Organic Reaction Mechanisms: Neighbouring Group Participation

Summary

This lecture discusses Neighboring Group Participation (NGP) in nucleophilic substitution reactions, focusing on the mechanism and its implications. NGP involves two consecutive SN2 reactions: an intramolecular step where a neighboring group acts as a nucleophile, followed by an intermolecular reaction. The process results in a cyclic intermediate and ultimately leads to retention of configuration through inversions. The rate of NGP reactions depends solely on the substrate, highlighting the unique role of internal nucleophiles. Key examples include the reactions involving oxygen and sulfur as neighboring groups, showcasing their impact on reaction speed and configuration changes.

Takeaways

• 😀 Neighboring Group Participation (NGP) is a mechanism where a neighboring group acts as a nucleophile in a reaction, impacting the outcome.
• 😀 In SN2 reactions, an external nucleophile attacks a carbon atom, leading to the formation of a transition state with a leaving group.
• 😀 The NGP mechanism involves two successive nucleophilic substitution reactions: the first is intramolecular and the second is intermolecular.
• 😀 In NGP, the intramolecular SN2 reaction leads to the formation of a cyclic intermediate and causes the first inversion of configuration.
• 😀 The second SN2 reaction (intermolecular) restores the original configuration, resulting in a net retention of configuration through inversions.
• 😀 The rate of NGP reactions depends solely on the substrate, as the intramolecular SN2 reaction is slow, while the intermolecular reaction is fast.
• 😀 Common features of NGP mechanisms include the formation of cyclic intermediates and the significantly faster reaction rates compared to normal SN2 reactions.
• 😀 Atoms or groups within the molecule that can act as nucleophiles include those with lone pairs of electrons, such as oxygen, sulfur, and nitrogen.
• 😀 Examples of NGP include the alkaline hydrolysis of 2-bromopropanoic acid and the acetolysis of 4-methoxybutyl borosilicate.
• 😀 Mustard gas hydrolysis showcases sulfur as a neighboring group, highlighting the mechanism's relevance to toxic reactions.

Q & A

What is the primary focus of the lecture on neighboring group participation (NGP)?

The lecture focuses on the role of neighboring groups in nucleophilic substitution reactions, particularly how they act as nucleophiles in the NGP mechanism.

How does a normal SN2 reaction differ from a neighboring group participation reaction?

In a normal SN2 reaction, an external nucleophile attacks the carbon atom bonded to a leaving group. In contrast, in NGP, a neighboring group within the same molecule acts as the nucleophile, facilitating the reaction more efficiently.

What are the two types of reactions involved in neighboring group participation?

NGP involves two successive nucleophilic substitution reactions: the first is an intramolecular SN2 reaction and the second is an intermolecular SN2 reaction.

What happens to the configuration of the molecule during NGP?

NGP involves two inversions of configuration due to the two SN2 reactions, resulting in the final product retaining the original configuration.

Why is the rate of NGP reactions dependent only on the substrate?

The rate of NGP reactions depends solely on the substrate because the first step is slow and is the rate-determining step, while the second step is fast and involves an external nucleophile.

What is the significance of cyclic intermediates in NGP?

Cyclic intermediates are a crucial feature of NGP, as their formation is integral to the mechanism and allows for the retention of configuration after the nucleophilic attacks.

Can you provide an example of how oxygen acts as a neighboring group in NGP?

One example is the alkaline hydrolysis of 2-bromopropanoic acid, where the OH⁻ group acts as a neighboring group, leading to the formation of a cyclic intermediate and ultimately a product that retains the configuration.

How much faster are NGP reactions compared to normal intermolecular substitution reactions?

NGP reactions are thousands of times faster than normal intermolecular substitution reactions due to the proximity of the nucleophile and leaving group within the same molecule.

What role does sulfur play in neighboring group participation reactions?

Sulfur can also act as a neighboring group participant due to its lone pair of electrons, as seen in the base-catalyzed hydrolysis of mustard gas, where sulfur facilitates nucleophilic attack.

What will the next lecture focus on regarding neighboring group participation?

The next lecture will cover other neighboring groups, specifically halogens and nitrogen, and their roles in neighboring group participation reactions.