Nucleophilic Addition: Videos & Practice Problems

Nucleophilic addition is a fundamental mechanism in organic chemistry where a nucleophile, which is typically negatively charged or has a lone pair of electrons, attacks the electrophilic carbon of a carbonyl group. This results in the formation of a tetrahedral intermediate. The carbonyl carbon is electrophilic due to the partial positive charge it carries, making it highly reactive towards nucleophiles. The final product of nucleophilic addition is often a substituted alcohol, depending on the nucleophile used. This mechanism is crucial for various organic reactions, including reductions and the formation of organometallic compounds.

The mechanism of nucleophilic addition involves several steps. First, the nucleophile, which has a high electron density, attacks the electrophilic carbon of the carbonyl group. This attack forms a new bond, resulting in a tetrahedral intermediate. Since carbon cannot have five bonds, the double bond between carbon and oxygen breaks, giving the oxygen a negative charge. This intermediate is then protonated by an acid or proton donor, leading to the formation of a substituted alcohol. The general mechanism can be represented as:

${R-C=O}_2+N-\to {R-C-O-}_2+H+\to {R-C-\mathrm{OH}}_2$

Common nucleophiles used in nucleophilic addition reactions include:

• Hydride (H^-): Often used in reductions, adding two hydrogens across a double bond.
• Cyanide (CN^-): Adds a cyano group to the carbonyl carbon, forming a substituted alcohol.
• Alkynides: Strong nucleophiles that add an alkynyl group to the carbonyl carbon.
• Organometallic compounds: Such as Grignard reagents (RMgX) and organolithium compounds (RLi), which add alkyl or aryl groups to the carbonyl carbon.

These nucleophiles demonstrate the versatility of nucleophilic addition in organic synthesis.

A tetrahedral intermediate is a key structure formed during the nucleophilic addition mechanism. When a nucleophile attacks the electrophilic carbon of a carbonyl group, the carbon-oxygen double bond breaks, and the carbon forms a new single bond with the nucleophile. This results in a carbon atom bonded to four different groups, creating a tetrahedral geometry. The intermediate is crucial for the reaction to proceed, as it eventually leads to the formation of the final product, often a substituted alcohol. Understanding the tetrahedral intermediate is essential for grasping the overall mechanism of nucleophilic addition.

Nucleophilic addition is closely related to reduction reactions, particularly when the nucleophile is a hydride ion (H^-). In such cases, the hydride ion attacks the electrophilic carbon of the carbonyl group, leading to the formation of a tetrahedral intermediate. This intermediate is then protonated to form an alcohol. The addition of two hydrogens across the carbonyl double bond is characteristic of a reduction reaction. Therefore, nucleophilic addition with hydride nucleophiles is a common method for reducing carbonyl compounds to alcohols in organic synthesis.