Ch. 13 - Alcohols and Carbonyl CompoundsSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Johnny Betancourt

A Grignard reagent is an alkyl-magnesium halide complex that is extremely nucleophilic and basic. It is often used to make carbon-carbon bonds through addition or substitution reactions. They are also known as organomagnesium halides.

Structure of a Grignard:

​Generic Grignard R-MgX​Generic Grignard R-MgX

The Grignard reagent’s structure is an alkyl anion with a magnesium halide complex. The two most common ways to draw it are shown above; the first way shows a bond between the alkyl group (shown as “R”) and the magnesium, and the second way shows two ions. Notice that in the ionic representation the positive charge is on the whole magnesium halide complex. The usual halide used is Br to create MgBr, but MgCl and MgI complexes are also used. 

Preparation:

Preparing a Grignard reagent is actually very simple! All that needs to be done is to add elemental magnesium to an alkyl halide in an aprotic solvent like diethyl ether or THF. Let’s prepare ethylmagnesium bromide real quick:

Preparation of GrignardPreparation of Grignard

Reactions:

Given that the Grignard has a negatively charged carbon, it can act as an extremely powerful nucleophile and base. Let’s explore some examples of reactions Grignards undergo using ethylmagensium bromide as our nucleophile. Keep in mind that these reactions usually take place in a dry ether solvent and are then “quenched” with water.

1. Acid-base:

Grignard as baseGrignard as base

Here we have the Grignard deprotonating water. It will primarily acts as a base over a nucleophile if given the opportunity. This is why we can't use water or other protic solvents for Grignard reactions! I’ve drawn both versions of the Grignard reagent, but they’re totally equivalent. 

2. Epoxides:

Grignard and epoxideGrignard and epoxide

When reacting with epoxides (aka oxiranes), Grignard reagents attack the less-substituted side. This is no different from any other anionic nucleophile; they tend to attack the side that isn’t as sterically hindered. This particular reaction created a secondary alcohol.

3. Nucleophilic addition:

Nucleophilic additionNucleophilic addition

Grignard reagents will react with aldehydes and ketones at the electrophilic carbonyl carbon in a reaction called nucleophilic addition. Reactions with an aldehyde produce a secondary alcohol, and reactions with a ketone produce a tertiary alcohol.

4. Nucleophilic acyl substitution:

Grignards can also participate as nucleophiles in nucleophilic acyl substitution reactions. Let’s see how that works with a carboxylic acid:

How to ruin your GrignardHow to ruin your Grignard

Reacting a Grignard directly with a carboxylic acid will only result in a ruined Grignard! It’ll react with that acidic hydroxyl group instead of the carbonyl carbon. So, how can we get it to react at the carbonyl? We have to swap that hydroxyl group with an aprotic group like a chlorine or alkoxy group.

Nucleophilic acyl substitutionNucleophilic acyl substitution

Using thionyl chloride, we can convert the carboxylic acid into an acyl chloride (acid chloride). The Grignard can then react with the carbonyl carbon without an issue. Since the first substitution creates a ketone, the Grignard will attack again to produce a tertiary alcohol.

5. Carbonation:

Last one! Reacting a Grignard with carbon dioxide (CO2) is a great way to produce a carboxylate, which can then be protonated to form a carboxylic acid. Let’s check out the mechanism:


Carbonation of GrignardCarbonation of Grignard

So that’s it for reactions of Grignards! To see how the other organometallics (including organolithiums and Gilman reagents) react, check out my videos here. Good luck studying!



Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.


Additional Problems
For the reaction below, draw the structure of the appropriate compound. Indicate stereochemistry where it is pertinent.
Grignard reagents can react with aldehydes, ketones and esters in order to produce alcohols. Give the product for the following reaction
What is the product of the following reaction? A) I B) II C) III D) IV E) V
Your task is to synthesize 2-phenyl- 2-hexanol through a Grignard synthesis. Which pair(s) of compounds listed below would you choose as starting materials?
Besides attacking carbonyl groups, Grignard Reagents can react with other functional groups. Give the product for the following reaction
Which of the following terms best describes the reactive nature of a Grignard reagent? A) carbocation B) electrophile C) free radical D) carbene E) nucleophile
Complete the following reaction supplying the missing product and showing correct regio- and stereochemistry where applicable. If a racemic or diastereomeric mixture forms show all stereoisomers; if no reaction takes place, write N.R.
Complete the following reaction supplying the missing product and showing correct regio- and stereochemistry where applicable. If a racemic or diastereomeric mixture forms show all stereoisomers; if no reaction takes place, write N.R.
Write the structure of the principal organic product of the following: Cyclopentyllithium with formaldehyde in diethyl ether, followed by dilute acid.   
Provide the reagents to accomplish the following transformation. Then show the mechanism as to how the Ester and Aldehyde below can produce the same Alcohol.
Which compound will form a racemic mix (2 enantiomers) when treated with CH 3Li (followed by an acid quench)?
Give the product for the reaction given below. 
When compound 1 is treated with methyl Grignard, the product will be 1) chiral (one compound). 2) a racemic mixture (two compounds). 3) two chiral diastereomers (two compounds). 4) two racemic diastereomers (four compounds). 5) achiral (the product does not have stereocenters).
Predict the organic product of the following reaction. When appropriate, be sure to indicate stereochemistry. If more than one product is formed be sure to indicate the major product. Draw your answer in skeletal form. You will be graded on the product your draw from the reaction no other information is needed for this question.
Predict the product of the following reactions showing stereochemistry when applicable. If there is no reaction, just write “no reaction” in the box.
DRAW THE MOLECULAR STRUCTURE OF THE FOLLOWING REACTION PRODUCT(S). Two major organic products (after workup) from the reaction of (S)-2-methylcyclohexanone (Lewis/Kekule structure above at right) with ethylmagnesium bromide.
Predict the products of the reaction shown.
Predict the product(s) of the following reaction: A) A mixture of I and II B) A mixture of I and III C) A mixture of II and III D) A mixture of II and IV E) A mixture of III and IV
Which product is formed from the following transformation?
What would be the product from this reaction?
What is the product of this Grignard reaction?
Review the problem below and solve.
What will be the  major product of the following reaction? Pay careful attention to the stereochemistry of the product.
Grignard reagents can react with aldehydes, ketones and esters in order to produce alcohols. Give the product for the following reaction
Propose an acceptable mechanism for the reaction of the following epoxide shown below with an excess of ethylmagnesium bromide, then protonation with dilute acid.
Addition of methyl lithium (H 3CLi) to chiral aldehyde A, followed by aqueous acid quench, affords
Predict the product of the following reaction. Assume an acid quench.
Fill the boxes with the appropriate reactant, reagents, or product to achieve the given transformation. Some boxes require more than one step. If a stereocenter is created, draw both enantiomers and write racemic under the structure. Use wedges and dashes to indicate stereochemistry. If more than one product is possible, you only need to write the major product
Write the structure of the principal organic product of the following:tert-Butylmagnesium bromide with benzaldehyde in diethyl ether, followed by dilute acid. 
Provide the mechanism for the following reaction. Be sure to include all intermediates, formal charges and arrows depicting electron movement.
Predict the product:
Predict the product:
Predict the major product for the following reaction, paying attention to the regio- and stereochemistry where appropriate.  
Compound 1 is chiral. When treated with excess Grignard reagent, the product will bea) chiral (one compound).b) a racemic mixture (two compounds).c) two chiral diastereomers (two compounds).d) two racemic diastereomers (four compounds).e) achiral (the product has no stereocenters).
Draw the major organic product or reactant in the boxes provided for each reaction. Aqueous work up assumed where necessary.
What combination of reagents would not form the alcohol shown after an aqueous workup?
What is the result between acetic acid and phenyl magnesium bromide (PhMgBr) followed by treatment with aqueous acid?          (a) Acetophenone          (b) Phenyl actetate          (c) Phenylacetic acid, PhCH2CO2H          (d) Benzene and acetic acid          (e) None of the above
Give the major product for the following reaction.
Grignard reagents can react with aldehydes, ketones and esters in order to produce alcohols. 
Grignard reagents can react with aldehydes, ketones and esters in order to produce alcohols. 
Give the major product of the following reaction.
Provide the structure of the major organic product in the reaction shown below. 
For the reaction below: Draw the structure of the major organic product. Use the wedge/hash bond tools to indicate stereochemistry.
Grignard reagents undergo a general and very useful reaction with ketones. The product of the above reaction has the following spectroscopic properties: propose a structure. • MS: M+ = 114 • IR: 3450 cm-1 • 1H NNR: 0.90 δ (3H, triplet): 1.44 δ (2H, quartet): 1.56 δ (4H, triplet): 175 δ (4H, triplet): 3.65 δ (1H, singlet) • 13C NMR: 8.0, 24.2, 31.8, 40.1, 88.7 δ                               • You do not have to consider stereochemistry.                              • You do not have to explicitly draw H atoms.                              • In cases where there is more than one answer, just draw one.
Draw the major product(s) for the following reaction:
Draw the structure(s) of the major organic product(s) of the following reaction. 
Input the SMILES string for the skeletal structure of the major organic product produced in the following reaction.
Provide the reagents necessary to carry out the following conversion.
Provide the major organic product of the reaction below. 
Epoxides: reaction of 2-ethyloxirane with EtMgBr and aq. workup. Draw the structure of the organic product that is formed when the compound shown below treated with water.
Predict the product for the following reaction. 
Predict the product for the following reaction.
Predict the product for the following reaction sequence.
Draw the principal organic product for the reaction of 2-iodopropane with magnesium in diethyl ether followed by CH3C(CH2CH3)=O in diethyl ether, and then followed by dilute acid. Click the "draw structure" button to launch the drawing utility.
Draw the structures of organic compounds A and B. Omit all byproducts. 
Provide the major organic product of the reaction below.  
What is the product of this reaction?
What is the major organic product obtained from the following sequence of reactions? a. 3-methyl-2-butanol b. 3-methyl-2-butene c. 2-methylbutane d. 3-methyl-1-butanol
What is the major organic product obtained from the following reaction?