Grignard Reagent Reaction Mechanism (2023)


This organic chemistry video tutorial discusses how to use the grignard reagent to reduce ketones and aldehydes into secondary and tertiary alcohols. It also explains how to reduce esters and acid chlorides to alcohols using the grignard reagent.


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In this video we're gonna focus on reactions associated with the grignard reagent.

So let's talk about how to make it let's say, if we have one bromo butane.

And if we react it with magnesium metal, magnesium will insert itself between the carbon and bromine atoms given you a grignard reagent.

Now, what you need to know about the grignard reagent is the carbon that is attached to the magnesium atom that carbon is a nucleophilic carbon.

It bears a partial negative charge.

Magnesium has is positively charged.

And this bromine atom is negatively charged I like to think of it this way as the carbon having a negative charge, the magnesium as having a positive two charge and the bromide ion as having a negative.

Charge either case you need to realize that this carbon is nucleophilic now let's work on an example from.

So here we have an aldehyde functional group and we're gonna react it with methyl.

Magnesium bromide, followed by h3o plus.

So what do you think the major product of this reaction will be so in the first step, the nucleophilic grignard reagent will attack the carbonyl carbon causing the pi bonds break.

And keep in mind this carbon has a partial negative charge and so it's attracted to the partially positive, carbon atom of the carbonyl functional group, and so we're gonna get an oxygen for negative charge.

And here is the methyl group that we've added to the aldehyde.

So now in the next step, the oxygen with a negative charge is going to receive a proton from the hydronium ion so it's going to grab a hydrogen turn in into a secondary alcohol.

And so this is the major product for this reaction now let's work on another example.

So here we have cyclopentanone and let's react it with will use the same actually let's use a different reagent.

This time methyl, magnesium bromide so feel free to pause the video and work on this example.

So we could follow the same process.

So the grignard reagent will attack the carbonyl carbon from the back given us an alkoxide ion.

And here is the ethyl group that we've added to it now in the next step it's going to pick up a hydrogen.

And so this is gonna give us a tertiary alcohol this time.

And so this is the major product for the reaction.

So anytime you mix a grenade reagent with a ketone you're going to get a tertiary alcohol.

So now let's move on to our next example.

So here we have normal benzene.

And in the first step we're going to react it with magnesium, and then in the second step carbon dioxide.

And then in the third step h3o, plus so feel free to pause the video and work on this problem.

So once we add magnesium to bromobenzene, magnesium will insert itself between this carbon atom and this bromine atom.

So this is gonna give us phenol magnesium bromide now in the next step it's going to react with carbon dioxide.

So this carbon is partially positive, but the carbon attached to the magnesium atom that carbon is partially negative and so it's going to attack this carbon breaking one of its PI bonds.

And so now we have benzoate.

We also have the magnesium ion in a solution with the bromide ion.

So if you want to you could ride this like this, you could attach the oxygen with a negative charge to MGB R.

If you want to but I'm not going to worry about the magnesium and the bromine atom at this time.

So the last step is to react it with h3o plus.

And so the final product for this reaction is benzoic acid.

Now, let's move on to our next example.

So what happens if we mix an ester with a grignard reagent? So we're gonna react it with ethyl, magnesium bromide, followed by h3o plus now, when we act in a grignard reagent with an aldehyde or a ketone, you can only add one our group, but with esters and acid chlorides, you can add to our groups.

So in this example, you'll see that we're gonna add two methyl groups to the ester.

So let's, go ahead and begin.

So this is gonna be the first nucleophilic addition methyl, magnesium bromide will attack the carbonyl carbon giving us a tetrahedral intermediate and so here's.

The ethyl group that we've added at this point that's, the first R group.

Now we do have a relatively decent leaving group compared to this group.

So we can kick out the methoxide ion.

And thus we're gonna get a ketone.

Now this same grinev, reagent can react with the ketone so it's going to attack the carbonyl carbon given us an alkoxide ion.

So here is the second R group, but I'm gonna write it out for this problem.

So this is ch2 ch3.

And here we have another one.

So now the last step is to react this with h3o, plus turning this into an alcohol.

So what we have is a tertiary alcohol.

And so this is the major product for the reaction as you can see the Grenada V agent, reacts twice with the ester.

It adds to our groups to it.

Now, sometimes you might be given the reactant and the product of a reaction, and you need to determine the reagent that's needed to convert the reactant into the product, which is what we have in.

This example.

So what do we need in order to make this compound? So we'll, turn in the aldehyde into a secondary alcohol.

And notice that these four carbons were already present.

And so what we added were these carbons, so our grignard reagent will need to contain this group.

So basically on this carbon, you need to add the grinev agent.

And so basically all I did was draw what I saw right there and just add em gbr to that carbon atom.

So that's gonna be the first step and remember when converting the aldehyde into an alcohol, you only need to add the grinev agent once so we only need one equivalent of this grinev agent.

And then in the second step, we simply need to use h3o plus and so that's, how you can determine the reagents that you need in order to go from this aldehyde into the secondary alcohol.

Now, let's work on another example.

So here we have an acid chloride.

And we wish to convert it to a tertiary alcohol.

What reagents do we need? So we already have these six carbons.

Well, we need to add our these two propyl groups and recall that when mixing a grineer agent with an acid chloride or an ester to our groups will be added.

And those two our groups are the same.

We need to add two propyl groups.

So in step one I need two equivalence of propyl, magnesium bromide.

And, then in step two just h3o plus that's all we need to do.

Now the mechanism, by which the grinev agent reacts with an acid chloride is virtually the same.

When it reacts with an ester.

The only difference is instead of having an och3 group you have a CL group which is about a leaving group go ahead and try this problem let's say we have one bromo butane and in the first step we're gonna be acting with magnesium and then in a second step ethylene oxide and then h3o plus in the third step what is the major product of that reaction so let's take this one step at a time so let's take butyl bromide and let's react it with magnesium so this is going to give us butyl magnesium bromide and then in the next step we're gonna react out with ethylene oxide and so the green reagent, will attack one of these carbons because it's symmetrical doesn't, really matter which side we attack so we're gonna add two carbons to our four carbon chain.

So we're gonna have a total of six carbons.

And so on the last carbon that carbon is the carbon that's gonna bear the oxygen with a negative charge.

And in the next step we're gonna react us with the hydronium ion.

So in the end, we are going to get a primary alcohol.

So we have a total of six carbons.

And so this is called one hexanol so that's how you can make primary alcohols from alkyl halides using the grinev reagent and so that's it for this video.

Thanks for watching.


What is the mechanism of action of Grignard reagent? ›

Grignard reagents react rapidly with acidic hydrogen atoms in molecules such as alcohols and water. When a Grignard reagent reacts with water, a proton replaces the halogen, and the product is an alkane. The Grignard reagent therefore provides a pathway for converting a haloalkane to an alkane in two steps.

Why would a Grignard reaction fail? ›

The problem here is that Grignard reagents are strong bases, and will react with even weak acids (like alcohols). If we try to make a Grignard on a molecule with an acidic functional group, we'll end up destroying our Grignard instead.

What is the primary limitation of the Grignard reaction? ›

The primary limitation for Grignard reaction : This reaction can't takes place in presence of water or any acidic proton like S-H,O-H,etc. It can destroy the alkyl magnesium halide and form alkane.

How do you know your Grignard reaction is ready? ›

The reaction mixture becoming white and opaque: This is a good indication that the Grignard reagent is forming. The white and opaque appearance is due to the formation of a suspension of the Grignard reagent in the ether solvent.

What is the mechanism of reaction of alcohol with Grignard reagent? ›

The Grignard reagent reacts with aldehydes and ketones to form alcohol. The first step of the reaction is the nucleophilic addition of Grignard reagent to the carbonyl group to form an adduct. Hydrolysis of the adduct yields an alcohol ( R - C - OH ) .

What is the reaction mechanism of Grignard reagent with carbon dioxide? ›

Grignard reagents react with dry ice (solid CO2) followed by aqueous acid work-up to give carboxylic acids. CO2 can be thought of as a being a dicarbonyl compound : O=C=O. Note that the carboxylic acid contains one extra C atom compared to the original halide from which the Grignard reagent was prepared.

What are the errors in Grignard reaction? ›

Grignard reagents are a source of nucleophilic carbon - a strong nucleophile - which opens the epoxide by attacking the least hindered end in an SN2 fashion. Common errors: (1) wrong nucleophile used (i.e. Br- instead of "CH3-"). (2) Incorrect regiochemistry. (3) wrong functional group in the product.

What is the problem with Grignard reaction? ›

The disadvantage of the Grignard reagents is that they readily react with protic solvents (such as water), or functional groups with acidic protons, such as alcohols and amines.

What can Grignard not react with? ›

Grignard reagents will not perform SN2 reactions with alkyl halides. They are also not compatible with carboxylic acids or alcohols.

Which statement is wrong about the Grignard reagent? ›

Explanation: It is supposed that the Mg−C bond is strongly polar covalent, not ionic. Grignard's reagents are less reactive than organosodium, -potassium and -lithium compounds, that is the reason why it is more convenient to work with them.

When can you not use Grignard reagent? ›

As discussed above, Grignard and organolithium reagents are powerful bases. Because of this they cannot be used as nucleophiles on compounds which contain acidic hydrogens.

Are Grignard reagents unstable? ›

In this aspect, they are similar to organolithium reagents. Pure Grignard reagents are extremely reactive solids. They are normally handled as solutions in solvents such as diethyl ether or tetrahydrofuran; which are relatively stable as long as water is excluded.

How do you improve a Grignard reaction? ›

The reactivity may be further increased by the addition of alkali salts, usually potassium iodide. Rieke's magnesium metallates in quantitative yield, alkyl chlorides or bromides at room temperature, and even unreactive alkyl fluorides can be converted into Grignard compounds <74JA1775>.

What makes a good Grignard reagent? ›

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!

What functional groups are incompatible with Grignard reagents? ›

Alcoholic solvents and water are incompatible with Grignard reagents and organolithium reagents. Aldehydes, ketones, esters, amides, halides, -NO2, -SO2R, and nitriles are examples of reactive functional groups. Electrophilic or acidic functional groups cannot exist in the solvent or alkyl halides.

What type of reaction is a Grignard reaction? ›

The Grignard reaction (French: [ɡʁiɲaʁ]) is an organometallic chemical reaction in which carbon alkyl, allyl, vinyl, or aryl magnesium halides (Grignard reagent) are added to the carbonyl groups of either an aldehyde or ketone. This reaction is important for the formation of carbon–carbon bonds.

What is the purpose of the Grignard reaction experiment? ›

The purpose of this experiment was to reduce the carbonyl-containing compound benzophenone to the alcohol compound trimethylmethanol.

Why can't Grignard reagents react with water? ›

Water or alcohols would protonate and thus destroy the Grignard reagent, because the Grignard carbon is highly nucleophilic. This would form a hydrocarbon.

What happens when Grignard reagent reacts with ether? ›

Ether is also used as a solvent since it reacts with Grignard reagents forming a stable complex. The Magnesium-halogen bond is ionic and solvates the carbon-oxygen bond of ether thus forming a stable complex and increases the ability of the Grignard reagent to react.

What is the reaction between ethyl alcohol and Grignard reagent gives? ›

$ \Rightarrow $ Grignard reagent reacts with ethanol to produce alkane. Note: Always remember that the alkyl group of Grignard reagent is used in the newly formed alkane.

What happens to excess Grignard reagent? ›

Grignard reagent is a strong nucleophile. It undergoes nucleophilic addition reaction when it reacts with ester and produces ketone which on further addition gives tertiary alcohol.

What are the precautions for Grignard reaction? ›

Since Grignard reagents react violently with water, never allow product to get in contact with water during storage. Handle and store under nitrogen, protect from moisture. Avoid extremes in temperature and direct sunlight. Avoid storing next to strong oxidizing agents, fluorine, chlorine, and perchlorates.

Why are Grignard reagents destroyed by acid? ›

Carboxylic acid derivatives will yield varying results.

Grignards are destroyed in the presence of carboxylic acids. While we can react them with derivatives, carboxylic acids are too acidic and will destroy the Grignard, just as the Grignard would attack any acid or polar protic solvent.

Why only magnesium is used in Grignard reagent? ›

The magnesium metal used in the synthesis contains a layer of oxide on the surface that prevents it from reacting with the alkyl bromide. The pieces of metal must be gently scratched while in the ether solution to expose fresh surface area so that the reaction can commence.

Which Grignard is not possible? ›

The correct Answer is DThe Grignard reagent is a very powerful base, in effect it contains a carbanion. Thus, it is not possible to prepare a Grignard reagent from an group that contains an acidic hydrogen , by an acidic hydrogen, we mean any hydrogen more acidic than the hydrogen atoms of an alkane or alkene.

Why glucose does not react with Grignard reagent? ›

This is because the aldehyde group in glucose is involved in hemiacetal formation and thus is not free.

What is the best solvent for Grignard reagent? ›

The most commonly used organic solvents for Grignard reactions are diethyl ether (Et2O) and THF; in fact, a number of Grignard reagents in both of these solvents are commercially available.

Which can form Grignard reagent most easily? ›

We can prepare Grignard reagents in the lab easily by adding halogen to alkane to make haloalkanes. Further adding magnesium in the presence of dry ether to haloalkanes and it leads to formation of Grignard reagents.

What is the best solvent for Grignard? ›

Diethyl ether is an especially good solvent for the formation of Grignard reagents for two reasons. The Grignard carbon is highly basic and reacts with the acidic protons of polar solvents like water to form an alkane.

Why do you add iodine to Grignard reaction? ›

Addition of iodine is to help remove any MgO on the surface of the Mg. Removing MgO allows for Mg and the aryl/alkyl halide to come in contact and react.

How do you quench a Grignard reaction? ›

Quenching Grignards
  1. Remove your RBF from the oil bath, and place it in an ice bath. This tends to make the quench less angry. ...
  2. Add water, DROPWISE. Dropwise means dropwise! ...
  3. Add 10% sulfuric acid, DROPWISE. ...
  4. Extract into the solvent of your choice (often ether), dry, evaporate, do whatever else is necessary.
Aug 15, 2021

Which alcohol is most reactive towards Grignard reagent? ›

Aldehydes are more reactive towards the Grignard reagent or the nucleophilic substitution reaction than the ketone.

Is a Grignard reaction sn1 or SN2? ›

Grignards act like a nucleophile in an SN2 reaction.

What is the radical mechanism of Grignard reagent? ›

Radical Mechanism

Quantum-chemical calculations indicate that the homolytic cleavage of the Mg–CH3 bond in the solvated Grignard reagent CH3MgCl(THF)n requires a high energy of 66.6 kcal mol1 for n = 2, which is not lowered by increasing solvation (66.4 kcal mol1 for n = 3).

What is the mechanism of phenol from Grignard reagent? ›

From Grignard Reagent

Chlorobenzene or bromobenzene will be converted into phenyl magnesium halide in the presence of dry ether. The Grignard reagent produces phenol when it reacts with oxygen and is hydrolyzed by mineral acid.

What is the mechanism of epoxide with Grignard reagent? ›

Epoxide opens as the electrophile is generated by the addition of the alkyl group by Grignard reagent on epoxide. This when subjected to acidic conditions leads to the formation of a primary alcohol. Hence, reaction of epoxides with Grignard reagent generates primary alcohols.

What type of reaction is Grignard reagent? ›

Grignard reaction is an organometallic chemical reaction in which alkyl, allyl, vinyl or aryl-magnesium halides (Grignard reagent) are added to the carbonyl group in aldehyde or ketone. This reaction is important for the formation of carbon-carbon bonds.

How do you identify SN1 and SN2 mechanism? ›

Strong nucleophiles have negative charges but exceptions to this rule are halogens with negative charges and resonance stabilized negative charges. Strong nucleophiles indicate SN2 reactions while weak nucleophiles indicate SN1 reactions.

Why are Grignard reactions not reversible? ›

Question: R20 Grignard reactions are not reversible, because carbanions do not function as When treated with hydrogen cyanide (HCN), aldehydes and ketones are converted nto equilibrium favors formation of the For most aldehydes and unhindered ketones, the .

What does a Grignard reagent not react with? ›

Grignard reagents do not typically react with organic halides, in contrast with their high reactivity with other main group halides. In the presence of metal catalysts, however, Grignard reagents participate in C-C coupling reactions.

Why is Grignard reagent hard nucleophile? ›

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.

Why does water stop a Grignard reaction? ›

Water can destroy all or some of your Grignard reagent by acting as an acid. Remember that many good nucleophiles are also good bases. Since water is a strong acid, it can protontate the Grignard reagent to yield its conjugate acid, effectively derailing your reaction.

Which Grignard reagent is more reactive? ›

Hence the compound is given in option A i.e., Formaldehyde will be most reactive with Grignard's reagent.

What is the mechanism of Grignard reagent with acid chloride? ›

Acid chlorides react with Grignard reagents to produce tertiary alcohols. Two equivalents of the Grignard reagent are needed because the first equivalent reacts to form a ketone which then reacts with the second equivalent.

What is the mechanism of alkyl halide with Grignard reagent? ›

In a Grignard reaction, an alkyl halide reacts with magnesium metal in an anhydrous ether solvent to create an organometallic reagent. The Grignard reagent is highly reactive and is used to prepare many functional groups.

What is the general mechanism of epoxidation? ›

“Mechanism” The currently accepted mechanism for epoxidation is complex, with 14 electrons flowing in a single step. This can be simplified/approximated by showing the movement of only 10 electrons (Scheme 8.30). Typically, having this many electrons flowing in a single reaction step would be highly unlikely.

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