12.10
Preparation of Aldehydes and Ketones from Carboxylic Acid Derivatives
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Q1: Why can't carboxylic acids be used to prepare aldehydes with strong reducing agents?
Aldehydes are more reactive than carboxylic acids, so they get over-reduced to alcohols when exposed to strong reducing agents like LAH. This makes carboxylic acids ineffective for aldehyde preparation since the aldehyde product is reduced faster than the starting material, preventing selective aldehyde formation.
Q2: What carboxylic acid derivative works best for preparing aldehydes with mild reducing agents?
Acid chlorides are easily reducible carboxylic acid derivatives that successfully give aldehydes using mild reducing agents. They are more reactive than carboxylic acids, allowing selective reduction to the aldehyde stage without over-reduction to alcohols. This selectivity makes acid chlorides ideal for aldehyde synthesis.
Q3: How does the Rosenmund reduction prevent over-reduction of aldehydes?
Rosenmund reduction uses hydrogenation of acid chlorides over a poisoned catalyst. Catalytic poisoning inhibits the over-reduction of aldehydes to alcohols, allowing the reaction to stop at the aldehyde stage. This selective deactivation of the catalyst maintains control over the reduction process and prevents further unwanted reactions.
Q4: What reagent can stop Grignard reduction of acid chlorides at the ketone stage?
The Gilman reagent (R2CuLi) is a milder reducing agent that stops Grignard reduction at the ketone intermediate. Standard Grignard reagents reduce acid chlorides all the way to tertiary alcohols, but the Gilman reagent provides better selectivity for ketone formation without further reduction to alcohols.
Q5: How can esters be converted to aldehydes without over-reduction?
Esters can be reduced to aldehydes using DIBAL-H at dry ice temperature. This low-temperature condition prevents over-reduction, allowing selective conversion to the aldehyde product rather than further reduction to tertiary alcohols. The cold temperature slows the reaction rate and improves selectivity.
Q6: Why can't ketones be prepared directly from esters?
Ketones cannot be prepared directly from esters because ketones are more reactive than esters and tend to over-reduce to tertiary alcohols. Once the ketone forms from ester reduction, it continues to react with the reducing agent, preventing selective ketone formation and leading to unwanted alcohol products.
Q7: How does Friedel-Crafts acylation prepare aryl ketones from carboxylic acid derivatives?
Aryl ketones are prepared by Friedel-Crafts acylation, where an acid chloride is treated with benzene and aluminum chloride (AlCl3). This electrophilic aromatic substitution directly forms the ketone product without requiring subsequent reduction steps. The acid chloride acts as the acylating agent in this reaction.