Thorpe–Ingold effect: Difference between revisions

Latest revision as of 05:20, 16 February 2025

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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-'''Thorpe–Ingold effect''' (also known as the '''geminal effect''' or the '''ligand proximity effect''') is a phenomenon observed in [[organic chemistry]] where the rate of a chemical reaction or the stability of molecules is affected by the presence of substituents in the vicinity of the reactive site or the bond being formed or broken. This effect is particularly significant in reactions involving the formation or cleavage of carbon-carbon bonds adjacent to a quaternary carbon center. The Thorpe–Ingold effect is named after the British chemists Jocelyn Field Thorpe and Christopher Kelk Ingold, who first described this phenomenon in the early 20th century.
+{{DISPLAYTITLE: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 can be attributed to several factors, including steric hindrance, electronic effects, and the preorganization of reactants. Steric hindrance occurs when the bulky substituents near the reactive site prevent the approach of reactants or the proper alignment of molecules for the reaction to proceed. Electronic effects involve the donation or withdrawal of electron density by substituents, which can stabilize or destabilize transition states and intermediates. Preorganization refers to the spatial arrangement of atoms or groups within a molecule that predisposes it towards a certain reaction pathway, thereby lowering the activation energy required for the reaction to occur.
+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 has wide-ranging applications in [[synthetic chemistry]], including the design of more efficient and selective synthetic routes. One of the most notable applications is in the field of [[cycloaddition]] reactions, where the effect is utilized to promote the formation of cyclic compounds with desired configurations. It also plays a crucial role in the synthesis of [[lactones]], [[lactams]], and other cyclic structures by facilitating ring-closure reactions. Additionally, the Thorpe–Ingold effect is instrumental in the development of [[polymer chemistry]], influencing the properties of polymers by affecting the reactivity of monomers and the stereochemistry of polymerization reactions.
+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]].
-==Mechanism==
+[[File:LactonizationRates.png|thumb|right|300px|Effect of geminal substituents on lactonization rates.]]
-The mechanism by which the Thorpe–Ingold effect influences chemical reactions involves a combination of steric and electronic factors. In reactions where steric hindrance is predominant, the presence of bulky groups near the reactive site can significantly slow down or even prevent certain reactions from occurring. On the other hand, electronic effects can either stabilize or destabilize the transition state of a reaction, depending on the nature of the substituents. For example, electron-donating groups can stabilize carbocation intermediates, while electron-withdrawing groups can stabilize carbanion intermediates. The preorganization of reactants, facilitated by the spatial arrangement of substituents, can also lower the activation energy of a reaction, making it more favorable.
 ==Examples==
-One classic example of the Thorpe–Ingold effect is observed in the [[Diels-Alder reaction]], where the presence of alkyl groups adjacent to the dienophile can enhance the reaction rate by facilitating the proper orientation of the diene and dienophile for cycloaddition. Another example is the accelerated cyclization of [[gamma,delta-unsaturated carbonyl compounds]] to form five- or six-membered rings, where the proximity of substituents plays a crucial role in determining the efficiency and selectivity of the ring closure.
+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.
-==Conclusion==
+==Related pages==
-The Thorpe–Ingold effect is a fundamental concept in organic chemistry that has profound implications for the design and synthesis of organic molecules. By understanding and exploiting this effect, chemists can develop more efficient and selective synthetic strategies, leading to the creation of novel compounds with a wide range of applications in medicine, materials science, and beyond.
+* [[Organic chemistry]]
+* [[Intramolecular reaction]]
+* [[Lactone]]
+* [[Transition state]]
 [[Category:Organic chemistry]]
-[[Category:Chemical reactions]]
-{{Chemistry-stub}}