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 will work much more efficiently and with more understanding.
Grignard Synthesis of Benzoic Acid
Preparation: M&B sect. 3.16 and 19.7
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 be then treated with carbon
dioxide to form benzoic acid. The sequence is explained in
M&B Sect 19.7 (Equation I).
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 will work much more efficiently and with more understanding.
Procedure: Obtain a 150 mm piece of magnesium ribbon. Hold one end and the the other remove the residue on the ribbon by scraping it with a spatula, scissors or pliers to obtain a shiny surface. Cut at least 0.12 g of the shiny ribbon in 2-3 mm pieces (do not handle the pieces) onto a folded piece of paper on the balance. Transfer the magnesium pieces in the 5 mL conical vial and add the dry spin vane and one small crystal of iodine and 300 無 (=0.3 mL) of anhydrous ether. Be prepared to add more ether to maintain the liquid level to at least 300 無 if it becomes necessary
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 510 無 of bromobenzene in 700 無 of anhydrous ether in the 3 mL vial using the delivery pipettes provided. Cap the vial with a polyethylene top.
Draw half of the bromobenzene solution into the syringe and insert it through the polyethylene cap 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 無 of ether, then transfer this to the reaction via the syringe. Adjust the total volume to 3 mL with the addition of additional 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 removing 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), 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, 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 solubility of benzoic acid is 68g/L of boiling water and 1.7g/L of ice cold water. 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. Recork and shake the mixture thoroughly, and transfer the aqueous layer to the clean 5 mL conical vial (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 vial is placed in a beaker 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. Remove some crystals with a capillary tube for a melting point of the crude product. The rest is to be recrystallized from hot water below.
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 solution 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. Measure the melting point of the recrystallized benzoic acid and compare it to the melting point of the crude product. Weigh the product. Turn in your product with your write-up in a sealed plastic bag.
Data: 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.
Questions:
1. Outline the synthesis of deuteriobenzene, DC6H5.
2. Outline the synthesis of C-14 labeled acetic acid: H3C-14C-OOH
3. a) How many mL of boiling water will dissolve 68 mg of benzoic acid?
b) After this solution is cooled in ice water, how many grams
of benzoic acid are recrystallized?
References:
"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
"M&B": Morrison, R.T., and Boyd, R.N. Organic
Chemistry, 6th ed., Prentice Hall: Englewood Cliffs, NJ, 1992
Rev. Spring, 1998