The Thorpe–Ingold effect, gem-dimethyl effect, or angle compression is an effect observed in

chemistry Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that covers the Chemical element, elements that make up matter to the chemical compound, compounds made of atoms, molecules and ions ...

where increasing

steric hindrance Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

favours ring closure and intramolecular reactions. The effect was first reported by Beesley, Thorpe, and Ingold in 1915 as part of a study of

cyclization reaction A cyclic compound (or ring compound) is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where a ...

s. It has since been generalized to many areas of chemistry. The comparative rates of

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

formation (lactonization) of various 2-hydroxybenzenepropionic acids illustrate the effect. The placement of an increasing number of methyl groups accelerates the cyclization process. : LactonizationRates

One application of this effect is addition of a

quaternary carbon A quaternary carbon is a carbon atom bound to four other carbon atoms. For this reason, quaternary carbon atoms are found only in hydrocarbons having at least five carbon atoms. Quaternary carbon atoms can occur in branched alkanes, but not in lin ...

(e.g., a

gem A gemstone (also called a fine gem, jewel, precious stone, or semiprecious stone) is a piece of mineral crystal which, in cut and polished form, is used to make jewelry or other adornments. However, certain rocks (such as lapis lazuli, opal, a ...

-di

methyl group In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

) in an

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloalk ...

chain to increase the

reaction rate The reaction rate or rate of reaction is the speed at which a chemical reaction takes place, defined as proportional to the increase in the concentration of a product per unit time and to the decrease in the concentration of a reactant per unit ...

and/or

equilibrium constant The equilibrium constant of a chemical reaction is the value of its reaction quotient at chemical equilibrium, a state approached by a dynamic chemical system after sufficient time has elapsed at which its composition has no measurable tendency ...

of cyclization reactions. An example of this is an

olefin metathesis Olefin metathesis is an organic reaction that entails the redistribution of fragments of alkenes (olefins) by the scission and regeneration of carbon-carbon double bonds. Because of the relative simplicity of olefin metathesis, it often create ...

reaction: In the field of

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

foldamers In chemistry, a foldamer is a discrete chain molecule (oligomer) that folds into a conformationally ordered state in solution. They are artificial molecules that mimic the ability of proteins, nucleic acids, and polysaccharides to fold into w ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...

s containing quaternary carbons such as

2-aminoisobutyric acid 2-Aminoisobutyric acid (also known as α-aminoisobutyric acid, AIB, α-methylalanine, or 2-methylalanine) is the non-proteinogenic amino acid with the structural formula H2N-C(CH3)2-COOH. It is rare in nature, having been only found in meteorites, ...

are used to promote formation of certain types of helices. : image:tiemethathesis.PNG One proposed explanation for this effect is that the increased size of the substituents increases the angle between them. As a result, the angle between the other two substituents decreases. By moving them closer together, reactions between them are accelerated. It is thus a kinetic effect. : image:Thorpeingoldeffect.PNG The effect also has some thermodynamic contribution as the

in silico In biology and other experimental sciences, an ''in silico'' experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon' (correct la, in silicio), referring to silicon in computer chips. It ...

strain energy In physics, the elastic potential energy gained by a wire during elongation with a tensile (stretching) force is called strain energy. For Linear elasticity, linearly elastic materials, strain energy is: : U = \frac 1 2 V \sigma \epsilon = \frac ...

decreases on going from

cyclobutane Cyclobutane is a cycloalkane and organic compound with the formula (CH2)4. Cyclobutane is a colourless gas and commercially available as a liquefied gas. Derivatives of cyclobutane are called cyclobutanes. Cyclobutane itself is of no commercial ...

to 1-methylcyclobutane and 1,1-dimethylcyclobutane by a value between 8 kcal/mole and 1.5 kcal/mole. A noteworthy example of the Thorpe-Ingold effect in supramolecular catalysis is given by diphenylmethane derivatives provided with guanidinium groups. These compounds are active in the cleavage of the RNA model compound HPNP. Substitution of the methylene group of the parent diphenylmethane spacer with cyclohexylidene and adamantylidene moieties enhances catalytic efficiency, with gem dialkyl effect accelerations of 4.5 and 9.1, respectively. : 550px

References

{{DEFAULTSORT:Thorpe-Ingold effect Physical organic chemistry Chemical kinetics Stereochemistry

See also

References