
Resonance stabilisation of the conjugate base: A proton whose loss creates a conjugate base stabilised by resonance (e.g. carboxylic acid O-H, where the resulting carboxylate delocalises over two oxygens) will be the most acidic.
Inductive effects: Electronegative atoms or electron-withdrawing groups near the acidic proton stabilise the conjugate base and increase acidity. Fluorine atoms adjacent to a carboxylic acid (as in difluoroacetic acid) lower the pKa significantly.
Hybridisation of carbon: sp C-H > sp2 C-H > sp3 C-H in acidity (more s-character holds electrons more tightly).
Worked examples from the practice problems (Q3):
A molecule with a carboxylic acid O-H, an alcohol O-H, and a C-H: the carboxylic acid O-H is most acidic because the carboxylate conjugate base is resonance-stabilised.
A molecule with an alcohol O-H, a C-H, and a thiol S-H: the thiol S-H is typically most acidic (pKa ~10) compared to a simple alcohol O-H (pKa ~16).
A molecule with a carboxylic acid O-H and an ammonium N-H: the carboxylic acid O-H (pKa ~4 to 5) is more acidic than an ammonium N-H (pKa ~10).
A molecule with a difluoro-substituted carboxylic acid O-H and an alcohol O-H: the difluoroacid O-H is most acidic. The fluorines withdraw electron density inductively, stabilising the carboxylate.
Alpha-hydrogens between two carbonyls (1,3-dicarbonyl compounds): the C-H between two C=O groups is unusually acidic (pKa ~9 to 13) because the resulting enolate is stabilised by resonance into both carbonyls.
An aldehyde alpha-C-H next to an amine N-H: the alpha-C-H next to one carbonyl (pKa ~20) is less acidic than an ammonium N-H (pKa ~10 to 11), but a secondary amine N-H (pKa ~35 to 40) is far less acidic than the alpha-C-H. Context matters: check whether the nitrogen is protonated (ammonium) or neutral (amine).
pK_a = -\log K_apK_b = -\log K_bpK_a + pK_b = 14 \quad (\text{in water at 25°C})K_{eq} = \frac{K_a(\text{acid})}{K_a(\text{conjugate acid})} = 10^{(pK_a(\text{CA}) - pK_a(\text{A}))}When Keq > 1, the equilibrium favours products. When Keq < 1, the equilibrium favours reactants.
A difference of 1 pKa unit means a tenfold difference in acid strength.
Students often think a lower pKa means a weaker acid. It is the opposite: lower pKa = stronger acid.
Students confuse pKa with pKb. pKa describes how easily a species donates a proton. pKb describes how easily a species accepts a proton. They are related by pKa + pKb = 14, but they measure different things.
Students assume oxygen-based acids are always more acidic than sulphur-based ones because oxygen is more electronegative. Sulphur's larger size and greater polarisability can make S-H bonds easier to break, so thiols are often more acidic than comparable alcohols.
Students forget that an ammonium ion (-NH3+) is a completely different species from a neutral amine (-NH2) when ranking acidity. The ammonium ion is quite acidic (pKa ~10), while a neutral amine N-H is very weakly acidic (pKa ~35 to 40).
⚠️ Expect questions asking you to assign pKa or pKb to a specific transformation. Have the common pKa ranges memorised: carboxylic acids (~4 to 5), phenols (~10), thiols (~10), alcohols (~16), ammonium ions (~10), alpha-hydrogens next to one carbonyl (~20), alpha-hydrogens between two carbonyls (~9 to 13).
⚠️ Equilibrium direction is a near-certainty on this exam. Always compare pKa values on both sides of the equation. The side with the higher pKa acid is favoured.
⚠️ "Most acidic proton" questions test your ability to rank multiple functional groups on one molecule. Practise identifying every acidic site, then ranking by conjugate base stability.
⚠️ Watch for inductive effects from halogens (especially fluorine). Difluoro- or trifluoro-substituted acids are significantly stronger than their unsubstituted counterparts.
True or false: A molecule with pKa = 4 is a weaker acid than one with pKa = 10. (False. Lower pKa = stronger acid.)
Fill in the blank: In an acid-base equilibrium, the reaction favours the side with the ______ acid and ______ base. (weaker, weaker)
True or false: A thiol (R-SH) is typically less acidic than an alcohol (R-OH). (False. Thiols are generally more acidic.)
Fill in the blank: pKa + pKb = ______ in water at 25°C. (14)
True or false: The C-H between two carbonyl groups is more acidic than a typical alkyl C-H. (True.)
Q: A phenol (pKa ~10) reacts with an amine. The resulting ammonium ion has a pKa of ~11. Does the equilibrium favour products or reactants?
A: Products. The ammonium ion (pKa ~11) is the weaker acid, so the equilibrium lies towards it.
Q: Rank the following in order of decreasing acidity: carboxylic acid O-H, alcohol O-H, thiol S-H, ammonium N-H.
A: Carboxylic acid O-H (pKa ~4 to 5) > thiol S-H (pKa ~10) ≈ ammonium N-H (pKa ~10) > alcohol O-H (pKa ~16).
Q: A molecule contains both a carboxylic acid group and an alcohol group. Which proton is most acidic and why?
A: The carboxylic acid O-H. Its conjugate base (carboxylate) is stabilised by resonance across two equivalent oxygen atoms, giving it a pKa of ~4 to 5 compared to ~16 for a simple alcohol.
Q: How do adjacent fluorine atoms affect the acidity of a carboxylic acid?
A: They increase acidity by withdrawing electron density through the inductive effect, stabilising the carboxylate conjugate base. Each additional fluorine further lowers the pKa.
Q: In the reaction of a thiol with an amine, identify the acid, base, conjugate acid, and conjugate base.
A: The thiol is the acid (A), the amine is the base (B), the thiolate is the conjugate base (CB), and the ammonium ion is the conjugate acid (CA).
This material connects directly to alkene addition reactions (covered in the next set of notes), where the first step of acid-catalysed hydration is a proton transfer from H2SO4 to the alkene. Understanding which proton transfers are favourable tells you whether a reaction will proceed.
It also links to nucleophilic substitution and elimination, where leaving-group ability correlates with conjugate-base stability, and to carbonyl chemistry later in the course, where enolate formation depends on alpha-hydrogen acidity.
Tags: pKa, pKb, acid dissociation constant, conjugate acid, conjugate base, Brønsted-Lowry, equilibrium, thiol acidity, phenol acidity, inductive effect, resonance stabilisation, most acidic proton, alpha hydrogen, carboxylic acid, ammonium ion, CHM 255, organic chemistry acid-base, Purdue