Chp9-6 Elimination Mechanisms in Cyclohexanes

Overview

• Focus on elimination reactions in cyclic systems, especially six‑membered rings.
• Compare E2 vs E1 in cyclohexanes and how conformation affects rate.
• Examine competition between E1 and E2 for tertiary alkyl halides.
• Integrate all four mechanisms (SN1, SN2, E1, E2) and conditions favoring each.
• Use structure of alkyl halide, base strength, and base bulkiness to predict products.

E2 Elimination in Cyclohexane Rings

• In E2 on cyclohexane, leaving group and hydrogen must be axial and anti‑periplanar.
• Axial alignment allows correct orbital overlap for anti‑elimination and double bond formation.
• Equatorial substituents are not parallel/anti; they cannot be eliminated in an E2 step.
• Therefore, only conformers with both β‑H and leaving group axial can react by E2.

Conformational Effects and Equilibrium

• Many cyclohexanes exist in equilibrium between two chair conformers.

• Often, the more stable conformer has substituents equatorial and is unreactive in E2.

• E2 occurs from the less stable conformer if that is the one with axial leaving group and β‑H.

• The reaction rate depends on:

  • How much of the reactive (axial) conformer is present at equilibrium.
  • The equilibrium constant (K_eq) for interconversion of conformers.

• Large K_eq toward reactive conformer → faster E2.

• Small K_eq toward unreactive conformer → slower E2.

Examples: Neomenthyl Chloride vs Menthyl Chloride

• Neomenthyl chloride:

  • More stable conformer places bulky methyl and isopropyl equatorial.
  • This forces chlorine axial and the relevant hydrogen axial on the opposite side.
  • This more stable conformer is also the E2‑reactive one → fast E2.

• Menthyl chloride:

  • More stable conformer places chlorine, methyl, and isopropyl all equatorial.
  • Chlorine equatorial → cannot undergo E2 in this conformer.
  • Less stable conformer has Cl, Me, and i‑Pr all axial:
    • Only this conformer can react by E2.
    • Very little of this conformer is present → slow E2.

E1 Elimination in Cyclohexane Rings

• E1 is not concerted; it proceeds via carbocation formation.
• Chlorine/leaving group position (axial vs equatorial) does not limit E1.
• Steps:
  • Leaving group departs → carbocation intermediate.
  • Base removes β‑H from any suitable adjacent carbon.
• Because no strict geometric requirement (no anti‑periplanar need), equatorial halides can still undergo E1.

Competition Between E1 and E2 in Tertiary Alkyl Halides

• Tertiary alkyl halides can undergo both E1 and E2.
• Primary and secondary alkyl halides do not form stable carbocations:
  • They undergo E2 only (no E1).

Rate Laws

• Overall elimination rate for tertiary alkyl halides:

  • Rate_total = Rate_E2 + Rate_E1.
  • Rate_E2 ∝ [alkyl halide][base] (bimolecular).
  • Rate_E1 ∝ [alkyl halide] (unimolecular; independent of base concentration/strength).

• Both E1 and E2 give the same alkene product; only mechanisms differ.

Effect of Base Strength and Concentration

• Strong base, high concentration:

  • Increases Rate_E2 (depends on [base]).
  • Favors E2 mechanism for tertiary alkyl halides.

• Weak base, low concentration:

  • E2 is slow (base is weak and dilute).
  • E1 (only dependent on [substrate]) is relatively favored.

• Summary for tertiary alkyl halides:

  • Strong base, high [base] → E2 favored.
  • Weak base, low [base] → E1 favored.

Deciding Between SN1, SN2, E1, and E2

• An alkyl halide can, in principle, undergo: SN1, SN2, E1, or E2.
• But only certain pairs compete under given conditions:
  • SN2 vs E2 under strong base (good nucleophile) conditions.
  • SN1 vs E1 under weak base (poor nucleophile) conditions.
• Combinations like SN1 with E2, or SN2 with E1, are not considered competing pairs.

Role of Alkyl Halide Structure

• Primary and secondary alkyl halides:
  • Cannot form stable carbocations.
  • Only SN2 and E2 mechanisms possible.
• Tertiary alkyl halides:
  • Too hindered for SN2.
  • Can form stable carbocations.
  • Mechanisms possible: SN1, E1, and E2.

Strong Base Conditions: SN2 vs E2

• Strong bases (e.g., hydroxide, ethoxide) are also good nucleophiles.
• Under these conditions, SN2 and E2 compete.

Reactivity Trends

• SN2:
  • Fastest: primary > secondary > tertiary (tertiary essentially does not react via SN2).
• E2:
  • Fastest: tertiary > secondary > primary.

Primary Alkyl Halides (Strong Base)

• Primary halides:
  • Best for SN2, worst for E2.
  • Under strong base/good nucleophile:
    • Primarily give substitution (SN2) products.
    • Elimination minor.

Secondary Alkyl Halides (Strong Base)

• Secondary halides are middle for both SN2 and E2.

• Both substitution and elimination occur.

• Distribution depends on:

  • Base strength.
  • Base bulkiness (steric hindrance).

• Weak base (still nucleophilic):

  • Substitution (SN2) is favored.

• Strong base:

  • Elimination (E2) increasingly favored, especially if bulky.

• Example trends:

  • Strong base like ethoxide or sec‑butoxide → mostly elimination product from secondary halide.
  • Weaker base (acetate) → mostly or entirely substitution product.

Effect of Base Bulkiness

• Bulky strong bases (e.g., tert‑butoxide):

  • Sterically hindered from backside attack for SN2.
  • Remove β‑H more easily → favor E2.

• Less bulky strong nucleophiles:

  • Can approach the carbon for backside attack → favor more SN2.

• Strategy:

  • To maximize substitution: use weaker, less bulky base/nucleophile.
  • To maximize elimination: use stronger, bulkier base.

Tertiary Alkyl Halides (Strong Base)

• Tertiary halides cannot undergo SN2 (too hindered).
• Under strong base:
  • Only E2 occurs.
  • Strong base removes β‑H while leaving group departs (concerted).

Weak Base Conditions: SN1 vs E1

• Weak bases/poor nucleophiles favor SN1/E1 mechanisms.
• Only tertiary alkyl halides can participate (need a stable carbocation).

Mechanism Overview

• First step: ionization of tertiary alkyl halide → carbocation + leaving group.
• Then two possibilities:
  • Nucleophile attacks carbocation → substitution (SN1).
  • Base removes β‑H → elimination (E1).

Product Preference under SN1/E1 Conditions

• Substitution usually dominates:

  • Forming substitution product requires only bond formation to carbocation.
  • No extra bond breaking beyond leaving group departure.
  • Energetically easier than removing a β‑H and forming a new π bond (E1).

• Elimination (E1) still occurs, but in smaller proportion.

• This is important:

  • Tertiary halides have no SN2 pathway.
  • SN1 is the main way to obtain substitution products for tertiary halides.
  • If E1 were overwhelmingly dominant, substitution would be difficult.

Choice of Conditions for Tertiary Halides

• Want substitution:
  • Use weak base/poor nucleophile → SN1/E1 conditions.
  • Substitution favored over elimination because it is easier.
• Want elimination:
  • Use strong base → E2 dominates.
  • E2 is favored with strong base (no SN2 path available for tertiary).

Summary Table of Mechanisms and Conditions

Overall Mechanism Selection

Key Decision Rules

• First, identify alkyl halide:
  • Primary or secondary → only SN2/E2.
  • Tertiary → SN1/E1 or E2 possible.
• For primary:
  • Strong base → SN2 dominates (little E2).
• For secondary:
  • Weak, small nucleophile → substitution favored.
  • Strong, bulky base → elimination favored.
• For tertiary:
  • Strong base → E2.
  • Weak base → SN1 (with some E1).

Key Terms and Concepts

• E2 elimination:
  • Bimolecular; base and substrate in rate law.
  • Concerted; requires anti‑periplanar β‑H and leaving group.
• E1 elimination:
  • Unimolecular; substrate only in rate law.
  • Stepwise via carbocation intermediate.
• SN2:
  • Bimolecular nucleophilic substitution; backside attack, inversion.
• SN1:
  • Unimolecular nucleophilic substitution; carbocation intermediate, racemization.
• Axial vs equatorial positions:
  • In cyclohexane, axial substituents are perpendicular to ring plane.
  • Equatorial substituents lie roughly in the plane; usually more stable for bulky groups.
• Base strength:
  • Strong base: high tendency to remove proton (e.g., OH⁻, RO⁻).
  • Weak base: poor proton acceptor, often weak nucleophile.
• Base bulkiness:
  • Bulky: sterically hindered (e.g., tert‑butoxide); favors E2 over SN2.
  • Small: less hindered; can favor SN2.

Next Steps / Practice

• Practice chair conformations:
  • Identify axial vs equatorial substituents.
  • Determine which conformer allows E2 (axial β‑H and leaving group).
• For given reaction conditions:
  • Classify the substrate (primary, secondary, tertiary).
  • Identify base strength and bulkiness.
  • Decide between SN2 vs E2 or SN1 vs E1.
  • Predict major products (substitution vs elimination).
• Work through worksheet problems focusing on:
  • Choosing mechanism.
  • Predicting whether substitution or elimination is favored.