cxeeniment 14 Optical Resolution of Co(en)33+ Note: This experiment requires 6 hours spread over two laboratory periods. One fascinating and important property of molecules is that they often exist in right- or left-hand forms, Such forms are called enantiomers or optical isomers, the latter term referring to the ability of such isomers to rotate the plane of polarized light. If equal amounts of the two enantiomers are present in a sample, the optical effects of the right- and left-hand forms cancel and no net rotation of light is seen, Such samples are called racemic mixtures. In the present experiment, you will synthesize a racemic mixture of a coordination complex, and then sepa- rate it into its two enantiomers. Optical activity is frequently associated with organic molecules containing an asymmetric carbon atom, as, for example, in lactic acid. OH HO, Hoc—c, a X cls He 7 a if Optical activity, however, is a far more general phenomenon and may be found in any molecule that cannot be superimposed upon its mirror image. In inorganic chemistry, there are many examples of optically active compounds that come in right- and left-hand forms. Although a few tetrahedral inorganic compounds have been resolved into their enantiomers, optical activity in octahedral transi- tion metal complexes has been studied far more extensively. Many octahedral complexes of transition metals can be resolved into two enantiomers. Some of the earliest work in this area was done in 1912 by Alfred ‘Werner on Co(en)s** (where en = NH2CH2CH2NH;). The enantiomers of Co(en)s** that he resolved have the structures shown in Figure 14-1. 143144 Part Ill / COORDINATION CHEMISTRY A (4) enantiomer A) enantiomer Figure 14-1 : ‘Structures of the enantiomeric forms of Co(en);*. One of the isomers rotates plane polarized light toward the right (dextrorotatory) while the other isomer rotates the light by the same amount in the opposite (levorotatory) direction. These directions are designated (+) and (—) (or some- times d and 1), respectively. Because of the availability of sodium arc lamps as a light source, light of 589.3-nm wavelength (the sodium D line) is frequently used in the determination of the rotations. Passing this light through a polarizing prism gives plane polarized light, whose electric field variation is shown in Figure 142, Polarizing innalyest len mien f Optically set Taw, S oak plane Aotated tee ‘Sodium polarized plane am ven vont Figure 14-2 Schematic of an optical polarimeter. In order for the rotated polarized light to pass through the analyzer prism, this prism must be rotated, relative to the polarizing prism, to the right or left by an angle that is equal to the rotation caused by the sample. Thus, the direction and number of degrees of rotation (2) may be measured experimentally. As in any form of spectroscopy, the size of the rotation depends not only on the nature of the optically active material but also on the length, (in decimeters), of the light path through the sample and the concentration, ¢ (in g mL~"), of the samplesnperiment 14 / Optical Resolution of Co(en)s** in a solvent. A parameter called the specific rotation [2], has been defined as follows: iz a) The wavelength, 2, of light is also specified. If the rotation is measured at the wavelength of the sodium emission line at 589.3 nm (as is commonly done), the specific rotation is designated (1). . A unit that is frequently of more value for comparison between compounds is the molecular rotation, [1], Mal, i, = AH Because M is the molecular weight of the substance, [/], is relative measure of its rotatory power on a molecular basis. The rotatory power of a substance varies with the wavelength of the light employed. Thus, it is possible for a molecule to be dextrorotatory toward light of 589,3-nm wavelength, but levorotatory at another wavelength. The values of [M]; as a function of wavelength are shown for (+)Co(en);°* in Figure 14-3. This plot is called an optical rotatory dispersion (ORD) curve. Because the values of [M], for enantiomers at any given wavelength are of the same magnitude but of opposite sign, the ORD curve of (—)Co(en);°* may be obtained by rotating the curve for (+)Co(en)3** by 180° around the 0° line in the figure. 4000" Sodium tine at 589.3 nm 200° ie (mn, =2000° ~4000° 400 500 600 700 nm Figure 14.3 Optical rotatory dispersion curve for A(+)Co(en)s°* 145146 IIL COORDINATION CHEMISTRY Although its optical activity indicated that (+)Co(en);** must have one of the structures shown in Figure 14-1, the correct structure was not determined until 1954. By means of a special X-ray technique, @ Japanese research group established the absolute configuration of (+)Co(en)s°* as being that shown on the left in Figure 14-1. To show that the absolute configuration is known, the con- vention of using A to designate this configuration has generally been adopted. Its mirror image, (—)Co(en)s**, must then have the absolute configuration shown on the right of Figure 14-1. It is labeled A(—)Co(en);**. Although the lower case letters d and indicate the nature of the optical absorption at a particular wave- length, and the upper case Greek letters A and A designate the handedness of the molecular structure, it is important to remember that these phenomena are not simply related. Molecules with A configurations can be levorotatory, for example. Most biological compounds such as nutrients and drugs are optically active (and often only one enantiomer occurs in nature). In recent years, the study of optical activity in metal complexes has assumed great importance because opti- cally active metal catalysts allow the selective synthesis of enantiomerically pure organic compounds. An example of an optically active metal catalyst is shown below: (Cote CHa Py TS. ve m oo (alkene) {Catal (akene)..., The preparation, resolution, and characterization of the optical isomers of Co(en);** are the objects of this experiment. The preparation of the complex is similar to that used in the preparation of Co(NH;)sCP* in Experiment 13. A solution, of Col! is oxidized in the presence of en to give the Coll! complex Co(en)s**. The oxidant is hydrogen peroxide CoCh-6H20 + 3en-2HCl — [Cofen)s]Ch + 6H,0 + 6HCI [Cofen);]Ch + }NaOH + 3 HCl + } HhO, + } HO —> [Cofen)s]Cls:}NaCl-3H20 In the present experiment, the resulting [Co(en)3]Cly -} NaCl - 3 H;0 is iso- lated as a mixture of the two optically active isomers, and is then resolved by crystallization in the presence of the optically active anion (+)tartrate [abbre- vated (-+)tart].Experiment 14 / Optical Resolution of Co(en)s3~ 147 In the present case, [(+)Co(en)s][(+-)tart]Cl is less soluble than [(—)Co€en)s(+)tart]Cl and preferentially crystallizes from solution as the pen- tahydrate: (4)Cofenys** | Ctand= %, { [CHColensl+tar}ct-5 120 | (-)Cofen)3** 10, [(-)Co(en)s]{(-+)tart]Cl where the | symbol next to a formula indicates that the compund precipitates from solution. The [(+)Co(en)s][(+)tart]Cl, whose [2] xg, is +102° , is subse- quently converted to [(-+)Co(en)s]Is » H2O by addition of I>. The [ago of the iodide salt is +89°, [4)Cofen)s}[(+)tart]Cl + 31” —+ [(+)Co(en)s]1s-H2O | + (+)tar? + Cr The other optical isomer, [(—)Co(en):Jls, is obtained by adding I~ to the solu- tion from which [(+-)Co(en)3][(+)tart]CLS HO was previously precipitated. The solid that precipitates with I” is a mixture of both (+) and (-) isomers of {Co(en):]l- HO, although it is enriched in the (—) isomer. Interestingly, [(-)Cofen)3}I3 HzO is much more soluble in warm water than the racemate and may be extracted into solution, which on cooling reprecipitates the desired enantiomer, ((—)Co(en)s]I3-H20, whose [2}559, = -89°. You will establish the optical purities of the isolated (+) and (—) enantiomers by measuring their specific rotations. Finally, it will be shown that the resolved compound may be racemized by boiling an aqueous solution of one of the enantiomers in the presence of activated charcoal. EXPERIMENTAL PROCEDURE ‘Tris(ethylenediamine)cobalt(III) Chloride, [Co(en);|Cl-} NaCl-3 HO. Put 6.0 g (25 mmol) of CoCl,-6 HO, 13.3 g (100 mmol) of ethylenediamine dihydrochloride, and a str bar in a 250-mL beaker and add approximately 25 mL of water. Stir for a minute or so to dissolve the cobalt salt. The mixture will appear a cloudy pink. Then add 8.0 g (200 mmol) of sodium hydroxide pellets and stir. A cloudy orange solution is formed. Stir for a few minutes until the sodium hydroxide is completely dissolved. Add 20 mL (20 mmol) of 3% HzO, (adjust amounts if a different concentration of hydrogen peroxide is used). The solution darkens upon addition of the peroxide. Dilute the mixture to 50 mL, and heat to boiling for a few minutes on a stirring hot plate until the cloudiness dis- appears. Remove the stir bar from the hot solution with a “magnet wand”, and then place the beaker in ice and let it cool for 30 min. With a suction filtration apparatus (see Fig. 13-1) and a 150-mL medium porosity glass frit, collect the fine orange to yellow-orange needles that have formed in the cooled beaker. Wash the crystals on the frit first with 50 mL of 95% ethanol and then with 20 mL of diethyl ether. Pull air through the crystals on the frit until they are dry and have warmed to room temperature. Record the yield. The filtered solution can be discarded.148 Part Ill | COORDINATION CHEMISTRY Resolution of the Tris(ethylenediamine)cobalt(II1) Ton Put 6.0 g (14.0 mmol) of [Co(en)3JCls-}NaCl-3H20, 2.6 g (17.4 mmol) of (+)tartaric acid, and a stir bar in a 100-mL beaker and add 20 mL of water (adjust the quantities if you use a different amount of the cobalt starting mate- rial), Then add 1.4 g (35 mmol) of sodium hydroxide, and cover the beaker with a watch glass. Gently stir the mixture, and heat on a stitting hot plate for a few ‘minutes until the solids completely dissolve. Remove the stir bar with a “magnet wand", and then let the solution cool to room temperature overnight, (If the solution is to be left for more than 24 h, seal the mouth of the beaker with Par- afilm®,) Here is a good stopping point for the first day's work. ‘After 24 h, collect the parallelepiped-shaped dark orange crystals with a suc- tion filtration apparatus and a 60-mL medium porosity glass frit. Transfer the filtrate to a beaker and save this solution, which contains the other isomer. After you have transferred the filtrate out of the suction filtration apparatus, wash the crystals on the frit first with 20 mL of a 1:1 mixture of water and acetone, and then with 20 mL of pure acetone. Pull air through the crystals of [-)Co(en)sI{(+)tart]Cl-5 HO until they are dry and have warmed to room temperature. Record the yield. To determine the specific rotation of this compound, dilute approximately 0.5 g of the sample to a solution volume of 10 mL. Introduce this solution into a 1-dm (where dm = decimeter) polarimeter tube, tilting the tube as necessary to remove bubbles from the light path. Following the manufacturer's instructions, first adjust the polarimeter so that the angle of rotation is zero when there is no sample in the instrument. Then introduce the polarimeter tube containing the sample solution into the polarimeter, and measure the sign and magnitude of the rotation. If the instrument requires visual matching of fields, darkening the room is helpful. Calculate [a}s59 5 for [(+)Co(en):][(+)tart]Cl 5 H20. To convert the tartrate salt to [(-+)Co(en)s]Is-H20, put 2.0 g (3.9 mmol) of [(+)Co(en)s][(+)tart]Cl-5 H20 in a 50-mL beaker. If the crystals are large, break them into smaller pieces with a spatula. Add one pellet of sodium hydroxide, a stir bar, and 15 mL of water (adjust amounts if more or less than 2.0 g of {(+)Co(en)s][{(+)tart]Cl-5 H20 is used). With stirring, heat on a stirring hot plate for a few minutes until all the solids dissolve (do not heat for more than 5 min or the cobalt complex will racemize). Add 3.6 g (24 mmol) of NaI. Continue heating and stirring for 1 min, cool the solution in an ice bath, suction filter, and wash the crystals with an ice cold solution of 3 g of Nal in 10 mL of water to remove the tartrate. Wash the crystals with 10 mL of ethanol and then with 10 mL of acetone, allow the {(-+)Co(en)s]Is-H30 to air-dry, and determine the yield. Mea- sure the [@]ggp of the product using a solution of approximately 0.5 g of sample in 10 mL of water. To isolate [(—)Co(en)s]I-H20, dilute the filtrate from which [(+)Co(en)s][(+)tart]Cl-S H20 was precipitated (sce previous discussion) to 30 mL. Add one pellet of sodium hydroxide. Heat the solution until the sodium hydroxide dissolves and add with stirring 8.5 g (57 mmol) of Nal. Cool the solution in an ice bath, collect the impure {(-)Co(en)s]fy-H20 precipitate by fil- tration, and wash the precipitate with a solution of 3 g of Nal dissolved in 10 mL of water. To purify, dissolve the precipitate, with stirring, in 35 mL of water at 50°C. Filter off the undissolved racemate and add 5 g of Nal to the filtrate.Experiment 14 / Optical Resolution of Co(en)s?* Crystallization of [(—)Co(en)s]ls-H2O occurs on cooling. Collect the precipitate by filtration, wash with 95% ethanol and then with acetone, and finally air-dry. Determine the yield and evaluate (2.0 Racemization of (+)Co(en),** or (—)Co(en);** Dissolve approximately 1 g of either {(-+)Co(en)sls-H30 or [(—)Co(en)s]ls-H20 ina minimum volume of warm water. Add a small amount of activated charcoal and boil the solution for approximately 30 min. Then filter the solution while hot, and add a few grams of Nal to aid in the precipitation of the racemate. Wash the product with a few milliliters each of 95% ethanol and acetone, and then air-dry. Determine [aqys 3 of the preciptiated [Co(en)s]ls-Hz0 racemate. REPORT Include the following: 1. Percentage yields of [Cofen);JCls-} NaCl-3 HO, [(+)Co(en)s]{(+)tart]Cl- 5 HO, [(-+)Co(en)s]ls-H20, and [(—)Co(en)s]f-H20. 2. The [algo and [M]ogy, values for the above complexes. (If an ORD. spectrometer is available, record their ORD curves.) 3. If [als of pure {(+)Co(en)s]Is"H20 is +89°, what percentage of your sample of this compound is actually this enantiomer? Assume that the only impurity is [(—)Co(en);]Is-H)O. Do the same calculation for your sample of [(—)Co(en)s]1s-H20. 4, The [a)sg9 3 of the [Co(en)s]]s-HzO, which is isolated from boiling a solution of (4) or (—) Co(en);** with activated charcoal. PROBLEMS Plot an ORD curve for (—)Co(en);** analogous to that given in Figure 14-3 for (+)Co(en)3** 2. If you were to resolve an unknown complex, M(en);**, how would you know ‘whether or not your resolved products were optically pure? 3. Draw structures of the geometrical and optical isomers of Co(gly)s, where aly = NH2CH:COO~ 4, Why is it not possible to resolve Co(en); 5, Draw structures of the optical isomers of Co(EDTA)-, where EDTA = ((O;CCH,)2NCH;CH,N(CH,CO2~)2. Assume that both nitrogen atoms land one oxygen in each carboxylate “arm” coordinate to Co. 6. In the preparation of Co(en);**, what is the purpose of the hydrogen peroxide? 7. In the purification of both (+) and (-) [Co(en)s]Is-H20, the compounds were washed with water containing Nal. What was the purpose of the Nal? 8. Outline methods for analyzing ((-+)Co(en)s]ls:H2O for its Co and I content. 9. The optically active tris(oxalato) complex, Cr(C20,);*", racemizes faster than it exchanges oxalate with free CO," in solution. This latter fact was determined by using radioactive “C labeled C04?" in solution. Postulate a ‘mechanism for the racemization. 2+ 149150 Part lll | COORDINATION CHEMISTRY INDEPENDENT STUDIES A. Confirm the four-ion nature of [Co(en)s]Is-HzO by measuring its molar con- ductance (see Experiment 13). B. Measure the 'H NMR spectrum of [Co(en)s]ls-H20 in D:0 solvent. (Beattie, IK. Acc. Chem, Res. 1971, 4, 253.) C. Prepare and resolve (Ni(o-phen)3}(ClO4)2, where o-phen is 1,10-phenanthro- line, into its d and / enantiomers. (Kaufman, G. B.; Takahashi, L. T, Inorg. ‘Synth, 1966, 8, 227.) D. Record and compare the UV-vis spectra of the optical isomers of [Cofen)s]ly-H:0. E, Prepare the cage complexes [Co(dinosar)f* or [Co(sepulchrate)["* from racemic or from enantiomerically pure samples of Co(en);**. Dinosar and sepulchrate are hexamine ligands that encapsulate the cobalt atom. (Harrowfield, J. M.; Lawrance, G. A.; Sargeson, A. M. J. Chem, Educ. 1985, 62, 804; Gahan, L. R.; Healy, P. C.; Patch, G. J. J. Chem. Educ. 1989, 66, 445.) F. Prepare and resolve the carbon-free optically active compound [Co{(OH),Co(NH;)3}3]°*. (Kauflman, G. B.; Pinnell, R. P. Inorg. Synth. 1960, 6, 176. Yasui, T.; Ama, T.; Kauffman, G. B. Inorg. Synth. 1992, 29, 169.) REFERENCES Resolution and Characterization of Co(en)s?* Bell, C. F. Syntheses and Physical Studies of Inorganic Compounds, Pergamon: New York, 1972, Chapter 22. A summary of physical studies of Co(en)s°* Broomhead, J. A.; Dwyer, F, P.; Hogarth, J. W. Inorg. Synth. 1960, 6, 183 (Cramer, R. E.; Huneke, J.T. Jnorg. Chem. 1975, 14, 2565. Infrared spectrum of Co(en);** ‘Techniques of Optical Activity Lever, A. B. P, Jnorganic Electronic Spectroscopy, 2nd ed., Elsevier: New York, 1984. Woldbye, F. in Technique of Inarganic Chemistry, Jonassen, H. B; Weissberger, A., Eds, Wiley: New York, 1965, Vol. IV, p 249, Instrumental methods, theory and survey of the Titerature of optical rotatory dispersion and circular dichroism, Optical Activity Douglas, B. E5 Saito, Y., Eds. Stereochemistry of Optically Active Transition Metal Com- ‘pounds, ACS Symposium Series 119, American Chemical Society: Washington DC, 1980, ‘A compilation of research results in the field. Hawkins, C.. Absolute Configuration of Metal Complexes, Wiley: New York, 1971. Theory of ‘optical activity in transition metal complexes, Kaufman, G. B. Coord Chem. Rev, 1974, 12, 105. Historical account of Alfted Werner's research on optically active coordination compounds, ‘Mason, 8, F, Molecular Optical Activity and the Chival Discriminations, Cambridge University: ‘New York, 1982. Theory of optical activity and spectroscopic methods. Saito, Y. Inorganic Molecular Dissymmetry, Springer-Verlag: Berlin, 1979. Text on optically ‘active inorganic complexes. Shields, T, P.; Barton, J. K. Biochemisnry 1998, 34, 15037, The use of optically active Ri ‘complexes to recognize and cleave sequences of DNA. ‘yon Zelewsky, A. Stereochemistry of Coordination Compounds, Wiley: New York, 1996. Wilkins, R. G. Kinetics and Mechanism of Reactions of Transition Metal Complexes, 2nd ed, VCH: New York, 1991. Review of rates and mechanisms of coordination compounds.