Detailed Study Notes on Multistep Mechanisms: SN1, E1, SN2, E2, and Radical Reactions
CHAPTER 8: An Introduction to Multistep Mechanisms: SN1 and E1 Reactions and Their Comparisons to SN2 and E2 Reactions
8.1 THE UNIMOLECULAR NUCLEOPHILIC SUBSTITUTION (SN1) REACTION: INTERMEDIATES, OVERALL REACTANTS, AND OVERALL PRODUCTS
Mechanism for the general SN1 reaction
Step 1: The leaving group departs from the substrate, creating a carbocation intermediate.
Step 2: Nucleophile attacks the carbocation, forming the final product.
Overall Reactants, Overall Products, and Intermediates
Step 1:
Reactants are the nucleophile (Nu) and the substrate (C-L).
Intermediate: Carbocation (C⁺) formed after leaving group departure.
Step 2:
Overall reaction leads to the nucleophilic substitution product (Nu-C⁻) and the leaving group (L).
8.2 Free Energy Diagram of an SN1 Reaction
The free energy diagram has two humps connecting the reactants to the products, indicating two separate elementary steps inherent to the SN1 mechanism.
8.3 THE KINETICS OF SN2, SN1, E2, AND E1 REACTIONS: EVIDENCE FOR REACTION MECHANISMS
Evidence for the different mechanisms of SN1, SN2, E1, and E2 comes from their respective reaction kinetics.
Rate Laws:
SN2: Rate =
SN1: Rate =
E2: Rate =
E1: Rate =
Rate Laws for SN2 and SN1
The rates of SN1 and SN2 reactions differ in dependence on reactant concentrations:
SN2:
SN1:
Rate-Determining Steps
The rate-determining step (slow step) dictates the overall reaction rate.
Species appearing as reactants in the rate-determining step will affect overall reaction rate.
Rate-Determining Step of an SN1 Reaction
The first step (formation of a carbocation from the substrate) is the rate-determining step in an SN1 reaction.
Free-Energy Diagram of an SN1 Reaction
The energy barrier for Step 1 is the effective energy barrier for the overall reaction.
The free energy is plotted against the reaction coordinate.
Carbocation Stability
Carbocations classified by degree of alkyl substitution:
Stability sequence: Methyl < 1° < 2° < 3°
Carbocations can undergo stabilization via resonance when charge can be delocalized.
7.9 CARBOCATIONS AND CHARGE STABILITY
Carbocations, such as allyl cations, exhibit stabilization through resonance structures (e.g., benzyl cations).
Relative Stabilities of Carbocations
Stability of carbocations goes as follows:
Methyl < 1° < 2° < 3° < Allyl < Benzyl
7.7 CARBOCATION REARRANGEMENTS
1,2-Hydride Shifts: A hydrogen atom and its electrons migrate to adjacent carbon.
1,2-Alkyl Shifts: An alkyl group migrates to the adjacent carbon instead of a hydride.
1,2-Alkyl Shift
Specific case of 1,2-alkyl shift is a 1,2-methyl shift where a methyl group migrates.
Rule 4: Favorable 1,2-Hydride and 1,2-Methyl Shifts
Energetically favorable shifts usually occur faster than other steps in the mechanism.
Evaluating Different Possible Rearrangements
Rearrangement only occurs with increasing stability; if no stability gain occurs, rearrangement does not take place.
7.8 THE DRIVING FORCE FOR CHEMICAL REACTIONS
Driving force reflects how much a reaction favors products over reactants.
It increases with:
Greater charge stabilization in products
Greater total bond energy in products
Charge Stability Favored over Bond Energy
Charge stability generally favors products, but bond energy preferences can influence reactions.
Hyperconjugation
Stability of carbocations increases due to a phenomenon called hyperconjugation, where hydrogen atoms assist in stabilizing the positive charge through overlap of C-H bonds with empty p orbitals of adjacent carbons.
8.5 STEREOCHEMISTRY OF NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS
Differences in stereochemistry may arise from SN1/SN2 and E2/E1 reactions despite producing similar products.
Stereochemistry of an SN1 Reaction
When an SN1 reaction occurs on a stereochemically pure substrate, both the R and S enantiomers are produced.
Loss of the Stereocenter
The mechanism results in potential stereochemical changes leading to both enantiomers due to carbocation intermediate being planar, allowing for attack from both sides.
Ion Pair in an SN1 Reaction
Formation of an ion pair with carbocation and leaving group, with a preference for backside attack by the nucleophile.
Production of Diastereomers in an SN1 Reaction
Reactant can yield both diastereomers when it has multiple chiral centers, depending on approach.
Rule 1: Avoid the Appearance of Incompatible Acids & Bases
Strong acids should not appear under basic conditions; similarly, strong bases should not appear under acidic conditions.
Proton transfer steps are typically fast and should be placed strategically within mechanisms to avoid incompatibility.
Strong and Weak Acids and Bases
Definitions based on their comparison to H₃O⁺ for acids and HO⁻ for bases:
Strong acids: pK₁ < 0
Strong bases: pK₂ > 14
Examples include:
Strong acids: H₃O⁺, HCl
Weak acids: NH₃, H₂O
Strong bases: HO⁻, H₂N⁻
Weak bases: Cl⁻, Br⁻
Proposed Mechanisms and Resulting Products
Mechanism under acidic conditions may involve unreasonable steps or contradict established acid-base compatibilities.
Radical Mechanisms & Free Radicals
Free radicals are species with unpaired electrons, highly reactive, and generated via processes like homolysis.
Application in radical halogenation processes, producing alkyl halides through stepwise mechanisms.
Termination Steps
In radical processes, termination occurs when radicals couple to form stable species, effectively ending the reaction cycle.
Kinetics of Radical Halogenation show relative reactivities, with F₂ > Cl₂ > Br₂ > I₂, indicating practical applications in selectivity across alkyl substrates.
Quantifying Selectivity of Chlorination and Bromination
Chlorination yields a flatted ratio, favoring 2° over 1°; bromination demonstrates higher selectivity toward stable radical formations.
Conclusions
The relative stability of carbocations and radicals heavily influences the reaction pathways and products, crucial knowledge for mastering organic reaction mechanisms and behaviors.