Aldehydes and Ketones

By James Ashenhurst

Grignard Reagents For Addition To Aldehydes and Ketones

Last updated: December 1st, 2022 |

Grignard Reagents: Their Formation, Reactions, And Reaction Mechanisms


Today’s reagent is one that most students have experience in making at some point or another. Grignard reagents are formed by the reaction of magnesium metal with alkyl or alkenyl halides. They’re extremely good nucleophiles, reacting with electrophiles such as carbonyl compounds (aldehydes, ketones, esters, carbon dioxide, etc) and epoxides. They’re also very strong bases and will react with acidic hydrogens (such as alcohols, water, and carboxylic acids).

Similar to or the same as: very similar to organolithium reagents.

Formation Of Grignard Reagents

Grignard reagents are made through the addition of magnesium metal to alkyl or alkenyl halides. The halide can be Cl, Br, or I (not F). It’s slightly easier to make Grignards from the iodides and bromides, however. Note what’s happening here – the magnesium is “inserting” itself between the carbon and the halide. This halide the “X” referred to when we refer to Grignard reagents as “RMgX”.


Reaction Of Grignard Reagents With Aldehydes To Give Secondary Alcohols

One of the most common uses of Grignard reagents is in their reaction with aldehydes and ketones to form alcohols. In the first step, the Grignard forms the carbon-carbon bond. This results in an alkoxide (the conjugate base of an alcohol). To form the alcohol, it’s necessary to add acid at the end of the reaction (in what’s called the “workup” step). This is shown here as “H3O+” (the “X” is just the counter-ion, a spectator here)


Reaction Of Grignard Reagents With Ketones To Give Tertiary Alcohols

The reaction behaves similarly with ketones. Again, there’s nothing special about the Cl here – it all depends on how you made the Grignard in the first place.


Grignards Add Twice To Esters And Acid Halides

Grignard reagents will also add to esters. What makes these reactions a little more complicated is that they add twice. The net result (after addition of acid) is a tertiary alcohol. This is also the case for acid halides (acyl halides) and anhydrides. One notable exception is carboxylic acids (more on that below).



Addition Of Grignard Reagents To Epoxides

Another important reaction of Grignard reagents is that they will add to epoxides to form carbon-carbon bonds. One thing to keep in mind here is that the tendency is for them to add to the less substituted end of the epoxide – that is, the less sterically hindered end. You can think of this reaction as being essentially similar to an SN2 reaction. After addition of acid, an alcohol is obtained.


Reaction Of Grignard Reagents With Carbon Dioxide To Give Carboxylic Acids

Grignard reagents also add to carbon dioxide (CO2) to form carboxylates, in a reaction similar to their reactions with ketones and aldehydes. The carboxylates are converted to carboxylic acids after addition of acid (such as our trusty H3O(+) ).


Grignard Reagents Are Strong Bases – Protonation (And Deuteration)

Finally, since Grignard reagents are essentially the conjugate bases of alkanes, they’re also extremely strong bases. This means that sometimes acid-base reactions can compete with their nucleophilic addition reactions. One common situation where this crops up is when Grignard reagents are added to carboxylic acids. It’s easy to forget that carboxylic acids… are acids. This means that instead of adding to the carbonyl, they react with the proton instead and form the carboxylate salt.


This can also be used to convert alkyl halides to alkanes. First you treat it with magnesium, and then you treat the Grignard with a strong acid. This gives you the alkane. You can also use this to introduce deuterium (D) into molecules! The first step is to make the Grignard reagent. The second is to treat that Grignard with a deuterated acid such as D2O. This gives you the deuterated alkane!

Mechanism: Addition Of Grignard Reagents To Aldehydes And Ketones

So how does it work? The key to the Grignard reagent is actually very simple. When you think about the relative electronegativities of carbon (2.5) and magnesium (1.1), the bond between carbon and magnesium is polarized toward carbon. That means that carbon is more electron rich than magnesium and is actually nucleophilic! Here’s a closer look.


In the reaction of Grignards with aldehydes, the carbon attacks the carbonyl carbon and performs a 1,2-addition to give an alkoxide. In the second step, acid is added to give you the alcohol.

(Advanced) References and Further Reading

  1. Grignard, V. C. Acad. Sci. 1900, 130, 1322-1324
    The original paper by Victor Grignard describing a new method for alcohol synthesis from hydrocarbons.
  2. Victor Grignard and Paul Sabatier: Two Showcase Laureates of the Nobel Prize for Chemistry
    Henri B. Kagan
    Chem. Int. Ed. 2012, 51, 2-9
    DOI: 10.1002/anie.201201849
    For those interested in the history of science, this is a historical perspective on the lives of Victor Grignard and Paul Sabatier, and gives insight into their lives, how they made their seminal discoveries, and the impact of their work, among other things.
  3. Mechanical activation of magnesium turnings for the preparation of reactive Grignard reagents
    Karen V. Baker, John M. Brown, Nigel Hughes, A. Jerome Skarnulis, and Ann Sexton
    The Journal of Organic Chemistry 1991 56 (2), 698-703
    Sometimes the formation of a Grignard reagent using Mg metal can be challenging, and various methods for activating the metal surface have been developed, including mechanical activation by dry-stirring Mg turnings under an inert atmosphere for several hours.

    The following 3 papers are mechanistic studies on the formation of Grignard reagents:
  4. The Mechanism of Formation of Grignard Reagents: Trapping of Free Alkyl Radical Intermediates by Reaction with Tetramethylpiperidine-N-oxyl
    Karen S. Root, Craig L. Hill, Lynette M. Lawrence, and George M. Whitesides
    Journal of the American Chemical Society 1989 111 (14), 5405-5412
    DOI: 10.1021/ja00196a053
  5. Mechanism of Grignard Reagent Formation. The Surface Nature of the Reaction
    M. Walborsky and Janusz Rachon
    Journal of the American Chemical Society 1989 111 (5), 1896-1897
    DOI: 10.1021/ja00187a063
  6. Mechanism of Grignard Reagent Formation. Comparisons of D-Model Calculations with Experimental Product Yields
    John F. Garst and Brian L. Swift
    Journal of the American Chemical Society 1989 111 (1), 241-250
    DOI: 10.1021/ja00183a037
    K. Stille, Antonio M. Echavarren, Robert M. Williams, and James A. Hendrix
    Org. Synth. 1993, 71, 97
    DOI: 10.15227/orgsyn.071.0097
    The second step in this procedure includes the synthesis of p­-anisylmagnesium bromide, which can be a tricky Grignard reagent to prepare and requires special activation of Mg with methyl iodide.




Comment section

78 thoughts on “Grignard Reagents For Addition To Aldehydes and Ketones

  1. Hello,
    I was just thinking that the reaction to make a grignard is exothermic and reacts spontaneously. Furthermore, oxido/ reduction reactions are thermodynamic reactions (Delta G = -nF(delta)E). Hence, can I conclude that the reaction to make a grignard is under thermodynamic control ?
    This feels counter intuitive since the formed organometallic compound is much more reactive and much more unstable then the halogenated one.
    I hope you will be able to enlighten me in where I am going wrong.
    Thanks for all your great work.

    1. Hi – it’s exothermic, and is thermodynamically favored.

      Thermodynamic control is when you can choose the product distribution of an equilibrium mixture by changing the temperature. There is no equilibrium between the Grignard product and the starting materials.

  2. Greetings! First of all Thank you for creating this website!
    Aldehydes and Ketones too are acidic, for eg., acetone can act as an acid, so why don’t they give acid-base reaction with Grignard reagent. Is it because it is a weak acid? Are there any priority order like when will acid-base reaction occur and when nucleophillic addition? Thank you for your help!

  3. Greetings! First of all thank you so so much for creating such a wonderful website!
    Can Cyclohexane be used as a solvent for grignard reagent? My textbook said it can’t be, what can be the reason? It doesn’t seem to have any acidic hydrogen either.

  4. What if there are all like aldehydes ketones esters acid halide on same compound , which will react first?

    1. That would be a really bad synthesis design, since it’s unwise to have so many functional groups present on the same molecule. But between these, aldehydes are likely the most reactive.

    1. Usually doesn’t work out the way you want it to (i.e. substitution). Electron transfer followed by reduction of alkyl halide and elimination are both common side reactions. Depends on identity of alkyl halide and the substitution pattern.
      Even with a cuprate (Gilman reagent) getting a substitution reaction to work on a secondary carbon can be very challenging.

    1. They deprotonate carboxylic acids, but do not react further. The resulting O(-) is a very strong pi donor to the carbonyl carbon, which greatly reduces its electrophilicity. Organolithium reagents do add to carboxylic acids however.

  5. Reaction of grignard reagent with alcohol (zerevitnov’s reaction) is not given here….rest of the content is very good.

  6. Hey James, today I came across this question it reads as ” if CH3MgBr is taken in excess, then how many moles of CH3MgBr will be consumed in the reaction ”
    I solved it and came to the conclusion that only 2 moles of CH3MgBr are required but the answer is 3 pls help me ASAP.

    1. 1) Look for acidic protons (e.g. alcohols). See any? I do. They’ll perform an acid base reaction.
      2) Acid chloride. How many equivalents of Grignard does it react with?
      Total = 3

    1. It doesn’t make sense to add H3O+ and then H+, because H3O+ represents aqueous workup and you’d be heating a biphasic mixture.

      However I think what you’re getting at is that once you perform the workup, you get an alcohol. If you heat the alcohol with acid, you’ll likely get some kind of elimination reaction.

  7. Can grignard react with something like dihydropentalene?
    What would happen if we two moles of grignard (in first attack I believe it will make one side aromatic)?

    1. Sounds like you’re asking for the solution to an exam problem. Sure. It’s a strong base. In the case of two equivalents, I think you should check what the resulting structure would be from removing two protons and count the resulting number of pi electrons.

  8. Hi James, I had a question that’s been on my mind for quite a while since I started taking ochem II. Why is it that we never see Grignards reacting with the alpha hydrogen on ketones and esters and instead opt for attacking the carbonyl in a substitution reaction even though the difference in pKas theoretically allow such a deprotonation to be possible (pKa 50 vs pKa ~20 and 25 respectively)?

    1. Hi Jon. Acid base reactions *can* occur but usually only on ketones which have a lot of steric hindrance.
      Part of it stems from the difference between why acid-base reactions are fast on heteroatoms (e.g. OH) relative to carbon. (aka “the principle of least motion”)
      Acid-base reactions on heteroatoms like OH are fast because there is very little reorganization of the bonds around the atom after deprotonation.
      In contrast on an alpha carbon, the carbon has to rehybridize from sp3 to sp2, meaning that the other two C-H bonds have to move as well.
      Another subtle factor is that an acid-base reaction on the alpha carbon of a ketone requires that the C-H be aligned with the pi system of the carbonyl (so that deprotonation results in a resonance-stabilized anion). So for an acid-base reaction to occur, the collision between the reactants has to coincide with the C-H bond on the alpha carbon being in the right conformation. There is no such conformational barrier for reaction at the C=O bond and assuming that nothing gets in the way of the Grignard on its approach to the carbonyl (i.e. no steric hindrance) the reaction should be fast. I realize this sounds somewhat hand-wavy, but it’s an attempt to backwards rationalize why acid base reactions are relatively slow in this instance.

    1. Oxygen, yes, although it should be protected as an ether and not have O-H. Nitrogen also possible but on complex substrates it’s usually easier to do metal-halogen exchange.

  9. What does the X signify in the reaction of the Grignard with carbon dioxide? Is it a hydrogen halide or does any acid work?

  10. Can just an alkene react with a grigard reagent? Like not the formation of a grignard but after it is formed can it react with an alkene?

    1. The short answer is no. The electons in a C-C pi bond in an alkene are shared relatively equally between the carbons, with the result that neither carbon has any significant partial positive charge. Alkenes are unreactive. Contrast that to a C=O bond, where carbon is partially positive and oxygen is partially negative; Grignard reagents are much more reactive in that situation.

  11. Both ketone and ether dont have acidic hydrogen then why does grignard reagent reacts with ketone and not with ether?

    RMgX + R’OR’ —-> ROR’ + MgX(OR’)
    Can the above reaction occur?

    If it occurs then why grignard reagent is put in dry ether?

  12. grignards are definitely up their in my list of most favorite reactions. i still think the sandmeyer and clemmensen would win in a fight.

  13. For Grignard reactions, how would you perform the reaction if you have the MgBr-cyclohexane and react it with ethanol then an aqueous acid?

  14. Hi I bought all your guides and the app, but the app isnt updated since 2012, while the chemistry sure hasn’t changed for an orgo course and i dont buy paying, i am, curious if there will be any updates in the future.

  15. Can Grignard attack carbon dioxide twice, since the carbon in the carboxylate after initial Grignard attack would still have a positive delta charge? And subsequent protonation create a geminal?

    1. No, just once. Attack on a carboxylate would not occur – the carbonyl carbon is quite electron rich owing to donation of the carboxylate electrons (pi donation)

    1. Same thing! Water is a strong enough acid to protonate the alkoxide. [Extra detail, feel free to skip: this will form HO- and ROH . Why doesn’t the reaction just go in reverse, since ROH is of similar acid strength to water? The key is to add a large excess of water. Since there will be a much larger concentration of water, equilibrium drives it forward to the alcohol.]

  16. We recently did a grignard synthesis in lab using diethyl ether as the solvent and it said that the signs of reaction were cloudiness of the precipitate and bubbles showing up on the magnesium but I can’t figure out what kind of gas these bubbles would be…Would they be the diethyl ether?

    1. Great question. It tends to initiate electron-transfer type reactions that end up leading to cleavage of the R-X (X being halogen) bond. Grignards tend to be clusters in solution and so they are more sterically hindered than they might appear. The solution is to make them into organocuprates (Gilman reagents) by using CuBr or the like. Then SN2 reactions work well (particularly on primary substrates). James

  17. Thanks for all your work on these pages! Can you talk about how a Grignard reagent would react with a carboxylate salt, vs. a carboxylic acid? Would they not react? I’m being ask to show the products of a carboxylate salt (ethyl butanoate) and a methyl Grignard followed by a water workup. My guess is the salt and Grignard won’t react (because these salts are pretty stable) and the water will simply protonate forming the carboxylic acid. Thoughts?

  18. “Greg Nard added an equivalent of 3,4-epoxy-4-methylcyclohexanol (Figure 1) to an ether solution of methyl magnesium bromide and then added dilute hydrochloric acid. He expected that the product would be a diol (Figure 2). He did not get any of the expected product. What product did he get?” i have tried everything for the answer i cannot figure it out

    1. Sounds like it just deprotonated the hydroxyl group at the 1 position in the ring, assuming your substrate is 3,4-epoxy-4-methylcyclohexan-1-ol. That alkoxide could probably then go open that epoxide to make a product I can’t name, but should look like a dicyclohexylether with the methyl and erstwhile epoxide OH on one of the rings alpha to the ether linkage. So no diol from having the Grignard open the epoxide because the -OH is too acidic a proton to have in the presence of the CH3MgBr.

      1. Ooooh, or you might get a cool intramolecular attack if you throw your substrate in a chair conformation an let the O- attack the epoxide that way. I don’t know. It’s worth building a model or sketching it out. If you were running a very dilute solution of substrate such that two of those molecules finding each other were a very rare prospect, the intramolecular possibility would win.

        1. In the intramolecular case, though, you’d end up opening the epoxide at the more substituted side to get two 5-membered rings sharing the C-O-C bridge (gotta get the model out for this one!) instead of 4+6…I think…

  19. If you were trying to synthesize a product using Grignard chemistry, and the Grignard reactant (R-MgBr) also contained an ester and the other reactant were an aldehyde, would the Grignard reactant possibly react with itself before it reacted with the aldehyde?

    1. Yes, it would react with itself. That’s why you need to protect groups that can undergo Grignard addition such as aldehydes, ketones, and esters. Although for esters you can’t protect them so much as just keep them as alcohols and oxidize up after the reaction is complete.

      1. Because fluorine is the smallest element among the halogens and fluorine forms covalent bond with carbon atom which is strong so in order to break such kind of bond vigorous conditions must be apply therefore

  20. Hello James,

    Since grignard reagents deprotonate alcohol.
    Will it affect the reaction between grignard and aldehyde to produce secondary alcohol?

    1. The Grignard addition alone generates the alkoxide. A separate acid workup is necessary to protonate the alkoxide to the secondary alcohol.

  21. Do the carbocations formed during the reaction of aldehydes and ketones with grignard reagent stabalize by 1-2methyl shift or hydride shift???

  22. I recently came across the interesting set of reactions between Grignard reagents and (terminal) propargylic chlorides. SN2′ substitution gives allenes with a new C-C single bond, along with a mess of other stuff resulting from deprotonation of the terminal alkyne…including the venerable alkylidene carbene, perhaps my favorite obscure intermediate in all of organic chemistry!

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.