Chapter 9
Downloaded by NORTH CAROLINA STATE UNIV on October 4, 2012 | http://pubs.acs.org Publication Date: October 1, 1997 | doi: 10.1021/bk-1997-0670.ch009
Effect of Functional Groups on the Solubilities of Coumarin Derivatives in Supercritical Carbon Dioxide 1
1
2
2
2
Y. H.Choi ,J.Kim ,M. J. Noh , E. S.Choi ,and K.-P. Yoo 1
College of Pharmacy, Seoul National University, 151-742, Seoul, Korea Department of Chemical Engineering, Sogang University, C.P.O. Box 1142, Seoul, Korea
2
Solubilities of the basic coumarin, five mono-substituted derivatives (7hydroxy-, 7-methoxy-, 7-methyl-, 6-methyl- and 4-hydroxy-coumarin) and three di-substituted derivatives (6,7-dihydroxycoumarin, 7-hydroxy coumarin-4-acetic acid, and 7-methoxycoumarin-4-acetic acid) in supercriticalCO were measured in a range of temperatures 35~50 °C and pressures 8.5~25 MPa. In general, mono-substituted coumarin derivatives were less soluble than the basic coumarin in CO . The degree of solubility tends to increase in the order of 7-methyl-, 7methoxy-, 7-hydroxy-, and 4-hydroxycoumarin. However, in the case of 6-methylcoumarin, it was unusually more soluble than the basic coumarin by several times in CO over the entire experimental conditions. Furthermore, the di-substituted coumarin derivatives were extremely less soluble than the basic coumarin and monosubstituted coumarins. For each coumarin derivative, optimum equilibrium conditions which gives maximum solubility inCO were reported. 2
2
2
2
It has been experimentally proven that supercritical C 0 can be an efficient alternative solvent over the conventional organic liquid solvents for many cases of selective extraction of bioactive substances from natural plants (1-4). The supercritical fluid extraction (SFE) is more economical than liquid solvent extraction (5-8). It is the usual cases that the total extracts from natural plants with any means are supposed to contain many compounds and their numerous substituted derivatives. Thereby, whenever one intends to obtain a highly purified target substancefromthe total extract it is essential to know at least the quantitative solubility behavior of each solute in a specific supercritical solvent. The information of phase equilibrium behavior between a solute and a solvent are imperative for the preliminary evaluation of an economic viability of the SFE on process for a given sample material. 2
110
© 1997 American Chemical Society
In Supercritical Fluids; Abraham, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1997.
9. CHOI E T A L . Solubilities of Coumarin Derivatives in Supercritical C0
Downloaded by NORTH CAROLINA STATE UNIV on October 4, 2012 | http://pubs.acs.org Publication Date: October 1, 1997 | doi: 10.1021/bk-1997-0670.ch009
2
Thus, many investigators have been reported the phase equilibrium data of natural substances in supercriticalfluids(9-77). However, such reliable thermodynamic data are extremely scarce in most cases. Take for instance, reports on the quantitatively compared solubility for a specific natural substance together with its derivatives are extremely limited. Thus, in the present study, we placed our attention on the solubility measurement of coumarin and its derivatives over a wide range of supercritical conditions. Since coumarin and its substituted derivatives have been known for their strong bioactivities such as antibiotic, antitumor, vasodilatory and anticoagulant (72), some researchers have been concerned with the extractability of these substances from plants with supercritical CO2 (73-75). However, no systematic and quantitative solubility studies are demonstrated yet for the purpose of reliable process design. Thus, in the present study, we placed our attention on a comparative measurement of several coumarins in supercritical C0 . Among numerous types of coumarins, we illustratively selected nine types of coumarins with emphasis on the fixed positions (e.g., C-4 and C-7 position as shown in Figure 1) and tried to measure their respective solubilities. Tested derivatives include coumarin derivatives substituted by with methyl-, methoxy-, hydroxy-, and acetic acid group, respectively. 2
Experimental Chemicals. Reagent-grade (
