Mosher Ester Analysis - Department of Chemistry and Physics

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catalyst, 4-dimethylaminopyridine (DMAP) is used. DMAP facilitates the process both by acting as a base and by forming activated acylpyridinium derivatives (below) from DCC and from the O-acylisourea. These are much more reactive as the pyridine is an excellent leaving group. This accelerates the reaction severalfold over the uncatalyzed reaction. H 3C N CH 3 N N c-Hx N H c-Hx Procedure Wear gloves. DCC and DMAP are very toxic. You will be provided with a culture tube containing a scalemic solution of 6.0 L of 1-phenylethanol in 1 mL of dry CH2Cl2. To this add a stir bar and 13 mg of (R)-(+)- or (S)-(-)-MTPA as directed by your instructor. Be sure to record which enantiomer of MTPA you use. Also be sure to cap the tube quickly to minimize any moisture entry after each addition of reagent. A nitrogen balloon and septum can be used if you wish. Cool the flask in an ice bath and add 12 mg of DCC and a spatula point (~1-2 mg) of DMAP in sequence. Add the DCC to the reaction as soon as it is weighed as it tends to pick up moisture in the air. Stir the solution for 5 minutes in the ice bath, and then 25 minutes at room temperature, during which time dicyclohexylurea will precipitate. While you are waiting on the reaction to complete, experiment with different TLC systems to determine if your reaction has finished. Spot 1-phenylethanol, DCC, DMAP, MTPA, and your reaction separately on the TLC plate and develop. Visualize the plate with UV light and circle the spots with a pencil. Begin with 1:1 hexane-ethyl acetate and evaluate several mixtures until you find one that separates all of the components well, especially the product. This mixture will be used for preparative TLC to purify the product. Also while you are waiting on the reaction to complete, prepare two large test tubes for exraction of the reaction mixture. To one tube add 2 mL of 5% NaHCO3 and to the second add 2 mL of saturated NaHCO3. When the reaction is judged to be complete or 30 minutes passed, add 2 drops of water and stir an additional 10 minutes. Then, add one mL of CH2Cl2 and 2 mL of 5% acetic acid to the culture tube and swirl vigorously. Using a pipet, transfer the organic layer to the test tube containing 5% NaHCO3 and swirl as before. Repeat this for the tube containing saturated NaHCO3. Prepare a pipet drying column plugged with glass wool and filled with ~3 cm of anhydrous Na2SO4. Clamp the tube in place and place a tared 10 mL round bottom flask below to collect the eluent. Add the organic phase from the last tube and allow it to pass through the column and collect in the flask. Once all of the organic phase has been added and the top of the liquid reaches the Na2SO4, wash the column twice with 2 mL CH2Cl2. Remove the solvent by rotary evaporation and remove any traces under high vacuum for no more than a minute or two (The instructor will show R O N N CH 3 CH 3
you how to do this). Obtain a crude yield, dissolve the product in CDCl3 and obtain a 1 H NMR spectrum of the crude ester. Preparative Thin-Layer Chromatography The Mosher ester will be purified by preparative thin-layer chromatography. This is essentially the same as what you use for monitoring your reactions, only on larger scale. We will use a large developing tank, and large, thickly coated plates. The plates we are using are capable of separating around 10-20 mg, depending on separation efficiency. Unlike flash chromatography, no specific Rf value is required. Simply identify a solvent system which will adequately separate your compounds and develop the plate. The technique does have limitations, however. The large surface area of the silica, combined with its mildly acidic nature tend to promote air oxidation of sensitive functionalities such as aldehydes, amines, and reactive double bonds. Also, the method is rather expensive to perform on other than small scale separations. Nonetheless, it is of great utility in difficult separations of small amounts of material, such as extracts of natural products and separation of diastereomers. In the second part of this experiment, you will separate the products of your Mosher ester reaction by preparative TLC and characterize your product by 1 H and 19 FNMR. Preparative TLC Procedures 1. Set up TLC Developing tank. a. Examine TLC’s in various solvent systems (TLC hood) if you have not yet determined an optimal composition. b. Dissolve your sample in 1.0 mL CH2Cl2 or use the NMR sample directly. c. Perform a TLC on your material using that system. (Don’t forget to cospot with your starting material). d. Make up 100 mL of your chosen solvent system and put it in the tank. 2. Prepare your TLC plate. a. Set up the solvent streaker (Have the instructor help you.) b. Draw a pencil line about 1” from the bottom of the plate. c. Set the streaker up so that the tip of the capillary traverses this line as you draw it along the benchtop. d. Fill the streaker with your solution. The reservoir will only hold around 0.25-0.5 mL. e. Streak the plate on the line you drew. Try to keep the thickness of your band between 1-3mm. Wave your hand over the plate to assist drying. f. Refill the reservoir again and repeat. g. Clean the reservoir with acetone. Dry it under a nitrogen flow. Give it to the next person to use. Be gentle with the streaker. We only have one and if broken, it will end our experiment. 3. Develop your plate. a. Place your plate in the developing tank. b. Develop the plate until the solvent front reaches within one inch of the top. This will take about an hour. Be sure to check the plate every 15 minutes to see its progress.
Page 1 and 2: Mosher Analysis of Enantiomeric Pur
Page 3: This is an exceptionally mild metho
Page 7: Plate 20 cm x 20 cm 2.5 mm layer th

Mosher Ester Analysis - Department of Chemistry and Physics

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