Preparation of a Phenylalcohol by a Grignard Reaction

CH344Bruce A. Hathaway

1

The Reaction

Br MgBrM g

ether

1.

2. HCl, HOH

R1 C R2

O

R1 C R2

OH

2-butanone 2-pentanone 3-pentanone

2

CH3 C

O

CH2CH3 CH3 C

O

CH2CH2CH3 CH3CH2 C

O

CH2CH3

Safety Issues

• Bromobenzene causes eye and skin irritation, and inhalation, ingestion, or skin absorption may be harmful. Avoid contact with the liquid and do not breathe its vapors.

• Ethyl ether is extremely flammable and may be harmful if inhaled. Do not breathe its vapors and keep it away from flames and hot surfaces.

• Magnesium can cause dangerous fires if ignited; keep it away from flames and hot surfaces.

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The Apparatus• Put some cotton in the

drying tube, followed by CaCl2, then by more cotton.

• Put the iodine, Mg, and a stir bar in the round-bottomed flask before you assemble the apparatus.

• Assemble the apparatus, then remove the thermowell by removing the stirrer; then replace the stirrer.

• Start the water flowing slowly through the condenser.

Thermowell

Water In

Water Out

To transformer

Drying tube

Neoprene AdapterThermometer Adapter

WestCondenser

ClaisenAdapter

AdditionFunnel

Ground-GlassStopper

Magnetic Stirrer

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Reaction of Bromobenzene• Add a crystal of iodine to the round-bottomed

flask. • Weigh out about 0.7 - 0.8 grams of magnesium

turnings into a weigh boat. • Transfer them to a mortar, and grind them for

about a minute, to expose the shiny magnesium. • Weigh 0.6 - 0.7g (record exactly what you use) of

clean, dry magnesium turnings and transfer then to the round-bottomed flask.

• Add a stir bar to the round-bottomed flask.

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Reaction of Bromobenzene• Weigh 4.0g of dry bromobenzene into a 25 mL

dry Erlenmeyer flask and dissolve it in 5 mL of anhydrous ethyl ether.

• Transfer this solution to the addition funnel and stopper it, placing a tiny strip of filter paper between the stopper and the neck of the funnel.

• Add the bromobenzene solution all at once to the reaction flask.

• Replace the bromobenzene solution in the addition funnel by 8 mL of anhydrous diethyl ether.

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Reaction of Bromobenzene

• Begin stirring the solution, and observe the reaction mixture closely for evidence of a reaction, such as cloudiness and the evolution of bubbles from the magnesium surface.

• If the reaction does not begin within 5 minutes or so, consult your instructor.

• When the reaction mixture begins to boil quite vigorously without external heating, add the ether drop by drop at a rate just sufficient to keep the reaction mixture boiling.

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Reaction of Bromobenzene• When all the ether has been added, let the reaction

continue until the boiling has nearly stopped, then use a heating mantle or thermowell to heat the reaction mixture under gentle reflux for another 15-20 minutes.

• The reflux ring of condensing ether should be in the lower third of the condenser.

• If a significant amount of ether evaporates, reducing its volume in the reaction flask, replace it with fresh anhydrous ether.

• Do not stop at this point, because the phenylmagnesium bromide solution will not keep for long.

• Remove the thermowell, but keep the reaction stirring while you do the next part.

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Reaction of Phenylmagnesium Bromide• Dissolve 1.4-1.5g of 2-butanone, or 1.7-1.8g of 2-

pentanone or 3-pentanone, in 20 ml of anhydrous diethyl ether in a dry Erlenmeyer flask and place it in the addition funnel.

• When the reaction mixture has cooled so that the ether is no longer boiling, add this solution drop by drop to the reaction mixture with shaking or magnetic stirring.

• The addition rate should be sufficient to keep the ethyl ether boiling gently without external heating.

• When the addition is complete, use a heating mantle or thermowell to heat the reaction mixture under gentle reflux for another 30 minutes.

• Remove the thermowell to allow the reaction to cool.

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Reaction of Phenylmagnesium Bromide

• After the reaction mixture has cooled to room temperature, add 5 mL of water drop by drop through the addition funnel while shaking or stirring, and then add 25 mL of 5% (1.4 M) hydrochloric acid. (We are using 1M HCl).

• Wait for the reaction to subside and continue stirring or shaking until most or all of the white solid has dissolved (some magnesium may remain undissolved).

• If any undissolved white solid remains, detach the reaction flask from the apparatus and use a spatula to break up the solid, then shake the capped flask, adding enough diethyl ether or 5% HCl as needed to dissolve all of the solid.

• There must be at least 20 mL of ether in the reaction mixture at this time; if necessary, add diethyl ether to replace any ether that evaporated.

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Separation of the Product

• If there is undissolved magnesium present, remove it by gravity filtration through your Hirsch funnel without filter paper, washing the magnesium with a small amount of diethyl ether.

• Transfer the reaction mixture to a separatory funnel, and shake gently to mix the layers thoroughly.

• Allow the layers to separate, then drain out and discard the lower aqueous layer.

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Separation of the Product

• Carefully wash the ether layer with 15 mL of 5% aqueous sodium bicarbonate.

• Then wash the ether layer with 15 mL of saturated aqueous sodium chloride.

• Dry the ether solution over anhydrous magnesium sulfate, and filter it into a dry round-bottomed flask.

• Evaporate the ether using a rotovap. Put the round-bottomed flask in your drawer until next lab period.

• Hopefully, everyone will get at least this far!• We will stop here for the day.

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Thin Layer Chromatography

• Draw a pencil line 1 cm from the bottom of a silica-gel TLC plate.

• Make 2 tic marks on the line. • Dissolve a tiny amount of your product in

several drops of acetone, and spot it on one of the tic marks.

• Finally, spot the TLC standard of biphenyl on the remaining tic mark.

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Thin Layer Chromatography• Make sure you write down what compound is

spotted on each tic-mark in your notebook. • Check the TLC plate under a UV lamp to

determine if you spotted enough material. • Put a folded piece of filter paper in a 400 mL

beaker, and add 10 mL of 1:19 ethyl acetate:hexane solvent.

• Swirl the beaker to wet the filter paper, and then place the TLC plate in the beaker.

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Thin Layer Chromatography• Cover the beaker with a watch glass, and allow the

solvent to rise within 1-2 cm of the top of the plate. • Remove the plate, draw a pencil line at the solvent

front, wave the plate in the air to evaporate the solvent off of it, and check the plate under a UV lamp.

• Be sure to circle all of the spots. • Pour the solvent into the “Non-Halogenated Water-

Insoluble Organic Waste" bottle.• Keep the TLC plate: you will be turning it in with your

report.

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Finishing Up• When you are finished with the hexanes filtrate,

pour it into the “Non-Halogenated Water-Insoluble Organic Waste" bottle in the hood.

• You will take an IR spectrum of your product.• I will collect your product during the next lab

period. • Label a product vial as follows:

– Product name– Weight– Melting point range– Your name(s)

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