RECOVERY OF OPTICAL ISOMER AND SOLVENT IN OPTICAL RESOLUTION, REUSE OF SOLVENT BY RECYCLING, AND REUSE OF OPTICAL ISOMER

Abstract: A method of recovering and reusing a solvent and an optical isomer, characterized by providing a packed bed, which is disposed in the passage for circulating a solvent and packed with a packing material for optical resolution, with a port for feeding an eluent, a port for withdrawing an extract containing an optical isomer which is readily absorbed by the packing material, a port for feeding a liquid containing a mixture of optical isomers, and a port for withdrawing a raffinate containing an optical isomer which is difficultly adsorbed by the packing material, in this order; employing a pseudo-moving-bed system wherein these ports are sequentially moved in the direction of liquid flow in the packed bed; recovering the solvent and the optical isomer from the obtained extract and/or raffinate; and returning the recovered solvent to the passage for circulating a solvent, or alternatively if the solvent is not recovered, heating the extract or raffinate to racemize an undesired optical isomer and reusing the solvent containing the racemate for the separation of the optical isomers according to the pseudo-moving-bed system.

Description: The present invention relates to processes for recovering optical isomers and a solvent, a process for using the solvent by circulation and a process for reusing the optical isomers. In particular, the present invention relates to processes for recovering optical isomers and a solvent, wherein the optical isomers can be efficiently separated from each other and the solvent used for the optical resolution can be efficiently recovered, a process for using the solvent by circulation, wherein the solvent recovered by the recovering process of the present invention is reused for the effective utilization of the solvent, and a process for reusing the optical isomers, wherein the intended optical isomers obtained by the optical resolution are reused without being discarded so as to further improve the efficiency of the optical resolution. It is well known that optical isomers have different effects on the living body, though they are chemically the same. Therefore, it is an extremely important problem in the industrial fields of medicines, pharmacy, biochemistry, etc., to prepare an optically pure compound in order to improve the efficacy of the medicine per unit quantity and to prevent drug-induced sufferings caused by adverse reactions of the drug. For the separation of such an optical isomer mixture, i.e., optical resolution of them, a diastereomer method, crystallization method, enzyme method, separating membrane method or the like has been employed heretofore. However, such a method is generally unsuitable, since the kinds of the compounds which can be optically resolved are usually limited. Although chromatography can be employed for the optical resolution, as for example disclosed in FR-A-2593409, the chromatographic methods known at present are of a batch type and hence cannot avoid discontinuous and unstationary operations, which is unsuitable for the mass processing. Further this chromatographic method has another defect that since a large amount of an eluent is necessitated and the concentration of the intended compound in the eluate is low, much energy and complicated steps are necessitated for the recovery. EP-A-471082 which is a prior art document according to Article 54(3) EPC discloses a process for separating optical isomers in a simulated moving bed system, characterized by introducing a solution containing an optical isomer mixture and a desorbing liquid Into a packed bed containing an optical resolution packing therein and naving front and rear ends thereof connected to each other endlessly via a fluid passage to circulate a fluid unidirectionally and at the same time drawing out a solution comsining one of the separated Isomers and another. solution containing the other isomer from the packed bed, wherein a port for Introducing a desorbing liquid, a port for drawing out a solution containing·a strongly adsorbabie optical isomer, i.e. an extract, a port for Introducing a solution containing an optical isomer mixture, and a port for drawing out a Solution containing a weakly adsorbable optical Isomer, i.e. a raffinate, are arranged In the packed bed in this order along the direction of fluid flow and the positions of these ports are successively moved in the direction of fluid flow in the packed bed intermittently. JP-A-1-119339 discloses a column packing for optical isomer separation, wherein an optically active fat-soluble crown compound is adsorption-carried by a carrier treated with a specific silane coupling agent. An object of the present invention is to provide a novel process which can separate optical isomers and a solvent efficiently from a large amount of a mixture comprising the optical isomers. Another object of the present invention is to provide a process for efficiently separating each of optical isomers and a solvent from a large amount of a mixture comprising the optical isomers and also reusing the recovered solvent. The invention which solves the above problem relates in a first embodiment to a process for recovering optical isomers and a solvent in optical resolution by introducing a liquid containing an optical isomer mixture and an eluent into a packed bed containing packings for optical resolution, having both ends connected to each other through a fluid passage to be endless and circulating the liquids therein by one-way flow, and simultaneously recovering a liquid containing one optical isomer and a liquid containing the other optical isomer which are separated from the packed bed, characterized by arranging an inlet for the eluent, an outlet for a liquid (extract) containing a strongly adsorbable optical isomer, an inlet for the liquid containing an optical isomer mixture, and an outlet for a liquid (raffinate) containing a weakly adsorbable optical isomer in this order in the direction of liquid flow onto the packed bed, and recovering the solvent and the optical isomers from the extract and/or raffinate obtained with a simulated moving bed system, the eluent-feeding line, the line for feeding the liquid containing the optical isomer mixture and the respective ejecting lines being moved at a distance corresponding to one unit packed bed in the direction of liquid flow in the bed, said operation being successively conducted, wherein the solvent is separated from the extract and/or raffinate obtained with the simulated moving bed system with an evaporator and/or a still. In a second embodiment the present invention relates to a process for recovering optical isomers and a solvent in optical resolution by introducing a liquid containing an optical isomer mixture and an eluent into a packed bed containing packings for optical resolution, having both ends connected to each other through a fluid passage to be endless and circulating the liquids therein by one-way flow, and simultaneously recovering a liquid containing one optical isomer and a liquid containing the other optical isomer which are separated from the packed bed, characterized by arranging an inlet for the eluent, an outlet for a liquid (extract) containing a strongly adsorbable optical isomer, an inlet for the liquid containing an optical isomer mixture, and an outlet for a liquid (raffinate) containing a weakly adsorbable optical isomer in this order in the direction of liquid flow onto the packed bed, and recovering the solvent and the optical isomers from the extract and/or raffinate obtained with a simulated moving bed system, the eluent-feeding line, the line for feeding the liquid containing the optical isomer mixture and the respective ejecting lines being moved at a distance corresponding to one unit packed bed in the direction of liquid flow in the bed, said operation being successively conducted, wherein the optical isomer as an antipode in the extract or raffinate is racemized and the resultant liquid containing an optical isomer mixture is returned into the inlet for the liquid containing an optical isomer mixture. Further, the invention relates to the above mentioned processes for recovering optical isomers and a solvent, wherein the packing for optical resolution has a particle diameter of 1 to 100 µm, the invention relates to the above mentioned process according to the second embodiment for recovering optical isomers and a solvent in optical resolution, wherein the solvent is separated from the extract and/or raffinate obtained with the simulated moving bed system with an evaporator and/or a still, the invention rerates to the above mentioned processes for recovering optical isomers and a solvent in optical resolution, wherein the above evaporator and/or still is of reduced pressure type, the invention relates to a process for using a solvent by circulation. characterized by returning the solvent recovered by the above mentioned processes into the fluid passage, the invention relates to the above mentioned process for using a solvent by circulation. wherein the recovered solvent has a purity of at least 98% and, the invention relates to a process for reusing an optical isomer, wherein the optical isomer as an antipode in the above mentioned extract or raffinate of the process according to the first embodiment is racemized and the resultant liquid containing an optical isomer mixture is returned into an inlet for a liquid containing an optical isomer mixture. In the following the drawings are briefly described. Fig. 1 is a drawing for illustrating one example of the apparatuses usable for conducting the processes of the present invention. Fig. 2 is a drawing for illustrating another example of the apparatuses usable for conducting the processes of the present invention. 1 to 12: unit packed bed 13: line for feeding eluent 14: line for ejecting extract 15: line for feeding liquid containing optical isomer mixture 16: line for ejecting raffinate 17: recycle line 18: circulation pump 19: first falling film evaporator 20: second falling film evaporator 21: forced film evaporator 22: recovery tank 23: reservoir 24: racemization tank 25: still The present invention will be described in detail in the following. A. Simulated moving bed: In the simulated moving bed system, use is made of, for example, a simulated moving bed as shown in Fig. 1 which is divided into a plurality of (for example, 12 or 8) unit packed beds arranged in series in the liquid passage in which liquid is circulated. The liquid is unidirectionally circulated in the liquid passage. The number of the unit packed beds in the simulated moving bed is not limited to those described above, but can be suitably selected depending on the scale and from the viewpoint of reaction engineering. The simulated moving bed has an inlet for an eluent, an outlet for ejecting a liquid (extract) containing an optical isomer strongly adsorbable on the packing, an inlet for a liquid containing an optical isomer mixture, and an outlet for ejecting a liquid (raffinate) containing an optical isomer weakly adsorbable on the packing in this order in the direction of liquid flow, and they can be intermittently moved in the direction of liquid flow in the packed bed. The simulated moving bed system per se is well known as described in, for example, Japanese Patent Publication-B No. 15681/1967. However, the simulated moving bed system has heretofore been employed only for the production of fructose, separation of maltose and recovery of co-enzymes and no process has been described at all for separating optical isomers by this system. In the simulated moving bed system shown in Fig. 1, an inlet for an eluent, an outlet for an extract, an inlet for a liquid containing an optical isomer mixture and an outlet for a raffinate are provided for every three unit packed beds. These inlets and outlets are intermittently moved by means of, for example, rotary valves. - Kind of packings for optical resolution and the like - Each unit packed bed contains packings having an optical resolving ability. The packings include those for optical resolution made of an optically active polymeric compound and a low-molecular compound having an optical resolving ability. Examples of the optically active polymeric compounds include polysaccharide derivatives (such as esters and carbamates of cellulose and amylose), polyacrylate derivatives, packings comprising a polyamide derivative carried by silica gel, and packings prepared by granulating the polymer per se without using any silica gel. Examples of the low-molecular compounds having an optical resolving ability include crown ethers and derivatives thereof and cyclodextrin and derivatives thereof. These low-molecular compounds are usually employed by being supported on a support such as silica gel. Commercially available packings for optical resolution are also usable. Examples of preferred ones include CHIRALCEL OB (registered trade name), CHIRALCEL OD (registered trade name), CROWNPAK CR(+) (registered trade name), CHIRALCEL CA-1 (registered trade name), CHIRALCEL OA (registered trade name), CHIRALCEL OB (registered trade name), CHIRALCEL OK (registered trade name), CHIRALCEL OJ (registered trade name), CHIRALCEL OC (registered trade name), CHIRALCEL OF (registered trade name), CHIRALCEL OG (registered trade name), CHIRALPAK WH (registered trade name), CHIRALPAK WM (registered trade name), CHIRALPAK WE (registered trade name), CHIRALPAK OT(+) (registered trade name), CHIRALPAK OP(+) (registered trade name), CHIRALPAK AS (registered trade name) and CHIRALPAK AD (registered trade name) all of which are products of Daicel Chemical Industries, Ltd. - Particle diameter of packing - Although the average particle diameter of the packing varies depending on, e.g. the kind of the optical isomers to be resolved and the volume flow rate of the solvent flowing in the simulated moving bed, it is usually 1 to 100 µm, preferably 5 to 75 µm. In order to keep they pressure drop in the simulated moving bed on a low level, it is desirable to regulate the average particle diameter of the packing to 15 to 75 µm. When the average particle diameter of the packing is within the above-described range, the pressure drop in the simulated moving bed can be reduced to, for example, 98,07 N/cm 2 (10 kgf/cm 2 ) or below. On the contrary, as the average particle diameter of the packing increases, the number of the theoretical adsorption plates decreases. Therefore when only the number of the practical theoretical adsorption plates is to be attained, the average particle diameter of the above-described packing is usually 1 to 50 µm. - Eluent - The eluents to be fed through the inlet for an eluent include, for example, organic solvents such as alcohols, e.g. methanol, ethanol and isopropanol, hydrocarbons, e.g. hexane, and aqueous salt solutions such as aqueous copper sulfate solution and aqueous perchlorate solution. The eluent is suitably selected depending on the kind of the compounds to be optically resolved. - Optical isomer to be optically resolved - The optical isomer mixture to be fed through an inlet for a liquid containing an optical isomer mixture is not particularly limited. The optical isomer mixture may comprise various compounds used, for example in the fields of medicines, agricultural chemicals, foods, feeds or flavors, such as thalidomide (a medicine), EPN (an organophosphorus agricultural chemical), monosodium glutamate (a chemical seasoning) and menthol (a flavor), and also optically active alcohols and optically active esters. - Steps in the simulated moving bed system - The separation of optical isomers by adsorption with the simulated moving bed system of the present invention is conducted by the continuous circulation of the basic steps including those of adsorption, concentration, desorption and recovery of the eluent, which will be described below. (1) Adsorption step: When an optical isomer mixture is brought into contact with packings, an optical isomer (strongly adsorbable component) easily adsorbable on the packing is adsorbed and the other optical isomer (weakly adsorbable component) difficultly adsorbable on the packing is recovered as the raffinate together with the eluent. (2) Concentration step: The packing having the strongly adsorbable component adsorbed thereon is brought into contact with a part of an extract which will be described below to expel the weakly adsorbable component remaining on the packing, thereby concentrating the strongly adsorbable component. (3) Desorption step: The packing containing the strongly adsorbable component thus concentrated is then brought into contact with the eluent to expel this component from the packing to discharge it as the extract together with the eluent from the simulated moving bed. (4) Eluent-recovering step: The packing on which substantially only the eluent is adsorbed is then brought into contact with a part of the raffinate, whereby a part of the eluent contained in the packing is recovered as an eluent recovery. The present invention which will be described in more detail with reference to the attached drawings is as follows. In Fig. 1, numerals 1 to 12 refer unit packed beds containing packings, and they are connected to each other through a liquid passage. Numeral 13 refers to an eluent-feeding line, 14 to an extract ejecting line, 15 to a line for feeding a liquid containing an optical isomer mixture, 16 to a raffinate ejecting line, 17 to a recycle line and 18 to a circulation pump. In the arrangement of the unit packed beds 1 to 12 and lines 13 to 16 shown in Fig. 1. the unit packed beds 1 to 3 take part in the desorption step, the unit packed beds 4 to 6 in the concentration step, the unit packed beds 7 to 9 in the adsorption step, and the unit packed beds 10 to 12 in the eluent-recovering step. In this simulated-moving bed, the eluent-feeding line, the line for feeding a liquid containing an optical isomer mixture and the respective ejecting lines are moved at a distance corresponding to one unit packed bed in the direction of solvent flow by, for example, operating valves at predetermined time intervals. Accordingly, in the second stage, the unit packed beds 2 to 4 take part in the desorption step, the unit packed beds 5 to 7 in the concentration step, the unit packed ones 8 to 10 in the adsorption step and the unit packed ones 11 to 1 in the eluent-recovering step. By successively conducting such an operation, the respective steps move at a distance corresponding to one unit packed bed, and the separation treatment of the optical isomer mixture is conducted continuously and efficiently. The extract thus ejected with the simulated moving bed system comprises an optical isomer having an optical purity of as high as at least 90%, for example, at least 95% or even at least 98%, contained in the solvent, and the raffinate comprises the other optical isomer having an optical purity of as high as that described above in the solvent. ―Another embodiment of the simulated moving bed - The simulated moving bed to be used in the processes of the present invention is not limited to that shown in Fig. 1 but another simulated moving bed shown in Fig. 2 is also usable. In the arrangement of unit packed beds 1 to 8 and lines 13 to 16 shown in Fig. 2, the unit packed bed 1 takes part in the elution and recovering steps, the unit packed beds 2 to 5 in the adsorption step, the unit packed beds 6 and 7 in the concentration step, and the unit packed bed 8 in the desorption step. In such a simulated moving bed, the liquid-feeding lines and ejecting lines are moved at a distance corresponding to one unit packed bed in the direction of liquid flow by, for example, operating valves at predetermined time intervals. Accordingly, in the next arrangement of the unit packed beds, the unit packed bed 2 takes part in eluent-feeding step, the unit packed beds 3 to 6 in the adsorption step, the unit packed beds 7 and 8 in the concentration step, and the unit packed bed 1 in the desorption step. By successively conducting such an operation, the separation treatment of the optical isomer mixture is conducted continuously and efficiently. B. Recovery of the solvent: In the present invention, one or both of the extract and raffinate obtained according to the above-described simulated moving bed system are sent to the solvent-recovering step. The recovery of the solvent and separation of the optical isomers from the extract and/or raffinate can be conducted in an evaporator and/or a still. The evaporator and the still are preferably of reduced pressure type. The evaporator of reduced pressure type is preferred, since the optical isomers can be separated without denaturalizing them by heating, since oxidation can be prevented and the evaporation temperature can be lowered. The evaporators usable herein are preferably film evaporators such as a forced film evaporator, ascending film evaporator, falling film evaporator, or stirred liquid film evaporator. These evaporators are usable either singly or in combination of two or more evaporators of the same or different types. The stills are preferably molecular stills such as a batchwise molecular still, falling film molecular still or centrifugal film molecular still. These molecular stills of reduced pressure type are able either singly or in combination of two or more stills of the same or different types. In the processes of the present invention, it is preferred that the extract and/or raffinate ejected from the simulated moving bed is separated in a separator comprising a combination of two or three kinds of falling film evaporator and forced film evaporator, since the use of the combination of the two or three apparatuses can reduce the residence time in these apparatuses, thereby preventing the racemization advantageously. A combination of two or more apparatuses of the same kind arranged in series or a combination of them with the molecular still is also desirable. Specifically, as shown in Fig. 1, the extract is concentrated to about 30 to 50% in the first falling film evaporator 19, then to about 40 to 70% in the second falling film evaporator 20, and further to about 60 to 99% in a forced film evaporator 21. The solvent recovered with the evaporator is usually stored in a recovery tank temporarily. In Fig. 1, numeral 22 refers to a recovery tank for temporarily storing recovered solvent. The concentrate containing an optical isomer obtained by the concentration with the evaporator is temporarily stored in a reservoir. Numeral 23 in Fig. 1 refers to the reservoir. On the other hand, the raffinate contains another optical isomer, which is an antipode of the optical isomer contained in the extract, and the solvent. The recovery of the solvent from the raffinate can be conducted in the same manner as that of the recovery of the solvent from the extract. C. Reuse of the solvent: In the processes of the present invention, the solvent recovered as described above is recycled for use as the eluent or reused for the preparation of a liquid containing an optical isomer mixture. In such a case, the purity of the solvent to be reused is at least 98%. For obtaining such a purity, the use of a still is preferable. In Fig. 1, the concentration of the solvent stored in the recovery tank 22 is increased to a necessary purity in a still 25. When the above purity can be kept, the separation of the optical isomers can be efficiently conducted by the simulated moving bed system. D. Reuse of the optical isomers: In the processes of the present invention, it is also preferred to convert an optical isomer which is not an intended antipode contained in the extract or raffinate into the racemic modification by heating and then to return the solvent containing the racemic modification into the line for feeding a liquid containing an optical isomer mixture after, if necessary, adjusting the concentration of the liquid. In this case, the extract or raffinate can be directly racemized, or the racemization can be conducted by treating a solution containing an optical isomer obtained after recovering the solvent from the extract or raffinate, or the racemic modification thus obtained can be dissolved in a fresh solvent to obtain a solution containing the racemic modification. The racemization of the optical isomer can be conducted by heating or by using an enzyme. In either case, well-known racemization methods can be suitably selected. Irrespective of the employed racemization method, the racemization conditions are suitably determined depending on the kind of the optical isomer. In Fig. 1, the raffinate is heated in a racemization tank 24 and the solvent containing the racemic modification thus obtained is returned into a line 15 for feeding a liquid containing an optical isomer mixture. By thus separating a desired optical isomer as, for example, the extract and, on the other hand, heating the raffinate containing an undesired optical isomer to form a racemic modification to be reused, an intended optical isomer can be separated further efficiently. Although the intended optical isomer is contained in the extract in the above description of the present invention given with reference to the drawings, the intended optical isomer may be contained in the raffinate in another case. In the latter case, the term "extract" in the above description referring to the extract is to be replaced by "raffinate", so that the matter can be easily understood. According to the present invention, an optical isomer mixture can be continuously and efficiently separated and the solvent can be recovered after the use. Since the recovered solvent can be reused as the solvent circulating through the simulated moving bed, the solvent is not wasted and the amount of the eluent used is small, so that a closed system having a high efficiency with respect to solvent can be obtained. Further, the adsorption efficiency is improved by regulating the average particle diameter of the packing for optical resolution to be packed in the simulated moving bed to 1 to 100 µm. In addition, by racemizing the optical isomer which is an antipode contained in the raffinate or extract separated in the simulated moving bed system, the raffinate or extract can convert a solution containing a racemic modification. And since the solution is reused as a liquid containing an optical isomer mixture to be fed, the intended optical isomer can be separated in a high yield. Examples The following Examples will further illustrate the present invention, which by no means limit the present invention. (Example 1) A simulated moving bed apparatus shown in Fig. 1, which was prepared by connecting twelve columns having an inner diameter of 2 cm and a length of 50 cm as the unit packed beds to each other and filling them with packings for optical isomer resolution (CHIRALCEL OB having a particle diameter of 20 µm; a product of Daicel Chemical Industries, Ltd.), was used. In this simulated moving bed apparatus were arranged the columns so that every three unit packed beds took part in the adsorption step, concentration step, desorption step and eluent-recovering step. 6 ml/min of 1,3-butanediol diacetate (total isomer concentration: 1,000 mg/ml) was fed as a liquid containing an optical isomer mixture. 27.9 ml/min of a liquid mixture of hexane and isopropanol (volume ratio: 9/1 ) was fed as the eluent. The solvent circulating the solvent circulation passage was the same as the eluent. 26.6 ml/min of an extract containing a strongly adsorbable optical isomer (concentration: 103.7 mg/ml: optical purity: 98% e.e.) was obtained through the outlet for the extract of the simulated moving bed apparatus. On the other hand, 7.3 ml/min of a raffinate containing a weakly adsorbable, other optical isomer (concentration: 411.4 mg/ml; optical purity: 98% e.e.) was obtained through the outlet for the raffinate of the simulated moving bed apparatus. The extract obtained as described above was fed into the first falling film evaporator at 70°C under atmospheric pressure. The concentrate obtained in this evaporator was fed into the second falling film evaporator at 43°C under 6,66 kPa (50 Torr)and then the concentrate obtained in this second evaporator was fed into a forced film evaporator at 10°C under 6,66 kPa (50 Torr) to give a concentrate containing the strongly adsorbable optical isomer in a concentration of at least 98% from the forced film evaporator. The solvent recovered from the respective evaporators was stored in the reservoir. On the other hand, the raffinate obtained as described above was heated at 90°C for 5 h to give a solution containing a racemic modification. The solvent stored-in the reservoir was reused as the circulating solvent in the simulated moving bed apparatus, and the solution containing the racemic modification in the heating tank was returned into the line for feeding a liquid containing an optical isomer mixture. By the above process, the strongly adsorbable optical isomer having an optical purity of 98% e.e. could be obtained in an amount of at least 83% based on the racemic modification fed into this system. (Comparative Example 1) The separation was conducted batchwise by using the same packing and the same starting material as those in Example 1 and a single column to compare the throughput and the utilization rate of the eluent. The results are given in Table 1. Simulated moving bed process Batchwise process Throughput per unit packing per unit time (mg/ml-bed·min) 2.4 0.084 Utilization rate of eluent (mg/ml-feed) 0.0093 2.0 It is apparent from this Table 1 that the employment of the simulated moving bed process is superior to that of the batchwise process in the throughput and the utilization rate of the eluent. (Example 2) The same apparatuses as those of Example 1 were used except that columns having an inner diameter of 3 cm and a length of 100 cm were used as the unit packed column and CHIRALCEL OB having an average particle diameter of 30 to 50 µm was used as the packing. 6 ml/min of α-phenylethyl alchol (total isomer concentration: 1,000 mg/ml) was fed. 61.4 ml/min of a liquid mixture of hexane and isopropanol (volume ratio: 9/1) was fed as the eluent. The solvent circulating the solvent circulation passage was the same as the eluent. 58.5 ml/min of an extract containing a strongly adsorbable optical isomer (concentration: 28.6 mg/ml; optical purity: 98% e.e.) was obtained through the outlet for the extract of the simulated moving bed apparatus. On the other hand, 8.9 ml/min of a raffinate containing a weakly adsorbable, other optical isomer (concentration: 336 mg/ml; optical purity: 98% e.e.) was obtained through the outlet for the raffinate of the simulated moving bed apparatus. The extract obtained as described above was treated in the same manner as that of Example 1 to give a concentrate containing the strongly adsorbable optical isomer in a concentration of at least 98% by weight. The solvent recovered from the evaporator and the molecular still was stored in the reservoir. The solvent stored in the reservoir was reused as the circulating solvent in the simulated moving bed apparatus, and the raffinate was treated in the same manner as that of Example 1. The resultant solution containing a racemic modification was returned into the line for feeding a liquid containing an optical isomer mixture. (Comparative Example 2) The separation was conducted batchwise by using the same packing and the same starting material as those of Example 2 and a single column to compare the throughput and the utilization rate of the eluent. The results are given in Table 2. Simulated moving bed process Batchwise process Throughput per unit packing per unit time (mg/ml-bed· min) 0.53 0.014 Utilization rate of eluent (mg/ml-feed) 0.02 4.5 (Example 3) A simulated moving bed apparatus shown in Fig. 2, which was prepared by connecting eight columns having an inner diameter of 2 cm and a length of 15 cm as the unit packed beds to each other and filling them with packings for optical isomer resolution (CHIRALCEL OB having a particle diameter of 45 µm; a product of Daicel Chemical Industries, Ltd.) was used. 5.9 ml/min of a mixed solution containing 4,200 ppm of racemic modification of α-phenylethyl alcohol was fed as a liquid containing an optical isomer mixture in the simulated moving bed apparatus. 24.2 ml/min of a liquid mixture of hexane and isopropanol (volume ratio: 90/10) was fed as the eluent. The solvent circulating the solvent circulation passage was the same as the eluent. The liquid-feeding lines and ejecting lines were moved at a distance corresponding to one unit packed bed in the direction of liquid flow by automatically switching an eight-way rotary valve at intervals of 3 min to continuously conduct the treatment at 25°C in a certain period of time. 20.2 ml/min of an extract containing a strongly adsorbable optical isomer [(R)-(+)-α-phenylethyl alcohol] (concentration: 613.4 ppm; optical purity: at least 99.9% e.e.) was obtained through the outlet for the extract of the simulated moving bed apparatus. On the other hand, 9.7 ml/min of a raffinate containing a weakly adsorbable, other optical isomer (concentration: 1,251.5 ppm; optical purity: at least 99.9% e.e.) was obtained through the outlet for the raffinate of the simulated moving bed apparatus. The pressure drop in this simulated moving bed apparatus was 7.9 kg/cm 2 . The extract obtained as described above was fed into the same solvent recovering apparatuses as those of Example 1 to give a concentrate containing the strongly adsorbable optical isomer in a concentration of 98% by weight and the solvent having a purity of at least 99% by weight. The recovered solvent was stored in the reservoir. The solvent stored in the reservoir was reused in the fluid passage in the simulated moving bed apparatus, and the raffinate was converted into a solution containing a racemic modification by heating and returned into the line for feeding a liquid containing an optical isomer mixture.

Claims: A process for recovering optical isomers and a solvent in optical resolution by introducing a liquid containing an optical isomer mixture and an eluent into a packed bed containing packings for optical resolution, having both ends connected to each other through a fluid passage to be endless and circulating the liquids therein by one-way flow, and simultaneously recovering a liquid containing one optical isomer and a liquid containing the other optical isomer which are separated from the packed bed, characterized by arranging an inlet for the eluent, an outlet for a liquid (extract) containing a strongly adsorbable optical isomer, an inlet for the liquid containing an optical isomer mixture, and an outlet for a liquid (raffinate) containing a weakly adsorbable optical isomer in this order in the direction of liquid flow onto the packed bed, and recovering the solvent and the optical isomers from the extract and/or raffinate obtained with a simulated moving bed system, the eluent-feeding line, the line for feeding the liquid containing the optical isomer mixture and the respective ejecting lines being moved at a distance corresponding to one unit packed bed in the direction of liquid flow in the bed, said operation being successively conducted, wherein the solvent is separated from the extract and/or raffinate obtained with the simulated moving bed system with an evaporator and/or a still. A process for recovering optical isomers and a solvent in optical resolution by introducing a liquid containing an optical isomer mixture and an eluent into a packed bed containing packings for optical resolution, having both ends connected to each other through a fluid passage to be endless and circulating the liquids therein by one-way flow, and simultaneously recovering a liquid containing one optical isomer and a liquid containing the other optical isomer which are separated from the packed bed, characterized by arranging an inlet for the eluent, an outlet for a liquid (extract) containing a strongly adsorbable optical isomer, an inlet for the liquid containing an optical isomer mixture, and an outlet for a liquid (raffinate) containing a weakly adsorbable optical isomer in this order in the direction of liquid flow onto the packed bed, and recovering the solvent and the optical isomers from the extract and/or raffinate obtained with a simulated moving bed system, the eluent-feeding line, the line for feeding the liquid containing the optical isomer mixture and the respective ejecting lines being moved at a distance corresponding to one unit packed bed in the direction of liquid flow in the bed, said operation being successively conducted, wherein the optical isomer as an antipode in the extract or raffinate is racemized and the resultant liquid containing an optical isomer mixture is returned into the inlet for the liquid containing an optical isomer mixture. The process for recovering optical isomers and a solvent in optical resolution according to claim 1 or 2, wherein the packing for optical resolution has a particle diameter of 1 to 100 µm. The process for recovering optical isomers and a solvent in optical resolution according to claim 2, wherein the solvent is separated from the extract and/or raffinate obtained with the simulated moving bed system with an evaporator and/or a still. The process for recovering optical isomers and a solvent in optical resolution according to claim 1 or 4, wherein the evaporator and/or still is of reduced pressure type. A process for using a solvent by circulation, characterized by returning the solvent recovered by the process according to claim 1 or 2 into the fluid passage set forth in claim 1 or 2. The process for using a solvent by circulation according to claim 6, wherein the recovered solvent has a purity of at least 98%. A process for reusing an optical isomer, wherein the optical isomer as an antipode in the extract or raffinate set forth in claim 1 is racemized and the resultant liquid containing an optical isomer mixture is returned into the inlet for a liquid containing an optical isomer mixture.

Inventors: NEGAWA MASAKAZU, SHOJI FUMIHIKO, NEGAWA, MASAKAZU, SHOJI, FUMIHIKO
Applicants: DAICEL CHEM, DAICEL CHEMICAL INDUSTRIES, LTD.
Application year: 1992
Main classification: C07B57
IPC codes: C07C29, C07C69, C07C33, B01D15, C07B57, C07C67