Alkyne Chemistry Notes

Carbon Nucleophiles and Epoxides

  • Epoxides (Oxiranes) can react with carbon nucleophiles to form new carbon-carbon bonds.
  • Example 1: Reaction of an epoxide with sodium methoxide (NaOCH3) in methanol (CH3OH) leads to 2-methoxyethanol. The methoxide attacks the epoxide, opening the ring.
  • Example 2: Reaction of an epoxide with sodium cyanide (NaCN) in water (H₂O) results in 3-hydroxypropanenitrile. The cyanide ion attacks the epoxide.

Forming C-C Bonds Using Epoxides in Synthesis

  • Epoxide ring opening can be used to create C-C bonds in synthesis.
  • A retrosynthetic approach can be used when planning out the synthesis.

Mechanism for Epoxide Opening with an Alkynide Anion

  • Step 1: Formation of Alkynide Anion. React alkyne (RC≡CH) with a strong base like sodium hydride (NaH) to form an alkynide anion (RC≡C⁻).
    RC≡CH + NaH → RC≡CNa + H_2
  • Step 2: SN2 Attack. The alkynide anion acts as a nucleophile and attacks the epoxide in an SN2 reaction, opening the ring. The nucleophile attacks the less substituted carbon of the epoxide.
  • Step 3: Acid Workup. After the SN2 reaction, protonate the resulting alkoxide with dilute acid (H2SO4, H2O) to obtain the alcohol.
  • Overall Reaction:
    RC≡CNa + Epoxide → R-C≡C-C-C-OH

Electrophilic Addition of Strong Brønsted Acid to Alkynes

  • Alkynes react with hydrogen halides (e.g., HCl, HBr) to produce geminal dihalides, where both halogen atoms are on the same carbon.

Mechanism for Electrophilic Addition to Alkynes

  • Step 1: Electrophilic Addition. H^+ adds to the alkyne to form a vinylic carbocation. The more stable carbocation is formed.
  • Step 2: Coordination.
  • Step 3: Electrophilic Addition. Halide ion (e.g., Cl^-) attacks the carbocation to form a vinylic halide.
  • Step 4: Coordination.
  • Resonance stabilization of the vinylic carbocation intermediate contributes to the reaction.

Acid-Catalyzed Hydration of Alkynes: Ketone Synthesis

  • Acid-catalyzed hydration of alkynes produces ketones, not alcohols.

Increasing the Yield of Acid-Catalyzed Hydration

  • Use a stronger Brønsted acid catalyst than sulfuric acid to increase the yield.

Mechanism for Acid-Catalyzed Hydration of Alkynes

  • Step 1: Electrophilic Addition. H^+ adds to the alkyne to form a vinylic carbocation. The vinylic carbocation intermediate is resonance stabilized.
  • Step 2: Coordination. Water molecule coordinates to the carbocation.
  • Step 3: Proton Transfer. Water deprotonates the coordinated water molecule to form an enol.
  • Step 4 & 5: Tautomerization. The enol tautomerizes to the more stable keto form via proton transfer.

Keto Form Favored

  • The keto form is generally favored over the enol form due to greater total bond energy in the keto form.

Alkynes and Oxymercuration-Reduction

  • Alkynes undergo Markovnikov addition of water via oxymercuration.
  • An unstable enol is initially produced, which tautomerizes to the more stable keto form.

Tautomerization and Hydrolysis of Mercuric Enol

  • Reduction with NaBH_4 is not required to remove the mercury(II) substituent.
  • The mercurinium ion intermediate opens to produce a mercuric enol, which tautomerizes to a mercuric ketone.
  • The mercuric ketone is hydrolyzed by water to produce the enol.
  • The enol form tautomerizes to the more stable keto form.

Ketones from Alkynes Examples

  • Phenylethyne to Phenylethanone: Phenylethyne reacts with H2O and HgCl2 to yield phenylethanone (82%).
  • Hex-1-yne to Hexan-2-one: Hex-1-yne reacts with H2O, HgSO4, and H2SO4 in acetic acid to yield hexan-2-one (80%).
  • Markovnikov addition on terminal alkynes produces ketones.

Ketones from Internal Alkynes

  • Internal alkynes can be converted to ketones.
  • A mixture of isomeric ketones will be produced.

Summary of Alkyne Chemistry

  • Alkyne Structure. Discusses the structure of alkynes.
  • Deprotonation. Formation of alkynides with strong bases.
  • Elimination. Synthesis of alkynes from dihalides.
  • Oxymercuration. Markovnikov addition of water to give ketones.
  • Reduction. Reduction of alkynes to alkenes and alkanes.
    • Alkyne to (Z)-alkene: Use Lindlar's catalyst with H_2.
    • Alkyne to (E)-alkene: Use Na in liquid NH_3 at -78 °C.
    • Alkyne to alkane: Use Pd/C (10%) with H_2.
  • Alkylation of Terminal Alkynes.
    • React alkyne with n-BuLi, followed by an alkyl halide (R_1X).

Synthesized Alkynes Using E2 Elimination Reactions

  • The leaving group is in a vinylic position (attached to a C=C double bond).
  • Vinylic halides are resistant to nucleophilic substitution and elimination reactions.

Elimination of a Vinylic Halide Examples

  • Specific examples demonstrating elimination reactions to form alkynes.

Formation of Terminal Alkynes

  • Formation of a terminal alkyne requires an acid workup when using very strong bases.
  • Bases such as NaH and NaNH_2 can irreversibly deprotonate a terminal alkyne.

Mechanism for Terminal Alkyne Formation

  • Step 1: E2 Elimination. Strong base removes a proton and halide ion leaves, forming an alkyne.
  • Step 2: Proton Transfer. The strong base deprotonates the terminal alkyne.
  • Step 3: Proton Transfer. Acid workup is necessary to reprotonate the terminal alkyne.

More Examples of Alkyne Formation

  • 1,1-Dichloropentane to Pent-1-yne: React 1,1-dichloropentane with 3 equivalents of NaNH2, followed by H2O and heat.
  • 1,2-Dibromo-1-phenylethane to Phenylethyne: React 1,2-dibromo-1-phenylethane with KOH in CH_3OH and heat.