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I understand that a Grignard reagent can act both as a base and a nucleophile. It acts as a base in the presence of a proton source (eg: alcohols, amine, water, etc). But when reacting with a ketone or an aldehyde, it acts as a nucleophile and uses a specific reaction mechanism. Why isn't that same reaction mechanism not viable for reaction with carboxylic acid?

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Why is this reaction mechanism wrong? Is the formation of a diol not possible due to repulsions or is there some other reason?

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    $\begingroup$ Grignard reagent is a superbase. It would rather take the acid's hydrogen rather than attack electrophilic carbon. $\endgroup$ – Huy Ngo Feb 16 '17 at 10:42
  • $\begingroup$ Not sure if I would call a Grignard a superbase, but it will react with the proton in a carboxylic acid rather than reacting as a ncuelophile on the carbonyl carbon $\endgroup$ – Nuclear Chemist Jun 6 '18 at 7:52
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    $\begingroup$ Also worth noting that an organolithium will deprotonate the carboxylic acid, and then attack the carboxylate ion to give a doubly-deprotonated gem-diol, which then reverts to a ketone upon work-up. This is because organolithium compounds are more nucleophilic than Grignards. This is an alternative to the answer about using a Grignard + a nitrile. $\endgroup$ – Bryan Hanson Jul 8 '18 at 23:13
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@Huy ngo says it all. A Grignard reageant will react first with just about any hydrogen that has even a modicum of proton donation capability, before "resorting" to the slower nucleophilic attack.

To get a ketone (in most cases), remove the dissociable proton by using a nitrile instead. This forms an intermediate imine which is hydrolysed to a ketone after water/acid workup:

$\ce{CH_3MgI + CH_3COOH -> }$ just a salt

$\ce{CH_3MgI + CH_3CN -> (CH3)2C=N-M ->[H2O] (CH3)2C=O}$.

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  • $\begingroup$ Grignard addition to a nitrile usually needs a copper salt added to get decent yields of ketone. $\endgroup$ – Waylander Jul 8 '18 at 12:43

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