192
P MUNEGUMI ET AL.
rotation of the samples. Infrared absorption spectra were measured with
a Shimadzu FTIR-8400S.
obtained crystals depended on the frequency of the ultra-
sound irradiation used. Crystallization of p-toluenesulfonate
of valine benzyl esters (D-rich 5) with a 20% e.e. in 2-propa-
nol gave a final e.e. of 94%. However, preferential crystalliza-
tion of 4 and 6 did not succeed. Sonication increased the
rate of preferential crystallization. This research demon-
strates the first preferential crystallization of p-toluenesulfo-
nate of valine benzyl esters and an acceleration of crystalliza-
tion using sonication.
Preferential Crystallization
The substituted benzenesulfonates [(L)-4, (D)-4, (L)-5, and (D)-5]
of the L- and D-valine benzyl esters were mixed at different molar ratios
(total mass 5 400 mg) and dissolved in 2-propanol as the solvent. This
solution was seeded with a 1.0-mg enantiomer crystal at 258C. After
seeding, the solution in a glass Erlenmeyer’s flask (10 ml) surrounded
by water bath at 258C was irradiated for 2 min form the bottom of the
flask by ultrasound. The obtained crystal after 4 min’s standing was fil-
tered.
EXPERIMENTAL
Chemicals
Determination of DL-ratio in Benzyl Valinate Crystal
The D-valine and L-valine used were purchased from Nippon Kayaku
and Nippon Rika, respectively. The benzyl alcohol, substituted benzene
sulfonic acids, and benzene used were purchased from Kanto Chemical.
Crystal of p-toluenesulfonate of valine benzyl ester dissolved in a solu-
tion of HClO4 aq. (pH 2) – CH3CN 70:30 was injected into a high-per-
formance liquid chromatograph equipped with a chiral column (OA-
8000, Sumika Analytical Center).
Preparation of Substituted Benzenesulfonates (4, 5, 6) of
Valine Benzyl Ester
LITERATURE CITED
D-Valine (150 mmol, 17.6 g), benzyl alcohol (450 mmol), and p-tolue-
nesulfonic acid monohydrate (165 mmol, 31.4 g) were mixed in benzene
(80 ml). The resulting mixture was refluxed for a period of 23 h to
remove the evolved water using azeotropic condensation from the benzyl
alcohol and valine (D- or L-) to give p-toluenesulfonate of valine benzyl
ester (44.8 g, 79%). After several recrystallization stages, pure crystals
1. Eliel EL. Stereochemistry of carbon compounds. New Delhi: TATA
McGraw-Hill Publishing Company Ltd; 1975. p 486.
2. Collet A, Brienne N-J, Jacques J. Optical resolution by direct crystalliza-
tion of enantiomer mixtures. Chem Rev 1980;80:215–230.
3. Jacques J, Collet A, Wilen S. Enantiomers, racemates, and resolutions.
Florida: Krieger Publishing Company; 1981. p 447.
24
were obtained (13.9 g, yield 5 31%), mp 5 154–1578C, [a]D 5 13.3, C
5 1.0, ethanol, and mp 5 153–1568C, [a]D24 5 –3.6, C 5 1.0, ethanol for
p-toluenesulfonates of D- and L-valine benzyl esters [(D)-5 and (L)-5],
respectively.
4. Coquerel G. Preferential crystallization In: Sakai K, Hirayama N, Tamura
R, editors. Novel optical resolution technologies, topics of current chem-
istry, Vol.269. Berlin, Heidelberg: Springer-Verlag; 2007, p 1–51.
5. Coquerel G. Amabilino DB. The nanoscale aspects of chirality in crystal
growth and heterogeneous equilibria. In: Amabilino DB, editor. Chirality
at the nanoscale, Weinheim: Wiley-VCH; 2009, p 305–348.
Benzenesulfonates [(D)-4 and (L)-4] of valine benzyl esters were pre-
21
pared by the similar manner in the yield of 73%, mp 5 184–1868C, [a]D
5 12.5, C 5 1.0, ethanol, and 77%, mp 5 184–1868C, [a]D21 5 –2.8, C 5
1.0, ethanol, respectively.
6. Tamura R, Takahashi H, Fujimoto D, Ushio T. Mechanism and scope of
preferential enrichment, a symmetry-breaking enantiomeric resolution
phenomenon. In: Sakai K, Hirayama N, Tamura R, editors. Novel optical
resolution technologies, topics of current chemistry, Vol. 269. Berlin,
Heidelberg: Springer-Verlag; 2007. p 53–82.
2,5-Dimethyl-benzenesulfonates [(D)-6 and (L)-6)] of valine benzyl
esters were prepared by neutralization of free valine benzyl esters
extracted from (D)-5 and (L)-5 with 2,5-dimethyl-benzenesulfonate (3c).
Because the products were pure but oils, further purification was not car-
ried out.
7. Ajinomoto Co. Japanese Patent 18,470 (1962). Chem Abstr 1963;59:11659.
8. Ajinomoto Co. British Patent 969,128 (1964). Chem Abstr 1965;62:13232.
9. Japanese Patent Application 62-096454 (1962).
Apparatus
10. Mason TJ, Lorimer JP. Applied sonochemistry. Weinheim: Wiley-VCH;
2002. p 19.
The melting point of the benzyl valinate crystals was measured using
a Buchi 530. Separation of diastereomers was performed using a high-
performance liquid chromatograph system, comprising a Hitachi L-6000
pump, an L-4200 detector, and a D-2500 chromato-integrator. A Sumichi-
ral OA-8000 chiral analytical column was used to resolve the enantiom-
ers. Sonication was carried out using a Yamato Bransonic B-1200 sonica-
tor at 45 kHz and a Velvo-clear VS-100 III sonicator at 28 and 100 kHz.
A Jusco DIP-181 digital polarimeter was used to measure the optical
11. The Noguchi Institute, French Patent 1,389,840 ( 1965). Chem Abstr
1965;63:5740.
12. Higaki K, Ueno S, Koyano Y, Sato K. Effect of ultrasonic irradiation on
crystallization behavior of tripalmitoylglycerol and cocoa butter. JAOCS
2001;78:513–518.
13. Wang H, Lu Y, Zhu J, Chen H. Sonochemical fabrication and characteri-
zation of stibnite nanorods. Inorg Chem 2003;42:6404–6411.
Chirality DOI 10.1002/chir