Thorpe–Ingold effect

The Thorpe–Ingold effect is a concept in organic chemistry that describes the influence of geminal substituents on the rate of intramolecular reactions. This effect is particularly significant in reactions where a molecule undergoes a transformation that involves the formation of a ring structure, such as lactonization.

Overview

The Thorpe–Ingold effect, also known as the gem-dimethyl effect, is named after the chemists Jocelyn Field Thorpe and Christopher Kelk Ingold. It refers to the observation that the presence of two substituents on a carbon atom adjacent to a reactive center can accelerate the rate of certain intramolecular reactions. This is primarily due to the reduction in the effective distance between the reacting centers, which facilitates the formation of cyclic transition states.

Mechanism

The effect is attributed to the steric and electronic influence of the geminal substituents. These substituents can:

• Increase the rate of reaction by reducing the entropy of activation. The presence of bulky groups can pre-organize the molecule into a conformation that is closer to the transition state.
• Influence the electronic environment of the reactive center, potentially stabilizing the transition state.

Applications

The Thorpe–Ingold effect is particularly important in the synthesis of cyclic compounds. It is often exploited in the design of synthetic pathways where the formation of a ring is a key step. For example, in the synthesis of lactones, the presence of geminal substituents can significantly enhance the rate of lactonization.

Effect of geminal substituents on lactonization rates.

Examples

One classic example of the Thorpe–Ingold effect is observed in the cyclization of dicarboxylic acids to form lactones. When geminal methyl groups are present, the rate of lactonization is increased compared to when these groups are absent. This is illustrated in the accompanying image, which shows the effect of geminal substituents on lactonization rates.

Related pages

• Organic chemistry
• Intramolecular reaction
• Lactone
• Transition state