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Reactivity and molecular recognition: amine methylation by an introverted ester
Byron W Purse1, Pablo Ballester, Julius Rebek
1The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Journal of the American Chemical Society
|December 4, 2003
Summary
This study details a host molecule reacting with tertiary amines, forming a complex that significantly accelerates the reaction rate. This supramolecular effect enhances reaction speed by over 20,000 times.
Area of Science:
- Supramolecular Chemistry
- Organic Reaction Mechanisms
- Host-Guest Chemistry
Background:
- Host molecules with inwardly directed functional groups can influence chemical reactions.
- Tertiary amines are common nucleophiles in organic synthesis.
- Supramolecular chemistry offers opportunities for reaction rate acceleration.
Purpose of the Study:
- To investigate the reaction between a host molecule possessing a methyl ester and various tertiary amines.
- To characterize the resulting host-guest complex.
- To determine the kinetic parameters and understand the mechanism of supramolecular-assisted reaction acceleration.
Main Methods:
- Synthesis and characterization of the host molecule.
- Reaction monitoring with a series of tertiary amines.
- Kinetic analysis of the reaction between the host and 2-(dimethylamino)ethanol.
- Determination of activation parameters (enthalpy and entropy).
Main Results:
- A host-guest complex formed between the host carboxylate and a guest quaternary ammonium salt.
- Reaction rates are highly dependent on the steric fit of the amine within the host cavity.
- Kinetic study yielded activation parameters: DeltaH = 25.1 ± 0.5 kcal mol⁻¹, DeltaS = 12 ± 2 cal mol⁻¹ K⁻¹.
- An estimated rate acceleration of >2 x 10⁴ fold was observed due to supramolecular effects.
Conclusions:
- The host molecule effectively binds tertiary amines, forming a complex that facilitates product formation.
- Supramolecular complexation significantly enhances reaction rates compared to uncatalyzed reactions.
- The observed rate acceleration is attributed to the preorganization of reactants in the transition state within the host cavity.
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