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Organic Chemistry
Table of Contents
Unit 11 Overview: Alkyl Halide Reactions: Substitutions & Eliminations
11.1 The Discovery of Nucleophilic Substitution Reactions
11.2 The SN2 Reaction
11.3 Characteristics of the SN2 Reaction
11.4 The SN1 Reaction
11.5 Characteristics of the SN1 Reaction
11.6 Biological Substitution Reactions
11.7 Elimination Reactions: Zaitsev’s Rule
11.8 The E2 Reaction and the Deuterium Isotope Effect
11.9 The E2 Reaction and Cyclohexane Conformation
11.10 The E1 and E1cB Reactions
11.11 Biological Elimination Reactions
11.12 A Summary of Reactivity: SN1, SN2, E1, E1cB, and E2

Nucleophilic substitution reactions are key in organic chemistry. The SN2 mechanism involves a backside attack by a nucleophile, causing inversion of configuration at the electrophilic carbon. This process is crucial for understanding how molecules transform.

SN2 reactions follow second-order kinetics, depending on both nucleophile and substrate concentrations. Factors like nucleophilicity, steric hindrance, and solvent choice affect reaction rates. Knowing these details helps predict and control organic transformations in various applications.

The SN2 Reaction Mechanism and Kinetics

Mechanism of SN2 reactions

  • SN2 bimolecular nucleophilic substitution reaction involves a nucleophile and an electrophilic substrate (alkyl halide or tosylate)
  • Nucleophile attacks the electrophilic carbon from the backside, opposite to the leaving group
  • As the nucleophile approaches, the carbon-leaving group bond begins to break
  • Transition state has the nucleophile, central carbon, and leaving group aligned in a linear configuration
    • Central carbon partially bonded to both the nucleophile and the leaving group
    • Transition state has a pentacoordinate carbon with a trigonal bipyramidal geometry
  • Reaction proceeds to completion with the formation of a new nucleophile-carbon bond and the departure of the leaving group
  • Inversion of configuration occurs at the electrophilic carbon due to the backside attack by the nucleophile
  • If the substrate is chiral, the product will have the opposite stereochemistry (R to S, or S to R)
    • This results in the formation of stereoisomers

Kinetics of SN2 reactions

  • Rate equation for an SN2 reaction: $Rate = k[Nu][RX]$
    • $k$ rate constant
    • $[Nu]$ concentration of the nucleophile
    • $[RX]$ concentration of the alkyl halide substrate
  • Rate depends on the concentrations of both the nucleophile and the substrate
    • Doubling either concentration will double the reaction rate
    • Doubling both concentrations will quadruple the reaction rate
  • Reaction is first-order with respect to the nucleophile and first-order with respect to the substrate
    • Overall reaction order is second-order (1 + 1 = 2)
  • Second-order kinetics consistent with the bimolecular nature of the SN2 mechanism
    • Rate-determining step involves both the nucleophile and the substrate in a single step

Stereochemistry in SN2 products

  • SN2 reactions proceed with inversion of configuration at the electrophilic carbon
  • When the substrate is a chiral alkyl halide, the stereochemistry of the product can be predicted
    1. Determine the absolute configuration of the starting alkyl halide (R or S)
    2. The product will have the opposite configuration due to inversion
      • R substrate will yield an S product
      • S substrate will yield an R product
  • Example: (R)-2-bromobutane undergoing an SN2 reaction with NaOH
    • (R)-2-bromobutane substrate, OH- nucleophile
    • Product will be (S)-butan-2-ol, as the reaction inverts the configuration at the chiral carbon

Factors Affecting SN2 Reactions

  • Nucleophilicity: The strength of the nucleophile affects the rate of the SN2 reaction
  • Steric hindrance: Bulky substituents on the electrophilic carbon can slow down or prevent SN2 reactions
  • Solvent effects: The choice of solvent can influence the rate and outcome of SN2 reactions

Key Terms to Review (36)

First-order reaction: A first-order reaction in organic chemistry, specifically within the context of reactions of alkyl halides and nucleophilic substitutions and eliminations, is a chemical reaction whose rate depends on the concentration of only one reactant. These reactions have a rate constant that directly correlates with the lifespan of the reactive species involved, making their kinetics simple to analyze.
Alkyl halide: An alkyl halide is an organic compound in which one or more hydrogen atoms in an alkane (saturated hydrocarbon) have been replaced by a halogen atom (fluorine, chlorine, bromine, or iodine). This substitution results in a molecule with distinct chemical and physical properties compared to its alkane precursor.
Second-order reaction: A second-order reaction is one in which the rate of reaction depends on the concentration of two reactants or on the square of the concentration of a single reactant. In the context of SN2 reactions, this means that both the nucleophile and substrate concentrations affect the reaction rate.
SN2 reaction: In organic chemistry, an SN2 reaction is a type of nucleophilic substitution where a nucleophile strongly attacks an electrophilic center in one step, leading to the simultaneous displacement of a leaving group. This reaction mechanism is characterized by its bimolecular nature, involving two reacting species in the rate-determining step.
Rate equation: In the context of organic chemistry and specifically within the topic of SN2 reactions, a rate equation expresses the relationship between the rate of the chemical reaction and the concentration of the reactants. It quantitatively describes how reaction speed increases or decreases with changes in reactant concentrations.
Chiral environment: A chiral environment is a spatial arrangement in which the distribution of parts lacks an internal plane of symmetry, often leading to different interactions with other chiral molecules. This concept is crucial in organic chemistry, especially when considering how molecules recognize and react with each other based on their three-dimensional shape.
Anti stereochemistry: Anti stereochemistry describes the spatial arrangement in a chemical reaction where two substituents are positioned on opposite sides of a double bond or ring structure after the reaction. It is particularly relevant in the halogenation of alkenes, resulting in products where the added atoms are located across from each other.
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.
Bimolecular reaction: A bimolecular reaction in organic chemistry involves two reactant molecules coming together to undergo a chemical change. It is characterized by a second-order reaction rate, meaning the rate depends on the concentration of both reactants.
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.
Rate constant: The rate constant is a numerical value that represents the speed of a chemical reaction, specifically how quickly reactants are converted to products in a given reaction. In the context of SN2 reactions in organic chemistry, it helps determine the rate at which an alkyl halide undergoes nucleophilic substitution.
Stereochemistry: Stereochemistry is the study of the three-dimensional arrangement of atoms in molecules and how this arrangement affects the chemical and physical properties of the substance. It examines the spatial orientation of atoms and their relationship to one another, which is crucial in understanding many organic chemistry concepts.
Steric Hindrance: Steric hindrance, also known as steric strain or steric effect, refers to the repulsive forces that arise between atoms or groups of atoms in a molecule due to their physical size and spatial arrangement. This phenomenon can significantly impact the stability, reactivity, and conformations of organic compounds.
Stereoisomers: Stereoisomers are molecules that have the same molecular formula and connectivity, but differ in the three-dimensional arrangement of their atoms in space. This spatial arrangement of atoms leads to different physical and chemical properties, even though the atoms are connected in the same way.
Chiral: Chirality refers to the geometric property of a molecule or object that makes it non-superimposable on its mirror image. Chiral molecules are an important concept in organic chemistry, as they are central to understanding topics such as racemic mixtures, reaction stereochemistry, and the SN2 reaction.
Nucleophile: A nucleophile is a species that donates a pair of electrons to form a covalent bond with another atom or molecule. Nucleophiles are central to understanding many organic reactions, including polar reactions, electrophilic addition reactions, and nucleophilic substitution reactions.
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.
Solvent Effects: Solvent effects refer to the influence that the surrounding solvent environment can have on the behavior and properties of chemical reactions, molecules, and spectroscopic measurements. The nature and polarity of the solvent can significantly impact the energetics, kinetics, and outcomes of various organic chemistry processes.
Backside Attack: A backside attack is a type of nucleophilic substitution reaction where the attacking nucleophile approaches the carbon atom from the opposite side of the leaving group. This orientation of the attack is a key characteristic that distinguishes the SN2 reaction mechanism from the SN1 reaction mechanism.
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.
Alkyl Halide: An alkyl halide is a type of organic compound that consists of an alkyl group (a hydrocarbon chain) bonded to a halogen atom (fluorine, chlorine, bromine, or iodine). These compounds are important intermediates in many organic reactions, including polar reactions, elimination reactions, and substitution reactions.
Rate Constant: The rate constant is a measure of the reactivity of a chemical reaction, representing the speed at which the reaction occurs. It is a fundamental parameter in the study of chemical kinetics and is crucial for understanding the dynamics of chemical processes.
Nucleophilicity: Nucleophilicity refers to the ability of a species to donate electrons and form a covalent bond with an electrophilic center. It is a key concept in organic chemistry that governs the reactivity and selectivity of many important reactions, including substitution, addition, and elimination reactions.
SN2 Reaction: The SN2 reaction, or bimolecular nucleophilic substitution, is a type of organic reaction where a nucleophile attacks the backside of a carbon atom bearing a leaving group, resulting in the displacement of the leaving group and the inversion of stereochemistry at the carbon center.
(S)-butan-2-ol: (S)-butan-2-ol is the stereoisomer of butan-2-ol in which the hydroxyl group is in the S configuration. It is a secondary alcohol with four carbon atoms and is an important compound in the context of the SN2 reaction, a type of nucleophilic substitution reaction.
Electrophilic Substrate: An electrophilic substrate is a molecule or atom that is attracted to and reacts with electron-rich species, such as nucleophiles, in chemical reactions. It is a key concept in understanding the SN2 reaction mechanism.
(R)-2-bromobutane: (R)-2-bromobutane is an organic compound with the chemical formula CH3CH(Br)CH2CH3. It is an enantiomer of 2-bromobutane, with the bromine atom in the R configuration. This compound is particularly relevant in the context of the SN2 reaction, a type of nucleophilic substitution reaction.
Inversion of Configuration: Inversion of configuration refers to the stereochemical change that occurs when a carbon atom bearing four different substituents undergoes a nucleophilic substitution reaction, resulting in the reversal of the spatial arrangement of the substituents around that carbon.
Tosylate: A tosylate is a functional group or a salt derived from tosylic acid, which is a sulfonic acid. Tosylates are commonly used as leaving groups in $\text{S}_\text{N}2$ reactions, a key topic in organic chemistry.
Rate Equation: The rate equation, also known as the rate law, is a mathematical expression that describes the relationship between the rate of a chemical reaction and the concentrations of the reactants. It is a fundamental concept in the field of chemical kinetics, which focuses on the study of reaction rates and the factors that influence them.
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.
Second-Order: Second-order refers to the kinetic order of a chemical reaction, specifically the rate at which the concentration of reactants changes over time. In a second-order reaction, the rate of the reaction depends on the concentration of two reactants, with the overall reaction order being the sum of the individual orders for each reactant.
Pentacoordinate Carbon: A pentacoordinate carbon is a central carbon atom that is covalently bonded to five other atoms, resulting in a trigonal bipyramidal molecular geometry. This unique arrangement is an important consideration in the context of the SN2 reaction mechanism.
Trigonal Bipyramidal Geometry: Trigonal bipyramidal geometry is a molecular shape that occurs when a central atom is bonded to five other atoms, with three atoms forming a trigonal planar base and two atoms forming the apices of the pyramid. This arrangement results in a three-dimensional structure with a characteristic shape.
Bimolecular: Bimolecular refers to a reaction that involves the collision and interaction of two reactant molecules to form the products. This term is particularly relevant in the context of the SN2 reaction, which is a type of nucleophilic substitution reaction.
First-Order: First-order is a kinetic term that describes a reaction where the rate of the reaction is directly proportional to the concentration of a single reactant. In other words, the rate of the reaction only depends on the concentration of one of the reactants.