Question

Reaction of a primary or secondary amine with diethyl carbonate under controlled conditions gives a carbamic ester. CCOC(=O)OCC CCCCCN CCOC(=O)NCCCF Diethyl carbonate Butylamine Ethyl \(N\)-butylcarbamate Propose a mechanism for this reaction.

Short answer

Answer: The three main steps in the reaction mechanism are: 1) Nucleophilic attack of amine on diethyl carbonate, forming a tetrahedral intermediate, 2) Intermediate rearrangement, resulting in the formation of a carbamate species and ethanol, and 3) Deprotonation of the carbamate intermediate by ethanol, leading to the formation of ethyl N-butylcarbamate and regenerating butylamine.

Step-by-step solution

Nucleophilic attack of amine on diethyl carbonate

In the first step, the lone pair of electrons on the nitrogen atom in the butylamine will attack one of the carbonyl carbon atoms in diethyl carbonate, forming a tetrahedral intermediate species (and breaking the carbonyl double bond). This is a nucleophilic addition.

Intermediate rearrangement

Now, the negatively charged oxygen atom, which gained two electrons during the nucleophilic addition, will reclaim its electron pair and close the carbonyl double bond once again, forming a new C=O bond. Simultaneously, the ethoxy group (OEt) attached to the same carbon atom will leave as an ethanol molecule, resulting in the formation of an intermediate carbamate species and ethanol.

Deprotonation of the carbamate intermediate

The ethoxy group (now in the form of ethanol) acts as a weak base and deprotonates the nitrogen in the carbamate intermediate to create ethyl N-butylcarbamate (the desired final product) and regenerate butylamine molecule. After these three steps, the mechanism is complete. The amine molecule has successfully reacted with diethyl carbonate to form a carbamic ester (ethyl N-butylcarbamate).

Key concepts

Nucleophilic Attack in Organic Chemistry

Understanding nucleophilic attack is foundational in organic chemistry. It represents a chemical process where a nucleophile, which is a species with a lone pair of electrons, seeks out an electrophilic center – typically a carbon atom with a partial positive charge.

For instance, during the synthesis of a carbamic ester, a primary or secondary amine acts as the nucleophile. The lone pair of electrons on the nitrogen atom is attracted to the electrophilic carbon of the carbonyl group in diethyl carbonate. When the nucleophilic nitrogen makes contact with the electrophilic carbon, a bond forms, which is accompanied by the breaking of the carbonyl double bond. This results in the creation of a tetrahedral intermediate – a step crucial to the mechanism of carbamate formation.

Explaining the essence of nucleophilic attack in such transformations helps students visualize how new bonds are formed and is crucial to understanding multiple reaction pathways in organic synthesis.

Intermediate Rearrangement in Reaction Mechanisms

Many organic reactions involve an intermediate rearrangement, a step where the structure of the intermediate changes before the final product is formed. In the context of carbamic ester synthesis, after the nucleophilic attack creates a tetrahedral intermediate, a rearrangement occurs.

This rearrangement is characterized by an intramolecular shift of electrons. The initially formed tetrahedral intermediate possesses a negatively charged oxygen that had gained a pair of electrons during the nucleophilic attack. This oxygen now pushes its electron pair back down, reforming the carbonyl bond. At the same time, the alkoxide leaving group (in this case, ethoxy) is expelled, leaving as ethanol. A new intermediate, the carbamate, is thus formed.

Understanding the intermediate rearrangement is crucial because it provides insight into how reaction intermediates can stabilize themselves through the movement of electron pairs and the roles different atoms play in these processes.

Deprotonation in Carbamate Formation

The final stage of the carbamic ester synthesis is the deprotonation of the intermediate. Deprotonation is a common theme in many organic reactions; it is a process whereby a proton (H⁺) is removed from a molecule.

In our example, the ethanol created in the rearrangement step serves as a weak base and abstracts a proton from the nitrogen atom on our intermediate carbamate. This deprotonation facilitates the creation of the final product: the ethyl N-butylcarbamate. Through deprotonation, a neutral and more stable molecule is formed as the nitrogen atom goes from being positively charged to neutral.

Highlighting the importance of deprotonation helps students appreciate the role of bases in finalizing the structure of a molecule and in maintaining the balance between reactants and products during a chemical transformation.