Grignard reaction
Classical Grignard reaction | |||||||||||
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Named after | Victor Grignard | ||||||||||
Reaction type | Coupling reaction | ||||||||||
Reaction | |||||||||||
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Organic Chemistry Portal | grignard-reaction | ||||||||||
RSC ontology ID | RXNO:0000014 | ||||||||||
The Grignard reaction (French:
(R2 or R3 could be hydrogen)
History and definitions
Grignard reactions and reagents were discovered by and are named after the French chemist
The reaction of an organic halide with magnesium is not a Grignard reaction, but provides a Grignard reagent.[8]
Classically, the Grignard reaction refers to the reaction between a ketone or aldehyde group with a Grignard reagent to form a primary or tertiary alcohol.[1] However, some chemists understand the definition to mean all reactions of any electrophiles with Grignard reagents.[9] Therefore, there is some dispute about the modern definition of the Grignard reaction. In the Merck Index, published online by the Royal Society of Chemistry, the classical definition is acknowledged, followed by "A more modern interpretation extends the scope of the reaction to include the addition of Grignard reagents to a wide variety of electrophilic substrates."[9] This variety of definitions illustrates that there is some dispute within the chemistry community about the definition of a Grignard reaction.
Shown below are some reactions involving Grignard reagents, but they themselves are not classically understood as Grignard reactions.
Reaction mechanism
Because carbon is more
Conditions
The Grignard reaction is conducted under anhydrous conditions.[3] Otherwise, the reaction will fail because the Grignard reagent will act as a base rather than a nucleophile and pick up a labile proton rather than attacking the electrophilic site. This will result in no formation of the desired product as the R-group of the Grignard reagent will become protonated while the MgX portion will stabilize the deprotonated species.
To prevent this, Grignard reactions are completed in an inert atmosphere to remove all water from the reaction flask and ensure that the desired product is formed.[13] Additionally, if there are acidic protons in the starting material, as shown in the figure on the right, one can overcome this by protecting the acidic site of the reactant by turning it into an ether or a silyl ether to eliminate the labile proton from the solution prior to the Grignard reaction.
Variants
Other variations of the Grignard reagent have been discovered to improve the chemoselectivity of the Grignard reaction, which include but are not limited to: Turbo-Grignards, organocerium reagents, and organocuprate (Gilman) reagents.
Turbo-Grignards
Turbo-Grignards are Grignard reagents modified with lithium chloride. Compared to conventional Grignard reagents, Turbo-Grignards are more chemoselective; esters, amides, and nitriles do not react with the Turbo-Grignard reagent.[14]
Heterometal-modified Grignard reagents
The behavior of Grignard reagents can be usefully modified in the present of other metals. Copper(I) salts give
See also
- Grignard reagent
- Wittig reaction
- Horner–Wadsworth–Emmons reaction
- Barbier reaction
- Bodroux-Chichibabin aldehyde synthesis
- Fujimoto-Belleau reaction
- Organolithium reagents
- Sakurai reaction
- Indium mediated allylation
- Alkynylation
References
- ^ ISBN 978-0-471-72091-1
- ^ Chapter 19: Carboxylic Acids. Organic Chemistry 4e Carey. mhhe.com
- ^ ISBN 978-0-12-800780-8, retrieved November 6, 2023
- Org. React.8: 28–58.
- ISBN 978-0-08-052349-1.
- ^ texte, Académie des sciences (France) Auteur du (January 1, 1900). "Comptes rendus hebdomadaires des séances de l'Académie des sciences / publiés... par MM. les secrétaires perpétuels". Gallica. Retrieved April 23, 2023.
- ^ Grignard, V. (1900). "Sur quelques nouvelles combinaisons organométaliques du magnésium et leur application à des synthèses d'alcools et d'hydrocabures". Compt. Rend. 130: 1322–25.
- doi:10.1351/goldbook.
- ^ a b "Grignard Reaction | The Merck Index Online". www.rsc.org. Retrieved April 23, 2023.
- .
- ISSN 0002-7863.
- S2CID 210709021.
- ^ Carey, Francis A. "Grignard reagent". Britannica.
- S2CID 257765567.
- ISSN 1460-4744.