j .m., and rodrigues, a.e. chiral separation by smb ......pais, l.s., loureiro, j .m., and...
TRANSCRIPT
Pais, L.S., Loureiro, J .M., and Rodrigues, A.E.
Chiral Separation by SMB Chromatography
in ISCD'98 1oth Intemational Symposiu"' o11 Chiral Dimimination, Vienna, Austria, August 30 - September 2, 1998. (poste1j
10th International Symposium on Chiral Discrimination
Vienna Hilton August 30- September 2, 1998
JSC:J) arlic ip anl6
a~habelica/ order aJ o/ _A.uguJl, 2 7 0
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Chairman: Wol fgang Lind ne r
Institu te of Ana lytical Chemistry University o f Vien na, Wiihringerst rasse 38 A-1090 Wien, Austria e-mail : Ch ira 198@olivin .a nc. u nivie. a c. a t Fax +4 3- 1-3 15-1826 h ttp:l/www. a ne. u n ivi e . ac.at!Chi r a 198
Bankers: Salzburg e r Spa rkasse, Ba n k Code 20404, Accou nt No. 2500 392506
ISCD'98 Secretariat SEMACO
Fi rmianst rasse 3 A-5020 Salz burg, Austria
e-mai l: [email protected] Fax +43-662-826 878-4
Tel. +43-662-826 878
16
ORTELLI Didier Univ. of Geneva 30 quai Emest- Anserment Switzerland
Te/.:41 22 702 6477 Fa1:.: 41 22 781 51 93 E-mail [email protected]
OURYUPIN Andrei Central Customs Labor. of the State Customs 11/5 Novozavodskaya str. Russia
Tel.: Fax.: 7 95 449 83 49 E-mail
PAIS Luis L.S.R.E.-Laboratory of Separation and Reaction Engineering Rue dos Bragas Portugal
Te/. :351 2 2041669 Fax.: 351 2 2041674 E-mai/
PALOMBI Laura University of Rome "La Sapienza", Dept Chemistry PI. A. Moro 5 Italy
Te/.:39 6 49913638 Fax. : 936 4991 E-mail [email protected]
PE'TER Ma'ria Albert Szent-Gyorgyi Medical University Eotvos u. 6 POB 121 Hungary
Tel.: 36 62 454 000 Fax.: 36 62 310 604 E-m ail [email protected] _u-szeged. hu
PEARS Robert REGIS TECHNOLOGIES 8210 Austin Ave USA
Te/.:84 7 583 7649 Fax.: 847 9671214 E-mail [email protected]
PERRY Robert Gill Jermings & Every 7 Eldon Street United Kingdom
Te/.:44 1713 7713 77 Fax.: 44171 5771310 E-mail [email protected]
PERSSON Bengt-Arne Astra Hassle AB Sweden
Te/. :46 31 776 1327 Fax.: 46 31 776 3760 E-m ail [email protected]. astra.com
PESCITELLI Gennaro CNR University ofPisa via Risorgimento 35 Italy
Tel.: Fax.: E-mail
PFEIFFER Jens Universitat Tuebingen
Te/. :49 7071 2976260
Alle der Morgenstelle 18 Germany
Fax.: 49 707129 5538 [email protected]
PIRKLE H. William University of Illinois, Depart. of Chemistry 600 S. Mathews Street USA
Tel.: Fax.:/2172448068 E-mai/
PRANGLE Anita University of Sunderland Wahrncliffe street United Kingdom
Te/.:191 515 2577 Fax.: 191 515 2502 E-mail [email protected]
ISCD '98 Scientilic Program- Posters 11 http://w\vw.anc. univie.ac.at/Chiral98/posters2.1
I of9
1Oth Intetnational Symposium on Chiral Discrimination, ISCD'98
August 30- September 2 1998 in Vienna (Austria)
[Topics] [[History l] [Pro!!ram] [Exhibition]
Scientific Program - Posters Session 11
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POSTER SESSION I
Topics
Al Fundamental Aspects ofChirality, Molecular Recognition and Molecular Modelling, Suprastructural Phenomena, Chiral Polymers
B Novel Developments in Asymmetric Synthesis Including Chemocatalysis
C Asymmeh·ic Synthesis using Biocatalysis and Enzymatic Methods
D 1 Gas- and Liquid Phase Separation Techniques (LC, CE, CEC, MEKC, GC)
g Enantioseparation via Crystallographic Techniques
POSTER SESSION II
Topics
A2 Fundamental Aspects of Chirality, Molecular Recognition and Molecular Modelling, Suprastructural Phenomena, Chiral Polymer
D2 Gas- and Liquid Phase Separation Techniques (LC, CE, CEC, MEKC, GC)
E Preparative Enantiomer Separation Techniques including Chromatography (LC, GC, CCC) and Membrane Teclmology
G Chiral Aspects in Pharmacology, Pharmacokinetics, Pharmacodynamics, Drug Binding, etc.
H Chiroptical Spectroscopy, NMR, lnshumentation, etc.
POSTER SESSION 11
Tuesday/Wednesday, September 1/September 2, 1998
8/ 1/2002 11 :341
ISCD '98 Scientific Program- Posters 11 http://www.anc.univ ie.ac .at!Chira198/postcrs2.t
5 of 9
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY OF BINAPHTHYL DERIVATIVES ENANTIOMERS ON NEW CHOLIC ACID-BASED STATIONARY PHASES. APPROACH OF THE CHIRAL RECOGNITION MECHANISM
Vaton-Chanvrier L., Combret Y. and Combret J.C. ; Mt. St. Aignan (France)
BISBENZYLISOQUINOLINE ALKALOIDS AS COMPLEXA TION AGENTS Millership J.; Belfast (Northern Ireland)
RESOLUTION OF THE DIASTEREOMERS OF SB-238592-DB BY CAPILLARY ELECTROPHORESIS USING NONIONIC SURF ACT ANTS
Hadley M.R. and Gilges M.; Tonbridge (UK)
ENANTIOSEPARATION OF SOTALOL ON A CBH-I BASED CHIRAL PHASE: EFFECT OF COLUMN TEMPERATURE
Fulde K. and Frahm A.W.; Freiburg (Ge1many)
SELECTIVITY TUNING IN CHIRAL GAS CHROMATOGRAPHY Krupcik J., Spanik I. and Sandra P.; Bratislava (Slovak Republik)
ON THE USAGE OF CYCLODEXTRINS IN GC AND CE. Koppenhoefer B., Wuerthner S., Jakob A., Juvanecz Z. and Szeitli G.; Budapest (Hungary)
CHIRAL KBS: A KNOWLEDGE-BASED SYSTEM FOR CHIRAL SEPARATIONS !j] Torres-Lapasio J.R., Maftouh M., Vander Heyden Y., Vargas M.G. and Massart D.L. ; Brussels (Belgium)
F Preparative Enantiomer Separation Techniques including Chromatography (LC, GC, CCC) and Membrane Technology
DEVELOPMENT OF ENANTIOSELECTIVE LARGE SCALE PREPARATIVE SEPARATIONS Cox G., Dapremont 0., Suteu C. and Murakami T.; Illkirch (France)
OPTIMISA TION OF THE PREPARATIVE ENANTIOMERIC SEPARATION OF AN ALPHA-HYDROXY ACID BY LIQUID CHROMATOGRAPHY ON TWO DERIVATISED POLYSACCHARIDE (DAICEL TYPE) STATIONARY PHASES
Suteu C., Cox G. and Amberg W.; Illkirch (France)
CHIRAL SEPARATION BY SMB CHROMATOGRAPHY Pais L.S., Loureiro J.M. and Rodrigues A.E.; Porta Codex (Porhtgal)
PRODUCTIVITY OF DIFFERENT CHIRAL STATIONARY PHASES FOR PREPARATIVE ENANTIOSEPARATION BY SIMULATED MOVING BED (SMB)-CHROMATOGRAPHY
Schulte M. and Ludemann-Homburger 0.; Dannstadt (Gennany)
811/2002 11: 34 p
Introduction ·Concept of Simulated Moving Bed:
1st UOP patent (1 961) Sorbex processes.
• Applications:
Petroleum refining and petrochemicals (Parex and Molex processes)
Carbohydrate industry (production of fructose from corn syrup)
(Sarex process)
·The SMB technology has recently found new applications in the areas of biotechnology, pharmaceuticals and fine chemistry.
lSRf
SMB Principle ·Flow scheme that takes advantages of continuous and countercurrent movement of liquid and solid without actual movement of the adsorbent.
•The adsorbent bed is divided into a number of fixed-bed columns, while the inlet and outlet lines move simultaneously one column at fixed time ~ intervals in the direction of the liquid phase flow.
•Advantages of SMB chromatography: lt is a continuous process; Can perform low selectivity separations; Reduction in eluent consumption and adsorbent requirements.
LSR£ 2
----- - · - ----· ··-- ------ ·- ~ . --- - - - -· .
Section I!
Section IV
Schemalic diagram of a Simulated Moving Bed
IS RE 3
Ob.iectives
• Modeling strategies of a Simulated Moving Bed unit
• SMB simulation and study of the influence of operating parameters
on the SMB performance
• Optimization of the SMB operation conditions
• Experimental operation of a SMB pilot unit
(Licosep 12-26, NOVASEP, France)
lSRE 4
Modeling ·Two main strategies:
The SMB model: considers the real shift of the injection and collection points.
The TMB (true moving bed) model: considers liquid and solid flow in opposite directions.
·For practical purposes, optimization and . choice of SMB configuration (length of each section) can be safely carried out on the basis of analogy with TMB mode ling.
Reference: Pais, Lourelro and Rodrigues, 'Modeling Strategies for Enantiomers Separation by SMB Chromatography', A/ChE J., 44, 561·569 (1998).
!SHE 5
Model equauons for the steadv-state TMB model
Mass balance in a volume elemerzt of the bedj:
d 2cij dcij (1-E) • DL. ---v · - ---k(q .. -q··)= O
J dz.2 1 dz. E lj IJ
1'vlass balance in the particle: dq.. •
u5 -d11 +k(q .. -qij)=O Z IJ
Boundary conditions for section j:
:=0: DL1 dcij
Cij "" --T=cij,O Vj Z
: = Lj: cij = cij+/,0 extract, raffinate nodes
and
IS BE
v, cij =-cij+l,O
v,v
!!J1L V F Cij = Cij+l,O _ _f_C .
VJI VI/ I
qij = qij+l,O
eluent node
feed node
The TMB model considers:
• Axial dispersion flow for the bulk fluid phase
• lntraparticle mass transfer rate described by the
linear driving force approximation
• The model can handle .. any.kind of adsorption isotherm
aolltl ci~ulatlon
Uquid recircultlliOn
Schemauc diagram of a True Moving Bed
lSRE 6
Global balances:
Vf = Vfl' +v£ eluent node
vu=vf-VX
vm = vu+ vF
vw = vm-vR
extract node
feed node
rnffinate node
Multicompmze/!t adsorption equilibrium i.wlherm:
q;j = f A(cA1,c81J andq;j = f o(cAj•cBj)
1 - E
E
Model parameters
Ratio between solid and fluid volumes
V.
r 1 = ...1.. Ratio between fluid and solid velocities lis
V·L· Pe 1 = :..J.::L Peel et number
Dij
kL· a 1 = --1 Number of mass transfer units
"• Adsorption equilibrium parameters have to be added to the list above.
lSHE 8
Simulation twesults Ur---~--~~------~
99% H--~-·
Ttn
--t.o.ss·' -·k=O.rs"'
U 1 I u u To l lJ
lnnuence of IIlo mass llansfer resistance on llle separaUon region ltarget99%J
Optimum operation conditions (99% vertex) k (s-1) Oe Ox OF OR 0.5 18.29 17.62 6.80 7.47 0.1 22.70 16.90 2_39 8.19
Sy>tem: bl-naphthol enantiomers SAIB Op613tion conditions: 0Ft0e=Ox+OR=25.ll9 mllmin
Sv.1lch time Interval: 3 min Recycling flow rate; 35.38 mllmin
Creed= 2.9 g/1 each enantiomer v-1 beG. 446 m1
LSRE
' . 0,1--..1
Separauon region In a lh versus QF plot Region flll1ited by closed squares:
separation region lor a 95% purity criteria.
9
Open squares: path of equal raffinate and extract purities. (mass lranslercoefficient /r-0.1 s·l)
·Since the objective of the SMB operation is to obtain the two pure enantiomers, the path of equal purities is the optimum trajectory that must be followed.
•The optimum will result from a trade-off between solvent consumption and productivity, purity and recovery requirements, and system robustness.
ISRE 11
Elfect of the extractllow-rate on llle SMB performance
i = a=r-e ~i::-.~ . ; .... .. ~ , 7, ··:!·. ·- ··
l ·-,--- ·., 1=1 E-+.: i \,<~; .. 17 "f:-t'" 11 \ lA~ I
'"' e ,., t .! ..
"' ..
... tl ln u ,.. . ~ .. ~ .........
ll 14 ll u :u u lt
!.utanR--.l~l
• The deviation of the extract flow-rate from its optimum value drastically affects the performance of one or the other enantiomer, depending on which direction Ox is changed.
IS RE
OpUmum purtUes and recoveries as a runcuoa ollbe feed now rate.
~ r-~----~--.-~==~·
I • Q,IMWool
Solvent consumpUon and adsorbent producUv11V as a runcuoa ollbe reed now rata.
10
References: Pais, Loureiro and Rodrigues
lSRE
Chem. Engng Sci., 52, 245-257 (1997). J. Chromatog. A, 769, 25-35 (1997). J. Chromatog. A, submitted (1998).
12
Systems studied
Separauon of chlral epoXide enanuomers CX1
1.1
0 . H
(Sandoz Pharma, Base/, Swi!zerland) ocn ..
Stationary phase: microcrystalline cellulose triacetate (dp=45 J..lm)
Mobile phase: methanol Temperature: 25 oc
011
otl
Separauon of hi-naphthol enanuomers ~ (Aidrich, USA, Cat. No. 10, 465-5)
Stationary phase: Pirkle type, DNBPG-Silica (dp=25-40 J..lffi)
Mobile phase: heptane-isopropanol (72!281
Temperature: 25 oc LSRE
lSOE
comparison between experimental and model results
- ·~ ~
"
bl-naphlbol enanUomers
chlral epoxide enanuomers
13
15
I I
Ope111ation SMB pilot unit:
LICOSEP 12-26 (Novasep, France)
Experimental performance parameters . System PUX(% PUR(% RCX(% RCR(%
Chlral epaxld•
Si-naphthol
System
Chlral epolldo
Bi-nCijl_hthol
lSBE
90.0 92.0 94.0 91.1 93.0 96.2 97.3 91.6
SC(mVg) PR (g/day !bed) (Q~ +Qf.) F cF QF(Cd. + I!)
QF(CF +C~) Yb.J
400 52 1200 GB
Slll)lllllnaiiUncolllllUoa.
"""' 10122-
5 Ui ZI20 or ~.00
1.52 2:05
Bklloh!hel tB 10.5 i
2-2·2·2 25
l!I(ID"""*'' 2.!l V5 35.Ja llis 16.110 ] .61 g.og
Conclusions
14
·The SMBITMB packages are important learning and training tools used to predict the effect of operating variables on the process performance, and so the choice of the best conditions for the SMB operation.
• The regions for enantiomer separation can be numerically predicted, considering non-linear competitive adsorption isotherms, dispersion and mass transfer resislances phenomena. The mass transfer resistance phenomenon affects (reduces) the separation region of both enantiomers.
• Ox versus OF plot provides a practical tool for choosing the better SMB operating conditions. The optimum will result from a trade-off between solvent consumption and productivity, purity and recovery requirements, and system robustness.
LSHE 16
..