Chiral porous organic cage used as stationary phase for gas chromatographic separation of chiral and achiral compounds

doi:10.3724/SP.J.1123.2024.01025

Abstract

Abstract:

Porous organic cages (POCs) are a new type of molecular material. The well-defined cavities, abundant host-guest recognition ability, and good solubility of POCs render them attractive for use in various fields such as molecular recognition, gas adsorption, molecular containers, sensing, catalysis, chromatographic separation. In this study, a chiral POC (CPOC) was synthesized via the Schiff base condensation of 4,4',4″,4″'-(ethene-1,1,2,2-tetrayl)tetrabenzaldehyde with (R,R)-1,2-cyclohexanediamine. CPOC was characterized using nuclear magnetic resonance (NMR) spectroscopy, Fourier transform-infrared (FT-IR) spectroscopy, mass spectroscopy (MS), and thermogravimetric analysis (TGA). The FT-IR spectrum of CPOC showed a strong peak at 1638 cm^-1, which was attributed to imine (-C=N-) absorption, as well as absorption peaks at 2928 and 2856 cm^-1, which were attributed to the stretching vibrations of -CH₂- and -CH-, respectively. MS analysis of CPOC revealed peaks at m/z=1801.9797, m/z=901.9914, and m/z=601.6631, corresponding to [M+H]⁺, [M+2H]²⁺, and [M+3H]³⁺, respectively, and indicating a molecular formula of CPOC (C₁₂₆H₁₂₀N₁₂). The TGA curve of CPOC indicated high thermal stability up to 360 ℃; thus, the material is suitable for use as a stationary phase for gas chromatography (GC). CPOC was coated on the inner wall of a capillary column using the static coating method to prepare a GC column. Scanning electron microscopy (SEM) was used to characterize the coating condition of the fabricated column. The SEM images showed that the column had a uniform coating with a thickness of approximately 200 nm. Column efficiency was determined to be 3500 plates/m using n-dodecane as a target at 120 ℃. The polarity of the CPOC stationary phase was evaluated using McReynolds constants, which were measured using benzene, 1-nitropropane, 2-pentanone, pyridine, and 1-butanol as probe molecules at 120 ℃. The average McReynolds constant was 152, indicating that CPOC is a moderately polar stationary phase. The ability of the column to separate organic mixtures, isomers, and chiral compounds was subsequently investigated. All components of the four organic mixtures (n-alkanes, aromatics, n-alcohols, and Grob mixtures) tested achieved baseline separation on the column. In addition, nine positional isomers of disubstituted benzenes were well separated, and seven (o,m,p-nitrotoluene, o,m,p-nitrochlorobenzene, o,m,p-nitrobromobenzene, o,m,p-bromotoluene, o,m,p-dichlorobenzene, o,m,p-chloroaniline, and o,m,p-bromoaniline) achieved baseline separation. Some polar and apolar structural isomers, such as pentanol, dimethylphenol, dimethylaniline, butanol, and C9 aromatic hydrocarbon isomers, were also well separated on the column. Five cis/trans-isomers (nerol/geraniol, cis/trans-1,3-dichloropropene, cis/trans-1,2,3-trichloropropene, cis/trans-citral, and cis/trans-decahydronaphthalene) were baseline-separated on the column. More importantly, the column successfully separated 12 chiral compounds, indicating good chiral separation ability. Among these chiral compounds, five (ethyl 3-hydroxybutyrate, a valine derivative, a glutamic acid derivative, 1,2-butanediol diacetate, and 1,2-epoxybutane) achieved baseline separation. Six of these chiral compounds (ethyl 3-hydroxybutyrate, the valine derivative, the glutamic acid derivative, 1,2-epoxybutane, epichlorohydrin, and epibromohydrin) could not be separated on a β-DEX 120 column but were well separated on the developed column. Moreover, the separation efficiency of 1,2-butanediol diacetate and the isoleucine derivative on this column was better than that on the β-DEX 120 column. Separation of the glutamic acid derivative and o,m,p-nitrotoluene was performed before and after the column was used for repeated injections to explore its repeatability. The retention times and selectivity observed after 80, 160, and 500 injections were nearly unchanged compared with those obtained following the first use of the column, indicating that the column has good repeatability. The column was conditioned at 280 ℃ for a certain period to examine its thermal stability. Separation of 3-hydroxybutyrate and o,m,p-nitrochlorobenzene after the column was conditioned at 280 ℃ for 2, 4, or 8 h revealed no obvious changes compared with the first use of the column, indicating that the column had good thermal stability. Thus, CPOC is a stationary phase with good application potential for GC.

Key words: gas chromatography (GC), stationary phase, chiral separation, porous organic cage (POC)

CLC Number:

O658

HUANG Bin, CHEN Juan, WANG Bangjin, ZHANG Junhui, XIE Shengming, YUAN Liming. Chiral porous organic cage used as stationary phase for gas chromatographic separation of chiral and achiral compounds[J]. Chinese Journal of Chromatography, 2024, 42(9): 891-902.

Figures/Tables 14

Fig. 1 Synthesis of chiral porous organic cage (CPOC) TFA: trifluoroacetic acid.

Fig. 2 NMR spectra of CPOC a.1H NMR spectrum; b.13C NMR spectrum.

Fig. 3 (a) FT-IR spectrum, (b) ESI-MS spectrum and (c) nitrogen sorption isotherm and pore size distribution curve of CPOC

Fig. 4 Thermogravimetric analysis (TGA) spectrum of CPOC

Fig. 5 SEM images of (a) empty capillary column and (b) CPOC-coated capillary column (CPOC column)

Fig. 6 Separation chromatograms of four organic mixtures on the CPOC column Temperature programs: a. 70 ℃ for 0.5 min, then increased to 200 ℃ at a heating rate of 20 ℃/min under a N2 linear velocity of 16.4 cm/s; b. 90 ℃ for 1.5 min, then increased to 200 ℃ at a heating rate of 35 ℃/min and under a N2 linear velocity of 15.2 cm/s; c. 80 ℃ for 0.5 min, then increased to 195 ℃ at a heating rate of 20 ℃/min under a N2 linear velocity of 14.9 cm/s; d. 110 ℃ for 1.5 min, then increased to 205 ℃ at a heating rate of 20 ℃/min under a N2 linear velocity of 15.6 cm/s. Peak identifications: a. n-alkanes (1. n-pentane, 2. n-hexane; 3. n-heptane; 4. n-octane; 5. n-nonane; 6. n-decane; 7. n-undecane; 8. n-dodecane; 9. n-tridecane); b. alkylbenzenes (1. benzene; 2. toluene; 3. ethylbenzene; 4. n-propylbenzene; 5. n-butylbenzene; 6. n-pentylbenzene); c. n-alcohols (1. methanol; 2. ethanol; 3. 1-propanol; 4. 1-butanol; 5. 1-pentanol; 6. 1-hexanol; 7. 1-heptanol; 8. 1-octanol); d. Grob mixture (1. 2,3-butanediol; 2. n-decane; 3. n-undecane; 4. n-nonanal; 5. n-octanol; 6. 2,6-dimethylaniline, 7. methyl decanoate, 8. dicyclohexylamine, 9. methyl undecanoate).

Fig. 7 Separation chromatograms of disubstituted benzene positional isomers on the CPOC column

Table 1 Separation parameters of disubstituted benzene positional isomers on the CPOC column

Positional isomer	T^a)/ ℃	v^b)/ (cm/s)	Separation factor (α)		Resolution (R_s)
Positional isomer	T^a)/ ℃	v^b)/ (cm/s)	α₁	α₂	R_s1	R_s2
o,m,p-Nitrotoluene	170	15.1	1.38	1.21	6.06	3.80
o,m,p-Nitrochlorobenzene	175	14.8	1.10	1.13	2.22	2.77
o,m,p-Nitrobromobenzene	190	15.9	1.06	1.17	1.57	3.75
o,m,p-Chlorotoluene	130	16.1	1.22	1.10	2.68	1.40
o,m,p-Bromotoluene	155	14.6	1.18	1.06	3.45	1.57
o,m,p-Dichlorobenzene	140	14.9	1.10	1.09	1.93	1.74
o,m,p-Dibromobenzene	170	15.6	1.06	1.12	1.18	2.36
o,m,p-Chloroaniline	180	15.2	1.73	1.06	17.62	1.65
o,m,p-Bromaniline	195	15.1	1.78	1.10	18.39	1.94

Fig. 8 Separation chromatograms of structural and cis/trans-isomers on the CPOC column Peak identifications: a. 1-5. 2-methyl-2-butanol, 3-methyl-2-butanol, 3-pentanol, 2-methylbutanol, 1-pentanol; e. 1-4. iso-propylbenzene, n-propylbenzene, 1,2,3-trimethylbenzene, 1,3,5-trimethylbenzene; g. 1-3. 2,2-dimethylbutane, 2-methylpentane, n-hexane.

Fig. 9 Enantioseparation chromatograms of chiral compounds on the CPOC column

Table 2 Enantioseparation data of chiral compounds on the CPOC-based GC column

Racemate	CPOC-based GC column					β-DEX 120 column
Racemate	T/ ℃	k₁	α	R_s	v/(cm/s)	T/ ℃	k₁	α	R_s	v/(cm/s)
Ethyl 3-hydroxybutyrate	160	0.86	1.30	5.46	15.1	100	4.25	1.00	-^b)	13.5
Valine^a)	155	0.81	1.22	4.87	15.3	95	5.21	1.00	-^b)	15.1
Glutamic acid^a)	185	1.01	1.29	7.16	14.9	160	6.66	1.00	-^b)	15.6
1,2-Epoxybutane	70	1.79	1.21	5.01	14.6	40	1.54	1.00	-^b)	14.3
1,2-Butanediol diacetate	175	1.16	1.08	1.77	16.2	135	2.64	1.02	1.11	15.5
Isoleucine^a)	165	1.61	1.05	1.30	15.3	95	9.80	1.02	1.03	15.0
1,3-Butanediol diacetate	180	2.41	1.04	0.86	14.1	140	2.65	1.03	1.52	15.0
Epichlorohydrin	90	4.19	1.02	0.70	13.9	65	2.82	1.00	-^b)	14.3
Epibromohydrin	95	5.12	1.06	1.18	15.0	70	5.74	1.00	-^b)	14.3
β-Butyrolactone	110	1.51	1.04	0.74	14.6	80	3.45	1.02	1.15	13.5
γ-Valerolactone	120	2.62	1.02	0.64	15.5	105	4.95	1.03	1.45	13.5
2-Octanol acetate	160	0.75	1.01	0.60	15.9	110	3.87	1.10	5.25	14.3

Fig. 10 Molecular structure of CPOC and molecular dimensions of the tested racemates a. side view; b. vertical view; c. molecular dimensions.

Fig. 11 Repeatability of the CPOC column a. Chromatograms obtained at the beginning of the column be used; b, c and d. chromatograms obtained after the column was undergone 80, 160 and 500 injections, respectively.

Fig. 12 Thermal stability of the CPOC column a. Chromatograms of the column without high temperature treatment; b, c and d. chromatograms obtained after the column was conditioned at 280 ℃ for 2 h, 4 h and 8 h, respectively.

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