Haloalkanes & Haloarenes: SN1, SN2 & Elimination

1. Classification & Nomenclature

Haloalkanes (alkyl halides): R-X where X = F, Cl, Br, I. Classified as primary (1°), secondary (2°), tertiary (3°) based on the carbon bearing the halogen.

Haloarenes (aryl halides): Ar-X where X is directly bonded to the aromatic ring. Much less reactive toward nucleophilic substitution due to resonance stabilization of the C-X bond.

Vinyl halides: X on a C=C carbon (CH₂=CHX). Very unreactive toward SN₁/SN₂. Allyl/Benzyl halides: X on carbon adjacent to C=C or aromatic ring. Very reactive (SN₁ due to resonance-stabilized carbocation; SN₂ due to partial $\pi$ character in TS).

Key haloalkane and haloarene structures:

Chloromethane (methyl halide):

tert-Butyl chloride (3-degree):

Chlorobenzene (aryl halide):

Benzyl chloride (reactive toward both SN₁ and SN₂):

2. SN₂ — Bimolecular Nucleophilic Substitution

Mechanism: One-step, concerted. Nu:- attacks from the BACK side of C-X bond → pentacoordinate transition state → leaving group departs. No intermediate.

Key Features:

• Rate = k[substrate][nucleophile] — second order
• Stereochemistry: Complete inversion of configuration (Walden inversion) — backside attack
• Substrate reactivity: CH₃X > 1° > 2° >> 3° (steric hindrance blocks backside attack)
• Nucleophile: Strong nucleophiles required (OH-, CN-, I-, RS-, R₂N-)
• Solvent: Polar aprotic solvents best (DMSO, DMF, acetone — don't solvate Nu:-)
• Leaving group: Better LG = faster reaction (I- > Br- > Cl- > F-)

3. SN₁ — Unimolecular Nucleophilic Substitution

Mechanism: Two-step. Step 1 (slow, RDS): C-X bond breaks → carbocation + X-. Step 2 (fast): Nu:- attacks carbocation.

Key Features:

• Rate = k[substrate] — first order (independent of [Nu])
• Stereochemistry: Racemization (planar carbocation attacked from both faces). Slight preference for inversion if ion pair remains associated.
• Substrate reactivity: 3° > 2° > 1° > CH₃X (more stable carbocation = faster ionization)
• Nucleophile: Weak nucleophiles suffice (H₂O, ROH) since Nu attacks AFTER rate-determining step
• Solvent: Polar protic solvents best (H₂O, ROH — stabilize carbocation and LG through solvation)
• Carbocation rearrangement: Possible! Less stable cations rearrange to more stable ones (1,2-shifts)

4. Elimination Reactions (E₁ and E₂)

E₂ — Bimolecular Elimination:

• Concerted: Base abstracts $\beta$-H while LG departs simultaneously
• Anti-periplanar geometry required (H and X are 180° in the Newman projection)
• Rate = k[substrate][base]; strong bulky bases favor E₂ (KOtBu, LDA)
• Zaitsev product (more substituted alkene) with non-bulky base; Hofmann product (less substituted) with bulky base
• Competes with SN₂ for 1° and 2° substrates

E₁ — Unimolecular Elimination:

• Two-step: Carbocation forms first (like SN₁), then base removes $\beta$-H
• Zaitsev product dominant (thermodynamic control)
• Rate = k[substrate]; occurs alongside SN₁ with 3° substrates in protic solvents

5. SN₁/SN₂/E₁/E₂ Decision Framework

6. Haloarenes — Low Reactivity and Exceptions

Aryl halides (PhX) resist SN₁ and SN₂:

• SN₂ blocked: sp2 carbon, backside attack impossible (ring blocks approach)
• SN₁ blocked: Phenyl cation (sp hybridized) is extremely unstable

Exceptions (when haloarenes DO react):

• Nucleophilic aromatic substitution (SNAr): Activated by strong EWG at ortho/para. PhX with 2,4-dinitro → substitution via Meisenheimer complex (addition-elimination)

2,4-Dinitrochlorobenzene (activated for SNAr):

• Benzyne mechanism: PhX + NaNH₂ → aniline (via benzyne intermediate — elimination-addition). Benzyne detected by isotope labeling.
• Ullmann coupling: 2ArX + Cu → Ar-Ar (high T)
• Dow process: PhCl + NaOH (300°C, 300 atm) → PhONa → PhOH

C-X bond characteristics in PhX: The C(sp2)-X bond has partial double bond character (lone pair on X donates into ring), making it shorter and stronger than C(sp3)-X. This resonance stabilization is the fundamental reason for low reactivity.

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