Reactions of Acetylide Anions

Reactions of Acetylide Anions with Alkyl Halides (SN2)

Acetylide anions are excellent nucleophiles and readily react with alkyl halides via an SN2 (bimolecular nucleophilic substitution) mechanism. This reaction is a cornerstone of alkyne synthesis, allowing for the formation of new carbon-carbon bonds and the extension of carbon chains.

SN2 Mechanism

In the SN2 reaction, the acetylide anion (nucleophile) attacks the alkyl halide, displacing the halide ion (leaving group) from the opposite side. This "backside attack" leads to an inversion of stereochemistry at the carbon center. The reaction is generally favored with primary alkyl halides due to less steric hindrance.

Examples

• Reaction with a primary alkyl halide:
  HC≡C⁻Na⁺ + CH₃CH₂Br → HC≡CCH₂CH₃ + NaBr
• Chain extension:
  R-C≡C⁻Li⁺ + CH₃(CH₂)₄Br → R-C≡C(CH₂)₄CH₃ + LiBr

Competition with E2 Elimination

Because acetylide anions are also strong bases, they can compete with E2 (bimolecular elimination) reactions, especially with secondary and tertiary alkyl halides or at elevated temperatures. E2 reactions lead to the formation of alkenes instead of the desired substituted alkyne. Bulky bases like t-butoxide will favor E2. For example, if you tried to react an acetylide with a secondary halide like isopropyl bromide, you'd get a significant amount of elimination product (propene) in addition to the substitution product.

Limitations

• Steric Hindrance: SN2 reactions are highly sensitive to steric hindrance. Acetylide anions react efficiently with unhindered primary alkyl halides. However, reactions with secondary and tertiary alkyl halides are significantly slower and often favor E2 elimination.
• Aryl Halides: Acetylide anions do not react with aryl halides (e.g., bromobenzene) due to the poor leaving group ability of the halide and the inability of the acetylide to perform a backside attack on the aromatic ring.
• Vinyl Halides: Similar to aryl halides, vinyl halides are generally unreactive toward acetylide anions.

Therefore, when synthesizing alkynes using acetylide anions, it is crucial to choose appropriate alkyl halides (generally primary) to minimize or avoid E2 elimination and ensure the desired SN2 substitution occurs efficiently.

Key Concepts and Further Points

• Stability of Acetylide Ions: The increased acidity of alkynes is primarily due to the stability of the resulting acetylide ion. This stability arises from two key factors:
  • Resonance Stabilization: The negative charge on the acetylide ion is somewhat delocalized, contributing to its stability.
  • s-Character and Charge Density: The negative charge resides in an sp orbital with high s-character. s orbitals are closer to the nucleus, meaning the electron density of the negative charge is held closer to the carbon nucleus, compacting the charge and stabilizing the anion. This is the *primary* reason for the increased acidity.
• Basicity of Acetylide Ions: Acetylide ions are not only strong nucleophiles but also strong bases. This basicity is important to consider when choosing reaction conditions.