* The organomagnesium halides are known as Grignard reagents. These are extremely important reagents developed by the French chemist François Auguste Victor Grignard, who was awarded the Nobel Prize in 1912 in Chemistry for this work.

The Grignard reagent is represented as R-Mg-X, where

    R = alkyl / aryl / alkenyl / allyl group

    X = Cl / Br / I

* The reactions involving Grignard reagents, as sources of nucleophiles, are usually referred to as Grignard reactions.



* The Grignard reagents are prepared by the action of activated magnesium (Rieke magnesium) on organic halides in suitable solvents like Diethyl ether, Et2O or Tetrahydrofuran, THF in anhydrous conditions

preparation of grignard reagent

* This is an oxidative insertion of magnesium between carbon and halogen bond, which involves oxidation of Mg(0) to Mg(II). The mechanism of this reaction if not quiet conclusive.

* The Grignard reagents are in equilibrium with the dialkylmagnesium species R2Mg and MgX(Schlenk equilibrium).

schlenk equilibrium grignard reagent

* In the formation of Grignard reagent, the polarity of carbon attached to the halide group is reversed. This reversal in polarity is called as umpolung.


Activation of magnesium metal:

* Magnesium metal is usually unreactive due to formation of oxide layer on its surface. Hence it should be activated by dislodging this layer. It is achieved by adding small amount of iodine or 1,2-dioiodoethane or by using ultrasonic sound. 

This problem can also be obviated  by using Rieke magnesium, which is in the form of highly reactive small particles of magnesium with large surface area. It is prepared by reducing MgCl2 with lithium metal. 


* Ether solvents like Diethyl ether, Et2O or Tetrahydrofuran, THF or Dimethoxyethane, DME or Dioxane are most suitable for the preparation of Grignard reagents. It is because they are not only unreactive with magnesium but also dissolve and stabilize the Grignard reagents by forming Lewi's acid base complexes.

complexation of grignard reagent with ether solvent molecules

* The major disadvantage of Grignard reagents is they react with protic compounds like water, alcohols, thiols etc. Hence the reaction must be carried out under anhydrous conditions avoiding moisture.

* These reagents must not be exposed to air as they also react with oxygen by giving peroxide species which are converted to corresponding alcohols during hydrolytic workup. To avoid this, it may be preferable to carry out the reaction in nitrogen or argon atmosphere.

grignard reagent reaction 1-2b


* The alkyl Grignard reagents are prepared from the corresponding chlorides or bromides or iodides. The order of reactivity of alkyl halides with magnesium is  RCl < RBr < RI. Alkyl fluorides are seldom used due to much less reactivity.

* The alkenyl and phenyl Grignard reagents are prepared from the corresponding bromides or iodides in more effective co-ordinating solvent like THF. 

E.g. Vinyl bromide and bromobenzene can be converted to corresponding Grignard reagents by reacting them with magnesium metal in anhydrous THF.

grignard reagent 1-3

* The alkynyl Grignard reagents are prepared by deprotonating 1-alkynes with another Grignard reagent like Ethylmagnesium bromide.

E.g. Propyne can be deprotonated with ethylmagnesium bromide to give propynylmagnesium bromide.

grignard reagent 1-4

* The allylic Grignard reagents  may undergo coupling reactions. Hence they are generated in situ whenever required in the Grignard reactions.

* Grignard reagents can also be prepared by transmetallation

E.g. Alkyllithiums can give Grignard reagents when treated with magnesium salts.




* The Grignard reagents are highly basic and can react with protic compounds like water, acids, alcohols, 1-alkynes etc., by giving corresponding alkanes.

E.g. Ethylmagnesium bromide liberates ethane gas when treated with water.

grignard reaction 1-6

The reaction of Grignard reagent with D2O can be used to introduce a deuterium atom selectively at a particular carbon atom.

deuterolysis of grignard reagent 1-6b

* However the Grignard reagents are less basic than organolithiums and hence are more suitable nucleophiles for carbon-carbon bond formation.

* The Grignard reagents are used as sources of carbon nucleophiles (carbanions) and can react with electrophilic centers. The addition reactions involving Grignard reagents with compounds containing polarized multiple bonds like aldehydes, ketones, esters, acid halides, nitriles, carbon dioxide etc., are termed as Grignard reactions.

* The reactivity of carbonyl compounds with Grignard reagents follow the order: aldehydes > ketones > esters > amides


* The first step in the Grignard reaction is the nucleophilic addition of Grignard reagent to the polar multiple bond to give an adduct which upon hydrolytic workup gives the final product like alcohol. 

E.g. The mechanism of reaction with a carbonyl compound is shown below.

grignard reaction 1-7



 Following is the summary chart of applications of Grignard reagent in modern organic synthesis.

Grignard reaction    Product

R-Mg-X + 

 Formaldehyde ( HCHO )


 A primary alcohol:  R-CH2-OH 
 Aldehyde (R'-CHO)


 A secondary alcohol: R'-CH(OH)-R
 Ketone (R'-CO-R")


 A tertiary alcohol: R'-CR"(OH)-R
 Ester (R'-COOR")


 A tertiary alcohol: R'-CR(OH)-R
 Acid halide (R'-COX)


 A tertiary alcohol: R'-CR(OH)-R


 A carboxylic acid: R-COOH


 A dithionic acid: R-CSSH


 A sulphinic acid: R-SOOH


 A sulphonic acid: R-SO2OH
 nitriles (R'-CN)


 A ketone: RCOR'
 Hydrogen Cyanide (HCN)


 An aldehyde: RCHO
 Oxiranes (epoxides)


 Weinreb amide


 A ketone


 A nitrile


 An amine


 Alkyl iodide


 A thiol
 halides of B, Si, P, Sn


 compounds with C- hetero atom bonds


1) The addition of Grignard reagents to formaldehyde furnishes primary alcohols.

E.g.  The addition of  Ethylmagnesium iodide to formaldehyde followed by hydrolytic workup furnishes Propyl alcohol, a primary alcohol.

grignard reaction 1-8


2) The Grignard reaction with aldehydes other than formaldehyde gives secondary alcohols.

E.g. The addition of Methylmagnesium iodide to acetaldehyde gives Isopropyl alcohol.

grignard reaction 1-9


3) The addition of Grignard reagent to ketones furnishes tertiary alcohols.

E.g. The addition of Methylmagnesium iodide to acetone gives tert-Butyl alcohol.



The carbonyl carbon of an unsymmetrical ketone is a prochiral center. Therefore the addition of a Grignard reagent  can take place on either face of the carbonyl group with equal chance. Hence a racemic mixture is formed in absence of asymmetric induction.


formation of racemic mixture from unsymmetric ketone 1-10b1

However a mixture of diastereomers is formed when the ketone or aldehyde contains at least one chiral center. The predominant stereoisomer formed in this case can be predicted by using Cram's rule. 

E.g. The reaction of (R)-2-phenylpropanal with ethylmagnesium bromide, an achiral Grignard reagent furnishes the (R,R)-2-phenyl-3-pentanol as major product.

application of cram's rule in grignard reaction 1-10b2

Side reactions:

However, the abstraction of an α-hydrogen by Grignard reagent (in this case it acts as a base) is observed with sterically hindered ketones to furnish an enolate intermediate. The protic workup of the enolate ends up in the recovery of the starting ketone.

 recovery of sterically hindered ketone in grignard reaction 1-10c

If the Grignard reagent contains a β-hydrogen, reduction of carbonyl compound by hydride transfer may compete with the desired addition reaction (see below). Hence the Grignard reagent with smallest possible alkyl group is to be used to avoid this side reaction. Also the use of corresponding organolithium compounds is advisable to suppress the enolization products.

 grignard reaction reduction side reaction 1-10d

It is also observed that the tertiary magnesium alkoxides bearing a β-hydrogen, may undergo a dehydration reaction during protic workup, and thus by giving an elimination product, alkene instead of alcohol.


elimination of tertiary alkoxide during hydrolytic workup


4) The esters are less reactive than aldehydes and ketones. However they give tertiary alcohols with excess (2 moles) of Grignard reagent. The initial addition product formed will decompose to a ketone which reacts with the second Grignard reagent to furnish the tertiary alcohol finally.

E.g. Ethyl acetate reacts with two moles of phenylmagnesium iodide and thus by furnishing 1,1-diphenylethanol, a tertiary alcohol. 



5) The acid halides also react with 2 moles of Grignard reagent to furnish tertiary alcohols. Again the reaction proceeds through the intermediate ketone.

E.g. Acetyl chloride reacts with two moles of Ethylmagnesium bromide to furnish 3-methylpentan-3-ol.

grignard reaction 1-12

However, it is also possible to get the ketone in higher yields by using one mole of Grignard reagent.


6) The Grignard reagents react with carbon dioxide to give carboxylic acids.

E.g. Methylmagnesium chloride gives acetic acid when reacted with carbon dioixide.

grignard reaction 1-13

    An analogous reaction of Grignard reagent is observed with carbon disulphide, CS2, to give alkanedithionic acid.

E.g. Ethanedithionic acid can be prepared by reacting methylmagnesium chloride with carbon disulphide, CS2.

grignard reagent reaction alkanedithionic acid preparation 1-13b 

    Also in another analogous reaction with sulfur dioxide, SO2, an alkanesulphinic acid is formed.

E.g. Methanesulphinic acid is formed when methylmagnesium chloride reacts with sulfur dioxide, SO2.

grignard reaction with sulfur dioxide 1-13c

    Whereas, alkane sulphonic acids are formed with sulfur trioxide, SO3.

alkane sulphonic acid preparation from grignard reagent 1-13d

7) The nitriles furnishes ketones with Grignard reagents.

E.g. Acetonitrile gives acetone when reacted with methyl magnesium iodide.

grignard reaction 1-14

    However, aldehydes are obtained with hydrogen cyanide, HCN.

grignard reaction with HCN 1-14b 

8) The oxiranes (epoxides) furnish alcohols with Grignard reagents.

E.g. Secondary butyl alcohol is obtained when 2-methyloxirane reacts with methylmagnesium iodide. 

The less substituted carbon of oxirane is substituted by the alkyl group of Grignard reagent.

grignard reaction 1-15


9) Addition of an N-methoxy-N-methyl amide, also known as Weinreb amide, RCON(Me)OMe, to the Grignard reagent gives a ketone. Initially the Grignard reagent is added to the Weinreb amide, which further undergoes hydrolysis to furnish ketone.

E.g. The addition of n-butylmagnesium bromide to the following Weinreb amide furnishes 3-heptanone.

grignard reagent reaction weinreb amide 1-16

10) The Grignard reagents are also used to prepare nitriles by reacting them with cyanogen or cyanogen chloride.

11) Amines can be prepared by reacting these reagents with Chloramine, NH2Cl.

reaction with chloramine to furnish amines 1-18

12) The alkyl iodides can be prepared via Grignard reagents. The alkylmagnesium chlorides or bromides are treated withIodine to get corresponding alkyl iodides.

reaction with iodine 1-19

13) A Wurtz like coupling reaction is also possible when the Grignard reagent is treated with an alkyl halide to furnish an alkane. Indeed it is a side reaction that may be possible during the preparation of Grignard reagent. This reaction is catalyzed by Cuprous (CuI) ions.

Wurtz like Grignard reaction 1-20

14) Just like oxygen, the sulfur atom is also inserted into the Grignard reagent, which gives a thiol upon protic workup.

insertion reaction with elemental sulfur

15) The Grignard reagent is also used in the making of bond between a carbon and other hetero atom like B, Si, P, Sn etc. These applications are depicted in the following reactions.

application of Grignard reagent in making of bond between carbon and other hetero atom 1-22

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PAGE CREATED BY DR ANTHONY MELVIN CRASTO M.SC, Ph.D (ORGANIC CHEMISTRY,24+ years experience in the field of research and development, currently with Glenmark, Mumbai India

Ентоні  アンソニー  Αντώνιος  安东尼    แอนโทนี   Энтони   אַנטאַני  Антхони  एंथनी  안토니  أنتوني


Principal scientist, GLENMARK-GENERICS LTD

Navi mumbai, INDIA



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The Grignard reaction is simple enough. It involves a Grignard reagent - that's some kind of carbon, attached to a magnesium salt - adding to a carbonyl compound such as an aldehyde, ketone, or ester.

The reaction with ketones and aldehydes is pretty straightforward: Grignard reagents are nucleophiles, and they add to the electrophilic carbonyl carbon, breaking the C=O bond and forming an alcohol after acid is added.

Things get a little bit more complicated with esters. If you add an excess of Grignard reagent, it adds to the carbonyl carbon too. Except in this case, it doesn't stop there. One of the lone pairs on the newly negative oxygen atom can re-form a π bond with the neighboring carbon. This results in breakage of the bond between the carbon and the OR, which leads to its ejection and the overall formation of a ketone. But it doesn't stop there. Now we have a ketone, which reacts really well with Grignard reagents - and we add a second equivalent, forming a new alcohol (after the acid workup).

What about carboxylic acids? You might expect they'd behave the same as esters. But no. Grignard reagents are strong bases, see, and when combined with a carboxylic acid, they're protonated. The resulting negatively charged carboxylate salt (that's the conjugate base of a carboxylic acid) is then pretty much impregnable to nucleophilic attack due to the strongly donating O(-) group. So it just sits there in solution until acid is added, giving us back our starting material.

Let's go back to esters for a minute. You might think that if you added only one equivalent of Grignard reagent, you could just get it to stop at the ketone stage. Well……no. What happens is that the rate of the elimination reaction is fast - faster than addition of Grignard to the ester - and the ketone outcompetes the ester for reagent. So at the end of the day you end up with a product where two equivalents of Grignard have added, and about half an equivalent of leftover ester.

Which brings up the next point: ketones and aldehydes are more reactive than esters. [The order of reactivity, by the way, goes aldehyde > ketone > > ester]. So if you have a molecule with a ketone and an ester on it, and you add one equivalent of Grignard reagent, it will add to the ketone selectively.

But watch out! When you add to a ketone or aldehyde, you form a new alkoxide (negatively charged oxygen). These are good nucleophiles! If the alkoxide oxygen is 5 or 6 bonds away from the ester - and if it can reach - it is possible for it to attack the ester carbonyl, doing a [1,2]-addition / [1,2]-elimination reaction to form a lactone (cyclic ester).

Why do 5 and 6- membered rings form quickly, whereas 3, 4, 7 (and higher) membered rings do not? Long story, but that's just the way it is. It's yet another thing you need to watch out for.

Finally, we come to this last example. We have a ketone and an ester. We can't form a ring. You might think it would just add to the ketone here. Again, not the case. This time, it turns out that having those two carbonyl groups in close proximity has made the protons on the adjacent CH2 group very acidic. The Grignard, being a strong base, simply removes a proton and doesn't add to the carbonyl carbon at all. [Yet another complicating factor: ketones like this one are largely present in their enol form, due to a stabilizing hydrogen bond between the O-H and the ester carbonyl oxygen.]. After acidic workup, we end up with starting material.

The lesson:  Functional groups and reagents can interact in funky ways that can be rationalized in retrospect, but are damn hard for a newbie to predict. It's part of what makes organic chemistry challenging and frustrating, to be sure,  but also deep and rewarding. That's just the way it is, folks.

Key points:

1) Some reagents can act both as nucleophiles and as bases. The trick is identifying when this is.

2) Aldehydes are more reactive towards nucleophiles than ketones, which are more reactive than esters.

3) Once a Grignard adds to an ester, there ain't no stoppin' it.

4) Five and six-membered ring formation is fast.

5) 1,3-dicarbonyls are unusually acidic, and this can complicate Grignard reactions.   Search

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