Alkylation Monosodium Acetylide

Alkyl Halide Reactions: Monosodium Acetylide Alkynylation

Monosodium Acetylide + Alkyl Halides | OrgoSolver

Alkylation of Alkyl Halides with Monosodium Acetylide (NaC≡CH)

Monosodium acetylide is a linear, strongly basic carbon nucleophile generated from acetylene (HC≡CH) or another terminal alkyne. It performs a backside SN2 on methyl and primary alkyl halides to deliver terminal alkynes in a single substitution, while the same basicity pushes secondary and tertiary halides toward E2. Allylic and propargylic substrates can drift to SN2′, giving allenes after γ-attack. This guide packages all three outcomes—SN2, competing E2, and optional SN2′—into one repeatable workflow with reagent overlays, solver defaults, and QA pointers.


Quick Summary

  • Reagents & conditions: Preformed NaC≡CH or generated in situ from acetylene with strong base; polar aprotic solvents (DMSO, DMF, MeCN, THF), 0 °C → room temperature; quench with water or weak acid.
  • Substrate outcomes:
    • Methyl & primary → SN2 → terminal alkyne with inversion at the reacting carbon.
    • Secondary & tertiary → E2 dominates because the acetylide is a strong base.
    • Allylic & propargylic → SN2 (with an optional SN2′ overlay that can furnish allenes).
  • Leaving groups: I ≈ Br ≫ Cl; sulfonates (OTs, OMs, OTf) behave as excellent leaving groups.
  • Stereochemistry: SN2 gives Walden inversion; E2 respects anti-periplanar geometry; SN2′ can scramble allylic configurations.
  • Not supported: Vinylic and aryl halides do not undergo SN2; cross-coupling chemistry is required instead.


Mechanism

SN2 Path (Primary / Benzylic Focus)

Use when the electrophile is methyl, primary, or benzylic (allylic primary also qualifies).

  1. Step 1 — Backside approach
    The acetylide lone pair aligns anti to the C–X bond, aiming directly into the σ* orbital.
    Step 1: acetylide approaches anti to the C–X bond
    Acetylide engages the σ* orbital while X⁻ begins to depart.
  2. Step 2 — Product release (Walden inversion)
    Bond formation to carbon and bond breaking to the leaving group occur simultaneously; the umbrella at that carbon flips and the terminal alkyne is released.
    Step 2: terminal alkyne product with inversion
    Walden inversion accompanies terminal alkyne formation; the halide leaves off-panel.

    For allylic or propargylic substrates, the Mechanism Solver exposes an optional SN2′ overlay from this view to show the allenic rearrangement.

E2 Competition (Secondary / Tertiary)

Displayed automatically for secondary or tertiary substrates; toggle-able warning for strongly β-branched primaries.

  1. Step 1 — Anti alignment
    Identify a β-hydrogen anti to the leaving group (trans-diaxial on cyclohexanes).
    Step 1: acetylide overlay highlights the anti β-hydrogen
    Anti-periplanar geometry is mandatory; align the NaC≡CH overlay with the β-H before drawing arrows.
  2. Step 2 — Concerted β-elimination
    The acetylide abstracts the β-hydrogen while C–X breaks to give an alkene (Zaitsev or Hofmann depending on sterics).
    Step 2: acetylide removes Hβ as the halide leaves
    The NaC≡CH overlay donates its lone pair into Hβ while the C–X bond collapses to the alkene.
  3. Step 3 — Alkene product
    The elimination furnishes the alkene plus leaving group.
    Step 3: alkene product after NaC≡CH elimination
    The alkene appears once the β-H is removed and X⁻ departs.


Worked Examples

  • Primary bromide → terminal alkyne (SN2): 1-bromobutane (primary) treated with NaC≡CH in DMSO (0 °C → rt) delivers 1-pentyne with inversion at C‑1.
  • Tertiary bromide → alkene (E2): 2-bromo-2-methylpropane (tert-butyl bromide) under heated NaC≡CH conditions eliminates to 2-methylpropene; anti alignment is enforced before arrows.
  • Allyl bromide → propargyl vs. allene mixture: Allyl bromide in DMF with NaC≡CH gives both the direct propargyl substitution and the SN2′ allenic product (overlay toggle).
Reactant: 1-bromobutane (primary) Reagent: NaC≡CH under polar aprotic conditions Product: 1-pentyne with inversion

Primary SN2 — clean terminal alkyne formation.

Reactant: tert-butyl bromide (tertiary) Reagent: heated NaC≡CH conditions Product: 2-methylpropene (alkene)

Tertiary → E2 — acetylide acts as a strong base to give 2-methylpropene.

Reactant: allyl bromide (allylic) Reagent: NaC≡CH in DMF at rt Products: propargyl vs. allenic outcomes

Allylic — highlight the SN2 vs SN2′ mixture.


Scope & Limitations

  • Great matches: Methyl, unhindered primary, benzylic, and allylic halides; sulfonate esters behave similarly.
  • Challenging: Secondary halides lean toward E2; neopentyl primaries are painfully slow for SN2.
  • Off-limits: Vinylic and aryl halides do not undergo SN2 with acetylide; consider cross-coupling strategies instead.
  • Leaving groups: Iodides and bromides perform best; chlorides usually need solvent optimization or halide exchange first.
  • Over-alkylation control: When starting from acetylene, manage equivalents to avoid immediate dialkylation unless desired.


Practical Tips

  • Generate the acetylide first (base then electrophile) and keep everything anhydrous to prevent quenching.
  • Use polar aprotic solvents and moderate temperatures to favor substitution; heating invites E2.
  • For allylic/propargylic cases, preview the SN2′ overlay so students anticipate allenic products.
  • Quench carefully with water or a weak acid; small terminal alkynes can be volatile, so isolate promptly.
  • Consider counter-ion effects: complexing Na⁺ (e.g., crown ether) can boost nucleophilicity but also enhance elimination risk.


Exam-Style Summary

  • Primary or methyl halides plus NaC≡CH → terminal alkynes via SN2 with inversion.
  • Secondary or tertiary halides default to E2; always enforce the anti-periplanar requirement when drawing products.
  • Allylic and propargylic substrates can undergo SN2′ to allenes—know when to present the alternate pathway.
  • Neopentyl substrates are notorious for failed SN2; expect sluggish reaction or elimination, and explain the steric rationale.
  • Poor leaving groups (e.g., unactivated chlorides) stall; propose halide exchange or sulfonate formation before alkynylation.
  • Never assign this reaction to vinyl or aryl halides—the mechanism is simply not viable.


Interactive Toolbox

  • Mechanism Solver — flip between SN2, E2, and SN2′ frames with the exact RDKit artwork used above.
  • Reaction Solver — select the NaC≡CH button to see how substrate class, solvent, and temperature shift the dominant pathway.
  • IUPAC Namer — verify the names of the alkyne, alkene, or allene predicted by your mechanism sketches.


Related Reading