METHOD FOR AN AUTOMATIC LIQUID-LIQUID EXTRACTION

Abstract

The invention relates to a method for automated liquid-liquid extraction. The method comprises the steps of: i) providing an extraction device, ii) providing a vessel with a hydrophilic phase and a hydrophobic phase, wherein at least one component to be extracted is contained in one of the two phases, iii) determining a conductivity difference L.sub.ist between the hydrophilic phase and the hydrophobic phase using a conductivity sensor.

The upper phase is extracted at at least two different speeds v.sub.1 to v.sub.n, wherein the last speed v.sub.n is slower than a previous speed v.sub.n1, preferably slower than v.sub.1 to v.sub.n1.

Claims

1-16. (canceled)

17. A method for automated liquid-liquid extraction comprising the steps of: i) providing an extraction device, ii) providing a vessel with a hydrophilic phase and a hydrophobic phase, wherein at least one component to be extracted is contained in one of the two phases, iii) determining a conductivity difference L.sub.ist between the hydrophilic phase and the hydrophobic phase by means of a conductivity sensor; wherein the upper phase is extracted at at least two different speeds v.sub.1 to v.sub.n, wherein the last speed v.sub.n is slower than a previous speed v.sub.n1.

18. The method according to claim 17, wherein the conductivity sensor is guided through the phases in such a way that determined conductivities L.sub.1 to L.sub.n are determined associated with heights of the sensor H.sub.1 to H.sub.n.

19. The method according to claim 17, wherein the velocities v.sub.1 to v.sub.n are discrete velocities.

20. The method according to claim 17, wherein step iii) comprises the steps of: a) determining the conductivity in the upper phase L.sub.o, b) determining the conductivity in the lower phase L.sub.u, c) determining a fictitious phase boundary value L.sub.f according to [(L.sub.uL.sub.o)/phase boundary factor]+L.sub.o, if the hydrophilic phase is the lower phase or determining the fictitious phase boundary value L.sub.f according to [(L.sub.oL.sub.u)/phase boundary factor]+L.sub.u, if the hydrophilic phase is the upper phase.

21. The method according to claim 17, wherein, if in step iii) the conductivity difference L.sub.soll between the phases falls below a target value, an extraction aid is added.

22. The method according to claim 17, wherein v.sub.1 is set as a function of L.sub.ist.

23. The method according to claim 17, wherein v.sub.n is set as a function of L.sub.ist.

24. The method according to claim 17, wherein the suction of the upper phase takes place at at least two different distances a.sub.1 to a.sub.n from the phase boundary.

25. The method according to claim 24, wherein at least one of the first suction speed v.sub.1 is between 50 ml/min and 150 ml/min; and the second suction speed v.sub.2 is between 10 ml/min and 30 ml/min.

26. The method according to claim 17, wherein, in particular after step iii), an intermediate phase is detected, comprising the steps of: a) determining the height H.sub.f, which corresponds to the conductivity L.sub.f, b) determining the conductivity L.sub.fx with the conductivity sensor at the position H.sub.fx, c) determining the conductivity L.sub.f+y with the conductivity sensor at position H.sub.f+y, d) determining the liquid level H.sub.liquid, e) determining the conductivity L.sub.liquid at position H.sub.liquid, f) determining the conductivity L.sub.lowest the lowest level, wherein the presence of the intermediate phase is indicated by at least one of L.sub.f+yL.sub.liquidL.sub.soll and L.sub.lowestL.sub.fxL.sub.soll.

27. The method according to claim 26, wherein suction and discharging of the intermediate phase takes place in the presence of the intermediate phase.

28. The method according to claim 17, wherein the purity of the sensor is determined prior to a determination of the phase boundary and, if necessary, a cleaning step of the sensor is carried out.

29. The method according to claim 17, wherein a pH value of the hydrophilic phase is adjustable.

30. An extraction apparatus for carrying out a method according to claim 17.

31. The extraction apparatus according to claim 30 comprising a pH meter.

32. A computer program comprising instructions that cause the extraction device according to claim 30 to perform the method comprising the steps of providing the extraction device, providing a vessel with a hydrophilic phase and a hydrophobic phase, wherein at least one component to be extracted is contained in one of the hydrophilic and the hydrophobic phases, determining a conductivity difference L.sub.ist between the hydrophilic phase and the hydrophobic phase by means of a conductivity sensor, wherein the upper phase is extracted at at least two different speeds v.sub.1 to v.sub.n, wherein the last speed v.sub.n is slower than a previous speed v.sub.n1.

Description

[0068] The invention is explained in more detail below using FIGS. 1 and 2 and Examples 1 to 3 as examples. The explanations are not intended to be restrictive. It shows:

[0069] FIG. 1 a flowchart of the individual steps of the method according to the invention.

[0070] FIG. 2 a schematic representation of the suction of the upper phase at different speeds.

[0071] FIG. 1 illustrates the method using individual process steps as examples. In the first step 1, an extraction device is provided. A hydrophilic, inorganic phase 2 is fed to this extraction device, followed by an organic solvent 3 as the hydrophobic, organic phase. The two phases are mixed with stirring 4 and, after a rest period for phase separation, a conductivity difference L.sub.ist between the hydrophilic phase and the hydrophobic phase is determined in step 5 using a conductivity sensor. To do this, the conductivity sensor is lowered to 5 mm above a determined phase boundary and the conductivity in the upper phase is measured. The conductivity sensor is then lowered completely into the lower phase and the conductivity of the lower phase is measured. If the conductivity difference L.sub.ist is greater than the target value L.sub.soll of 0.05 mS/cm, the upper phase is first suctioned off at 100 mL/min in step 6 and then at 20 ml/min (FIG. 2).

[0072] If L.sub.ist is below L.sub.soll of 0.05 mS/cm, the phase separation is not sufficient and brine is added to the mixture in accordance with step 7. The conductivity difference is then determined again in accordance with step 5 and, if L.sub.ist>L.sub.soll, suction is carried out in accordance with step 6 at two different speeds.

[0073] Alternatively, it is possible to index an intermediate phase in step 5. For this purpose, a conductivity value 2 mm above the phase boundary is determined L.sub.f+2 mm (L.sub.f+y) and a conductivity value 3 mm below the uppermost level is determined L.sub.liquid. If the conductivity difference is <0.05 mS/cm, this process is carried out with the lower phase. A conductivity value 2 mm below the phase boundary is determined L.sub.f2 mm (L.sub.fy) and a conductivity value at the lowest point is determined L.sub.lowest. If the conductivity difference is >0.05 mS/cm (L.sub.soll) in one of the two cases, the intermediate phase is indexed and this is suctioned off in step 8 and ejected again to enable phase separation. The conductivity is then determined again according to step 5 and if L.sub.ist>L.sub.soll the upper phase is suctioned off according to step 6.

[0074] FIG. 2 schematically shows the extraction step 6 from FIG. 1 with two different speeds. In FIG. 2A, the organic phase 12 is suctioned off at a distance a from the phase boundary 11 at a speed of 100 mL/min via a suction hose 17. Subsequently, a protruding residue 16 of the organic phase 12 is suctioned off at a speed of 20 mL/min, as shown schematically in FIG. 2B. What remains is the inorganic phase 13 with the meniscus 15 of the upper phase 15, which can be mixed or diluted by adding an add-on volume of approx. 5 mL twice, which would roughly correspond to the height of the phase 16, and suctioned off.

EXAMPLE 1

[0075] A reaction mixture of acetic acid benzyl ester, benzyl alcohol, acetic acid, sulphuric acid and by-products was extracted as follows:

[0076] The reaction volume of 39 mL was diluted with 15 mL H.sub.2O in a vessel of the extraction device, a robotic system, 2 mL brine was added as extraction agent and 25 mL ethyl acetate was added. The extraction mixture was mixed for 10 seconds with stirring strength 15. A phase separation was carried out during 60 sec waiting time.

[0077] Firstly, the conductivity was measured at the lift position 0 mm (L.sub.air) and resulted in a conductivity value of 0.0000 mS, indicating a clean sensor.

[0078] The conductivity was then measured at the lift height or lift position of 79 mm. The lift position was calculated using the following formula

[Lift height total (118 mm)+distance sensor to tube (11 mm)volume reaction mixture 39 ml*volume factor 0.8dilution 15 ml*volume factor 0.8brine 2 ml*volume factor 0.85 mm]: 0.009460586 mS.(1)

[0079] The conductivity was then measured at a lift height of 118 mm: 2.036342 mS.

[0080] The conductivity phase limit value L.sub.f was calculated: 0.516181 mS.

[0081] The sensor was then raised to a lift height of 79 mm and slowly lowered until the conductivity of 0.516181 was exceeded. The final lift height was determined to be 85 mm.

[0082] The lift was lowered to 67 mm (phase boundary 85 mm-distance sensor to tube 11 mm-2 mm) and the upper phase was suctioned off at 100 mL/min and collected in a separate vessel.

[0083] The lift was then lowered to 72 mm (phase limit 85 mm-distance sensor to tube 11 mm-7 mm) and the phase was suctioned off at 20 mL/min and collected in a separate vessel.

EXAMPLE 2

[0084] The first extraction was carried out according to example 1.

[0085] Another 25 mL of ethyl acetate was then added to the residue. The extraction mixture was mixed for 10 seconds with a stirring strength of 15. The phase separation takes place during a waiting time of 60 seconds.

[0086] The conductivity was measured at the 0 mm lift position and gave a value of 0.07 mS. The sensor was contaminated. The sensor was moved to the wash position and rinsed with 10 mL acetone and then dried for 60 seconds with the stirrer running. The tubes were rinsed with brine.

[0087] The conductivity was then determined at a lift height of 80 mm (85 mm from the first extension5 mm) according to formula (1): 0.0292257 mS. The conductivity was then determined at a lift height of 118 mm: 1.776728 mS. The conductivity at the phase boundary value was calculated as 0.466101 mS.

[0088] The lift was lowered to 69 mm (phase boundary 87 mm-distance sensor to tube 11 mm7 mm) and the upper phase was suctioned off at 100 mL/min and collected in a separate vessel.

[0089] The lift was then lowered to 74 mm (phase boundary 87 mm-distance sensor to tube 11 mm2 mm) and the remainder of the upper phase was suctioned off at 20 mL/min and collected in a separate vessel.

[0090] Subsequently, 25 mL of ethyl acetate were added as an add-on volume, suctioned off and collected in a separate vessel.

[0091] The aqueous phase was then suctioned off and discarded.

EXAMPLE 3

[0092] In example 3, the steps according to examples 1 and 2 were carried out and then washed.

[0093] The ethyl acetate phases from examples 1 and 2 were placed in an extraction beaker and mixed with 15 mL Na.sub.2CO.sub.3. The extraction mixture was then mixed for 10 seconds at stirring strength 15 and the phase separation was allowed to take place for 60 seconds.

[0094] Firstly, the conductivity was measured at the lift position 0 mm (L.sub.air) (0.0007 mS), which did not result in a contaminated sensor.

[0095] The conductivity was then measured at a lift height of 112 mm (0.001934008 mS), the conductivity was measured at a lift height of 118 mm (0.7977153 mS) and the phase limit value was determined (0.200879 mS).

[0096] The sensor was raised to a lift height of 112 mm and slowly lowered until the conductivity of 0.200879 was exceeded. This resulted in a final lift height of 114 mm. The lift was lowered to 96 mm (phase limit 114 mmdistance sensor to tube 11 mm7 mm) and the phase was suctioned off at 100 mL/min and collected. The lift was then moved to 101 mm (phase limit 109 mmdistance sensor to tube 11 mm2 mm) and the phase was suctioned off and collected at 20 mL/min.

[0097] Subsequently, 25 mL ethyl acetate are added as an add-on volume, suctioned off and collected. The lift is lowered to 118 mm and the pH value is determined. The pH value was 7.8. The aqueous phase was suctioned off and discarded.

[0098] The collected extracts were placed in the extraction beaker and mixed with 15 mL of water. The extraction mixture was then mixed for 10 seconds at stirring strength 15 and the phase separation was waited for 60 seconds. First, the conductivity was measured at the 0 mm lift position (0.0007 mS), which did not result in a contaminated sensor. The conductivity was then measured at the 112 mm lift height:

[Lift height total 118 mm+distance sensor to tube 11 mmvolume H.sub.2O 15 ml*volume factor 0.85 mm]: 0.001134568 mS

[0099] The conductivity was measured at a lift height of 118 mm (0.045342 mS). The difference in conductivity was too small, so 2 mL of brine was added to the extraction mixture.

[0100] The extraction mixture was then mixed again for 10 seconds at stirring strength 15 and the phase separation waited for 60 seconds. Firstly, the conductivity was measured again at the 0 mm lift position (0.0009 mS), which did not result in a contaminated sensor. The conductivity was then measured at the 110 mm lift height:

[Lift height total 118 mm+distance sensor to hose 11 mmvolume H.sub.2O 15 ml*volume factor 0.8brine 2 mL*volume factor 0.85 mm]: 0.001735 mS

[0101] The conductivity was measured at a lift height of 118 mm (1.667378 mS).

[0102] The conductivity phase limit was determined to be 0.418146 mS.

[0103] The sensor was raised to a lift height of 110 mm and slowly lowered until the conductivity of 0.418146 was exceeded. This resulted in a final lift height of 113 mm. The lift was lowered to 95 mm (phase limit 113 mmdistance sensor to tube 11 mm7 mm) and the phase was suctioned off at 100 mL/min and collected. The lift was then raised to 100 mm (phase limit 109 mmdistance sensor to tube 11 mm2 mm) and the phase was suctioned off and collected at 20 mL/min.

[0104] Subsequently, 25 mL of ethyl acetate were added as an add-on volume, suctioned off and collected. The aqueous phase was discarded.