Grignard Synthesis of Benzoic Acid
Introduction:
In 1900, a French chemist, Victor Grignard, discovered that haloalkanes reacted with magnesium in diethyl ether solution. His discovery led to the whole field of organometalic reagents which have provided modern organic chemists with one of their most versatile tools. As a result of his pioneering work, Grignard received the Nobel Prize in Chemistry in 1912.
Below is my rendition of a 'Grignard clock' which summarizes some of the more important molecular transformations that can be realized by reacting phenylmagnesiumbromide with the appropriate reagents. Keep in mind, that these Grignard reactions are not limited to arenes, but work equally well for alkanes as well. It might be a rewarding experience for you to familiarize yourself with the specific reaction conditions that would produce each of the following products:
The very reactivity that makes the Grignard reaction so flexible also proves
to be its biggest weakness. Grignard reagents are so reactive that low
yields and/or mixtures are often obtained unless the chemist is extremely
careful in choosing the reaction conditions. Intramolecular reactions are
common if another electrophilic site is present on the same molecule. In
addition, even traces of water or other solvents can result in products other
than those intended.
Synthetic issues aside, there is one very big safety issue when using Grignard
reagents, the common use of diethyl ether as the solvent. Consider that
the boiling point of diethyl ether is 35 °C while your hands are normally about
37 °C. As you can see, simply holding a container of diethyl ether in
your hands is enough to cause it to boil. That is why it is absolutely
imperative that NO FLAMES are
allowed in the lab during this experiment! Also run the reaction under
your snorkel hoods to minimize ether vapors in the lab.
Purpose:
The purpose of this experiment is to synthesize benzoic acid through a two step
Grignard reaction:
The first step involves the generation of the Grignard reagent through the
reaction of bromobenzene with magnesium turnings in anhydrous ether:
Traditionally, this Grignard reagent has been shown as above, with a carbon on
the phenyl ring forming a highly polarized covalent bond with the magnesium.
However, new evidence, suggests that an equilibrium between this
covalent structure and a biphenyl magnesium salt exists:
Instead of a covalent bond, you now have a fully ionic salt. While this
salt provides a better explanation of why Grignard reagents are such
exceptional nucleophiles, it does pose interesting questions regarding
solubility. Either way, a Grignard reagent possess a high concentration of
electrons that make it perfect for attacking electron deficient sites.
Grignard reactions tend to be an excellent test of a student's laboratory
technique. They tend to either provide an excellent yield of the desired
product or none at all. However, there is one potential byproduct of this
reaction. Biphenyl can be produced if the bromobenzene is added too
quickly to forming Grignard reagent. Although it can be easily removed
from the desired product, it will reduce your yield:
Procedure:
Before you come into lab, make sure you have filled in your table of reagents
and products. You will need these values (particularly the molecular
formula and molecular weight) to determine the identify of your products and to
calculate your final yield. You will also need to come to lab with IRs of
your starting materials and expected product(s) already in your notebooks (General Chemistry Links).
Finally, it is important that you know exactly what you are going to be doing
so you can work more efficiently:
IF YOU DO NOT UNDERSTAND ANY
ASPECTS OF THE
- Make sure you have thoroughly cleaned, rinsed, and dried your glassware. ANY traces of soap, water or acetone will ensure that this reaction will fail. To remove any traces of acetone, conduct a final rinse with ether.
- Start assembling your apparatus by clamping up a Claisen adapter. Next, add a condenser (make sure your water hoses are tight, NO water leaking) to one leg of this Claisen adapter. To the other leg, attach a small separatory funnel. Attach a dying tube containing calcium chloride to the condenser.
- Add 0.1 moles of magnesium turning, and a magnetic stirring bar to a 100 mL round bottom flask.
- Attach the flask to the bottom of the Claisen adapter.
- Add 30 mL of anhydrous ether to the apparatus through the separatory funnel.
- Add a single, small crystal of iodine to the reaction flask.
- Set your magnetic stir motor for a gentle stirring. Turn on the water to the condenser as low as possible and check to make sure there are NO LEAKS.
- Pour a solution of 0.1 mole bromobenzene and 30 mL anhydrous ether into the separatory funnel.
- Add approximately 10 mL of this solution to the round bottom to initiate the Grignard reaction.
- Within 5 minutes you should notice the ether start to reflux and the solution turn a muddy brown (cloudy) color. If your reaction does not start within 10 minutes, you may attempt the following:
- Use a dry glass stirring rod to gently crush one of the magnesium turnings against the bottom of the flask. Be very careful not to break the flask. If the reaction does not start, try the next step.
- Gently heat the flask to boiling with your aluminum bead bath. Swirl it gently and remove the heat. If the boiling does not continue on its own, proceed to the next step.
- Add one or two small crystals of solid iodine. If there is still no reaction, proceed to the next step.
- Tough Luck: you have to start all over! Dispose of all reagents properly and make ABSOLUTELY sure that everything is clean and DRY.
- Add the remainder of the bromobenzene solution dropwise (1-2 drops per second).
- Heat the reaction as neccesary to maintain the reflux for another 30 minutes (use a 100 mL heating mantel with the Variac set to 10). You may have to add absolute ether if the volume decreases.
- At this point, there should be little if any magnesium left and the reaction should be a clear, dark color. Allow the reaction to cool to room temperature, remove the round bottom flask and cap it.
- Weigh a little more than 0.1 mole of freshly prepared powered dry ice into a DRY 250 mL beaker.
- Place the beaker in an ice bath and transfere all of the Grignard to the beaker. Swirl or stir this mixture until there is no more activity. Allow the product to remain in the ice bath.
- Prepare a solution containing approximately 10 mL of concentrated HCl and 20 g of ice.
- SLOWLY add this solution to the beaker containing your Grignard product and stir until there is no more activity.
- Keep adding HCl until you see two layers. You may need to add 30-40 mL of ether to replace any lost in the exothermic neutralization.
- Transfer both layers to a separatory funnel and remove the aqueous layer.
- Wash the ether layer with two 25 mL portions of distilled water.
- Extract the benzoic acid with three 20 mL portions of 10% sodium hydroxide (sodium benzoate is soluble in water but not ether). Save these extracts. Dispose of the ether in the solvent beaker in the hood.
- Cool the sodium hydroxide extracts in an ice bath. Carefully acidify with concentrated HCl by adding the acid dropwise until the solution is strongly acidic to pH paper and no more product has precipitated. Note: do not add too much HCl or you may get an additional precipitate of sodium chloride.
- Recover the benzoic acid by vacuum filtration.
- Recrystallize your product from hot water and dry it an 80 °C oven for 5-10 minutes.
- Determine your yield and purity (m.p., and IR), and turn in your product in a properly labeled vial:
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Conclusions:
- If the molar ratio of bromobenzene and carbon dioxide is 1:1, why do you use an excess of carbon dioxide?
- How much benzoic acid did you produce and how pure was it?
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