Grignard Reaction: Grignard Reaction: Preparation of Preparation of TriphenylmethanolTriphenylmethanol

BackgroundBackground

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.

This reagent was discovered by Victor Grignard around 1900.

R'-X + Mg [ R'-X ]- + Mg+ R' - MgXδ- δ+

BackgroundBackground

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.

The Grignard reaction results in the formation of a carbon-carbon bond.

Grignard reagents are extremely strong bases that can react violently with hydroxyliccompounds such as water or alcohols:

Experimental TechniquesExperimental Techniques

C

O

OCH3+MgBr COMgBr

3

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 dibromoethanecan help to clean the surface of the magnesium.

Today's experiment is preparation of triphenylmethanol using a Grignard reagent.

COMgBr

3

H2SO4COH

3

BrMg

EtherMgBr . 2Et2O

MgBr . 2Et2O + C

O

H3CO

Mechanism:

CH3CO

OBr-Mg

+2

MgBr . 2Et2O CO

+

+ BrMgOCH3C O MgBr- +

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 (CaCl2)

5. a nitrogen or argon line supplying a dry, inert atmosphere (not today)

C O MgBr C O HH3O+- +

Cautions:NO washing glassware with water – today! Use acetone if necessary.

Et2O (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 ºC so DO NOT set max setting for the

temperature controller. USE 40 ºC 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 oxidefrom magnesium metal surface using mortar and pestle.

Experimental ProceduresExperimental Procedures

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 CaCl2as the drying agent.

USE WARM WATER BATH 40 ºC 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 air.

Do not use the hot plate!!!

Equipment SetEquipment Set--UpUp

Drying columns are to be placed at the opening of the addition funnel and the condenser

1. Grignard Reagent Preparation:1. Grignard Reagent Preparation:

100 mL RB flask containing 2 grams magnesium metal

A water-cooled condenser keeps ether (Et2O) vapors from escaping

Dry the entire assembly from the bottom to top with your heat gun.

Put drying tubes in place while the equipment is hot. (AFTER HEATING)

TA provides 9 mL bromobenzene.

Then add bromobenzene and 50 mLEt2O 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.

When the reaction begins (cloudy or grayish), you will see bubbles in solution.

If no reaction begins after 5 minutes, go get your TA.

If the reaction doesn’t start: TA adds 3-5 drops dibromoethane or a couple of crystals I2.

Continue to monitor the reaction.

Once reaction begins, add the remaining solution of bromobenzene in Et2O (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 ºC warm water bath to avoid overheating the system.

1. Grignard Reagent Preparation:1. Grignard Reagent Preparation:

2. 2. TriphenylmethanolTriphenylmethanol Preparation: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 Et2O into the addition funnel.

Slowly add from the funnel to the cooled solution.

Reflux for 30 min with 40 ºC warm water bath.

RMgX

Prepare 25 grams crushed ice and 50 mL 10% H2SO4

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.)

3. Quenching:

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 layer through the stopcock.

Aqueous layer- Discard

Wash ether layer with saturated NaCl (1/3 volume of ether layer).

Dry ether layer over Na2SO4 then filter through cotton plug in glass funnel into preweighed round bottomed flask.

Remove ether using rotary evaporation. Use house vacuum to remove last ether traces.

SAVE small sample of crude product for TLC.

Might see fine layer between top and bottom phases so it should be removed through stopcock (may be metal bits)

4. Work-up of the Reaction:

Keep the top layer (ether layer)

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.

Perform TLC on the crude product, petroleum ether extract, and pure productby 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.

5. Characterization of Your Product:

4. Work-up of the Reaction (Week 2):