Question

Provide a mechanism for the following transformation. Be careful. This problem is much harder than it looks at first. Hint: The mechanism involves a lactone intermediate. COC(=O)CCC(=O)OC Mixture of stereoisomers (35\%)

Short answer

The mechanism involves lactonization leading to a lactone intermediate, followed by ring opening and reesterification, forming a mixture of stereoisomers.

Step-by-step solution

Identify the Starting Material

The starting material is dimethyl glutarate (given by SMILES notation: COC(=O)CCC(=O)OC). This compound has two ester groups.

Lactonization (formation of the lactone intermediate)

Under acidic conditions, one of the ester groups reacts intramolecularly with the hydroxyl group adjacent to the other ester group to form a lactone. This typically involves the cyclic ester (lactone) formation reaction.

Ring Opening of Lactone

The formed lactone can undergo hydrolysis under basic or acidic conditions to form a carboxylic acid and an alcohol.

Esterification of Opened Lactone

The carboxylic acid can further react with an alcohol to reform the ester groups, leading to a mixture of products (stereoisomers) containing ester functionalities.

Key concepts

lactonization

Lactonization is a crucial step in many organic synthesis processes. It involves the formation of a lactone, which is a cyclic ester, from a hydroxy acid. In the specific exercise we're looking at, dimethyl glutarate undergoes lactonization.
Under acidic conditions, the compound's hydroxy group reacts intramolecularly, that is, within the same molecule, with one of the ester groups.
This reaction forms a cyclic structure known as a lactone. It's a key reaction because it forms a stable ring structure, which is essential for further transformations.
The newly formed bond within the ring stabilizes the molecule and sets the stage for subsequent reactions that can transform the lactone into other useful compounds.

intramolecular reactions

Intramolecular reactions are reactions that occur within a single molecule. These are important in organic chemistry because they can lead to the formation of ring structures and other complex molecules.
In the exercise, an intramolecular reaction occurs during the lactonization step. Here, one part of the molecule reacts with another part of the same molecule, rather than with a different molecule.
This intramolecular reaction is beneficial because it can occur more quickly and efficiently compared to intermolecular reactions, where two different molecules need to collide and react.

ester hydrolysis

Ester hydrolysis is the breaking down of an ester into its component alcohol and carboxylic acid. This can happen under acidic or basic conditions.
In the context of the exercise, hydrolysis happens after the lactone is formed. The lactone undergoes hydrolysis, breaking open the ring and producing a carboxylic acid and an alcohol.
Understanding ester hydrolysis is critical because it often leads to the generation of functional groups that can undergo further chemical transformations.
Once the ester group is broken down, the resulting carboxylic acid can be turned back into an ester or other functional groups through additional reactions.

stereoisomers

Stereoisomers are molecules that have the same molecular formula and sequence of bonded atoms but differ in the three-dimensional orientation of their atoms. They are important in organic chemistry because different stereoisomers of a compound can have different chemical and biological properties.
In the exercise, the final product is a mixture of stereoisomers. This happens because, after the lactone is hydrolyzed and the carboxylic acid is re-esterified, there are multiple ways the atoms can arrange in space.
This leads to different stereoisomers forming as products, which means the chemical reaction doesn't produce a single, uniform product but rather a mix of molecules that are stereoisomers of each other.