Carboxylic acids, conversion hindrance

Nitriles are most commonly prepared via the conversion of carboxylic acids to primary amides, followed by dehydration with boiling acetic anhydride, or other commonly employed dehydration reagents, e.g. SOCI2 or POCI3. This is a useful synthesis for amide, because it is not limited by steric hindrance. Alkyl nitriles can be prepared by the action of metal cyanides on alkyl halides (see Section 5.5.2). 

Carboxylic acids can be activated in several ways, such as conversion to the corresponding acid chlorides, imidazole amides, anhydrides, or by using coupling reagents such as DCC. We chose pivaloyl chloride for initial development, because the hindrance of the pivaloyl group should favor the desired selectivity with the corresponding mixed anhydride 11. 

An unnecessarily detailed description has been published of the conversion of functionali d carboxylic acids to methyl ketones via the corresponding acid chlorides more significantly functionalized examples of this reaction have been already reported. An explanation has been offered to account for the lack of steric hindrance in the acid chloride in such a ketone synthesis, where the organocopper species is formed in situ from Grignard reagents and copper(i) chloride. The change in relative reactivity... 

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