Liquid purification or separation – Processes – Liquid/liquid solvent or colloidal extraction or diffusing...
Reexamination Certificate
2000-08-28
2002-11-26
Fortuna, Ana (Department: 1723)
Liquid purification or separation
Processes
Liquid/liquid solvent or colloidal extraction or diffusing...
C210S638000, C210S321870, C095S044000
Reexamination Certificate
active
06485650
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to the separation of enantiomers or a racemic mixture, into the specific isomers.
Stereoisomers are those molecules which differ from each other only in the way their atoms are oriented in space. Stereoisomers are generally classified as diasteromers or enantiomers; the latter embracing those which are mirror images of each other, the former being those which are not. The particular arrangement of atoms that characterize a particular stereoisomer is known as its optical configuration, and are generally identified as either + or − (also D or L) (and d or l) or R or S.
Though differing only in orientation, the practical effects of stereoisomerism may be important. For example, the biological and pharmaceutical activities of many compounds are strongly influenced by the particular configuration involved. Many compounds are only of widespread utility when provided in a given stereoisomeric form. Therefore, it is the separation of enantiomers that presents a special problem because their physical properties are identical. This is particularly true when involving a racemic mixture; that is, a mixture that comprises equal amounts of enantiomers having different optical configurations. Separation of the racemate into its respective enantiomers, generally known as a resolution, is, therefore, a process of considerable importance and challenge.
A number of techniques for separating enantiomers are known in the art such as various chromatographic methods or enzyme-catalyzed reactions. Most, however, are useful for obtaining small analytical quantities and are not practical for separating larger quantities for commercial purposes. One such method is known as an indirect separation which involves reacting the enantiomers with an optically pure chiral derivatizing agent. A direct method of separation is much like the indirect method involving the formation of a diasteromeric species which is transient, with the stability of one species differing from the other.
Another method described in U.S. Pat. Nos. 4,800,162 and 5,077,217 utilizes multi-phase and extractive enzyme membrane bioreactors for the resolution of racemic mixtures of optically active compounds.
Liquid membranes have been used for separating enantiomers as discussed in the book Chiral Separation, Applications and Technology, S. Ahuja, Editor; American Chemical Society, 1997, Chapter 11, pp. 309-334. One system is described on pp. 329-330, where two membrane modules are employed.
U.S. Pat. No. 5,080,795 to Pirkle et al. employs a similar supported chiral liquid membrane and a chiral carrier which selectively complexes with one of the two enantiomeric optical configurations. However, the liquid membrane present in the Pirkle et al. patent is used in a totally different manner so that in fact the apparatus is in effect a contactor rather than a liquid membrane. The disclosed apparatus has a different principle of operation and different engineering basics compared to the apparatus employed in the present invention. As is clearly shown in the Pirkle et al. patent, the liquid membrane must flow from the source phase containing the feed liquid to the receiving phase containing the solution enriched with one enantiomer. In that respect, the method of separating enantiomers disclosed by Pirkle et al. is totally different from the method of this invention.
Thus, although liquid membranes have been known to be useful in separating chiral enantiomers, they have never been used commercially because, depending on the design and the materials used, the separation modules or parts thereof deteriorate rather quickly or the necessary ingredients such as the liquid membrane or the carrier are partially lost in the process and the separation must be periodically interrupted to replace or replenish them. Furthermore, the prior art methods are often batch processes and, even if continuous, could not be adapted for a large scale continuous separation. Such processes do not provide the necessary rate of transport and the degree of separation in a reasonable time period to make them feasible for large scale commercial enantiomer separation. These deficiencies are resolved and eliminated by the method of this invention.
DETAILED DESCRIPTION
The present invention is directed to a method for separating or resolving enantiomers in a supported liquid membrane module which comprises a liquid membrane, feed fluid containing a racemic mixture and a sweep fluid into which the separated enantiomer passes, such that said feed fluid and said sweep fluid are adjacent to, but on opposite sides of, said liquid membrane and the feed fluid and the sweep fluid have a substantially continuous interfacial contact along the length of the liquid membrane, said method comprising:
a) contacting liquid membrane with said feed fluid;
b) transporting preferentially one enantiomer from the feed fluid into the liquid membrane;
c) contacting liquid membrane with said sweep fluid;
d) transporting the enantiomers from the liquid membrane into the sweep fluid; and
e) recovering the enantiomers from the sweep fluid.
The feed fluid may be composed only of the enantiomers or optionally it may also contain a solvent. If the enantiomers are solid, then a solvent must be employed to dissolve the solid enantiomers. If the enantiomers are liquid, a solvent is usually not absolutely necessary but it may be desirable to employ a solvent. If the selectivity of one enantiomer by the liquid membrane is high, then substantially only one isomer will transport through the membrane and the separation of the isomers will be substantially complete. Optionally, the liquid membrane may also contain a phase transfer agent (PTA) which can be any chemical agent to aid the partitioning of an enantiomer from the feed fluid into the liquid membrane. The feed fluid pH could be adjusted to favor the solubility of the enantiomers in the liquid membrane. Likewise, the sweep fluid pH could be adjusted to favor the solubility of the enantiomers in the sweep fluid.
The solvent that may be employed in the feed must dissolve the enantiomers but it must be different than the solvent in the liquid membrane and it must be substantially immiscible with the liquid membrane. Nevertheless, the solvent could be the same as the solvent in the sweep.
Those skilled in the art will be informed what solvents could be used for a particular enantiomer and the literature provides much information in this regard. For example, a discussion is provided in Chiral Separations, S. Ahuja, ed., (1996) p. 283.
A membrane is a semi-permeable barrier that spatially divides two solutions of different concentrations and controls the solute exchange rate between them. A liquid membrane can serve as a membrane between two other liquid phases provided it is immiscible with those liquid phases. The liquid membrane in the invention consists of a liquid that is immiscible with the feed and the sweep fluids and preferentially dissolves the enantiomer that is to be isolated. The liquid membrane optionally may also contain a carrier and a phase transfer agent (PTA). The need for a carrier and a PTA will depend on the enantiomers that are being separated, the degree of solubility of the desired enantiomer in the liquid membrane (i.e., the solvent present in the liquid membrane), the enantios electivity and the flux rate across the membrane.
A chiral carrier is a material that enhances the rate of selective transport of an enantiomer. Generally, a chiral carrier complexes preferentially with one enantiomer in the liquid membrane or dissolves preferentially one enantiomer. In effect, the carrier increases the solubility of one enantiomer in the liquid membrane. This facilitates the transport of the complexed or the preferentially soluble enantiomer through the liquid membrane. Thus, a solvent used as a liquid membrane could conceivably act as a carrier. The uncomplexed carrier and the carrier complexed with an enantiomer should be substantially immiscible with the feed and sweep fluids. The carrie
Facilichem, Inc.
Fortuna Ana
Hudak Shunk & Farine Co.
LandOfFree
Liquid membrane separation of enantiomers does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Liquid membrane separation of enantiomers, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Liquid membrane separation of enantiomers will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2938405