Synthesis and Base-Catalyzed Decarboxylative Elimination of Dibromocinnamic Acid

Background: trans-Cinnamic acid, C₆H₅-CH=CH-COOH, more systematically named 3-phenylpropenoic acid, is treated with Br₂ to form dibromocinnamic acid, C₆H₅-CHBr-CHBr-COOH, more systematically known as 2,3-dibromo-3-phenylpropanoic acid. The stereochemistry of bromine addition to the alkene will result in a racemic mixture of either RR + SS (from a syn addition of Br₂) or of RS + SR product (from an anti syn addition). The two possible racemates are diastereomers of each other.

C₆H₅-CH=CH-COOH + Br₂ in CHCl₃ ® C₆H₅-CHBr-CHBr-COOH

trans either RR+SS or RS+SR

The dibromocinnamic acid is then treated with one of several different reagent-solvent mixtures to bring about the elimination of HBr and CO₂ to form b -bromostyrene, C₆H₅-CH=CHBr:

C₆H₅-CHBr-CHBr-COOH ® C₆H₅-CH=CHBr + HBr + CO₂

either cis or trans

• If an aprotic solvent and a base are used for this conversion, the Br^- and CO₂ will be anti-periplanar (see McM Fig 11.17) as they leave the reactant and the elimination will result in a cis product. The most used aprotic solvent (solvents not having –OH or –NH groups – see McM, p. 383) is acetone. This reaction is an E-2 reaction.

  On the other hand, the b -bromostyrene product will be predominately trans, if the mechanism of elimination is E-1. This reaction is carried out in protic solvents (McM p. 395-6) and involves two steps. The first step is the loss of Br^- to form the carbocation: C₆H₅-C⁺H-CHBr-COOH. The carbocation formed has ample time to freely rotate about the C⁺H¾ CHBr bond and establish a predominant conformation in which the Br is distanced from the C₆H₅ group. Subsequent loss of H⁺ and CO₂ produces the less sterically hindered trans b -bromostyrene.

Procedure: To 1.0 g of trans-cinnamic acid in a 25 ml Erlenmeyer flask add 5 ml of chloroform. Warm and swirl the mixture on the steambath until the solid is dissolved. Cool the solution to room temperature and then add 0.7 ml of a 10 M solution of Br₂ in chloroform. Bring the mixture to a boil on the steam bath and let it stand at room temperature 15 minutes. Cool the mixture to 5^o and isolate the solid with suction using a spatula and a Hirsch funnel. Rinse the Erlenmeyer with a few ml of chloroform, re-cool and collect additional solid. With the spatula, tamp the solid to remove chloroform by suction. Transfer the solid to a pre-weighed screw-cap vial. Record the mass and melting point of the dibromocinnamic acid product.

Conversion of dibromocinnamic acid to b -bromostyrene. To 40 mg of dibromocinnamic acid in a 13 x 120 mm test tube is added 1 ml of one of the following solvents:

a) 5% aqueous AgNO₃

b) water containing 40 mg of K₂CO₃

c) reagent acetone containing 40 mg of K₂CO₃

d) methanol containing 3% AgNO₃

Swirl the contents and note any reaction. Suspend the test tube in a 55^o C water bath for 15 min and note any changes.

For the methanol and acetone reactions, evaporate the solvent completely by tilting the tube in a crystallizing dish of hot water. Cool the tube and agitate the resulting solid with 1 ml of CH₂Cl₂. With a Pasteur pipette transfer the mixture to a filter/drying tube containing glass wool and Na₂SO₄ clamped above a pre-weighed 20 ml screw cap vial labeled "c" or "d" as appropriate. After the solution has passed, evaporate the CH₂Cl ₂ on the steam bath; lay the vial horizontally on the steam bath to ensure that all the solvent is removed. Reweigh the vial and add your name and the mass of the product to the label.

For the water based experiments [ a) or b)] cool the tube and add 1 ml of CH₂Cl₂. Swirl the contents thoroughly. Transfer the CH₂Cl₂ layer to a filter/drying tube containing glass wool and Na₂SO₄ clamped above a pre-weighed 20 ml screw cap vial labeled either "a" or "b". After the solution has passed, evaporate the CH₂Cl ₂ on the steam bath; lay the vial horizontally on the steam bath to ensure that all the solvent is removed. reweigh the vial and add your name and the mass of the product to the label.

Note the odor of the product formed. Trans-b -bromostyrene is reported to have a hyacinth like odor.

Data treatment:

1. Use a reaction chart ("Common Practices..") to calculate the theoretical yield. Also calculate the percent of theoretical yield of dibromocinnamic acid you obtained from cinnamic acid.

2. Determine which C₆H₅-CHBr-CHBr-COOH product was obtained by comparing this melting point to the two possibilities, (RS, SR): mp 204^o C or (RR, SS): mp 91-93^o C.

3. Given that the reactant was trans-cinnamic acid, determine whether the addition of Br₂ to it was anti or syn to form the product you obtained. Show your reasoning with stereochemical drawings.

4. Most references characterize the RR, SS or the RS, SR racemates of dibromocinnamic acid as either "erythro" or "threo". These terms refer to compounds with two chiral centers having similar attached groups. If these similar groups line up so that they could eclipse each other the compound is erythro. The term "erythro" would change to "meso" if the similar groups became identical to each other. On the other hand threo refers to a diastereomer of erythro; it applies to the compound if similar groups could never line up so as to eclipse each other. Prime examples are erythrose and threose carbohydrates. In the dibromocinnamic acid case, both chiral centers have bromine atoms and both have hydrogen atoms, leaving the C₆H₅- and the –COOH to be "similar":

Which is the RS,SR racemate – erythro or threo? Which is the RR,SS racemate?

5. Report mass of b -bromostyrene you obtained

6. Include the ¹H NMR spectrum of your product. From it, calculate the percent of dibromocinnamic acid that underwent E-2 reaction and that underwent E-1 reaction

7. Give full stereochemical drawings - sawhorse and Fischer projections – for each reaction to explain the formation the b -bromostyrene of the products you obtained from dibromocinnamic acid.

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References:

Mesdaugh, H and Puechberty, A. J Chem. Educ. 1991, 68, 515.

Strom, L. A., Anderson, J. R. and Gandler, J. R. J. Chem. Educ. 1992, 69, 588.

Mayo, D. W., Pike, R. M. and Trumper, P. K Microscale Organic Chemistry, 3^rd Ed. Wiley: New York, 1994, pp. 525-536.

Reference: Corvari, L, McKee, J. R., and Zanger, M. J. Chem. Educ. 1991, 68, 161.

Revised Summer, 1998