UNIT-1: Halogenated Hydrocarbon

Alkyl Halides: Methods of Preparation

Alkyl halides (haloalkanes) are organic compounds in which one or more hydrogen atoms of an alkane are replaced by halogen atoms ( fluorine, chlorine, bromine, or iodine). They are represented by the general formula R-X, where R is an alkyl group and X is a halogen atom.

1. Preparation from Alcohols

Alcohols undergo nucleophilic substitution reactions when treated with suitable halogenating reagents to form alkyl halides.

• Reaction with Hydrogen Halides (HX): Alcohols react with halogen acids to form alkyl halides and water.

  R-OH + HX -> R-X + H2O

  Notes: Reactivity order of alcohols is 3° > 2° > 1° due to carbocation stability. Hydrochloric acid requires anhydrous zinc chloride (ZnCl2) as a catalyst (Lucas Reagent) for primary and secondary alcohols, whereas tertiary alcohols react instantly at room temperature without a catalyst.
• Reaction with Phosphorus Halides: Alcohols react with phosphorus trihalides (PCl3, PBr3, PI3) or phosphorus pentachloride (PCl5) to yield haloalkanes.

  3 R-OH + PCl3 -> 3 R-Cl + H3PO3

  R-OH + PCl5 -> R-Cl + POCl3 + HCl

• Reaction with Thionyl Chloride (SOCl2 - Darzen's Process): This is the most preferred laboratory method for preparing alkyl chlorides because the by-products (SO2 and HCl) are gaseous and escape easily, leaving behind pure alkyl chloride.

  R-OH + SOCl2 -> R-Cl + SO2 + HCl

2. Preparation from Hydrocarbons

• Free Radical Halogenation of Alkanes: Alkanes undergo free radical substitution with chlorine or bromine in the presence of ultraviolet light or heat. This method often produces a mixture of mono- and poly-haloalkanes.

  CH4 + Cl2 (in UV light) -> CH3Cl + HCl

• Hydrohalogenation of Alkenes: Addition of hydrogen halides (HX) across the double bond of alkenes yields haloalkanes. Unsymmetrical alkenes follow Markovnikov's Rule (the hydrogen atom adds to the double-bonded carbon with more hydrogen atoms). In the presence of organic peroxides, HBr adds according to Anti-Markovnikov's Rule (Kharasch Effect).

  R-CH=CH2 + HX -> R-CH(X)-CH3

3. Halogen Exchange Reactions

• Finkelstein Reaction: Synthesis of alkyl iodides by reacting alkyl chlorides or bromides with sodium iodide (NaI) in dry acetone. NaCl or NaBr precipitates in acetone, driving the equilibrium forward.

  R-Cl + NaI (in acetone) -> R-I + NaCl

• Swarts Reaction: Synthesis of alkyl fluorides by heating alkyl chlorides or bromides with metallic fluorides such as AgF, Hg2F2, CoF2, or SbF3.

  R-Br + AgF -> R-F + AgBr

Nucleophilic Substitution Mechanisms (SN1, SN2, SNi)

The polar carbon-halogen bond (C^δ+ - X^δ-) makes the carbon atom electrophilic and susceptible to attack by electron-rich species called nucleophiles (Nu⁻).

1. SN1 Mechanism (Substitution Nucleophilic Unimolecular)

The SN1 reaction is a step-wise nucleophilic substitution reaction where the rate depends only on the concentration of the substrate.

• Kinetics: First-order kinetics. Rate = k[R-X].
• Step 1 (Slow / Rate-Determining Step): Heterolytic cleavage of the C-X bond to form a planar carbocation intermediate and a halide leaving group.

  R-X -> R⁺ + X⁻ (Slow)

• Step 2 (Fast Step): Attack of the nucleophile on either face of the planar carbocation to yield the substitution product.

  R⁺ + Nu⁻ -> R-Nu (Fast)

• Stereochemical Aspect: Because the carbocation intermediate is trigonal planar (sp² hybridized), the nucleophile has an equal probability of attacking from either the front or back side. This results in complete or partial racemization (an equimolar mixture of d- and l-enantiomers).
• Substrate Reactivity Order: 3° Alkyl Halide > 2° Alkyl Halide > 1° Alkyl Halide > CH3X. This follows the stability order of the intermediate carbocation.

2. SN2 Mechanism (Substitution Nucleophilic Bimolecular)

The SN2 reaction is a single-step concerted process where bond-breaking and bond-making happen simultaneously.

• Kinetics: Second-order kinetics. Rate = k[R-X][Nu⁻].
• Mechanism: The nucleophile attacks the sp³ hybridized carbon from the side opposite to the leaving group (backside attack). A single pentacoordinate transition state is formed, where the nucleophile-carbon bond is partially formed and the carbon-halogen bond is partially broken.

  Nu⁻ + R-X -> [Nu---R---X]‡ -> Nu-R + X⁻

• Stereochemical Aspect: Backside attack causes complete inversion of configuration (commonly known as Walden Inversion), similar to an umbrella turning inside out in strong wind.
• Substrate Reactivity Order: CH3X > 1° Alkyl Halide > 2° Alkyl Halide > 3° Alkyl Halide. Bulky substituents on carbon hinder the approach of the nucleophile (steric hindrance), dramatically lowering the reaction rate.

3. SNi Mechanism (Substitution Nucleophilic Internal)

The SNi reaction is an internal nucleophilic substitution mechanism that occurs with complete retention of configuration.

• Example: Reaction of alcohols with thionyl chloride (SOCl2) in the absence of base/pyridine.
• Mechanism: First, the alcohol reacts with SOCl2 to form an alkyl chlorosulfite intermediate (R-O-SO-Cl) with the elimination of HCl. The alkyl chlorosulfite then dissociates into an ion-pair where the chloride ion is positioned internally on the same side as the departing SO2 group. The chloride attacks from the front side, maintaining the original spatial arrangement.

  R-OH + SOCl2 -> R-O-SO-Cl + HCl -> R-Cl + SO2

• Effect of Pyridine: If pyridine is added to the reaction mixture, it neutralizes HCl to form pyridinium chloride, releasing free chloride ions (Cl⁻). These free chloride ions attack from the backside, switching the pathway to an SN2 mechanism with inversion of configuration.

4. Effect of Solvent on Substitution Mechanisms

Nucleophilic Substitution vs. Elimination

Alkyl halides containing β-hydrogens can undergo either nucleophilic substitution (SN1/SN2) or β-elimination (E1/E2) when treated with a nucleophile/base. Substitution forms an alcohol/ether/halide, while elimination forms an alkene.

Factors Influencing Substitution vs. Elimination

• Nature of Substrate:
  • Primary (1°) alkyl halides predominantly undergo SN2 substitution with strong nucleophiles.
  • Tertiary (3°) alkyl halides undergo E2 elimination with strong bases, or SN1/E1 mixtures with weak nucleophiles/bases.
• Strength and Size of Nucleophile/Base:
  • Strong, unhindered nucleophiles/weak bases (e.g., I⁻, Cl⁻, CN⁻, HS⁻) favor Substitution.
  • Strong, bulky bases (e.g., Potassium tert-butoxide, t-BuO⁻) favor Elimination (E2) due to steric hindrance preventing substitution attack.
• Temperature: Higher temperatures favor Elimination over substitution. Elimination reactions increase the number of product molecules (higher entropy, ΔS > 0), making the Gibbs free energy change (ΔG = ΔH - TΔS) more favorable at elevated T.
• Solvent Polarity: Highly polar protic solvents favor SN1/E1, whereas less polar or polar aprotic solvents favor SN2/E2.

Aryl Halides: Methods of Preparation

Aryl halides are halogen compounds in which a halogen atom is directly bonded to an aromatic ring (sp² hybridized carbon).

1. Direct Electrophilic Halogenation of Aromatic Rings

Benzene reacts with chlorine or bromine in the presence of Lewis acid catalysts (e.g., FeCl3, FeBr3, or AlCl3) in the dark at room temperature.

Ar-H + X2 (catalyst: FeX3) -> Ar-X + HX

2. Preparation from Diazonium Salts

A primary aromatic amine (e.g., aniline) is treated with sodium nitrite (NaNO2) and aqueous acid (HCl or H2SO4) at 273-278 K (0-5 °C) to prepare benzene diazonium chloride (Diazotization).

Ar-NH2 + NaNO2 + 2 HCl (0-5 °C) -> Ar-N2⁺ Cl⁻ + NaCl + 2 H2O

• Sandmeyer Reaction: Replacement of the diazonium group with chlorine or bromine using cuprous halide dissolved in the corresponding halogen acid.

  Ar-N2⁺ Cl⁻ + Cu2Cl2 / HCl -> Ar-Cl + N2

  Ar-N2⁺ Cl⁻ + Cu2Br2 / HBr -> Ar-Br + N2

• Gattermann Reaction: Modification of Sandmeyer reaction using copper powder in the presence of halogen acid.

  Ar-N2⁺ Cl⁻ + Cu / HCl -> Ar-Cl + N2 + CuCl

• Iodobenzene Formation: Heating diazonium salt solution directly with potassium iodide (KI).

  Ar-N2⁺ Cl⁻ + KI -> Ar-I + N2 + KCl

• Balz-Schiemann Reaction (Fluorobenzene Preparation): Treating diazonium salt with fluoroboric acid (HBF4) yields diazonium fluoroborate, which decomposes upon heating to give fluorobenzene.

  Ar-N2⁺ Cl⁻ + HBF4 -> Ar-N2⁺ BF4⁻ (heat) -> Ar-F + BF3 + N2

Nucleophilic Aromatic Substitution (SNAr and Benzyne Mechanisms)

Aryl halides are generally unreactive towards simple nucleophilic substitution reactions compared to alkyl halides. However, under specific conditions, nucleophilic substitution occurs via distinct pathways.

Why Aryl Halides are Inert to Simple Nucleophilic Attack

• Resonance Effect: The lone pair of electrons on halogen delocalizes with π-electrons of the benzene ring, imparting partial double-bond character to the C-X bond, making it shorter and stronger.
• Hybridization of Carbon: The C-X carbon in aryl halides is sp² hybridized (more s-character, highly electronegative), holding electrons more tightly than the sp³ carbon of alkyl halides.
• Instability of Phenyl Cation: Dissociation of aryl halide would form a unstable phenyl cation, ruling out an SN1 pathway.
• Electronic Repulsion: Electron-rich nucleophiles are repelled by the electron-dense π-cloud of the aromatic ring.

1. SNAr Mechanism (Addition-Elimination Pathway)

When strong Electron-Withdrawing Groups (EWG) like nitro (-NO2) are present at ortho and/or para positions relative to the halogen, nucleophilic aromatic substitution occurs under milder conditions.

• Step 1 (Addition - Slow, Rate-Determining Step): Nucleophile attacks the ipso-carbon bearing the halogen, breaking aromaticity to form a resonance-stabilized carbanion intermediate called a Meisenheimer Complex (or sigma complex).
• Step 2 (Elimination - Fast Step): Halide leaving group departs, restoring aromatic resonance energy.
• Role of -NO2 Group Position: The negative charge formed in the Meisenheimer intermediate is directly delocalized onto the oxygens of ortho and para nitro groups. Meta-nitro groups cannot stabilize the negative charge via resonance; hence, substitution is accelerated only at ortho/para positions.

2. Benzyne Mechanism (Elimination-Addition Pathway)

Unactivated aryl halides (lacking EWG) undergo nucleophilic substitution only under drastic conditions or with extremely strong bases (e.g., NaNH2 in liquid NH3 or NaOH at 300 °C).

• Step 1 (Elimination - Formation of Benzyne): Strong base (e.g., NH2⁻) abstracts an ortho-proton relative to halogen, followed by elimination of halide ion to generate a highly reactive, neutral intermediate containing a formal triple bond in the ring, called Benzyne.

  Ar-X + NH2⁻ -> Benzyne intermediate + X⁻ + NH3

• Step 2 (Addition): Nucleophile attacks either carbon of the triple bond in benzyne, followed by protonation from solvent to form substitution products.
• Cine Substitution: Because the nucleophile can attack both the carbon previously attached to halogen (direct substitution) and the adjacent carbon (cine substitution), a mixture of structural isomers is obtained.

Relative Reactivity of Halogen Derivatives

The reactivity of halogenated hydrocarbons towards nucleophilic substitution depends strongly on structural resonance stabilization and steric environments.

Comparison of Classes

• Allyl Halides (CH2=CH-CH2-X) & Benzyl Halides (C6H5-CH2-X):
  • Reactivity: Extremely High towards BOTH SN1 and SN2 mechanisms.
  • SN1 Justification: Ionization produces allylic (CH2=CH-CH2⁺) and benzylic (C6H5-CH2⁺) carbocations that are highly stabilized by resonance delocalization of π-electrons.
  • SN2 Justification: The adjacent π-system overlaps with the unhybridized p-orbital in the SN2 transition state, significantly lowering activation energy.
• Alkyl Halides (R-X):
  • Reactivity: Moderately high. Reactivity depends on substrate class (3° favors SN1; 1° favors SN2).
• Vinyl Halides (CH2=CH-X) & Aryl Halides (Ar-X):
  • Reactivity: Extremely Low / Unreactive under standard nucleophilic substitution conditions.
  • Justification: Conjugation of halogen lone pairs with double bond gives C-X bond partial double-bond character; carbon is sp² hybridized; vinylic/phenyl cations are highly unstable.

Overall Reactivity Summary Table