Lecture 12-3: The Grignard Reaction

Introduction

• Grignard Reaction is a multi-step reaction crucial for forming new carbon-carbon bonds.
• Products are typically alcohols: primary, secondary, or tertiary.

General Mechanism

1. Formation of Grignard Reagent

   • Reaction involves an alkyl halide (typically alkyl bromide) with magnesium in ether.
   • Magnesium inserts between carbon and halogen, forming a coordinate covalent bond (organometallic compound).
   • The carbon atom gains a negative charge, and the magnesium gains a positive charge.
   • The resultant compound is the Grignard Reagent.

2. Reaction with Oxygen-Containing Compounds

   • Grignard Reagent reacts with aldehydes, ketones, esters, or epoxides.
   • Carbon nucleophile from the Grignard Reagent adds to the carbon of the oxygen-containing compound.
   • Electrons in the double bond move onto the oxygen, forming an ionic salt with magnesium bromide.

3. Acid-Base Reaction

   • Protonation of the intermediate with a weak acid (often ammonium chloride) to form the alcohol.

Detailed Steps

Step 1: Formation of Grignard Reagent

• Alkyl halides can be primary, secondary, or tertiary.
• Halides can be vinyl or bonded to a benzene ring (phenyl halides).
• Ether is necessary to keep water away from the reaction.
• Grignard Reagent: carbon anion with a strong base character.
  • Must ensure dry conditions to prevent reaction with water which would yield alkanes rather than desired products.
  • Grignard Reagent acts as a strong nucleophile.

Step 2: Reaction with Oxygen Compounds

• Aldehydes:
  • Carbonyl bonded to R group and hydrogen.
  • Product: secondary alcohol.
• Ketones:
  • Carbonyl with two R groups.
  • Product: tertiary alcohol.
• Esters:
  • Two Grignard reagents add to the carbonyl carbon.
  • Product: tertiary alcohol.
• Epoxides:
  • Reaction at least substituted carbon atom.
  • Product can be primary, secondary, or tertiary alcohol.

Step 3: Acid-Base Reaction

• Neutralize the oxygen with a weak acid to yield the substituted alcohol.

Important Considerations

• Ensure absolutely dry glassware and reagents to prevent unwanted reactions with water.
• Grignard Reagent is versatile but must avoid water contamination to achieve desired alcohol synthesis.

Conclusion

• Grignard Reaction is crucial for synthesizing alcohols with new carbon-carbon bonds.
• Understanding the reaction conditions and steps is vital for successful application in synthetic chemistry.