Synthesis of Carboxylic Acids via FGI

Introduction to Strategies for Organic Synthesis, First Edition. Laurie S. Starkey. 2012 John Wiley Sons, Inc. Published 2012 by John Wiley Sons, Inc. 

Another FGI that gives carboxylic acid products is the hydrolysis of carboxylic acid derivatives, such as esters and nitriles. Such hydrolysis reactions can either be acid catalyzed (H3O+) or base promoted (1. NaOH, H2O 2. H3O ) and involve an acyl substitution mechanism (addition-elimination) that replaces any acyl leaving group with a hydroxyl group. The synthesis of carboxylic acids via nitriles is especially noteworthy since the introduction of the cyano group via Sn2 with CN involves the formation of a new C-C bond (adds one new carbon to the alkyl halide carbon chain). 

Synthesis of Carboxylic Acids via Ester or Nitrile Hydrolysis 

SYNTHESIS OF CARBOXYLIC ACIDS VIA GRIGNARD (RMgBr + CO2 RCO2H) 

Reacting of a Grignard reagent with carbon dioxide produces a carboxylic acid product upon workup. This synthesis converts an alkyl (or aryl) halide to a carboxylic acid while also extending the carbon chain by one carlion. 

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