1212
N. Someshwar, C. R. Ramanathan / Tetrahedron: Asymmetry 26 (2015) 1209–1213
(R)-(+)-1, obtained from methanol after evaporation, was found to
be >99% ee with 36% yield (Scheme 3).
(180 mL) and water (21 mL). The resulting mixture was stirred at
70 °C for 5 min and then a solution of (1R,2R)-2 (570 mg, 5 mmol)
in methanol (8 mL) was added dropwise. The overall proportion of
methanol and water was 9:1. The solution was refluxed for 12 h
and then cooled to room temperature. The precipitated diastere-
omeric salt (precipitate-I) was filtered and washed with cold
methanol (3 ꢁ 20 mL) and dried in vacuo. The precipitate-I was
decomposed with 6 M HCl and extracted with ethyl acetate
(3 ꢁ 100 mL). The combined organic layers were washed with sat-
urated sodium chloride solution and dried over anhydrous Na2SO4,
filtered and the solvent was evaporated in vacuo to afford the sca-
lemic (S)-(ꢀ)-1 with >81% ee (1.53 g, 41%).
3. Conclusion
In conclusion, we have established a simple and convenient
method for the resolution of racemic BINOL-3,30-dicarboxylic acid
( )-1 using (1R,2R)-trans-cyclohexane-1,2-diamine (1R,2R)-2 in
methanol and water mixture. The IR and single crystal X-ray anal-
ysis were used to prove the formation of diastereomeric salt A. This
resolution method can be used for the large scale production of
both isomers of BINOL-3,30-dicarboxylic acids in enantiomerically
pure form.
In order to enrich the enantiomeric purity of (S)-(ꢀ)-1, scalemic
(S)-(ꢀ)-1 (1.53 g, 4.1 mmol, >81% ee) was dissolved in a mixture of
methanol (74 mL) and water (9 mL) by heating the reaction mix-
ture at 70 °C for 5 min. To the clear solution, (1R,2R)-2 (373 mg,
3.28 mmol, 0.8 equiv) in methanol (4 mL) was added dropwise,
the resulting reaction mixture was stirred at reflux. After 12 h,
the reaction mixture was cooled down to room temperature. Pre-
cipitate-II thus obtained was filtered and washed with cold metha-
nol (3 ꢁ 20 mL) and dried in vacuo. The precipitate-II was
decomposed with 6 M HCl and extracted with ethyl acetate
(3 ꢁ 60 mL). The organic layers were combined, washed with satu-
rated sodium chloride solution and dried over anhydrous Na2SO4,
filtered and the solvent was evaporated using rotary evaporator
under reduced pressure. The isomer (S)-(ꢀ)-1 was obtained as a
pale yellow solid (1.27 g, 34%, >99% ee) and it was characterized
4. Experimental
4.1. General
Melting points reported are uncorrected and were measured
using
a BUCHI M-560, Buchi Labortechnik AG, Switzerland.
Infrared spectra were recorded on a Thermo Nicolet 6700 FT-IR
Spectrophotometer and are reported in frequency of absorption
(cmꢀ1). Mass spectra were measured with micro mass Q-TOF
(ESI-HRMS), 1H and 13C NMR were recorded on Bruker AVANCE
400 spectrometer. NMR spectra for the samples were measured
in DMSO-d6 using TMS as an internal standard. The chemical shifts
are expressed in d ppm down field from the signal of internal TMS.
Optical rotations were determined by a Rudolph Polarimeter
AUTOPOL IV. All solvents used in the reactions were distilled using
standard procedures. Racemic 2,20-dihydroxy-1,10-binaphthyl-3,
30-dicarboxylic acid (BINOL-3,30-dicarboxylic acid) ( )-1 was
prepared in three steps from 3-hydroxy-2-naphthoic acid using
reported procedures.7,8 The chiral resolving agent (1R,2R)-trans-
cyclohexane-1,2-diamine was obtained via classical resolution of
by 1H NMR and 13C NMR. Mp >290 °C; [
a]
25 = ꢀ189 (c 1.08, pyri-
D
dine), Lit. [
a]
D
25 = ꢀ189 (c 1.06, pyridine).1e Chiral HPLC analysis
of the corresponding dimethyl ester derivative: Chiralcel AD-H
column, hexanes/isopropanol 90:10, (flow rate: 1 mL/min,
detection at 254 nm) major enantiomer tR = 8.27 min, minor
enantiomer tR = 15.12 min.
The mother liquor (Filtrate-I, Scheme 3) was evaporated using a
rotary evaporator to obtain the residue. The residue was dissolved
in ethyl acetate and washed with 6 M HCl to remove trace amounts
of (1R,2R)-trans-cyclohexane-1,2-diamine 2 that was used in the
resolution. The solvent was removed under reduced pressure.
The (R)-(+)-1 was isolated as a pale yellow solid (1.68 g, 45%,
>90% ee). The scalemic (R)-(+)-1 (1.68 g, >90% ee) was dissolved
in methanol (35 mL) and allowed to stand at 5 °C for 24 h. The
solid material thus obtained was filtered off. The filtrate was con-
centrated using a rotary evaporator under reduced pressure. The
(R)-(+)-1 was obtained as a pale yellow solid (1.34 g, 36%, >99%
ee) and it was characterized by 1H NMR and 13C NMR. Mp
a
L
cis- and trans-mixture of cyclohexane-1,2-diamine using
-(+)-tartaric acid.10 Yields are given for isolated products showing
homogeneity on a TLC plate and no impurities detectable in the
NMR spectrum. The 2-hydroxy-3-naphthoic acid, TMEDA and CuCl,
a mixture of cis- and trans-cyclohexane-1,2-diamine, L-(+)-tartaric
acid were purchased from Sigma–Aldrich and used without further
purification. Analytical thin layer chromatographic tests were
carried out using precoated silica gel GF254 plates purchased from
Merck Specialties Private Ltd, India and the spots were visualized
by KMnO4 solution or UV light. Column chromatography was
carried out using Merck silica gel (100–200 mesh). All the glass-
ware were pre-dried at 120 °C for at least 6 h and assembled
while hot and cooled under a stream of dry nitrogen gas. In all
experiments, round bottom flasks and reaction tube of appropriate
size were used. Enantiomeric excess of corresponding dimethyl
ester derivative of samples was determined on Shimadzu HPLC
systems using the Daicel Chiralpak AD-H column. The absolute
configuration of sample was assigned by comparing the sign of
optical rotation.1e
>290 °C; [a] a]
25 = +189 (c 1.08, pyridine), Lit. [ 25 = +189 (c 1.06,
D D
pyridine).1e 1H NMR (400 MHz, DMSO-d6): d = 7.01–6.98 (m, 2H),
7.37–7.35 (m, 4H), 8.10–8.08 (m, 2H), 8.74 (s, 2H). 13C NMR
(100 MHz, DMSO-d6): d = 114.72, 116.43, 123.73, 124.10, 126.79,
129.32, 129.91, 132.72, 136.55, 154.17, 172.22. Chiral HPLC
analysis of the corresponding dimethyl ester derivative: Chiralcel
AD-H column, hexanes/isopropanol 90:10, (flow rate: 1 mL/min,
detection at 254 nm) minor enantiomer tR = 8.27 min, major
enantiomer tR = 15.12 min.
Full crystallographic data have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publi-
cations CCDC 1407947. These data can be obtained free of charge
on application to CCDC, 12, Union Road, Cambridge CB2 1EZ, UK;
fax: +44 (1223)336033; or e-mail: deposit@ccdc.cam.ac.uk.
Acknowledgements
We thank CSIR, New Delhi and DST, New Delhi, India for finan-
cial support. N.S. thank CSIR, New Delhi for SRF. We thank
Dr. Binoy K. Saha and Mr. S. V. Ganesh for solving crystal data.
We gratefully acknowledge the CIF, Pondicherry University for
NMR/IR data. DST-FIST programme and UGC-Special Assistance
Programme to Department of Chemistry, Pondicherry University
are gratefully acknowledged for XRD, HRMS and HPLC data,
respectively.
4.1.1. Resolution of ( )-2,20-dihydroxy-(1,10-binaphthalene)-
3,30-dicarboxylic acid (BINOL-3,30-dicarboxylic acid) ( )-1 using
(1R,2R)-trans-cyclohexane-1,2-diamine (1R,2R)-2
In a 500 mL two necked round bottom flask equipped with
reflux condenser, the racemic BINOL-3,30-dicarboxylic acid ( )-1
(3.74 g, 10 mmol) was dissolved in
a mixture of methanol