20 1 Alkylation of alkynide anions general principles

Deprotonation of Terminal Alkynes

  • Deprotonation Requirement

    • Terminal alkynes require a strong base for deprotonation.

    • Sodium Amide

      • pKa = 25 (strong base)

      • Ammonia pKa = 38 (weaker acid)

    • Reactions favor the formation of weaker acids and bases.

  • Example of Ineffective Base

    • Alkoxide (e.g. OEt)

      • Reaction: Generates carbon ion + ethanol.

      • Alkoxide pKa = 17 (weaker base)

    • Reaction not favored with alkoxide due to weaker base leading to unfavorable reaction direction.

Substitution Using Deprotonated Alkynes

  • Nucleophilic Substitution Reaction

    • Deprotonated alkyne can function as a nucleophile.

    • Performs substitution on a substrate with a good leaving group (SN2 reaction).

  • Substrate Considerations

    • Primary Substrates

      • Ideal for SN2 reactions.

    • Secondary and Tertiary Substrates

      • Tend toward elimination (E2 mechanism) instead of substitution.

Examples of Substitution vs. Elimination

  • Primary Substrate Example (Methyl Iodide)

    • Mechanism: Simple SN2

      • Nucleophile attacks, displacing leaving group and forming a substituted product.

  • Secondary Substrate Example

    • Reactions favor formation of alkene through elimination.

      • Reactions produce propene from secondary alkyl halide via proton transfer.

      • Mechanism: E2 reaction, competing against substitution for secondary and tertiary substrates.

Summary

  • In summary, using sodium amide as a strong base is crucial for effectively deprotonating terminal alkynes. Substitution reactions work best with primary substrates, while secondary and tertiary substrates are likely to undergo elimination reactions.

Deprotonation of Terminal Alkynes

Deprotonation Requirement

Terminal alkynes require a strong base for deprotonation to produce a carbanion. The acidity of terminal alkynes is due to the sp-hybridized carbon that is bonded to a hydrogen atom. Deprotonation leads to the formation of a carbanion, which is a crucial intermediate in subsequent reactions.

Sodium Amide

  • Sodium Amide (NaNH2) is commonly used as a strong base due to its high pKa of around 25, making it an effective deprotonator for terminal alkynes.

  • In contrast, ammonia, which has a pKa of 38, is a weaker acid and thus less effective for deprotonating terminal alkynes.

  • Reactions generally favor the formation of weaker acids and bases, aligning with the principle of stability in chemical equilibria.

Example of Ineffective Base

  • Alkoxides, such as ethoxide (OEt), have a pKa of approximately 17, categorizing them as a weaker base compared to sodium amide.

  • Although alkoxides can theoretically deprotonate terminal alkynes, the reaction is unfavorable due to the weaker base leading to a less stable carbon ion and a higher tendency to revert to the starting material. This results in the generation of carbon ion and ethanol in an equilibrium that does not favor product formation.

Substitution Using Deprotonated Alkynes

Nucleophilic Substitution Reaction

  • Once deprotonated, alkyne can act as a nucleophile, participating in nucleophilic substitution reactions with substrates containing good leaving groups, adhering to the SN2 mechanism.

Substrate Considerations

  • Primary Substrates:

    • Ideal candidates for SN2 reactions, as they allow for direct nucleophilic attack without steric hindrance. The mechanism involves the nucleophile attacking the substrate and displacing the leaving group, resulting in a substituted product.

  • Secondary and Tertiary Substrates:

    • These substrates tend to favor elimination reactions (E2 mechanism) over substitution due to steric hindrance and the stability of the transition state for elimination pathways.

    • For instance, secondary alkyl halides generally lead to the formation of an alkene through elimination, with reactions producing propene via the transfer of a proton during the E2 mechanism.

Examples of Substitution vs. Elimination

  • Primary Substrate Example (Methyl Iodide):

    • Mechanism: Simple SN2 where the nucleophile attacks methyl iodide, displacing the iodide ion and forming a substituted product, such as an alkyne derivative.

  • Secondary Substrate Example:

    • The mechanism favors elimination, transitioning to the formation of propene as the major product, showcasing how secondary and tertiary substrates lead more towards elimination in competitive scenarios.

Summary

In summary, using sodium amide as a strong base is crucial for effectively deprotonating terminal alkynes, establishing carbanions necessary for subsequent reactions. Substitution reactions are predominantly successful with primary substrates, while secondary and tertiary substrates are inclined to undergo elimination reactions, emphasizing the importance of substrate selection in synthesis involving deprotonated terminal alkynes.