E1 & E2 Elimination Reaction Mechanisms

• Elimination reactions form π bonds by removing hydrogen and leaving groups from adjacent carbons
• They possess the same leaving groups as substitution reactions

Main Elimination Mechanisms

• E1
• E2

Learning Objectives

• Draw mechanisms for both E1 and E2 elimination reactions with alkyl halides and alcohols
• Predict major products from elimination reactions
• Regiochemistry and stereochemistry can be predicted
• Predict favourability toward E1, E2, SN1, and SN2 reactivity based on reactants and conditions
• Incorporate substitution and elimination reactions into the synthesis of small molecules and maintain control of the reaction for a single product
• Predict the products of alcohol oxidation and draw their mechanisms

E2 Elimination Reactions

• E2 stands for elimination bimolecular
• Similar to SN2 in rate determination
• Proceeds through a single-step, concerted mechanism
• Requires a strong base
• The rate depends on the concentration of the substrate and the base

Alkene Nomenclature

• Alkenes are classified based on the number of non-H groups bonded to the C=C
  • Mono
  • Di
  • Tri
  • Tetra

Alkene Stability

• More substituted alkenes are more stable than less substituted ones
• Trans-alkenes are usually more stable than cis-alkenes

Regioselectivity

• Elimination reactions favour the most stable alkene product which occurs when the product is the more substituted alkene product (i.e., more alkyl substituents on π bond)
• Substituted alkenes are stabilized by hyperconjugation with connected alkyl groups
• Alkenes can also be stabilized by delocalization

Hofmann Product

• Bulky bases (i.e., 'BuO-) alter the regioselectivity of E2 reactions because they often favour the less stable (less substituted) alkene
• The less stable product is known as the Hofmann product
• This product Forms from removal of the more accessible (i.e., less hindered) proton

Stereochemistry of E2 Reactions

• In elimination reactions, many alkenes can be formed in either the Z or E configuration
• For E2 to proceed, all four atoms must lie in an antiperiplanar conformation
• Products can be predicted by examining possible antiperiplanar conformations
• Deprotonation of particular protons leads to different stereoisomers
• Constraints of ring systems can dictate the products formed
• Anti-periplanar conformation in cyclohexanes possible only if H and LG are in 1,2-trans-diaxial

Alkene Formation by E1 Elimination Reactions

• E1 stands for elimination unimolecular
• Like SN1, it has a unimolecular rate-determining step
• A carbocation intermediate is formed
• Usually involves weaker bases
• The rate of an E1 elimination only depends on the concentration of the substrate

Substrates for E1 Eliminations

• Similar to SN1, substrates that can form stable carbocation intermediates are the ones that undergo elimination via the E1 pathway.
• Typical leaving groups include halides, water, tosylate, etc
• The beta hydrogen to the carbocation is very acidic, so only a weak base is needed in the deprotonation step,

Stereoselectivity in E1 Reactions.

• E1 eliminations follow Zaitsev's rule
• E1 is less stereoselective than E2 because there's free rotation of the C-C bond in the carbocation so anti-periplanar arrangement isn't relevant anymore

Rearrangements in E1 Reactions

• Carbocations formed in E1 may be subject to rearrangement similar to SN1

Dehydration and Dehydrohalogenation

• Elimination reactions are classified by leaving group.
• Dehydrohalogenation is a loss of a hydrogen and a halogen from an alkyl halide that produces an alkene
• This can proceed via E1 or E2
• Dehydration is the loss of water from an alcohol that produces an alkene
• Dehydration requires a strong acid, like H2SO4, to activate the hydroxyl leaving group and can proceed via E1 or E2

Acid-Catalyzed Dehydration and Hydration

• The mechanism of E1 dehydration is the reverse of the mechanism for the hydration of alkenes
• Concentrations of H2SO4 and H2O can modify which direction is favoured

Substitution vs. Elimination

• Many bases can act as nucleophiles, and most nucleophiles can act as bases
• Hence nucleophilic displacement and elimination reactions often compete, though one of the two is usually favored

Strong Nucleophiles & Strong Bases

• e.g., HO, CH3O, HCEC

Good/Strong Nucleophiles & Weak Bases

• e.g., I-, Br -, Cl-, N3, CN-, CH3CO2, HS-, H2S

Weak Nucleophiles & Strong Bases

• e.g., H-, t-BuO-

Weak Nucleophiles & Weak Bases

• e.g., H2O, CH3OH

Methyl Halides

• Elimination reactions are impossible & substitution is exclusively SN2, no matter the nucleophile identity

Primary Halides

• Substitution occurs more readily than elimination and is almost exclusively SN2, particularly when using strong unhindered nucleophiles
• Elimination proceeds by E2 with strong non-nucleophilic bases (e.g., H- or t-BuO-)
• SN1 and E1 are very unlikely due to instability of primary carbocations

Secondary Halides

• Elimination proceeds by E2 with strong, non-nucleophilic bases(H- gives Zaitsev product, t-BuO gives Hofmann product)
• Substitution proceeds by SN2 with strong nucleophiles that are poor Brønsted bases
• SN2 and E2 occur together with strong nucleophiles that are also strong Brønsted bases
• SN1 and E1 occur together with weak nucleophiles/weak bases

Tertiary Halides

• SN2 is impossible
• E2 is very likely with strong Brønsted bases
• SN1 and E1 occur together with weak nucleophiles/weak bases

Effect of Temperature

• Substitution reactions: small change in entropy
• Elimination reactions: large change in entropy
• For borderline cases, heating the reaction can lead to increased amounts of the elimination product.
• Increasing the temperature will make the TAS+ term larger and will thus decrease the overall barrier for the energy of activation for elimination

Solvent Choice

• Bimolecular reactions (S2 and E2) use polar aprotic solvent
• Unimolecular reactions (SN1 and E1) need polar protic solvents
• Solvent choice is usually not the deciding factor.
• The structure of the electrophile and the strength of the nucleophile or base are more important.

Oxidation of Alcohols: An Elimination Reaction

• Primary alcohols oxidize to aldehydes
• Secondary alcohols oxidize to ketones
• tertiary alcohol have no removable hydrogen, so no oxidation possible

Chromium Oxidants

• Strong oxidants that will oxidize: 1º alcohols to carboxylic acids and 2º alcohols to ketones
• 2 conditions to achieve this: CrO3, H2SO4, H2O (a.k.a. Jones Reagent) and Na2Cr2O7, H2SO4, H2O
• The mixture produces H2CrO4, which is the active oxidant First oxidation produces the aldehyde, but it is not possible to stop the reaction there
• Since H2O is present, the aldehyde hydrate is formed, and undergoes a second oxidation to the carboxylic acid
• Mechanisms for two oxidation steps is the same as shown on the previous slide

Pyridinium Chlorochromate (PCC)

• Pyridinium chlorochromate (PCC) is a milder oxidant that can be used to selectively oxidize 1º alcohol to aldehyde
• Anhydrous conditions prevent over-oxidation of 1º alcohols
• PCC can also be used to oxidize 2º alcohols to ketones
• No water is present, therefor the aldehyde cannot form a hydrate, so no further oxidation is possible.