Organohalides

Definition and Structure

Organohalides are organic compounds containing a carbon–halogen (C–X) bond, where X is a halogen (F, Cl, Br, or I). Alkyl halides (haloalkanes) are a subset where the halogen is bonded to an sp3-hybridized carbon.

• General Formula: R–X, where R is an alkyl group and X is a halogen.

• Bond Trends: As the halogen atom increases in size, the C–X bond length increases and bond strength decreases. The bond is polar, making the carbon atom electrophilic.

Nomenclature

• Use the IUPAC system: Identify the longest carbon chain, number from the end nearest a substituent, and list halogen substituents alphabetically.

• Example: 2-bromopropane (Br on the second carbon of propane).

Preparation of Alkyl Halides

• Radical Halogenation: Alkanes react with Cl2 or Br2 under light (hv) to form alkyl halides via a radical mechanism (initiation, propagation, termination).

• Reactivity and Selectivity: Tertiary hydrogens are most reactive due to radical stability. Bromination is more selective than chlorination because of higher activation energy.

• Allylic Bromination: NBS (N-bromosuccinimide) with hv selectively brominates allylic positions via a resonance-stabilized allyl radical, often yielding multiple isomeric products.

• From Alcohols: Alcohols react with HX (where X = Cl, Br, I) to form alkyl halides. Tertiary alcohols react fastest.

• Special Reagents:

  • SOCl2 for alkyl chlorides

  • PBr3 for alkyl bromides

  • PI3 for alkyl iodides

Organometallic Reagents

• Grignard Reagents: Formed by reacting alkyl halides with Mg in ether:

• Grignard reagents are strong nucleophiles and bases, useful for forming C–C bonds.

• Organocuprates (Gilman Reagents): are softer nucleophiles than Grignards and can couple with primary alkyl halides to form new C–C bonds.

Redox Transformations

• Alkyl halides serve as starting materials for various oxidation-reduction reactions in organic synthesis.

Reactions of Alkyl Halides: Nucleophilic Substitutions

Electrophilicity and Reaction Types

Alkyl halides are electrophilic due to the polar C–X bond. They undergo nucleophilic substitution (SN1 and SN2) and elimination (E1 and E2) reactions. For this exam, focus is on substitution mechanisms.

SN2 Mechanism (Bimolecular Nucleophilic Substitution)

• Mechanism: Single-step, backside attack by nucleophile, leading to inversion of configuration (Walden inversion).

• Rate Law: (second-order kinetics).

• Substrate Reactivity: Methyl > 1° > 2° > 3° (steric hindrance slows reaction).

• Nucleophile Strength: Strong bases/negative ions increase rate. Trend: I– > Br– > Cl– > F–. Resonance stabilization decreases nucleophilicity.

• Leaving Group Ability: Good leaving groups are weak bases (I–, Br–, Cl–, TsO–); poor leaving groups include OH–, NH2–, OR–.

• Solvent Effects: Polar aprotic solvents (DMSO, DMF, acetone) enhance SN2 by increasing nucleophile strength; polar protic solvents slow SN2 due to hydrogen bonding.

SN1 Mechanism (Unimolecular Nucleophilic Substitution)

• Mechanism: Two-step: (1) Leaving group departs, forming a carbocation; (2) Nucleophile attacks the carbocation. Results in racemization due to planar intermediate.

• Rate Law: (first-order kinetics).

• Carbocation Stability: 3° > 2° > 1° > methyl (more substituted carbocations are more stable).

• Solvent Effects: Polar protic solvents stabilize the carbocation and accelerate SN1 reactions.

Alcohols and Phenols

Structure and Classification

• Alcohols: Compounds with an –OH group on an sp3 carbon (R–OH).

• Phenols: Compounds with an –OH group directly attached to an aromatic ring (Ar–OH).

• Classification: Based on the number of alkyl groups attached to the carbon bearing the –OH:

  • Primary (1°): One alkyl group

  • Secondary (2°): Two alkyl groups

  • Tertiary (3°): Three alkyl groups

Naming Alcohols and Phenols

• Longest chain containing –OH is the parent; suffix is “–ol”.

• Number the chain to give the –OH the lowest possible locant. Number can be placed before the parent name or before “–ol”.

• Example: 2-propanol or propan-2-ol.

Physical Properties

• Hydrogen bonding leads to high boiling points and water solubility for alcohols and phenols.

Acidity and Resonance

• Alcohols are weak acids (Ka ~10–16); phenols are more acidic (Ka ~10–10).

• Acidity increases with electron-withdrawing groups and decreases with electron-donating groups.

• Phenoxide ion is stabilized by resonance, increasing acidity.

Activation of Alcohols for Substitution

• Alcohols are poor leaving groups; activation is required for substitution reactions:

  1. Protonation with strong acid (e.g., HCl, HBr)

  2. Treatment with thionyl chloride (SOCl2) or PBr3

  3. Formation of tosylate (reaction with tosyl chloride and base, e.g., Et3N)

• Tosylates are excellent leaving groups due to resonance stabilization.

Preparation of Alcohols

• Solvolysis: Reaction of alkyl halides with H2O (usually via SN1 mechanism); can also yield ethers.

• Reduction of Carbonyls:

  • Aldehydes + NaBH4 or LiAlH4 → 1° alcohols

  • Ketones + NaBH4 or LiAlH4 → 2° alcohols

  • Carboxylic acids/esters + LiAlH4 → 1° alcohols

• Epoxide Ring Opening: Epoxides react with nucleophiles under acidic or basic conditions to yield alcohols (regioselectivity depends on conditions).

Protection of Alcohols

• Alcohols can be protected as silyl ethers (e.g., with TMSCl) to prevent unwanted reactions during multi-step syntheses.

Summary Table: Key Properties and Reactions

Additional info: The above notes expand on the brief study guide points, providing definitions, mechanisms, and examples for clarity and exam preparation.