Preparation of a Phenylalcohol by a Grignard Reaction CH344 Bruce A. Hathaway 1

The Reaction 2-butanone2-pentanone3-pentanone 2

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. 3

The Apparatus Put some cotton in the drying tube, followed by CaCl 2, 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. 4

Reaction of Bromobenzene Add a crystal of iodine to the round-bottomed flask. Weigh out about 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 g (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. 5

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. 6

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. 7

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 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. 8

Reaction of Phenylmagnesium Bromide Dissolve g of 2-butanone, or g 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. 9

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. 10

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. 11

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. 12

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. 13

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. 14

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. 15

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) 16