Chemistry · Organic chemistry · Year 3

SN1, SN2 and elimination

Replace a single bromine: why do we sometimes get inversion, sometimes a racemate, sometimes an alkene?

The situation

At the Navoiyazot complex in Navoi, polyvinyl chloride (PVC) is produced — pipes, window frames and linoleum are made from it. The monomer of PVC, vinyl chloride, is made worldwide mainly in two steps: chlorine is added to ethene to give 1,2-dichloroethane, which is then heated to strip off HCl. In a chemistry laboratory, students synthesise haloalkanes and ethers from alcohols. The same event happens everywhere — a halogen or OH group bonded to carbon leaves. Why does an optically active compound switch to the inverted configuration in one case, give a racemate in another, and in a third form an alkene instead of a substitution product?

Topic

Nucleophilic substitution and elimination. Navoiyazot PVC complex: dichloroethane from ethene and chlorine, then vinyl chloride by removing HCl. Then the organic synthesis laboratory: haloalkanes from alcohols and…

Key ideas

SN2: backside attack, Walden inversion
SN1: carbocation and solvolysis
E1/E2: Zaitsev and Hofmann

Formulas

v = k_{2} [RX] [Nu^{-}] (S_{N} 2), v = k_{1} [RX] (S_{N} 1)

SN2 is a single step, second order; SN1 has a slow ionisation step, first order.

\lg \frac{k}{k_{0}} = m Y

Grunwald–Winstein equation: Y is the ionising power of the solvent (in 80 % ethanol Y = 0; for t-BuCl m = 1).

k = \frac{1}{t} \ln \frac{1}{1 - x}, t_{1 / 2} = \frac{\ln 2}{k}

First-order kinetics: x is the fraction that has reacted by time t (indicator experiment).

Δ Δ G^{‡} = - R T \ln \frac{k_{1}}{k_{2}} \approx - 5.71 \lg \frac{k_{1}}{k_{2}} kJ/mol

The ratio of rates is set by the difference in barriers (25 °C): 10 times faster ⇔ barrier ≈ 5.7 kJ/mol lower.

CH_{2} = CH_{2} + Cl_{2} \overset{\overset{}{FeCl_{3}}}{\to} ClCH_{2} - CH_{2} Cl, ClCH_{2} - CH_{2} Cl \overset{\overset{}{t}}{\to} CH_{2} = CHCl + HCl

Vinyl chloride: electrophilic addition (40–70 °C), then dehydrochlorination (≈ 500 °C, the thermal radical route in industry).

Theory

Organic reactions: theories and classification

The history of organic chemistry first produced the theory of radicals (J. Liebig and F. Wöhler, 1830s: groups of atoms that pass unchanged through reactions — the benzoyl and ethyl “radicals”) and the theory of types (C. Gerhardt, A. Laurent: substances belong to the “type” of water, ammonia, HCl or hydrogen). In 1861 A. M. Butlerov set out the theory of chemical structure: in a molecule the atoms are joined in a definite order according to their valency, the properties of a substance depend on this structure as well as on its composition, and atoms influence one another. This explained isomerism: structural isomers (chain, position, interclass — butanol and diethyl ether, both C₄H₁₀O) and stereoisomers (geometric, optical). The classes of compounds are defined by the functional group: hydrocarbons, halogen derivatives, alcohols, ethers, aldehydes and ketones, carboxylic acids, amines and others. The mutual influence of atoms works through inductive (−I: Br, OH, C=O; +I: alkyl groups) and mesomeric (±M) effects and hyperconjugation. Acid–base theories: Arrhenius; Brønsted–Lowry (proton donor and acceptor); Lewis (electron-pair acceptor and donor — a nucleophile is a Lewis base); Pearson (hard and soft acids and bases: I⁻ is soft, easily polarised, a strong nucleophile but a weak base). Classification of reactions: by outcome — substitution (S), addition (A), elimination (E), rearrangement; by type of reagent — radical (R), nucleophilic (N), electrophilic (E). Symbols: $S_{N} 1$ , $S_{N} 2$ , $S_{E}$ , $S_{R}$ , $A_{E}$ , $A_{N}$ , $E 1$ , $E 2$ — the number is the number of species taking part in the rate-determining step (the SN1/SN2 and E1/E2 notation was introduced by C. Ingold and E. Hughes in the 1930s). Radical and electrophilic mechanisms are covered in the “Radical and electrophilic mechanisms” experiment.

SN2: back-side attack and Walden inversion

Bimolecular nucleophilic substitution takes place in a single step: the nucleophile approaches the carbon from the side opposite the C–X bond (180°), and the formation of the new bond and the breaking of the old one happen at the same time. In the transition state the three substituents lie in one plane, with Nu and X on partial bonds — the red arrows in the scene: the nucleophile's electron pair → the carbon, the electron pair of the C–X bond → X. As a result the substituents are flipped like an umbrella in the wind — the Walden inversion (the R/S label is recalculated each time by the CIP rules: if the priorities change, the letter may stay the same even after inversion). The rate is $v = k [RX] [Nu^{-}]$ . Substrate: steric hindrance at the back side decides — for bromides the relative rate is CH₃ ≈ 30, primary 1, secondary ≈ 0.02, tertiary ≈ 0; β-branching also slows the reaction (neopentyl ≈ 10⁻⁵). Nucleophile: a charged species is stronger than a neutral one (CH₃O⁻ > CH₃OH); nucleophilicity increases with basicity across a period (NH₂⁻ > OH⁻ > F⁻) and, down a group in a protic solvent, with polarisability (I⁻ > Br⁻ > Cl⁻ > F⁻) — small anions are strongly solvated by hydrogen bonds. Polar aprotic solvents (DMSO, DMF, acetone) leave the anion “naked”: the reaction CH₃I + Cl⁻ is ≈ 10⁶ times faster in DMF than in methanol (Parker), and the order of the halides changes towards F⁻ > Cl⁻ > Br⁻ > I⁻. The leaving group is better the weaker a base it is (the stronger its conjugate acid): I⁻ > Br⁻ > Cl⁻ ≫ F⁻; tosylate is very good, while OH⁻, RO⁻ and NH₂⁻ are poor (which is why an alcohol is protonated first). Allyl and benzyl halides are fast in both SN2 and SN1; vinyl and aryl halides (bromobenzene) do not undergo substitution by these routes.

SN1: carbocation, solvolysis, racemisation, rearrangement

Unimolecular substitution has two steps: slow ionisation (the C–X bond breaks heterolytically; the carbocation is a planar sp² carbon with an empty p orbital) and fast nucleophilic attack. The rate depends only on the substrate: $v = k [RX]$ . Carbocation stability: tertiary > secondary ≫ primary > CH₃⁺ (the +I effect of alkyl groups and hyperconjugation); allyl and benzyl cations are stabilised by resonance. In formic acid the solvolysis rates of the bromides are CH₃ 1 : C₂H₅ 1.7 : (CH₃)₂CH 45 : (CH₃)₃C ≈ 10⁸ — the reverse of the order in SN2. The nucleophile (often the solvent itself — solvolysis: water, alcohol) attacks the planar cation from both sides with almost equal probability, so an optically active substrate gives a racemate (in practice there is slightly more inversion, because the departing anion partly shields one side). A polar protic solvent solvates the ions and stabilises the transition state: the Grunwald–Winstein equation $\lg (k / k_{0}) = m Y$ ; for t-BuCl at 25 °C $k_{0}$ = 9.1·10⁻⁶ s⁻¹ (80 % ethanol, Y = 0), in pure ethanol Y = −2.03, in water Y = +3.49 — the more water, the more sharply the reaction speeds up. Carbocations rearrange: an H (hydride) or CH₃ from a neighbouring atom migrates with its electron pair, forming a more stable cation — 3-methylbutan-2-ol with HBr gives mainly 2-bromo-2-methylbutane. In the laboratory tert-butyl chloride is made from tert-butyl alcohol and concentrated HCl at room temperature by the SN1 route.

Elimination: E2, E1, Zaitsev and Hofmann; making alkenes

If the base removes a proton from the β-carbon, elimination takes place instead of substitution and a C=C bond forms. E2 is single-step, $v = k [RX] [B^{-}]$ ; the β-H and the leaving group must lie in one plane on opposite sides — anti-periplanar (in the scene the base, H and Br are close to one line). E1 goes through the carbocation shared with SN1; in the second step a weak base (the solvent) removes the β-H. Zaitsev's rule: usually the more substituted, more stable alkene is the main product — from 2-bromobutane + C₂H₅O⁻, 81 % but-2-ene and 19 % but-1-ene. A bulky base finds it hard to approach an internal, shielded hydrogen — if it takes a proton from the terminal CH₃, the Hofmann orientation (the less substituted alkene) increases. Competition (55 °C, C₂H₅ONa in ethanol): CH₃CH₂Br — 90 % SN2, 10 % E2; (CH₃)₂CHBr — 21 % SN2, 79 % E2; (CH₃)₃CBr — elimination only; (CH₃)₃CBr in pure ethanol (25 °C) — 81 % SN1, 19 % E1. A strong base and high temperature favour elimination; a weak base–strong nucleophile (I⁻, CN⁻, N₃⁻) and low temperature favour substitution (elimination increases the number of particles, ΔS > 0). Making alkenes (ways of forming a double bond): dehydrohalogenation of haloalkanes (KOH in alcohol), dehydration of alcohols (H₂SO₄, H₃PO₄, Al₂O₃), dehalogenation of vicinal dihalides with zinc, partial hydrogenation of alkynes over the Lindlar catalyst, dehydrogenation of alkanes, the Wittig reaction. Naming: the main chain contains the double bond, with the suffix “-ene” and the lowest possible number for the double bond (but-1-ene, 2-methylbut-2-ene); isomerism — chain, position of the double bond, cis/trans, and interclass with cycloalkanes. In industry vinyl chloride is made from 1,2-dichloroethane at ≈ 500 °C by thermal (radical-chain) removal of HCl; in the laboratory KOH solution in alcohol does the same job by the E2 route.

Alcohols: types, preparation, acid–base and chemical properties

Monohydric saturated alcohols $C_{n} H_{2 n + 1} OH$ — primary, secondary, tertiary; dihydric — glycols (ethylene glycol — antifreeze), diethylene glycol and polyethylene glycols (PEG, HO(CH₂CH₂O)ₙH — in cosmetics and medicines); trihydric — glycerol. Preparation: hydration of alkenes (industrially ethene + steam, H₃PO₄, ≈ 300 °C), hydrolysis of haloalkanes, reduction of carbonyl compounds and synthesis with Grignard reagents, fermentation; methanol industrially from synthesis gas: $CO + 2 H_{2} \overset{}{\to} CH_{3} OH$ (Cu/ZnO, 5–10 MPa, ≈ 250 °C); ethylene glycol — by hydrating ethylene oxide. Acid–base properties: in acidity alcohols are close to water — methanol is slightly stronger, the rest weaker (pKa: CH₃OH 15.5, H₂O 15.7, C₂H₅OH 15.9, (CH₃)₃COH ≈ 18; CF₃CH₂OH 12.4 — the −I effect); with alkali metals they give alkoxides; in a strong acid the oxygen is protonated (R–OH₂⁺, pKa ≈ −2) — the alcohol acts as a base. Chemical properties: replacement of OH by a halogen (HX: tertiary — SN1, primary — SN2; PCl₅, PBr₃, SOCl₂); dehydration — intramolecular (alkene; ≈ 170 °C for ethanol) or intermolecular (ether; ≈ 140 °C); oxidation — primary → aldehyde → acid, secondary → ketone, tertiary is oxidised only with difficulty; dehydrogenation — over heated copper (≈ 300 °C) a primary alcohol gives an aldehyde and H₂. Ethers: the Williamson synthesis (RO⁻ + R′X, SN2; R′ must be primary, otherwise E2 dominates), heating alcohols with H₂SO₄, and 1,4-dioxane — from diethylene glycol. Phase-transfer catalysis: a tetraalkylammonium or phosphonium salt (Q⁺X⁻) carries an anion (CN⁻, OH⁻) from the water into the organic phase — 1-chlorooctane barely reacts when heated with aqueous NaCN, but with 1–2 mol % of a phosphonium salt it gives the nitrile in ≈ 2 hours (Starks, 1971). From haloalkanes, organometallic compounds: $RX + Mg \overset{}{\to} RMgX$ (Grignard, in dry ether), $RX + 2 Li \overset{}{\to} RLi + LiX$ , the Wurtz reaction ( $2 RX + 2 Na \overset{}{\to} R - R + 2 NaX$ ) — their use is covered in the “Carbonyl compounds and synthesis” experiment. Uses: solvents, fuel (bioethanol), antifreeze, medicines and cosmetics, raw material for polymers. The school-level treatment is in “Alcohols and ethers”.

Lab work (L6–L8), safety and the model

L6 — synthesis of alkenes: cyclohexene (cyclohexanol + H₃PO₄, distillation, 83 °C), hept-1-ene, 2-methylbut-2-ene, pent-2-ene; the double bond is detected with bromine water (the colour disappears; details in “Radical and electrophilic mechanisms”). L7 — substitution at an sp³ carbon: ethyl bromide (ethanol + KBr + H₂SO₄, distilled under ice water), n-butyl bromide, ethyl iodide (red phosphorus + iodine), tert-butyl chloride (SN1); iodoform — the haloform reaction. L8 — ethers: dibutyl and diisoamyl ethers (with a water separator), 1,4-dioxane. Reactivity tests: NaI solution in acetone (NaBr and NaCl are insoluble in acetone — cloudiness is the sign of SN2) and AgNO₃ solution in ethanol (an AgBr precipitate is the sign of SN1). Kinetics: t-BuCl is hydrolysed in aqueous ethanol; the solution contains bromothymol blue and a little NaOH — as soon as the HCl that forms has neutralised the alkali, the colour changes from blue to yellow, the time is recorded, and the next portion is added. Safety: work with concentrated H₂SO₄ and HCl wearing safety goggles and gloves, pour acid into water, never the reverse; haloalkanes are alkylating, toxic substances — work in a fume cupboard; ethers and alkenes ignite very easily — use an electric heater, not a naked flame; dioxane and diethyl ether accumulate explosive peroxides on long storage; if alkali gets into the eyes, rinse immediately with plenty of water; never smell or taste reagents. Model: the relative SN2 rates and nucleophilicity are textbook values (25 °C), and the speed-up of the anions in an aprotic solvent is an approximate model (Parker order); the times in the test tubes are a model fitted qualitatively to experiment; Y values are linearly interpolated from the table, and the pH for the colour of bromothymol blue is calculated as in an ideal aqueous solution; the source of each product ratio (experiment or model) is stated in the result window; the molecules are schematic (1 Å ≈ 4.5 cm), the energy diagrams are schematic; laboratory time is accelerated.

Did you know?

In 1896 Paul Walden converted (−)-malic acid into (+)-malic acid with PCl₅ and then moist Ag₂O — the first example of converting one enantiomer into the other by chemical means; the phenomenon is called the “Walden inversion” after him.
In 1935 in London, E. Hughes and colleagues added radioactive iodide ions to optically active 2-iodooctane: the rate at which the optical activity fell turned out to be twice the rate of iodine exchange, within the accuracy of measurement — so each substitution inverts the configuration.

Inside the experiment

The experiment starts from a real-life situation: you predict the result, change the controls, run the experiment and draw a conclusion. Inside are missions, theory, a quiz and a guided tour in which the camera moves and explains the key points.

More experiments in this section

Acids, esters and soap — Grade 10
Carbohydrates: glucose and starch — Grade 10
Identifying organic substances — Grade 10
Stereochemistry and conformations — Year 2
Radical and electrophilic mechanisms — Year 3
The aromatic ring and azo dyes — Year 3
Carbonyl compounds and synthesis — Year 3
Heterocycles and DNA — Year 3
Amino acids and proteins — Year 3
Physics of macromolecules — Year 3