Synthesis of nitriles by nucleophilic displacement of halide from an alkyl halide is practical only with primary and secondary alkyl halides. It fails with tertiary alkyl halides. Why? What is the major product of the following reaction?

Nucleophilic substitution reactions are a fundamental class of reactions in organic chemistry where an electron-rich nucleophile strategically targets and replaces an electron-withdrawing group (often a halogen) on a carbon atom.

In the context of nitrile synthesis, the cyanide ion, bearing a negative charge due to its extra electron, is the nucleophile. It seeks out a positive or partially positive carbon atom that bears a leaving group, such as a halogen in an alkyl halide. The cyanide ion provides an electron pair to form a new carbon-nitrogen bond, resulting in the release of the leaving group and the formation of a nitrile.

This type of reaction is fundamental in organic synthesis because it helps create a wide variety of compounds by simply changing the nucleophile or the leaving group. It's essential for students to understand that the reactivity and outcome of these reactions significantly depend on the type of alkyl halide and the conditions under which the reaction occurs.

The S_N2 mechanism describes a bimolecular nucleophilic substitution where the bond formation and bond breaking occur simultaneously. 'S_N' stands for substitution nucleophilic, and '2' indicates that the rate-determining step involves two chemical species.

During this concerted process, the nucleophile attacks the electrophilic carbon from the opposite side of the leaving group, leading to an inversion of configuration at that carbon center, a phenomenon often compared to opening an umbrella inside out.

Key Characteristics of S_N2

• The reaction is a single, concerted step with no intermediates.
• The rate of reaction is dependent on the concentration of both the nucleophile and substrate.
• Steric hindrance significantly affects the rate of S_N2 reactions.
• An inversion of stereochemistry at the carbon center occurs.

Understanding these aspects is crucial for predicting the outcome of a synthesis task involving S_N2 reactions.

Steric hindrance is a concept that refers to the prevention of chemical reactions by the physical size of groups within the molecule. It plays a critical role in determining the feasibility and rate of many reactions in organic chemistry, including nucleophilic substitution reactions.

Tertiary alkyl halides are particularly problematic for S_N2 reactions due to the bulky nature of the alkyl groups attached to the central carbon atom. These groups occupy significant space around the reactive site, making it difficult for nucleophiles to approach and effectively collide with the electrophilic carbon.

Implications of Steric Hindrance

• Decreased reactivity in S_N2 reactions for tertiary alkyl halides.
• Preference of alternative reaction pathways, such as elimination or S_N1 mechanisms, for sterically hindered substrates.
• Designing synthesis routes requires careful consideration of steric effects.

A clear understanding of steric hindrance helps explain why certain reactions do not occur as expected and assists in the design of successful synthetic strategies.