NOVEL CHIRAL METAL COMPLEX AND USE THEREOF FOR ANALYZING CHIRALITY OF CHARGED COMPOUND BY 1H NMR SPECTROSCOPY

Abstract

Provided are novel ligand, a chiral metal complex including the same, and a use of the chiral metal complex for analyzing the chirality of a charged compound by .sup.1H NMR spectroscopy. The chiral metal complex of the present invention may be used as the chiral solvating agent to conveniently analyze the optical purity of charged compounds such as various amine derivatives, carboxylic acid derivatives, cyanohydrin derivatives and charged metal complexes by .sup.1H NMR spectroscopy.

Claims

1. A N.sub.2O.sub.2 ligand represented by following Chemical Formula 1: ##STR00026## wherein R.sub.1 and R.sub.2 are independently of each other (C1-C10) alkyl or (C6-C20) aryl, or R.sub.1 and R.sub.2 are linked via (C2-C6) alkylene to form a cycloaliphatic ring; and R.sub.3 and R.sub.4 are independently of each other hydrogen, (C1-C10) alkyl, (C6-C20) aryl, or halogen.

2. The N.sub.2O.sub.2 ligand of claim 1, wherein R.sub.1 and R.sub.2 are independently of each other methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, biphenyl, naphthyl or anthryl, or R.sub.1 and R.sub.2 are linked via (C3-C4) alkylene to form a cycloaliphatic ring; and R.sub.3 and R.sub.4 are independently of each other hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, biphenyl, naphthyl, anthryl, chloro, bromo or fluoro.

3. A metal complex represented by following Chemical Formula 2: ##STR00027## wherein R.sub.1 and R.sub.2 are independently of each other (C1-C10) alkyl or (C6-C20) aryl, or R.sub.1 and R.sub.2 are linked via (C2-C6) alkylene to form a cycloaliphatic ring; R.sub.3 and R.sub.4 are independently of each other hydrogen, (C1-C10) alkyl, (C6-C20) aryl, or halogen; when M is Al.sup.3+ or Sc.sup.3+, n is 1, and Y is H.sup.+, Li.sup.+, Na.sup.+, K.sup.+, Ag.sup.+, Cs.sup.+, NR.sub.4.sup.+, Mg.sup.+, Ca.sup.2+, Zn.sup.2+ or Al.sup.3+; and when M is Ti.sup.4+, n is 0, and Y does not exist.

4. The metal complex of claim 3, wherein R.sub.1 and R.sub.2 are independently of each other methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, biphenyl, naphthyl or anthryl, or R.sub.1 and R.sub.2 are linked via (C3-C4) alkylene to form a cycloaliphatic ring; R.sub.3 and R.sub.4 are independently of each other hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, biphenyl, naphthyl, anthryl, chloro, bromo or fluoro; M is Al.sup.3+, Sc.sup.3+ or Ti.sup.4+; n is 0 or -1; and Y does not exist, or is H.sup.+ or Na.

5. The metal complex of claim 3, wherein it is selected from following structures: ##STR00028## ##STR00029##

6. A method of measuring an optical purity of a chiral analyte by spectroscopy using the chiral metal complex of claim 3 as a chiral solvating agent.

7. The method of claim 6, wherein the spectroscopy is nuclear magnetic resonance (NMR) spectroscopy.

8. The method of claim 6, wherein the chiral metal complex is used in 0.1 equivalent or more relative to the chiral analyte.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0081] FIG. 1 is .sup.1H NMR spectra of Example 9 and Comparative Examples 1 to 6.

[0082] FIG. 2 is .sup.1H NMR spectra of Example 10 and Comparative Examples 7 to 12.

[0083] FIG. 3 is .sup.1H NMR spectra of Example 11 and Comparative Examples 13 to 18.

[0084] FIG. 4 is .sup.1H NMR spectra of Example 12.

[0085] FIG. 5 is .sup.1H NMR spectra of Example 13.

[0086] FIG. 6 is .sup.1H NMR spectra of Example 14.

DETAILED DESCRIPTION OF EMBODIMENTS

[0087] The advantages, features and aspects of the present invention will become apparent from the following description of the embodiments with reference to the accompanying drawings, which is set forth hereinafter. The present invention may, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the present invention to those skilled in the art. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments. As used herein, the singular forms a, an and the are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms comprises and/or comprising, when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.

[0088] Hereinafter, exemplary embodiments will be described in detail with reference to the accompanying drawings.

[0089] Commercially available compounds were used without additional purification or drying. .sup.1H NMR (400 MHz) and .sup.13C NMR (100 MHz) spectra were obtained using a Bruker Ascend 400 spectrometer. HRMS (high-resolution mass spectra) was obtained using a Bruker Daltonik microTOF-QII spectrometer.

Example 1

Preparation of Ligand 1a

[0090] ##STR00009##

[0091] Preparation of Compound S1

[0092] (R,R)-1,2-diaminocyclohexane (1.14 g, 10.0 mmol) and MeOH (20.0 mL) were mixed, and then 2,2-dihydroxybenzophenone (5.14 g, 24.0 mmol) was added thereto while stirring, and the stirring was continued at 50 C. for hours. The reaction mixture was filtered, and the separated solid was washed with ether, and then dried in vacuo, thereby obtaining title compound S1 as a yellow solid (4.41 g, 87%).

[0093] .sup.1H NMR (400 MHz, DMSO-d6) 15.55-15.27 (br, 2H), 9.81 (br, 2H), 7.39-7.32 (m, 2H), 7.26-7.20 (m, 2H), 7.12-6.81 (m, 8H), 6.73-6.61 (m, 4H), 3.56-3.45 (m, 2H), 1.88-1.69 (m, 2H), 1.58 (br, 2H), 1.32 (br, 2H), 1.09 (br, 2H); .sup.13C NMR (100 MHz, DMSO-d6) 171.5, 162.1, 154.0, 132.1, 130.7, 130.5, 128.5, 120.4, 119.5, 119.2, 117.5, 117.2, 115.8, 649.9, 30.9, 23.5; HRMS (EI m/z calcd for C.sub.32H.sub.30N.sub.2O.sub.4[H].sup.+: 507.2278. found: 507.2314.

[0094] Preparation of Compound 1a

[0095] Compound S1 (2.53 g, 5.00 mmol) and MeOH (25.0 mL) were mixed, and then NaBH.sub.4 (6 eq., 1.13 g, 30.0 mmol) was added portionwise at 0 C. while stirring, and the stirring was continued at 25 C. for 2 hours. All volatile residues were removed in vacuo, and then the reaction mixture was dissolved in EtOAc, and washed with brine. The organic layer was dried with MgSO.sub.4, and filtered and concentrated. Purification by reslurrying (CHCl.sub.3, 10.0 mL) gave title compound 1a as a white solid (1.66 g, 65%).

[0096] .sup.1H NMR (400 MHz, DMSO-d6) 8.29 (br, 6H), 7.10-7.02 (m, 6H), 6.80-6.78 (m, 4H), 6.75-6.70 (m, 4H), 6.65 (td, J=7.5, 1.1 Hz, 2H), 5.36 (s, 2H), 2.45 (br, 2H), 2.02 (br, 2H), 1.56 (br, 2H), 1.16 (br, 4H); .sup.13C NMR (100 MHz, DMSO-d6) 156.6, 155.8, 128.6, 128.2, 128.0, 127.9, 127.7, 126.7, 118.9, 118.5, 115.7, 115.5, 57.0, 55.5, 28.5, 22.9; HRMS (EI) m/z calcd for C.sub.32H.sub.34N.sub.2O.sub.4[H].sup.+: 511.2591. found: 511.2607.

Example 2

Preparation of Ligand 1b

[0097] ##STR00010##

[0098] Preparation of Compound S2

[0099] (R,R)-1,2-diphenylethylenediamine (2.12 g, 10.0 mmol) and MeOH (20.0 mL) were mixed, and then 2,2-dihydroxybenzophenone (5.14 g, 24.0 mmol) was added thereto while stirring, and the stirring was continued at 50 C. for hours. The reaction mixture was filtered, and the separated solid was washed with ether, and then dried in vacuo, thereby obtaining title compound S2 as a yellow solid (5.51 g, 91%).

[0100] .sup.1H NMR (400 MHz, DMSO-d6) 15.39-15.32 (br, 2H), 9.40 (br, 2H), 7.31-7.22 (m, 4H), 7.18-6.80 (m, 14H), 6.74-6.50 (m, 6H), 6.21-6.08 (m, 2H), 4.95-4.84 (m, 2H); .sup.13C NMR (100 MHz, DMSO-d6) 172.8, 161.9, 154.0, 139.8, 132.4, 131.1, 130.5, 128.0, 127.7, 127.0, 119.8, 119.5, 118.6, 117.7, 117.5, 117.2, 115.3, 71.8; HRMS (EI) m/z calcd for C.sub.40H.sub.32N.sub.2O.sub.4 [H].sup.+: 605.2435. found: 605.2476.

[0101] Preparation of Compound 1b

[0102] Compound S2 (3.02 g, 5 mmol) and MeOH (25.0 mL) were mixed, and then NaBH.sub.4 (6 eq., 1.13 g, 30.0 mmol) was added portionwise at 0 C. while stirring, and the stirring was continued at 25 C. for 2 hours. All volatile residues were removed in vacuo, and then the reaction mixture was dissolved in EtOAc, and washed with brine. The organic layer was dried with MgSO.sub.4, and filtered and concentrated. Purification by reslurrying (CHCl.sub.3, 10.0 mL) gave title compound 1b as a white solid (2.47 g, 81%).

[0103] .sup.1H NMR (400 MHz, DMSO-d6) 10.07 (br, 4H), 7.16-7.08 (m, 8H), 7.01-6.92 (m, 8H), 6.77 (dd, J=8.1, 1.0 Hz, 2H), 6.75-6.71 (m, 4H), 6.69 (dd, J=8.0, 1.1 Hz, 2H), 6.60 (td, J=7.5, 1.2 Hz, 2H), 4.94 (s, 2H), 3.79 (s, 2H); .sup.13C NMR (100 MHz, DMSO-d6) 155.9, 155.8, 139.6, 128.9, 128.2, 128.1, 128.0, 128.0, 128.0, 127.8, 127.7, 127.0, 125.8, 118.9, 118.4, 115.6, 115.5, 65.2, 55.5; HRMS (EI) m/z calcd for C.sub.40H.sub.36N.sub.2O.sub.4[H].sup.+: 609.2748. found: 605.2473.

Example 3

Preparation of Metal Complex Na[Al-1a]

[0104] ##STR00011##

[0105] Compound 1a (511 mg, 1.00 mmol) and MeOH (20.0 mL) were mixed to prepare a solution of compound 1a. NaOH (160 mg, 4.00 mmol) and MeOH (40.0 mL) were mixed to prepare a NaOH solution. The NaOH solution and AlCl.sub.3.6H.sub.2O (241 mg, 1.00 mmol) were added to the solution of compound 1a, and stirred at 25 C. for 2 hours. The reaction mixture was concentrated under reduced pressure, dissolved in EtOAc, and washed with brine. The organic layer was dried with Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure to obtain title compound Na[Al-1a] as an off-white solid (559 mg, 99%).

[0106] .sup.1H NMR (400 MHz, DMSO-d6) 7.08 (dd, J=7.5, 1.7 Hz, 2H), 6.95-6.86 (m, 4H), 6.78 (ddd, J=8.1, 7.1, 1.9 Hz, 2H), 6.62 (dd, J=8.1, 1.3 Hz, 2H), 6.38 (td, J=7.3, 1.3 Hz, 2H), 6.31 (dd, J=8.2, 1.2 Hz, 2H), 6.26 (td, J=7.2, 1.3 Hz, 2H), 4.87 (s, 2H), 3.77 (d, J=10.2 Hz, 2H), 2.48-2.41 (m, 2H), 2.23 (d, J=12.7 Hz, 2H), 1.65 (d, J=9.8 Hz, 2H), 1.27 (d, J=11.5 Hz, 2H), 1.01-0.90 (m, 2H); .sup.13C NMR (100 MHz, DMSO-d6) 162.3, 161.8, 130.4, 129.2, 128.5, 127.8, 127.3, 124.9, 120.1, 120.1, 113.4, 113.0, 63.3, 55.8, 27.3, 24.1; HRMS (EI) m/z calcd for C.sub.32H.sub.30AlN.sub.2NaO.sub.4[H].sup.+: 557.1991. found: 557.2035.

Example 4

Preparation of Metal Complex H[Al-1a]

[0107] ##STR00012##

[0108] Na[Al-1a] (278 mg, 0.500 mmol) and MeOH (5.00 mmol) were mixed, and then TFA (38.3 uL, 0.500 mmol) was added thereto, and stirred at 25 C. for 2 hours. The reaction mixture was dried, washed with cold MeOH, and then dried in vacuo to obtain title compound H[Al-1a] as an off-white solid (235 mg, 88%).

[0109] .sup.1H NMR (400 MHz, DMSO-d6) 7.18-7.14 (m, 4H), 6.99-6.93 (m, 4H), 6.64 (d, J=8.0 Hz, 2H), 6.59-6.54 (m, 4H), 6.48 (t, J=7.2 Hz, 2H), 5.07 (s, 2H), 4.61 (br, 2H), 2.45-2.36 (m, 2H), 2.21 (d, J=13 Hz, 2H), 1.63 (d, J=9.4 Hz, 2H), 1.29 (d, J=7.8 Hz, 2H) 0.96-0.85 (m, 2H); .sup.13C NMR (100 MHz, DMSO-d6) 160.9, 157.0, 130.0, 129.4, 129.3, 128.7, 128.3, 125.9, 120.2, 119.9, 117.5, 115.3, 62.9, 56.6, 27.2, 24.4; HRMS (EI) m/z calcd for C.sub.32H.sub.31AlN.sub.2O.sub.4[Na].sup.+: 557.1991. found: 557.1990.

Example 5

Preparation of Metal Complex Na[Al-1b]

[0110] ##STR00013##

[0111] Compound 1b (609 mg, 1.00 mmol) and MeOH (20.0 mL) were mixed to prepare a solution of compound 1b. NaOH (160 mg, 4.00 mmol) and MeOH (40.0 mL) were mixed to prepare a NaOH solution. The NaOH solution and AlCl.sub.3.6H.sub.2O (241 mg, 1.00 mmol) were added to the solution of compound 1b, and stirred at 25 C. for 2 hours. The reaction mixture was concentrated under reduced pressure, dissolved in EtOAc, and washed with brine. The organic layer was dried with Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure to obtain title compound Na[Al-1b] as an off-white solid (648 mg, 99%).

[0112] .sup.1H NMR (400 MHz, DMSO-d6) 7.21-7.14 (m, 6H), 6.94-6.89 (m, 4H), 6.86-6.84 (m, 4H), 6.76-6.73 (m, 4H), 6.65 (dd, J=8.2, 1.4 Hz, 2H) 6.49 (dd, J=8.2, 1.2 Hz, 2H) 6.34 (ddd, 15.1, 7.6, 1.1 Hz, 2H) 6.29 (td, J=7.3, 1.2 Hz, 2H), 4.31 (s, 2H), 4.14-4.07 (m, 2H), 3.88-3.83 (m, 2H); .sup.13C NMR (100 MHz, DMSO-d6) 162.1, 161.6, 136.3, 129.3, 129.1, 128.7, 128.3, 128.2, 128.1, 127.9, 127.6, 124.2, 120.3, 120.2, 113.7, 113.6, 64.7, 62.4; HRMS (EI) m/z calcd for C.sub.40H.sub.32AlN.sub.2NaO.sub.4[H].sup.+: 655.2148. found: 655.2167.

Example 6

Preparation of Metal Complex H[Al-1a]

[0113] ##STR00014##

[0114] Na[Al-1b] (327 mg, 0.500 mmol) and DCM (5.00 mmol) were mixed, and then TFA (38.3 uL, 0.500 mmol) was added thereto, and stirred at 25 C. for 2 hours. The reaction mixture was filtered, washed with cold MeOH, and then dried in vacuo to obtain title compound H[Al-1b] as an off-white solid (312 mg, 99%).

[0115] .sup.1H NMR (400 MHz, CD.sub.3CN) 7.24-7.11 (m, 6H), 6.99-6.70 (m, 16H), 6.99-6.97 (m, 6H) 6.85-6.78 (m, 6H), 6.74-6.70 (m, 2H), 6.48-6.45 (m, 2H), 4.63 (br, 2H), 4.60 (d, J=1.8 Hz, 2H), 4.32-4.25 (m, 2H); .sup.13C NMR (100 MHz, CD.sub.3CN) 135.6, 130.6, 130.0, 129.9, 129.8, 129.8, 129.4, 129.3, 128.7, 125.0, 121.6, 120.4, 65.3, 64.1; HRMS (EI) m/z calcd for C.sub.40H.sub.33AlN.sub.2O.sub.4[Na].sup.+: 655.2148. found: 655.2180.

Example 7

Preparation of Metal Complex Na[Sc-1a]

[0116] ##STR00015##

[0117] Compound 1a (511 mg, 1.00 mmol) and MeOH (20.0 mL) were mixed to prepare a solution of compound 1a. NaOH (160 mg, 4.00 mmol) and MeOH (40.0 mL) were mixed to prepare a NaOH solution. The NaOH solution and Sc(OTf).sub.3 (492 mg, 1.00 mmol) were added to the solution of compound 1a, and stirred at 25 C. for 2 hours. The reaction mixture was concentrated under reduced pressure, dissolved in EtOAc, and washed with brine. The organic layer was dried with Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure to obtain title compound Na[Sc-1a] as an off-white solid (568 mg, 99%).

[0118] .sup.1H NMR (400 MHz, DMSO-d6) 7.11 (d, J=6.2 Hz, 2H), 6.91 (d, J=7.4 Hz, 2H), 6.86 (t, J=7.5 Hz, 2H), 6.75 (t, J=7.5 Hz, 2H), 6.32 (t, J=7.3 Hz, 2H), 6.28 (d, J=8.1 Hz, 2H), 6.23-6.19 (m, 4H), 4.91 (s, 2H), 3.44 (d, J=9.4 Hz, 2H), 2.53-2.57 (m, 2H), 2.33 (d, J=10.9 Hz, 2H), 1.63 (d, J=7.7 Hz, 2H), 1.25-1.15 (m, 2H), 0.99-0.88 (m, 2H).

Example 8

Preparation of Metal Complex [Ti-1a]

[0119] ##STR00016##

[0120] Compound 1a (511 mg, 1.00 mmol) and methanol (10.0 mL) were mixed to prepare a solution of compound 1a. Ti(OiPr).sub.4 (0.296 mL, 1.00 mmol) was added to the solution of compound 1a, and stirred at 25 C. for 2 hours. The reaction mixture was filtered, and then washed with methanol. The solid compound was dried to obtain title compound [Ti-1a] as a yellow solid (477 mg, 86%).

[0121] .sup.1H NMR (400 MHz, DMSO-d6) 7.46 (dd, J=7.6, 1.7 Hz, 2H), 7.22 (dd, J=7.7, 1.8 Hz, 2H), 7.10 (ddd, J=8.0, 7.3, 1.7 Hz, 2H), 6.97 (ddd, J=8.1, 7.2, 1.8 Hz, 2H) 6.76 (td, J=7.4, 1.2 Hz, 2H), 6.58 (td, J=7.4, 1.2 Hz, 2H) 6.52 (dd, J=8.0, 1.2 Hz, 2H), 6.33 (dd, J=8.1, 1.2 Hz, 2H) 6.07 (d, J=8.2 Hz, 2H), 5.36-5.28 (m, 2H), 2.69-2.79 (m, 2H), 2.32-2.28 (m, 2H), 1.65-1.67 (m, 2H), 1.48-1.40 (m, 2H), 0.95-0.84 (m, 2H).

Example 9 and Comparative Examples 1 to 6

Measurement of Optical Purity of Rac-1-Phenylethylamine by .SUP.1.H NMR Using Chiral Solvating Agents

[0122] As shown in following Table 1, various chiral solvating agents and rac-1-phenylethylamine were dissolved in an NMR solvent at 25 C., and then measurement of .sup.1H NMR spectra was carried out, thereby confirming whether two enantiomers are classified, and the results are illustrated in FIG. 1. (a) in FIG. 1 is .sup.1H NMR of a methyl group of rac-1-phenylethylamine in CD.sub.3OD.

TABLE-US-00001 TABLE 1 Chiral solvating agent .sup.1H NMR of a methyl NMR solvent group of rac-1- (concentration phenylethylamine Racemic Type mM) (ppm) separation Example 9 Metal complex H[Al- CD.sub.3OD 1.57, 1.52 O ((b) in 1b] prepared in (10) FIG. 1) Example 6 [00017] Comparative Example 1 ((c) in FIG. 1) D-Mandelic acid [00018] CD.sub.3OD (10) 1.62 X Comparative Example 2 ((d) in FIG. 1) Mecoprop-P [00019] CD.sub.3OD (10) 1.62 X Comparative Example 3 ((e) in FIG. 1) Dichloroprop-P [00020] CD.sub.3OD (10) 1.62 X Comparative Example 4 ((f) in FIG. 1) ()-Pirkle's Alcohol [00021] CD.sub.3OD (10) 1.38 X Comparative Example 5 ((g) in FIG. 1) Eu(tfc).sub.3 [00022] CD.sub.3OD (10) 1.38 X Comparative Example 6 ((h) in FIG. 1) -cyclodextrin [00023] D.sub.2O (10) 1.41 X

[0123] It was confirmed that two enantiomers were separated only in the case of using the chiral solvating agent of the present invention (Example 9), as compared with the existing solvating agents (Comparative Examples 1 to 6).

Example 10 and Comparative Examples 7 to 14

Measurement of Optical Purity of DL-Alanine by .SUP.1.H NMR Using Chiral Solvating Agents

[0124] As shown in following Table 2, various chiral solvating agents and DL-alanine were dissolved in an NMR solvent at 25 C., and then measurement of .sup.1H NMR spectra was carried out, thereby confirming whether two enantiomers are classified, and the results are illustrated in FIG. 2. (a) in FIG. 2 is .sup.1H NMR of a methyl group of DL-alanine in CD.sub.3OD.

TABLE-US-00002 TABLE 2 Chiral solvating agent .sup.1H NMR of NMR methyl solvent group of (concen- DL- tration alanine Racemic Type mM) (ppm) separation Example 10 Metal complex CD.sub.3OD 1.44, 1.40 ((b) in H[Al-1b] (10) FIG. 2) prepared in Example 6 Comparative D-Mandelic CD.sub.3OD 1.47 X Example 7 acid (10) ((c) in FIG. 2) Comparative Mecoprop-P CD.sub.3OD 1.47 X Example 8 (10) ((d) in FIG. 2) Comparative Dichloroprop-P CD.sub.3OD 1.47 X Example 9 ((e) in (10) FIG. 2) Comparative ()-Pirkle's CD.sub.3OD 1.46 X Example 10 Alcohol (10) ((f) in FIG. 2) Comparative Eu(tfc).sub.3 CD.sub.3OD 1.90 X Example 11 (10) ((g) in FIG. 2) Comparative -cyclodextrin D.sub.2O 1.47 X Example 12 (10) ((h) in FIG. 2)

[0125] It was confirmed that two enantiomers were separated only in the case of using the chiral solvating agent of the present invention (Example 10), as compared with the existing solvating agents (Comparative Examples 7 to 12).

Example 11 and Comparative Examples 13 to 18

Measurement of Optical Purity of Rac-2-Methylbutylamine by .SUP.1.H NMR Using Chiral Solvating Agents

[0126] As shown in following Table 3, various chiral solvating agents and rac-2-methylbutylamine were dissolved in an NMR solvent at 25 C., and then measurement of .sup.1H NMR spectra was carried out, thereby confirming whether two enantiomers are classified, and the results are shown in the FIG. 3. (a) in FIG. 3 is .sup.1H NMR of a methyl group of rac-2-methylbutylamine in.

TABLE-US-00003 TABLE 3 Chiral solvating agent NMR .sup.1H NMR of a solvent methyl group (concen- of rac-2- tration methylbutylamine Racemic Type mM) (ppm) separation Example 11 Metal CD.sub.3CN 0.80, 0.78 ((b) in complex (10) FIG. 3) H[Al-1b] prepared in Example 6 Comparative D-Mandelic CD.sub.3CN 0.86 X Example 13 acid (10) ((c) in FIG. 3) Comparative Mecoprop-P CD.sub.3CN 0.85 X Example 14 (10) ((d) in FIG. 3) Comparative Dichloroprop-P CD.sub.3CN 0.86 X Example 15 (10) ((e) in FIG. 3) Comparative ()-Pirkle's CD.sub.3CN 0.84 X Example 16 Alcohol (10) ((f) in FIG. 3) Comparative Eu(tfc).sub.3 CD.sub.3CN 1.33 X Example 17 (10) ((g) in FIG. 3) Comparative -cyclodextrin D.sub.2O 0.92 X Example 18 (10) ((h) in FIG. 3)

[0127] It was confirmed that two enantiomers were separated only in the case of using the chiral solvating agent of the present invention (Example 11), as compared with the existing solvating agents (Comparative Examples 13 to 18).

[0128] When the metal complex of the present invention H[Al-1b] is used as the chiral solvating agent, peak separation was observed in a polar protic solvent such as CD.sub.3OD or CD.sub.3CN, differently from the case of using the chiral solvating agents conventionally known in the art, from the Examples and Comparative Examples.

Example 12

Measurement of Optical Purities of

[0129] Amine or Positively Charged Compounds by .sup.1H NMR Using the Metal Complex H[Al-1b] of the Present Invention as a Chiral Solvating Agent

[0130] In order to confirm the chiral solvation degree of the metal complex of the present invention, a 1:1 mixture of the metal complex H[Al-1b] of the present invention and a chiral analyte was dissolved in an NMR solvent to 20 mM at 25 C., and then measurement of .sup.1H NMR spectrum was carried out. The results are illustrated in FIG. 4.

[0131] As the chiral analyte, an amine compound or positively charged compounds were used, and as the amine compound, rac-1-phenylethylamine (a), rac-3,3-dimethylbutan-2-amine (b), rac-1-(1-naphthyl)ethylamine (c), rac-2,3-dihydro-1H-inden-1-amine (d), rac-2-methylbutylamine (e), rac-2-phenyl-1-propanamine (f), rac-2-methylbutan-1-amine (g), 3-(2-methoxyphenyl)-3-methylpentan-1-amine (h), rac-2-methylpiperidine (i), 3-methylpiperidine (j), rac-cyclohexane-1,2-diamine (k), rac-N,N-dimethyl-1-phenylethylamine (l), DL-alanine (m), DL-phenylalanine (n), DL-valinol (o), DL-alaninol (p), and N-methyl-1-(2-(methylamino)naphthalen-1-yl)naphthalen-2-amine (q) were used, as the positively charged compound, [Fe(dmbp).sub.3].sup.+2 (dmbp=4,4-dimethyl-2,2-bipyridine) was used, and as the NMR solvent, CD.sub.3OD(a-d, i-n), CD.sub.3CN(e-h, o-q) or CDCl.sub.3 (r) was used.

Example 13

Measurement of Optical Purities of Carboxylic Acid Compounds by .SUP.1.H NMR Using the Metal Complex Na[Al-1b] of the Present Invention as a Chiral Solvating Agent

[0132] In order to confirm the chiral solvation degree of the metal complex of the present invention, a 1:1 mixture of the metal complex Na[Al-1b] of the present invention and a carboxylic acid compound as a chiral analyte was dissolved in an NMR solvent to 20 mM at 25 C., and then measurement of .sup.1H NMR spectrum was carried out. The results are illustrated in FIG. 5.

[0133] As the carboxylic acid compound, rac-2-Phenylpropionic acid (a), rac-2-methoxy-2-phenylacetic acid (b), rac-2-bromopropionic acid (c), rac-2-bromo-3-methylbutanoic acid (d), rac-2-methylbutanoic acid (e), rac-3-phenylbutanoic acid (f), rac-mandelic acid (g), rac-3-chlorophenyl-2-hydroxyacetic acid (h), rac-2-(methylsulfinyl)benzoic acid (i), and rac-2-hydroxy-2-phenylacetonitrile (j) were used, and as the NMR solvent, CDCl.sub.3 (a-f), CD.sub.3CN (g, h, j) or CD.sub.3OD (i) was used.

Example 14

Measurement of Optical Purities of Commercial Drugs by .SUP.1.H NMR Using the Metal Complex M[Al-1b] (M=H.SUP.+ or Na) of the Present Invention as a Chiral Solvating Agent

[0134] In order to confirm the chiral solvation degree of the metal complex of the present invention, a 1:1 mixture of the metal complex M[Al-1b] (M=H.sup.+ or Na) of the present invention and a commercial drug as a chiral analyte was dissolved in an NMR solvent to 20 mM at 25 C., and then measurement of .sup.1H NMR spectrum was carried out. The results are illustrated in FIG. 6.

[0135] The commercial drugs are difficult to be subjected to chromatography analysis due to high polarity and low solubility in an organic solvent, and the commercial racemic drugs were used as the chiral analyte, and their structures are as follows:

##STR00024## ##STR00025##

[0136] For the commercial drugs a-d, H[Al-1b] was used as the chiral solvating agent, and for the commercial drugs e-I, Na[Al-1b] was used as the chiral solvating agent. In addition, as the NMR solvent, CD.sub.3CN (a-c, h), CDCl.sub.3 (e, f), C.sub.6D.sub.6 (d, i) or CD.sub.3OD (g) was used.

[0137] It is seen from the above Examples that the chirality of various chiral compounds such as various amine derivatives, carboxylic acid derivatives, cyanohydrin derivatives, charged metal complexes, and commercial racemic drugs may be analyzed by .sup.1H NMR, in the case of using the metal complex of the present invention as the chiral solvating agent.

[0138] The chiral metal complex of the present invention is a chiral octahedral complex having a A or A configuration at a metal center due to the binding of the ligand of the Chemical formula 1, and it is possible to stereoselectively control or chirality at the metal center.

[0139] Further, the chiral metal complex of the present invention may be used as a highly efficient and practical chiral solvating agent in the measurement of the optical purity of all compounds charged with chiral charge which was regarded as being difficult to be subjected to chromatography analysis, such as a commercial racemic drug which is difficult to be subjected to chromatography analysis due to high polarity and low solubility in an organic solvent. Traditionally only the non-polar solvent was used so that the range of the analyte was extremely limited, however, in the present invention, the chiral metal complex is used as the chiral solvating agent, thereby allowing the polar solvent as well as the non-polar solvent to be used, and thus, even the analyte which has high polarity and was not able to be previously used as the analyte may be used.

[0140] Further, the chiral metal complex of the present invention may show sufficient peak separation to measure an optical purity in a polar solvent for measuring .sup.1H NMR with only a sub-stoichiometric amount, and extend the stereocenter of the analyte from a charged functional group to position.

[0141] Accordingly, the chiral metal complex of the present invention may be used as a widely used chiral solvating agent for charged chiral compounds.