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Related Concept Videos

E2 Reaction: Kinetics and Mechanism02:45

E2 Reaction: Kinetics and Mechanism

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SN2 substitutions and E2 eliminations of alkyl halides proceed via a concerted pathway. While the nucleophile attacks the alpha carbon in SN2 reactions, it functions as a strong base and abstracts a beta hydrogen in the E2 mechanism. The rate-limiting transition state in E2 elimination reactions is characterized by partially broken carbon–hydrogen and carbon–halogen bonds and a partially formed pi bond between the alpha and beta carbons. The beta hydrogen and halide are eliminated...
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E2 Reaction: Stereochemistry and Regiochemistry02:43

E2 Reaction: Stereochemistry and Regiochemistry

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Elimination reactions of alkyl halides can yield one or more alkenes depending on the specific regiochemical and stereochemical considerations. While the regiochemistry of the reaction governs the location of the double bond in the product, the stereochemical requirements often influence the geometry.
When a substrate with two different β hydrogens undergoes an E2 elimination, the presence of a strong base can yield two regioisomeric alkenes. The more-substituted alkene is the major...
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SN2 Reaction: Stereochemistry02:23

SN2 Reaction: Stereochemistry

9.7K
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not...
9.7K
Base-Catalyzed Ring-Opening of Epoxides02:26

Base-Catalyzed Ring-Opening of Epoxides

8.7K
Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile...
8.7K
SN2 Reaction: Transition State02:26

SN2 Reaction: Transition State

10.0K
An SN2 reaction of an alkyl halide is a single-step process in which bond formation between the nucleophile and the substrate and bond breaking between the substrate and the halide occurs simultaneously through a transition state without forming an intermediate.
When the nucleophile approaches the electrophilic carbon with its lone pairs, the halide acts as a leaving group and moves away with the electron-pair bonded to the carbon. Dotted partial bonds represent the bonds being formed or broken...
10.0K
Ethers to Alkyl Halides: Acidic Cleavage02:18

Ethers to Alkyl Halides: Acidic Cleavage

6.1K
Ethers are generally unreactive and unsuitable for direct nucleophilic substitution reactions since the alkoxy groups are strong bases and, therefore, poor leaving groups. However, ethers readily undergo acidic-cleavage reactions. Ethers can be converted to alkyl halides when heated with strong acids such as HBr and HI in a sequence of two substitution reactions.
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SN 2 versus E2 Competition of Cyclic Ethers.

Thomas Hansen1, Pascal Vermeeren1, Kim W J Zijderveld1

  • 1Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute of Molecular and Life Sciences (AIMMS) Vrije Universiteit, Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam (The, Netherlands.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|June 20, 2023
PubMed
Summary

Ring strain significantly impacts ether reactions. Increasing strain favors SN2 over E2 pathways, especially for strong bases, altering reaction mechanisms in cyclic ethers.

Keywords:
Lewis baseactivation strain modeldensity functional calculationsnucleophilicityprotophilicityring strain

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Area of Science:

  • Physical Chemistry
  • Organic Chemistry
  • Computational Chemistry

Background:

  • Understanding reaction mechanisms is crucial in organic chemistry.
  • The interplay between substrate structure and reaction pathways influences chemical reactivity.
  • Lewis base reactions with ethers are fundamental transformations.

Purpose of the Study:

  • To investigate the effect of ring strain on the competition between SN2 and E2 reaction pathways in ethers.
  • To elucidate how varying substrate ring size influences the preferred reaction mechanism.
  • To determine the role of Lewis base strength in dictating reaction outcomes.

Main Methods:

  • Quantum chemical calculations using relativistic density functional theory (ZORA-OLYP/QZ4P).
  • Systematic variation of ether substrate from acyclic to 3-membered rings to increase ring strain.
  • Employing a diverse set of Lewis bases (halides, hydroxides, alkoxides, thiolates).

Main Results:

  • Increasing ring strain in ethers significantly lowers the activation energy for the SN2 pathway.
  • Conversely, ring strain generally increases the activation energy for the E2 pathway.
  • A mechanistic switch from E2 to SN2 is observed for strong Lewis bases as ring size decreases.

Conclusions:

  • Ring strain is a critical factor controlling the competition between SN2 and E2 reactions in ethers.
  • Smaller cyclic ethers preferentially undergo SN2 reactions, especially with strong nucleophiles.
  • Weak Lewis bases consistently favor the SN2 pathway due to its lower intrinsic distortion energy.