Grignard Reaction: Preparation of Triphenylmethanolwl Background > Grignard reagents are highly reactive organometallic reagents generated by treating alkyl or aryl halides with magnesium metal in the presence of an anhydrous ether. > The reaction proceeds like a strong base reaction & & R-X + Mg ——*> [R'X] + Mgt ——> R'-MgX > This reagent was discovered by Victor Grignard around 1900.wl Background > A Grignard reagent is capable of reacting with many different substrates such as carbonyl compounds, alkyl halides and other organometallic reagents. > The addition of Grignard reagents to carbonyl compounds such as aldehydes, ketones, and esters yields the corresponding secondary and tertiary alcohols. Oo) O- Mg*X OH Il I H30 + ! R'—MgX + A—C—A RGR —=——- APR a R R Q @) >» The Grignard reaction results in the formation of a carbon-carbon bond. > Grignard reagents are extremely strong bases that can react violently with hydroxylic compounds such as water or alcohols: R—MgBr + H—-OH ——+ R—H + HOMgBrExperimental Techniques > In the laboratory, initiation of the Grignard reaction is sometimes very slow. Because of the presence of air, a coating of magnesium oxide forms on the magnesium metal turnings. > To initiate the reaction, adding a small crystal of iodine or a drop of dibromoethane can help to clean the surface of the magnesium. > Today's experiment is preparation of triphenylmethanol using a Grignard reagent. ~ ethe: é \ > Br + Mg —_ (_ M98 bromobenzene magnesium phenylmagnesium bromide Ore OL (Cm (ree = (Oha Mg Br stein ether a 2640 ang “ C pope OG~ 2 2E,0 gad + BigoCh,Water sensitive chemical reactions require: 1. thoroughly dried glassware (no visible water!) 2. rigorously dried, anhydrous grade reagents 3. heat gun dried glassware (eliminate invisible water!) 4. a drying tube packed with a drying agent (CaCl,) 5. a nitrogen or argon line supplying a dry, inert atmosphere (not today)vv v v wl Experimental Procedures NO washing glassware with water — today! Use acetone if necessary. Et,0 (diethyl ether) is extremely flammable!!! Adequately grease all joints to avoid leakage of fumes. Use only fresh (new) anhydrous diethyl! ether. The boiling point of diethyl ether is 35 °C so DO NOT set max setting for the temperature controller. USE 40 °C water bath set on top of heating mantle. Also, dry your 10 mL graduated cylinder and 100 mL Erlenmeyer flask with the heat gun before use and tightly cover with aluminum foil Remove the magnesium oxide from magnesium metal surface using mortar and pestle.wl Equipment Set-Up > No boiling chips with the Mg. > Assemble as shown on right, except need to add drying tubes. Your TA will show you how to assemble the drying tubes with CaCl, as the drying agent » USE WARM WATER BATH 40 °C as heat, source, using the large beaker. Place the bath on wire gauze on top of the heating mantle. Monitor the temperature during the reaction. > DO NOT use Aluminum Foil around the set-up! Remove the heat source when you open the reflux set up to the ai Do not use the hot plate!!!wl 1. Grignard Reagent Preparation: A water-cooled condenser keeps ether (Et,0) vapors, > Put drying tubes in place while the from escaping equipment is hot, (AFTER HEATING) >_TA provides 9 mL bromobenzene. Then add bromobenzene and 50 mi Et,0 into the additional funnel > Add just enough of the solution of bromobenzene in ether to cover Mg then let the solution sit for 5 min to initiate reaction. Warm with hands. f 100 mL RB flask containing 2. grams magnesium metal > Dry the entire assembly from the bottom to top with your heat gun. > When the reaction begins (cloudy or grayish), you will see bubbles in solution. > Ino reaction begins after 5 minutes, go get your TA.wl 1. Grignard Reagent Preparation: > If the reaction doesn't start: TA adds 3-5 drops dibromoethane or a couple of crystals Ip. > Continue to monitor the reaction. > Once reaction begins, add the remaining solution of bromobenzene in Et,O (NOT too slow and NOT all at once) by steady dripping. > Maintain a gentle reflux for 30 minutes — the applied heat will expedite the reaction. Monitor the 40 °C warm water bath to avoid overheating the system.wl 2. Triphenylmethanol Preparation: ® Cool RMgX solution in ice bath for 5 min before going to the next step. > You will use the existing set-up for the next step. DO NOT EXPOSE SOLUTION TO AIR!!! Add 5 g methyl benzoate and 15 mL Et,0 into thi idition funnel » Slowly add from the funnel to the cooled solution. » Reflux for 30 min with 40 °C warm water bath. 3. Quenching: » Prepare 25 grams crushed ice and 50 mL 10% H,SO, then add them into your E.flask. > When you finish refluxing the reaction mixture for 30 min, pour it into that E.flask. (O - is protonated and the bases are neutralized.)wl 4. Work-up of the Reaction: > Stir or swirl to dissolve lumps in your E.flask — you may use a stirring rod to gently break up lumps. > Transfer the solution to a separatory funnel, then drain the aqueous through the stopcock. Keep the top layer (ether layer) Might see fine layer between || we top and bottom phases so it layer should be removed through stopcock (may be metal bits) +—— Aqueous layer- Discard > Wash ether layer with saturated NaCl (1/3 volume of ether layer). > Dry ether layer over Na,SO, then filter through cotton plug in glass funnel preweighed round bottomed flask. > Remove ether using rotary evaporation, Use house vacuum to remove last ether into traces. > SAVE small sample of crude product for TLC.wl 4. Work-up of the Reaction (Week 2): » Triturate residue in distilling flask with cold petroleum ether (not diethyl ether). ...to reduce to fine particles or powder by rubbing, grinding, bruising, or the like. > Decant petroleum ether (SAVE small sample of ether for TLC). > Recrystallize from isopropyl alcohol to obtain the pure product. 5. Characterization of Your Product: > Perform TLC on the crude product, petroleum ether extract, and pure product by using diethyl ether to dissolve all solids and using petroleum ether as your eluent. > Measure the mass and mp, and calculate % yield. Grading is 50% for write up and 50% for results.