METHOD FOR CONDUCTING DERACEMIZATION USING TAYLOR FLOW AND A DEVICE THEREFOR

Abstract

The present invention relates to a method for conducting deracemization using Taylor flow and a device for conducting the same. With respect to the deracemization of a racemate, it may be efficiently conducted with improved rapidity when a racemate-containing fluid is placed under Taylor flow.

Claims

1. A method of deracemization of a racemate, comprising: a first step for supplying a racemate-containing fluid to a reaction zone of a reactor, which comprises an inner cylinder having a surface with a first temperature (T.sub.1), an outer cylinder having a surface with a second temperature (T.sub.2), and a reaction zone between the inner cylinder and the outer cylinder; and a second step for stirring the racemate-containing fluid under Taylor flow by rotating the inner cylinder while immobilizing the outer cylinder.

2. The method of claim 1, wherein the racemate-containing fluid is supplied as a batch type or continuous type.

3. The method of claim 1, wherein the racemate is NaClO.sub.4, clopidogrel, fructose, threonine, carvone, thalidomide, ethambutol, naproxen, penicillin, propranolol, carvedilol, or 1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazole-1-yl)pentan-3-one.

4. The method of claim 1, wherein the racemate-containing fluid is an aqueous solution containing a racemate.

5. The method of claim 1, wherein T.sub.1=T.sub.2 or T.sub.1T.sub.2.

6. The method of claim 1, wherein the temperature difference between T.sub.1 and T.sub.2 is 1 C. to 50 C. when T.sub.1T.sub.2.

7. The method of claim 1, wherein a rotational speed of the inner cylinder is adjusted to meet the condition 1<Ta/Ta.sub.c<160, wherein Ta is a Taylor Number under an applied condition in the second step and Ta.sub.c is a critical Taylor Number.

8. The method of claim 1, wherein an enantiomeric excess (ee) value of at least 50% is obtained within 24 hours.

9. The method of claim 1, wherein an ee value of at least 50% is obtained within 12 hours when T.sub.1T.sub.2.

10. A device for deracemization of a racemate comprising an inner cylinder having a surface with a first temperature (T.sub.1), an outer cylinder having a surface with a second temperature (T.sub.2), a reaction zone between the inner cylinder and the outer cylinder, and an inlet for providing a racemate-containing fluid within the reaction zone, wherein the racemate is deracemized by stirring the racemate-containing fluid in the reaction zone under Taylor flow by rotating the inner cylinder while immobilizing the outer cylinder.

11. The device of claim 10, wherein the device is operated in a batch type or continuous type.

12. The device of claim 10, wherein T.sub.1=T.sub.2 or T.sub.1T.sub.2.

13. The device of claim 10, wherein the temperature of the inner cylinder and the outer cylinder is adjusted by a heat exchanger for heat generation or heat absorption.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0040] FIG. 1 schematically shows a reactor for the deracemization reaction according to an exemplary embodiment of the present invention.

[0041] FIG. 2 shows a variation of an enantiomeric excess (cc) according to time when the deracemization reaction using the isothermal Taylor flow is carried out according to the present invention.

[0042] FIG. 3 is an outline of the deracemization reaction which uses the non-isothermal Taylor flow according to the present invention.

[0043] FIG. 4 shows a variation in temperatures of the cold surface (outer cylinder) and hot surface (inner cylinder), and an average temperature of a solution within a reaction zone, according to time, when using the non-isothermal Couette-Taylor reactor according to an exemplary embodiment of the present invention.

[0044] FIG. 5 shows a result of the deracemization reaction using the non-isothermal Couette-Taylor reactor.

DETAILED DESCRIPTION OF THE INVENTION

[0045] Hereinbelow, the present invention will be described in detail with accompanying exemplary embodiments. However, the exemplary embodiments disclosed herein are only for illustrative purposes and should not be construed as limiting the scope of the present invention.

Example 1

Deracemization Reaction Using Isothermal Taylor Flow

[0046] As shown in FIG. 1, a reactor for the deracemization reaction according to an exemplary embodiment was prepared.

[0047] The deracemization reaction was carried out using the prepared reactor for the deracemization reaction, and the result thereof was investigated. The process for carrying out the deracemization reaction will be described in more detail.

[0048] First, NaClO.sub.4 (100 g) was dissolved in water (100 mL) to prepare a NaClO.sub.4 solution. Additionally, the NaClO.sub.4 solution having the initial temperature of 33 C. was placed in the reactor for the deracemization reaction, and was then cooled to finally reach 20 C. at each different cooling rate, as shown in Table 1 below. Induction time, the time taken to obtain the first crystal from the time-point of initiating the cooling, was measured, and an enantiomeric excess (ee) value was then measured at the time-point above, thereby indicating such value as the initial enantiomeric excess (ee) value.

[0049] Thereafter, the deracemization was induced by rotating the inner cylinder in the reactor at a different rotational speed, calculated respectively according to the range of Ta/Ta.sub.c, as shown in Table 1 below.

TABLE-US-00001 TABLE 1 Presented rotation speed [rpm] (applied range Flow regime Ta/Ta.sub.c value) Ta/Ta.sub.c < 1 Laminar Couette flow 10 (0.9) 1 < Ta/Ta.sub.c < 3 Laminar Taylor vortex flow 30 (2.7) 3 < Ta/Ta.sub.c < 13.3 Wavy vortex flow 100 (8.99) 13.3 < Ta/Ta.sub.c < 18 Quasy-periodic wavy wortec 180 (16.20) flow 18 < Ta/Ta.sub.c < 33 Weakly turbulent vortex flow 300 (27.00) 33 < Ta/Ta.sub.c < 160 Turbulent Taylor vortex flow 500 (44.99)

[0050] The enantiomeric excess (ee) values were measured in each bath time by differing the bath time in the reactor and the result thereof is shown in Table 2 below.

TABLE-US-00002 TABLE 2 Solution Initial Setting Cooling Rotation Induction Ini. Bath Concent Temp. Temp. rate speed time ee time Final ee [g/100 ml] [ C.] [ C.] [ C./min] [rpm] [min] [%] [h] [%] 1 100 33 20 0.12 500 90 0.81 (L) 10 81.25 (L) 91 0.769 (L) 10 84.28 (L) 87 0.629 (D) 10 81.82 (D) 85 0.412 (D) 1 29.79 (D) 89 0.6211 (D) 1 31.43 (D) 2 100 33 20 0.37 500 24 0.569 (D) 10 63.13 (D) 26 0.56 (L) 10 67.36 (L) 29 0.402 (L) 10 66.22 (L) 26 0.226 (D) 1 10.07 (D) 24 0.157 (L) 1 9.79 (L) 25 0.213 (L) 1 8.16 (L) 25 0.207 (D) 1 6.422 (D) 26 0.272 (L) 1 6.782 (L) 27 24 100 (D) 3 100 33 20 0.57 500 16 0.12 (D) 10 50.82 (D) 14 0.22 (L) 10 51.50 (L) 14 0.36 (L) 10 54.51 (L) 15 0.42 (L) 1 8.35 (L) 13 0.212 (D) 1 7.47 (D) 4 100 33 20 0.68 500 12 0.152 (D) 10 40.12 (D) 12 0.493 (D) 1 5.73 (D) 10 0.22 (L) 1 8.15 (L) 11 0.513 (L) 1 6.631 (L) 5 100 33 20 0.37 300 27 0.22 (L) 10 49.64 (L) 29 0.319 (L) 1 5.938 (L) 28 0.426 (D) 1 3.136 (D) 28 0.24 (L) 1 2.296 (L) 28 0.182 (D) 1 7.134 (D) 27 0.388 (D) 1 3.006 (D) 27 0.339 (L) 1 2.778 (L) 27 0.215 (L) 1 4.425 (L) 6 100 33 20 0.37 180 29 0.389 (D) 1 3.018 (D) 28 0.306 (L) 1 4.478 (L) 29 0.437 (L) 1 3.208 (L) 30 0.322 (L) 1 4.784 (L) 28 0.465 (L) 1 5.603 (L) 29 0.358 (D) 1 6.273 (D) 29 0.524 (D) 10 35.87 (D) 7 100 33 20 0.37 100 29 0.495 (D) 1 1.288 (D) 29 0.4651 (D) 1 2.351 (D) 30 0.352 (L) 1 2.301 (L) 30 0.372 (D) 1 5.975 (D) 31 0.197 (L) 1 6.369 (L) 31 0.408 (L) 1 3.338 (L) 30 0.126 (D) 1 4.109 (D) 31 0.433 (L) 1 6.796 (L) 31 0.369 (L) 10 24.42 (L) 8 100 33 20 0.37 30 31 0.264 (L) 1 2.627 (L) 32 0.324 (D) 1 2.866 (D) 30 0.258 (D) 1 1.493 (D) 32 0.469 (D) 1 2.644 (D) 20 32 0.210 (D) 1 1.639 (D) 31 0.127 (L) 1 1.259 (L) 33 0.154 (L) 1 3.571 (L) 31 0.302 (D) 1 2.692 (D) 9 100 33 20 0.37 800 23 0.79 (L) 10 79.73 (L) 10 100 33 20 0.37 1100 16 0.86 (L) 10 91.49 (L)

[0051] The result of Table 2 shows that the ee value was less than 1% during the initial stage, but an ee value of at least 20% was obtained within 10 hours when the deracemization reaction using the isothermal Taylor flow according to the present invention was conducted.

[0052] Additionally, an ee value of at least 99% was obtained within 20 hours when the deracemization reaction using the isothermal Taylor flow according to the present invention was conducted. Specifically, it was confirmed that an ee value of at least 99% was shown within 20 hours from the result of the deracemization reaction on the sample (), in which the initial ee value was 0.569% (D) when the cooling rate (0.37 C./min) was applied, and the sample (), in which the initial ee value was 0.81% (L) when the cooling rate (0.12 C./min) was applied, among samples in Table 2 above (FIG. 2).

Example 2

Deracemization Reaction Using Non-Isothermal Taylor Flow

[0053] The deracemization reaction was conducted using the reactor and conditions corresponding to Example 1, except the temperature swing was possible during the deracemization in the inside of the Taylor reactor by differing the temperature of the inner Couette-Taylor reactor from that of the outer Couette-Taylor reactor as shown in FIG. 3.

[0054] Specifically, the surface of the outer cylinder was the cold surface while the surface of the inner cylinder was the hot surface. FIG. 4 shows a variation in temperatures of the cold surface (outer cylinder) and hot surface (inner cylinder), and an average temperature of a solution within a reaction zone, according to time, when using the non-isothermal Couette-Taylor reactor according to an exemplary embodiment of the present invention.

[0055] As a result, it was confirmed that an ee value of at least 99% was obtained when using the non-isothermal Couette-Taylor reactor, in which the temperature difference of the inside and outside is 3 C., thereby carrying out the efficient deracemization process compared to the isothermal Couette-Taylor reactor (FIG. 5).