Skip to content Skip to navigation


You are here: Home » Content » Grignard Reaction



What is a lens?

Definition of a lens


A lens is a custom view of the content in the repository. You can think of it as a fancy kind of list that will let you see content through the eyes of organizations and people you trust.

What is in a lens?

Lens makers point to materials (modules and collections), creating a guide that includes their own comments and descriptive tags about the content.

Who can create a lens?

Any individual member, a community, or a respected organization.

What are tags? tag icon

Tags are descriptors added by lens makers to help label content, attaching a vocabulary that is meaningful in the context of the lens.

This content is ...

Affiliated with (What does "Affiliated with" mean?)

This content is either by members of the organizations listed or about topics related to the organizations listed. Click each link to see a list of all content affiliated with the organization.
  • Rice Digital Scholarship

    This module is included in aLens by: Digital Scholarship at Rice UniversityAs a part of collection: "Chem 215 Spring08"

    Click the "Rice Digital Scholarship" link to see all content affiliated with them.

Recently Viewed

This feature requires Javascript to be enabled.

Grignard Reaction

Module by: Mary McHale. E-mail the author

Lab 3: Grignard Reaction


The purpose of this laboratory exercise is to perform a classic method for the synthesis of secondary alcohols: the addition of a Grignard reagent to an aldehyde (other than formaldehyde).

Background Information

After the most remarkable discovery by Victor Grignard in 1900, organometallic (An organic compound containing a metal atom directly attached to a carbon) compounds are very useful in organic synthesis. This discovery changed the course of organic chemistry and earned him the Nobel Prize in 1912. We now refer to such compounds as Grignard Reagents.

The Grignard reaction is one of the characteristic reactions of carbonyl compounds. It is especially useful as a means of forming new carbon-carbon bonds, something that we haven't seen much of until now. In this type of reaction a C-M bond is present (C=carbon and M=metal) which is covalent in nature. The metal is usually magnesium but lithiummore reactive and is also used. The more polar the C-M bond is, the more will be its reactivity. The reactivity order is known from electrochemical series:

M= Li> K> Ca> Na> Mg> Al> Zn> Fe> Sn etc

Traditionally alkyl magnesium halides are known as Grignard reagent (R-Mg-X).

Figure 1
Figure 1 (graphics1.jpg)

All kinds of alkyl halides react (Iodides are more reactive than bromides which in turn are more reactive than chlorides) and amazingly, even bromobenzene and other aryl bromides and iodides react easily with magnesium. This is particularly surprising since the aromatic halogen is so unreactive. For example, it is inert to refluxing with aqueous sodium hydroxide at temperatures in excess of 200˚C. The unshared pair of electrons on ether oxygen complexing with the Mg is believed to contribute to the stability of the reagent. Note: Aryl halides (ArX) and vinyl halides that are inert to nucleophilic substitution are reactive with this Grignard reaction.

Preparation and Mechanism of Grignard reagent:

The mechanism of Grignard reagent (GR) is not clear till today, but it is believed that the reaction is taking place on the metal surface. Since GR does not react with aprotic solvents (e.g. ether, THF etc), these solvents are widely used. The mechanism of formation of GR as follows: it goes via one electron transfer, followed by rapid combination of organic group with the metal center. From the mechanistic point of view, carbon-bromine bond should be broken prior to the reaction with magnesium.

Figure 2
Figure 2 (graphics2.jpg)

Solutions of some Grignard reagents such as methylmagnesium bromide, ethylmagnesium bromide, and phenylmagnesiumbromides are commercially available. Here is an example of Grignard reaction which explains the effect of solvent.

Figure 3
Figure 3 (grigt.png)

The Grignard reagent is made from the direct reaction of magnesium with an alkyl halide.

Figure 4
Figure 4 (graphics3.jpg)

The key to the function of the Grignard reagent is the reversal of the normal polarity of bonds to carbon (This type of reversal of polarity in carbon center is known as Umpolung). Because magnesium is more electropositive than carbon the carbon acquires a δδ size 12{δ - {}} {} charge whereas carbon, when it has a charge at all, usually has δ+δ+ size 12{δ+{}} {} charge from bonding to halogens, oxygen, and nitrogen.

Figure 5
Figure 5 (umpolung.png)

This δδ size 12{δ - {}} {}carbon consequently has significant nucleophilic character. The Grignard reagent reacts well as a nucleophile with the δ+δ+ size 12{δ+{}} {}-carbon of the carbonyl group as a target. The C=O π-bond is broken and the carbonyl becomes an alcohol. In the process, a new carbon-carbon bond is formed between the Grignard reagent and the carbonyl carbon - now the alcohol carbon.

Figure 6
Figure 6 (grig_mech.png)

The intermediate alkoxymagnesium salt is neutralized by acid in the work-up to produce the alcohol product. Before we go on to look at more Grignard reactions with carbonyl groups, here is a problem for you to try.

  1. Identify the product (A-E) (5 points)
Figure 7
Figure 7 (graphics4.jpg)


Figure 8
Figure 8 (graphics5.jpg)

Addition of GR to carbonyls:

GR adds to a carbonyl compounds to generate alcohols. A more modern interpretation extends the scope of the reaction to include the addition of Grignard reagents to a wide variety of electrophilic substrates:

Figure 9
Figure 9 (grig_rxns.png)
Figure 10
Figure 10 (3794411.png)

Depending upon the amount of GR used and the substrate, it can give different types of products after working up the reaction. Here is an example:

Figure 11
Figure 11 (graphics6.jpg)

Addition of GR to α, β unsaturated carbonyls:

GR adds to carbonyl center mainly in two fashions. Alkyl lithium halides add only in 1, 2-fashion because R-Li is a more reactive organometallic compound than others, so it prefers to add to most HARD carbonyl carbon center (since it is more electrophilic in nature). On the other hand, R2CuLiR2CuLi size 12{R rSub { size 8{2} } ital "CuLi"} {}or RMgX/Cu2+RMgX/Cu2+ size 12{R - ital "MgX"/ ital "Cu" rSup { size 8{2+{}} } } {} adds only in 1,4- fashion, because C-4 is soft towards electrophilicity and soft cuprate reagents prefer to add only to soft centers according to HSAB (Hard Soft Acid Base ) theory. Traditional GR (alkyl magnesium halide) is intermediate in its’ reactivity, so a mixture of 1, 2- and 1, 4- addition product is obtained. Here is an example of a GR adding to a α, β unsaturated carbonyl compound:

Figure 12
Figure 12 (graphics7.jpg)

Most alcohols can be produced by a Grignard reaction. In deciding how to do this carry out the reaction, think about the Grignard reaction in reverse: if your target alcohol had been the result of a Grignard reaction, what would the carbonyl compound have to be? What would the Grignard reagent have to be?

Consider the scheme below for the synthesis of 1-phenyl-1-butanol via a Grignard reaction. Two different ways to synthesize this compound are shown. Can you think of a third?

Figure 13
Figure 13 (gscheme.png)

Important Facts:

Grignard reagent (RMgX) is a very polar reagent and a very strong Lewis base and therefore will be easily protonated by water, which acts as a strong acid when in contact with a Grignard reagent. The reagent’s reaction with water produces a gelatinous metal hydroxide. Since it reacts rapidly with the acidic hydrogen atom, the reaction must be carried out under dry conditions since even a small amount of moisture can destroy the reagent. The reactivity of Grignard reagent depends on mainly two factors:

1. Types of metal center (Li> K> Mg etc)

2. Types of halides present (I> Br> Cl) and

3. Types of solvent used.

In presence of different functional groups, the order of reactivity of GR is as follows:

Figure 14
Figure 14 (graphics8.jpg)

Our Experiment:

In this experiment, the addition of a nucleophilic Grignard reagent (1-methylbutylmagnesium bromide), to the electrophilic carbonyl carbon of an aldehyde (propanal) is performed.

Figure 15
Figure 15 (graphics9.jpg)

The product obtained is a 2° alcohol, 4-methyl-3-heptanol. A mixture of diastereomeric products is formed as the product contains two chiral centers. It is possible to vary the structure of both the Grignard reagent and the aldehyde; a wide variety of 2° alcohols is prepared by this route. Primary alcohols result when formaldehyde is used as the aldehyde. Secondary alcohols may also be obtained with these reagents when ethyl formate, an ester, acts as the electrophile. This latter reaction, however, requires two molar equivalents of the Grignard reagent. The mechanism for the reaction is as follows.

Figure 16
Figure 16 (graphics10.jpg)

PreLab Questions (Total 10 points)

Click here for the Pre-Lab

Name(Print then sign): ___________________________________________________

Lab Day: ___________________Section: ________TA__________________________

This assignment must be completed individually and turned in to your TA at the beginning of lab. You will not be allowed to begin the lab until you have completed this assignment.

1. A small crystal of iodine is used during the preparation of ‘Grignard reagent’-Why? (1 point)

2. Which solvent can we use in the preparation of GR except ether? (1 point)

3. Why is the addition of the GR to propanal solution done over the period of 30 minutes? (2 points)

4. Write the major product of the following reactions: (4 points)

graphics11.jpg graphics12.jpg

5. How will you synthesize the following molecule? (2 points)

Figure 17
Figure 17 (graphics13.jpg)

from tertBu-Br, dry ether, D2OD2O size 12{D rSub { size 8{2} } O} {} and Mg(0).


You will be assessed on:

  • Completion of Pre lab questions.
  • Write-up in your Lab Notebook (see Lab Notebook Guidelines)
  • Analysis of product by Infrared and NMR Spectroscopy
  • Completion of Post lab questions.

Materials Required

Equipment Chemicals

  • Water Bath 1. 2-bromopentane
  • Stir bar 2. Mg metal, Iodine crystals
  • Round bottom flask (10mL) 3. Propanal
  • Hirsch funnel 4. Diethyl ether
  • Beaker 5. 3M HCl, NaOH
  • Glass rod (for recrystalisation) 6. Sodium sulfate (anhydrous)


Wear gloves all the time, especially working with NaOH, HCl. Keep safety glasses on all the time.

Experimental Procedure

Part 1: Preparation of Grignard reagent

Part 2: Grignard reaction

Part 3: Isolation of product

Part 4: Characterization of product

NOTE: All the glassware used in the preparation of the Grignard reagent should be cleaned and dried in an oven at 110°C for at least 30 minutes, so you will need to plan on attending 15 minutes early on that day, dry your glassware and then attend the pre-lab lecture. (Use your glassware when it reaches room temperature, pressure builds up inside the apparatus) You will dry your glassware in the following way.  Show up to the lab 15 minutes early and dry your glassware in the oven.  The TA in charge of the lecture will then start his/her lecture on schedule.  Place all your glassware that you will need into a beaker with your name on it.  Place this in one of the ovens in the lab.  Do not put any non-glass parts in the oven.

NOTE: Check septum you are going to use for Grignard reaction. There should be no "open" holes. If septum has an obvious hole, it should be replaced with a new one.

Part 1:

Preparation of 1-Methylbutyl Magnesium Bromide:

1. Prepare a 5.0 mL conical vial containing a magnetic spin vane and equipped with a condenser. Weigh and place 75 mg (approximately 3-4 pellets) of magnesium in the vial, and then add a small crystal of iodine (Do not add excess iodine), followed by 500 µL of anhydrous ether.

NOTE: Metal magnesium you will be provided with has a coil shape and has been cut into small pieces. This material should be handled with forceps only. Four to five small pieces of Mg weigh about 75 mg.

NOTE: Plastic syringes tend to get stuck when filled with ethyl ether. Be ready to push a bit harder on a syringe plunger when adding liquid to the reaction mixture.

2. Prepare a solution of 520 µL of 2-bromopentane in 600 µL of anhydrous diethyl ether in a dry 5 mL conical vial. Use a syringe to deliver each solution. TA will do that.

3. After the assembly has cooled to room temperature, then draw the 2-bromopentane solution into a 1.0-mL syringe and then insert the syringe needle through the rubber septum on the top of the condenser. (Do not heat the closed system, it may explode!!!!)

4. While stirring the heterogeneous mixture, slowly add 6-8 drops of the 2-bromopentane ether solution to initiate the formation of the Grignard reagent. The evolution of tiny bubbles from the surface of the magnesium is evidence of a reaction.


5. When the reaction has started, slowly add the remainder of the 2-bromopentane-ether solution drop wise over a 3 to 5-min period. Warm the reactants slightly. Upon completion of this addition, draw the rinse in the capped vial into the syringe and add it through the septum in a single portion to the reaction vial. Stir the resulting solution for 15 min.


Do not overheat. Overheating will cause loss of ether solvent. (The b.p. of ether is 34.6 °C.) Small fragments of magnesium may remain at the end of the addition of the alkyl halide.

6. Cool the gray-colored solution of Grignard reagent to room temperature.

Preparation of Propanal (Propionaldehyde)

1. Prepare a solution of the aldehyde by weighing 100 µL of propanal into a tared, oven-dried, 3 mL conical vial followed by the addition of 200 µL of anhydrous diethyl ether. Cap the vial after solution is ready. The propanal is the limiting reagent and therefore an accurate weight should be recorded for the yield calculations. TA

Part 2: Grignard reaction

1. Now add the propanal solution carefully, with stirring, to the Grignard reagent over a period of about 30 sec at such a rate as to keep the ether solvent at a steady reflux.

2. Rinse the vial that contained the propanal solution with 100 µL of anhydrous diethyl ether and add to the Grignard reagent. This step insures that all the propanal is added to the Grignard reagent.

3. Stir the reaction mixture for 5 min and then allow it to cool to room temperature. Remove the conical vial and take off the cap. It is recommended that the vial be placed in a beaker to prevent tipping and loss of product.

Part 3: Isolation of Product

1. Hydrolyze the magnesium alkoxide salt by addition of 2.0 mL of water. Stir the resulting mixture for 5 min. A two-phase (ether-water) reaction mixture develops as the magnesium salt is hydrolyzed. Remove any unreacted magnesium.


The addition of water causes the evolution of heat. An ice bath should be handy to cool the solution if it begins to reflux rapidly.

2. Now add 4-5 drops of 3 M HCl. Remove the vial, cap it, and stir it at room temperature for 5 min. Remove the vial from the stir plate and test the aqueous layer with litmus paper. The solution should be slightly acidic. Too much or too little aqueous HCl will cause problems in the subsequent workup procedure. Be careful in this step. NOTE: The water layer is the bottom layer. You will need to withdraw a few drops of the aqueous layer with a Pasteur pipette and drip it onto the litmus paper.

3. Remove the magnetic spin vane with forceps and set it aside to be rinsed with an ether wash. Cap the vial tightly, shake it, vent carefully, and allow the layers to separate.

4. Using a Pasteur pipette, transfer the aqueous (lower) layer to a clean 5.0 mL vial (see picture below). Save the ether layer since it contains the crude reaction product.


5. Now wash the aqueous layer that you have previously transferred to a 5.0-mL vial, with three 1.0-mL portions of diethyl ether:

6. Hold the magnetic spin vane with clean forceps and rinse it with the first portion of ether as it is added to the vial. Upon addition of each portion of ether (using a calibrated Pasteur pipette, see picture below), cap the vial, shake it (or use a Vortex mixer), vent carefully, and allow the layers to separate. With the aid of a Pasteur pipette, remove each subsequent ether (i.e. top) layer and combine it with the ether solution retained above. After the final extraction, do not forget to save the aqueous (lower) layer until you have isolated and characterized the final product.

Figure 18
Figure 18 (graphics15.jpg)

NOTE: Pipette calibration: 1.0ml (diagram shows a previous version where we only used 0.5 mL. NOW we use 1.0 mL.) of ether which will give approximately 1.0 in height of solvent in the pipette above its "shoulder"

7. Extract the combined ether fractions with 2.0-mL of cold water to remove any acidic material.

8. Dry the ether solution by transferring it, using a Pasteur pipet, to a Pasteur filter pipet filled with 0.5g of anhydrous sodium sulfate. The elute is collected in a test tube. In the hood, remove the ether solvent from the elute by simply, putting the solution on an evaporation dish and allow the ether to evaporate.

Alternate Method of Removing Solvent: 1. Attach a Pasteur pipette to an air-line, turn the air on (gently) and place pipette in test tube to evaporate the ether (Ask TA for demonstration). 2. Gently warming the elute in a hot water bath to concentrate the solution to a weight less than 90 mg.

Part 4: Purification and Characterization

1. The product, 4-methyl-3-heptanol, will be used as is with no further purification. Once all the solvent is gone, mass the product and the test tube (the mass of which has already been recorded). Assuming no impurities, calculate the yield (remember, one of the reagents was taken in excess though).

2. Take this sample and dissolve in it in a small amount of methylene chloride (add 2 mL first then add 1 mL each time if you really need it). Prepare two TLC plates. On each plate spot both of the starting materials as well as the product mixture and standard provided by TA (i.e. four spots on each plate). Run one TLC plate in 100% Methylene Chloride, the other in 1:9 ethyl acetate: hexane. Record both plates under UV light and with the p-Anisaldehyde stain.

3. Calculate the RfRf size 12{R rSub { size 8{f} } } {} of all of the compounds for both plates. Draw TLC plates in the notebook.

4. One sample will be taken for NMR and GC-MS studies.

Waste Disposal

Syringes and needles are to be disposed separately. Needles will go into the Sharps waste basket and syringes in the waste basket. Pipettes should not go into the Sharps waste basket. Organic and inorganic waste should be disposed in their proper containers.Approximate Lab time: 2-2.30 hours

Report Questions (Total 30 points)

(Click here for the Report Form

Note: In preparing this report you are free to use references and consult with others. However, you may not copy from other students’ work or misrepresent your own data (see honor code).

Name(Print then sign): ___________________________________________________

Lab Day: ___________________Section: ________TA__________________________

1. Explain why Grignard reagents cannot be prepared from an organic halide that also contains a hydroxyl (-OH), a carboxyl ( CO2HCO2H size 12{ - ital "CO" rSub { size 8{2} } H} {}), a thiol (-SH), or an amino ( NH2NH2 size 12{ - ital "NH" rSub { size 8{2} } } {}) group. (2 points)

2. Why does the 2-bromopentane not appear under UV light for TLC? (2 points)

3. Draw and show your RfRf size 12{R rSub { size 8{f} } } {} calculations for each TLC run. Which solvent was better? (3 points)

4. Show your theoretical and percent yield calculations. (4 points)




5. Draw the structure of your product and assign a proton to each peak in your NMR spectrum. Try and determine, if any, the impurities are in the sample. (4 points)

6. An NMR and GC-MS of the product are provided. What information can you obtain from the GC-MS? (5 points)

7. Write the major product of the following reactions: (10 points)

Figure 19
Figure 19 (graphics16.jpg)
Figure 20
Figure 20 (graphics17.jpg)
Figure 21
Figure 21 (graphics18.jpg)
Figure 22
Figure 22 (graphics19.jpg)
Figure 23
Figure 23 (graphics20.jpg)

8. Identify the compounds (A-F). (Extra credit 6 points)

Figure 24
Figure 24 (graphics21.jpg)

Content actions

Download module as:

PDF | EPUB (?)

What is an EPUB file?

EPUB is an electronic book format that can be read on a variety of mobile devices.

Downloading to a reading device

For detailed instructions on how to download this content's EPUB to your specific device, click the "(?)" link.

| More downloads ...

Add module to:

My Favorites (?)

'My Favorites' is a special kind of lens which you can use to bookmark modules and collections. 'My Favorites' can only be seen by you, and collections saved in 'My Favorites' can remember the last module you were on. You need an account to use 'My Favorites'.

| A lens I own (?)

Definition of a lens


A lens is a custom view of the content in the repository. You can think of it as a fancy kind of list that will let you see content through the eyes of organizations and people you trust.

What is in a lens?

Lens makers point to materials (modules and collections), creating a guide that includes their own comments and descriptive tags about the content.

Who can create a lens?

Any individual member, a community, or a respected organization.

What are tags? tag icon

Tags are descriptors added by lens makers to help label content, attaching a vocabulary that is meaningful in the context of the lens.

| External bookmarks