Lecture Notes on SN1, SN2, E1, and E2 Reactions

Overview

• Methyl Substrate: Proceeds using SN2 mechanism regardless of solvent or base.
• Primary Substrate:
  • SN2 unless bulky base is used, which leads to E2.
  • Strong, unhindered base (e.g., hydroxide) favors SN2, but E2 can occur if the substrate is sterically hindered.
• Bulky Bases: Favor E2 reactions; example: tert-butoxide.

Reaction Mechanisms

SN2 Reactions

• Works with non-hindered substrates.
• Requires a good nucleophile and an aprotic solvent.
• Backside attack leads to inversion of configuration.
• Example: Reaction with sodium cyanide and acetone results in SN2 with inversion.

E2 Reactions

• Major mechanism with secondary alkyl halides using strong bases.
• No rearrangements; leads to more stable alkenes (Zaitsev's rule).
• Bulky bases favor less substituted alkenes (Hofmann product).

SN1 and E1 Reactions

• Tertiary Substrate: SN1 and E1, independent of solvent; protic favors SN1, heat favors E1.
• Involves carbocation intermediate and potential for rearrangement.
• Example: tert-butyl chloride with water proceeds via SN1/E1.

Factors Influencing Mechanisms

• Secondary Alkyl Halides: Can vary between SN1/SN2/E1/E2 based on nucleophile strength, substrate hindrance, and solvent type.
  • Aprotic solvents + good nucleophiles favor SN2.
  • Protic solvents favor SN1/E1.
  • Strong bases favor E2.
• Tertiary Alkyl Halides:
  • SN2 not feasible due to steric hindrance.
  • Strong bases favor E2.

Special Cases

• Methyl Substrate with Bulky Base: Only SN2 is possible, as E2 requires at least two carbon atoms.
• Sterically Hindered Primary Substrates: Can lead to E2 even with strong bases.

Examples

Example 1: 2-Bromobutane with Sodium Cyanide and Acetone

• Mechanism: SN2 due to good nucleophile and aprotic solvent.
• Product: Inverted configuration of the starting material.

Example 2: Tert-Butyl Chloride with Water

• Mechanism: SN1/E1 due to tertiary substrate and protic solvent.
• Products: Alcohol (SN1) and alkene (E1).

Example 3: Reaction with Methoxide and Methanol

• SN2 Product: Inversion; minor product due to competition with E2.
• E2 Product: More stable alkene (Zaitsev product) is major.

Example 4: Methyl Bromide with Tert-Butoxide

• Mechanism: SN2 exclusively due to lack of alternative pathways.
• Product: An ether.

Example 5: Butyl Bromide with Methoxide and Methanol

• Mechanism: SN2 predominant due to unhindered substrate and strong base.

Key Takeaways

• Reaction mechanism depends on substrate structure, type of nucleophile/base, and solvent.
• Hindrance: Steric hindrance favors elimination (E2) over substitution (SN2).
• Solvents: Protic solvents favor SN1, aprotic favor SN2.