Lesson 25: Organic Reaction Mechanisms (HL) HL ONLY

At HL, organic chemistry stops being a catalogue of reactions and becomes a language: mechanisms (Reactivity 3.3–3.4, HL). The grammar has one punctuation mark — the curly arrow, which shows a pair of electrons moving: the arrow starts where the electrons are (a lone pair, a bond, a negative charge) and ends where they go (a new bond, or an atom that takes the pair). Single-headed fish-hook arrows move single electrons in radical chemistry. Two species drive every polar mechanism: the nucleophile (electron-pair donor — OH⁻, CN⁻, NH₃, H₂O — seeking a positive or δ+ centre) and the electrophile (electron-pair acceptor — carbocations, δ+ carbons, Br₂ polarised by an alkene). Arrows always flow nucleophile → electrophile. Bond breaking is heterolytic (both electrons to one atom, ions form) or homolytic (one each, radicals form), and examiners literally mark the arrows — an arrow starting at an atom rather than at its bond or lone pair is a lost mark wearing correct chemistry.

Nucleophilic substitution: S_N1 versus S_N2

Halogenoalkanes react with nucleophiles at the δ+ carbon bearing the halogen. Two mechanisms cover the family. S_N2 (bimolecular): the nucleophile attacks from the side opposite the C–X bond while the bond breaks — one step, one transition state, the carbon inverts like an umbrella in the wind (inversion of configuration). Rate = k[RX][Nu]: both species in the step. Favoured by primary substrates (little steric hindrance), strong nucleophiles, and it gives one stereochemical product. S_N1 (unimolecular): the C–X bond breaks first (slow, rate-determining) forming a planar carbocation, which the nucleophile then attacks from either face — a racemic mixture if the carbon was chiral. Rate = k[RX] only. Favoured by tertiary substrates, because alkyl groups stabilise carbocations by electron donation (inductive effect and hyperconjugation), in the order 3° > 2° > 1° — the same stability order that governs Markovnikov addition. Reactivity of the halogens runs RI > RBr > RCl ≫ RF (bond strength falls, polarisability rises). Solvent matters: polar protic solvents stabilise ions and accelerate S_N1; the reactions are tested experimentally by the rate of halide release (AgNO₃ in ethanol precipitates AgX as it forms).

Electrophilic addition and substitution

Alkenes are nucleophiles: the π electrons attack electrophiles. In bromination, Br₂ approaches the double bond, is polarised (Brδ+...Brδ−), and the π pair forms a C–Br bond, leaving a carbocation (or bromonium ion), which Br⁻ completes. HBr addition follows Markovnikov's rule — H adds to the carbon already richer in hydrogens — because that places the positive charge on the more substituted, more stable carbocation; the rule is a consequence, and HL answers must argue through the intermediate, not quote the slogan. Benzene refuses this chemistry: its delocalised π system (Lesson 5) would be destroyed by addition, so benzene undergoes electrophilic substitution — nitration (HNO₃/H₂SO₄ generating the NO₂⁺ electrophile) and halogenation (FeBr₃ polarising Br₂) — replacing H while keeping the ring's aromatic stability. The energetic bookkeeping is the explanation: addition to benzene costs the ~152 kJ mol⁻¹ delocalisation energy; substitution keeps it.

Free-radical substitution and the synthesis mindset

UV light breaks Cl₂ homolytically (initiation), chlorine radicals abstract H from alkanes, and the chain propagates (each radical generating another) until two radicals collide (termination). The mechanism explains the facts of Lesson 16: the need for UV, the mixture of products (radicals are indiscriminate), and trace ethane in chlorination mixtures (CH₃· + CH₃· termination). Synthesis design then assembles the whole repertoire into routes: work backwards from the target (retrosynthesis), one functional-group interconversion per step, choosing reagents from the course's map — alkane →(X₂, UV) halogenoalkane →(OH⁻, heat) alcohol →([O], H⁺) aldehyde/acid, with alkene hydration and esterification branching off. Each arrow of a route must carry its reagents and conditions; an unlabelled arrow is a hope, not a synthesis.

Worked example 1: predicting mechanism and stereochemistry

Predict the mechanism and products when (a) 1-bromobutane reacts with aqueous NaOH, and (b) 2-bromo-2-methylpropane reacts with water. (a) 1-Bromobutane is primary: S_N2 dominates. OH⁻ attacks the C–Br carbon from the back as Br⁻ leaves, in one step; butan-1-ol forms, with inversion at the carbon (stereochemically invisible here because the carbon is not chiral — note it anyway). Rate = k[RX][OH⁻]: halving either concentration halves the rate. (b) 2-Bromo-2-methylpropane is tertiary: S_N1. The C–Br bond ionises slowly to the planar (CH₃)₃C⁺ carbocation — stabilised by three electron-donating methyl groups — and water attacks rapidly from either face; 2-methylpropan-2-ol forms. Rate = k[RX] only: the nucleophile's concentration does not appear, so diluting the water (as solvent, hard to test) or changing [OH⁻] leaves initial rates unchanged if ionisation stays rate-limiting. The contrast is the examinable core: identical reagents, opposite kinetics and stereochemistry, both predictable from one structural glance — the degree of substitution at the reacting carbon.

Worked example 2: comparing hydrolysis rates — mechanism made measurable (practical)

Add equal amounts of 1-bromobutane, 2-bromobutane and 2-bromo-2-methylpropane to separate tubes of aqueous ethanolic silver nitrate at the same temperature: Ag⁺ precipitates AgBr as Br⁻ is released by hydrolysis (ethanol co-solvent dissolves the halogenoalkanes). The tertiary compound clouds almost instantly, the secondary within minutes, the primary only slowly on warming — the carbocation-stability order S_N1-style, visible. Bromobenzene gives no precipitate at all: the C–Br bond has partial double-bond character from conjugation with the ring and the ring carbon cannot be attacked from behind (and a phenyl cation is prohibitively unstable) — aryl halides are inert to these mechanisms, a result that *defines* the boundary of the model. As experimental design: control temperature (water bath — rates are temperature-sensitive and the comparison collapses otherwise), equal concentrations and volumes, and time to first cloudiness as a semi-quantitative rate proxy (1 ÷ t), with the judgement endpoint acknowledged as the dominant uncertainty (±1–2 s on fast runs is a large percentage — the tertiary run may need dilution or a cooler bath to become measurable). Rate of precipitate formation also depends on AgBr solubility and nucleation, so conclusions are comparative, not absolute — say so. This experiment is the standard school evidence for the S_N1 trend precisely because its flaws are so discussable.

Nature of Science — and the real world

Mechanisms are inference at its most rigorous: intermediates too short-lived to isolate are inferred from kinetics, stereochemistry (Walden's inversion was a puzzle for decades) and isotope labelling — then, spectacularly, carbocations were eventually observed directly in superacids (Olah, Nobel 1994), and femtosecond spectroscopy now films transition states themselves. The S_N1/S_N2 framework organises solvent choice in industry, the design of prodrugs (esters hydrolysed by exactly these mechanisms in the body), and the environmental persistence of halogenated pollutants — DDT's inertness is Lesson 25's bromobenzene argument in field dress. Understanding *how* bonds break is understanding which molecules survive.

Common mistakes

• Curly arrows drawn from atoms or positive charges instead of from bonds/lone pairs/negative charges — arrows track electrons, so they start on electrons.
• Assigning S_N1 to primary or S_N2 to tertiary substrates; mechanism follows substitution pattern first.
• Markovnikov quoted without the carbocation-stability reason, or applied backwards (the H goes to the carbon with more hydrogens already).
• Forgetting that S_N1 at a chiral centre gives a racemic mixture (attack from both faces of the planar ion), while S_N2 gives inversion — stereochemistry is the examiner's mechanism detector.

IB Exam Experience

Question 1. What is the rate expression for the hydrolysis of 2-bromo-2-methylpropane by water?

• (A) Rate = k[(CH₃)₃CBr][H₂O]
• (B) Rate = k[(CH₃)₃CBr]
• (C) Rate = k[H₂O]
• (D) Rate = k[(CH₃)₃CBr]²

Question 2. When HBr adds to propene, the major product is 2-bromopropane. What is the best explanation?

• (A) Bromine is more electronegative than carbon
• (B) The reaction proceeds through the more stable secondary carbocation rather than the primary one
• (C) Hydrogen adds to the carbon with fewer hydrogens
• (D) The product with bromine on the terminal carbon is less stable

Question 3. Which compound hydrolyses fastest with aqueous silver nitrate in ethanol?

• (A) 1-Chlorobutane
• (B) 1-Bromobutane
• (C) 2-Bromo-2-methylpropane
• (D) Bromobenzene

Answer key. 1. (B) — S_N1: only the halogenoalkane participates in the rate-determining ionisation step. 2. (B) — Markovnikov selectivity is carbocation stability: H⁺ adds to give the secondary carbocation, which Br⁻ then captures. 3. (C) — tertiary substrate, best leaving group of the set, stable tertiary carbocation: fastest by the S_N1 pathway; bromobenzene does not react at all under these conditions.

Structured question (Paper 2 style). (a) Outline the S_N2 mechanism for the reaction of bromomethane with hydroxide ions, using curly arrows, and state the rate expression. [4] (b) Explain why 2-bromo-2-methylpropane hydrolyses by a different mechanism, referring to the intermediate formed. [3] (c) Predict the stereochemical outcome when (R)-2-bromobutane undergoes hydrolysis under conditions favouring S_N1, and explain your answer briefly. [2] Marking notes. (a) Single concerted step drawn: arrow from OH⁻ lone pair to the carbon, arrow from the C–Br bond to Br [2 — one per correct arrow]; transition state shown with partial bonds (HO...C...Br) and δ charges [1]; rate = k[CH₃Br][OH⁻] [1]. (b) The substrate is tertiary: ionisation gives a tertiary carbocation [1]; stabilised by three electron-donating alkyl groups (inductive effect/hyperconjugation), lowering the activation energy of ionisation [1]; the slow ionisation is rate-determining (S_N1), with rapid attack by water afterwards [1]. (c) A racemic mixture (equal (R) and (S) alcohol) [1]; the planar carbocation intermediate is attacked with equal probability from either face [1].

IA idea: Investigate how the rate of hydrolysis of a tertiary halogenoalkane varies with the water content of an ethanol–water solvent, interpreting the trend through carbocation stabilisation and solvent polarity.

Carbonyl chemistry and condensation: the mechanism family completes itself

Esters hydrolyse by the mechanism family this lesson completes. Under acid catalysis, water attacks the ester carbonyl carbon (activated by protonation), through a tetrahedral intermediate, expelling the alcohol — addition then elimination, the carbonyl pattern, driven backwards by excess water and forwards (esterification) by removing it: Lesson 13's equilibrium wearing a mechanism. Under alkali the hydrolysis is effectively irreversible because the carboxylate product resists nucleophilic attack (its negative charge repels OH⁻) — which is why soap is made with NaOH and cannot un-make itself in the pan. Amides form when amines attack carbonyl compounds, and the peptide bond of proteins is an amide: its partial double-bond character (delocalisation from Lesson 5) makes it planar and unusually strong — the structural fact on which all of Lesson 20's biochemistry stands. For synthesis design, file the carbonyl pattern beside S_N1, S_N2 and electrophilic addition: identify the electrophilic carbon, the nucleophile, and what leaves — nearly every transformation in the HL repertoire is one of the four, and exam synthesis questions are graded by whether reagents, conditions and mechanism class are all correctly named at each step.