bruice-oc9-lecture-powerpoint-ch09.pptx

Chapter 9: Substitution and Elimination Reactions of Alkyl Halides

Overview of Reactions

• Substitution Reactions: Electronegativity group is replaced by another group.

• Elimination Reactions: Electronegativity group is eliminated along with a hydrogen.

Electrophiles and Nucleophiles

• Electrophiles: Compounds in Group II that have an electron-withdrawing group attached to an sp3 carbon.

• Nucleophiles: Reactants that donate an electron pair in nucleophilic substitution reactions.

Families of Group II

• Group II includes: X = F, Cl, Br, I; R-X, R-OH, R-OR, etc.

• Alkyl halides (first family of Group II) have good leaving groups.

Substitution Mechanisms

• Nucleophilic Substitution (SN1 and SN2): SN1 involves a unimolecular rate-determining step; SN2 involves a bimolecular rate-determining step and back-side attack.

• Kinetics and Rate Law: Determining factors affecting reaction rate include reactant concentration.

  • For SN2, doubling the concentration doubles the rate.

Relative Reactivity in SN2 Reactions

• Reactivity Order: Methyl halide > 1° alkyl halide > 2° alkyl halide > 3° alkyl halide.

• Inverted configuration when halogen is bonded to a chiral center, leading to inverted product configuration in SN2.

Experimental Evidence for SN2

• Both alkyl halide and nucleophile in transition state of the rate-limiting step.

• Relative rate favors primary > secondary > tertiary alkyl halides.

Steric Hindrance in Reactions

• Steric Hindrance: Affects reactivity; more crowded transition states are higher in energy.

• Methyl halides react fastest due to lower steric hindrance; tertiary halides react slowest.

Mechanisms Summary of SN1 and SN2

• SN1: Two-step mechanism with carbocation intermediate; rate depends on stability of carbocation.

• SN2: One-step mechanism with a bimolecular transition state; product has an inverted configuration compared to reactant.

Nucleophile and Base Strength

• A negatively charged species is a stronger base and better nucleophile than its neutral counterpart.

Solvents and Effect on Reactions

• Protic vs. Aprotic Polar Solvents: Protic solvents stabilize nucleophiles more than aprotic solvents.

• In protic solvents, nucleophility decreases while in aprotic solvents, it remains stronger.

Base Influence on Elimination Reactions

• Strong bases favor E2 reactions; weak bases favor E1 reactions.

• Major products depend on structure and substitution of alkyl halide.

Stereochemistry in Elimination Reactions

• E2 Reactions: Lead to major alkene product with bulky groups on opposite sides due to anti elimination.

• Zaitsev’s Rule: More substituted alkene is generally favored, with exceptions under specific conditions.

Summary of Products from Substitution and Elimination

• Primary Alkyl Halides: Only undergo SN2 reactions.

• Secondary Alkyl Halides: Can undergo both SN2 and E2, depending on the base.

• Tertiary Alkyl Halides: Favor SN1 and E1 reactions with elimination favored under certain conditions.

Special Cases

• Benzylic and Allylic Halides: Undergo both SN2 and E1 due to stable carbocations.

• Vinylic and Aryl Halides: Cannot undergo SN2 or SN1 reactions due to instability of carbocations.

Designing a Synthesis and Learning Objectives

• Ability to predict products of substitution and elimination reactions based on substituent groups, stereochemistry, and reaction conditions.