neutralization with 1 mol/ L KOH solution, the aqueous phase was
extracted repeatedly with dichloromethane. The organic phases
were combined, washed with water and brine, dried over MgSO4,
and filtered. Evaporation of the organic solvent gave 5.0 g of a
pasty white solid in 91% yield. 1H NMR (300 MHz, CDCl3): δ
9.42 (1H, br s), 7.26 (2H, s), 6.73 (1H, s), 3.34 (1H), 2.45 (1H, m),
2.29 (6H, s), 1.68 (2H, br s), 1.02 (3H, d, J ) 6.9 Hz), 0.85 (3H, d,
J ) 6.9 Hz).
ω-Undecylenyl
L-valine-3,5-dimethylanilidocarbamate (8).
L-Valine-3,5-dimethylanilide (7 , 2.20 g) was added under stirring
to a solution of ω-undecylenyl 4-nitrophenylcarbonate (3 ) and tri-
ethylamine (1.52 g) in 60 mL of dry tetrahydrofuran. The resulting
reaction mixture was heated at reflux overnight, diluted with 100
mL of ethyl acetate, and washed with water and saturated sodium
bicarbonate solution. The organic phase was dried over MgSO4,
filtered, and evaporated under vacuum to give a crude product,
which was purified by flash chromatography on silica gel using
ethyl acetate/ hexane (1:3) to yield 3.51 g (84%) of the product as
a pale-yellow viscous oil. 1H NMR (300 MHz, CDCl3): δ 8.34 (1H,
br s), 7.15 (2H, s), 6.72 (1H, s), 5.82 (1H, m), 5.53 (1H, d, J ) 9.0
Hz), 5.03-4.90 (2H), 4.18 (1H, m), 4.07 (2H), 2.27 (6H, s), 2.14
(1H, m), 2.02 (2H, m), 1.60 (2H, m), 1.49-1.18 (12H), 1.02 (6H).
Silica-Based Chiral Stationary P hase (CSP 1 ). Dimethyl-
chlorosilane (15 mL) and chloroplatinic acid (25 mg), which had
been dissolved in 40 mL of tetrahydrofuran, were added to a 100
Figure 1. Structures of analytes used in this study.
A Waters HPLC system consisting of two 510 HPLC pumps, a
717 plus autosampler, and a 486 UV detector and Waters
Millenium 2010 software were used throughout. 1,3,5-Tri-tert-
butylbenzene (TTBB) was used to determine column void volume
under normal phase HPLC conditions.
Racemic Analytes. N-(3,5-Dinitrobenzoyl)-R-amino acid meth-
yl ester and alkyl amides I-III were prepared by methods similar
to those previously reported.18 Analyte IV was prepared by
allowing homocysteine thiolactone to react with 3,5-dinitrobenzoyl
chloride in the presence of triethylamine in dichloromethane. 1H
NMR and IR spectra are in agreement with the assigned structures
shown in Figure 1.
P reparation of the Chiral Selector. ω-Undecylenyl 4 -ni-
trophenylcarbonate (3 ). ω-Undecylenyl alcohol (1 , 2.55 g) was
added to a solution of 4-nitrophenyl chloroformate (2 , 3.10 g) in
75 mL of anhydrous pyridine/ tetrahydrofuran (1:2 by volume) at
0 °C with stirring. After the addition, the reaction mixture was
allowed to warm up to room temperature and stirred overnight
under nitrogen. The solution was diluted with ethyl acetate and
washed with 1 mol/ L HCl, water, and brine. The organic phase
was dried over MgSO4, filtered, and evaporated under vacuum to
afford 4.45 g of oily product 3 (89%). 1H NMR (300 MHz,
CDCl3): δ 8.30 (2H, d, J ) 6.91 Hz), 7.43 (2H, d, J ) 6.91 Hz),
5.83 (1H, m), 4.97 (2H), 4.29 (2H, d, J ) 6.72 Hz), 2.05 (2H, m),
1.76 (2H, m), 1.58-1.23 (12H).
mL round-bottom flask containing 2.4 g of ω-undecylenyl L-valine-
3,5-dimethylanilidocarbamate (8 ) in 15 mL of dry toluene. The
reaction mixture was heated at 60 °C for 2 h with stirring under
nitrogen, and the excess dimethylchlorosilane was removed with
two small portions of dry toluene. The mixture was then treated
with a solution of 10 mL of absolute ethanol, 10 mL of triethyl-
amine, and 10 mL of diethyl ether. After the precipitated tri-
ethylamine hydrochloride was removed by filtration, the filtrate
was concentrated and chromatographed on a silica gel column
with 3:1 dichloromethane/ hexane to afford 2.80 g of the chiral
ethoxyorganosilane as a yellow oil in 89% yield. 1H NMR (300
MHz, CDCl3): δ 8.38 (1H, br s), 7.12 (2H, s), 6.70 (1H, s), 5.65
(1H, d, J ) 8.7 Hz), 4.17 (1H, m), 4.10 (2H, quart, J ) 7.1 Hz),
4.06 (2H), 2.25 (6H, s), 2.13 (1H, m), 1.61 (2H, m), 1.49-1.12
(19H), 1.05 (6H), 0.51 (2H), 0.08 (6H, s).
Dried silica beads (2.20 g) were added to a solution of the
above chiral ethoxyorganosilane (2.75 g) in 15 mL of dry toluene.
The resulting slurry was heated at reflux under nitrogen for 24
h. These chirally modified silica beads were washed thoroughly
with dichloromethane and methanol. The content of chiral
selector functionalities in silica beads is 0.20 mmol/ g according
to the result of elemental analysis (C, 6.5; H, 0.52; N, 0.50).
Uniformly Sized Macroporous P oly(glycidyl methacrylate-
co-ethylene dimethacrylate) Beads. The monodisperse porous
poly(glycidyl methacrylate-co-ethylene dimethacrylate) (GMA-
EDMA) beads (9 ) were prepared according to a staged templated
suspension polymerization process reported elsewhere.19 The
content of epoxide groups (1.53 mmol/ g) was determined by
volumetric titration.20
N-(ter t-Butoxycarbonyl)-
2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline (EEDQ, 8.54 g)
was added to a solution of N-(tert-butoxycarbonyl)- -valine (4 , 6.52
L-valine-3,5-dimethylanilide (6).
L
g) in 45 mL of anhydrous dichloromethane with stirring, followed
by addition of 4.18 g of freshly distilled 3,5-dimethylaniline (5 ).
The resulting reaction mixture was stirred overnight and then
washed successively with dilute aqueous HCl, water, and brine.
The organic phase was dried over MgSO4 and filtered. Evapora-
tion of the filtrate in vacuo followed by crystallization from
dichloromethane affords 9.04 g of the product, 6 , in 94% yield. 1H
NMR (300 MHz, CDCl3): δ 8.66 (1H, br s), 7.12 (2H, s), 6.66
(1H, s), 5.52 (1H, d, J ) 8.3 Hz), 4.16 (1H, m), 2.18 (6H, s), 2.12
(1H, m), 1.43 (9H, s), 1.11 (6H).
Reduced Beads, 10. To a slurry of 2.0 g of the GMA-EDMA
beads 9 in 25 mL of dry tetrahydrofuran were added 10 mL of 1
mol/ L NaBH3CN in tetrahydrofuran and a small amount of
bromocresol green indicator. Boron trifluoride diethyl etherate
L
-Valine-3 ,5 -dimethylanilide (7 ). N-(tert-Butoxycarbonyl)-
L-valine-3,5-dimethylanilide (6 , 8.0 g) was placed in a 250 mL
round-bottom flask containing 120 mL of 1:1 trifluroacetic acid/
acetic acid solution, and the resulting mixture was stirred at
ambient temperature for 6 h. The reaction mixture was concen-
trated in a rotary evaporator and poured into 25 mL of water. After
(19) Smigol, V.; Svec, F. J. Appl. Polym. Sci. 1 9 9 2 , 46, 1439-1448.
(20) Jay, R. R. Anal. Chem. 1 9 6 3 , 35, 667-668.
62 Analytical Chemistry, Vol. 69, No. 1, January 1, 1997