Synthesis and Resolution of Chiral Cobalt Complexes

Robert Samples

Abstract
Fractional crystallization is an important technique in organic chemistry used to separate a
racemic compound by exploiting the solubility differential of the + and stereoisomers of its salt with
a chiral compound. The tartrate salt of the Cobalt ethylene diamine complex can be precipitated as
chiral crystals easily and thus are an ideal model for chiral seperations. The efficiency of separation
was be determine by comparing polarimetry results with literature values or standards.
Introduction
N H
H N

H
N

N H
H N
C o

C o
H N
N H

N
H

H N
N H

O H

H
N
N
H

H O
O H
O

O H

Fig. 1: Left- [-Co(en)3] Center: [-Co(en)3] Right: (+)-tartaric acid

Salts of chiral cations with chiral acids can be fractionally crystalized so that one isomer is
seperated selectively by exploiting solubility differences between the two cation sterisomers. These
salts can then be converted into the hydrogen iodide salts so that enatiomeric excess can be measured
using linear polarimetry and circular dichroism without interference of the chiral resolving agent.
Linear polarimetry utilizes the ability of a chiral molecules to rotate linear polarized light by measuring
the angle change between input and output linear polarizers compared to the solvent. The the degree of
rotation can be compared to a literature value to establish the enatiomeric excess of the compound.
Circular dichroism utilizes pulses of left and right circularly polarized light that are absorbed
differently by + and stereoisomers of a compound to calculate the purity.
Materials and Methods
Materials
Cobalt (II) chloride hexahydrate (98%), Ethylenediamine dihydrochloride (98%), Sodium
Iodide ( 99.5%), L-(+)-tartaric acid (99%), Diethyl Ether (ethanol stabilized, 99%), and Sodium
hydroxide (98%) were purchased from Alfa-Aesar with no further purification. 30% hydrogen peroxide
(ACS Reagent Grade) from alfa-aesar was diluted with deionized water to 3% by volume. Acetone
(ACS Reagent Grade) was purchased from Pharmaco-Aaper. Ethanol (95%) and DI water were
obtained from the Hall-Atwater solvent system.
Synthesis of racemic [Co(en)3]Cl3 . NaCl trihydrate
6.000 g (25 mmol) CoCl2 hexahydrate, 13.300 g (100 mmol) ethylene diamine hydrocholride
and 2 ml water in a 250 ml beaker and stirred until the cobalt salt dissolved to yield a pink
uncomplexed solution. 8.110 g (0.2028 mmol) NaOH was added to the solution and allowed to
dissolve affording a nearly opaque dark red solution of cobalt ethylene diamine complex solution. The
solution was diluted to 50 ml volume with DI water and and boiled until homogenous and then cooled
on an ice bath for 30 minutes. The needle like dark orange crystals were filtered through a 150 ml

medium ceramic frit filter and washed with 50 ml 95% ethanol and the 20 ml diethyl ether and allowed
to dry affording 3.2392 g (6.70 mmol, 26.7% yield) [Co(en)3]Cl3 . NaCl . 3 H2O .
Fractional crystalization of [-Co(en)3][(+)tartrate]Cl hexahydrate
3.000 g (6.212 mmol) [Co(en)3]Cl3 . NaCl . 3 H2O, 1.310 g (8.73 mmol) with the
remaineder retained for analysis, (+)tartaric acid and 10 ml water was placed in a 100 ml beaker and
stirred until the cobalt salt was dissolved. 0.7 g (13 mmol) NaOH was added and the beaker covered
with a watch glass and gently heated until all solids dissolved to afford a dark orange solution. This
solution was allowed to cool overnight to precipitate crystals but as racemic hexagonal crystals were
formed the solution was reheated and allowed to precipitate stereoselectively.
The dark orange crystals of the cobalt salt were filtered out using a 50 ml medium frit ceramic
filter and washed with 20 ml 50% acetone in water followed by 20 ml 100% acetone. The crystals
were allowed to dry and then were weighed and 500 mg aliquoted for later analysis. 1.5622 g product
was collected (3.678 mmol, 58% yield)
Conversion to [-Co(en)3]I3 .monohydrate
1.5622 g (3.678 mmol) of [-Co(en)3][(+)tartrate]Cl hexahydrate and 10 ml of a sodium
hydroxide solution containing 1 pellet NaOH/15 ml. The solution was gently heated for 10 minutes
with stirring until all solids dissolved and then 2.3985 g (16.1 mmol) sodium iodide added and the
solution heated for an additional minute. The solution was cooled on an ice bath and the precipitate
filtered and washed with 10 ml 30% w/v NaI in water solution, then 10 ml 95% ethanol and finally 10
ml acetone and allowed to air dry before weighing. 1.5155g [-Co(en)3]I3 .monohydrate (2.362
mmol, 64% yeild)
Isolation of [-Co(en)3]I3 . monohydrate
The filtrate from the previous section containing the opposite stereoisomer was rotovaped to
remove organic solvent and diluted to 30 ml with water and 1 pellet NaOH added. The solution was
gently heated until the hydroxide was dissolved and 8.5g NaI (57 mmol) and the solution and stirred to
dissolve. The solution was cooled on an ice bath to percipitate the dark orange iodide salt. The salt was
filtered through a medium frit ceramic filter and washed with 10 ml ice cold 30% w/v NaI in water
solution. The solids were redissolved in 35 ml water with heating at 50 C and filtered to remove
insoluble impurities. The filtrate was cooled on an ice bath following the addition of 5 grams of NaI.
These resultant purified crystals were filtered as before and washed with a small amount of 95%
ethanol and then acetone and then allowed to air dry before being weighed. 866.5 mg product was
afforded (1.35 mmol, 21% yield relative to racemic chloride)
Characterization
UV-Vis spectrophotemetry was conducted on a Hitachi U-2900 Spectrophotemeter with 1.25
mg/ml [-Co(en)3]I3 .monohydrate and 5.00 mg/ml [-Co(en)3][(+)tartrate]Cl hexahydrate and 5.00
mg/ml [-Co(en)3]I3 . Monohydrate samples. Linear polarity was conducted using a Vernier chemical
polarimeter.

Results
Overall Yield was low as detailed in Table 1. 58% for [-Co(en)3][(+)tartrate]Cl hexahydrate, 9.44%
for [-Co(en)3]I3 .monohydrate and 5.4% for [-Co(en)3]I3 . Between both isomers only 7.42% of the
cobalt was recovered.
Table 1: Yields for various intermediates and products
Step
[-Co(en)3]
[Co(en)3]Cl3 . NaCl . 3 H2O
synthesis

[-Co(en)3]
26.70%

Tartrate formation and Fractional

crystallization

58%

0%

Conversion to Iodide

64%

21%

Total

9.44%

5.40%

Polarimetry
Table 2: Linear polarimetry results and enatiomeric excess values
Trial[[-Co(en)3][(+)tartrate]Cl [-Co(en)3]I3 . H2O
Co(en)3]
6 H2O
0.02 g/ml 1.04 dm path
[(+)tartrate]Cl 0.0252 g/ml 0.425 dm path
hexahydrate

[-Co(en)3]I3 . H2O
0.025 g/ml 0.83 dm path

Blank

86.666

88.435

162.120

86.955

89.040

161.680

87.011

88.984

161.750

87.014

89.133

161.620

Mean

86.993

89.052

161.683

obs

0.327

0.617

-0.437

31.600

29.660

-21.450

ee

31%

33%

24%

Mol %

66%

67%

63%

The specific rotations of the [-Co(en)3][(+)tartrate]Cl 6 H2O, [-Co(en)3]I3 . H2O, and [Co(en)3]I3 . H2O were measured using linear polarimetry in DI water as detailed in Table 2. The
enatiomeric excess for the products was 31%, 33%, and 24% respectively.

UV-vis analysis
1.2
1

abs

0.8
0.6

Tartrate
(-)-Iodide
(+)-Iodide

0.4
0.2
0
300

350

400

450

500

550

600

650

700

750

800

Wavelength (nm)

Fig. 2: UV-Vis spectra of [-Co(en)3][(+)tartrate]Cl 6 H2O , [-Co(en)3]I3 . H2O, and [Co(en)3]I3 . H2O
Table 3:UV-Vis data of [-Co(en)3][(+)tartrate]Cl 6 H2O,[-Co(en)3]I3 . H2O , and [-Co(en)3]I3 .
H2O
[-Co(en)3]
[-Co(en)3]I3 . H2O
[-Co(en)3]I3 . H2O
[(+)tartrate]Cl 6 H2O
Concentration (mg/ml)

5.0000

5.0000

1.2500

Abs

0.2346

0.9959

0.6845

max

474.0000

466.0000

468.0000

Molar Absorbance

2.0000

12.3500

33.9500

Circular Dichroism
Table 4: Circular Dichroism data
[-Co(en)3]
[(+)tartrate]Cl 6 H2O
0
Wavelength

[-Co(en)3]I3 . H2O

[-Co(en)3]I3 . H2O

0.55710400

0.04561100

-0.02681970

490

431

427

0.8
0.6

0.4
0.2

[-Co(en)3]I3 . H2O
[-Co(en)3]I3 . H2O

0
250 300 350 400 450 500 550 600 650 700 750
-0.2
-0.4
Wavelength (nm)

0.8
0.7
0.6

0.5
0.4
0.3
0.2
0.1
0
250 300 350 400 450 500 550 600 650 700 750
-0.1
wavelength (nm)

Fig. 3: Top: Circular dichroism spectra of [-Co(en)3]I3 . H2O

and [-Co(en)3]I3 . H2O Bottom: Circular dichroism spectra of
[-Co(en)3]I3 . H2O

Discussion
Synthesis of the chiral cobalt compounds was successful but yields and resolution were poor.
The similarity in enatiopurity between the [-Co(en)3] tartrate and iodide salts suggests that the
fractional crystalization resulted in poor resolution and that isomerisation did not occur at a later time.
The [-Co(en)3]I3 . H2O was less enatiopure, likely because of the additional heating steps involved
in the removing acetone and ether from the filtrate. Yields and chiral resolution could be improved by
finding better fractional crystallization solvents, attempting to recover more of the chloride in the initial
synthesis, and using other acids for chiral resolution which may produce salts that are easier to
separate.
References
Jensen, H. P.; Galsbl, F. Crystal circular dichroism spectra of the tris(ethylenediamine)cobalt(III)
chromophore. Direct measurement of transitions to both E and A2 excited levels. Inorg. Chem. 1977,
16, 1294.
J. A. Broomhead, F. P. Dwyer, J. W. Hogarth (1960). Rochow, Eugene G., ed. "Resolution of the
Tris(Ethylenediamine)Cobalt(III) Ion". Inorganic Syntheses VI: 183186. doi:10.1002/9780470132371