Alkyl Halides

Alkyl halides (R–X, where X = F, Cl, Br, I) are the workhorses of synthetic organic chemistry — they undergo two major reaction families: nucleophilic substitution (S_N1, S_N2) and elimination (E1, E2). The AAMC MCAT content outline expects you to predict mechanism, product, and reactivity for any given alkyl halide.

AAMC content categories. This chapter spans three subtopics — Nomenclature/Structure/Reactivity, Nucleophilic Substitution Reactions, and Elimination Reactions.

Nomenclature, Structure and Reactivity

An alkyl halide is an alkane in which one (or more) hydrogen has been replaced by a halogen. The C–X bond is polarized δ⁺C–Xδ⁻ — the carbon is electrophilic and is the center of all subsequent reactivity.

IUPAC nomenclature

Treat the halogen as a substituent (fluoro-, chloro-, bromo-, iodo-).
Choose the longest chain containing the halogen-bearing carbon; number it so that the halogen has the lowest locant.
Examples: CH₃Cl = chloromethane, CH₃CH₂Br = bromoethane, (CH₃)₂CHCl = 2-chloropropane, (CH₃)₃CBr = 2-bromo-2-methylpropane.

Classification (1°, 2°, 3°)

Primary (1°): Halogen on a carbon bonded to one other carbon. Example: CH₃CH₂Br.
Secondary (2°): Halogen on a carbon bonded to two other carbons. Example: (CH₃)₂CHBr.
Tertiary (3°): Halogen on a carbon bonded to three other carbons. Example: (CH₃)₃CBr.

Bond strength and reactivity trends

C–X bond strength: C–F > C–Cl > C–Br > C–I (longer bond, weaker).
Reactivity in S_N/E reactions: R–I > R–Br > R–Cl > R–F (weaker bond breaks more easily).
Polarity: C–F most polar, but its bond strength keeps fluoroalkanes inert.

Preparation

From alcohols

R–OH + HX → R–X + H₂O (HI > HBr > HCl).
R–OH + PCl₃/PCl₅ → R–Cl.
R–OH + SOCl₂ → R–Cl + SO₂↑ + HCl↑ (cleanest method — gaseous by-products).

From alkenes

CH₂=CH₂ + HBr → CH₃CH₂Br. With unsymmetrical alkenes, addition follows Markovnikov's rule: H goes to the C with more H's, X to the C with fewer H's (carbocation stability).

Wurtz reaction

2 R–X + 2 Na ⟶{dry ether} R–R + 2 NaX. Used to make symmetrical alkanes; doubles the carbon count. Example: 2 CH₃Br + 2 Na → CH₃–CH₃ + 2 NaBr.

Nucleophilic Substitution Reactions

A nucleophile (Nu⁻) replaces the halide leaving group. Two competing mechanisms: S_N2 (one step, bimolecular) and S_N1 (two step, via carbocation).

S_N2 mechanism — bimolecular, one step

Nu⁻ + R–X → [Nu···R···X]^‡ → Nu–R + X⁻.
· Rate = k[R–X][Nu⁻] — second-order overall.
· Backside attack → inversion of configuration (Walden inversion).
· Favored by: 1° > 2° >> 3° (steric); strong nucleophile; polar aprotic solvent (DMSO, acetone).

S_N1 mechanism — unimolecular, two steps

Step 1 (slow): R–X → R⁺ + X⁻.
Step 2 (fast): R⁺ + Nu⁻ → R–Nu.
· Rate = k[R–X] — first-order in halide only.
· Carbocation intermediate is planar → racemic mixture.
· Favored by: 3° > 2° >> 1° (carbocation stability); weak nucleophile; polar protic solvent (water, alcohol); good leaving group.

Common nucleophilic substitutions

R–X + OH⁻ → R–OH (alcohol).
R–X + CN⁻ → R–CN (nitrile, extends chain by 1 C).
R–X + R′O⁻ → R–O–R′ (Williamson ether synthesis).
R–X + NH₃ (excess) → R–NH₂ (amine).
R–X + AgNO₂ → R–NO₂ (nitroalkane); R–X + KNO₂ → R–O–N=O (alkyl nitrite). Ambident-nucleophile MCQ favorite.

Common trap. A 3° alkyl halide does NOT undergo S_N2 — the bulky alkyl groups block the back-side approach of the nucleophile. Instead, with a strong base it gives mostly E2; with a weak nucleophile in protic solvent it gives S_N1.

Elimination Reactions

A β-hydrogen and the halide leave together to give an alkene. Like substitution, elimination has two flavours: E2 (one step, bimolecular) and E1 (two step, via carbocation).

E2 mechanism — concerted

R₂CH–CHR′–X + B⁻ → R₂C=CHR′ + BH + X⁻.
· Rate = k[R–X][B⁻] — second-order.
· H and X depart anti-periplanar in one step.
· Favored by: strong, hindered base (KO^tBu, OEt⁻); high temperature; 3° > 2° > 1°.

E1 mechanism — via carbocation

Step 1 (slow): R–X → R⁺ + X⁻.
Step 2 (fast): R⁺ ⟶{−H⁺} alkene.
· Rate = k[R–X] — first-order.
· Same conditions as S_N1 (3°, polar protic solvent, weak base); the two compete.

Saytzeff (Zaitsev) rule

The major elimination product is the more substituted (more stable) alkene. Example: 2-bromo-2-methylbutane ⟶{KOH/ethanol} 2-methylbut-2-ene (major) + 2-methylbut-1-ene (minor).

S_N vs E — how to choose

1° halide + strong nucleophile: S_N2.
1° halide + bulky strong base (KO^tBu): E2.
2° halide + strong base/nucleophile: S_N2 vs E2 — mixture; high temperature favors E2.
3° halide + strong base: E2 dominates.
3° halide + weak nucleophile / polar protic solvent: S_N1 + E1 mixture.

Quick mnemonic. "One stays, two attack." S_N1/E1 are unimolecular — only the substrate is in the rate law; S_N2/E2 are bimolecular — substrate and nucleophile/base are both in the rate law. 1° loves S_N2; 3° loves S_N1/E1.

S_N1 vs S_N2 vs E1 vs E2 — the four mechanisms at a glance
Property	S_N1	S_N2	E1	E2
Steps	2 (carbocation intermediate)	1 (concerted)	2 (carbocation intermediate)	1 (concerted)
Molecularity	Unimolecular	Bimolecular	Unimolecular	Bimolecular
Rate law	rate = k[RX]	rate = k[RX][Nu]	rate = k[RX]	rate = k[RX][B]
Substrate preference	3° > 2° > 1°	1° > 2° > 3° never (CH₃X fastest)	3° > 2° > 1°	3° > 2° > 1° (with bulky base)
Nucleophile / base	Weak Nu (H₂O, ROH)	Strong Nu (OH⁻, CN⁻)	Weak base (H₂O)	Strong, often bulky base (KO^tBu)
Solvent	Polar protic (water, alcohol)	Polar aprotic (DMSO, DMF, acetone)	Polar protic	Polar protic / aprotic, hot
Stereochemistry	Racemization (planar carbocation)	Inversion (Walden inversion)	Mixture, usually Zaitsev product	Anti-periplanar elimination, Zaitsev
Rearrangements	Possible (carbocation)	None	Possible (carbocation)	None
Effect of heat	Modest increase	Modest increase	Favored	Strongly favored

Worked MCQs

Five MCQs that capture the high-yield testing patterns for this chapter. Read the explanation even when you get the answer right — that's where the deeper concept lives.

Q1. Which alkyl halide undergoes S_N2 reaction the fastest?

CH₃Br
(CH₃)₂CHBr
(CH₃)₃CBr
(CH₃)₃CCH₂Br (neopentyl)

S_N2 requires backside attack on the carbon bearing the leaving group. Bromomethane is the least hindered. Tertiary halides cannot undergo S_N2; neopentyl is also strongly hindered by the bulky t-butyl group adjacent to it.

Q2. 2-bromo-2-methylpropane reacts with aqueous ethanol predominantly via:

S_N2
S_N1
E2
Free-radical substitution

A 3° alkyl halide in a polar protic solvent with a weak nucleophile (water/ethanol) ionizes to a stable 3° carbocation, which is then captured by the solvent — the textbook S_N1 setup. (Some E1 alkene also forms.)

Q3. The Wurtz reaction of two molecules of bromoethane in dry ether with sodium gives:

Ethene
Propane
n-butane
Hexane

Wurtz couples two R–X to give R–R: 2 CH₃CH₂Br + 2 Na → CH₃CH₂–CH₂CH₃ (n-butane) + 2 NaBr.

Q4. Dehydrohalogenation of 2-bromo-2-methylbutane with hot alcoholic KOH gives mainly:

2-methylbut-1-ene
2-methylbut-2-ene
3-methylbut-1-ene
Pentene

By Saytzeff's rule, the more highly substituted (more stable) alkene is the major product. Removing a β-H from C-3 gives 2-methylbut-2-ene (trisubstituted). Removing one from the methyl on C-2 would give the disubstituted 2-methylbut-1-ene as a minor product.

Q5. Which of the following has the strongest C–X bond?

CH₃F
CH₃Cl
CH₃Br
CH₃I

Bond strength decreases down the halogen group as the C–X bond gets longer (C–F > C–Cl > C–Br > C–I). For the same reason, fluoroalkanes are the least reactive in S_N/E reactions and iodoalkanes the most.

Quick Recap

Reactivity in S_N/E: R–I > R–Br > R–Cl > R–F (bond strength inverse).
S_N2: 1°, strong Nu, polar aprotic, inversion, second-order rate.
S_N1: 3°, weak Nu, polar protic, racemization, first-order rate.
E2: strong/bulky base, second-order, anti-periplanar, follows Saytzeff.
E1: 3°, weak base, polar protic, competes with S_N1.
SOCl₂ = cleanest alcohol → chloride conversion (gaseous SO₂ + HCl).
Wurtz: 2 R–X + 2 Na → R–R + 2 NaX (symmetrical alkanes).

Test yourself. Take a timed practice test or browse topic-wise MCQs to lock these concepts in.

Alkyl Halides

Nomenclature, Structure and Reactivity

IUPAC nomenclature

Classification (1°, 2°, 3°)

Bond strength and reactivity trends

Preparation

Nucleophilic Substitution Reactions

Common nucleophilic substitutions

Elimination Reactions

SN vs E — how to choose

Worked MCQs

Quick Recap

S_N vs E — how to choose