Lab 4: Resolution of 1-Phenylethylamine

Transcription

1 Lab 4: Resolution of 1-Phenylethylamine Reference: Ault, A. J. Chem. Educ. 1965, 42, 269. Readings: Loudon, Ch 6 esp. section 6.8 Enantiomeric Resolution (pg 224). Summary In this experiment (S)-( )-1-phenylethylamine will be isolated. Racemic (1)- phenylethylamine will be reacted with enantiomerically pure to form diastereoisomeric salts which can be resolved by selective crystallization from methanol. The isolated salt will be converted to the optically active free base by treatment with sodium hydroxide. A polarimeter will be used to determine the optical rotation of the product, from which we can determine ee and evaluate the efficiency of our resolution. mirror plane H CH 3 NH 2 (R)-(+)-1-phenylethylamine Introduction H 2 N (S)-(-)-1-phenylethylamine H The first person to demonstrate that molecules could be chiral was the French microbiologist and chemist Louis Pasteur. Pasteur recalls his excitement at the profound discovery he made after painstaking work under a microscope to separate two enantiomeric forms of tartaric acid crystals and then subsequently analyzing the crystals using a polarimeter: "I remember hurrying from the laboratory and grabbing one of my chemistry assistants and excitedly telling him that 'I have made a great discovery... I am so happy that I am shaking all over and am unable to set my eyes against the polarimeter.' At this time, I was twenty-five years old and had only been doing research for two years. " The universe is an asymmetrical whole. I am inclined to thinking that life as manifested is a function of the asymmetry of the universe......life is dominated by asymmetrical actions. I can even imagine that all living species are primordially in their structure, in the external forms, a function of cosmic asymmetry. -Louis Pasteur

2 The isolation of a single enantiomer from a racemic mixture can sometimes be accomplished by a process know as chiral resolution. (R)-1-Phenylethylamine (pictured above) cannot be superimposed with its mirror image. These two nonsuperimposible stereoisomers are enantiomers, thus they have identical physical properties (e.g. melting point, boiling point, and solubility in methanol). When a racemic mixture (a 1:1 ratio of enantiomers) of 1-phenylethylamine is reacted with a single enantiomer of tartaric acid, two diastereomeric salt complexes form. These complexes are not mirror images of one another since only a single enantiomer of tartaric acid is used in the reaction. Thus, (R)-amine, (R, R)-tartaric acid complex and (S)-amine, (R, R)-tartaric acid complex are formed. H CH 3 NH 2 (R)-(+)-amine + H 2 N + H Me diastereomeric salts H CH 3 NH 3 + H 3 N (R)-(+)-amine more soluble remains in solution less soluble crystallizes from solution Unlike enantiomers, diastereomers have different physical properties, so we would expect that the above complexes should have different solubilities in methanol. In fact these two diastereomeric complexes have a significant solubility difference in methanol. The (R)-amine, (R, R)-tartaric acid complex is more soluble in methanol than the (S)-amine, (R, R)-tartaric acid complex. We will take advantage of this difference by selectively crystallizing out the (S)- amine, (R, R)-tartaric acid complex from a methanolic solution. nce the solid (S)-amine, (R, R)-tartaric acid complex is isolated, treatment with excess sodium hydroxide will convert the salt to the free amine (organic soluble) and disodium tartrate (aqueous soluble). Drawing on your acid/base extraction skills, you soon will have a sample of 1-phenylethylamine that should predominantly consist of (S)-( )-1-phenylethylamine. Now let s discuss how to analyze the enantiomeric composition of your sample. H 3 N ph = 13 H 2 N +

3 Enantiomers do not interact with plane-polarized light in the same way, a phenomenon that chemists have made good use of. Recall that light is a wave that consists of electric and magnetic fields. A regular beam of light has electric fields that oscillate in all directions perpendicular to the direction of beam travel. A beam of light with an electric field oscillating in only a single plane is called plane-polarized light, or more simply polarized light. You may own a pair sunglasses that contain polarizing lenses that permit transmission of only plane-polarized light, thus greatly reducing the amount of light that reaches your eyes. A regular beam of light has electric fields that oscillate in all directions perpendicular to the direction of travel. A beam of planepolarized light has an electric field that oscillates in only one direction. When plane-polarized light is passed through a single enantiomer of a chiral molecule (or a solution of a single enantiomer of a chiral molecule), the plane of polarization is rotated. When the opposite enantiomer is used, the plane of polarization is rotated in an equal and opposite direction. Samples that rotate polarized light are said to be optically active. The magnitude of this rotation, α, is reported in degrees by a device called a polarimeter. A schematic of a polarimeter is shown below. If the light has been rotated in a clockwise direction, the α is assigned a positive (+) value; if the light has been rotated in a counterclockwise direction, the α is assigned a negative ( ) value. plane of original polarized light plane of polarized light after passing through an "optically active" solution Polarimeter Schematic regular light polarizer planepolarized light sample cell with optically active material rotated plane-polarized light detector

4 For a given enantiomer the degree of rotation α is dependent on the concentration of the compound (c), the path length of the sample cell (l), and the wavelength of light that is used. Typically, the yellow light of a sodium lamp (the D line of Na, wavelength = 589 nm) is used as a light source. The equation below can be used to calculate the specific rotation, [" ] D, of a sample, which is a constant for a single enantiomer of a chiral compound in a given solvent. For neat samples, the concentration (c) is taken to be the density of the compound. specific rotation concentration (g/ml) D = (c) (l) observed rotation (degrees) length of sample cell (dm) A racemic mixture will not rotate polarized light and is said to be optically inactive. Any excess of one enantiomer over the other will result in the rotation of polarized light, with the maximum rotation occurring when the sample consists of a single enantiomer. The enantiomeric excess (ee) of a compound can be calculated using the equation below. The ee of a racemic mixture is 0% while the ee of a single enantiomer is 100%. ee = % of the major enantiomer - % of the minor enantiomer By comparing the specific rotation of a sample prepared in the laboratory with the published specific rotation of an enantiomerically pure sample, one can calculate the optical purity of the sample. If the relationship between concentration and rotation is linear, then optical purity = ee. [" ] obs " ( 100) = optical purity [ ] lit Procedure Using a steam bath, heat 16.0 g of (2R,3R)-(+)-tartaric acid and 225 ml of methanol in a 500 ml Erlenmeyer flask. When this solution is almost boiling, slowly add 12.1 g of racemic 1-phenylethylamine. Adding the amine too fast will result in the mixture boiling over Swirl the mixture until everything has dissolved. Remove the flask from the steam bath allow it to cool to room temperature. Since crystallization must be allowed to occur slowly, cover the top of the flask with aluminum foil, label the flask, and place it where your TF instructs until your next lab period. Continue from here during next lab period

5 Upon your return, prismatic crystals of ( )-amine-(+)-tartrate should have crystallized out from the solution. Collect the crystals using a Büchner funnel, and dispose of the mother liquor (What does the mother liquor contain?... tell us in your lab report). Rinse the crystals with a little cold methanol. Yields at this point are typically around 9 g (record yours). Partially dissolve the crystals in 45 ml water and carefully basify with 50% aqueous sodium hydroxide (~ 6 ml) to ph 13. You have now converted the amine salt to the organic-soluble free amine, or free base. Leave the mixture stirring for 30 minutes, and check the ph again to ensure that it is still basic. If not, add more hydroxide and wait a further 30 minutes. Transfer the mixture to a separatory funnel and extract with ether (3 X 25 ml). Dry the extracts over MgS 4, filter, and remove the ether on the rotovap. With the help of your TF obtain the optical rotation of your neat final product, and from that value, calculate the ptical Purity. You may be asked to pool your product with that of your neighbors at the direction of your TF. Literature Data (S)-( )-1-phenylethylamine: [" ] D = 30, c = 0.1 g/ml in Et; density = g/ml Cleanup The sodium hydroxide solution should be disposed of in the Basic Aqueous Waste. MgS 4, filter paper, and excess tartaric acid should be put in the Solid Waste. The phenylethylamine, methanol, and ether go in the Non-halogenated rganic Waste. dds and Ends Methanol is toxic and is readily absorbed through the skin. Take care in its handling and use. Steam baths belong in the cabinets beneath the sinks. Variacs and heating mantles go in the cabinets beneath the rotovaps. Common glassware should be rinsed with acetone and placed in the shopping carts for washing. Needle-like or fluffy crystals sometimes form (not the desired prismatic) which after work up lead to 1-phenylethylamine with " Possible Quiz Questions [ ] D = 19 to 21. 1) Why must you add the amine to the hot methanol / tartaric acid mixture slowly? 2) Which of the following are optically active? ptically inactive? (2R, 3R)-tartaric acid racemic 1-phenylethylamine (S)-1-phenylethylamine 2) If you accidentally used (2S, 3S)-tartaric acid instead of (2R, 3R)-tartaric acid, what would happen? When would you first notice the mistake? 3) What would happen if you did not add the 50% Na solution to the amine tartrate salt prior to extracting the amine with diethyl ether?

6 4) Where does the (R)-1-phenylethylamine end up? 5) The procedure calls for the crystals to be rinsed with 20 ml of cold methanol. Why must the methanol be cold? 6) If your 1-phenylethylamine is found to have no optical rotation, what is the %ee of your mixture? What percentage of each enantiomer do you have?