Question

A chemist in need of 2,2 -dimethylpentanoic acid decided to synthesize some by reaction of 2 -chloro-2-methylpentane with \(\mathrm{NaCN}\), followed by hydrolysis of the product. After the reaction sequence was carried out, however, none of the desired product could be found. What do you suppose went wrong?

Short answer

Elimination occurred instead of substitution due to the tertiary halide, preventing the desired product formation.

Step-by-step solution

Understand the Reaction Sequence

The chemist intends to convert 2-chloro-2-methylpentane into 2,2-dimethylpentanoic acid. This involves two main steps: first, substituting the chlorine in 2-chloro-2-methylpentane with a cyano group using NaCN, then hydrolyzing the resulting nitrile to form a carboxylic acid.

Analyze the Cyanide Substitution Step

In the first step, the chemist reacted 2-chloro-2-methylpentane with NaCN. Typically, cyanide ions (\(\text{CN}^-\)) perform nucleophilic substitution on primary or secondary alkyl halides. However, 2-chloro-2-methylpentane is a tertiary halide.

Evaluate the Result of Substituting a Tertiary Halide

Tertiary halides are prone to elimination reactions rather than substitution due to steric hindrance. Therefore, rather than forming the desired nitrile, elimination likely occurred, forming an alkene instead.

Consider the Impact of the Elimination Product

Since an alkene was formed in the initial step instead of the desired nitrile, the hydrolysis step could not produce 2,2-dimethylpentanoic acid, as no nitrile was present to hydrolyze into the carboxylic acid.

Key concepts

Nucleophilic Substitution

In organic chemistry, nucleophilic substitution is a fundamental reaction where a nucleophile, a species rich in electrons, bonds with or "attacks" a carbon atom, replacing a leaving group such as a halogen. This reaction is particularly common with primary and secondary alkyl halides due to their less bulky structure, allowing the nucleophile to approach the carbon atom easily.
Nucleophilic substitution reactions generally fall into two types: SN1 and SN2.

• SN1 (Unimolecular Nucleophilic Substitution) involves two steps, where the leaving group departs before the nucleophile attacks, forming a carbocation intermediate. This reaction is more common with tertiary halides because they can stabilize the carbocation due to their greater electron-donating ability.
• SN2 (Bimolecular Nucleophilic Substitution), on the other hand, occurs in a single step, with the nucleophile attacking as the leaving group leaves, requiring less steric hindrance for direct access to the carbon.

In the chemist's experiment with 2-chloro-2-methylpentane—a tertiary halide—the reaction did not proceed as an SN2 nucleophilic substitution. This occurs because the steric hindrance from the bulky groups around the carbon prevents the approach of the nucleophile, leading to an alternative reaction pathway.

Tertiary Halides

Tertiary halides are organic compounds in which a halogen atom, like chlorine or bromine, is attached to a carbon that is connected to three other carbon atoms. Due to this structure, these halides are surrounded by bulky groups, which significantly influences their reactivity patterns in chemical reactions.
The central issue with reactions involving tertiary halides, such as 2-chloro-2-methylpentane, is the steric hindrance. The crowded environment around the carbon prompts these halides to prefer reactions that do not involve direct attack by a nucleophile. This structural influence causes tertiary halides to:

• Favor elimination reactions over nucleophilic substitutions because elimination can occur without the nucleophile needing to directly approach the crowded carbon atom.
• React via SN1 mechanisms, which involve the formation of a more stable carbocation that doesn't require immediate direct contact between the nucleophile and the central carbon.

In the chemist’s attempted reaction, the steric hindrance discouraged the nucleophile from substituting on the tertiary carbon of 2-chloro-2-methylpentane, thus steering the reaction towards elimination.

Elimination Reactions

Elimination reactions are processes where elements are removed from a molecule, forming a double bond, or alkene, in the structure. These reactions include two types: E1 and E2, which often occur as alternatives to substitution when the substrate is unable to accommodate a nucleophile due to steric hindrance.

• E1 (Unimolecular Elimination) involves two steps similar to SN1, where the leaving group departs forming a carbocation, followed by deprotonation to form the alkene.
• E2 (Bimolecular Elimination) is a one-step process where the base removes a proton while the leaving group is expelled, simultaneously forming the double bond.

In the case of tertiary halides, such as 2-chloro-2-methylpentane, elimination is favored because it avoids the congestion at the carbon atom. This reaction can proceed even in the presence of a strong nucleophile if the steric hindrance is too high for direct substitution. In the chemist's experiment, the elimination reaction constituted the path of least resistance, resulting in an alkene instead of the desired nitrile, preventing the formation of 2,2-dimethylpentanoic acid in the hydrolysis step later.