Difficulty: Intermediate | Prerequisites: General chemistry acid-base theory, Lewis structures, electronegativity trends.
This material sits at the foundation of every reaction mechanism you will meet in Organic Chemistry II. Before you can predict whether a reaction follows SN1, SN2, E1 or E2, you need to judge acid-base strength, nucleophilicity, carbocation stability, and aromaticity. Stereochemistry, intermolecular forces and spectroscopy round out the toolkit: they tell you what product forms, what physical properties it has, and how you confirm its identity in the lab. If you are rejoining the course after a gap, start here before tackling specific reaction chapters.
Acid strength comes down to how stable the conjugate base is, and stability follows a clear pecking order: resonance, inductive effects, electronegativity, then size. Whether a substrate undergoes substitution or elimination depends on nucleophile strength, base bulk, and the degree of the carbon bearing the leaving group. Carbocation stability, aromaticity rules, stereochemical assignments (R/S, E/Z), intermolecular forces and basic IR/NMR signals tie the rest together.
Conjugate base
The species that remains after an acid donates a proton. In simple terms, strip off the H⁺ and whatever is left is the conjugate base.
Resonance stabilisation
Delocalisation of charge across two or more atoms through overlapping p orbitals. Think of it as the charge being spread thin instead of stuck on one atom, which makes the species much more stable.
Inductive effect
Stabilisation (or destabilisation) of charge through sigma bonds by electron-withdrawing or electron-donating groups. Groups like Cl and NO₂ pull electron density away through the bond framework.
Nucleophile
An electron-rich species that donates a pair of electrons to an electrophilic carbon. Think of it as the attacker in a substitution reaction.
Electrophile
An electron-poor species that accepts a pair of electrons. The carbon bearing a leaving group is a common electrophilic centre.
Leaving group
The group that departs with the bonding electrons during substitution or elimination. Better leaving groups are weaker bases (more stable once they leave).
Carbocation
A carbon bearing a formal positive charge. Stability follows: resonance-stabilised > 3° > 2° > 1° > methyl.
Aromaticity
A special stability found in cyclic, planar, fully conjugated systems with 4n+2 pi electrons (Hückel's rule). In simple terms, if the ring hits all four criteria, it gets a large stabilisation bonus.
Chirality / stereocentre
A carbon bonded to four different groups, making the molecule non-superimposable on its mirror image. R/S labels describe the spatial arrangement.
Intermolecular forces (IMFs)
Attractive forces between molecules: hydrogen bonding, dipole-dipole, and London dispersion. More or stronger IMFs mean higher boiling points.
Chemical shift (NMR)
The position of a signal in an NMR spectrum, measured in ppm. Electronegative neighbours pull the signal downfield (higher ppm).
The central rule: a stronger acid has a more stable conjugate base. When you are asked to compare acid strength, compare conjugate-base stability.
Stability ranking of the factors that stabilise a conjugate base, from most to least important:
Resonance – Delocalising the negative charge over multiple atoms is the single strongest stabilising factor. Carboxylate anions (two equivalent oxygens) are far more stable than simple alkoxide ions.
Inductive effects – Electron-withdrawing groups such as Cl, NO₂ and CF₃ pull electron density away through sigma bonds, stabilising nearby negative charges. The effect weakens with distance.
Electronegativity of the atom bearing the charge – Within the same row of the periodic table, more electronegative atoms hold negative charge more comfortably. Oxygen holds a negative charge better than nitrogen, which holds it better than carbon.
Size of the atom bearing the charge – Going down a column, larger atoms spread the charge over a bigger volume. HI is a stronger acid than HF because I⁻ is far larger than F⁻.
Hybridisation and acidity: sp carbons are more acidic than sp² carbons, which are more acidic than sp³ carbons. The greater s-character in the orbital holding the lone pair keeps the electrons closer to the nucleus, stabilising the conjugate base.
sp > sp² > sp³ acidity (terminal alkynes > alkenes > alkanes)
The nature of the attacking species steers the reaction:
Strong nucleophile (good electron donor, not necessarily strong base) – favours SN2. Examples: I⁻, CN⁻, RS⁻.
Strong, bulky base (hindered, poor nucleophile) – favours E2. Examples: t-BuO⁻ (potassium tert-butoxide), LDA.
Weak nucleophile / weak base – favours SN1 or E1, depending on conditions. Examples: H₂O, ROH. These pathways need a stable carbocation to form first.
A quick decision filter: if the species is strong and unhindered, think SN2. If it is strong and bulky, think E2. If it is weak, the substrate's ability to form a carbocation drives the choice between SN1 and E1.
Carbocations are key intermediates in SN1, E1 and many addition reactions. Their stability determines whether these pathways are viable.
Stability order:
Resonance-stabilised (allylic, benzylic) – the positive charge is delocalised into a pi system. Most stable class.
3° (tertiary) – three alkyl groups donate electron density through hyperconjugation and induction.
2° (secondary) – two alkyl groups. Moderate stability.
1° (primary) – one alkyl group. Rarely formed in solution; SN1/E1 at a primary carbon is almost never seen.
Methyl – no alkyl groups at all. Essentially does not form.
Benzylic and allylic carbocations gain extra stability from resonance with the adjacent pi system. Aryl (vinyl) cations, where the positive charge would sit on an sp² carbon locked in the ring plane, are unstable and do not form under normal conditions.
Carbocation rearrangements (hydride and methyl shifts) occur when a less stable carbocation can become a more stable one. Always check for rearrangement when an SN1 or E1 intermediate forms.
A compound is aromatic if it meets all four requirements:
Cyclic – the conjugated system forms a closed ring.
Planar – all atoms in the ring lie in the same plane, allowing continuous p-orbital overlap.
Fully conjugated – every atom in the ring has a p orbital contributing to the pi system.
4n+2 pi electrons (Hückel's rule) – the ring contains 2, 6, 10, 14 ... pi electrons.
Heteroatom effects:
Nitrogen can donate its lone pair into the ring to satisfy the 4n+2 count (as in pyrrole). When nitrogen's lone pair is not needed for aromaticity, it sits in an sp² orbital in the plane of the ring (as in pyridine) and the compound is still aromatic.
Boron breaks aromaticity when it creates an empty p orbital in the ring that disrupts full conjugation.
Anti-aromatic systems have 4n pi electrons (4, 8, 12 ...) in a cyclic, planar, fully conjugated ring. They are less stable than the equivalent open-chain compound and will distort out of planarity to avoid anti-aromaticity.
R/S (Cahn-Ingold-Prelog) for stereocentres:
Assign priority to the four substituents on the stereocentre using atomic number (higher atomic number = higher priority).
Orient the molecule so the lowest-priority group (4) points away from you (into the page).
Trace a path from priority 1 to 2 to 3. Clockwise = R (rectus). Counter-clockwise = S (sinister).
If you cannot physically rotate the molecule, you can assign priorities with group 4 pointing towards you and then reverse the answer.
E/Z for double bonds:
At each carbon of the double bond, rank the two substituents by Cahn-Ingold-Prelog priority.
If the two higher-priority groups are on the same side of the double bond, the configuration is Z (zusammen, "together").
If the two higher-priority groups are on opposite sides, the configuration is E (entgegen, "opposite").
Z roughly corresponds to cis and E to trans, but E/Z is the more precise and universally applicable system.
The strength of intermolecular forces determines boiling point, melting point and solubility.
Ranking from strongest to weakest:
Hydrogen bonding – requires an H bonded to O, N or F, plus a lone pair on another O, N or F nearby. Strongest common IMF.
Dipole-dipole interactions – between polar molecules with permanent dipoles. Weaker than H-bonding.
London dispersion forces – present in all molecules. Strength increases with molecular weight and surface area. The only IMF in nonpolar molecules.
More or stronger IMFs = higher boiling point. A molecule capable of hydrogen bonding will generally have a significantly higher boiling point than a similar molecule that can only manage dipole-dipole interactions.
Infrared (IR) spectroscopy identifies functional groups by the bonds that absorb specific frequencies:
O-H stretch – broad absorption, typically around 2500-3300 cm⁻¹ (carboxylic acid) or 3200-3600 cm⁻¹ (alcohol). The breadth is the giveaway.
C=O stretch – strong, sharp absorption near 1700 cm⁻¹. One of the most recognisable signals in IR. Exact position shifts slightly for esters, amides and anhydrides.
N-H stretch – medium absorption around 3300-3500 cm⁻¹. Primary amines show two peaks, secondary amines show one.
Nuclear magnetic resonance (NMR) tells you about the carbon-hydrogen framework:
Chemical shift (δ, in ppm) – electronegative groups pull signals downfield (to higher ppm). A proton next to oxygen or a halogen appears further downfield than one surrounded by alkyl groups.
Splitting pattern (n+1 rule) – a proton with n equivalent neighbouring protons appears as n+1 peaks. A proton with two neighbours appears as a triplet, with three neighbours as a quartet, and so on.
Integration – the area under each signal is proportional to the number of protons producing it.
Conjugate-base stability hierarchy: Resonance > Inductive (Cl, NO₂) > Electronegativity > Atom size
Hybridisation and acidity: sp (50% s) > sp² (33% s) > sp³ (25% s)
Carbocation stability: Resonance-stabilised ≈ benzylic/allylic > 3° > 2° > 1° > methyl
Hückel's rule for aromaticity: 4n+2 pi electrons (n = 0, 1, 2, 3 ...)
IMF strength ranking: H-bonding > dipole-dipole > London dispersion
NMR splitting: Number of peaks = n + 1 (where n = number of equivalent adjacent protons)
Acid-base chemistry underpins drug design: most pharmaceuticals are weak acids or bases, and their ionisation state at physiological pH determines whether they can cross cell membranes.
Intermolecular forces explain why ethanol (H-bonding) is miscible with water while diethyl ether (dipole only) is not, which is why ether works as an extraction solvent in the lab.
IR and NMR spectroscopy are the standard tools in any chemistry or biochemistry lab for confirming that a synthesis produced the intended product.
Students often confuse nucleophilicity with basicity. A good nucleophile attacks carbon; a good base abstracts a proton. Iodide is an excellent nucleophile but a weak base. tert-Butoxide is a strong base but a poor nucleophile because of its steric bulk.
Students often think that electronegativity is the most important factor in conjugate-base stability. Resonance beats electronegativity every time. Acetic acid is far more acidic than ethanol, even though both have the charge on oxygen.
Students often assume 4n+2 is the only criterion for aromaticity. A compound must also be cyclic, planar and fully conjugated. Cyclooctatetraene has 8 pi electrons, but it is not anti-aromatic in practice because it puckers out of planarity to avoid anti-aromatic destabilisation.
Students sometimes apply the n+1 rule to non-equivalent protons or forget that equivalent protons do not split each other.
⚠️ Ranking acids by conjugate-base stability is one of the most commonly tested question types on the ACS exam. Be ready to compare two or more compounds and explain which factor dominates.
⚠️ Deciding between SN1/SN2/E1/E2 from the nucleophile/base and substrate is a near-certain exam question. Practise the decision tree until it is automatic.
⚠️ Aromaticity questions often present unusual heterocycles and ask whether the lone pair is part of the pi system. Know the difference between pyrrole-type and pyridine-type nitrogen.
⚠️ IR and NMR interpretation questions usually give a spectrum and ask you to identify the functional group or propose a structure. The O-H broad peak and C=O sharp peak at 1700 are the two signals you must recognise instantly.
True or false: A stronger acid always has a more stable conjugate base. (True)
Fill in the blank: An sp-hybridised carbon is more acidic than an sp³-hybridised carbon because it has greater ______ character. (s)
True or false: Iodide (I⁻) is both a strong nucleophile and a strong base. (False, it is a strong nucleophile but a weak base.)
Fill in the blank: For a compound to be aromatic it must have ______ pi electrons according to Hückel's rule. (4n+2)
True or false: In NMR, a proton adjacent to an electronegative atom appears upfield (at lower ppm). (False, it appears downfield at higher ppm.)
Q: Rank the following in order of increasing acidity: ethanol, acetic acid, phenol. Explain your reasoning.
A: Ethanol < phenol < acetic acid. Ethanol's conjugate base (ethoxide) has the charge localised on one oxygen. Phenol's conjugate base (phenoxide) delocalises the charge into the aromatic ring. Acetic acid's conjugate base (acetate) delocalises the charge equally over two oxygens, giving the greatest stabilisation.
Q: A secondary alkyl bromide is treated with sodium iodide in acetone. Which mechanism dominates, and what is the stereochemical outcome?
A: SN2 dominates. Iodide is a strong, unhindered nucleophile, and acetone is a polar aprotic solvent. The product forms with inversion of configuration at the stereocentre.
Q: Cyclopentadienyl anion (C₅H₅⁻) is aromatic. Explain why.
A: It is cyclic, planar, fully conjugated (each carbon has a p orbital) and has 6 pi electrons (4 from the two double bonds plus 2 from the lone pair on the sp² carbon). 6 = 4(1)+2, satisfying Hückel's rule.
Q: A compound shows a broad O-H absorption and a sharp peak near 1710 cm⁻¹ in its IR spectrum. What functional group is present?
A: A carboxylic acid. The broad O-H and the sharp C=O near 1710 cm⁻¹ together are the signature of a -COOH group.
Q: In the ¹H NMR spectrum, a proton appears as a quartet. How many equivalent neighbouring protons does it have?
A: Three. By the n+1 rule, a quartet means n = 3.
Acid-base and nucleophile/base distinctions feed directly into the SN1/SN2/E1/E2 decision framework covered in the companion study notes on organic reactions. You will use conjugate-base stability reasoning again when predicting leaving-group ability.
Carbocation stability shows up in every reaction that proceeds through a carbocation intermediate: alkene additions (HX, hydration), SN1, E1, and Friedel-Crafts alkylation of benzene.
Spectroscopy ties into synthesis: after running a reaction, IR and NMR are how you confirm the product. Every chapter from here on will refer back to these signals.
Brønsted-Lowry acid, Lewis acid, conjugate acid-base pair, pKa, proton transfer, nucleophilicity vs basicity, steric hindrance, polar aprotic solvent, polar protic solvent, carbocation rearrangement, hydride shift, methyl shift, Wagner-Meerwein rearrangement, Hückel's rule, anti-aromatic, non-aromatic, CIP priority rules, chiral centre, enantiomer, diastereomer, R configuration, S configuration, E isomer, Z isomer, hydrogen bonding, van der Waals forces, London dispersion, dipole moment, IR absorption, carbonyl stretch, NMR chemical shift, coupling constant, splitting pattern, integration, downfield, upfield, shielding, deshielding