Synthesis Reactions in Organic Chemistry

Overview of Synthesis Reactions

• Focus on synthesis reactions involving alkenes, Grignard reagents, and various examples.

Reaction Mechanisms

Acetylene to Acetal Ion

• Reagents: Sodium amide (NaNH2)
• Mechanism:
  • NH2- ion as a strong base removes hydrogen from acetylene (alkyne).
  • Produces acetal ion (nucleophilic carbon with a negative charge).

Formation of Carbon-Carbon Bonds

• Mechanism:
  • Nucleophilic acetal ion attacks electrophilic carbon in alkyl halide.
  • Formation via SN2 reaction.

Synthesis Examples

Example 1

• Objective: Convert alkyne to alkene with additional carbon chains.
• Steps:
  1. Use sodium amide to generate acetal ion.
  2. Add alkyl halide (e.g., 1-bromobutane) for chain extension.
  3. Reduce alkyne to alkene using sodium in liquid ammonia.

Example 2

• Objective: Add different R groups to an alkyne.
• Steps:
  1. Remove hydrogen using sodium amide.
  2. Add alkyl bromides sequentially for different R groups.
  3. Convert alkyne to cis-alkene using Lindlar’s catalyst (hydrogen gas with poisoned palladium).

Grignard Reagents

Mechanism

• Reagent: Methyl magnesium bromide.
• Reaction: Nucleophilic carbon from Grignard reagent attacks electrophilic carbon in carbonyl compounds.
• Product: Formation of alcohols (e.g., tertiary alcohol from ketone).

Synthesis Examples

• Objective: Add carbon atoms to a ketone or aldehyde.
• Reagents:
  • Grignard reagents (e.g., phenyl magnesium bromide) and acid (H2O+).

Special Cases

• Acid Chlorides & Esters:
  • Grignard reagents add two R groups.
  • Use Gilman reagents (organocopper compounds) to stop at ketone stage.

Reaction Mechanisms for Specific Conversions

Conversion of Acid Chloride to Ketone

• Reagent: Gilman reagent (e.g., R2CuLi).
• Mechanism: Attacks carbonyl carbon, stops at ketone.

Conversion of Esters

• Reagent: DIBAL (diisobutylaluminium hydride).
• Mechanism: Reduces ester to aldehyde.

Reagent Preparation

Grignard Reagents

• Preparation: Add magnesium to alkyl halide.
• Mechanism: Magnesium inserts into carbon-halogen bond.

Organolithium Reagents

• Preparation: Use lithium with alkyl halide.
• Mechanism: Lithium replaces halogen, forms R-Li.

Advanced Synthesis Techniques

Coupling Reactions

• Gilman Reagents: Used for combining different alkyl groups.

Witting Reaction

• Objective: Convert ketone to alkene.
• Reagent: Phosphonium ylides.

Summary

• Synthesis reactions involve strategic use of reagents to transform functional groups.
• Techniques involve nucleophilic substitutions, reductions, and carbon-carbon bond formations.
• Understanding mechanisms is critical for predicting reaction outcomes and planning synthetic routes.