Question

Which of the following alkyl halides would be the most reactive in an \(\mathrm{SN}^{2}\) reaction? (a) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{Br}\) (b) CC(C)CBr (c) CC(C)(Br)c1ccccc1 (d) CC(Br)Cc1ccccc1

Short answer

(a) is the most reactive for an SN2 reaction due to minimal steric hindrance.

Step-by-step solution

Understand the SN2 Reaction Mechanism

The SN2 mechanism involves the substitution of a leaving group by a nucleophile in one concerted step. This typically occurs in primary alkyl halides because there is less steric hindrance around the carbon being attacked by the nucleophile.

Analyze the Structure of Alkyl Halides

Examine the structural formulas for each option: (a) is a primary alkyl halide with a bromine leaving group. (b) is a secondary alkyl halide with a bromine leaving group. (c) is a tertiary alkyl halide with a bromine leaving group attached to an aromatic ring. (d) is a benzylic bromide, where the bromine is attached to a carbon adjacent to an aromatic ring.

Determine Steric Hindrance

SM2 reactions favor less hindered sites. Primary alkyl halides (like option a) are less hindered compared to other options. Terioary (like c) are the most hindered due to bulky groups, making them poor candidates for SN2 reactions.

Consider the Effect of Aromatic Rings

Option (d) is a benzylic halide and generally shows increased reactivity in SN2 reactions due to the resonance stabilization of the transition state, making it more reactive than typical secondary alkyl halides.

Identify the Most Reactive for SN2

Weighing steric effects and resonance, the primary alkyl halide (a) is preferred for SN2 due to minimal steric hindrance compared to secondary or tertiary halides, even considering the aromatic stabilization in (d).

Key concepts

Alkyl Halides

Alkyl halides are compounds where one or more hydrogen atoms in an alkane have been replaced by a halogen (F, Cl, Br, I). These compounds are crucial in organic chemistry due to their reactivity and role in various chemical reactions.
Alkyl halides are reactive due to the polar carbon-halogen bond, which is susceptible to nucleophilic attacks. This bond is characterized by the halogen being more electronegative than carbon, pulling electron density toward itself. Consequently, the carbon becomes partially positive, making it a prime target for nucleophiles (species that donate electron pairs).

• Types of Alkyl Halides: Primary, secondary, and tertiary, depending on how many carbon atoms the carbon attached to the halogen is connected to.
• Reactivity: Their nature impacts their role in various reactions, especially nucleophilic substitutions like SN2 reactions.

Nucleophilic Substitution

Nucleophilic substitution is a fundamental class of reactions in organic chemistry where a nucleophile replaces a leaving group attached to a sp³-hybridized carbon. The SN2 reaction is a type of nucleophilic substitution that occurs in a single, concerted step.
This means the nucleophile attacks the carbon simultaneously as the leaving group departs.
In SN2 reactions:

• Bimolecular Mechanism: SN2 stands for 'substitution nucleophilic bimolecular', indicating that the rate of reaction depends on the concentration of both the nucleophile and the substrate.
• Backside Attack: The nucleophile attacks from the opposite side of the leaving group, leading to inversion of configuration at the carbon center.
• Preference for Less Hindered Substrates: Due to steric considerations, SN2 reactions are fastest in primary alkyl halides and slow down significantly in secondary, and even further hindered in tertiary alkyl halides.

Steric Hindrance

Steric hindrance refers to the prevention of chemical reactions by the physical presence of bulky groups at or near a reactive site.
In the context of SN2 reactions, steric hindrance can significantly impact the reaction's rate by creating physical barriers that impede the approaching nucleophile.

• Impact on SN2 Reactions: Primary alkyl halides are favored in SN2 reactions due to less steric hindrance. Secondary alkyl halides may react, but at a slower rate, while tertiary halides are typically unreactive due to excessive bulk.
• Consequence of Backside Attack: Since SN2 reactions require the nucleophile to approach from the opposite side of the leaving group, any group that blocks this approach increases steric hindrance.
• Optimizing Conditions: Choosing less hindered reactants and solvent systems can alleviate steric hindrance and enhance the efficiency of SN2 reactions.

Primary and Secondary Alkyl Halides

Primary and secondary alkyl halides are differentiated based on the carbon atom to which the halogen is attached.
In primary alkyl halides, the carbon atom connected to the halogen is attached to only one other carbon atom, making them very reactive in SN2 reactions.
Secondary alkyl halides, conversely, have the carbon attached to two other carbon atoms, which introduces more steric hindrance compared to primary alkyl halides. In SN2 reactions:

• Reactivity: Primary alkyl halides react rapidly due to minimal steric impedance, while secondary alkyl halides react more slowly and may compete between SN2 and other mechanisms.
• Consideration for Tertiary: Tertiary alkyl halides are typically unsuitable for SN2 reactions due to extensive steric hindrance, often leading them towards SN1 reactions.

Resonance Stabilization

Resonance stabilization plays a significant role in chemical reactivity by stabilizing transition states during reactions.
In cases like benzylic halides, where a halogen is adjacent to a benzene ring, resonance stabilization can enhance reactivity. Here's how it benefits SN2 reactions:

• Enhanced Reactivity: For benzylic halides, the benzene ring can delocalize the positive charge during the transition state, stabilizing the complex and facilitating nucleophilic substitution.
• Exceptions to Steric Hindrance: Even when steric hindrance is present, resonance can sometimes offset its effects, making benzylic positions reactive despite their bulkier structure.
• Comparison with Typical Halides: This type of stabilization is in contrast to typical primary and secondary alkyl halides, which do not benefit from this resonance effect.