Experiment 2

Grignard Synthesis: Synthesis of Benzoic Acid and of Triphenylmethanol

Background

In this experiment, you will prepare the Grignard reagent, phenylmagnesium bromide.  

Phenylmagnesium bromide will be used to produce either benzoic acid (reaction with CO2) or triphenylmethanol when reacted with benzophenone (or ethyl benzoate). The organic portion of the Grignard reagent functions as a carbanion nucleophile.  After reaction, the desired product (an alcohol, as shown here) is formed after acidic hydrolysis.  

You must keep your reaction apparatus and reagents completely dry because water functions as an acid, and would cleave the Grignard reagent producing benzene.  All glassware must be thoroughly clean and dry.  After washing any glassware, you should remove any visible appearance of water with a heat gun, and then bake your glassware for at least 30 minutes at 110oC.  While you are drying your glassware, you should assemble a drying tube containing CaCl2 and place it in the oven too.  Be certain not to put any plastic items into the oven because they could melt or become distorted.  

Please note that the Grignard reagent that you prepare, is used for two separate reactions. The first is for the synthesis of benzoic acid (Part A) and the second if for the preparation of triphenylmethanol (Part B). After the Grignard reagent is prepared, both Part A (Day 1) and Part B (Day1) experiments must be performed. In other words, all of the Grignard reagent will be reacted the day it is made, half of which is used in Part A in a beaker containing the dry ice, and the other half used in Part B, in the same glassware as used to prepare the Grignard reagent.

Preparation of the Grignard reagent, phenylmagnesium bromide

The reaction apparatus is setup as follows (all items must be clean and dry):

(The other glassware, such as beakers and graduated cylinders, which will be used for dispensing and measuring the anhydrous ether, should also have been baked.)

The reaction is set up and performed as follows (Prepare an ice bath to cool the solution if the reaction becomes too vigorous):

Cloudiness and bubbles at the surface of the metal are indicators that the reaction has begun.  This may take up to 5-10 minutes.  If no reaction is apparent at the end of 5 min, add a small crystal of iodine.  If the reaction still doesn't start, consult the instructor, and you will likely need to start over.  

Once the reaction has started, turn on the cooling water in the condensor and start the stirrer.  Add the remainder of the bromobenzene/diethyl ether solution slowly, and dropwise, to maintain a steady reflux.  Too rapid addition might result in the formation of diphenyl (draw the structure and predict the reaction mechanism).  This addition step should take about 45 min.  After the bromobenzene solution has been added, rinse the addition funnel with an additional 3 mL of anhydrous diethyl ether and add this rinse to the round-bottom flask.  

Fit the flask with a heating mantle and reflux gently for an additional 15 min.  The final Grignard mixture should be cloudy and most of the Mg metal should be gone.  Cool the mixture to room temperature and then add enough anhydrous diethyl ether to give a final of volume of about 40 mL in the reaction flask. The Grignard reagent must be used immediately after it has cooled.

You will use the Grignard reagent for the two reactions described in Parts A and B.Use about half (~20 mL) of the freshly prepared phenylmagnesium bromide (Grignard reagent) for each of these reactions (you do not need to measure precisely in a graduated cylinder).

The Grignard reagent must be used the day it is prepared, and the Day 1 section for each experiment must be performed the same day you made the Grignard reagent.

Caution:  Diethyl ether is volatile and an anesthetic (it can make you dizzy and lightheaded).  At no time is ether allowed to be in the open lab unless it is in a covered, or closed container (e.g., stoppered separatory funnel or other container).  Always dispense ether in the hood, and replace the lid immediately after use.  Use of ether in any open container must be conducted in the hood (e.g., ether in a beaker, or during filtrations).  Ether can be used in a separatory funnel outside the hood.  No exceptions will be allowed!

Part A. Synthesis of Benzoic Acid from Phenylmagnesium Bromide

Day 1:

The formation of benzoic acid is shown below.

When the phenylmagnesium bromide has cooled to room temperature, transfer about half of the Grignard reagent (keep the remaining half in the reaction vessel for reaction in Part B) as quickly as possible to a beaker containing about 5 g of crushed dry ice (excess dry ice is not a problem, as it will sublime).  After crushing the dry ice in a mortar and pestal, transfer it to the beaker as quickly as possible to avoid water condensation.  After you have added the phenylmagnesium bromide, cover the reaction container with a watch glass until all the dry ice has sublimed.  The Grignard reaction product should appear as a viscous glassy mass with a brownish color.

Hydrolyze the Grignard adduct by slowly adding about 10 mL of 3 M HCl, with stirring, to the beaker.  Any unreacted Mg will dissolve in the excess HCl (make certain that the liquid is acidic, using litmus paper).  You should also have two distinct phases in the beaker (the upper ether phase and the lower aqueous phase).  If any solids are present, except for excess Mg, you should add a little more ether (which should dissolve the organic material).  If the solid does not dissolve into the ether phase, you might add an additional amount of HCl.  The benzoic acid, which is mostly insoluble in water, will be dissolved in the ether phase, since the acid is not ionized in acidic solution. Transfer both phases to a flask for storage until the next lab period.  Rinse the beaker with a little ether and then transfer this wash material to the storage flask.  At this point, you should place a ground-glass stopper into the top of the flask, and wrap with parafilm until the next lab period.  Be sure to label your flask.  The ether layer contains dissolved benzoic acid.

Be sure to do the Day 1 experiment for Part B today with the remaining Grignard reagent!

STOP AND STORE THIS PART OF THE EXPERIMENT UNTIL THE NEXT LAB PERIOD!

Day 2:

To purify your benzoic acid, transfer all of your material into a small separatory funnel.  You might need to wash the storage flask with a little ether to make certain all your organic material has been transferred (are crystals still in your flask?).  Let the two phases separate and remove the lower aqueous phase, which will be discarded, but keep all material until you are sure you have the correct material.  If two phases are not apparent, you might try adding a little extra water, or HCl.  After the aqueous phase has been removed, wash the top ether phase which contains the dissolved benzoic acid with 5% NaOH, which will convert the benzoic acid into the benzoate ion which partitions into the lower aqueous layer.  Collect and save the basic aqueous layer after each wash.  Repeat the 5% NaOH extraction one or two more times, collecting the lower aqueous layer and combining with the previous washes.  Any diphenyl will stay in the ether phase, allowing you to collect only benzoic acid.  (Use minimal amounts of wash solution.  Each NaOH wash should contain less than 10 mL of NaOH solution.  Keep your wash volumes small, to allow for optimal crystallization of the benzoic acid.)

Heat the combined aqueous phases to boiling in the hood, using a heating plate, until all the ether has boiled (no flames allowed).  Cool the alkaline solution and precipitate the benzoic acid by add enough 6 M HCl to make the solution acid to litmus.  Cool (to reduce the amount of dissolved benzoic acid) and collect the solid by vacuum filtration.  Repeat the crystallization step, to repurify the benzoic acid, and collect the crystals by filtration.  Use ice cold water to wash the container of crystals during the filtration step.  Allow the crystals to dry thoroughly unti the next lab period at room temperature in a dessicator.  

STOP AND STORE THIS PART OF THE EXPERIMENT UNTIL THE NEXT LAB PERIOD!

Day 3:

Weigh the solid and calculate the percentage yield of benzoic acid.  Determine the melting point of the dry and recrystallized benzoic acid.

Part B. Synthesis of Triphenylmethanol from Benzophenone and Phenylmagnesium Bromide

Reaction of phenylmagnesium bromide with benzophenone is shown below.  This reaction, like the reaction to produce the benzoic acid must be completed the first day, immediately after preparing the Grignard reagent.

Day 1:

This part of the experiment must be performed during the first day of this lab using the Grignard reagent not used to make the benzoic acid (Part A, Day 1).

Preparation of triphenylmethanol.

Cool the reaction only if it is required to control the mildly exothermic reaction.  Evidence of reaction will be the formation of a a bright red solution which will eventually precipitate as a white solid.  Remove the Claisen adaptor, and attach the condensor unit (with drying tube attached) directly to the reaction round bottom flask.

The reaction is completed either by refluxing the mixture for 30 minutes (do this reflux only if you have 45 min or more to the end of the laboratory period), or stoppering the flask with the calcium tube attached (to keep it dry, and letting the mixture stand overnight, or until the next lab period, afterwhich refluxing is not necessary.  (This later option is actually the best procedure since you will not be back into the lab for a few days.)  The rest of the reaction will be completed during the next lab period.

STOP AND STORE THIS PART OF THE EXPERIMENT UNTIL THE NEXT LAB PERIOD!

Day 2:

Pour the reaction mixture into a 250-mL Erlenmeyer flask containing 25 mL of 10% sulfuric acid and about 20 g of ice (too much ice is not a problem, it will just melt).  Use ordinary diethyl ether (it does not need to be anhydrous ether from this point forward) and 10% sulfuric acid to rinse the reaction flask.  Swirl the flask well to promote hydrolysis of the addition compound.  The basic magnesium salts are converted to Mg2+ ions along with formation of the triphenylmethanol.  

Pour the entire mixture into a separatory funnel (rinse the flask with diethyl ether), shake, and draw off the bottom aqueous layer (should be the aqueous mixture, being more dense than the diethyl ether).  Shake the ether solution with 10% sulfuric acid to further remove Mg2+ ions, and, as a last step, wash with saturated NaCl to remove the water dissolved in the ether (the salt solution allows the aqueous and ether layers to separate more effectively).  

Note: It is important to note that quantities of the wash liquids is not critical, and it is sufficient to use about one-third of the volume of the ether for each wash with the aqueous solutions.

To effect drying of the ether solution, pour the ether layer into an Erlenmeyer flask, add about 3 g of anhydrous CaCl2 (use chunks, not the round pellets) and swirl the flask from time to time.  After about 5 min, remove the CaCl2 chunks by gravity filtration (do not use a vacuum) into a new flask.  Rinse the drying agent in the filter with a small amount of ether.  Add 15 mL of ligroin (66-77oC ligroin; ligroin is an organic solvent sometimes referred to as pertroleum ether, but it is not an ether chemically) and concentrate the ether-liqroin solutions using a heating plate in the hood, to vent the ether.  Evaporate slowly until crystals of triphenylcarbinol just begin to separate and let the crystallization proceed, first at room temperature, and then at 0oC after most of the crystals are formed.  Perform a vacuum filtration and collect your crystals.   Concentration of the mother liquor may yield a second crop of crystals, but it is not necessary.  Store the crystals in the dessicator oven until the next lab period.

STOP AND STORE THIS PART OF THE EXPERIMENT UNTIL THE NEXT LAB PERIOD!

Day 3:

The product should be colorless.  Determine a melting point, which should be below 160oC.  A typical will be about 2.5 g.  How well did you do?

Determination of percent yield

You will need to determine percent yield, based on the appropriate starting material.  What is the correct reagent to base your benzoic acid yield on?  What is the correct reagent for basing your yield of triphenylmethanol based on?  How much starting reagent do you have, for these calculations?  Assume that half of your reagent was used to produce the benzoid acid, and the other half to produce the triphenylmethanol.  If you believe that you used a different proportion, then use the proportion you believe was used (e.g., if you believe you used 40% of the prepared Grignard reagent for benzoic acid formation, then, base your yield on this ratio, instead of the half and half amount described above).

Compound MW Amount Needed mmol mp bp Density ηD
Bromobenzene 157.02 4.5 mL (6.75 g) (use pipettor) 43.0 -31oC 130oC 1.491 1.5590
Diethyl ether, dry 74.12 20.0  mL     34.5oC 0.708 1.3530
Magnesium 24.3 1.0 g 41.0        
Benzophenone 182.21 3.4 g 18.7 48oC 305oC    
Benzoic acid 122.1232 --- --- 122.4oC --- 1.08  
Triphenylmethanol 260.34     163oC 360oC    
Biphenyl 154.21     72oC 255oC 0.992  
(Iodine) 253.81 ~3-5 small crystals   113oC 184oC 4.930  
(Dibromoethane) 187.87 20 drops   10oC 133oC 2.180 1.5385
Ligroin ---            

NOTES:

  1. For extractions and washes, use about 1/3 to 1/2 of the initial volume of the phase that you washing with the washing solution, or usually less than 10 mL of wash solution or solvent.  Determine which phase contains the material you want (upper or lower phase).  Do not throw away any material until you know it is not needed.
  2. Diethyl ether must be used in the hood at all times, except when the ether is in a closed container.  Make certain the ether bottle is kept tightly capped when not in use.  This means putting the lid back on after you use it.  Do not ever use ether to rinse or clean glassware, always use acetone, or soap and water.  Ether is only used for extractions or a solvent for reactions.
  3. Replace all lids on any bottle or reagent container immediately after you use the chemical.  Never leave lids off of the container.

QUESTIONS

  1. Benzene is often produced as a side-product during Grignard reactions using phenylmagnesium bromide.  Show the reaction by which this product is produced, including a fully balanced equation.
  2. Write a balanced equation for the reaction of benzoic acid with hydroxide ion.  Why is it necessary to extract the ether layer with sodium hydroxide?
  3. Show reactions for preparing each of the following compounds by the Grignard method:

Go To Experiment: ChemDraw 1 2 3 4 5 6 7 8 9 10
Return to Chem211 Experiment Protocols Index

Copyright © Donald L. Robertson (Modified: 01/23/2007)