Question

Grignard Reaction with a Ketone: Triphenylmethanol

Introduction: The purpose of this lab is to prepare phenylmagnesium bromide, a Grignard reagent, and react it with benzophenone to give triphenylmethanol. Grignard reagents are very reactive and must be synthesized in an environment free of water or any other source of potential proton donor. Once made, the Grignard reagent will do a nucleophilic attack on the carbonyl carbon of the ketone, benzophenone. The result is an alkoxide that is then protonated to give the alcohol, triphenylmethanol. The purity of the final product will then be characterized by melting point determination and IR spectroscopy.

Physical Constants
Compound	molecular weight (g/mol)	density (g/mL)	b. p. (°C)	m.p. (°C)
bromobenzene	157.02	1.5	156	-31
magnesium	24.3	1.74	1090	648
benzophenone	182.21	n/a	305	48
iodine	253.8	n/a	184	113
diethyl ether	74.12	0.73	34.5	-116

Chemical Procedure:

Week 1: Note: the first step may be completed the week before the scheduled lab, or any time the lab is open prior to the scheduled lab.

Clean and dry (in the oven for 15 minutes) all glassware used in the initial portion of the lab. This includes a 3 mL conical vial, two screw cap vials, Claisen head, drying tube, and spin vane.   CAREFULLY place hot items in a dessicator to cool. Cooling may take upwards of a half hour.

After cooling to room temperature, assemble the apparatus drawn above.

Attach a tared 3 mL conical vial with a spin vane to a Claisen adaptor.

One of the Claisen heads should be connected to a drying tube filled with blue CaCl₂.

The other Claisen head should have a septum with lid on the top. (See Figure 1.)

To the conical vial add 18 mg of Mg ribbon, a small crystal of iodine (to react with the MgO and “clean” the surface of the magnesium), and appr. 0.1 mL ether.

In a screw capped vial, prepare a solution of 113 mg bromobenzene in appr. 0.4 mL Et₂O.

Transfer the bromobenzene solution with a 1.0 mL syringe to the septum on Claisen head but DO NOT DEPRESS THE PLUNGER TO ADD THE SOLUTION TO THE MAGNESIUM YET.

Add an additional 0.3 mL Et₂O to the now empty screw capped vial as a rinse and set aside.

With slow stirring, add 6-8 drops of the bromobenzene solution to the reaction to form the Grignard reagent. Formation of a slightly cloudy solution is evidence of initiation of the reaction.

Once the reaction is initiated, add the remainder of the bromobenzene solution slowly over a 3-5 minute period. Unless you have added a larger crystal of iodine, the purple iodine color should have disappeared by this point.

Add the ether rinse to the reaction in a single portion.

Heat the reaction to reflux (very gentle boiling) until the Grignard reagent has been formed (as evidenced by all of the magnesium disappearing). Reflux no longer than ½ hour. During this time, keep the solvent level constant by occasionally adding more ether to the reaction vial.

Allow the solution to cool to room temperature.

Prepare a solution of 105 mg of benzophenone in 0.3 mL of anhydrous Et₂O in a dry vial with a cap.

Draw the solution into a 1.0 mL syringe and insert syringe via the septum attached to the Claisen head into the reaction.

Add 0.3 mL of Et₂O to the now empty vial and cap (a rinse for the vial that contained the benzophenone solution) and set aside for later use.

Carefully, with stirring, add the benzophenone solution to the Grignard reagent over a 30 second period or such that the temperature is no more than a gentle reflux. The solution usually turns a bright pink color at this point.

After addition, add the rinse in a single portion.

Stir the reaction for 2-3 minutes and allow to cool to room temperature.

Remove the Claisen head. Frequently during the cooling period the reaction will solidify as the relatively insoluble alkoxide salt forms.

POSSIBLE STOPPING POINT – If you are stopping here, cap your vial. The ether solvent will probably evaporate by the next lab period. If so, just add more ether at the beginning of the next period.

Hydrolyze the magnesium alkoxide salt by careful addition of dropwise 3 M HCl via Pasteur pipet and break up solid with stirring rod at same time.

Continue to add acid until litmus paper tests acidic. A two layer reaction mixture forms as solid dissolves (ether - top/water - bottom).

   Remove the spin vane.

Cap vial, then shake and vent well.   Allow the layers to separate.

Transfer the bottom aqueous layer to a clean 5.0 mL conical vial.

Wash the acidic aqueous layer with three 0.5 mL portions of Et₂O, and then rinse the spin vane with ether too and add to the vial.

After each extraction, combine the ether layers (the organic layer which contains your organic product) into a small beaker.

Set aside the aqueous layers until experiment is complete, just to be sure that we don’t throw away the desired layer by mistake….

Now extract the ether layers with 0.5 mL cold water to remove any acid residue.

Combine the bottom water layer with other aqueous layers.

Dry the ether solution with Na₂SO₄. The solution should be clear (not cloudy) when dry.

POSSIBLE STOPPING POINT

Transfer ether solution to a tared beaker with a boiling stone and boil off the ether solvent in the hood.

Obtain the weight of the crude product.

Assess the purity of the crude product by TLC using methylene chloride as the mobile phase. (R_f of triphenylmethanol is 0.6 and for biphenyl is 0.9).

Most students will have a large dot at 0.6 (the desired triphenylmethanol product) and a small dot at 0.9 (the undesired byproduct, called biphenyl). The biphenyl forms from the Grignard reagent reacting with itself in a radical like reaction. The chances of producing a lot of biphenyl markedly increase if there were mistakes made in the formation of the Grignard reagent, usually not maintaining adequate solvent during the entire reflux process. Whatever the cause, we now need to separate the desired product from the biphenyl impurity.

Add 2 mL ligroin (petroleum ether) to the crude product. Ligroin is a mixture of hydrocarbons, so is very nonpolar and will readily dissolve the nonpolar biphenyl impurity. The desired triphenylmethanol product is not very soluble in ligroin and hopefully remains as a solid.

Pipette off the pet ether liquid and leave the solid triphenylmethanol in the beaker.

Repeat the process by adding a second portion of ligroin.

Check the purity of the remaining solid by TLC.

Repeat the ligroin washes, if necessary, ideally until the solid is one spot by TLC. Comment on the purity of your product by the TLC analysis.

Allow the product to air dry or oven dry briefly.

Weigh the purified triphenylmethanol and calculate percent yield.

Obtain the melting point of triphenylmethanol (m.p. 164 ^oC). Comment on purity.

Obtain IR spectrum of triphenylmethanol and compare to reference.

NOTE: the ligroin washings remove the biphenyl impurity from the triphenylmethanol product. Another potential impurity is the benzophenone starting material. Any traces of benzophenone, however, should be readily apparent by analysis of the experimental IR spectrum.

Assigned Questions:

Show complete arrow pushing mechanisms for the formation of the major and minor products.

2-What was the purpose of adding the iodine to the magnesium?

3-Why is ligroin able to separate your compounds?

4-Occasionally, some of the benzophenone is purified with the triphenylmethanol. How would you detect the presence of benzophenone using the IR?

Answer 1

Answer –

1) We are given phenylmagnesium bromide, a Grignard reagent, and react it with benzophenone to give triphenylmethanol

Reaction –

benzophenone он triphenylmethanol

2) The purpose of adding the iodine to the magnesium is the cleaning the surface of Mg metal. When we added ionide to the Mg then there is reacted with oxide formed on the Mg metal, means iodine reacts with MgO and clean the surface of Mg meatal, so we will get pure Mg metal rather than impure.

3) The product of reaction triphenylmethanol is not soluble in the ligroin, because ligroin is hydrocarbon and which is very nonpolar and triphenylmethanol is polar, so they are not soluble in each other, so triphenylmethanol easily separated from the impurities like biphenyl, Biphenyl is nonpolar and easily dissolve in ligroin and get easily remove from the product.

4) If in the product there are some amount of benzophenone then we can detect using the IR. For product triphenylmethanol there is major peak for –OH which is around 3000-3300 cm^-1 and in the benzophenone the major peak in IR is for carbonyl and it is around 1680 to 1700 cm^-1.So if in our product there is impurity like benzophenone then there is show peak around 1680 to 1700 cm^-1and we can easily detect the benzophenone in the triphenylmethanol.