exam 4!!

Haloalkanes and Organohalogen Compounds

• Definition: Organohalogen compounds are organic molecules containing carbon and halogen atoms.
    - Types include:
      - Haloalkanes (Alkyl Halides): Alkane with halogen. General formula: C_nH_(2n+1)X, where X = F, Cl, Br, I.
      - Haloalkenes (Alkenyl or Vinylic Halides): Alkenes with halogens.
      - Haloarenes (Aryl Halides): Aryl group with halogen.
    - Example: CH₃X (methyl halide).

• Classification of Haloalkanes:
    - Primary (1°) alkyl halide: attached to one carbon.
    - Secondary (2°) alkyl halide: attached to two carbons.
    - Tertiary (3°) alkyl halide: attached to three carbons.
    - Allylic halide: halide adjacent to a double bond.
    - Benzylic halide: halide adjacent to a benzene ring.

Haloalkane Nomenclature

• Naming conventions:
    - Similar to alkanes and alkenes; halogen substituents indicated as ‘halo’ (e.g., fluoro, chloro, bromo, iodo).
    - Example of naming: 2-bromopropane.

Preparation of Haloalkanes

• Methods:
    - From alkenes: via addition of HX (hydrogen halides) and X₂ (halogens).
    - From alkynes: via addition of HX and X₂.
    - From alkanes: through radical reactions (discussed later).
    - From alcohols: yet to be discussed.

Radical Halogenation of Alkanes

• Example: Radical chlorination of methane (CH₄).

• Conditions:
    - Use Cl or Br as halogen.

• Reactivity:
    - Fluorine (F): too reactive (exothermic).
    - Iodine (I): not reactive enough (endothermic).

Free Radicals

• Definition: A free radical is an atom or molecule with at least one unpaired valence electron.
    - Like carbocations, carbon radicals are electron deficient.

• Formation: Produced via homolytic bond cleavage.
    - Movement of one electron represented by fishhook arrows.

Energetics of Free Radical Halogenation

• Gibbs-Helmholtz Equation:
    - $ext{∆G° = ∆H° − T∆S°}$

• Predicting ΔH° using bond dissociation enthalpies (BDEs).

• Factors influencing BDE:
    - Bond strength (as X-Y bond strength increases, BDE increases).
    - Radical stability (as radical stability increases, BDE decreases).

• ΔH° calculation:
    - $ext{ΔH° = BDE of X−Y bond}$

Bond Dissociation Enthalpies

• Table of BDE (kcal/mol):
    - CH₃—H: 105, CH₃—Cl: 84, CH₃—Br: 72.
    - More examples:
      - H—Cl: 103, Cl—Cl: 59, Br—Br: 46.

Calculating ΔH° for Radical Reactions

• Formula:
    - $ext{ΔH° = Σ(BDEs of bonds broken) - Σ(BDEs of bonds formed)}$

• Example: Methane and chlorination:
    - Reaction: CH₄ + Cl₂ → CH₃Cl + HCl.

Mechanism of Free Radical Halogenation

• General Steps:
    1. Initiation: Light or heat homolytically cleaves weak bonds, forming free radicals.
    2. Chain Propagation:
        - A radical reacts with a molecule, forming a new radical.
    3. Termination: Deactivation of radicals through pairing.

Rate-Determining Step

• The first propagation step (formation of the carbon radical) is the rate-determining step (RDS).

Radical Stability

• Stabilized through hyperconjugation (overlap of half-filled p-orbital with adjacent σ-bonding orbitals).

• Resonance: Delocalization of the unpaired electron stabilizes radicals significantly.

• Destabilizing factors: Electron withdrawing groups/atoms destabilize radicals.

Regioselectivity of Bromination vs. Chlorination

• Contrasts:
    - Chlorination: Unselective; all products form.
    - Bromination: Selective; one or few major products form.

• Experimental yields demonstrate differences in selectivity for Cl (62% and 38%) versus Br (0% and 100%).

Rate-Determining Step in Regioselectivity

• Hammond's Postulate: Related species that are closer in energy are also closer in structure.
    - Exothermic reaction: Transition state closer to reactants.
    - Endothermic reaction: Transition state closer to products.

Reactivity of H Atoms in Radical Chlorination/Bromination

• Highlights:
    - Radical chlorination: 3° H reacts slightly faster than 1° H.
    - Radical bromination: 3° H reacts significantly faster than 1° H.

Allylic Bromination

• Reagent Used: N-Bromosuccinimide (NBS).

• Mechanism:
    1. Initiation: N-Br → N + •Br.
    2. Chain Propagation: Formation of allylic bromides.
    3. Termination: Formation of Br₂ from free radicals.

Radical Addition of HBr to Alkenes

• Initiation: Formation of radicals from initiators such as di-tert-butyl peroxide and benzoyl peroxide.

• Mechanism includes:
    1. Initiation.
    2. Chain propagation.
    3. Termination.

Nucleophilic Substitution and β-Elimination

• Nucleophilic Substitution: SN1 and SN2 mechanisms.

• β-Elimination: E1 and E2 mechanisms demonstrated by dehydrohalogenation examples.

Nucleophilic Substitution in Haloalkanes

• Various nucleophiles will react with alkyl halides to form diverse products such as alcohols, ethers, thiols, etc.

SN2 Reaction Mechanism

• Mechanisms include backside attack, leading to inversion of configuration.

• Rate expression: $ext{rate = k [RX] [Nu−]}$

SN2 Examples and Mechanisms

• Example: Williamson ether synthesis utilizing sodium ethoxide and bromoethane.

SN1 Reaction Mechanism

• Non-SN2 due to carbocation formation; multiple influencing factors.

• Rate expression: $ext{rate = k [RX]}$

SN1 Reaction Details

• Dependent on leaving groups and the structure of the electrophile (greater stability leads to higher reaction rate).

SN1 Solvent Dependence

• Solvolysis reactions where solvents act as nucleophiles. Best solvents are polar protic.

Stereochemistry of SN1 and SN2

• SN1 results in a mix of inversion and retention; whereas SN2 results in consistent inversion of configuration.

Formation of Aryl and Alkyl Sulfonates

• Reactions forming sulfonates via SN2 and nucleophilic substitution.

Acid-Catalyzed Dehydration of Alcohols

• Mechanism involves acid catalysts, resulting in elimination reactions and creating alkenes.

Pinacol Rearrangement

• Converts 1,2-diols to carbonyl compounds using acid.
    - Mechanism of dehydration results in the formation of pinacol from glycol.

Oxidation of Alcohols

• Different oxidation agents lead to various products: aldehydes, ketones, carboxylic acids based on the type of alcohol.

Periodic Acid Oxidation of Glycols

• Only cis-glycols can undergo oxidation with HIO₄.
    - Mechanism descriptions and effects of regioselectivity, solvents, etc. are essential in the rest of the reactions discussed.