CHEM230 Exam 4 Study Guide: Substitution, Elimination, Alcohols, and Ethers

Chapter 7: Chemistry of Alkyl Halides – Substitution and Elimination

SN2 Reactions

The SN2 (bimolecular nucleophilic substitution) mechanism is a fundamental reaction in organic chemistry, characterized by a single concerted step where the nucleophile attacks the substrate as the leaving group departs.

• Product Prediction: Stereochemical outcome is inversion at the reactive center (Walden inversion).

• Factors Affecting SN2: Substrate structure (methyl > primary > secondary > tertiary), strength of nucleophile, quality of leaving group, and solvent effects (polar aprotic solvents favor SN2).

• Mechanism: One-step, concerted process.

Example: Reaction of methyl bromide with hydroxide ion to yield methanol and bromide ion.

E2 Reactions

The E2 (bimolecular elimination) mechanism involves the removal of a proton and a leaving group in a single concerted step, resulting in the formation of a double bond.

• Major Concepts:

  • Regioselectivity: Zaitsev's rule (the more substituted alkene is favored unless a bulky base is used).

  • Stereoselectivity: Anti-coplanar geometry is required for optimal orbital overlap.

• Mechanism: Base abstracts a proton anti to the leaving group, forming an alkene.

Example: Dehydrohalogenation of 2-bromobutane with ethoxide to yield 2-butene.

Comparisons and Mechanistic Details

• Comparison of SN1, SN2, E1, and E2: Includes mechanism, rate law, substrate structure, nucleophile/base strength, and solvent effects.

• Unimolecular vs. Bimolecular: SN1/E1 are unimolecular (rate depends only on substrate), SN2/E2 are bimolecular (rate depends on both substrate and nucleophile/base).

• Competing Pathways: Factors that favor substitution vs. elimination (e.g., strong base favors E2, strong nucleophile favors SN2).

• Mechanism of Alkyl Halide Reactions: Predicting products and stereochemistry based on mechanism and reactants.

• Reactivity Order: Allylic and benzylic halides are more reactive due to resonance stabilization.

Table: Comparison of SN1, SN2, E1, and E2 Mechanisms

Mechanism	Rate Law	Substrate Preference	Nucleophile/Base	Solvent	Stereochemistry
SN1	Rate = k[substrate]	3° > 2°	Weak OK	Polar protic	Racemization
SN2	Rate = k[substrate][nucleophile]	Me > 1° > 2°	Strong	Polar aprotic	Inversion
E1	Rate = k[substrate]	3° > 2°	Weak OK	Polar protic	Mix (Zaitsev)
E2	Rate = k[substrate][base]	3° > 2° > 1°	Strong base	Polar aprotic	Anti-coplanar

Chapter 12: Alcohols and Phenols – Synthesis and Reactions

Preparation and Reactions of Alcohols

Alcohols are versatile organic compounds that can be synthesized and transformed through various mechanisms.

• Oxidation and Reduction: Alcohols can be oxidized to aldehydes, ketones, or carboxylic acids depending on their structure and the oxidizing agent.

• Activation for Substitution/Elimination: Alcohols can be converted to better leaving groups (e.g., tosylates) or activated with acids for substitution (SN1/SN2) or elimination (E1/E2).

• Reactions with Halogen Acids: Alcohols react with HX to form alkyl halides (SN1 or SN2 depending on substrate).

• Reactions with Lewis Acids: Alcohols can be converted to alkyl halides using reagents like SOCl2 or PBr3.

• Reduction: Carbonyl compounds can be reduced to alcohols using hydride reagents (e.g., NaBH4, LiAlH4).

Example: Oxidation of a primary alcohol to a carboxylic acid using chromic acid.

Reactions of Alcohols with Sulfonates and Ethers

• Formation of Tosylates: Alcohols react with tosyl chloride to form tosylates, which are good leaving groups for SN2 reactions.

• Williamson Ether Synthesis: Alcohols can be converted to ethers via SN2 reaction with alkyl halides.

Chapter 13: Ethers, Epoxides, and Their Sulfur Analogs

Preparation and Reactions of Ethers

Ethers are commonly synthesized via the Williamson ether synthesis and can undergo cleavage under acidic conditions.

• Williamson Ether Synthesis: SN2 reaction between an alkoxide ion and a primary alkyl halide.

• Acidic Cleavage: Ethers can be cleaved by strong acids (e.g., HI, HBr) to yield alkyl halides and alcohols.

• Epoxide Formation and Opening: Epoxides are three-membered cyclic ethers that can be opened by nucleophiles under acidic or basic conditions, often with regioselectivity.

Example: Synthesis of diethyl ether from ethanol and sodium metal, followed by reaction with ethyl bromide.

Table: Summary of Alcohol and Ether Reactions

Reaction	Reagents	Product	Mechanism
Alcohol to Alkyl Halide	HX, SOCl2, PBr3	Alkyl halide	SN1 or SN2
Alcohol to Tosylate	Tosyl chloride (TsCl)	Alkyl tosylate	SN2
Williamson Ether Synthesis	Alkoxide + Alkyl halide	Ether	SN2
Ether Cleavage	HI, HBr	Alkyl halide + Alcohol	Acidic cleavage
Epoxide Opening	Nucleophile (acidic or basic)	Alcohol	Ring opening

Possible Complete Mechanisms

• Alkyl halide (SN2, E2, SN1, E1, elimination, NaBH4 reduction)

• Alcohols (activation, oxidation, cleavage of ethers, reduction using opening)

Topics Not Covered

• Mechanisms involving PBr3, SOCl2, or certain oxidations (DMP, Swern, PCC)

• Nomenclature for Spectroscopy

Additional info: The above guide is based on a topic list for an Organic Chemistry II exam, focusing on substitution and elimination mechanisms, alcohol and ether chemistry, and related mechanistic details. The tables summarize key comparisons and reaction types for efficient exam review.