Source: CHEM 237 Organic Chemistry, University of Washington
Difficulty: Intermediate | Prerequisites: General chemistry (atomic structure, electronegativity, bonding basics)
This chapter is the bridge between general chemistry and organic reactivity. Everything in organic chemistry comes back to how electrons move between molecules, and this chapter sets up the framework for understanding that. You need a working knowledge of electronegativity, Lewis structures, and formal charge before diving in. If acid-base equilibria from gen chem still feel shaky, revisit those first, because this material builds directly on them.
Acids donate protons (Bronsted) or accept electrons (Lewis); bases do the reverse. The strength of an acid is measured by its pKa: lower pKa means stronger acid. Equilibrium in acid-base reactions always favours the side with the weaker acid and weaker base, and you can calculate Keq directly from the pKa values of the reactants and products.
Bronsted acid
A species that donates a proton (H⁺). Think of it as anything that can hand off a hydrogen ion to something else.
Bronsted base
A species that accepts a proton (H⁺). In simple terms, it grabs the hydrogen that the acid gives up.
Lewis acid
A species that accepts an electron pair. Think of it as an electron-poor species looking for electrons.
Lewis base
A species that donates an electron pair. In simple terms, it has spare electrons and shares them.
Nucleophile
A species that donates an electron pair to form a new bond. Think of it as a Lewis base that is specifically forming a bond to carbon or another atom in a reaction.
Electrophile
A species that accepts an electron pair from a nucleophile. In simple terms, it is electron-poor and attracts electron-rich species.
Nucleophilic atom / nucleophilic centre
The specific atom on the nucleophile that donates the electron pair. This is where the new bond forms.
Electrophilic atom / electrophilic centre
The specific atom on the electrophile that accepts the electron pair.
pKa
The negative logarithm of the acid dissociation constant (Ka). Lower pKa means stronger acid. Think of it as a ranking system for acid strength: the smaller the number, the more readily the acid gives up its proton.
pKb
The negative logarithm of the basicity constant (Kb). Related to pKa by the equation pKa + pKb = 14.
Keq (equilibrium constant)
A number that tells you how far a reaction proceeds towards products. For acid-base reactions, Keq can be calculated from the pKa values of the acids on each side.
Conjugate acid-base pair
An acid and the base it becomes after losing a proton (or a base and the acid it becomes after gaining one). Every acid-base reaction has two conjugate pairs.
Formal charge
The charge assigned to an atom in a molecule assuming all bonding electrons are shared equally. Calculated as: valence electrons minus (lone pair electrons + number of bonds). Helps determine which Lewis structure is most stable.
Bronsted-Lowry model focuses exclusively on proton (H⁺) transfer
Bronsted acid: donates H⁺
Bronsted base: accepts H⁺
Every Bronsted acid-base reaction produces a conjugate acid-base pair
Lewis model is broader and focuses on electron pair transfer
Lewis acid: accepts an electron pair (electron-pair acceptor)
Lewis base: donates an electron pair (electron-pair donor)
All Bronsted acids are Lewis acids, but not all Lewis acids are Bronsted acids
The Lewis framework is more useful in organic chemistry because most organic reactions involve electron pair movement rather than simple proton transfer
Key relationship: nucleophiles are Lewis bases acting in the context of bond formation; electrophiles are Lewis acids accepting those electrons
A nucleophile donates an electron pair to form a new covalent bond
The nucleophilic centre is the specific atom doing the donating
Nucleophiles are electron-rich: they have lone pairs or pi electrons available
An electrophile accepts an electron pair from the nucleophile
The electrophilic centre is the specific atom that receives the electron pair
Electrophiles are electron-poor: they carry a positive charge, a partial positive charge, or an empty orbital
The interaction between nucleophile and electrophile is the foundation of nearly every organic reaction mechanism
Example from the notes: in glycine (H₂NCH₂CO₂H), the nitrogen lone pair makes it a nucleophilic centre, while the carbonyl carbon is electrophilic because the electronegative oxygen pulls electron density away from it
Lower pKa = stronger acid. This is the single most important relationship to internalise.
Equilibrium in an acid-base reaction always favours the side with the weaker acid and weaker base. The reaction "runs downhill" towards the more stable (less reactive) species.
You can calculate Keq from pKa values:
log Keq = pK(BH) − pK(AH)
Keq = 10^(pK of acid in products − pK of acid in reactants)
The Henderson-Hasselbalch equation connects pH and pKa:
pH = pKa + log([A⁻]/[AH])
Useful for buffer problems and for predicting the protonation state of a molecule at a given pH
Relationship between pKa and pKb:
pKa + pKb = 14 (for any conjugate pair in water)
Acid strength ranking from the notes: H₂SO₄ > HF > HNO₂ > H₂CO₃
Basicity ranking from the notes: HCl⁻ > H₂O > NH₃ > CH₄ (conjugate bases get stronger as conjugate acids get weaker)
Formal charge = valence electrons − (lone pair electrons + number of bonds)
Example from the notes: CH₃N can be drawn two ways
As H₂C=NH (with a double bond): C has formal charge +1 (4 − 3 = +1), N has formal charge −1 (5 − 6 = −1)
These formal charges tell you the molecule is polar and help predict reactivity
Structure corresponds to reactivity: the way you draw a molecule (which bonds, which lone pairs) directly determines how it reacts. Two valid Lewis structures for the same molecular formula can represent completely different compounds with different chemistry.
Resonance structures that minimise formal charge are more stable and more significant contributors to the resonance hybrid
Formal charge
Formal charge = valence electrons − (lone pair electrons + number of bonds)
Equilibrium constant from pKa values
log Keq = pKa(BH) − pKa(AH)
Keq = 10^(pKa of acid in products − pKa of acid in reactants)
Henderson-Hasselbalch equation
pH = pKa + log([A⁻] / [AH])
pKa and pKb relationship
pKa + pKb = 14
Acid-base chemistry is the backbone of drug design: most drugs are weak acids or bases, and their pKa determines whether they can cross cell membranes (only the uncharged form passes through lipid bilayers). The Henderson-Hasselbalch equation is used routinely in pharmacology to predict how much of a drug will be absorbed in the stomach (pH ~2) versus the intestine (pH ~7).
Students often confuse Lewis acids with Bronsted acids. A Bronsted acid must donate H⁺. A Lewis acid only needs to accept an electron pair, so BF₃ is a Lewis acid but not a Bronsted acid.
Students often think a lower pKa means a weaker acid. The opposite is true: lower pKa = stronger acid.
Students often conflate nucleophile and base. A nucleophile attacks an atom (usually carbon) to form a new bond. A base attacks a proton. The same species can act as both, but the distinction matters for predicting reaction outcomes.
Students often forget that equilibrium favours the weaker acid/base side. If you are asked "which direction does this reaction go," compare pKa values: the reaction proceeds towards the side with the higher pKa (the weaker acid).
⚠️ Be able to rank acids by pKa and predict which direction an acid-base equilibrium will go. This appears on nearly every exam.
⚠️ Know the difference between Lewis and Bronsted definitions. Expect a question that asks you to identify a Lewis acid that is not a Bronsted acid.
⚠️ Formal charge calculation is a guaranteed exam skill. Practise until you can do it without thinking.
⚠️ Be able to identify nucleophilic and electrophilic centres in a molecule, especially in amino acids and carbonyl compounds.
True or False: All Bronsted acids are Lewis acids. (True)
True or False: A species with a pKa of 4 is a stronger acid than a species with a pKa of 10. (True)
Fill in the blank: Equilibrium favours the side with the ______ acid. (weaker)
True or False: A nucleophile donates a proton. (False, it donates an electron pair to form a bond)
Fill in the blank: Formal charge = valence electrons − (______ + number of bonds). (lone pair electrons)
Q: HF has a pKa of ~3.2 and CH₃COOH has a pKa of ~4.75. If HF reacts with CH₃COO⁻, which direction does the equilibrium favour?
A: Equilibrium favours the products (CH₃COOH + F⁻), because the reaction moves towards the weaker acid (CH₃COOH, pKa 4.75) and weaker base (F⁻).
Q: Identify the nucleophilic and electrophilic centres in glycine (H₂NCH₂CO₂H).
A: The nitrogen atom is the nucleophilic centre (it has a lone pair available for bond formation). The carbonyl carbon is the electrophilic centre (it carries a partial positive charge due to the electron-withdrawing oxygen atoms).
Q: Calculate the formal charge on carbon and nitrogen in H₂C=NH.
A: Carbon: 4 valence electrons − (0 lone pair + 3 bonds) = +1. Nitrogen: 5 valence electrons − (2 lone pair + 3 bonds) = 0. (Note: the notes show C: 4−3 = +1 and N: 5−6 = −1 for an alternative structure.)
Q: Is BF₃ a Bronsted acid, a Lewis acid, or both?
A: Lewis acid only. BF₃ has an empty p orbital that can accept an electron pair, but it has no proton to donate.
Q: If the pKa of the ammonium ion (NH₄⁺) is 9.25, what is the pKb of ammonia (NH₃)?
A: pKb = 14 − pKa = 14 − 9.25 = 4.75.
This connects to Chapter 4 (alkene/alkyne chemistry) because the acidity of C-H bonds varies with hybridisation (sp > sp² > sp³), which is explained by s-character and pKa. Understanding pKa here lets you predict whether a base will deprotonate an alkyne.
This connects to nucleophilic addition and substitution reactions (Chapters 7+) because every mechanism in those chapters starts with a nucleophile attacking an electrophile. The language and concepts from this chapter are the vocabulary for everything that follows.
This connects to biochemistry because amino acids (like glycine from the notes) exist as zwitterions at physiological pH, and predicting their charge state requires the Henderson-Hasselbalch equation.
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