13.9 : Preparation of Carboxylic Acids: Carboxylation of Grignard Reagents

Grignard reagents undergo carboxylation to synthesize carboxylic acids with one more carbon atom than the starting Grignard reagent.

Here, the Grignard reagent acts as a nucleophile. It first attacks the electrophilic carbon of carbon dioxide to form a metal carboxylate, resulting in the formation of a new carbon–carbon bond.

Next, the metal carboxylate is acidified to generate the free carboxylic acid product.

As Grignard reagents are synthesized from organic halides, carboxylation of a Grignard reagent is a suitable method to convert an organic halide to a carboxylic acid. Here, the organyl group can be an alkyl, vinyl, or aryl.

For example, tert-butyl chloride can be converted to its corresponding one-carbon-higher carboxylic acid in substantial yield.

Recall that Grignard reagents are strong bases and powerful nucleophiles. Hence, organic halides bearing functional groups incompatible with Grignard reagents are seldom used in this two-step formation of carboxylic acids.

Carboxylic acids can be prepared by the carboxylation of Grignard reagents (RMgX). This method is convenient for converting alkyl (primary, secondary or tertiary), vinyl, benzyl, and aryl halides to carboxylic acids with one additional carbon than the starting RMgX.

Grignard reagent synthesis, reaction mechanism diagram, organic chemistry, carboxylic acid formation.

The carboxylation mechanism involves two steps. In the first step, the nucleophilic attack of the Grignard reagent on the electrophilic site of the carbon dioxide generates the magnesium salt of the carboxylate ion. In the subsequent step, it undergoes protonation by aqueous acid to yield carboxylic acid.

Grignard reaction mechanism, diagram, organic chemistry, showing nucleophilic addition to carbonyls.

For the second step, the proton source is added after completion of the first step (reaction between the Grignard reagent and carbon dioxide) because of the less compatibility of the proton source with the Grignard reagent.

The major drawback of this method is the presence of substituents incompatible with the Grignard reagent (such as –OH, –NH, –SH, or –C=O) on the aryl or alkyl halides.

Tags

Carboxylic Acids Grignard Reagents Carboxylation Nucleophilic Attack Magnesium Salt Carboxylate Ion Protonation Aqueous Acid Alkyl Halides Aryl Halides Reaction Mechanism Electrophilic Site Substitution Incompatibility

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