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Title About Thin Layer Chromotography Thin-Layer and Column mobile phase is easily controllable. Chromatography: Identifying an Using pure solvents alone, or a Unknown Analgesic, Determining an combination of different solvents, allows Ideal Mobile Phase and Monitoring for the possibility of an infinite range of the Progress of the Mitsunobu polarities. Pure solvents alone range Reaction. from polar to non-polar and mixtures of solvents will result in a wider variety of Ben Zene polarities. The choice of mobile phase is crucial for a clean separation. If the Nazareth College of Rochester, 4245 East Ave, Rochester New York 14618 solvent chosen is too polar the components will move too close to the [email protected] solvent front and likewise if the solvent is not polar enough the components will Aspirin was compared to five standard remain too close to the origin. In either analgesics using thin-layer scenario, separation is poor. The ideal chromatography (TLC). The ideal mobile phase will move the components mobile phase solvent for the Mitsunobu about half way between the origin and reaction was determined as 35% ethyl the solvent front. acetate and 65% hexane. The progress of Two common types of a Mitsunobu reaction was monitored chromatography are thin-layer using column chromatography and TLC. chromatography (TLC) and column chromatography. TLC is useful for Chromatography is an efficient separating and identifying unknown and relatively simple technique for components of a mixture using pnly separating and identifying components small amounts of the mixture. In TLC, of a mixture. The components are the stationary phase consists of silica or separated because they have different alumina coated on a glass or plastic affinities to two distinct phases. One plate. For large separations or phase is stationary, while the other is purifications where the product is mobile. needed for further experiments, column In most chromatography chromatography is advantageous. The experiments, either silica, or alumina, stationary phase in a column serves as the stationary phase.1 Silica chromatography experiment is also silica and alumina are both polar and their or alumina packed into a column with a polarity remains constant throughout the constraint at one end or into a buret. experiment. The term absorbent is Although 20-50 g of the silica or commonly used when referring to the alumina per gram of sample will often stationary phase. A mobile phase suffice, some separations require ratios consists of a solvent that moves up a of 200:1 or higher.2 It is important to plate by capillary action or down a select a column that will completely column due to gravity. Unlike the contain the absorbent with about 10-15 stationary phase, the polarity of the cm to spare and the height of the column 3 should be at least ten times its diameter. 1 Lehman J.W. Operational Organic Chemistry. A Problem-Solving Approach to the Laboratory Course, Third ed; Prentice Hall: Upper Saddle 2 Lehman, pp 618. River, NJ, 1999; pp 618. 3 Lehman, pp 619. In a previous experiment, a between the movements of the spot to common analgesic was isolated from a the movement of the solvent front 2. prepared mixture by extraction. The Because this ratio is the movement of a common analgesic and five standard spot in relation to the distance the analgesics (salicylamide, ibuprofen, solvent front moved, the solvent front aspirin, acetaminophen and caffeine) does not need to reach any specific point were analyzed using TLC. The unknown before it is removed from the developing and the five standards were all UV chamber. Rf values ensure the ability to visible. Because the analgesics travel compare the spots from two or more different distances up the plate they must different plate, assuming that the mobile have different affinities to the mobile phase used remained constant for all the phase. In this experiment the mobile plates. phase was 200:1 ethyl acetate: acetic acid. The spot for the unknown was view under a UV lamp to be between the spots of aspirin and acetaminophen 1. We knew that the analgesic could not be acetaminophen because acetaminophen is too weak to react with HCl of the aqueous layer in the extraction mentioned previously.4 We concluded, then, that the unknown was most likely Rf = X/Y aspirin. Figure 3 The Rf values for the analgesic TLC plates are given in Table 1. There is a difference of 0.066 between the Rf value for the unknown and the Rf value for acetaminophen, and there is a -0.077 difference between the Rf values of the unknown and aspirin. Table 1 Figure 1 Analgesic Rf Value Acetaminophen (A) 0.476 By simply looking at different Salicylamide (S) 0.738 TLC plates, it is often difficult to 0.362 compare the movement of the spots. In Aspirin (Asp) 0.619 order to compare the spots, Rf values are Ibuprofen (I) 0.785 calculated. An Rf value is the ratio Caffeine (C) 0.362 unknown (#2) 0.542 4 Knoerzer, T. Fall Organic Chemistry Exp. #3. 2002. The differences between the http://www.pub.naz.edu:9000/~organic/fall/fallor unknown spot and the two standard spots ganic/labstuff/fallexp3.htm are very close which poses difficulties for identification, even though we know the unknown is not acetaminophen. Ideally, the unknown, aspirin and acetaminophen should be spotted on another TLC plate using a solvent that is not as polar as the mobile phase. A slightly less polar solvent would move the spots towards the middle of the plate, away from the solvent front and hopefully yield more distinct Rf values. The method of chromatography is also used for purification. In a synthesis of α–Acyl-Functionalized Figure 3 Azacycles, part of a reaction was found to contain 77% of the desired product by 5 “chromatographic purification.” sm PPh3 p sm PPh3 p sm PPh3 p sm PPh3 p 100% EtOAc 90% EtOAc 75% EtOAc 50% EtOAc 10% hexane 25% hexane 50% hexane sm p p PPh3 sm PPh3 sm PPh3 p 35% EtOAc 25% EtOAc 100% hexane 65% hexane 75% hexane Figure 4 5 Occiato, E.G.; Prandi, C.; Ferrali, A.; Guarna, A.; Deagostino, A.; Venturello, P. J. Org. Chem.2002, Vol. 67, No. 20, 7144-7145. Monitoring the progress of a reaction is and move more components down the a third application of chromatographic column than were desired. After techniques. collecting ten fractions, the first, fifth In order to monitor the progress and tenth fractions were analyzed by of the Mitsunobu reaction, we needed to TLC in order to find out if the samples determine the ideal mobile phase for contained pure components. The first separation using TLC. Seven mobile fraction contained a faint spot while the phases consisting of different quantities fifth fraction was pure. The tenth of ethyl acetate (EtOAc) and hexane fraction contained the desired product were tested using TLC. Because the along with a faint impurity spot. The ten reactants and products were UV visable, fractions were combined together the plates were viewed under a UV lamp because we were more concern with 4. The ideal mobile phase is somewhere separation than of complete purity. The in the range of 50% (EtOAc): 50% combined ten fractions will be used for hexane to 35% EtOAc: 65% hexane. further experiments. Both the 50:50 and 35:65 mixtures of ethyl acetate: hexane moved the spots Experimental Section halfway up the plate. The lower spots in the PPh3 and P lanes are the same Identification of aspirin. To separate material, a byproduct, meaning that the solutions of ethanol were added the reactant mixture is not pure 3. However, unknown, salacyimide, aspirin, caffeine, because there is no starting material or acetaminophen and ibuprofen. The triphenylphosphine (PPh3) left in the mobile phase used was 200:1 ethyl product (P) lane, the reaction went to acetate: acetic acid. Spots were viewed completion. under a UV lamp. As for the other mobile phase solvents, 100% EtOAc solvent was too Determination of the ideal mobile polar and the spots moved too far up the phase in order to monitor the progress plate. Likewise, the 100% hexane of the Mitsunobu reactoin. The mobile solvent was very non-polar and the spots phases tested were 100% ethyl acetate stayed too close to the origin. (EtOAc), 90% EtOAc and 10% hexane, Once the ideal mobile phase was 75% EtOAc and 25% hexane, 50% determined, column chromatography EtOAc and 50% hexane, 35% EtOAc was used to monitor the progress of the and 65% hexane, 25% EtOAc and 75% Mitsunobu reaction mixture. Collecting hexane, and 100% hexane. Spots were fractions from column chromatography viewed under a UV lamp. is valuable for large separations and purifications, especially when the Column chromatography. To a buret components are needed for further column of 36 cm in length and 2.5 cm in testing or reactions. The desired product diameter was added 1.5 cm of sand, of the Mitsunobu reaction, was separated followed by 15 cm of dry 70-30 mesh using a 1:9 ethyl acetate: hexane mobile silica, followed by 1.5 cm of sand. The phase. The ideal mobile phase was not column was packed with a 1:9 hexane: used at the beginning of the EtOAc mobile phase. The column was chromatography because the 35% flashed with nitrogen. Ten fractions were EtOAc 65% hexane would be too polar collected and the first, fifth and tenth fractions were tested using TLC with a 35% ethyl acetate, 65% hexane mobile phase. Supporting Information Available: Lehman, John. Operational Organic Chemistry: A Problem-Solving Approach to the Laboratory Course, Third edition. Prentice Hall: Upper Saddle River, NJ, 1999; pp 116, 617 – 630.
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