WO2006087556A1 - Procédé de séparation - Google Patents

Procédé de séparation Download PDF

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Publication number
WO2006087556A1
WO2006087556A1 PCT/GB2006/000547 GB2006000547W WO2006087556A1 WO 2006087556 A1 WO2006087556 A1 WO 2006087556A1 GB 2006000547 W GB2006000547 W GB 2006000547W WO 2006087556 A1 WO2006087556 A1 WO 2006087556A1
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Prior art keywords
host
membrane
guest
process according
solution
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PCT/GB2006/000547
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English (en)
Inventor
Andrew Guy Livingston
Andrew Timothy Boam
Nazlee Faisal Ghazali
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Membrane Extraction Technology Ltd
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Publication of WO2006087556A1 publication Critical patent/WO2006087556A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/02—Reverse osmosis; Hyperfiltration ; Nanofiltration
    • B01D61/04—Feed pretreatment
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/02—Reverse osmosis; Hyperfiltration ; Nanofiltration
    • B01D61/025—Reverse osmosis; Hyperfiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/02—Reverse osmosis; Hyperfiltration ; Nanofiltration
    • B01D61/027—Nanofiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/145—Ultrafiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/147—Microfiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/16—Feed pretreatment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B57/00—Separation of optically-active compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2311/00—Details relating to membrane separation process operations and control
    • B01D2311/04—Specific process operations in the feed stream; Feed pretreatment

Definitions

  • the present invention relates to separating enantiomers or isomers.
  • the process of the present invention relates to separating enantiomers or isomers through a combination of formation and decomposition of molecular complexes with membrane filtration.
  • Isomers are molecules with the same molecular formula but different chemical structure.
  • Enantiomers are chiral molecules which have the same molecular formula and chemical structure, but differ only in their spatial orientation. Though they differ only in their orientation, the practical effects of stereoisomerism of enantiomers are often significant and important. For example, the biological and pharmaceutical activities of many compounds are strongly influenced by the spatial configuration involved. For many chiral compounds, the utility of the compound may be improved by enrichment in one or other enantiomer.
  • Diastereomeric resolutions are known in the art and are used when the enantiomers to be separated have acidic or basic functionality. Resolving agents are added that enable molecular complexes to form through proton transfer from acid to amine. This technique is described for example in "CRC Handbook of Optical Resolutions via Diasteromeric Salt Formation” Kozma D., 2002 ISBN: 0849300193. Further enhancements on this technique are described in US 6,465,684 which discusses the use of families of resolving agents. US 4,800,162 and US 5,077,217 utilise multiphasic and extractive enzyme bioreactors for the resolution of racemic mixtures.
  • Enzymes have been used as chiral selectors for separation of ibuprofen, where the enzyme-ibuprofen complex was separated from the liquid phase using an ultrafiltration membrane ("Membrane Assisted Chiral Resolution of Pharmaceuticals: Ibuprofen Separation By Ultrafiltration Using Bovine Serum Albumin as Chiral Selector” Bowen WR and Nigmatullin RR Separation Science and Technology 37 (14) 3227-3244 (2002)).
  • an ultrafiltration membrane Membrane Assisted Chiral Resolution of Pharmaceuticals: Ibuprofen Separation By Ultrafiltration Using Bovine Serum Albumin as Chiral Selector” Bowen WR and Nigmatullin RR Separation Science and Technology 37 (14) 3227-3244 (2002).
  • the application of chiral selectors with molecular weights under 10,000 directly to a solution phase has been limited by the lack of means both to separate the chiral selector - guest complex from homogenous solution and to separate the chiral selector from the guest molecule.
  • Inclusion complexes are formed by the non-covalent insertion of guest molecules into host lattices, where the hosts are crystalline solids. This may occur when the solid host is suspended as a powder in a solution containing the guest molecules, or when both host and guest are dissolved into a solution and then crystallised from that solution through evaporation of solvent or solvent exchange.
  • Chiral host molecules have been employed to separate enantiomers of a guest molecule through inclusion complexation. "Inclusion Complexation as a Tool in Resolution of Racemates and
  • TADDOLs Two Derivatives
  • Inclusion complexation results in a solid phase comprising the crystals of the host compound and guest molecule, usually suspended in a solvent.
  • the enantiomer that has been less preferentially complexed into the host crystals may be removed by distillation, or the crystals may be separated from the solvent by simple solid-liquid filtration, leaving a mother liquor enriched in the non-complexed enantiomer.
  • the crystals may subsequently be heated under vacuum to release the enantiomer which has preferentially adsorbed into the host crystals.
  • the need for a vacuum distillation step to release the adsorbed enantiomer is one of the limitations of this technique.
  • Membrane processes are well known in the art of separation science, and can be applied to a range of separations of species of varying molecular weights in liquid and gas phases (see for example "Membrane Technology” in Kirk Othmer Encyclopedia of Chemical Technology, 4 th Edition 1993, VoI 16, pages 135-193).
  • Nanofiltration is a membrane process utilising membranes whose pores are in the range 0.5-5 nm, and which have MW cutoffs of 200-1000 Daltons. Nanofiltration has been widely applied to filtration of aqueous fluids, but due to a lack of suitable solvent stable membranes has not been widely applied to separation of solutes in organic solvents.
  • US Patent Nos 5,215,667; 5,288,818 5,298,669 and 5,395,979 describe the use of a hydrophobic membrane to separate water-soluble noble metal ionic phosphine ligand complex catalysts from aldehyde containing hydroformylation reaction mediums comprising aqueous solutions, emulsions or suspensions of said catalysts.
  • US 5,681,473 describes the application of solvent-resistant composite membranes to the separation of organic-solubilised rhodium-organophosphite complex catalyst and free organophosphite ligand from a homogeneous non-aqueous hydroformylation reaction mixture.
  • the present invention addresses the problems of the prior art.
  • the present invention provides a process for separating enantiomers or isomers present in a liquid phase through formation and then subsequent decomposition of a host-guest complex coupled to membrane nanofiltration, comprising the steps of: (a) providing a first solution comprising at least two enantiomers or isomers A and B of a guest molecule; (b) adding a host molecule to this first solution; (c) forming a host-guest complex, such that the ratio between the enantiomers or isomers A and B in the host-guest complex is enriched in A over B relative to the same ratio in the first solution; (d) substantially separating the host-guest complex from the non-complexed B enantiomer or isomer; (e) decomposing the host-guest complex into the host and guest molecules to form a second solution; (f) providing a selectively permeable membrane having a first surface and a second surface; (g) separating the guest molecule and host molecule present in the second solution by
  • the first solution comprises at least two enantiomers A and B of a guest molecule and a solvent.
  • the decomposition of the host-guest complex into host and guest molecules in step (e) is effected by the addition of a solvent.
  • the solvent added in step (e) is different in composition from the solvent present in the first solution of step (a).
  • the solvent added in step (e) is the same in composition as the solvent present in the first solution of step (a).
  • the decomposition of the host-guest complex into host and guest molecules in step (e) is effected by altering the temperature of the first solution from an initial temperature at which the host-guest molecule complex exists to a temperature at which it decomposes into host and guest molecules.
  • a solution enriched in the B enantiomer or isomer from Step (d) is subjected to further separation to separate the guest molecule from the host molecule and host-guest complex present through the steps of: (h) providing a selectively permeable membrane having a first surface and a second surface; (i) separating the guest molecule from both the host molecule and host-guest complex by transferring the guest molecule from the first surface to the second surface across the membrane as in step (g).
  • the separation in step (d) is carried out by membrane filtration.
  • the separation step (d) is carried out on a homogeneous solution using nanofiltration so that the host molecule and host-guest complex are retained and non-complexed B enantiomer or isomer is passed through the membrane.
  • solvent is added during filtration in step (d) to increase the extent to which non-complexed B enantiomer or isomer is separated from the host-guest complex enriched in A.
  • the solution containing the guest molecule resulting from step (g) is further enriched in enantiomer or isomer A through repeating the process one or more times using the solution resulting from step (g) as the feed solution in step (a).
  • the host molecule is not completely soluble in the first solution in step (b), so that it forms a solid phase and the host-guest complex may be separated from the first solution by means including solid-liquid filtration in step (d).
  • the solution formed when the host molecule is added to the first solution in step (b) may be a homogeneous liquid solution.
  • Step (c) may be carried out by altering the composition of this homogeneous liquid through means such as evaporation or addition of a further solvent to the solution, so that the host-guest complex forms a solid phase.
  • At least one solvent may be added to the at least one guest molecule to comprise the first solution.
  • the host molecule may be dissolved or suspended in at least one solvent prior to addition to the first solution in step (b).
  • the host molecule remaining at the first surface of the membrane at step (g) is used again in step (b) after drying or transfer into a suitable solvent, thereby reducing the requirement of the process for fresh host molecule.
  • a selectively permeable membrane will be familiar to one of skill in the art and includes a membrane which will allow the passage of the guest molecule while retarding the passage of both the host molecule and host-guest complex.
  • the selective permeability may be defined in terms of membrane rejection Ri, a common measure known by those skilled in the art and defined as:
  • guest will be familiar to those skilled in the art of separation sciences (see for example “Inclusion Complexation as a Tool in Resolution of Racemates and Separation of Isomers” Lipowska-Urbanczyk Z and Toda F, Chapter 1 in “Separations and Reactions in Organic Supramolecular Chemistry” John Wiley and Sons (2004) ISBN-0-470-085448-0).
  • a “guest” molecule includes an organic molecule which in preferred embodiments may have a molecular weight in the range 50 - 5,000 Daltons, and which exists in at least two enantiomeric forms or in at least two isomeric forms.
  • a “host” molecule includes an organic molecule which in preferred embodiment may have a molecular weight in the range 200 - 10,000 Daltons, and which is added to the first solution to cause host-guest complexes enriched in A relative to B to form.
  • host-guest complex will be well understood by those skilled in the art of separation sciences (see for example “Inclusion Complexation as a Tool in Resolution of Racemates and Separation of Isomers” Lipowska-Urbanczyk Z and Toda F, Chapter 1 in “Separations and Reactions in Organic Supramolecular Chemistry” John Wiley and Sons (2004) ISBN-0-470-085448-0).
  • a "host-guest complex” includes a complex formed by chemical interaction of one or more host molecules with one or more guest molecules.
  • a “solvent” will be familiar to those skilled in the art and may include an organic or aqueous liquid. Preferred solvents have a molecular weight less than 300 Daltons. It is understood that the term solvent also applies to a mixture of solvents. GB 2 373 743 provides further examples of solvents that the skilled reader will be aware of.
  • the process may be carried out continuously so that any of steps (a) to (i) are performed simultaneously.
  • the process may be carried out discontinuously.
  • the membrane f ⁇ ltrations of steps (g) and (i) may each comprise two or more sequential membrane filtrations.
  • more than one selectively permeable membrane may be employed, so that the membranes used in steps (g) and (i), or in sequential filtrations in any one of these steps, may be different. This allows the membrane to be chosen to provide the best combination of solvent flux and solute rejection for a specific composition of the solution to be contacted with the membrane.
  • step (b) there may be more than one host molecule added in step (b), and more than one of these host molecules and the host-guest complexes formed may be retained by membrane filtration in steps (g) or (i).
  • the host molecule or the host guest complex can attach itself loosely to the membrane surface. In these cases it can be readily washed off using fresh solvent.
  • the host molecule or host-guest complex can begin to form crystals or other solids as solvent passes through the membrane and solute concentration in the retained liquid rises. In these cases the solids may be re-dissolved in fresh second solvent or the solids may be kept from reducing the flux of the membrane to an unacceptable level by operating with a high fluid velocity at the liquid-membrane interface, or by addition of sufficient solvent to the system to maintain the components in solution.
  • the membrane may be backflushed using either solvent or gas, to remove deposited material and improve flux.
  • step (d) it may be necessary to heat or cool the solutions prior to contact with the membrane in steps (g) or (i).
  • the guest molecule will have a molecular weight of above 50 Daltons; yet more preferably above 100 Daltons, and yet more preferably above 200 Daltons.
  • Guest molecules may be any molecule which exists in enantiomeric or isomeric form, including by way of non-limiting example alcohols, ketones, aldehydes, esters, ethers, amides, amines, nitrosamines, N-heterocycles, nitriles, sulfoxides, sulfides, aromatics, biaryls, phosphrous containing compounds, esters of hydroxy or amino acids, cyanohydrins, alkoxylactones, oximes, oxaziridines.
  • alcohols ketones, aldehydes, esters, ethers, amides, amines, nitrosamines, N-heterocycles, nitriles, sulfoxides, sulfides, aromatics, biaryls, phosphrous containing compounds, esters of hydroxy or amino acids, cyanohydrins, alkoxylactones, oximes, oxaziridines.
  • the host molecule will have a molecular weight of above 200 Daltons; yet more preferably above 300 Daltons, and yet more preferably above 400 Daltons.
  • the host molecule will form a host-guest complex which is enriched in enantiomer or isomer A relative to enantiomer or isomer B compared to the relative concentrations of A and B in the first solution.
  • Host molecules include by way of non-limiting example chiral selectors reported in the prior art discussed above and compounds which can be used in the inclusion complexation technology of the prior ait. Suitable host molecules include those described in "Chiral Separation Techniques - A Practical Approach" Second Edition, Edited by G.
  • Diols including TADDOLs and their derivatives, BINOLs, acetylene alcohols, cinchonium salts, cyclodextrins and crown ethers may all be employed as host molecules.
  • solvents will be chosen with regard to solubility of guest molecules, host molecules, and host-guest complexes, viscosity, and miscibility with other solvents, among other factors such as cost and safety.
  • Suitable inert solvents are numerous and well known to those skilled in the art.
  • suitable solvents include aromatics, alkanes, ketones, glycols, chlorinated solvents, esters, ethers, amines, nitriles, aldehydes, phenols, amides, carboxylic acids, alcohols and dipolar aprotic solvents, and mixtures thereof.
  • solvents include toluene, xylene, benzene, styrene, anisole, chl ⁇ robenzene, dichlorobenzene, chloroform, dichloromethane, dichloroethane, methyl acetate, ethyl acetate, butyl acetate, methyl ether ketone (MEK), methyl iso butyl ketone (MEBK), acetone, ethylene glycols, ethanol, methanol, propanol, butanol, hexane, cyclohexane, dimethoxyethane, methyl tert butyl ether (MTBE), diethyl ether, adiponitrile, N 5 N dimethylfomamide, dimethyl sulfoxide, dioxane, nitromethane, nitrobenzene, pyridine, carbon disulfide, tetrahydrofuran, N-
  • the membrane of the present invention can be configured in accordance with any of the designs known to those skilled in the art, such as spiral wound, plate and frame, shell and tube, and derivative designs thereof.
  • the membranes may be of cylindrical or planar geometry.
  • the membrane of the present invention may be a porous or a non-porous membrane. Suitable membranes will have a rejection for both the host molecule and host-guest complex that is greater than the rejection for the guest molecule.
  • the membrane of the present invention may be formed from any polymeric or ceramic material which provides a separating layer capable of preferentially separating the guest molecule from both the host molecule and host-guest complex in steps (g) or (i).
  • the membrane is formed from or comprises a material selected from polymeric materials suitable for fabricating microfiltration, ultrafiltration, nanofiltration or reverse osmosis membranes, including polyethylene, polypropylene, polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF), polyethersulfone, polyacrylonitrile, polyamide, polyimide, cellulose acetate, and mixtures thereof.
  • the membranes can be made by any technique known to the art, including sintering, stretching, track etching, template leaching, interfacial polymerisation or phase inversion. Yet more preferably the membrane is prepared from an inorganic material such as by way of non-limiting example silicon carbide, silicon oxide, zirconium oxide, titanium oxide, or zeolites, using any technique known to those skilled in the art such as sintering, leaching or sol-gel processes.
  • the membrane is non-porous and the non-porous, selectively permeable layer thereof is formed from or comprises a material selected from modified polysiloxane based elastomers including polydimethylsiloxane (PDMS) based elastomers, ethylene-propylene diene (EPDM) based elastomers, polynorbornene based elastomers, polyoctenamer based elastomers, polyurethane based elastomers, butadiene and nitrile butadiene rubber based elastomers, natural rubber, butyl rubber based elastomers, polychloroprene (Neoprene) based elastomers, epichlorohydrin elastomers, polyacrylate elastomers, polyethylene, polypropylene, polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF) based e
  • the membrane comprises a reinforcing material selected from an external mesh and support.
  • a reinforcing material selected from an external mesh and support.
  • Such tubes or sheets may be reinforced to increase their burst pressure, for example by overbraiding tubes using fibres of metal or plastic, or by providing a supporting mesh for flat sheets.
  • the additional component may be a supporting layer.
  • the supporting layer may be a porous support layer.
  • Suitable materials for the open porous support structure are well known to those skilled in the art of membrane processing.
  • the porous support is formed from or comprises a material selected from polymeric material suitable for fabricating microfiltration, ultrafiltration, nanofiltration or reverse osmosis membranes, including polyethylene, polypropylene, polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF), polyethersulfone, polyacrylonitrile, polyamide, polyimide, and mixtures thereof.
  • the rejection performance of the membrane may be improved by pre-soaking the membrane in one or more of the solvents to be used in the membrane separation.
  • the process may be performed in a continuous, semi-continuous or discontinuous (batch mode) manner.
  • the process may be performed using dead-end or cross-flow filtration.
  • the pressure may be supplied through a suitable pump or through a pressurizing gas, or through any other device designed to exert pressure at the first surface of the membrane.
  • FIG. 1 shows a schematic of one embodiment of the process.
  • Step 1 A first solution comprising guest molecule in the form of enantiomer or isomer A and enantiomer or isomer B dissolved in Solvent C (1) is added to a mixing chamber (2) equipped with a nanof ⁇ ltration membrane (3).
  • a solution or slurry of crystals of host molecule H dissolved or suspended in Solvent C (4) is added to the mixing chamber and a host-guest complex HA forms between enantiomer or isomer A and host molecule H in the mixing chamber.
  • Step 2 Pressure is applied to the mixing chamber through an inert gas added to the mixing chamber (5).
  • Step 3 Solvent D is added (8) to the solution in the mixing chamber while a mixture containing Solvent C and Solvent D passes through the membrane and exits the chamber (9).
  • Step 4 Fresh Solvent C (10) is added to the mixing chamber while a mixture containing Solvent C and Solvent D passes through the membrane and exits the chamber (11). This alters the composition of the solution in the mixing chamber as Solvent C replaces Solvent D.
  • Step 5 When the solution in the mixing chamber comprises substantially host molecule H dissolved or suspended in Solvent C, this stream may be recycled (12) back into the first stage and added as stream (4). In some cases host molecule H and the host guest complex HA may be partially insoluble in Solvent C, and soluble in Solvent D, so that there is a slurry present in Steps 1 and 2 which dissolves in Step 3 and re-precipitates in Step 4.
  • FIG. 2 shows another embodiment of the process.
  • Step 1 A first solution comprising guest molecule in the form of enantiomer or isomer A and enantiomer or isomer B dissolved in Solvent E (13) is added to a mixing vessel (14).
  • a solution of host molecule H dissolved in Solvent E (15) is added to the mixing vessel.
  • Step 2 - Solvent E is then removed via evaporation (16) from the mixing chamber, and a solid host-guest complex HA forms between enantiomer or isomer A and host molecule H in the mixing vessel.
  • Enantiomer or isomer B remains in the mixing vessel as an oily liquid.
  • Step 3 Solvent F is added (17) to the mixing vessel.
  • the host-guest complex HA remains a solid and is suspended as a slurry in Solvent F.
  • Enantiomer or isomer B dissolves into Solvent F.
  • Step 4 - The slurry in the mixing vessel (14) is transferred to a mixing chamber (2) equipped with a nanofiltration membrane (3). Pressure is applied to the mixing chamber through an inert gas added to the mixing chamber (5). A portion of the liquid from the mixing chamber passes through the membrane carrying enantiomer or isomer B and exits the chamber (18).
  • Fresh Solvent F is fed to the mixing chamber (19) to carry further enantiomer or isomer B from the system with stream (18). This substantially removes enantiomer or isomer B from the mixing chamber.
  • Step 5 Fresh Solvent E is added (20) to the solution in the mixing chamber while a mixture containing Solvent E and Solvent F passes through the membrane and exits the chamber (21). This alters the composition of the solution in the mixing chamber as Solvent E replaces Solvent F. As further Solvent E is added the host-guest complex HA decomposes and enantiomer or isomer A passes through the membrane with Solvent E and traces of Solvent F and exits the chamber (21). This substantially removes enantiomer or isomer A from the mixing chamber.
  • Step 6 Fresh Solvent E (22) is added to the mixing chamber while a mixture containing Solvent E and Solvent F passes through the membrane and exits the chamber (23).
  • Step 7 When the solution in the mixing chamber comprises substantially host molecule H dissolved in Solvent E, this stream may be recycled (23) back into the first stage and added as stream (15).
  • Enantiomeric excess is defined for two enantiomers A and B as:
  • the guest molecule is 1-phenylethanol (PE)
  • the host molecule is (4R,5R)- 2,2-Dimethyl-o:, a,a',a -tetraphenyldioxolane-4,5-dimethanol (TADDOL) and
  • STARMEMTM organic solvent nanofiltration membranes manufactured by W.R,Grace and Co Limited are used. Racemic PE and TADDOL were obtained commercially.
  • STARMEMTM122 membranes are integrally skinned asymmetric membranes prepared as generally described in US 5,264,166 and US 6,180,008. The 122 membrane has a nominal molecular weight cutoff of 220 Daltons, obtained by plotting rejection Ri versus molecular weight for a series of n-alkanes dissolved in toluene, and taking the nominal molecular weigh cutoff by interpolation of this curve at a rejection of 90%.
  • MET Membrane Extraction Technology
  • Rejections were determined using an Osmonics/Desal (USA) SEPA-ST test cell Membrane discs were cut from A4 sheets in circular discs 49 mm in diameter, giving an active membrane area of 16.9 cm 2 . AU experiments were carried out in a fume cupboard. The cell was pressurised with compressed nitrogen gas at pressures of 5-50 bar. The volume of feed solution was 20 mL and the volume of permeate was measured with a measuring cylinder. Rejections were determined by equation (1) using a solution of 4.35 mM PE in toluene, and a solution of 7.1 mM TADDOL in toluene.
  • Vf-feed volume (ml); Vp-volume permeated through membrane (ml), and Vr-retained volume
  • Table 1 illustrate the combination of PE, TADDOL and STARMEMTM122 are suitable for use in the claimed process.
  • Racemic PE (0.262g) was added to a mixture of TADDOL (1.002g) in 20 ml toluene. After stirring for one hour, the mixture was evaporated to remove the toluene, leaving a damp solid residual. 50 ml hexane was then added to this damp solid residual and the slurry stirred for 24 hours. The solid material was recovered using a vacuum filter with a microfiltration membrane. 0.846g of TADDOL-PE complex was recovered, with an enantiomeric excess of 60% in S-PE.
  • Vf-feed volume (ml); Vp-volume permeated through membrane (ml), and Vr-retained volume; Cf- feed concentration, Cp permeate concentration, Cr - retentate concentration. BD - below detection.
  • the PE recovered in the methanol permeate had an enantiomeric excess of 60% in S-PE.
  • TADDOL-PE complex 0.61 Ig of the TADDOL-PE complex was dissolved in 50 ml methanol and transferred to the SEPA-ST cell from Example 1. This was subjected to three filtrations as in Example 1, providing an overall recovery of S-PE of 96% at an enantiomeric excess of 86% in S- PE. This example illustrates that TADDOL may be re-used in multiple resolutions.
  • Racemic PE (0.262g) was added to a mixture of TADDOL (1.002g) in 20 ml toluene. After stirring for one hour, the mixture was evaporated to remove the toluene, leaving a damp solid residual. 50 ml hexane was then added to this damp solid residual and the slurry stirred for 24 hours. The solid material was recovered using a vacuum filter with a microfiltration membrane. 0.846g of TADDOL-PE complex was recovered, with an enantiomeric excess of 86% in S-PE.
  • Example 1 0.8 g of the TADDOL-PE complex was dissolved in 50 ml toluene and transferred to the SEPA-ST cell fitted with a STARMEMTM122 membrane as in Example 1. This was subjected to three filtrations as in Example 1, except that toluene was used in all filtrations in place of methanol. The recovered S-PE had an ee of 86%.
  • racemic PE (0.262g) was added to a slurry of TADDOL (1.002g) suspended in 20 ml hexane in the SEPA-ST cell fitted with a STARMEMTM122 membrane as in Example 1.
  • the cell was mixed vigorously with a magnetic stirrer to maintain the solids in suspension. After stirring for ten hours, the slurry was subjected to three filtrations in which 20 ml hexane was added and the suspension filtered to reduce the volume back to the starting volume of approximately 21 ml.
  • the ee of the PE permeating the membrane with the hexane was 83% in R-PE.
  • Racemic PE (0.262g) was added to this slurry of TADDOL in 20 ml hexane. After stirring for ten hours, the slurry was subjected to a three filtrations in which 20 ml hexane was added and the suspension filtered to reduce the volume back to the starting volume of 20 ml. The ee of the PE permeating the membrane with the hexane was 81% in R-PE.
  • Racemic PE (0.256g) was added to a slurry of TADDOL (1.042Ig) suspended in 40 ml of a mixture of toluene and hexane (33wt% toluene, 67wt% heptane) in the SEPA-ST cell fitted with a STARMEMTM122 membrane as in Example 1.
  • the cell was mixed vigorously with a magnetic stirrer to maintain the solids in suspension and the cell and contents were held at 22 0 C. After stirring for 2 hours, the slurry was subjected to a filtration in which 25 ml of liquid was permeated through the membrane to leave a residual volume of 15 ml.
  • the ee of the PE permeating the membrane with the solvent mixture was 36 % in R-PE.
  • a further 25 ml of a mixture of toluene and hexane (33wt% toluene, 67wt% heptane) was then added to the cell above the membrane, and the contents of the cell (now around 40 ml) were heated to 5O 0 C and stirred for 30 minutes. The mixture was then filtered to remove 17 ml of liquid. The ee of the PE permeating the membrane with the liquid was 85% in S-PE. At the completion of this step, the cell was cooled to ambient, depressurized and opened, and a slurry containing 1.008 g TADDOL and 0.006 g of PE was observed remaining above the membrane. This illustrates how altering the temperature can be used to decompose the host-guest complex.
  • Racemic ⁇ -methylbenzylamine ( ⁇ MBA) (0.606g) was added to a slurry of TADDOL (2.33g) suspended in 100 ml octane in the SEPA-ST cell fitted with a STARMEMTM122 membrane as in Example 1.
  • the cell was mixed vigorously with a magnetic stirrer to maintain the solids in suspension. After stirring for ten hours, the slurry was subjected to a filtration in which 50 ml liquid was removed by permeation through the membrane.
  • the ee of the ⁇ MBA permeating the membrane with the octane was 26 % in R-PE.
  • the cell was then de-pressurized and the solid material found above the membrane was recovered using a vacuum filter with a microfiltration membrane.
  • 0.587g of TADDOL- ⁇ MBA complex was recovered, with an enantiomeric excess of 89% in S- ⁇ MBA.
  • ⁇ MBA 0.575g of the TADDOL- ⁇ MBA complex was dissolved in 50 ml methanol and transferred to the SEPA-ST cell fitted with a STARMEMTM122 membrane. This was subjected to filtration using 2 x 50 ml additions of methanol. The ⁇ MBA recovered in the permeate had an enantiomeric excess of 85%.
  • Racemic Methyl Phenyl Sulfoxide (MPS) (C 6 H 5 SOCH 3 ) (0.875g) was added to a slurry of TADDOL (1.45g) suspended in a mixture of toluene and hexane (50wt% toluene, 50wt% heptane) in a glass reaction tube.
  • the tube was mixed vigorously with a magnetic stirrer to maintain the solids in suspension.
  • the solution initially containing solids was heated from 3O 0 C to 5O 0 C, at which point the solids became dissolved. After stirring for two hours, the tube was cooled again to 3O 0 C and the solids re-appeared. The solid material was recovered using centrifugation. 0.76g of TADDOL- MPS complex was recovered.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Water Supply & Treatment (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nanotechnology (AREA)
  • Organic Chemistry (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

Procédé pour la séparation d'énantiomères ou d'isomères présents dans une phase liquide grâce à la formation et ensuite à la décomposition subséquente d'un complexe molécule hôte-molécule incluse couplées à la nanofiltration sur membrane, comprenant les étapes consistant à : (a) obtenir une première solution comprenant au moins deux énantiomères ou isomères A et B d'une molécule incluse ; (b) ajouter une molécule hôte à cette première solution ; (c) former un complexe molécule hôte-molécule incluse, de façon à ce que la proportion relative des énantiomères ou isomères A et B dans le complexe molécule hôte-molécule incluse soit enrichie en A par rapport à B par rapport à la première solution ; (d) séparer en grande partie le complexe molécule hôte-molécule incluse de l'énantiomère ou isomère B non complexé ; (e) décomposer le complexe molécule hôte-molécule incluse en molécules hôte et incluse pour former une seconde solution ; (f) obtenir une membrane sélectivement perméable ayant une première surface et une seconde surface ; (g) séparer la molécule incluse et la molécule hôte en transférant la molécule incluse de la première surface vers la seconde surface à travers la membrane en mettant en contact la seconde solution avec la première surface. Dans l'étape (g), la pression au niveau de la première surface est supérieure à la pression au niveau de la seconde surface et la membrane est une membrane sélectivement perméable de façon à ce que le rejet (Rmolécule hôte) de la molécule hôte soit supérieur au rejet (Rmolécule incluse) de la molécule incluse.
PCT/GB2006/000547 2005-02-17 2006-02-16 Procédé de séparation WO2006087556A1 (fr)

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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102743984A (zh) * 2012-06-01 2012-10-24 新加坡三泰水技术有限公司 纳米多孔陶瓷复合反渗透膜及其制备方法
WO2014134666A1 (fr) * 2013-03-06 2014-09-12 University Of Western Sydney Procédé et dispositif de séparation de mélanges
WO2015085295A3 (fr) * 2013-12-07 2015-10-29 Novomer, Inc. Membranes de nanofiltration et procédés d'utilisation
US10099989B2 (en) 2015-02-13 2018-10-16 Novomer, Inc. Distillation process for production of acrylic acid
US10099988B2 (en) 2015-02-13 2018-10-16 Novomer, Inc. Process for production of acrylic acid
US10221278B2 (en) 2011-05-13 2019-03-05 Novomer, Inc. Catalytic carbonylation catalysts and methods
US10221150B2 (en) 2015-02-13 2019-03-05 Novomer, Inc. Continuous carbonylation processes
US10597294B2 (en) 2014-05-30 2020-03-24 Novomer, Inc. Integrated methods for chemical synthesis
US10858329B2 (en) 2014-05-05 2020-12-08 Novomer, Inc. Catalyst recycle methods
US10974234B2 (en) 2014-07-25 2021-04-13 Novomer, Inc. Synthesis of metal complexes and uses thereof
US11078172B2 (en) 2015-02-13 2021-08-03 Novomer, Inc. Integrated methods for chemical synthesis
CN114797487A (zh) * 2022-04-18 2022-07-29 西安交通大学 一种含螺双茚满结构聚酰亚胺有机溶剂纳滤膜的制备方法
CN115253696A (zh) * 2021-04-29 2022-11-01 天津膜天膜科技股份有限公司 手性分离膜及其制备方法
WO2023126186A1 (fr) 2021-12-29 2023-07-06 Universite D'aix-Marseille Procédé de préparation simultanée de produits énantiomères séparés à partir de substrats racémiques ou scalémiques

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5080795A (en) * 1990-05-23 1992-01-14 Research Corporation Technologies, Inc. Supported chiral liquid membrane for the separation of enantiomers
WO2002076588A1 (fr) * 2001-03-27 2002-10-03 Membrane Extraction Technology Limited Procede

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5167824A (en) * 1990-02-14 1992-12-01 Creative Biomolecules, Inc. Separation by carrier mediated transport
US5254258A (en) * 1991-09-17 1993-10-19 Research Corporation Technologies, Inc. Chiral selector useful for separation of enantiomers of β-amino alcohol compounds
US5256293A (en) * 1991-09-20 1993-10-26 Research Corporation Technologies, Inc. Separation of enantiomers of non-steroidal anti-inflammatory drugs and chiral selector therefor
WO2002092562A2 (fr) * 2001-05-11 2002-11-21 The Board Of Trustees Of The University Of Illinois Reactions enantioselectives a l'aide de catalyseurs chiraux par transfert de phase a deux composants dans des systemes multiphasiques

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5080795A (en) * 1990-05-23 1992-01-14 Research Corporation Technologies, Inc. Supported chiral liquid membrane for the separation of enantiomers
WO2002076588A1 (fr) * 2001-03-27 2002-10-03 Membrane Extraction Technology Limited Procede

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
D. SEEBACH ET AL.: "TADDOLs, their derivatives, and TADDOL analogues: versatile chiral auxiliaries", ANGEW. CHEM. INT. ED., vol. 40, 2001, pages 92 - 138, XP002381532 *
FUMIO TODA: "Inclusion complex crystals formed by alcohol host compounds", SUPRAMOLECULAR SCIENCE, vol. 3, no. 1-3, 1996, pages 139 - 148, XP002381533 *
N.F. GHAZALI, D.A. PATTERSON, A.G. LIVINGSTON: "Elucidation of the mechanism of chiral selectivity in diastereomeric salt formation using organic solvent nanofiltration", CHEM. COMMUN., 11 March 2004 (2004-03-11), pages 962 - 963, XP002381531 *
W.R. BOWEN, R.R. NIGMATULLIN: "Membrane-assisted chiral resolution of pharmaceuticals: Ibuprofen separatoin by ultrafiltration using bovine serum albumin as chiral selector", SEPARATION SCIENCE AND TECHNOLOGY, vol. 37, no. 14, 2002, pages 3227 - 3244, XP008064391 *

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US10221278B2 (en) 2011-05-13 2019-03-05 Novomer, Inc. Catalytic carbonylation catalysts and methods
CN102743984B (zh) * 2012-06-01 2014-10-08 新加坡三泰水技术有限公司 纳米多孔陶瓷复合反渗透膜及其制备方法
CN102743984A (zh) * 2012-06-01 2012-10-24 新加坡三泰水技术有限公司 纳米多孔陶瓷复合反渗透膜及其制备方法
WO2014134666A1 (fr) * 2013-03-06 2014-09-12 University Of Western Sydney Procédé et dispositif de séparation de mélanges
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US10858329B2 (en) 2014-05-05 2020-12-08 Novomer, Inc. Catalyst recycle methods
US10829372B2 (en) 2014-05-30 2020-11-10 Novomer, Inc. Integrated methods for chemical synthesis
US10597294B2 (en) 2014-05-30 2020-03-24 Novomer, Inc. Integrated methods for chemical synthesis
US10974234B2 (en) 2014-07-25 2021-04-13 Novomer, Inc. Synthesis of metal complexes and uses thereof
US10717695B2 (en) 2015-02-13 2020-07-21 Novomer, Inc. Distillation process for production of acrylic acid
US10738022B2 (en) 2015-02-13 2020-08-11 Novomer, Inc. Continuous carbonylation processes
US10626073B2 (en) 2015-02-13 2020-04-21 Novomer, Inc. Process for production of acrylic acid
US10221150B2 (en) 2015-02-13 2019-03-05 Novomer, Inc. Continuous carbonylation processes
US10099988B2 (en) 2015-02-13 2018-10-16 Novomer, Inc. Process for production of acrylic acid
US11078172B2 (en) 2015-02-13 2021-08-03 Novomer, Inc. Integrated methods for chemical synthesis
US11155511B2 (en) 2015-02-13 2021-10-26 Novomer, Inc. Distillation process for production of acrylic acid
US10099989B2 (en) 2015-02-13 2018-10-16 Novomer, Inc. Distillation process for production of acrylic acid
CN115253696A (zh) * 2021-04-29 2022-11-01 天津膜天膜科技股份有限公司 手性分离膜及其制备方法
CN115253696B (zh) * 2021-04-29 2023-09-22 天津膜天膜科技股份有限公司 手性分离膜及其制备方法
WO2023126186A1 (fr) 2021-12-29 2023-07-06 Universite D'aix-Marseille Procédé de préparation simultanée de produits énantiomères séparés à partir de substrats racémiques ou scalémiques
CN114797487A (zh) * 2022-04-18 2022-07-29 西安交通大学 一种含螺双茚满结构聚酰亚胺有机溶剂纳滤膜的制备方法

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