Organic compounds -- part of the class 532-570 series – Organic compounds – Silicon containing
Reexamination Certificate
2001-06-08
2004-05-11
Barts, Samuel A (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Silicon containing
C556S450000, C556S476000, C556S485000
Reexamination Certificate
active
06734318
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to fluorous triphase and other multiphase systems and, especially, to fluorous triphase and other multiphase systems for effecting reactions and/or separations.
References set forth herein may facilitate understanding of the present invention or the background of the present invention. Inclusion of a reference herein, however, is not intended to and does not constitute an admission that the reference is available as prior art with respect to the present invention.
In fluorous biphasic reaction methods, an organic substrate dissolved in an organic solvent and a fluorous catalyst (or precatalyst) dissolved in a fluorous solvent are contacted with any other needed reagents or reactants to form an organic product. Separation of the organic and fluorous liquid phases provides the product from the organic phase and the catalyst from the fluorous phase. See, for example, Horvath, I. T.; Rábai,
J. Science,
266, 72 (1994); Horvath, I. T.,
Acc. Chem. Res.,
31, 641 (1998); and U.S. Pat. No. 5,463,082.
Since fluorous biphasic reactions were introduced to organic synthesis by Horváth and Rábai, much attention has been paid to the strategic new option of fluorous techniques for conducting organic reactions and for separating reaction mixtures. A review of fluorous techniques is provided in Curran, D. P.,
Angew. Chem. Int. Ed. Engl.,
37, 1175 (1998). In general, fluorous techniques in organic synthesis can be classified into three categories: (1) fluorous biphasic reactions as described above; (2) fluorous liquid-organic liquid separation; and (3) organic liquid-fluorous solid separation.
Although the usefulness of fluorous techniques has been extended substantially in recent years, it remains very desirable to develop improved fluorous reaction and separation methods and apparatuses.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides method of reacting a first compound to produce a second compound including the steps of: contacting a first non-fluorous phase including the first compound with a first fluorous phase at a first phase interface, the first compound distributing between the first fluorous phase and the first non-fluorous phase; contacting the first fluorous phase with a second non-fluorous phase at a second phase interface; and including at least a third compound in the second non-fluorous phase that reacts with the first compound to produce the second compound, the second compound having a distribution coefficient less than the first compound (and preferably distributing preferentially in the second non-fluorous phase). This method can, for example be used to separate the second compound from unreacted first compound wherein, for example, the first compound is of a fluorous nature and distributes more readily into (or transports, diffuses or migrates more quickly through) the fluorous phase than does the second compound. In general, the fluorous phase serves as a barrier to prevent the two non-fluorous phases from mixing, but molecules that can transport, diffuse or migrate through the fluorous phase can pass from one side to the other. As used herein, the term “transport” includes unaided movement, migration or diffusion of a chemical substance or diffusion or migration assisted by a reagent.
The fluorous liquid phase(s) of the present invention can, for example, include any number of fluorous liquids as known in the art, including fluorous solvents. As used herein, the term “fluorous liquid” refers generally to a liquid and/or a liquid mixture that is rich in carbon-fluorine bonds. As used herein, the term “fluorous solvent” refers generally to a solvent and/or a solvent mixture that is rich in carbon-fluorine bonds. Fluorous solvents include fluorocarbons (for example, perfluorohexane and perfluoroheptane), fluorohydrocarbons, fluorinated ethers (for example, perfluorobutyltetrahydrofuran) and fluorinated amines (for example, perfluorotriethyl amine), among others. In general, fluorous liquids and solvents have Hildebrand solubility parameters less than about 14 MPa
1/2
. Many fluorous liquids and solvents are commercially available, and a partial list of commercially available and otherwise known fluorous liquids and solvents is contained in Barthel-Rosa, L. P.; Gladysz, J. A. “Chemistry in fluorous media: a user's guide to practical considerations in the application of fluorous catalysts and reagents”
Coord. Chem. Rev.,
192, 587-605 (1999).
As used herein, the term “liquid” refers generally to phases that take the shape of their container without necessarily filling it (J. N. Murrell and E. A. Boucher, “Properties of Liquids and Solutions” Wiley, N.Y., 1982, pp1-3). Non-viscous liquids fill a container quickly, while liquid phases with a high viscosity may take a perceptible time to fill a container. Examples of high-viscosity fluorous liquids include, for example, oligomeric mixtures such as the Krytox series available from DuPont.
The term “liquid” also includes supported liquids wherein, for example, the liquid is included in the pore space of a macro-porous or micro-porous support (for example, a liquid membrane). The term “liquid” further includes gel phases, which are formed, for example, by adding a gelling agent to a liquid phase, and plasticized liquid phases. The term liquid also includes solutions of nominally pure liquids and other chemical species dissolved in or suspended in them. For example, such dissolved species can be other liquids, solids that form a pseudophase (for example, perfluoroalkane sulfonate of perfluoroalkane carboxylate surfactants which may form reverse micelles or other pseudophases), transport agents or carriers (for example, metal chelators, metal complexes, organic molecular receptors or nanoparticles).
Non-fluorous phases of the present invention can generally be any non-fluorous liquid or solvent as known in the art. As used herein, the terms “non-fluorous liquid” and “non-fluorous solvent” refers generally to organic and aqueous liquids and solvents, respectively, and/or to mixtures thereof. Preferred non-fluorous liquids have a Hildebrand solubility parameter greater than about 17 MPa
1/2
, and more preferred non-fluorous liquids have a Hildebrand parameter greater than about 18 MPa
1/2
. Water and other aqueous liquid mixtures are suitable non-fluorous liquids for use in the present invention, as are many organic liquids including, but not limited to, acetonitrile, ethyl acetate, ethanol, methanol, tetrahydrofuran, dimethyl formamide, dimethyl sulfoxide, toluene and benzene. Non-traditional organic liquids such as ionic liquids can also be used.
In the methods of the present invention, the fluorous mutliphasic system preferably does not become substantially homogeneous at any point in the process. In this regard, the fluorous and non-fluorous phases preferably remain substantially immiscible during the course of the process. However, some mixing or miscibility at the phase boundary (interface) between the fluorous and non-fluorous phases is allowable and may even be helpful to promote the contact of the fluorous and non-fluorous phases and thereby facilitate exchange of certain components between the respective phases. In addition, the non-fluorous phase may distribute into the fluorous phase altering its composition during a reaction, separation or reaction/separation procedure. Likewise, the fluorous phase may distribute into the non-fluorous phase, altering its composition. The conditions for miscibility or immiscibility of many fluorous and non-fluorous liquids and liquid mixtures are well known, and unknown pairings can often be predicted by differences in Hildebrand solubility parameters or can be readily determined experimentally.
In one embodiment, the first non-fluorous phase includes at least one compound other than the first compound. The other compound has a distribution coefficient less than the first compound and preferably distributes preferentially into the first non-fluorous phase. In this embodiment, the other compound(s) ca
Curran Dennis P.
Linclau Bruno
Nakamura Hiroyuki
Sun Lifang
Weber Stephen G.
Bartony & Hare, LLP
Barts Samuel A
University of Pittsburgh
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