Bromine Addition Reaction of trans-Cinnamic Acid: Determination of the Stereochemistry of the Addition

Introduction

Bromine will be added across the carbon-carbon double bond of trans-cinnamic acid (E-1-phenyl-2-propenoic acid) to produce 2,3,-dibromo-3-phenylpropanoic acid and the identity of the stereoisomers formed will be determined by melting-point analysis.

There are four stereoisomers of 2,3,-dibromo-3-phenylpropanoic acid since it has two chiral centers and there is no symmetry These four stereoisomers consist of two pairs of enantiomers: a (2R,3S and 2S,3R) pair with a melting point of 202-204°C and a (2R,3R and 2S,3S) pair with a melting point of 93.5-95°C. The mechanism of the reaction determines whether the addition is syn or anti and thereby determines which pair of enantiomers is formed.

Additional Reading

Chapter 9  in Organic Chemistry, 2nd ed., by Klein

Techniques (from Techniques in Organic Chemistry, 4th ed., by Mohrig, Hammond and Schatz)

Measuring liquids with a Pasteur pipet and syringe, Figure 5.8, page 60.

Microscale vacuum filtration, Section 9.4

Mixed-solvent recrystallization, Chapter 15

Melting points, Chapter 14

Special Note: the bromine solution must be freshly prepared for each lab period.

Safety Information (from www.sciencelab.com MSDS information, except as noted)

• Acetic acid is very hazardous in case of skin contact (irritant), eye contact (irritant), ingestion, of inhalation. Hazardous in case of skin contact (corrosive, permeator), of eye contact (corrosive). Liquid or spray mist may produce tissue damage particularly on mucous membranes of eyes, mouth and respiratory tract. Skin contact may produce burns. Inhalation of the spray mist may produce severe irritation of respiratory tract.
• Bromine is hazardous in case of skin contact (irritant, permeator), of eye contact (irritant), of ingestion, of inhalation. Liquid or spray mist may produce tissue damage particularly on mucous membranes of eyes, mouth and respiratory tract. Skin contact may produce burns. Inhalation of the spray mist may produce severe irritation of respiratory tract. Wear gloves impermeable to bromine and use in a fume hood. Sodium thiosulfate or sodium bisulfite solution will be available to quench any spilled or extra bromine.
• trans-Cinnamic acid is slightly hazardous in case of skin contact (irritant), eye contact (irritant), ingestion, or inhalation.
• Cyclohexene is very hazardous in case of ingestion, hazardous in case of eye contact (irritant)) and inhalation (toxic to lungs). Slightly hazardous in case of skin contact (irritant).
• 2,3,-Dibromo-3-phenylpropanoic acid may be harmful via skin contact, inhalation, or ingestion. Avoid breathing dust. (data from www.sigmaaldrich.com which sells this compound for $100 for 50 mg!)
• Ethanol is flammable with a flash point (the temperature at which an ignition source 1 cm from the surface of the liquid will cause ignition) of 13-14°C. It is hazardous in case of  eye contact (irritant) and inhalation and slightly hazardous in case of skin contact.

Preparation Before Lab: In addition to writing the overall reaction above in your notebook also draw structures (Fischer and three-dimensional bond line) of each of the four possible stereoisomers, labeling each stereocenter with its R/S designation and indicating the pairs of enantiomers and their melting points. Remember that Fischer projections are conventionally drawn with the most oxidized carbon (in this case the carboxylic acid) at the top. Note that the carboxylic acid carbon is #1 for naming.

Procedure

1. Put 150 mg of trans-cinnamic acid and 0.6 mL of glacial acetic acid in a medium, dry test tube. Put the test tube in a 50°C water bath and wait until all of the trans-cinnamic acid dissolves. Add 1.0 mL of 1.0 M Br2 in acetic acid solution, using a Pasteur pipet equipped with a 1-cc syringe. Agitate the test tube to mix the contents.
2. Continue to heat at 50°C with occasional agitation until the original red-brown color of the reaction mixture fades to light orange and then continue to heat for 15 more minutes. If the reaction mixture becomes colorless, or nearly so, during the 15 minutes add more of the bromine solution dropwise until the color persists.  Note that persists means orange; if it is yellow, then add more bromine.
3. After the 15 minutes, remove the test tube from the water bath. If it is still orange, add a drop or two of cyclohexene to turn it to light yellow or colorless.
4. Cool the reaction mixture in an ice-water bath for at least 10 minutes. Also cool 10 mL of water in a separate container.
5. If no crystals appear after 10 minutes, and scratching with a glass stirring rod does not induce crystallization, then add half-mL portions of the chilled water with stirring and scratching until crystals persist. It is almost always necessary to do one or both of these things.
6. Leave in the ice bath for ten additional minutes after crystals form. Collect the product by vacuum filtration using a Hirsch funnel. Some of the apparent product may be solid acetic acid that will melt with washing. Wash the crystals with the ice-cold water that you chilled previously until the odor of acetic acid is nearly gone. Weigh the crude product and save a tiny amount for a melting point, in case the recrystallization fails.
7. Purify the product by mixed-solvent recrystallization using a 10-mL Erlenmeyer flask or a test tube.

1. Place the crude crystals and about 0.5 mL ethanol in the flask or tube, along with a boiling stick, and heat to boiling using a steam or water bath. Keep the boiling point of ethanol and the fact that you don’t want it to evaporate in mind.
2. If the solid doesn’t all dissolve, add a few drops of ethanol dropwise until it just dissolves.
3. Then add a water dropwise to the warmed solution until the solution just turns cloudy.
4. Then add ethanol dropwise to the still-heated solution until the cloudiness just clears..
5. Remove it from the heat source, allow it to cool to room temperature and then put it in an ice-water bath for at least 10 minutes. Isolate the crystals by vacuum filtration, using a clean Hirsch funnel and flask and a fresh piece of filter paper.

8. Transfer the crystals to a small beaker, label the beaker with your names and the experiment number, and place the beaker in your locker.
9. Weigh the recrystallized solid and determine its melting point the following week. If you need to do it the same week, dry it under a heat lamp first.
10. Cleanup: Pour the filtrates from both filtrations into the container for halogenated waste after first treating any that are yellow or orange with sodium bisulfite or sodium thiosulfate.

Analysis

Use the melting point of the product to determine which pair of enantiomers was formed and, therefore, whether the addition was syn or anti. Write the mechanism for the formation of each product formed, clearly showing the stereochemistry. Calculate the percent yield.

Your conclusion should include a clear statement of which products were formed, the corresponding mode of addition, and whether this is consistent with the generally-accepted mechanism. Consider what your melting point indicates about the purity of the product and, if it is not very accurate, whether or not it’s inaccurate enough so as to call into question the identity of the product. Although the conclusion should also include a statement about the percent yield of the product, remember that this is not the main focus of the lab. Also remember than any conclusion should start with a statement that mirrors the purpose statement written before the lab.

Practice Questions

1.   Suppose that a student obtains a product with a melting point of 129°C in this experiment. What compound or compounds are likely present?

2.   What substance might be obtained if water was present in the test tube used for the reaction?