Question

Chloroformates have the functional group \(\mathrm{R}-\mathrm{O} \quad \mathrm{Cl}\), in which \(\mathrm{R}\) is often a tert-butyl or benzyl group. A chloroformate is used in the following synthesis of the antibacterial drug linezolid (Zyvox). Based on your knowledge of carboxylic acid derivatives, predict the product of the following transformation used in a synthesis of linezolid (Zyvox). The new functional group created is called a carbamate. Carbamates are often used as protecting groups for amine groups during complex syntheses.

Short answer

Answer: The product of the transformation is a carbamate functional group with the structure R'-NH-CO-OR, where R' is derived from the original amine and R from the original chloroformate. The carbamate group serves as a protecting group for the amine during complex synthesis reactions.

Step-by-step solution

Identify the functional groups in reactants

Before the reaction, we should identify the main functional groups in both the amine and the chloroformate reactants. The amine has an R'-NH2 group, while the chloroformate has an R-O-Cl group.

Identify the nucleophile and electrophile

In this transformation, the amine group (R'-NH2) will act as the nucleophile because of the electron-rich nitrogen atom's lone pair, while the chloroformate's carbonyl carbon atom acts as the electrophile, being electron-deficient due to the two electronegative oxygen atoms.

Attack of the nucleophile

The nitrogen atom in the amine (R'-NH2) attacks the electrophilic carbonyl carbon atom of the chloroformate, converting it into a tetrahedral intermediate. The bond between the carbon and the chlorine atom weakens, building a negative charge on the chlorine atom.

Formation of carbamate

In the last step, the negatively charged chlorine atom takes the hydrogen atom from the newly formed N-H bond in the tetrahedral intermediate, leading to the formation of a carbamate functional group with the structure R'-NH-CO-OR. The chloride ion (Cl-) is released as a leaving group, completing the transformation. The product of this transformation used in the synthesis of linezolid is a carbamate functional group, R'-NH-CO-OR, where R' is derived from the original amine and R from the original chloroformate. The carbamate group serves as a protecting group for the amine during complex synthesis reactions.