D. A. House UniversW of Canterbury ~hristchurch,New zealand
I I
The Resolution of a Racemic Compound An experiment for the inorganic laboratory
Despite a n u m b e r of articles i n this J o u r n a l describing the resolution of racemic coordination compounds (1-3), t h e complexes used present certain difficulties for large scale application. For example, t h e use of expensive resolving agents (3)a n d ligands (2) o r potentially explosive perchlorate salts (2). O u r recent studies o n the resolution of cis- [CoCl(en)damine)]2+ complexes (4, 5)' seem to us to h a v e provided a n examole free from t h e undesirable features of t h e ahove procedures a n d t h e resolution of cis-[CoCl(en)ztMe?tH9)Iy+ ~ n w i d e sa simple case of t h e relativelv diffic u l t technique of racemic modification (6). Resolution of t h e racemic chloro chloride is achieved w i t h potassium (+)-tartrate(-Z)antimony(III) oxide and t h e (+)(+) diastereoisomeride i s practically insoluble i n cold water with almost n o contamcnation from t h e (-)(+) form. T h e (+) cation i s isolated a s t h e tetrashlorozincate(11) s a l t i n good yield b y t r e a t m e n t of t h e (+)(+)ShOT salt w i t h 6 M HC1, followed b y t h e addition of zinc chloride. Isolation of t h e (-) cation is m o r e difficult, as t h e filtrate i s only 60-80% optically pure. Use i s m a d e of t h e difference i n solubility of t h e racernic a n d (-) dithionate salts, with t h e racemic form heing t h e less soluble. T h e (-) dithionate s a l t is readily converted to t h e (-) ZnC12- s a l t b y recrystallization from HCI containing ZnCln.
.
Procedure
~rons.[CoC1~(enlr]CI.HC1.2H10 is prepared hy the method of Schlessinger (7, or Krishnamurthy ( 8 ) . I t is not necessary to use the anhydrous neutral salt but if this is available, a reductivn in the amount of amine used in the next step is necessary. Racemic cis-Chlorobis(ethylenediamine)methylaminecobaNlll) Chloride Hemihydrate, cis[CoC4en)2(MeNH~)]CI2- %Hz0 Slurry 10 g (0.028 mole) of powdered tmns-[CoCla(en)n]CbHCI. 2Ho0 in 10 ml of water and add 4.5 ml of 40% aaueous methvlnmine solution (0.058 mole) with stirring. The color of the reactiun rolution changes from green to red with the addition of the amtne. the temperature r w s slightly, and all the trans.dirhloro chloride dissolves. Leave the continuously stirred solution at room temperature for 5-10 mi". During this time, red crystals of cis-[CoCl(en)z(MeNH2)]C12 deposit. Add methanol (50 ml) in 10-ml portions making sure each lot is well mixed before making the next addition. Cool the resulting mixture in ice for 20 min and then filter the solution through a porosity 2 sintered glass crucible. Remove the mother liquor and wash the product with 2 X 15-ml portions of methanol, then 2 X 15-ml portions of ether, and suck dry. This product (6g, 68%) is sufficiently pure to proceed directly with the resolution. However, e small sample should be recrystallized as the Z n C P salt. The mother liquor contains the aqua or hydroro cations resulting from base hydrolysis of the chloro cation. Further quantities (-1 g) of the chloro chloride can be ohtained by heating the mother liquor with 10 ml of 12 M HCI on a steam bath until the original
-~~.~~
~
'Abbreviations used: MeNHn = methylamine; en = 1.2-diaminaethane; K(+)ShOT = potassium (+)-tartrate(-2)antimony(III) oxide = "tartar emetic? ORD = optical rotatory dispersion; CD = circular dichroism; the wavelengths of the Nao Lines (589 nm) are assumed if no subscript follows the sign of rotation. 124 / Journal of Chemical Education
orange color becomes a distinct red (-30 min). Any yellow Co(en)sst contaminating the original trans-dichloro chloride will precipitate during this heating and can he separated by decantation from the hot solution before cooling in ice. The ehloro chloride deposits as fine red needles. Anolysis: Calcd for [CoCl(en)r (MeNHz)]CI&HzO, CoCsHnN&l3.KH2O: C, 18.45; H, 6.81; N, 21.50%. Found: C, 18.55, H, 6.79; N, 21.65%. Racemic cis-[C~Cilen)~(MeNHz)] ZnCI., Dissolve 1 g of the crude chloro chloride in 20 ml of 0.1 M HCI and warm the solution to 40°C on a steam bath. Add 20 ml of 12 M HCI and 5 g of solid ZnCla. Red crystals deposit from the hot solution and crystallization is completed by ice cooling for 20 min. Filter the product through a porosity 3 sintered glass crucible, wash the crystals with 2 X 10-ml portions of acetone, and air dry. The yield is almost quantitative. Analysis: Calcd for [CoCl(en)t(MeNHn)]ZnClb, CoCsHrlNsZnC4: C, 13.26; H, 4.67; N, 15.46%. Found: C, 13.19; H, 4.69; N, 15.63%. Absorption Spectral Data: h, (nm), 6 (M-'em-'): max 527.72.8: min 420,16.4; malt 367,79.6. Resolution of the cis-[CoCilen)dMeNH2)]
'+
Ion
(Caution: All antimony compounds are toxic at low Levels. The Lethal dose of potassium (+)-tartrate(-2)antimony(III) oxide, K(+)SbOT, for man, is 130 mg. Vomiting usually occurs a t a dose of 30 mg, hut this is a dangerously high level if vomiting does not occur.) Dissolve 11 g (0.034 mole) of K(+)ShOT in 80 ml of water containing 2 g of (+)-tartaric acid by heating almost to hailing. Stir in 5 g (0.016 mole) of the crude [CoCl(en)2(MeNHz)]CInand eool the beaker in an ice bath for 15 min ,with frequent stirring of the solution. Filter the reddish-purple crystals of the (+)(+) diastereoisomeride through a porosity 2 sintered glass crucible and transfer the filtrate to a clean beaker. Wash the product with 2 X 10-ml portions of ice water, followed by 2 X 10 ml of acetone. The yield of the air dried material is -6 g, or -75% based an the amount of (+) chloro chloride used. The (+)(+)ShOT salt is not sufficientlv soluble in water for recrystallization. Anoi)o,s: Calcd for [CI,CI(~~)?~MPNH?J]~S~O-C~H.,~, CoCI:,HlsNsOl,Sb?CI: C , 19.1O; H.R.57: N.8 57%. Fuund.C. 19.20; H. 2.53; N . 8 . 7 h Isolation of (+)-[CoC[en),(MeNH2)]
ZnC14
Slurry 6 g of the (+)(+)diastereoisomeride with 40 ml of water and add 40 ml of 12 M HCI to the stirred suspension. Warm the resulting clear purple-red solution to -40°C on a steam bath and stir in 15 g of solid ZnClt. Maintain a temperature of -40°C until all the ZnCln has dissolved (1-2 min) and then cool the beaker in ice for 20 min with occasional stirring. Collect the purple-red crystals using a porosity 3 sintered glass crucible and treat as for the racemic ZnCldZ- salt. The yield of (+)-[CoCl(en)2(MeNH2)]ZnCI4 is -3 g or 70% based on the (+) chloro chloride available. Analysis: Calcd for [CoCl(en)?(MeNHz)]ZnC11;as above. Found: C, 13.52: H, 4.78: N, 15.38%. Isolation of ( - ) - [ c ~ c ( e n ) ~ ( M e N H ~S20e )] The mother liquor resulting from the preparation of the (+)(+)diastereoisomeride is 60-80% optically pure. Allow the solution to warm to room temperature and stir in 2 g of solid Na2S20e 2H20. Maintain stirring until all the added solid has dissolved. During this time (15 min) most of the racemic [CoCl(en)~(MeNH2)]S206 precipitates and is removed by filtration (yield 1.5 g). Analysis: Calcd for [CoCl(en)n(MeNHz)]S20e; CoCsHzlNsC1S20s: C, 14.80; H, 5.22: N, 17.26%. Found: C, 14.63; H, 5.46; N, 17.12%. Add a further 6 g of Na2S206.2H20 to the mother liquor and repeat the above procedure, only this time eool the beaker in ice for 20 min after all the added solid has dissolved. Filter the microcrystalline product through a porosity 3 sintered glass crucible, wash
ORD and CD Spectral Parameters for the
h-I+)-and A-I-I-[CaCllenl,lMeNH,)1
Cations in 0.1 M HCI a t Room TemPerature.a
If
rM11. deg M-' m-'
a The [ M I A a n d [Aslh valuer cited i n this table are -1.3% greater than those cited in Ref. (51,due in part to the more efficient resolution procedure described here. bThe cited wavelength9 Correspond to the N a D line a n d the maxima, minima, and crorr-over Points in the plot of [MI (or A e ) versus A (see the tig.).
carefully with 2 X 2 ml, then 2 X 10-ml portions of ethanol (it is difficult to avoid slight contamination from precipitated Na2Ss06. 2H20 at this stage) followed by 2 x 10-ml portions of acetone. The yield of the air dried (-)-[COCI(~~)~(M~NH~)]S~O~ is -1.5 g. Analysis: Calcd for [CoCl(en)z(MeNH~)]S206: as above. Found: C, 14.70;H, 5.07; N, 17.30%. The racemic and (-) (or (+)) dithionates are qualitatively distinguished hy the observation that -10 mg of the optically active form is readily soluble in 2 ml of water at room temperature, whereas the same quantity of the racemate is much less soluble. Preparation of ( - ) - [ C O C ( ~ ~ ) ~ ( M ~ N ZnC14 H~)] Add the 1.5 g of (-) dithionate salt to 15 ml of water and warm to 50°C on the steam bath. Add 15 ml of 1 2 M HCI, and then 5 g of solid ZnCh to the resulting clear red solution. Cool the heaker in ice for 15 min, during which time the (-) ZnCL2- salt deposits. Collect the crystals in a porosity 3 sintered glass crucible and proceed as for the racemate. The yield of 1.6 g corresponds to 37% hased on the amount of (-) chloro chloride in the racemate. Anolysis: Calcd for [CoCl(en)dMeNHd]ZnCk as above. Found: C, 13.29; H, 4.78: N, 15.33%. Chiroptical Parameters Rotations a t the Nan lines (589 nm) were measured using a Hilger Mk I1 Standard Polarimeter and the complete ORD and CD spectra (Fig. 1) were obtained with a JASCO ORD/CD/UV5 recording spectropolarimeter. A 0.203% solution of the (+) ZnC142- salt in 0.1 M HCI in a 0.05)' a t room tem2-dm tube gave a rotation of +(0.4 perature. This corresponds to [ n ] = ~ t ( 9 9 f 10) deg cm3 g-' dm-' and [MID = +(450 50) deg M-' m-I. More accurate measurements, using the JASCO instrument gave [MID = +(488 & 8) deg M-' m-I. For the (-) ZnC1d2- salt, [MID = -(485 8) deg M-'M-' m-I. A comparison of the full ORD curve (see the fig.) with that of A-(+)-[CoCl(en)vNH#+ (9. 1 0 ) shows that (+)-ICoCl(en).(5; lij. ( M ~ N H ~alsohes ) ] ~ the A absolute confi&r&n T h e comnlete chirontical oarameters for the (+) and (-)[~o~l(enj2(~e~ i o~kzare f l listed ~ + in the tab~d.
+
+
+
Additional Experlments Students may analyze their products for Co (12) or total halogen, and most of the supplemertary work suggested by Kauffman and Lindley (3) for the bromoammine analog can he suitably applied to the optically active chloromethylamine complex. If the zinc(I1) ion interferes (as in the reaction with OH-), the corresponding dithionate salts may he used. The solubilities of the racemic and active dithionate salts can be measured quantitatively by spectrophotometric analysis of the saturated solution a t constant temperature (13) and the X-ray powder patterns of the ra-
,so
'rn
'50
=-m*
%'
5%
cm
,",
spectrum 01 h - ( f ~ [ C & l ( e n ) ~ ~ e(N O~ W~, )CD ] ~spectrum of A(-~[c~Cl(enk(MeNH~)]~+ (CD). and visible absorption opechurn of rac[C&l(enk(MeNH2)]2+ ( A S ) in 0.1 M HCi at room temperature. Each or& nate division corresponds to f300 deg M'm-' in [MI and f0.060 M'cm-' in [As],respectivet$ ORD
cemic and active salts can also be measured. For the dithionate, the powder patterns of the racemic and active forms are almost identical, but this is not the case for the ZnCL2salts. The rate of racemization of the aqua ion h a s been measured (5). Acknowledgment I thank Mr Ian Kindred for helpful comments and Miss Helen Scott for providing the trans-[CoClz(en)2]CI.HCl2H20. I also thank the New Zealand University Grants Committee for providing funds to purchase instruments used in this work. Literature Cited 111 Kauffman, G. B.. andTskshashi. L. T.. J. CHEM. EDUC.,39.481119621.
121 KsuWman.G.B..Sugisaka,N..and Reid.1. K.. J. CHEM.EDUC..41.461 (1964). 131 Kauffman. G. B.,and Lindley, Jr.. E. V., J. CHEM. EDUC.51.425 (19741. 141 Kindred. I. J.. and House, D. A.. lnorg. Nvcl. Chsm. Led., LO. 25 (19741. (51 Kindrod.1. &and Hou~e.D.A..Imrg, Chim. Aeio, ld.18511975). 161 Wil1iems.F. T., J.CHEM.EDUC.,39.211 (1962). 171 Sehlerringer, G. G.. "Inorgenic Laboratory Pnpsrationr"Chemiea1 Publishing Co.. Inc.. New Yolk, 1962. P. 237. 181 Krilhnsmurthu.M.. J . Inore. N u 1 Chem.. 34.3916 119721 191 Garbett. K.,a~d~iilerd, R . ~ . , J .Chem. ~m..'6084(i9651: 1101 Norman. B. J.,Inora Chim. Act.. 1.177 (1967). (111 in or^. chem.. 9, I (i9701. (121 Hughe8.R. G.. Endieoff, J. F..Hoffman.M.Z..andHouae.D. A,, J.CHEM. EDUC., 46,140 (1960).
(131 Yamanari, K.,Hidada, J.,andShimurs,Y.,Bull. Chem. Soc J o n , 16,3724 119731.
Volume 53, Number 2 Februafy 1976 / 125
