Organic Chemistry MCAT Practice Exam

Which of the following conditions promotes nucleophilic addition to a carbonyl group?

1. Strong base presence

2. Use of a weak nucleophile

3. Absence of acid

4. High pH environments

The correct answer is: Use of a weak nucleophile

Nucleophilic addition to carbonyl groups is facilitated by conditions that promote the attraction of nucleophiles to the electrophilic carbonyl carbon. In this case, the use of a weak nucleophile can actually be effective in certain circumstances. While strong nucleophiles are typically more reactive and will engage with the carbonyl carbon more vigorously, weak nucleophiles can also participate in addition reactions if the carbonyl compound is sufficiently activated by other factors, such as the presence of a strong electron-withdrawing group or specific reaction conditions that stabilize the transition state. In practical applications, certain weak nucleophiles can react with carbonyls, especially if a polar protic solvent is used that might stabilize the ionized form of the nucleophile or if the carbonyl is converted to a more reactive form through protonation or complexation. This understanding is important when considering reaction conditions, since the presence of stronger bases or high pH can often lead to competing side reactions, such as enolate formation, rather than straightforward nucleophilic addition. Thus, while strong bases, high pH environments, and certain acids generally favor increasing reactivity of the nucleophile, they can also complicate the addition reaction if a balance isn't maintained.