Preparation of Alkyl Halides

Free Radical Halogenation of Alkanes

Alkyl halides can be synthesized by the halogenation of alkanes, a process that involves the substitution of a hydrogen atom with a halogen atom via a free radical mechanism. The selectivity and efficiency of this reaction depend on the halogen used.

• Chlorination produces a mixture of products due to low selectivity. It is mainly useful for alkanes where all hydrogens are equivalent.

• Bromination is highly selective, favoring the substitution at more substituted carbon atoms: 3° > 2° > 1°.

Example: Chlorination of cyclohexane and bromination of isobutane illustrate the difference in selectivity and product distribution.

Free Radical Allylic Halogenation

Allylic halogenation targets the carbon atom adjacent to a double bond (the allylic position). This process is especially efficient with bromine due to the resonance stabilization of the allylic radical intermediate.

• Allylic radicals are stabilized by resonance, making allylic halogenation highly selective and efficient.

• Bromination at the allylic position yields high product selectivity and yield.

Example: Bromination of cyclohexene at the allylic position forms 3-bromocyclohexene.

Mechanism of Allylic Bromination

The mechanism involves the abstraction of an allylic hydrogen atom to form a resonance-stabilized allylic radical, which then reacts with bromine to yield the allylic bromide.

• Both possible allylic radicals can react with bromine, leading to product formation at the allylic position.

N-Bromosuccinimide (NBS) as an Allylic Brominating Agent

N-Bromosuccinimide (NBS) is commonly used for allylic bromination because it maintains a low, steady concentration of Br2 in the reaction mixture, preventing unwanted side reactions.

• NBS reacts with HBr (formed during bromination) to regenerate Br2 in situ.

Example: Allylic bromination of 2,3-dimethylbut-2-ene with NBS and light yields the corresponding allylic bromide.

Reactions of Alkyl Halides

The SN2 Reaction (Bimolecular Nucleophilic Substitution)

The SN2 reaction is a fundamental mechanism in organic chemistry where a nucleophile replaces a leaving group (such as a halide) in a single, concerted step. This reaction is second order overall, depending on the concentrations of both the alkyl halide and the nucleophile.

• Mechanism: The nucleophile attacks the electrophilic carbon from the opposite side of the leaving group, resulting in inversion of configuration at the carbon center.

• Rate Law:

• Leaving Group: The halogen atom (e.g., I−) departs with its electron pair.

Example: Hydroxide ion reacts with iodomethane to produce methanol and iodide ion.

SN2 Reaction Mechanism

The SN2 mechanism is concerted, meaning bond formation and bond breaking occur simultaneously through a single transition state. The nucleophile approaches the substrate from the side opposite the leaving group, leading to a stereochemical inversion (Walden inversion).

• Transition State: Both the nucleophile and leaving group are partially bonded to the central carbon in the transition state.

• Product: The nucleophile replaces the leaving group, and the configuration at the carbon is inverted.

Additional info: The SN2 reaction is most efficient with primary alkyl halides and less hindered substrates. Tertiary alkyl halides are generally unreactive in SN2 reactions due to steric hindrance.