Grignard Synthesis of Triphenylmethanol
The following experiment has been adapted from experiments in Fieser and Williamson’s
Organic Experiments , seventh edition.
In 1912 Victor Grignard received the Nobel prize in chemistry for his work on the reaction that bears his name, a carbon-carbon bond-forming reaction by which almost any alcohol may be formed from appropriate alkyl halides and carbonyl compounds. The Grignard reagent is easily formed by reaction of an alkyl halide, in particular a bromide, with magnesium metal in anhydrous ether. Although the reaction can be written and thought of as simply:
R Br + Mg R Mg Br it appears that the structure of the material in solution is rather more complex. There is evidence that dialkylmagnesium is present:
R Mg Br R Mg R + MgBr
2 and that the magnesium atoms, which have the capacity to accept two electron pairs from donor molecules to achieve a four-coordinated state, are solvated by the unshared pairs of electrons on ether:
Et
O
Et
R Mg Br
Et
O
Et
The Grignard reagent is a strong base and a strong nucleophile. As a base it will react with all protons that are more acidic than those found on alkenes and alkanes. Thus, Grignard reagents react readily with water, alcohols, amines, thiols, etc., to regenerate the alkane
The starting material for preparing the Grignard reagent can contain no acidic protons.
The reactants are apparatus must all be completely dry; otherwise the reaction will not start. If proper precautions are taken, however, the reaction proceeds smoothly.
The magnesium metal, in the form of turnings, has a coat of oxide on the outside. A fresh surface can be exposed by crushing a piece under the absolutely dry ether in the presence of the organic halide. Reaction will begin at the exposed surface, as evidenced by a slight turbidity in the solution and evolution of bubbles. Once the exothermic reaction starts it proceeds easily, the magnesium dissolves, and a solution of the Grignard reagent is formed. The solution is often turbid and gray due to impurities in the magnesium. The reagent is not isolated but reacted immediately with, most often, an appropriate carbonyl compound:
O O
-
MgBr
+
R Mg Br +
R' R"
R' R"
R to give, in another exothermic reaction, the magnesium alkoxide. In a simple acid-base reaction this alkoxide is reacted with acidified ice water to give the covalent, ether-soluble alcohol and the ionic water-soluble magnesium salt:
O
-
MgBr
+
R' R" + HCl
R'
OH
R" + MgBrCl
R
R
Grignard - 1

The great versatility of this reaction lies in the wide range of reactants that undergo the reaction as shown below:
O
CH
O
CCH
2
OCH
3
H
HC(OC
2
H
5
)
3
CH
3
OCH
2
CN
OC(CH
3
)
3
COH
3
C
6
H
5
O
C OOC(CH
3
)
3
10
11
O
EtO C OEt
9
12
MgBr
1
3
4
8
2
H
2
O
(CH
3
O)
2
SO
2 7
6
5
O
2
CO
O
2
CH
3
H
CH
3
O
CH
OH
CCH
3
CH
3
O
C CH
2
CH
3
O
HCH
CH
3
OH
C CH
2
CH
3
CH
2
OH
OH
CO
CH
2
CH
2
OH
2
H
In every case except reaction 1 the intermediate alkoxide must be hydrolyzed to give the product.
The reaction with oxygen (reaction 2) is usually not a problem because the ether vapor over the reagent protects it from attack by oxygen, but this reaction is one reason why the reagent cannot usually be stored without special precautions. Reactions 5, 6 and 7 with ketones and aldehydes giving tertiary and secondary alcohols are among the most common. Reactions 8-12 are not nearly so common.
In the experiment we shall carry out another common type of Grignard reaction, the formation of a tertiary alcohol from two moles of the Grignard reagent and one of an ester. The initially formed product is unstable and decomposes to a ketone, which, being more reactive than an ester, immediately reacts with more Grignard reagent:
Grignard - 2

Br
Mg ether
Bromobenzene
MW 157.02
bp 156.4°C d 1.49
MgBr
+
CH
3
O
C
O
Methyl benzoate
MW 136.16
bp 199.6°C d 1.09
O
OCH
3
MgBr
OH
OMgBr
O
MgBr
Triphenylmethanol
MW 260.34
mp ~164°C
The primary impurity in the present experiment is biphenyl, formed by the reaction of phenylmagnesium bromide with unreacted bromobenzene. The most effective way to lessen this side reaction is to add the bromobenzene slowly to the reaction mixture so it will react with the magnesium and not be present in high concentration to react with previously formed Grignard reagent. The impurity is easily eliminated since it is much more soluble in hydrocarbon solvents than triphenylmethanol.
Experiment
*All manipulations must be done in your hood.*
Formation of the phenylmagnesium bromide (Phenyl Grignard) reagent
All apparatus and reagents must be absolutely dry . The Grignard reagent is prepared in a dry three-necked round-bottomed flask fitted with a long reflux condenser and a dropping funnel. A calcium chloride drying tube inserted into the thermometer fitment that will fit on the thermometer adapter and placed on the top of the condenser is also made ready. The flask, condenser, and magnesium (2 g = 0.082 mole of magnesium turnings) should be as dry as possible to begin with, and then the magnesium is placed in the flask, and the rest of the apparatus is assembled (except for the calcium chloride drying tube). The apparatus is heated gently but thoroughly with a cool luminous flame from the bottom to the top (note the appearance of water vapor condensing on the cool glass above the area you are heating--you need to drive that water up and out of the glassware). Do not overheat the magnesium. It will become deactivated through oxidation, or, if strongly overheated, can burn. Place the drying tube containing the calcium chloride onto your apparatus so that as the glassware cools, it pulls dry air through the calcium chloride. Cool to room temperature before proceeding! Extinguish all flames and wait until your instructor gives you anhydrous ether . Note that ether vapor is denser than air and can travel along bench tops and into sinks.
Grignard - 3

Make an ice bath ready in case control of the reaction becomes necessary, although this is usually not the case. Your instructor will pour into the flask, through the unused joint, 15 mL of absolute ether (absolutely dry, anhydrous). Being sure that your graduated cylinder is absolutely dry, add 9 mL (13.5 g = 0.086 mole) of bromobenzene. (More ether is to be added as soon as the reaction starts, but at the outset the concentration of bromobenzene is kept high to promote easy starting.) If there is no immediate sign of reaction, insert a dry stirring rod with a flattened end and crush a piece of magnesium firmly against the bottom of the flask under the surface of the liquid, giving a twisting motion to the rod. When this is done properly the liquid becomes slightly cloudy, and ebullition commences at the surface of the compressed metal. Be careful not to punch a hole in the bottom of the flask. Swirl the flask to provide fresh surfaces for contact, and, as soon as you are sure that the reaction has started, add 25 mL more absolute ether before spontaneous boiling becomes too vigorous. Note the volume of ether in the flask. Cool in ice if necessary to slow the reaction but do not overcool the mixture; the reaction can be stopped by too much cooling. Any difficulty in initiating the reaction can be dealt with by trying the following expedients in succession.
1.
Warm the flask with your hands or a beaker of warm water. Then see if boiling continues when the flask (condenser attached) is removed from the warmth.
2.
Try further mashing of the metal with a stirring rod.
3.
Add a tiny crystal of iodine as a starter.
4.
This can only be done with permission of the instructor: Start afresh, taking greater care with the dryness of apparatus and reagents.
Once the reaction begins, spontaneous boiling in the diluted mixture may be slow or become slow. If so, heat the flask with your heating mantle and reflux gently until the magnesium has disintegrated and the solution has acquired a cloudy or brownish appearance.
The reaction is complete when only a few small remnants of metal (or metal contaminants) remain. Check to see that the volume of ether has not decreased. If it has, add more anhydrous ether. Since the solution of Grignard reagent deteriorates on standing, the next step should be started at once.
Synthesis of Triphenylmethanol
Your instructor will pour 15 mL of anhydrous ether into your separatory funnel, and then you will add 5 g (0.037 mole) of methyl benzoate to the separatory funnel, and swirl to mix. Cool the flask containing phenylmagnesium bromide solution briefly in an ice bath. Run in the methyl benzoate solution slowly with only such cooling as is required to control the mildly exothermic reaction, which affords an intermediate addition compound that separates as a white solid. Swirl the flask continuously until the methyl benzoate is completely added. Complete the reaction by heating the mixture at reflux for one-half hour (hot water from the tap works well).
Pour the reaction mixture into a 250-mL Erlenmeyer flask containing 50 mL of 10% sulfuric acid and about 25 g of ice and use both ordinary ether and 10% sulfuric acid to rinse the flask. Swirl well to promote hydrolysis of the addition compound; basic magnesium salts are converted into water-soluble neutral salts and triphenylmethanol is distributed into the ether layer. An additional amount of ether (ordinary) may be required. Pour the mixture into a separatory funnel (rinse the flask with ether), shake, and draw off the aqueous layer. Shake the
Grignard - 4

ether solution with 10% sulfuric acid to further remove magnesium salts, and wash with saturated sodium chloride solution to remove water that has dissolved in the ether. The amounts of liquid used in these washing operations are not critical. In general, an amount of wash liquid equal to one-third of the ether volume is adequate.
To effect final drying of the ether solution, pour the ether layer out of the neck of the separatory funnel into an Erlenmeyer flask, add about 5 g of granular anhydrous sodium sulfate.
Swirl the flask from time to time, and after 5 min remove the drying agent by gravity filtration into a tared Erlenmeyer flask. Rinse the drying agent with a small amount of ether. Add 25 mL of 66-77 o
C ligroin and concentrate the ether-ligroin solutions (hot plate) in an Erlenmeyer flask in the hood. Evaporate slowly until crystals of triphenylcarbinol just begin to separate and then let crystallization proceed, first at room temperature and then at 0 o
C. The product should be colorless and should melt not lower than 160 o
C.
Turn in, as directed, the product in a vial labeled with your name, the name of the compound, its melting point, and the overall percent yield from methyl benzoate.
Cleaning Up Combine all aqueous layers, dilute with a large quantity of water, and flush the slightly acidic solution down the drain. The ether/ligroin mother liquor from the crystallization goes in the organic solvent container. Calcium chloride from the drying tube should be dissolved in water and flushed down the drain.
Questions
1. How would you make the following compound from diethylcarbonate and an appropriate
Grignard reagent?
HO
2.
3.
4.
What product would be obtained if your methyl benzoate were contaminated with D
2
O?
If you wanted just enough phenyl magnesium bromide to react completely with 100 mg of dry ice, how many grams of bromobenzene would you start out with (assume 100% conversion of bromobenzene to the Grignard reagent)?
How could you make 1-ethylcyclopentanol using a Grignard reaction?
Grignard - 5