J. Phys. Chem. 1994, 98, 6862-6864
6862
Chiral Discrimination in the Liquid Phase: Excess Volumes of Binary Mixtures of Amino Acid Derivatives? Luciano Lepori'a Istituto di Chimica Quantistica ed Energetica Molecolare del C.N.R., Via Risorgimento 35, 56126 Pisa, Italy
Bernhard Koppeaboefer'ps Institut f i r Organische Chemie, Universitiit Tiibingen, Auf der Morgenstelle 18, D- 72076 Tiibingen, Federal Republic of Germany
Received: January 28, 1994'
Volume changes on mixing the enantiomers of N-trifluoroacetylamino acid methyl esters (N-TFA-amino acidOMe) were determined at 25 OC by means of a high-precision vibrating-tube densimeter. The excess molar volumes (Ve) for the racemic mixtures of N-TFA-Ala-OMe 1, N-TFA-Val-OMe 2, and N-TFA-Leu-OMe 3, were found as Ve = 0.0098,-0.0458, and 0.035 cm3 mol-', respectively. For 2 and 3, these volumetric effects of discriminating interactions between enantiomers in the liquid phase are the largest ever observed.
Introduction Studies on the thermodynamic properties of solutions of optically active compounds are relevant in view of the heightened industrial interest in the resolution of enantiomers of active compounds,l inter alia, pharmaceuticals, pesticides, herbicides, and fragrances.2 It has been shown that discriminatory interactions of chiral molecules are effective in the liquid phase, too, although to a smaller degree than in the solid phase; polarimetric,' nuclear magneticresonance (NMR),' enthalpic,l-6and volumetric effects7-9 were observed. Extending precedingexperiments! we report here on the volume changes upon mixing the enantiomeric pairs of three amino acid derivatives,i.e.,the N-trifluoroacetyl methyl esters of alanine ( N -
\ R= Me
NH
1
TABLE 1: Gas Chromatography Data of N-TrifluoroncetylaminoAcid Methyl Esters on (L)-Chirasil-Val compound T,"C f'm.min t:fm, min TFA-Ala-OMe TFA-Val-OMe TFA-Leu-OMe
t Preliminary results were communicated at the 9th IUPAC Conference on Chemical Thermodynamics, Lisboa, Portugal, July 14-18, 1986. t Fax. +39-50-502270. t Fax. +49-7071-29760602. *Abstract published in Advance ACS Absrructs, May 15, 1994.
0022-3654/94/2098-6862$04.50/0
110
compound TFA-AA-OMe
bp, P O C , mbar
(R)-Ala (S)-Ala (R)-Val (S)-Val (=)-Leu (S)-Leu
91/19
(I
Experimental Section Materials. The title compounds were prepared from the corresponding amino acids. In the first step, the amino acids were reacted with thionyl chloride/methanol to give the amino acid methyl esters as hydroch10rides.l~The hydrochlorideswere treated with trifluoroacetic acid anhydride to yield the title compounds.14Js These were purified by double distillation with a spinning band column (1 m, Normag, Hofheim, FRG).l6 All samples used in the experiments were both of high chemical (>99.8%) and enantiomeric purity (>99%), as determined by
3.37 4.77 3.85
3.92 5.46 4.42
ro, min 0.92 0.92 0.98
TABLE 2: Physical Properties of N-Trifluoroacetylamino Acid Methyl Esters
i-Bu 3
TFA-Ala-OMe l),valine (N-TFA-Val-OMe 2), and leucine (NTFA-Leu-OMe 3). Exhibiting fairly large differences in enthalpies (Amand entropies ( A S ) of interaction with chiral stationary phases (CSPs) in gas-liquid chromatography(GLC)10-12 and significant chemical shift nonequivalence upon addition of a CSP in NMR experiments in tetrachloromethane solution,12 these compounds suggested themselves as promising targets for extraordinary large effects in the excess molar volume (VE) of mixing the enantiomers.
ao ao
aqo.7
50J0.7 51/o.a 5710.1 57/o.i
P.' R
~ m -(neat) ~
1.32224 1.32216 1.22430 1.22443 1.18702 1.18746
+51.7 -51.3 -7.5 +7.6 -29.0
chemical purity. I ee. W 99.9 99.8 99.9 99.9 99.9 99.8
99.0 99.6 99.9 99.9 g0.005
99.9
Averaged value of the density (at 25 "C)measured at different times.
GLC on ~-Chirasil-Vall~ (deactivated glass capillary column, 20 m X 0.25 mm) and D-chirasil-ValI* (deactivated glass capillary column, 20 m X 0.25 mm), respectively; the chromatographic data taken on L-Chirasil-Val, i.e., net retention times t :(R) and ti(9,respectively, and dead time to are compiled in Table 1. Some physicochemical properties,Le.,boiling point, bp, density, p, and optical rotation, [ a ]as~well as chemical and enantiomeric purities of the compounds investigated are collected in Table 2. Apparatus and Measurements. Density measurements were carried out with an A. Paar vibrating-tube densimeter capable of a precision of 3 X 1od g ~ m - ~Calibration . and test of the apparatus as well as the measuring procedure were described elsewhere.*J9 The liquid mixtures to be studied were made up by adding successivelyweighed amounts of a pure enantiomer to a given amount of the other (in the order of 2-3 g). At least eight measurements were carried out in two runs for each system examined, starting from one isomer and then from the other. For each mixture, the excess molar volume, VE, was determined through eq 1.
Here, p is the density at the mixture, Mis the molecular weight of either two components, X I and x2 are their mole fractions, and p~ and p2 are the densities of the pure liquids. Although pl and 0 1994 American Chemical Society
The Journal of Physical Chemistry, Vol. 98, No. 27, 1994 6863
Chiral Discrimination in the Liquid Phase
TABLE 3: Parameters a of Jlq 2 and Standard Deviations u for Representation of V of Enantiomeric Liquid Mixtures + (1 - x)Am at 25 O C A 4 4 , cm3 mol-' u, om3 mol-' TFA-Ala-OMe +0.0098 0.0007 -0.0458 TFA-Val-OMe 0.0008 +0.035' TFA-Leu-OMe 0.003' -0.00366 limonene 0.001l b +0.00266 a-pinene O.OOO4b -0.01576 2-methyl-1-butanol 0.00086 2-octanol +0.00876 0.00056 0.0005b carvone -0.00566 -0.0041C fenchone 0.0005c -0.0054b 0.00066 a-methylbenzylamine a Calculated from the value obtained for the RS + S system ( 4 4 = 0.0088 cm3 mol-', u = 0.0008 c m 3 mol-'), following a proceduredescribed in ref 8. * Reference 8. Reference 7.
0.02
m
R+S
\
7,
'\
E
5
N -T F A -A la -0Me
0
-
~~
I
0
-0.02
v
\
z
-0.04
~~
VE = ax(1 - x )
the representations of VE's are compiled. In the case of 3, the racemate instead of the (R)-isomer was employed. For the corresponding R + S system, the value of a was calculated, from that found for the RS S system, by taking into account the enantiomeric purity of the constituents.s For comparison, the parameters a of other pairs of optical antipodes studied so far, Le., two hydrocarbons, two alcohols, two ketones, and one amine, are reported in Table 3. Apparently, the excess volumes are small in magnitude ( a / 4 = VeXlo.s < 0.05 cm3 mol-') and have either positive or negative sign, depending on the enantiomeric pair examined. The volumetric effects for the valine derivative 2 and for the leucine derivative 3 are the largest ever observed,20 though being of opposite sign. Whereas the ( R ) - and (S)enantiomers of 2 are packed together more tightly in the racemic mixture than in the scalemic (enantiomerically enriched) liquid, the opposite holds true for 3. Similarly to YE, the scanty heats of mixing HE of enantiomers4J are small in magnitude (
