Question

Formation of Diastereomeric Salts

Pre Lab Quiz

1. What chemical makes up the cation portion of the diastereomeric salt?

                α -phenethylamine

                ethanol

                sulfuric acid

                ibuprofen

2. Two compounds are enantiomers if they:

                have different molecular formula

                are superimposable mirror images of each other.

                are non-superimposable mirror images of each other

                have the same molecular formula, different position of substituents

3. What form of Ibuprofen is most commercially available?

                racemic

                R

                S

4. (True or False) The chiral reagent (S)-phenethylamine is a racemic mixture.

                False

                True

5. Qualitatively, an IR spectrum of the S enantiomer will be ________, when compared to the IR spectrum of the R enantiomer

                very different

                identical

EXTRA INFO

During the first period you will isolate ibuprofen from the tablets. At this point you have a sample of racemic Ibuprofen. When you react this sample with S(-)-phenylethylamine (this is a pure enantiomer of phenylethylamine) only the S version of Ibuprofen will form a salt. The salt has two stereocenters so the formed salt is SS. The diastereomer salt RS does not form. During the second lab period you will recover enantiomerically pure (+)-(S)-ibuprofen by reacting the salt with acid to get back the pure enantiomer of S-(+)-Ibuprofen and the S-(-)-phenylethylamine. You will be using polarimetry to assess the success of your chiral resolution by determining the enantiomeric excess and optical purity of your sample.

PROCEDURES

During Lab

Isolation of Ibuprofen Procedure

1. Obtain 15 ibuprofen tablets (this is 200mg of ibuprofen per tablet).

2. Place the tablets in a 50 ml beaker equipped with a stir bar and add enough acetone to submerge them completely, which is about 25 mL.

3. Stir the tablets at room temperature in the acetone for 15-20 minutes. Make sure that you have vigorous stirring. There will be two magnetic stir bars to use in the hood

Workup for Isolation of Ibuprofen

4. Remove all acetone insoluble components via vacuum filtration in to a CLEAN AND DRY vacuum flask. Make sure you add a small amount of acetone to wet the filter paper before you start filtration. Pour in the sample slowly. Rinse the solid with two 5 mL aliquots of acetone. You are saving the liquid and discarding the solids. Discard the solids in the waste container in the hood.

5. Transfer the filtrate to a tared 100 mL round bottom flask.

6. Concentrate the ibuprofen by rotary evaporation. Do not do the rotary evaporation yourself. Your TA will rotovap your sample.

7. Record the mass of the crude ibuprofen collected.

8. Calculate the % recovery (assume each Ibuprofen tablet contains 200 mg Ibuprofen) of Ibuprofen isolation.

9. Characterize the crude ibuprofen by melting point and IR spectroscopy.

Formation of Diastereomeric Salt Procedure (This is the reaction you are running)

1. Add 30 mL of 0.25 M sodium hydroxide to the round bottom flask containing the crude ibuprofen. How many moles of Ibuprofen do you have?

2. Equip the round bottom flask with a Claisen head for a thermometer and condenser as well as a stir bar.

3. Heat the solution using a heating mantle to an internal temperature between 75 and 85 degrees Celsius while stirring. (Monitor the temperature by ensuring the thermometer bulb is a quarter of an inch away from the bottom of the flask).

4. Once the appropriate internal temperature is attained tell your TA. Your TA will check the pH of the solution, and make sure it approximately 6, then add 0.9 mL of S-(-)-α-phenethylamine (also known as L-(-) alpha-methylbenzylamine) slowly, by removing the thermometer and adding it through the adaptor. Precipitation will form almost immediately. How many moles of the amine were added? Which species is the limiting reagent? If you do not have an immediate ppt and your pH is too high your TA will add drops of concentrated sulfuric acid. The acid reduces the pH to the correct range (~7).

5. Continue heating the mixture between 75 and 85 degrees for 20 minutes while stirring.

Workup for the Formation of the Diastereomeric Salt

6. Remove the flask from heat and allow it to cool to room temperature.

7. Collect the salt by vacuum filtration using a Buchner funnel, washing the solid with a small amount (2-3 mL total) of ice cold water. Add a small amount of ice cold DI water to wet the filter paper. Pull out the stir bar with the tweezers, rinse the stir bar with water and return to the beaker in your hood. (Not returning the stir bar will result in loss of TA points for you and your hood partner- they are expensive.)

8. Record the mass of the obtained salt. Calculate the % yield of salt formation. Either the amine or Ibuprofen is the limiting reagent. Which one is it? Obtain a mp of the product. Store the salt in scintillation vials for the next laboratory session.

WHAT info is needed?

Answer 1

1. What chemical makes up the cation portion of the diastereomeric salt?

                α -phenethylamine

You are separating the diastereomeric mixtures of ibuprofen which is an acid. To form the salt, a base is needed. α -phenethylamine is the base that contains an amine as fnctional group.It forms salt with ibuprofen.

2. Two compounds are enantiomers if they:

are non-superimposable mirror images of each other

3. What form of Ibuprofen is most commercially available?

                racemic

Ibuprofen is a chiral acid. The enantiomers are difficult to separate. Hence the commercially available ibuprofen is a racemate.

4. The chiral reagent (S)-phenethylamine is a racemic mixture.

                False

The configuration S indicates that the molecule is optically pure. Racemic mixture contains 50% R and 50% S isomers.

5. Qualitatively, an IR spectrum of the S enantiomer will be ________, when compared to the IR spectrum of the R enantiomer

Identical

Enantiomers have only different optical rotation in their sign. Rest of the properties are same.