Haloalkanes

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Haloalkanes — Alkyl Halides (R-X)

Haloalkanes contain a halogen (F, Cl, Br, I) attached to a saturated carbon atom. They are classified as primary (1°), secondary (2°), or tertiary (3°) based on the number of carbon groups attached to the carbon bearing the halogen.

Classification:

• R-CH₂-X: Primary haloalkane (1°)
• R₂CH-X: Secondary haloalkane (2°)
• R₃C-X: Tertiary haloalkane (3°)

Nomenclature:

• 1-chlorobutane, 2-bromopropane, 2-chloro-2-methylpropane
• Vinyl chloride (CH₂=CH-Cl): Halogen attached to sp² carbon
• Allyl chloride (CH₂=CH-CH₂-Cl): Halogen on carbon adjacent to double bond

Physical Properties:

• Boiling point: RI > RBr > RCl > RF (iodo has higher MW, stronger London dispersion)
• For isomeric haloalkanes, branching decreases BP
• Density: Fluoroalkanes < 1; chloroalkanes ~1; bromo/iodoalkanes > 1 (sink in water)
• Insoluble in water but soluble in organic solvents
• Fluorinated compounds may have unique properties (Teflon: PTFE)

Key Reactions:

1. Nucleophilic Substitution (SN1 and SN2):

   • SN2: Backside attack, Walden inversion, rate ∝ [R-X][Nu⁻]
   • SN1: Unimolecular, carbocation intermediate, rate ∝ [R-X]
   • Steric hindrance favors SN1 for 3° > 2° > 1°
   • Good leaving group favors SN1
   • Strong nucleophile favors SN2

2. Elimination (E1 and E2):

   • E2: Bimolecular, anti-periplanar elimination, requires strong base
   • E1: Unimolecular, carbocation intermediate, occurs with weak bases

⚡ Exam tip: Hofmann and Saytzeff rules: In elimination, the more substituted alkene is favored (Saytzeff) under E1/E2 conditions. Hofmann product (less substituted alkene) is favored when bulky bases (like t-BuO⁻) are used or in Hofmann elimination (quaternary ammonium salts).

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Haloalkanes — Chemistry Study Guide

Nucleophilic Substitution Mechanisms:

SN2 Mechanism:

• Single step, concerted (bond making and breaking simultaneous)
• Backside attack of nucleophile on carbon bearing leaving group
• Walden inversion: Configuration inverts at reaction center (like umbrella turning inside out)
• Rate: v = k[R-X][Nu⁻] (second order)
• Stereochemistry: Inversion of configuration
• Substrate: Methyl > 1° > 2° (steric hindrance)
• Nucleophile: Strong, negatively charged (CN⁻, OH⁻, RO⁻, RS⁻)
• Leaving group: Better leaving group = faster (I⁻ > Br⁻ > Cl⁻ > F⁻)
• Solvent: Polar aprotic (DMSO, DMF) favors SN2 (doesn’t solvate nucleophile as much)

Example: CH₃-Br + OH⁻ → CH₃-OH + Br⁻ (inverted configuration if chiral substrate)

SN1 Mechanism:

• Two steps: (1) Slow ionization to carbocation; (2) Fast nucleophilic attack
• Rate: v = k[R-X] (first order)
• Intermediate: Flat trigonal planar carbocation (sp² hybridized)
• Stereochemistry: Racemization (equal attack from both faces, but front face slightly favored → partial racemization)
• Substrate: 3° > 2° > 1° (carbocation stability)
• Leaving group: Good leaving groups essential (X⁻ is stable when leaving)
• Solvent: Polar protic (water, alcohols) stabilizes carbocation and leaving group

Carbocation Stability: (CH₃)₃C⁺ > (CH₃)₂CH⁺ > CH₃-CH₂⁺ > CH₃⁺ Resonance stabilization, hyperconjugation increase stability.

Competition between SN1 and SN2:

• Methyl halides: Only SN2
• Primary alkyl: SN2 only (unless resonance stabilized like benzyl)
• Secondary: Both possible; conditions determine pathway
• Tertiary: SN1 only (SN2 blocked by sterics)

Neopentyl halide: Even though 1°, undergoes SN1/SN2 with great difficulty because carbocation rearrangement occurs or approach is sterically hindered.

Vinyl halides: Halogen attached to sp² carbon — C-X bond has partial double bond character, difficult to break. Vinyl chloride is unreactive toward SN1/SN2 under normal conditions.

• Example: CH₂=CH-Cl + NaOH → No reaction (usually)

Allyl chloride: Very reactive in SN1/SN2 because the carbocation intermediate is resonance-stabilized: [CH₂=CH-CH₂]⁺ ↔ [CH₂-CH=CH₂]⁺ (allylic carbocation)

Benzylic halide: Like benzyl chloride (C₆H₅-CH₂-Cl), very reactive in SN1 (benzylic carbocation stabilized by benzene ring).

Elimination Mechanisms:

E2 Mechanism:

• Concerted, bimolecular
• Anti-periplanar geometry required (H and leaving group on opposite sides)
• In cyclohexane: Trans diaxial elimination
• Rate: v = k[R-X][Base]
• Strong base required (OH⁻, RO⁻, NH₂⁻)
• Substrate: 3° > 2° > 1° (more substituted alkenes are more stable)

E1 Mechanism:

• Two steps: Carbocation formation, then deprotonation
• Rate: v = k[R-X] (first order)
• Same carbocation intermediate as SN1
• Competes with SN1; often both products observed
• Weak base can favor E1 if carbocation is highly stabilized

Saytzeff Rule: The more substituted alkene is the major product (stability: tetrasubstituted > trisubstituted > disubstituted > monosubstituted > ethylene)

Hofmann Rule: The less substituted alkene predominates when bulky bases are used (t-BuOK, DBU) or when the β-carbon is quaternary.

Zaitsev vs Hofmann:

• With small bases (OH⁻): Saytzeff (more substituted alkene)
• With bulky bases (t-BuO⁻): Hofmann (less hindered alkene)

Key Reactions of Haloalkanes:

1. Hydrolysis (Formation of Alcohols): R-X + H₂O → R-OH + HX (slow, for primary) R-X + NaOH(aq) → R-OH + NaX (better, aqueous) SN1 for 2°, 3°; SN2 for 1°

2. Formation of Alcohols (with alkali): Same as above, but OH⁻ is nucleophile

3. Formation of Ethers (Williamson Synthesis): R-O⁻ + R’-X → R-O-R’ + X⁻ Must use alkoxide + alkyl halide; SN2 mechanism Limitation: If using tertiary haloalkane, E2 competes heavily

4. Formation of Nitriles (R-X + CN⁻): R-X + NaCN → R-CN + NaX Important for chain elongation (one carbon added) Cyanohydrin formation from carbonyl: R-CHO + HCN → R-CH(OH)-CN

5. Formation of Amines: R-X + NH₃ → R-NH₂ + HX (primary amine) Further substitution can occur: R-NH₂ + R-X → R₂NH + HX (secondary) R₂NH + R-X → R₃N + HX (tertiary) R₃N + R-X → R₄N⁺X⁻ (quaternary ammonium salt)

6. Formation of Thioalcohols and Thioethers: R-X + NaSH → R-SH + NaX R-X + NaSR → R-S-R’ + NaX

7. Reaction with NaI (Finkelstein Reaction): R-Cl + NaI → R-I + NaCl (acetone solvent; I⁻ is good nucleophile,precipitate drives) Useful for preparing iodoalkanes from chloro/bromoalkanes

8. Reaction with Silver Salts: R-X + AgNO₂ → R-NO₂ + AgX (nitroalkane, N-bonded) R-X + AgNO₃ → R-ONO₂ + AgX (alkyl nitrite, O-bonded)

9. Wurtz Reaction (Coupling): 2R-X + 2Na → R-R + 2NaX (dry ether) For primary alkyl halides only; tertiary gives alkenes via elimination Mixed Wurtz: R-X + R’-X + 2Na → R-R’ + R’-R + R-R (mixture)

10. Nucleophilic Substitution with Acetate: R-X + CH₃COONa → CH₃COOR + NaX (formation of ester)

⚡ Exam tip: In SN1 reactions with optically active substrates, the product is partially racemized because the nucleophile can attack from either face of the planar carbocation. However, the front face (where the leaving group departed) is slightly more hindered, leading to slight inversion predominance.

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Haloalkanes — Comprehensive Chemistry Notes

Stereochemistry of SN2:

When an optically active 2-bromobutane undergoes SN2 with Br⁻:

• The nucleophile attacks from the back, opposite to the leaving group
• The configuration inverts completely (100% inversion)
• If (R)-2-bromobutane reacts: (S)-2-butanol is obtained
• This is Walden inversion

The carbon undergoing SN2 goes from sp³ to sp³* (pentacoordinated transition state) and back to sp³:

        Nu⁻
         |
      F---C---L
         |

In the transition state, the three substituents are planar.

Stereochemistry of SN1:

The carbocation is planar sp² hybridized with an empty p-orbital.

• Attack from either face gives enantiomers
• If front attack is slightly favored (leaving group blocks front slightly), product is slightly more inverted than retained
• Generally: slight excess of inversion (if any stereochemical preference at all)

Racemization: When (R)-2-chlorobutane undergoes SN1 hydrolysis:

• Forms (R)- and (S)-2-butanol in equal amounts (racemic mixture)
• The extent of racemization depends on ion-pairing effects

Carbocation Rearrangements:

Hydride Shift: (CH₃)₂CH-CH(Cl)-CH₃ (secondary) → After ionization: (CH₃)₂CH-CH⁺-CH₃ → Hydride shift from adjacent C: (CH₃)₂C⁺-CH₂-CH₃ (tertiary)

Methyl Shift: (CH₃)₂C(Cl)-CH₂-CH₃ → Ionizes to (CH₃)₂C⁺-CH₂-CH₃ (tertiary stable carbocation) If primary formed: methyl shift to give tertiary.

Wagner-Meerwein Rearrangement: In bicyclic systems, carbocations can undergo skeleton rearrangements to give more stable carbocations.

Driving Force for Rearrangement: Carbocations rearrange from less stable to more stable: Primary → Secondary → Tertiary Also: Non-resonance stabilized → Resonance stabilized

Neighboring Group Participation (NGP): When a neighboring group assists in the departure of a leaving group, stereochemistry can be retained.

• For example, when 2-bromo-1-phenylpropane undergoes solvolysis, the phenyl group can assist, leading to retained stereochemistry.
• The neighboring group forms a bridged intermediate (phenonium ion) that blocks one face.

E2 Anti-Elimination and Cyclohexane:

In cyclohexane derivatives, anti-periplanar geometry is required for E2:

• If H and leaving group are both axial on adjacent carbons → anti elimination
• For 1,2-disubstituted cyclohexanes: trans-diaxial gives anti-elimination; cis gives syn-elimination (less common)

Example: trans-1-chloro-2-methylcyclohexane + base → 1-methylcyclohexene (via diaxial) cis-1-chloro-2-methylcyclohexane → gives different product or requires different conditions.

Stereochemistry of E2 in Alkenes:

Anti-elimination gives:

• For 2-bromobutane: anti elimination gives trans-2-butene predominantly
• Syn-elimination is less common and requires heating (thermal syn-elimination)

Crown Ether Catalysis: Crown ethers (18-crown-6) complex with K⁺, making KMnO₄ soluble in nonpolar solvents (purple in benzene — phase transfer catalysis).

• Similarly, KOH becomes soluble in organic solvents with 18-crown-6
• This enhances SN2 rates dramatically

Phase Transfer Catalysts: Quaternary ammonium salts (R₄N⁺X⁻) can transfer ions between phases.

• Used in: Wurtz coupling, cyanide substitution, permanganate oxidations

Polyhalogenated Compounds:

CHCl₃ (Chloroform):

• Used as solvent, historically as anesthetic
• Decomposes in light: CHCl₃ + O₂ → COCl₂ + 2HCl (phosgene)
• Stored in dark bottles with ethanol (prevents decomposition)
• With AgNO₂: CHCl₃ + AgNO₂ → AgCl + CHCl₂NO₂ (chloropicrin, explosive)
• Reaction with alkali: CHCl₃ + NaOH → HCOONa + 3NaCl (formate)

CCl₄ (Carbon Tetrachloride):

• Non-flammable, dense, historically used as dry cleaning solvent
• With water: very slow hydrolysis
• Harmful to liver and kidneys; depletes ozone layer

Freons (CFCs):

• Trichlorofluoromethane (CCl₃F, Freon-11)
• Dichlorodifluoromethane (CCl₂F₂, Freon-12)
• Used as refrigerants and aerosol propellants
• Cause ozone depletion: Cl· + O₃ → ClO· + O₂; ClO· + O → Cl· + O₂
• One Cl atom can destroy ~100,000 ozone molecules

DDT and Organochlorine Pesticides:

• DDT: 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane
• Banned in many countries due to bioaccumulation and persistence
• Interferes with calcium metabolism in birds (thin eggshells)

Haloform Reaction:

CH₃-CO-R + 3NaOX → CHX₃ + R-COO⁻ + 3Na⁺ (where X = Cl, Br, I)

• Methyl ketones (and secondary alcohols with CH₃-CH(OH)- group) give haloform
• Iodoform test: Yellow precipitate of CHI₃ with I₂/NaOH
• Methyl ketones give iodoform: CH₃-CO-R + 3I₂ + 4NaOH → CHI₃↓ + R-COONa + 3NaI + 3H₂O

Iodoform Test — Compounds that Give Positive:

• All methyl ketones: CH₃-CO-R
• Acetaldehyde (CH₃CHO)
• Secondary alcohols with CH₃-CH(OH)- group (e.g., 2-propanol)
• NOTE: Phenyl methyl ketone (acetophenone) does NOT give iodoform

Mechanism of Haloform Reaction:

1. Halogenation of α-carbon (under basic conditions): CH₃-CO-CH₂-R + X₂ → CH₃-CO-CHX-R + HX 2.重复卤代直到所有α-H被取代
2. Hydroxide attacks carbonyl: forms tetrahedral intermediate
3. Cleavage: C-C bond breaks, gives carboxylate and CHX₃

Sulfur Mustard (Mustard Gas):

• bis(2-chloroethyl) sulfide: (ClCH₂CH₂)₂S
• Vesicant (blister agent), used in WWI
• Cyclizes to form an episulfonium ion (three-membered ring with S⁺)
• This episulfonium ion alkylates DNA, causing cell death

Preparation of Haloalkanes from Alcohols:

R-OH + HX → R-X + H₂O (requires ZnCl₂ catalyst for primary/secondary) R-OH + SOCl₂ → R-Cl + SO₂ + HCl (thionyl chloride method; clean, no rearrangement) R-OH + PCl₅ → R-Cl + POCl₃ + HCl R-OH + PCl₃ → R-Cl + H₃PO₃ (phosphorous acid; works for secondary, tertiary)

Dehydrohalogenation: R-CH₂-CH₂-X + KOH/alc → R-CH=CH₂ + KX + H₂O (E2) Rate: RI > RBr > RCl > RF (leaving group ability)

Relative Reactivity of Alkyl Halides:

In SN2: CH₃X > 1° > 2° > 3° (steric hindrance) In SN1: 3° > 2° > 1° > CH₃ (carbocation stability)

Relative Reactivity with Same R, Different X:

For the same alkyl group, reactivity in SN1/SN2 increases down the group (better leaving group): RI > RBr > RCl > RF

In elimination (E1/E2): RI > RBr > RCl > RF

Aryl Halides — Nucleophilic Aromatic Substitution:

Aryl halides with electron-withdrawing groups ortho/para can undergo SNAr (addition-elimination mechanism):

• NO₂ group at ortho/para positions activates ring toward nucleophilic attack
• Mechanism: Nu⁻ attacks ipso carbon → Meisenheimer complex (anionic sigma complex) → loss of X⁻

Benzyne Mechanism: When aryl halides lacking EWG undergo substitution with strong bases (NH₂⁻):

• 2KNH₂ + C₆H₅Br → C₆H₅NH₂ + KBr + KOH
• Mechanism: 2 NH₂⁻ deprotonates ortho position; elimination of Br⁻ gives benzyne; nucleophilic attack gives aniline
• Benzyne has a triple bond in the ring ( strained)
• This proves aryl halides can undergo substitution under forcing conditions

Comparative Study:

Property	SN2	SN1
Molecularity	Bimolecular	Unimolecular
Intermediate	None	Carbocation
Stereochemistry	Complete inversion	Racemization
Rate	∝ [R-X][Nu]	∝ [R-X]
Order of reactivity	1° > 2° > 3°	3° > 2° > 1°
Solvent	Polar aprotic	Polar protic
Neighboring group participation	No	Possible
Rearrangements	No	Yes

Uses of Haloalkanes:

• CHCl₃: Solvent, anesthetic (historical)
• CCl₄: Solvent, fire extinguisher (historical)
• Freons: Refrigerants (now restricted)
• DDT: Pesticide (banned/restricted)
• PVC (polyvinyl chloride): (CH₂-CHCl)ₙ — plastic
• Teflon (PTFE): (CF₂-CF₂)ₙ — non-stick coating
• Tritium (³H): Radioactive hydrogen in nuclear weapons

⚡ Exam tip: When asked about the product of an SN1/E1 reaction, always consider carbocation rearrangements. For example, 2-bromo-2-methylbutane might rearrange to give a more stable tertiary carbocation before reacting.

⚡ Exam tip: In JEE, distinguish between:

• Rate of formation of carbocation (depends on stability of carbocation)
• Rate of reaction (overall rate depends on RDS)
• Product distribution (thermodynamic vs kinetic control)

⚡ Exam tip: Vinyl halides and aryl halides do not undergo SN1/SN2 reactions. They undergo SNAr only if activated by EWGs (NO₂, CN) ortho or para to the leaving group. Unactivated aryl halides undergo benzyne mechanism only with very strong bases like NaNH₂ at high temperatures.

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