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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
  • $\begingroup$ Acid-base reactions are much faster than nucleophilic attack. $\endgroup$ – Apurvium Aug 27 at 11:15
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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), avoid the dissociable proton by using a nitrile instead, assisted by a copper salt. This forms an intermediate imine which is hydrolysed to a ketone after water/acid workup:

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

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

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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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It is known fact that organolithium compounds react with carboxylic acid to give ketones (e.g., Ref.1). Until recently, however, no report has been published on Grignard reagents on this manner. Now, it is evident that Grignard reagents can also be used to prepare ketones under specific conditions (Ref.2):

Grignard reagent and Carboxylic acid

References:

  1. Robert. Levine, Marvin J. Karten, “Reactions of carboxylic acids with organolithium compounds,” J. Org. Chem. 1976, 41(7), 1176–1178 (https://doi.org/10.1021/jo00869a020).
  2. Kilian Colas, A. Catarina V. D. dos Santos, Abraham Mendoza, “$\ce{i-Pr2NMgCl•LiCl}$ Enables the Synthesis of Ketones by Direct Addition of Grignard Reagents to Carboxylate Anions,” Org. Lett. 2019, 21(19), 7908–7913 (https://doi.org/10.1021/acs.orglett.9b02899).
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