11.8 The E2 Reaction and the Deuterium Isotope Effect
3 min read•may 7, 2024
E2 reactions are a key type of in organic chemistry. They involve a base removing a proton while a departs, all in one step. This creates a new carbon-carbon double bond.
Understanding E2 reactions is crucial for predicting organic reaction outcomes. The stereochemistry, substrate structure, and reaction conditions all play important roles in determining the products formed during these eliminations.
The E2 Reaction Mechanism
E2 reaction mechanism fundamentals
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Top images from around the web for E2 reaction mechanism fundamentals
Organic chemistry 13: Bimolecular beta elimination (E2) - regioselectivity and stereoselectivity View original
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- reaction occurs in a single concerted step
- Simultaneous removal of a proton and departure of a from a substrate molecule
- Base abstracts a proton from the -carbon while the leaving group departs from the -carbon
- Rate depends on the concentrations of both the substrate and the base
- Rate law: Rate = [substrate][base]
- Second-order overall, first-order in substrate and first-order in base
- involves partial bonding between the base and the -hydrogen, and partial breaking of the C-H and C-LG bonds
- Planar geometry with the -hydrogen, -carbon, and leaving group all in the same plane
- Factors affecting the rate include:
- Strength of the base: Stronger bases increase the reaction rate ()
- Stability of the alkene product: More stable form faster ()
- Steric hindrance: Bulky substituents near the reaction site slow down the reaction ()
Key components of the E2 reaction
- Elimination reaction: The is a type of elimination reaction where two molecules are involved in the rate-determining step
- Leaving group: The group that departs from the α-carbon during the reaction, typically a halide or tosylate
- : The hydrogen atom on the carbon adjacent to the carbon bearing the leaving group, which is removed by the base
- Concerted mechanism: The occurs in a single step, with simultaneous breaking and forming of bonds
Evidence for the E2 Mechanism
Deuterium isotope effect evidence
- Investigates the rate-determining step of the E2 reaction
- (D) is an isotope of hydrogen with one proton and one neutron in its nucleus
- is stronger than the due to the higher mass of deuterium
- Substrate containing a -deuterium undergoes an E2 reaction slower compared to the same substrate with a -hydrogen
- Breaking the C-D bond requires more energy than breaking the C-H bond
- Observed rate difference is called the (KIE)
- Significant KIE suggests cleavage of the C-H/C-D bond is involved in the rate-determining step
- Supports the concerted, one-step mechanism of the E2 reaction where the base abstracts the -hydrogen in the same step as the leaving group departs
- Magnitude of the KIE for the E2 reaction is typically between 2 and 7
- Larger KIE indicates a greater involvement of the C-H/C-D bond breaking in the rate-determining step
Stereochemistry of E2 Eliminations
Stereochemistry of E2 eliminations
- Determined by the geometry of the
- Periplanar geometry requires the -hydrogen, -carbon, and leaving group to lie in the same plane
- Arrangement allows for optimal orbital overlap and minimizes the energy of the transition state
- Periplanar requirement leads to
- -hydrogen and leaving group must be (on opposite sides) relative to the C-C bond
- Elimination occurs more readily when the leaving group is anti to the -hydrogen
- In cyclic systems, the leaving group must be axial for the E2 reaction to occur
- Axial leaving group allows for the necessary anti-periplanar arrangement with the -hydrogen
- Equatorial leaving groups cannot achieve the required periplanar geometry, making elimination difficult ()
- Stereochemistry of the resulting alkene depends on the stereochemistry of the substrate
- Anti-elimination of a syn-disubstituted substrate leads to the ()
- Anti-elimination of an anti-disubstituted substrate leads to the ()
- In cases where multiple -hydrogens are present, the more substituted or more stable alkene will be formed preferentially ()
- Due to the greater stability of the more substituted alkene and the lower energy of its transition state ( vs )
Key Terms to Review (37)
(E)-Alkene: (E)-alkenes, also known as trans-alkenes, are a type of alkene isomer where the two largest substituents are on opposite sides of the carbon-carbon double bond. This structural arrangement has important implications in the context of the E2 reaction and the deuterium isotope effect.
(Z)-alkene: (Z)-alkenes, also known as cis-alkenes, are a type of alkene where the two largest substituents are on the same side of the carbon-carbon double bond. This geometric isomerism has important implications for the reactivity and stability of these compounds, particularly in the context of the E2 reaction and the deuterium isotope effect.
1-Pentene: 1-Pentene is a linear alkene with the molecular formula C₅H₁₀. It is a colorless, volatile organic compound that is widely used in the chemical industry, particularly in the production of polymers and as a fuel additive.
2-butene: 2-butene is an unsaturated hydrocarbon with the molecular formula C4H8. It is an alkene with a carbon-carbon double bond located at the second carbon position of the four-carbon chain. This structural feature of 2-butene is central to understanding its behavior and properties in the context of various organic chemistry topics.
2-pentene: 2-pentene is a simple alkene with the molecular formula C$_{5}$H$_{10}$. It is an unsaturated hydrocarbon that contains a carbon-carbon double bond, and it is an important intermediate in organic chemistry reactions, particularly in the context of the E2 reaction and the deuterium isotope effect.
Alkenes: Alkenes are a class of unsaturated organic compounds characterized by the presence of a carbon-carbon double bond. They are an important functional group in organic chemistry, with a wide range of applications and reactivity. Alkenes are closely related to the topics of chirality, isomerism, electrophilic addition reactions, halogenation, hydration, the E2 reaction, infrared spectroscopy, 13C NMR spectroscopy, alcohol preparation, and the Wittig reaction.
Alkyl Halides: Alkyl halides are organic compounds that consist of an alkyl group (a hydrocarbon chain) bonded to a halogen atom (fluorine, chlorine, bromine, or iodine). They are widely used in organic synthesis and have various applications in chemistry and biology.
Anti periplanar: Anti periplanar configuration describes the spatial arrangement in a molecule where two substituents are positioned opposite to each other across a single bond, typically in a linear fashion. This configuration is particularly crucial for the E2 elimination reaction mechanism in organic chemistry, enabling the efficient removal of a hydrogen and a leaving group to form a double bond.
Anti-elimination: Anti-elimination is a type of elimination reaction in organic chemistry where the leaving group departs in the opposite direction from the hydrogen being removed, resulting in the formation of a new alkene product. This term is particularly relevant in the context of the E2 reaction and the deuterium isotope effect.
Anti-periplanar: The anti-periplanar arrangement refers to the spatial orientation of atoms or groups in an organic molecule where they are positioned on opposite sides of a planar carbon-carbon double bond or a carbon-carbon single bond. This specific arrangement is crucial in understanding certain types of organic reactions, particularly elimination reactions.
Beta Hydrogen: Beta hydrogen refers to the hydrogen atom that is located on the carbon atom that is two positions away from the reactive site in an elimination reaction. This beta hydrogen plays a crucial role in the mechanism and stereochemistry of elimination reactions, such as the E2 reaction and Zaitsev's rule.
Bimolecular Elimination: Bimolecular elimination, also known as the E2 reaction, is a type of elimination reaction in organic chemistry where two molecules (the substrate and a base) participate simultaneously in the rate-determining step to remove a leaving group and a hydrogen atom, resulting in the formation of an alkene product.
C-D Bond: The carbon-deuterium (C-D) bond is a type of covalent bond formed between a carbon atom and a deuterium atom. Deuterium is a stable isotope of hydrogen, with one proton and one neutron in the nucleus, compared to the more common hydrogen isotope with just one proton. The presence of the extra neutron in deuterium results in subtle differences in the physical and chemical properties of the C-D bond compared to the more familiar C-H bond.
C-H Bond: The C-H bond is a covalent bond formed between a carbon atom and a hydrogen atom. This bond is fundamental to organic chemistry and is present in a wide range of organic compounds, from simple alkanes to complex biomolecules. The C-H bond is crucial in understanding the structure, reactivity, and stability of organic molecules.
Cis-2-butene: cis-2-butene is a geometric isomer of the alkene 2-butene, where the two largest substituents (in this case, methyl groups) are positioned on the same side of the carbon-carbon double bond. This structural arrangement contrasts with the trans isomer, where the largest substituents are on opposite sides of the double bond.
Concerted Mechanism: A concerted mechanism refers to a reaction that occurs in a single, continuous step without the formation of any discrete intermediates. In a concerted mechanism, the bonds that are being formed and broken happen simultaneously, leading to the product in a single, coordinated process.
Cyclohexyl Bromide: Cyclohexyl bromide is an organic compound consisting of a cyclohexane ring with a bromine atom attached. It is an important intermediate in organic synthesis and is relevant in the context of the E2 reaction and the deuterium isotope effect.
Deuterium: Deuterium, also known as heavy hydrogen, is a stable isotope of hydrogen with a nucleus containing one proton and one neutron, compared to the more common hydrogen isotope which has only a single proton in its nucleus. The presence of the extra neutron in deuterium results in distinct physical and chemical properties that are highly relevant in the context of the E2 reaction and the deuterium isotope effect.
Deuterium isotope effect: The deuterium isotope effect in the context of organic chemistry, particularly during E2 reactions, is the observation that a reaction rate is altered when hydrogen (H) is replaced by its heavier isotope, deuterium (D). This effect can be utilized to explore reaction mechanisms, especially to distinguish between different types of nucleophilic substitution and elimination processes.
Deuterium Isotope Effect: The deuterium isotope effect refers to the kinetic and thermodynamic differences observed when a hydrogen atom in a chemical reaction is replaced with its heavier isotope, deuterium. This effect arises due to the differences in the physical and chemical properties between hydrogen and deuterium, which can influence the rate and equilibrium of chemical reactions.
E2 reaction: An E2 reaction is a bimolecular elimination reaction where a hydrogen atom is removed from a carbon adjacent to the one bonded to the leaving group, resulting in the formation of an alkene. This process involves a single concerted step, where both the base removing the hydrogen and the leaving group departure occur simultaneously.
E2 Reaction: The E2 reaction is an elimination reaction in organic chemistry where a base removes a hydrogen atom and a leaving group from adjacent carbon atoms, resulting in the formation of an alkene. This reaction is characterized by the simultaneous removal of the hydrogen and the leaving group, proceeding through a concerted mechanism.
Elimination Reaction: An elimination reaction is a type of organic reaction in which two atoms or groups are removed from a molecule, typically resulting in the formation of a carbon-carbon double bond or a carbon-carbon triple bond. This process is an important step in the synthesis of alkenes and alkynes, as well as in various other organic transformations.
Ethoxide: Ethoxide is a functional group consisting of an ethyl group (CH3CH2-) bonded to an oxygen atom. It is an important intermediate in various organic reactions, particularly in the context of E2 reactions, ester chemistry, and Claisen condensations.
Kinetic Isotope Effect: The kinetic isotope effect refers to the difference in the rate of a chemical reaction when a light isotope of an element is replaced by a heavier isotope of the same element. This effect arises from the differences in the zero-point energies and vibrational frequencies of the reactants, which can influence the activation energy and the rate of the reaction.
Leaving group: A leaving group in organic chemistry is an atom or group that detaches from the parent molecule during a nucleophilic substitution (SN2) reaction, forming a lone pair or negative ion. The ease with which a leaving group departs affects the rate and success of the reaction.
Leaving Group: A leaving group is a functional group or atom that is displaced or removed from a molecule during a chemical reaction. It is a key component in many organic reactions, particularly substitution and elimination reactions, as it facilitates the formation of a new bond or the creation of a new product.
NaOH: NaOH, or sodium hydroxide, is a highly alkaline chemical compound that plays a crucial role in various organic chemistry reactions and processes. It is a strong base that is widely used in a variety of applications, including the discovery of nucleophilic substitution reactions, the SN2 reaction, the E2 reaction, carbonyl condensations, and peptide sequencing through the Edman degradation.
Periplanar: Periplanar refers to the geometric arrangement of atoms or groups in a molecule where they are positioned in a plane that is perpendicular to the plane of the leaving group. This term is particularly relevant in the context of the E2 reaction and the deuterium isotope effect, as it describes the specific orientation required for an efficient elimination to occur.
Syn periplanar: Syn periplanar refers to the spatial arrangement in which atoms or groups involved in a chemical reaction, specifically in an E2 elimination reaction, are on the same side and in the same plane. This arrangement is crucial for the reaction to proceed efficiently as it allows for the optimal overlap of orbitals required for the formation and breaking of bonds.
Tert-Butoxide: tert-Butoxide is a powerful nucleophilic alkoxide ion that is commonly used as a base in organic chemistry reactions. It is derived from the tert-butyl alcohol and is a key player in the E2 elimination reaction and in understanding the deuterium isotope effect.
Tert-Butyl Group: The tert-butyl group is a bulky, three-dimensional substituent composed of three methyl groups attached to a central carbon atom. It is a common functional group in organic chemistry and has a significant impact on the conformations and reactivity of molecules.
Trans-2-butene: trans-2-butene is a geometric isomer of the alkene 2-butene, where the two largest substituents (in this case, methyl groups) are positioned on opposite sides of the carbon-carbon double bond. This structural arrangement has important implications for the stability and reactivity of the molecule.
Transition state: In organic chemistry, the transition state is a high-energy, temporary condition where reactants are transformed into products during a chemical reaction. It represents the point of maximum energy on the energy diagram before the formation of products.
Transition State: The transition state is a key concept in organic chemistry that describes the highest-energy intermediate along the reaction pathway. It represents the point where the reactants are being converted into products, with the system at its most unstable and energetically unfavorable configuration.
Zaitsev's Rule: Zaitsev's rule is a principle in organic chemistry that predicts the major product of an elimination reaction. It states that the major alkene product will be the one with the most substituted (most stable) double bond.
Zero-Point Energy: Zero-point energy is the lowest possible energy that a quantum mechanical system may have, corresponding to the ground state of the system. It is the energy that a system possesses even when all classical forces are removed. This concept is particularly relevant in the context of the E2 reaction and the deuterium isotope effect.