Grignard Synthesis of Benzoic Acid
Preparation: McMurry, sections 10.8 and 20.6.
Conversion of an organic halide into a Grignard reagent completely transforms the reactive character of the organic compound. Carbon bears partial positive charge when bonded to halogen but partial negative charge when the carbon is bonded to magnesium. The Grignard reagent is a very reactive nucleophile and base.
In this experiment you will make the Grignard reagent phenyl magnesium bromide; this
reagent will then be treated with carbon dioxide to form benzoic acid. The sequence
(Equation I) is explained in McMurry Sect 20.6.
As in any work, this experiment may not succeed the first time; be prepared to repeat it from the beginning. On the second try, you should be able to work much more efficiently and with more understanding.
Procedure: Avoid washing any of the equipment you are to about to use in this experiment up to the point where aqueous HCl is added. Traces of water will halt Grignard reactions.
Obtain a 150 mm piece of magnesium ribbon. Hold one end with forceps and with the other hand remove the residue on the ribbon by scraping it with a spatula, scissors or pliers to obtain a shiny surface. Cut 0.12 g of the shiny ribbon into 2-3 mm pieces (do not handle the pieces) onto a folded piece of paper to obtain the mass on the balance. Transfer the magnesium pieces to the 5 mL conical vial, add the dry spin vane, add one small crystal of iodine and add 500 ÁL (0.5 mL) of anhydrous ether. Be prepared to add more ether as necessary to maintain the liquid level at a minimum of 500 ÁL.
Assemble the rest of the apparatus as in Mayo, et al., Fig 3.24. Clamp the apparatus firmly to a stand.
In the hood, prepare a solution of 500 ÁL of bromobenzene in 1 mL of anhydrous ether in the 3 mL vial using the delivery pipettes provided. Cap this vial with a polyethylene top.
(*Note: Be certain the dry ice is ready before you initiate the reaction below.)
Draw half of the bromobenzene solution into the syringe and insert the needle through the polyethylene cap in the Claisen head as in the figure. While stirring the mixture below, add 6-8 drops of the bromobenzene solution. Evidence of reaction is the formation of tiny bubbles. When the reaction has started, add the remainder of the bromobenzene solution slowly over 3-5 min. The temperature should be maintained at about 40 oC to allow gentle refluxing (Mayo, et al., p. 29) of the ether. To the 3 mL vial add an extra 300 ÁL of ether, then transfer this to the reaction via the syringe. Adjust the total volume to 3 mL with the addition of more anhydrous ether. Reflux the mixture for 10 minutes, then allow the gray-brown solution of the Grignard reagent to cool to room temperature. What do you observe?
The Dry Ice (at least 1.0 g) is added in small chunks to the Grignard solution. Note the reaction as this is added. To convert the C6H5C(=O)-OMgBr, to benzoic acid (last step, Equation I), use a pipet to VERY SLOWLY add 1 mL of 6 N HCl and again observe the result. Test the aqueous layer with pH paper; it should be acidic. Remove the ether by gently heating the vial for 5 minutes on the steam bath. Cap the vial, mark it and set it in your drawer until the next laboratory period.
Preparation for the 2nd laboratory period: The benzoic acid has been synthesized, but it must be purified. Water soluble magnesium salts are removed by extracting away the water layer; but, a number of organic side products remain with the benzoic acid. These are side products of the Grignard reaction; small amounts of benzene are formed (Equation II, above), unreacted bromobenzene remains, and biphenyl, H5C6-C6H5, is formed from the reaction (Equation III).
The benzoic acid can be isolated from this mixture by taking advantage of its property as an acid. Only it can dissolve in aqueous NaOH (Equation IV) while the side products remain in the ether. After the ether-soluble side products have been removed, strong acid is again added to reverse this reaction in order to restore the benzoic acid.
Recrystallization of the crude product in water affords the purified benzoic acid. The amount of benzoic acid that can dissolve in water depends on the temperature of the water: 68g per liter if the water is boiling but only 1.7g/L if the water is ice cold. This disparity allows one to dissolve relatively large amounts of the benzoic acid in hot water; the solution is then cooled to produce a precipitate of purified benzoic acid which is recovered by vacuum filtration.
Procedure: Add 3 mL of ether (does it need to be anhydrous?) to the 5 mL vial and stir to dissolve the organic material. Allow the layers to separate, remove and discard the aqueous layer, add 1-2 mL more of deionized water, shake again, and remove the aqueous layer again; this process removes the water soluble magnesium salts.
To the ether solution add 0.7 mL of 10% sodium hydroxide. Recap and shake the mixture thoroughly, and transfer the aqueous layer to a clean 10 mL beakerl (does the vial have to be dry?) Re-extract the ether with a fresh 0.5 mL portion of aqueous NaOH, then with 0.5 mL of water. The ether solution can now be discarded. The beaker is placed in a small container of hot tap water for 5 minutes to evaporate the small amount of dissolved ether, then cooled and treated dropwise with concentrated HCl until the solution is acidic to pH paper. What do you observe? What reaction is taking place?
Cool the mixture to <10 oC and collect the white solid with the small Hirsch funnel on a paper disk using suction. Tamp the solid down to remove the water.
To recrystallize the product, transfer the crude benzoic acid to a 10 mL beaker and add 1/2 mL of hot deionized water. In the hood, boil the solution on the hot plate until the benzoic acid dissolves. If dissolution is not complete, add another 1/2 mL of water and reheat. Continue this process (of adding water and heating) until the benzoic acid is dissolved. Allow the solution to cool and observe the precipitate of white crystalline benzoic acid. Finally cool the mixture in an ice bath to maximize the amount of product.
Recover the crystals by vacuum filtration on the Hirsch funnel as before. Tamp the solid and allow air to suck through it. Once dry, transfer it to a preweighed plastic bag. Measure the melting point of the recrystallized benzoic acid and compare it to the melting point of the crude product.
Obtain IR data on your purified product. Fully interpret the peaks observed and comment on the purity of your sample based on this spectrum.
Reweigh and seal your product in a plastic bag. Attach this to a page in your notebook.
Results: Along with your observations, melting points, etc. create a
reaction table from the reaction sequence at the beginning of this handout. Write the
masses, densities, molar masses, molarities (where necessary - see the file "Common
Practices..") and the millimoles under each of the reagents: Mg, bromobenzene, CO2
and the 6M HCl. Determine the theoretical yield of benzoic acid and the percent of
theoretical that you recovered after recrystallization.
1. a) How many mL of boiling water will dissolve 58 mg of benzoic acid?
b) After this solution is cooled in ice water, how many grams of benzoic acid are recrystallized?
2. Outline the synthesis of deuteriobenzene, DC6H5. (Recall that deuterium, D, is a heavier isotope of hydrogen.)
3. For the synthesis of the C-14 labeled acetic acid: H3C-C14OOH, would you add unlabeled CO2 to the Grignard reagent formed from H314C-Br or would you add 14CO2 to the Grignard reagent formed from H3C-Br? Explain.
"Mayo et al.": Mayo, D.W., Pike, R.M., Butcher, S.S. and Trumper, P.K. Microscale Techniques for the Organic Laboratory; Wiley: New York, 1991
"McMurry": McMurry, John, Organic Chemistry, 5th ed., Brooks/Cole Publishing
Co.: Pacific Grove, CA, 2000.
Rev. Summer, 2000