Question

Primary amines react with esters to yield amides: \(\mathrm{RCO}_{2} \mathrm{R}^{\prime}+\mathrm{R}^{\prime \prime} \mathrm{NH}_{2} \rightarrow\) RCONHR" + R'OH. Propose a mechanism for the following reaction of an \(\alpha, \beta\) -unsaturated ester.

Short answer

The mechanism involves nucleophilic attack by amine, forming an amide and alcohol.

Step-by-step solution

Nucleophilic Attack

In the first step of the mechanism, the nitrogen atom in the primary amine (\( ext{R''NH}_2 \)) acts as a nucleophile. It attacks the carbonyl carbon of the ester \( ext{RCO}_2 ext{R'} \). This is facilitated by the partial positive charge present on the carbonyl carbon due to the electron-withdrawing nature of the oxygen atoms, leading to the formation of a tetrahedral intermediate.

Tetrahedral Intermediate Formation

The nucleophilic attack leads to the cleavage of the \( ext{C=O} \) double bond, forming a tetrahedral intermediate. At this intermediate stage, the negatively charged oxygen atom can stabilize the structure due to its electronegativity.

Collapse of the Tetrahedral Intermediate

The negatively charged oxygen atom in the tetrahedral intermediate donates its lone pair back to form a double bond, causing the \( ext{C-O} \) bond of the leaving \( ext{R'} \) group to break. This results in the formation of an amide \( ext{RCONHR''} \) and an alcohol \( ext{R'OH} \).

Key concepts

Nucleophilic Attack

In the process of amide formation from esters, the primary amine acts as a nucleophile. A nucleophile is a chemical species that donates an electron pair to form a chemical bond. In this reaction, the nitrogen atom in the amine (\( \mathrm{R''NH}_2 \)) is the nucleophile. It possesses a lone pair of electrons, making it ready to attack the electrophilic carbon atom in the ester (\( \mathrm{RCO}_2\mathrm{R'} \)).
This carbon is electrophilic due to the presence of the oxygen atom, which pulls electron density away from it, making it partially positive. This characteristic makes it susceptible to attacks by nucleophiles. The nucleophile-amide nitrogen approaches and attacks this carbon, forming a new bond between the amine group and the ester, subsequently leading to a crucial transformation in our chemical reaction pathway.

Tetrahedral Intermediate

Once the nucleophilic attack occurs, the carbonyl group of the ester (\( \mathrm{C=O} \)) undergoes a transformation. The attack results in the conversion of the double-bonded carbonyl oxygen into an array with a single bond to carbon and a resultant negative charge on oxygen. This is known as the tetrahedral intermediate.
During this step, the structure changes from a planar configuration to a tetrahedral one. The normally planar carbonyl carbon now has four substituents wrapped around it, similar to the four corners of a tetrahedron. This transitionary structure is stabilized by the negatively charged oxygen atom, which pulls electron density towards itself, maintaining the integrity of the intermediate structure.
The significance of the tetrahedral intermediate lies in its ability to reorganize chemical bonds leading to the eventual collapse and reformation of the double bond, which is essential in the conversion to an amide.

Amide Formation

The final step in this chemical mechanism involves the conversion of the intermediate into the desired products. The tetrahedral intermediate must undergo rearrangements that reform the double bond to oxygen. As the previously negatively charged oxygen donates its lone pair to reform the double bond, an adjacent bond is broken.
This bond breakup usually happens at the carbon-oxygen bond connecting the ester group that acts as the leaving group (\( \mathrm{R'} \)). This process results in the creation of the amide (\( \mathrm{RCONHR''} \)) and the byproduct alcohol (\( \mathrm{R'OH} \)).
The formation of an amide is crucial, as amides are notably stable and serve as key building blocks in both natural and synthetic chemistry. This mechanism showcases the elegance of organic chemistry reactions, transforming simple esters and amines into highly useful chemical entities.