What is the reaction between Grignard reagent and amide Grignard reagent and anhydride
The Correct Answer and Explanation is:
Reaction Between Grignard Reagent and Amide:
Grignard reagents do not effectively react with amides to form alcohols because amides are relatively unreactive towards nucleophilic attack due to resonance stabilization of the carbonyl group. Additionally, the nitrogen atom of the amide has a lone pair that delocalizes into the carbonyl, reducing its electrophilicity.
If a Grignard reagent is added to an amide, it can act as a strong base and deprotonate the amide nitrogen, but the typical nucleophilic addition to form an alcohol does not proceed efficiently. Excess Grignard reagent and harsh conditions can sometimes lead to over-addition, producing tertiary amines, but this is not a straightforward reaction and is generally avoided in standard organic synthesis.
Reaction Between Grignard Reagent and Anhydride:
Grignard reagents readily react with acid anhydrides to form tertiary alcohols after hydrolysis. The reaction proceeds in two steps:
Step 1: The Grignard reagent attacks one of the carbonyl carbons of the anhydride, leading to the formation of a ketone intermediate and a carboxylate ion.
Step 2: A second equivalent of the Grignard reagent attacks the newly formed ketone, resulting in an alcohol after aqueous workup.
General Reaction Example:
Suppose phenyl magnesium bromide (C₆H₅MgBr) reacts with acetic anhydride (CH₃COOCOCH₃)
Step 1:
C₆H₅MgBr + (CH₃CO)₂O → C₆H₅COCH₃ + CH₃COO⁻MgBr⁺
Step 2:
C₆H₅MgBr + C₆H₅COCH₃ → (C₆H₅)₂C(OMgBr)CH₃
After hydrolysis:
(C₆H₅)₂C(OH)CH₃
Thus, the final product is a tertiary alcohol.
Conclusion:
- Grignard reagents do not react efficiently with amides due to resonance stabilization and basic properties of nitrogen
- Grignard reagents react with anhydrides to form ketones which further react to give tertiary alcohols after hydrolysis
