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238 S. Schlosser et al. / Separation and Purification Technology 41 (2005) 237266

3.3. Ionic liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252

3.4. Toxicity and compatibility of solvent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252

3.5. Co-transport and competitive transport (selectivity) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

4. Membrane contactors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

4.1. Factors affecting the performance of contactors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

4.2. Modelling and mass-transfer characteristics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

5. Case studyrecovery of MPCA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258

Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

Nomenclature

A surface area (m2)

Aw arithmetic mean value of the inner and outer

geometric surface areas of fibers (m2)

c molar concentration of the solute (undissoci-

ated acid or acid in the complex) (mol m3)

D distribution coefficient ()

k individual mass-transfer coefficient (m s1)

Ke overall mass-transfer coefficient in the extrac-

tor (m s1)

Ks overall mass-transfer coefficient in the stripper

(m s1)

n molar flux (mol s1)

Ncs number of contactors in series ()Nct total number of contactors (both in parallel and

series) ()

re rate constant of the extraction reaction, Eq.(3)

(m s1)

rs rate constant of the stripping reaction, Eq.(4)

(m s1)

R overall mass-transfer resistance (s m1)

Re Reynolds number ()

u linear velocity of the flow (m s1)

V volumetric flowrate (m3 s1)

YMA/OA ratio of mineral acid to organic acid flux ()

Z concentration factor of the solute in the con-centrate (output from the stripper) defined by

relationZ = cR,n+1/cF1()

n+1 concentration ration+1 = cS,n+1/cS,n+1(ap-

proach to an equilibrium on the raffinate end

of the contactor in MBSE,cS,n+1 = DFcF,n+1)

()

porosity of the wall ()

e yield of the solute in extraction ()

conv conversion of the reagent in the stripping solu-

tion ()

Subscripts

0 initial value1 feedorstripping solution inlet end ofa HF con-

tactor or a series of contactors

2 raffinate or stripping solution outlet end of a

HF contactor or a series of contactors

b boundary layer in the bulk phase

e extractor (MBSE)

F feed phase, feed boundary layer

i inner surface of the fiber wall

n number of the contactor segments

o outside surface of the fiber wall

R stripping solution; stripping interface

s stripper (MBSS)S solvent phase, boundary layer in the solvent

w fiber wall

Abbreviations

6-APA 6-aminopenicillanic acid

AOT sodium di(2-ethylhexyl)sulfosuccinate (an-

ionic surfactant)

BLM bulk liquid membrane

CF HF cross-flow hollow fiber contactor

D2EHPA di(2-ethylhexyl)phosphoric acid

DLC double Lewis cell with layered BLM

DNNSA dinonylnaphtalenesulfonic acid

EC equilibrium cell for contacting two liquids

ELM emulsion liquid membrane

EXT solvent extraction

FSC flat sheet contactor

HF hollow fiber

MBSE membrane-based solvent extraction

MBSS membrane-based solvent stripping

MHS multimembrane hybrid system (LM between

two ion-exchange membranes)

MIBK methylisobutylketone


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S. Schlosser et al. / Separation and Purification Technology 41 (2005) 237266 239

Abbreviations

MPCA 5-methyl-2-pyrazinecarboxylic acid

PAA phenylacetic acid

PF HF parallel flow hollow fiber contactor

PT pertraction

RFC rotating film contactor with BLM

SLM supported liquid membrane

TOA trioctylamine

TOMAC trioctylmethylammonium chloride

TOPO trioctylphosphine oxide

1. Introduction

Recovery and concentration of organic acids, as well as

separation of acid mixtures, have attracted a great interest

of researchers, especially in connection with their recoveryfrom fermentation broths, reaction mixtures and waste solu-

tions. Several older reviews including membrane-based sol-

vent extraction (MBSE), pertraction, solvent extraction and

extractive fermentations or bioconversions have been pub-

lished[18]. These papers partly covered also recovery of

organic acids, but a need for an updated review in this area

was actual.

Several processes employing partitioning of components

on one or two L/L interfaces have been developed to achieve

separation of mixtures. Membrane-based solvent extraction

is a relatively new alternative of classical solvent extraction

where mass-transfer between immiscible liquids occurs from

the immobilised L/L interface at the mouth of pores of a mi-croporous wall, as shown inFig. 1a and in detail in Fig. 2.

Basic information on MBSE is given in papers[5,912]. The

solvent can be regenerated by MBSS where the solute is re-

extracted into the stripping solution. Another method of re-

generation could be distillation of the volatile solvent, etc.,

depending on properties of the system. A schematic flow

sheet of the simultaneous MBSE and MBSS processes with

closed loop of the solvent is shown in Fig. 3. In this way,

recovery of the solvent and concentration of the solute can

be achieved. Preferable contactors for MBSE and MBSS are

Fig. 1. Processes with immobilised L/L interface(s). (a) Membrane-based solvent extraction (MBSE), (b) pertraction through supported liquid membrane

(SLM), (c) pertraction through bulk liquid membrane (BLM) with two immobilised L/L interfaces in a hollow fiber (HF) contactor. F: feed (donor) phase, HF:

hollow fiber (microporous, hydrophobic), M: membrane phase, R: stripping (acceptor) solution, S: solvent.

Fig. 2. Detail view of the two-phase system in membrane-based solvent

extraction (MBSE).

hollow fiber contactors, which will be discussed in Section

4.

Extraction into capsules with a solvent, e.g. recovery of

phenylethanol (a product of phenylalanine bioconversion by

yeast)[13]or lactic acid from fermentation broth[14], at-tracted an interest, recently. The polymeric core of the cap-

sule prevents direct contact of the solvent with biomass. This

process could be regarded as a batch MBSE.

An interesting variant of MBSE with dual mechanism of

separation is extraction from an ion exchange membrane,

which has been suggested by Kedem and Bromberg [15]

and Isono et al.[16,17].The separation is performed by L/L

partitioning and is enhanced by an electrostatic rejection in

the ion exchange membrane, as will be described in Section

2.1.

A different approach used by Pronk [18] was revis-

ited by Isono et al. [19]. The fresh solvent with dissolved

reagents, N-(benzyloxycarbonyl)-l-aspartic acid (ZA) andl-phenylalanine methyl ester (PM), was supplied to the sys-

tem and dispersed (emulsified) in an aqueous solution with

enzyme (Thermoase C-160). The reagents were deliberated

to the aqueous phase where they reacted via enzymatic

reaction. The product,N-(benzyloxycarbonyl)-l-aspartyl-l-

phenylalanine methyl ester (ZAPM, which is an aspartame

precursor) was extracted to the solvent and removed from a

reactor through a hydrophobic microporous membrane. C4to

C7alcohols, preferably 1-hexanol and 1-heptanol, were used

as the solvent. This biphasic hybrid process with an enzyme


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Fig. 3. Flowsheet of MBSE with simultaneous regeneration of the solvent

by MBSS in HF contactors and recirculation of the solvent to extraction. In

both contactors the solvent flows in the contactor shell.

reaction and extractive separation allowed a continuous and

stable ZAPM production.

A process similar to extraction, which is based on the same

mechanisms, is pertraction (PT) through a liquid membranewhere both extraction and stripping of the solute are realized

in one equipmenta three-phase contactor with two L/L in-

terfaces [6,12,2023]. Three types of liquidmembranes (LM)

can be used, supported, bulk and emulsion LM. The sup-

ported liquid membrane (SLM) is formed by soaking the sol-

vent into pores of a microporous wall (with a pore diameter

preferably under 1m), as schematically shown in Fig. 1b.

As examples can be given pertraction of propionic acid[24],

lactic acid[25]and phenylalanine[26]through SLM. A se-

rious problem, which has not been solved up to now, is the

short lifetime of SLM. This shortcoming could be overcome

by using bulk liquid membranes (BLM), with advantage inthe hollow fiber (HF) contactor, shown inFig. 1c[6,2729].

No problem with lifetime of BLM occurs. This is paid by a

doubled wall and a thicker liquid membrane layer between

walls (bulk membrane), comparing with SLM, what results

in higher mass-transfer resistance[12].

A rotary disc pertractor with BLM was suggested in pa-

pers[20,30]and widely studied in Boyadzhiev group also

for recovery of organic acids[3134]. In this contactor hy-

drophilic discs are fixed on a rotating horizontal shaft. The

lower parts of thediscsare immersed in compartments, which

are alternately filled with the stripping solution and the feed.

The remaining parts of the discs, on which films of aque-

ous phases are formed due to rotation, are immersed in the

membrane phase. Mass transfer from the feed films into the

stripping solution films through the bulk liquid membrane

occurs.

Pertraction of acids from the feed into an emulsion of

the stripping solution is another configuration of the pertrac-

tion process. The continuous phase of emulsion acts as an

emulsion liquid membrane (ELM). In systems where aque-

ous solutions are separated, the membrane is formed from

the immiscible organic phase separating the aqueous feed

and the stripping solutions. Numerous papers on pertraction

of organic acids into emulsion have been published, e.g. for

lactic acid[35], phenylalanine[36,37], cephalosporin[38],

etc. Demirci et al.[39]suggested process where lactic acid is

pertracted into emulsion of the stripping solution flowing in

the shell of the HF contactor. Thus, contact of three phases

is realized in this system.

Several mechanisms to achieve transport of solute(s)

through the L/L interface or through a liquid membrane canbe utilised. The separation mechanism could be based on

differences in physical solubility of the solutes or their solu-

bilisation into the solvent or reverse micelles or on the chem-

istry and rate of chemical or biochemical reactions occur-

ring on L/L interface(s). The complexing or solubilisation

agentextractant (carrier in the liquid membrane) forms by

reversible reaction complex(es) or aggregate(s) with the so-

lute, which aresoluble in thesolventor membrane.The chem-

istry of reactive extraction andstripping in MBSE andMBSS,

as well as in PT, is identical with the classical solvent ex-

traction or stripping and is presented in several books, e.g.

[4,40,41].

Recently, enzymatic reactions on L/L interfaces were em-ployed to achieve separations [4247]. An example of the

mechanism of transport through LM facilitated by enzymatic

reactions is schematically shown in Fig. 4 [45]. The aque-

ous feed, e.g. a mixture of phenylacetic acid (PAA) and 6-

aminopenicillanic acid (6-APA) and the stripping phases flow

in the lumen of hydrophobic hollow fibers with microporous

walls. Fibers are immersed in the immiscible organic phase

forming a liquid membrane. Carboxylic acid RACOOH (in

this example PAA), reacts at the L/L interface with alcohol

(ethanol was added to the feed) under the catalytic action

of enzyme E1 (lipase Candida rugosa, CLR) and the ester

formed dissolves in the membrane (in this example 20 vol.%octanol in heptane) and is transported through it. On the

downstream L/L interface deesterification reaction proceeds

catalysed by ester E2 (lipase from porcine pancreas, PPL)

and PAA is deliberated to the stripping solution with a higher

pH than in the feed. The second acid RBCOOH (6-APA) is

not transported via this mechanism. Thus, separation of acids

occurs, in the mentioned example the separation factor was

as high as 10. Physical solubility of acid in the membrane

can be an additional mechanism of its transport through the

membrane.

To avoid direct contact of biomass with the liquid mem-

brane, whose components are not seldom toxic, a multimem-

brane hybrid system (MHS) with both extraction and strip-

ping L/L interfaces immobilised in ion-exchange polymer

membranes was suggested by Kedem et al. [48,49]. MHS

was studied for the separation of carboxylic acids by Wodzki

and coworkers[5052].

The aim of this paper is an overview of recent publica-

tions on membrane-based solvent extraction (MBSE) and se-

lected papers on pertraction and classical solvent extraction

(including L/L equilibrium measurements) of organic acids,

both with stress on works, where hollow fiber contactors are

applied or some less common acids are involved. Factors

influencing formulation or selection of the solvent or mem-


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Fig. 4. Scheme of the enzyme-facilitated transport of carboxylic acid through a bulk liquid membrane in a three-phase HF contactor, according Dai et al.[45].

brane phase for specific application will be discussed. Mass-

transfer characteristics of HF contactors will be presented, as

well. Based on experimental data a case study on recovery of

5-methyl-2-pyrazinecarboxylic acid (MPCA), an intermedi-

ate of industrial interest, by simultaneous MBSE and MBSS

will be discussed.

2. Recovery and separation of organic acids,

integrated and hybrid processes

There are several modes of operation of the separation

process to achieve therecoveryor separation of organic acids:

(a) Simple process for the separation of reaction mixtures,

e.g. downstream processing in biotechnologies, or waste

solutions.

(b) Integrated processes where separation is accomplished in

parallel equipment connected to a reactor by circulation

loop. An example of an integrated fermentation process

is shown inFig. 5and will be discussed in Section2.3.

(c) Hybrid systems where reaction(s) and separation are car-

ried out simultaneously in one equipment, as will be dis-

cussed in Sections2.2 and 2.4with an example shown in

Fig. 6.

It is worth to mention one of the first widely studied in-

tegrated processesextractive fermentation for ethanol pro-

duction, which has been intensively studied up to a small

pilot plant stage[5355]. Compared to the continuous con-

ventional fermentation of a 195 g/L glucose medium, the vol-

umetric productivity was more than doubled in an extractive

mode, with no deleterious effects on cell viability, specific

glucose consumption rate or ethanol yield. Despite a longer

effort, the economy of this process was not favourable to be

applied in a large scale[8].A similar situation could occur in

application of extractive processes connected with recovery

of organic acids from fermentation broth or other technolog-

ical streams. The present costs for HF contactors limit the

application of MBSE mostly to higher added value products

or to cases where both raffinate and concentrate could be

economically utilised.

Analytical applications of pertraction through supported

liquid membranes are wide, as reviewed in papers [5662].

The analysis of various organic acids has been studied in

papers[6366], amino acids in papers[6774], acidic drugs

Fig. 5. Schematic flowsheet of the fermentation unit with integrated MBSE and MBSS circuit for recovery of acids (product) from the fermentation broth.


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Fig. 6. Scheme of the three-phase system in a hybrid extractive membrane

reactor for enzymatic transformation of reactant.

[62,7577], herbicides[78]and phenols and their derivatives

in papers[7982]. Equipment with planar SLM[5659]and

SLM in a hollow fiber form[60,62,7578,8284]is used in

analytical applications.

2.1. Recovery of organic acids

Papers on MBSE and MBSS of various types of individual

organic acids and selected papers on their pertraction (mostly

in HF contactors) and extraction are listed in Tables 14.

Chemistry (mechanism) of L/L extraction, MBSE, MBSS

and pertraction are practically the same. Thus, information

on one process could be useful for another of the mentioned

processes. Papers on pertraction of organic acids through liq-

uid membranes facilitated by enzymatic reactions are given

inTable 5.

The recovery of phenol from the hydrocarbon fraction

with a phenol concentration of 24 wt.% by MBSS into an al-

kali solution has been recently applied industrially in Poland[85,86]. The capacity of the plant with two rigs in series,

each with eight parallel HF contactors Liqui Cel 4 in. 28in.

(Celgard) is about 650 kg h1. Both the hydrocarbon raffi-

nate with less than 0.02 wt.% of phenol and the phenolate

concentrate (2530 wt.%) are recycled back to the technol-

ogy producing the waste stream. This probably resulted in a

favourable economy of the process.

Processes for recovery of valuable organic acids of indus-

trial interest from aqueous waste solutions from an enzymatic

resolution process have been developed for dimethylcyclo-

propanecarboxylic acid (DMCCA)[87,88]and 5-methyl-2-

pyrazinecarboxylic acid (MPCA) [89,90] and will be dis-

cussed for the latter acid in Section5. Recovery of DMCCA

from a highly acidic waste solution with pH below 2 contain-

ing about 19 kg m3 of DMCCA by MBSE and MBSS or

pertraction was suggested[88].A solvent with 0.4 kmol m3

of TOA in n-alkanes (dodecane fraction) was used[29,87].

A recovery of more than 90% of DMCCA and a concentrate

with about 200 kg m3 of DMCCA was achieved.

Removal ofp-nitrophenol from an aqueous solution, sim-

ulating wastewater, by MBSE in HF contactors hasbeen stud-

ied by Tompkins and coworkers[91,92].Study on treatment

of wastewater containing nitrophenol by pertraction through

an emulsion liquid membrane is published in paper[93].

Recovery of sulfanilic acid from wastewater by MBSE in

HF modules with the fiber length of 33.5 cm and the inner

fiber diameter of 0.4 mm with the solvent containing 20%

trioctylamine, 30% octanol and 50% kerosene is described in

paper[158].The distribution coefficient of sulfanilic acid is

concentration dependent and its value is 1.42 and 26.03 at the

equilibrium aqueous concentrations 70.2 and 701.2 g m3

,respectively. MBSE was found to be an efficient process with

recovery of acid up to 90% in the given contactor. Removal

of aconitic and oxalic acids from cane molasses and from

mixtures of organic acids by pertraction through supported

liquid membranes studied McMurray and Griffin[114].

Enzymaticreactions on L/Linterfaces open a new interest-

ing way how to achieve separations. Papers on pertraction of

organic acids through liquid membranes facilitated by enzy-

matic reactions, described in Section1, are listed inTable 5.

Some papers will be presented in Section2.2in more detail.

2.2. Separation of organic acids

Separation of mixtures of organic acids by MBSE and

pertraction is discussed in papers presented inTable 6. Some

papers on separation of organic acids by pertraction through

a liquid membrane facilitated by enzymatic reactions are

shown also inTable 5.

Separation of long-chain unsaturated fatty acids, e.g. oleic

and linoleic acids, by MBSEbetweentwosolvents,acetonitril

andn-heptane, has been studied by Matsuba[175].Solvents

flowed countercurrently, acetonitril along the shell and n-

heptane in the lumen of a PTFE microporous tube (i.d. 2 mm,

pore size 1m, tube length 5 m). Introduction of the acid

mixture feed in the middle of the shell was advantageous.At low throughputs the equivalent length of one theoretical

stage was about 0.8 m and the purity of oleic acid of about

76%.

Isono et al. [16,17] studied a new process where

solvent extraction from a charged polymeric membrane

was performed in order to obtain a higher selectivity

by liquidliquid partitioning and electrostatic rejection ef-

fects.A ternary mixture ofN-(benzyloxycarbonyl)-l-aspartic

acid (ZA), l-phenylalanine methyl ester (PM), and N-

(benzyloxycarbonyl)-l-aspartyl-l-phenylalanine methyl es-

ter (ZAPM) was used as the model system. Using a positively

charged membrane, only ZAPM was extracted into the or-

ganic phase and separations between ZA or PM and ZAPM

were achieved. The utility of this hybrid separation system

was demonstrated. Tert-amyl alcohol was used as solvent and

Selemion AMV or ASV membranes. The membrane with a

smaller pore size showed higher selectivity.

Wodzki and Nowaczyk[52]studied separation of propi-

onic and acetic acid in pertraction through a multimembrane

hybrid system. Addition of an extractant, TOPO or TBP, to

n-hexane increased the flux through the multimembrane, but

the value of the separation coefficient decreased. The flux in

binary transport of acetic and propionic acids is larger than

the sum of fluxes of individual acids. It should be stressed that


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Table 1

Papers on MBSE or MBSS of carboxylic acids and selected papers on their pertraction (PT) and solvent extraction (EXT)

Acid Process Solvent (extractant/diluent) Contactor type Literature

Acetic acid MBSE TOA/(MIBK; octanol;n-alkanes) HF [94]

PT Amines/ n-alkanes FSC [24]

PT in MHS (TOA; TOPO; TBP)/hexane FSC [50,52]

EXT (Aliquat 336; TBP; TOPO; Alamine336)/xylene

EC [95]

EXT Tertiary amines/diluents EC [96]

Propionic acid MBSE; PT (SLM) Amines/ n-alkanes PF HF FSC [24]

MBSE TOA/xylene PF HF [97]

PT in MHS (TOA; TOPO; TBP)/hexane FSC [50,52]

Butyric acid MBSE, MBSS TOA/ n-alkanes CF HF [98100]

MBSE, MBSS Amines/(corn oil, oleyl alcohol) CF HF [101]

PT (BLM) TOA/ n-alkanes PF HF [98,102,103]

PT (layered BLM) TOA/n-alkanes DLC [104]

Valeric acid MBSE, MBSS Amberlite LA-2/toluene PF HF [105108]

EXT (Amines; Aliquat 3 36; T BP)/(kerosene; n-

heptane; toluene)

EC [109]

Dimethylcyclopropan-carboxylic acid (DMCCA) MBSE TOA/n-alkanes CF HF [87]

PT TOA/ n-alkanes PF HF [29,87,110]

5-Methyl-2-pyrazinecarboxylic acid (MPCA) MBSE, MBSS TOA/xylene CF HF [89,90,111]PT (layered BLM) TOA/xylene DLC [112]

Succinic acid MBSE n-Butanol FSC [113]

Aconitic, oxalic, malic acids PT (SLM) TBP/Shellsol 2046 FSC [114]

Abbreviations used are explained in Nomenclature.

Table 2

Papers on MBSE or MBSS of hydroxycarboxylic acids and selected papers on their pertraction (PT) and solvent extraction (EXT)


Lactic acid MBSE, MBSS PT Tertiary amines/(n-alkanes, isodecanol, isotridecanol) CF HF PF HF (PT) [115]

MBSE, MBSS Aliquat 336/Shellsol A PF HF [108,116]

MBSE TOPO/kerosene PF HF [117]

MBSE (TOA; TOPO)/(oleyl alcohol,n-hexane) PF HF [118]

MBSE Alamine 336/(kerosene, oleyl alcohol) PF HF [119]

MBSE, MBSS Alamine 336/2-octanol HF [120]

MBSE, MBSS (Amines; Aliquat 336)/(n-alkanes; oleyl alcohol) PF HF [121]

MBSE TOA/xylene CF HF [97]

MBSE TOMAC/oleyl alcohol PF HF [122]

MBSS TOMAC/oleyl alcohol PF HF [123]

MBSE, MBSS TOMAC/1-decanol CF HF [124]

MBSE into capsules with solvent TOPO, TOA, TBP Packed column [14]

PT Tertiary amines/(n-alkanes, isodecanol, isotridecanol) PF HF [115,125]PT (EML) TBP/(isooctane, SPAN80) HF [39]

PT (ELM) Amines/ n-alkanes Agitated vessel [35]

PT (SLM) TOA/xylene FSC [25]

EXT (Amines; TOA; TOPO; TOMAC; TBP)/(kerosene; hex-

ane; toluene; oleyl alcohol)

EC [126]

EXT (Amines; trialkylphosphinoxides)/(kerosene; oleyl alco-

hol)

EC [127]

EXT in situ Alamine 336/oleyl alcohol Agitated vessel [128]

Citric acid MBSE TOA/xylene CF HF [97,129]

PT (BLM) TOA/MIBK PF HF [130]

PT (SLM) Amines/(hydrocarbons, alcohols) FSC [25,131]

PT (ELM) Alamine 336/(n-alkanes and chloroform) Agitated vessel [132]



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Table 3

Papers on MBSE or MBSS of amino acids and antibiotics and selected papers on their pertraction (PT) and solvent extraction (EXT)


Phenylalanine MBSE Aliquat 336/(kerosene, isodecanol) PF HF [133,134]

MBSE, MBSS TOMAC/(n-heptane, hexanol) PF HF [135]

MBSE, MBSS Aliquat 336/xylene HF [136]

MBSE, MBSS D2EHPA/ n-alkanes CF HF [137]

MBSE AOT/oleyl alcohol PF HF [138]

PT (SLM) D2EHPA/ n-alkanes FSC [26]

PT (SLM) D2EHPA/ n-heptane HF [139]

PT (ELM) D2EHPA/dodecane Agitated vessel [36]

PT (ELM) D2EHPA/ n-alkanes Agitated column [140]

PT (BLM) D2EHPA/kerosene DLC [141]

PT (ELM) Agitated vessel [37]

PT (BLM) D2EHPA/ n-alkanes RFC [32]

l-Isoleucine PT (BLM) D2EHPA/kerosene DLC [142]

Phenylalanine, l-isoleucine EXT Reversed micelles with polyoyalkylene

copolymers/(octanol, xylene)

EC [143]

l-Lysine PT (BLM) D2EHPA/ n-alkanes RFC [31]

Tryptophan, dipeptide MBSE PT (SLM) AOT/oleyl alcohol PF HF [138]

Tryptophan MBSE Aliquat 336/Shellsol A PF HF [108]

N-(Benzyloxycarbonyl)-l-

aspartyl-l-phenylalanine methyl

ester

MBSE tert-Amylalcohol FSC [16,17]

Antibiotics: Penicillin G MBSE, MBSS Amberlite LA2/(kerosene, isodecanol) CF HF [144,145]

MBSE, MBSS Amberlite LA2/kerosene PF HF [146]

MBSE, MBSS Amberlite LA2/(butylacetate; decanol) HF [147]

PT PF HF [148]

PT (ELM) Amberlite LA2/kerosene Agitated column [149]

Cephalosporine MBSE Aliquat 336/ n-heptane PF HF [150]

PT (ELM) Aliquat 336/(n-heptane, kerosene) Agitated vessel [38]

Cephalexin [151]

Erythromycin PT (SLM) Decanol FSC [152]

Tylosin PT (BLM) Isodecanol; octanol RFC [33,34]

Bacteriocins (nisin, variacin,

carnocin)

EXT Alkanes, toluene, decanol, butylacetate EC [153]


Table 4

Papers on MBSE or MBSS of other organic acids, phenol and its derivatives and selected papers on their pertraction (PT) and solvent extraction (EXT)


Mevinolinic acid (MV-819) MBSS, MBSE Isopropyl acetate PF HF [154]

4-Methyltiazole, 4-cyanothiazole MBSE Toluene; benzene PF HF [155]

Diltiazem PT (BLM) Decylalcohol PF HF [156]

7-Aminocephalosporanic acid PT (BLM) Aliquat 336/butylacetate DLC [157]

p-Aminobenzenesulfonic acid MBSE TOA/(kerosene, octanol) PF HF [158]

2-Aminoethanesulfonic acid EXT Ionic liquids EC [159]

Nucleotides (adenosine derivatives) PT Quaternary ammonium salt/isooctane DLC [160]

Oxygenates (aromas) from citrus oil MBSE, MBSS Cyclodextrine derivatives PF HF [161]

Phenol MBSE Cyanex 923/kerosene PF HF [162]

MBSE, MBSS Cyanex 923/n-alkanes CF HF [163,164]

MBSE, MBSS 1-Decanol and other solvents CF HF [107,124,165]

MBSE N,N-di(1-methyl-heptyl) acetamide/kerosene PF HF [166]

MBSE Aliphatic alcohols PF HF [167]

MBSS Aromatic hydrocarbons CF HF [85,86]

MBSS MIBK PF HF FSC [168]

PT Cyanex 471X/ n-alkanes PF HF [169,170]

PT (BLM) Alkylcyclohexane PF HF [171,172]

PT (ELM) Shellsol T (paraffinic solvent) Agitated vessel [173]

Nitrophenol MBSE 1-Octanol PF HF [91]

MBSS 1-Octanol PF HF [92]

PT (ELM) Kerosene Agitated vessel [93]



9/30


Table 5

Papers on pertraction of organic acids through liquid membranes facilitated by enzymatic reactions on L/L interfaces

Acid(s) Enzyme(s) Liquid membrane Contactor type Literature

2-Phenoxypropionic, phenylacetic and man-

delic acids

Two lipases Isooctane (layered BLM) DLC [42,43]

Phenylacetic and mandelic acids; pheny-

lacetic acid and 6-amino-penicillanic acid

(separation of acids)

Two lipases 20vol.% octanol inn-heptane (BLM) Three phase PF HF [45]

Aromatic carboxylic acids Two lipases Isooctane and other HC (SLM) FSC [47]

Ionic liquids (SLM) FSC [174]

S,R-ibuprofen (separation of enantiomers) Two lipases Ionic liquids (SLM) FSC [46]

the transport rate in the MHS system is lower than through

a simple liquid membrane due to additional diffusion resis-

tance in ion-exchange membranes.

The separation of penicillin G from phenylacetic acid

(PAA) by pertraction through SLM with Amberlite LA-2 dis-

solved in 1-decanol, supported on a microporous polypropy-

lene membrane was studied by Lee [176]. The individual per-

meability of each component in the mixture was lower thanthat in a single component system. This suggests a strong

transport competition effect between components. The max-

imum separation factor was found to be 1.8 under a liquid

membrane resistance controlled mechanism.

Based on distribution coefficients of individual amino

acids Kelly [177] estimated separation factors as a ra-

tio of individual distribution coefficients for extractants

D2EHPA and dinonylnaphtalenesulfonic acid (DNNSA) dis-

solved in toluene were estimated. Separation factors calcu-

lated for pairs of amino acids were within the range of 2.0

(glycineaspartic acid) to 20.1 (alanineglycine) and should

be validated.

A lipase-facilitated selective and continuous separation ofdifficult-to-separate mixtures of organic acids has been de-

veloped in a HF contactor with BLM [45]. The contactor

consists of two bundles of well-mixed hydrophobic microp-

orous polypropylene hollow fibers. The solvent and separa-

tion mechanism used in this system are described in Section

1andFig. 4. Separation of two binary acid mixtures was

studied: (1) phenylacetic acid (PAA) and mandelic acids; (2)

PAA and 6-aminopenicillanic acid(6-APA). The stripping so-

lution enriched in PAA. The separation factors of PAA over

mandelic acid and PAA over 6-APA were as high as 20 and

10, respectively. Much higher enzyme activities and enzymestability were achieved in the HF contactor due to immobil-

isation of enzyme by adsorption and continuous removal of

the ester produced. The transport rate of PAA in the HF con-

tactor was 224 times higher than the maximum rate measured

in batch experiments.

2.3. Separation of isomers

Separation of isomers, especially enantiomers, attracted

a great interest of researchers. Related papers are listed in

Table 7.Hybrid processes for enzymatic resolution of enan-

tiomers or their derivatives are of great importance and aregiven in Table 8. Selective pertractionof enantiomers through

liquid membranes facilitated by enzymatic reactions on L/L

interfaces, presented in Table 5, can be also used for their sep-

aration. Lipase-facilitated transport of (S)-ibuprofen through

Table 6

Separation of mixtures of organic acids and their derivatives

Acids Separation process Solvent (extractant/diluent) Contactor type Literature

Oleic, linoleic acids MBSE Acetonitril and n-heptane(distribution be-

tween two organic solvents)

HF (single tube) [175]

N-(benzyloxycarbonyl)-l-aspartic

acid, l-phenylalanine methyl ester,

N-(benzyloxycarbonyl)-l

-aspartyl-l

-phenylalanine methyl ester

MBSE from charged membrane tert-Amyl alcohol FSC [16,17]

Acetic and propionic acids PT (MHS with BLM) No carrier/(C6C10 alkanes, toluene, cy-

clohexane, octanol, MIBK)

FSC [51]

(TBP, TOPO, TOA)/n-hexane FSC [50,52]

Penicillin G, phenylacetic acid PT (SLM) Amberlite LA-2/1-decanol FSC [176]

Lactic and citric acids PT (SLM) TOA FSC [25]

Amino acids EXT (D2EHPA; DNNSA)/toluene EC [177]

Succinic and acetic acids EXT Tertiary amine/(octanol;n-heptane) EC [178]

Binary mixtures of lactic, propionic,

dichloroacetic, trichloroacetic, and hy-

drochloric acids

EXT (Primene JMT, tris(2-ethylhexyl)amine,

TOA)/various diluents

EC [179]

Binary mixtures of lactic, glutaric, malic, and

maleic acids

EXT Primene JMT/various diluents EC [180]



10/30


Table 7

Separation of enantiomers, structural isomers and stereo-isomers

Isomers Selector (extractant)/diluent Separation process Contactor type Literature

Leucine N-n-dodecyl-l-hydroxyproline/octanol MBSE PF HF [184]

N-(3,5)-dinitrobenzoyl-leucine (S)-N(1-naphthyl)leucine ester or amide/ hex-

ane

MBSE, MBSS PF HFa [183]

Norephedrine, etc. R,R- andS,S-dihexyltartrate orR,R- and S,S-

tartaric acid/heptane

MBSE PF HF [185]

Propanolol (S,S)-di-n-dodecyltartrate/chloroform MBSE PF HF [108]

o-,p-Nitroaniline orcis-,trans-stilbene Cyclodextrin derivatives in aqueous BLM PT (BLM) PF HF [181]

Phenylalanine Cu(II) N-n-decyl-l-hydroxyproline/(Paranox

100, hexanol, decane)

PT (ELM) Batch mixer [186,187]

Amino acids Crown ethers/(2,2,4-trimethylpentane or

chloroform)

PT (layered BLM) DLC [188,189]

Series of amino acids hydrochlorides Nopol or (2S)-()-methyl-1-butanol PT (SLM) FSC [190]

Triptophan; -phenylethylamine Chiral phosphoric and phosphonic acid es-

ters/dihexylether

PT (SLM) FSC [72,74]

Mandelic acid Cinchonidine/(dodecane, decanol 1:1) PT (BLM) DLC [191]

Abbreviations used are explained in Nomenclature.a Hydrophilic fibers.

SLM based on ionic liquids is an example of this novel ap-proach[46]. Separation of structural isomers of o- and p-

nitroaniline and stereoisomers ofcis- and trans-stilbene by

pertraction in a HF contactor were presented by Mandal et al.

[181].Kinetic resolution of chiral aromatic amines with-

transaminase using an enzyme-membrane reactor combined

with MBSE of ketone in HF contactor increased enantiosep-

aration, as shown in paper[182].

Chiral selectors developed for chromatography could be

promising for larger scale separation of enantiomers by

MBSE in HF contactors. Chiral selectors derived from N-

(1-naphthyl)leucine have been used in a HF contactor with

hydrophilic fibers (Sepracor) to separate the enantiomers of

amino acid derivatives[183]. Enantiomeric purities exceed-

ing 95% have been obtained in a single pass through the

system.

A successful industrial application of hybrid system with

a HF contactor for production of the drug dilthiazem inter-

mediate was reported by Lopez and Matson [44]. A plant wasbuilt for enzymatic resolution of dilthiazem chiral interme-

diate in an extractive enzymatic membrane reactor. This is

the first published industrial application of HF contactors in

a hybrid bioreactor. A two (three) phase system involved in

this process is schematically shown inFig. 6.The enzyme is

entrapped in the macroporous sponge part of the hydrophilic

hollow fiber membrane made of a polyacrylonitrile copoly-

mer. Theenzyme is loadedto themembraneduring ultrafiltra-

tion of an aqueous enzyme solution flowing at the beginning

in the shell of a HF contactor. A dense layer of the mem-

brane (skin), retaining enzyme, is on the inner side of the

hollow fiber. After immobilisation of the enzyme in the wall,

a toluene solution of reactant, racemic ()-trans-methyl-

methoxyphenylglycidate, is flowing in the shell. In the fiber

lumen an aqueous buffer solution with bisulfite anion flows

countercurrently. The enzymatic deesterificationcatalysed by

lipaseproceedson theL/L interface. Thedeliberated (2S,3R)-

Table 8

Hybrid processes with enzymatic resolution of enantiomers or their esters

Enantiomers or

their esters

Preferentially transported

or formed compound

Enzyme Solvent

(membrane)

Separation

process

Contactor

type

Literature

()-trans-Methyl-

methoxyphenyl-glycidatein toluene

(2S,3R)-methoxyphenyl-

glycidic acid

Lipase Aqueous buffer MBSS PF HFa [44]

Phenylalanine methylesters d-Phenylalanine

methylester

-Chymotrypsin (D2EHPA, TOMAC,

AOT)/isooctane

MBSE PF HF [192]

1-Phenyl-1,2-ethanediol 2-Hydroxy-acetophenone Glycerol dehydroge-

nase

Hexane MBSE PF HF [193]

Phenylalanine methylesters l-Phenylalanine -Chymotrypsin solu-

tion in emulsion

n-Alkanes, cyclohexane,

kerosene

PT (ELM) Batch mixer [194]

Phenylalanine isopropylesters

hydrochloride

R-Phenylalanine Esterase S ubtilisin

Carlsberg

N,N-Diethyldodecan-

amide/dodecane

PT (SLM) PF HF [195]

Ibuprofen (S)-Ibuprofen Two lipases Ionic liquids PT (SLM) FSC [46]

1-(2-Naphthyl)-ethanol ester (S)-1-(2-Naphthyl)-

ethanol

Lipase Perfluoro-hexanes PT (layered BLM) U-tube [196]

Abbreviations used are explained in Nomenclature.a Hydrophilic fibers.


11/30


methoxyphenylglycidic acid is extractedto the buffer. The re-

quired product (2R,3S)-methyl-methoxyphenylglycidate re-

maining in toluene is an intermediate for dilthiazem synthe-

sis. In the commercial plant with a capacity of 75 tonnes per

year, which has been built in Japan, 24 contactors with a

surface area of 60 m2 each are installed.

Two chiral alcohols, (1R)-(+)-6,6-dimethylcyclo-[3.1.1]hept-2ene-2-ethanol (nopol) and (2S)-()-methyl-1-

butanol, immobilised in the pores of a polyethylene film

were used for the enantioselective transport of amino acid

hydrochloride as described by Bryjak et al. [190]. The

stereoselectivity of the pertraction varied from 0.39 to

1.52 depending on both the type of the chiral membrane

phase and the properties of the amino acid. SLM with

nopol was more efficient. Enzymatic resolution of racemic

1-phenyl-1,2-ethanediol was carried out by enantioselective

oxidation combined with MBSE in HF contactor. The

product inhibition is overcome by continuous extraction

[193].

Enantioselective transport of ibuprofen through SLM withionic liquid facilitated by enzyme (lipase) catalyzed reactions

on interfaces was studied by Miyako et al.[46,47]. Resolu-

tion of 1-(2-naphthyl)ethanol was achieved by a combina-

tion of an enzyme-catalysed kinetic resolution with a flu-

orous triphasic separative reaction[196]. Perfluorohexanes

were used as a liquid membrane. Highly enantioselective hy-

drolysis of (R,S)-phenylalanine isopropyl ester by Subtilisin

Carlsberg was achieved in a continuous production of (S)-

phenylalanine in a HF contactor with liquid membrane as a

reactor[195].

2.4. Bioproduction of organic acids integrated withseparation or downstream processing

A scheme of an integrated process for the fermentation

production of organic acids and MBSE with MBSS for re-

covery of acid from a broth is shown in Fig. 5. The installed

periodical bleed and feed operation of the fermenter may

lead to continual or semicontinual operation of fermentation

[197]. Removal of the product from a broth can avoid prod-

uct inhibition and increase the productivity of fermentation

[101,198,199]. The solvent can be regenerated by stripping,

as shown in Fig. 5, or in case of volatile acids (acetic and pro-

pionic acid) by vacuum distillation [200]. More lipophilic

acids with low water solubility in undissociated form, e.g.

DMCCA and MPCA, can be separated from the loaded strip-

ping solution by decreasing its pH well under acid pKawhen

organic layer of acid is formed. Lean stripping solution can

be recirculated to the MBSE. Papers on formation of inte-

grated or hybrid systems with MBSE, some of them using

HF contactors, are shown in Table 9.Design and optimisa-

tion of reactive extraction for organic acids recovery is also

addressed in literature[201203].

A fully integrated process for the microbial production

and recovery of the aromatic amino acid l-phenylalanine

is presented in papers[199,218,219]. Using a recombinant

l-tyrosine (l-Tyr) auxotrophic Escherichia coli production

strain, a fed-batch fermentation process was scaled-up from

a 20-L scale to 300-L pilot scale. In technical scale fer-

mentation l-phenylalanine was continuously recovered via

a fully integrated reactive extraction system with simulta-

neous MBSE and MBSS in HF contactors. This prevented

product inhibition of microbial l-phenylalanine production.Concentration factor higher than 4 was achieved in the strip-

ping phase. A doubling ofl-Phe/glucose yield was observed

when kerosene/D2EHPA was added to the fermentation so-

lution in the bioreactor to simulate a fully integrated l-

phenylalanine separation process. The final product purity

after l-phenylalanine precipitation was higher than 99%.

Production of propionic acid by fermentation is hindered

by low productivity and product inhibition[221]. An extrac-

tive fermentation process using a secondary amine extractant

and a HF contactor to selectively extract propionic acid from

the fermentation broth was developed to produce propionate

from lactose by Propionibacterium-Acidipropionici [209].

Compared to the conventional batch fermentation, the ex-tractive fermentation had five-fold higher productivity, more

than 20% higher propionate yield, higher final product con-

centration (75 g L1 or higher), and higher product purity.

Acetate and succinate production in the extractive fermen-

tation were significantly reduced. The improved fermenta-

tion performance can be attributed to the reduced product

inhibition and a possible metabolic pathway shift to favour

more propionic but less acetic and succinic acid production.

The process was stable and gave consistent long-term perfor-

mance over the 1.5-month period studied.

Cell immobilization to increase productivity and extrac-

tive fermentation to reduce product inhibition were investi-gated[198]. Propionic acid concentration in the extractive

fermentation was maintained at 13 g L1 by concurrent ex-

traction with a liquid extractant consisting of 40 vol.% trilau-

rylamine in oleyl alcohol (a final concentration of 71 g L1

propionic acid was obtained in non-extractive mode). Yields

of propionic and acetic acids were doubled and higher overall

productivities were obtained in the extractive fermentation.

The extractant also exhibited selectivity for propionic acid

over acetic acid, thus partially purifying the former. In both

fermentation modes, productivity was enhanced by cell im-

mobilization in calcium alginate beads. An economic analy-

sis of a modified version of the fermentation based on several

favourable assumptions showed that the extractive fermen-

tation could, at best, approach economic feasibility. For the

assumed conditions, the production cost of the propionic acid

was 1.16 US$ kg1. This cost was reduced to 0.94 US$ kg1

when the value of the acetic acid by-product was included.

An extractive fermentation process for production of bu-

tyric acid from glucose, using immobilised cells ofClostrid-

ium tyrobutyricum in a fibrous bed bioreactor, was developed

[101].The solvent with 10 vol.% of Alamine 336 in oleyl al-

cohol was used. Simultaneous MBSE and MBSS were done

in HF contactors forselective removal of butyric acid from the

fermentation broth. The fermentation pH was self-regulated


12/30


Table 9

Production of organic acids by extractive fermentations with integrated or in situ extractive separation of acid or with downstream recovery of acid from broth

Product Process for separation of acid Solvent (extractant/diluent) Contactor type Literature

Acetic and butyric acids PT (SLM) TOPO/kerosene FSC [204206]

EXT (Oleyl alcohol, isodecanol)/ kerosene EC [207]

Acetic acid MBSE Amines/(MIBK, chloroform) HF [94]

Propionic acid MBSE TOPO/kerosene PF HF [24,208]

EXT Trilaurylamine/(octanol, dodecanol,oleyl alcohol)

EC [200]

MBSE HF [198]

MBSE, MBSS Di-tridecylamine/oleyl alcohol PF HF [209]

Butyric acid MBSE, MBSS Amines/(corn oil, oleylalkohol) CF HF [101]

EXT in situ Hostarex A327/oleyl alcohol Agitated vessel [210,211]

Lactic acid MBSE in situ Alamine 336/oleyl alcohol HF in fermenter [119]

MBSE TOMAC/oleyl alcohol PF HF [122]

MBSE TOA, Amberlite LA2 PF HF [121]

PT (EML) TBP/isooctane, various other solvents

tested

PF HF [39]

EXT Alamine 336/oleyl alcohol EC, agitated vessel [212215]

EXT in situ Alamine 336/oleyl alcohol Agitated vessel [128]

EXT and electrodialysis (Amines, Cyanex 923)/(kerosene,

butylacetate, oleyl alcohol)

EC [127]

MBSE TOPO; TOA + TBP Packed column with capsules [14]

Gibberellic acid EXT Polyalkoxylates Mixer/settler [216,217]

l-Phenylalanine MBSE, MBSS 1030 vol.% D2EHPA/kerosene CF HF [199,218,219]

Penicillin G MBSE, MBSS or electrodialysis Amberlite LA2/(kerosene, isode-

canol)

PF HF [144]

Cephalosporin MBSE, MBSS Aliquat 336/ n-heptane PF HF [38]

Lincomycin EXT Octanol, decanol EC [220]


at pH 5.5 by an acid removal by extraction. Compared with

conventional fermentation, extractive fermentation resulted

in a much higher product concentration in stripping solution

of >300gL1 and product purity of 91% was achieved. It

also resulted in higher reactor productivity 7.4 g L1

h1

andbutyric acid yield of 0.45, g/g. Without on-line extraction to

remove the acid products, at the optimal pH of 6.0, the final

butyric acid concentration was only similar to 43.4 g L1,

butyric acid yield was 0.423, g/g, and reactor productivity

was 6.8gL1 h1. These values were much lower at pH 5.5:

20.4gL1, 0.38, g/g, and 5.11 g L1 h1, respectively. The

improved performance for extractive fermentation can be at-

tributed to the reduced product inhibition by selective re-

moval of butyric acid from the fermentation broth. The sol-

vent was found to be toxic to free cells in suspension, but not

harmful to cells immobilised in the fibrous bed. The process

was stable and provided consistent performance for the entire

2-week period of study.

Lactic acid production from cellulosic biomass by cellu-

lase and Lactobacillus delbrueckii in a fermenter-extractor

employing a bundle of microporous hollow fibers placed in

situ in the fermenter was studied[119].This bioreactor sys-

tem was operated under a fed-batch mode with continuous

removal of lactic acid by extraction. A solvent mixture of

20% Alamine 336, 40% oleyl alcohol, and 40% kerosene

was found effective in the extraction of lactic acid. A change

of pH from an initial value of 5.0 down to 4.3 improved the

overall performance of the simultaneous saccharification and

extractive fermentation over that of constant pH operation.

Recovery of diltiazem from an alkaline aqueous feed so-

lution as diltiazem malate in a l-malic acid containing aque-

ous strip stream using pertraction in a three phase hollow

fiber contactor has been studied [156]. The resistance to mass

transfer is primarily controlled by the feed side mass-transfercoefficient due to the high partition coefficient of diltiazem

for a decyl alcohol liquid membrane and the instantaneous

reaction in the strip side of the membrane. However, due

to larger thickness of the liquid membrane, the membrane

resistance is quite important, as well. In spite of the low dilti-

azem concentration in the feed solution, high concentrations

of diltiazem malate in the stripping solution were achieved. A

suggested diffusion model describes effectively the observed

behaviour of the HF contactor. A preliminary cost analysis

and comparison with packed bed column solvent extraction

shows that pertraction can be competitive.

2.5. Extractive biotransformations of organic acids in

integrated and hybrid systems

The chemical and pharmaceutical industry has primarily

relied upon established chemical methods for the synthesis

of target products and their intermediates, but is now turn-

ing more and more to enzymatic and biotechnological fer-

mentation processes. For the industrial implementation of

many biotransformations alternative methods are develop-

ing. Among them extractive separations employing solvents

in two and three phase systems integrated with transformation

or even forming hybrid system with biotransformation and


13/30


separation occurringin onespace. Good insight to this subject

can give books[2,4,222]and overview papers[3,7,223,224]

and a general book on biotransformations [225].Papers on

biotransformations of organic acids integrated with extrac-

tive separation of the product or realized in hybrid systems

are presented in Table 10. References to papers on hybrid

processes with enzymatic resolution of esters of enantiomersare given inTable 8.

An enzyme reactor integrated with MBSE in a HF contac-

tor was used for the synthesis ofN-(benzyloxycarbonyl)-l-

aspartyl-l-phenylalaninemethyl ester (ZAPM), the precursor

of the artificial sweetener, aspartame[230,231].The synthe-

sis of ZAPM in the reactor proceeded by an enzymatic re-

action between N-(benzyloxycarbonyl)-l-aspartic acid and

l-phenylalanine methyl ester in the aqueous phase. The syn-

thesized ZAPM in the aqueous phase was mainly extracted

into the organic phase and the aqueous phase concentration

could be kept low. This results in high conversion of ZAPM

in this system. The reaction model, which was based on the

material mass balance equations, was discussed to estimatethe performance of the extractive enzyme reactor system. It

was shown that, 1-hexanol and 1-heptanol were proper sol-

vents for this system[19]. An alternative approach with in

situ extraction and solvent removal through a microfiltration

membrane[19]is discussed in the introduction. Murakami

and Hirata[232]studied the same system and used in situ

extraction with butylacetate in an integrated mixer-settler. A

model of the enzymatic synthesis of taste dipeptides with si-

multaneous extraction in a HF contactor is presented in paper

[235].

Conversion of fumaric acid (FA) to l-malic acid (LMA)

was carried out in a bioreactor divided by two supportedliquid membranes into three compartments feed, reaction

and product [227]. SLM between the feed and reaction

compartments was made of TOPO (10 vol.%) in ethyl ac-

etate and was selective toward the substrate, fumaric acid.

The reaction/product compartments SLM, made of D2EHPA

(10 vol.%) in dichloromethane, was selective toward the

product, l-malic acid. Yeast engineered to overproduce the

enzyme fumarase wasimmobilised in smallglasslike beads of

the alginatesilicate solgel matrix and placed in the reaction

compartment and served as the catalyst. The conversion of

almost 100%, while in the industrial process only 70%, was

achieved. In contrast to the existing industrial biocatalytic

process resulting in l-malic acid salts, direct production of

the free acid is described.

3. Formulation of solvent and liquid membrane

Solvents used in the extraction of organic acids are mostly

not single components. The physical solubility of more hy-

drophilic acids in organic solvents is usually low. The dis-

tribution coefficients of such acids, like acetic acid, lactic

acid, and phenylalanine, in common hydrocarbon solvents or

ethers and higher alcohols, are well below 1. The addition of

solvation or complexing agents extractant (in case of liq-

uid membranes called carrier) to the base solvent diluent

can increase the partitioning of acid into the organic phase.

Several acidextractant complexes have a limited solubility

in the solvent resulting in the formation of a precipitate or a

second organic phase similarly as in the extraction of lactic

acid with TOA inn-alkanes. Selection of a proper diluent oran additional co-solvent, a modifier, can solve this problem.

An example is the useof a higher alcohol modifier, like isode-

canol in case of extraction of lactic acid with TOA extractants

[115].

Theselection of solventsfor theextraction of organic acids

or for their pertraction (the solvent forms a liquid membrane)

and some related general aspects are discussed in papers

[4,12,200,228,240243]. Computer-aided solvent design for

extractive fermentation directed mostly to ethanol fermenta-

tion is presented by Wang and Achenie [244]. In the selection

and formulation of the solvent several aspects should be con-

sidered for the given separation. Some of them will be dis-

cussed below together with solvents used in various systemslisted in overview tables.

3.1. Extractants

As follows fromTables 1 to 10agreat variety of solvents

and extractants were studied in extraction of organic acids.

The most important extractants (carriers) used in formulation

of solvents for MBSE, pertraction or extraction of organic

acids, with references to selected papers on L/L equilibrium

in these systems, are presented inTable 11.

Less common carriers of amino acids as microemul-

sions [138] and reverse micelles [135,245] were also studied.Oligomeric extractants (PPO, PEO) and their block polymers

forming reverse micelles have been examined for the trans-

port of phenol[246]and amino acids (Phe, isoleucin)[143].

Ionic liquids as solvents or extractants of organic acids are

discussed in Section3.3.

Matsumoto et al. observed synergistic extraction of lactic

acid[247]and other organic acids[248]when a mixture of

alkylamines and TBP was used. The value of the distribu-

tion coefficient of lactic acid in the solvent with 3 kmol m3

of TBP and 0.3 kmolm3 of TOA in n-hexane was 3.4

while for single extractants in n-hexane this value was well

below 1.

Higher concentration of the extractant (carrier) does not

necessarily leads to an increase of the mass-transfer rate de-

spite the fact that the value of the distribution coefficient

increases proportionally. With increasing concentration of

the carrier (TOA) from 0.2 to 0.6 kmol m3 the flux of bu-

tyric acid through a layered bulk liquid membrane increased

only by 16%, while the product of the diffusion coefficient

and the distribution coefficient (theoretical permeability) in-

creased 2.7 times[104]. Such behaviour can be related to

the kinetics of reactions of formation and/or decomposition

of the complexes [26,104,112,269] and will be discussed

below.


14/30

Table 10

Biotransformations of organic acids integrated with extractive separation of the product or realized in hybrid systems

Product Carbon source or reactant(s) (micro-

organism or biocatalyst)

Process for separation of the product Solvent

Itaconic acid Citric acid (Aspergillus terreus) Hybrid bioreactor with two SLM (D2EHPA, TOA)/(octanol;

dichloromethane)

Fumaric acid l-Malic acid (Sacharomyces cerevisiae) D2EHPA/dichloromethane

-Hydroxyisobutyric acid 2-Methyl-1,3-propanediol (Acetobacter

alei)

EXT TOPO/isooctane screening of

solvents

MBSE TOPO/isooctane

N-(Benzyloxycarbonyl)-l-aspartyl-

l-phenylalanine methyl ester

N-(Benzyloxycarbonyl)-l-aspartic

acid and l-phenylalanine methyl ester

(thermolysin)

MBSE tert-Amylacohol

EXT into dispersion + MF Hexanol, heptanol

EXT in situ Butylacetate

N-Formyl-l-aspartyl-l-

phenylalanine methyl ester

N-Formyl-l-aspartic acid and l-phenyl-

alanine methyl ester (thermolysin)

EXT in situ 1-Butanol

Dipeptide aspartam (ZalaPheOMe) ZAlaOH and PheOMe (thermolysin) EXTin situ Ethyl acetate

MBSE

Isovaleraldehyde Isoamyl alcohol (Gluconobacter oxy-

dans)

MBSE Isooctane

S-Phenylethanol Acetophenone ( dehydrogenase f rom Can-

dida boidinii)

MBSE Isooctane

2-Phenylethanol Phenylalanine (Sacharomyces cerevisiae) EXT Dibutyl sebacate

EXT in situ Oleic acid

3-Cyanobenzoic acid 1,3-Dicyanobenzene (hydratase from

Rhodococcus)

EXT Ionic liquid



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Table 11

The most important extractants (carriers) used in the formulation of solvents for MBSE, pertraction or extraction of organic acids and some related papers on

L/L equilibria in these systems

Abbreviation Trade name Extractant (carrier) Acid type Literature on L/L equilibria

Simple organic solvents (non-reactive) Carboxylic acids [240]

Phenol [165]

Amines and their salts Carboxylic and hydroxycarboxylic acids [109,241243,249252]

TOA Trioctylamine Carboxylic and hydroxycarboxylic acids [253258]Alamine 336 Trialkylamines with C8 and C10 n-

alkyls

Carboxylic and hydroxycarboxylic acids [96,212,259,260]

Hostarex A327 Trialkylamines with C8 to C12 n-

alkyls

Carboxylic acids [87]

Amberlite LA2 Di-alkylamines with branched

C12C15alkyls

Carboxylic acids [261,262]

Antibiotics [4,263]

TOMAC Trioctylmethylammonium chloride Carboxylic acids amino acids [264,265]

Aliquat 336 Tri-alkylmethylammonium chlo-

ride

Carboxylic and hydroxycarboxylic acids [95]

Amino acids [133]

Antibiotics [157]

D2EHPA Di-2-ethylhexylphosphoric acid Amino acids [26,36,266,267]

TBP Tri-n-butyl phosphate Carboxylic and hydroxycarboxylic acids [126,240,247]

TOPO Tri-n-octylphosphine oxide Carboxylic acids [268]

Cyanex 923 Tri-n-alkylphosphine oxides with

C6 and C8 n-alkyls

Phenol [163]

Another phenomenon arising from an increase of the car-

rier concentration in the LM phase is aggregation or forma-

tion of a microemulsion, which can block the interface re-

sulting in lower diffusion coefficients. With increasing con-

centration of D2EHPA in LM the value of the distribution

coefficient of phenylalanine increases proportionally. How-ever, the dependences of the flux through both the extrac-

tion and stripping interface of the layered BLM go through a

maximum [12]. This can be probably related to the formation

of a microemulsion observed at higher D2EHPA concentra-

tions as it was also observed in pertraction of phenylalanine

through SLM[26].

The solubility of extractant (carrier) in aqueous solutions

is an important parameter influencing its losses. It is con-

nected also with the solvent toxicity and compatibility and

will be discussed in Section 3.4. A low solubility of D2EHPA

in metal extraction applications, where solutions with high

salt concentrations and acidities are involved, may be not

the case in biotechnology applications where a low salinityand nearly neutral pH is typical. The solubility of D2EHPA

in aqueous solutions strongly depends on the salt concen-

tration. In pure water the solubility of D2EHPA is as high

as 956 ppm, in 0.1kmolm3 sodium sulphate solution it is

304 ppm whereas it is only 12 ppm in a 1 kmol m3 sodium

sulphate solution [40].Luetal. [270] published lower value of

D2EHPA solubility in waterat 25 C,whichis87.0gm3 and

at pH 1.98 is 52.7 g m3. Solubility of D2EHPA decreases

with increasing concentration of chlorides and HCl. Rela-

tively high solubility of D2EHPA results in a low lifetime of

SLM[26].

3.2. Diluents and modifiers

To find a suitable extractant (carrier) forming a com-

plex with the target solute is only half of the success. The

soluteextractant complex has to be soluble in the diluent

forming with the extractant a solvent. The achievement ofthis goal requires in many cases selection of an appropriate

diluent or addition of a modifier to the solvent, e.g. isodecanol

to n-alkanes and trioctylamine (TOA) in the solvent for lactic

acid [115]. The diluent type may have a great influence on the

solvent performance. In extraction of MPCA from solutions

with higher content of mineral salts with solvents contain-

ing TOA, the value of the distribution coefficient is much

higher for xylene as a diluent than forn-alkanes[271].When

considering separationintegrated with bioprocesstoxicity as-

pects should be taken into account, as discussed in Section

3.4.Lower alcohols, which are popular modifiers, should be

avoided. Isotridecanol, available as a technical product (Uni-

par, NL), is a good compromise[272].

The diluent effect in extraction of organic acids is ad-

dressed in papers[94,96,126,178,247,268]. The diluent ef-

fect in systems with enzymatic reactions studied Miyako et

al.[46,47]. In extraction of lactic acid with tertiary amines,

the value of the distribution coefficient of a 50% mixture of

Alamine 336 with oleyl alcohol was found to be higher than

that of pure amine[212].

Addition of 30 wt.% of isodecanol to the solvent with

0.4 mol dm3 of Hostarex A327 changed completely course

of concentration dependence of the distribution coefficient,

which value was increasing with decreasing concentration


16/30


of DMCCA in aqueous phase[29,87]. For the solvent with

0.4 mol dm3 of TOA inn-alkanes the value of the distribu-

tion coefficient of DMCCA was decreasing with decreasing

concentration of acid.

3.3. Ionic liquids

Ionic liquids (IL) are composed of organic cations and ei-

ther organic or inorganic anionsthat remainliquidovera wide

temperature range, including room temperature [273,274].

ILs are a new group of solvents or extractants of great interest

recently studied as potential green solvents [273,275277].

Practically zero vapour pressure of IL and temperature sta-

bility makes them attractive solvents in many applications

as reaction medium. A higher viscosity at room tempera-

tures could be their less favourable property. Solvent extrac-

tion of organic acids by ionic liquids was studied in papers

[278281], erythromycin by Cull et al.[239]and chlorophe-

nols by Bekou et al. [282]. Transport of amines and neutral

organic substances through liquid membranes from IL is ofconcern in papers of Fortunato et al. [283] and Branco et

al.[284].Pertraction of organic acids through liquid mem-

branes facilitated by enzymatic reactions on L/L interfaces

using IL as a liquid membrane was studied by Miyako et al.

[46,174].Tailoring of ionic liquids to achieve good partition-

ing of target solutes and acceptable viscosity of IL may lead

to interesting results.

Experiments with developmental IL show promising

results in extraction of organic acids, especially of lactic

acid [279281]. In extraction of butyric acid, lactic acid

and phenol fairly higher distribution coefficients were found

for solvents with tested developmental ionic liquid IL-Acompared to the solvents containing tertiary amines. The

value of the distribution coefficient of lactic acid is up to

30 at lower acid concentrations, what is promising. IL-A

acts as an extractant forming undissociated lactic acid/IL-A

complexes 1:1 and 2:1 (lactate anions are not extracted)

[281]. In the pertraction of LA through SLM the value of the

overall mass-transfer coefficient increases with decreasing

concentration of lactic acid in the aqueous phase what cor-

relates with increasing value of its distribution coefficient.

Increased concentration of the carrier IL-A did not change

the value of the mass-transfer coefficient in pertraction

of LA contrary to the increased value of the distribution

coefficient. This may indicates that the slower kinetics of theinterfacial reaction in decomposition of the complex plays a

role or higher viscosity of membrane is responsible of this.

Separation of taurine (2-aminoethanesulfonic acid) and

sodium sulfate by leaching a solid mixture by ionic liquids

is another example of their application[159].Dialkylimida-

zolium chloride ionic liquid as leaching agent and organic

solvent as precipitating agent (lower alcohols, like ethanol,

are effective) were developed. Selective separation of taurine

from a solid mixture containing a large amount of sodium

sulfate could be realized with 6798.5% yield in a single

separation step.

3.4. Toxicity and compatibility of solvent

Toxicity of the solvent for microorganismsor its inhibitory

effect on the catalytic activity of enzymes or the biologic ac-

tivity of the product are important properties of the solvent,

which have to be considered in their evaluation. Papers con-

cerning these items for the solvents or their components arelisted inTable 12.

The paraffin (probably paraffinic oil, not specified)

severely reduces the biological activity of the extracted bac-

teriocin nisin, while toluene, kerosene and isooctane were

found suitable[153].Strategies for reducing solvent toxicity

in extractive fermentations are discussed in paper[213]. Co-

immobilization of soybean oil with cells in carrageenan gel

beads decreased greatly toxic effect of Alamine 336 in lactic

acid fermentation. Toxicity of tertiary amine Alamine 336 to

Lactobacillus delbreuckiwas suppressed by the second stage

extraction of amines with oleyl alcohol before returning the

broth to the fermentation[212].

Logarithm of the distribution coefficient of a given com-pound in the n-octanol/water system, log P, is traditionally

used as a simple criterion to guide the choice of solvents for

biphasic enzymatic reactions from point of view of their bio-

compatibility with enzyme[200,285]. However recently, it

was found that log Pis not a very reliable parameter for the

solvent choice for enzymatic transformations[286].

Wider screening of 17 solvents and their components for

their toxicity toRhizopus arrhizusshowed that solvents with

tertiary amines (HostarexA327, TOA), secondaryamine with

isotridecanol as modifier and pure trihexylphosphate (THP)

are suitable from point of view of biomass compatibility

[272].Toxicity of alcohols decreased with increasing molec-ular mass. Octanol and isodecanol and solvents containing

them are toxic. Isotridecanol is medium toxic. Earlier study

[287] showed that TBP is practically lethal for fungi. Siebold

etal. [127] have found that except kerosene and oleyl alcohol,

the biocompatibilityof otherchemicalstested was unsatisfac-

tory for variousLactobacilli studied. Demirci et al.[39] tested

toxicity of various solvents in lactic acid biofilm fermenta-

tions withLactobacillus casei performed in solvent-saturated

media and found solvent with 5 vol.% of TBP in isooctane

acceptable. This result compared with TBP toxicity to fungi,

where TBP was found lethal, shows that toxicity tests should

be done for every microorganism of interest and cannot be

extrapolated.

Tong et al.[264]suggest to use a solvent with relatively

toxic extractant TOMAC in oleyl alcohol and remove dis-

solved TOMAC in adsorption column with ion-exchange

resin Amberlite IR-120B before returning the broth to fer-

menter. This resulted in satisfactory extractive fermentation

of lactic acid. A similar approach, but with L/L extraction of

secondary amine dissolved in the broth by oleyl alcohol in

the second stage before its returning to fermenter, was used

by Jin and Yang[209]in propionic acid production. Immo-

bilization of cells into calcium alginate gell reduces toxicity

of the solvent to microorganisms[198].


17/30


Table 12

Papers concerning toxicity of solvents or their components to micro-organisms or their compatibility with enzymes

Target product Micro-organism or enzyme Solvent or its components Literature

Propionic and acetic acids Propionibacterium acidipropionici Amine extractants, TOPO, solvents in kerosene [24]

Trilaurylamine/(octanol, dodecanol, oleyl alco-

hol)

[200]

Propionic acid Propionibacterium-acidipropionici Di-tridecylamine/oleyl alcohol [209]

Butyric acid Clostridium butyricum Hostarex A327 in oleyl alcohol; oleyl alcohol;trihexylphosphate; isotridecanol

[210]

Alamine 336/oleyl alcohol [101]

Lactic and itaconic acids, biomass grows Bacteria, yeasts, and fungi two of them each 11organicsolvents with5 extractants andsingle

diluents and modifiers

[287]

Lactic acid VariousLactobacilli (Amines, Cyanex 923)/(kerosene, butylacetate,

oleyl alcohol)

[127]

Lactobacillus delbreucki Tertiary amines [3]

Alamine 336/oleyl alcohol [128,212,213]

Rhizopus arrhizus 17organic solventswith 5 extractants andsingle

diluents and modifiers

[272]

Lactobacillus casei subsp. rhamnosus Amine extractants, TOPO, TBP, various dilu-

ents, Span 80

[39,288]

TOMAC/oleyl alcohol [264]

Lactobacillus rhamnosus Aliquat 336/kerosene [289]

TOPO, TOA + TBP in encapsulated solvents [14]

3 ionic liquids, toluene, hexane [290]

-Hydroxy-isobutyric acid Acetobacter alei (TOPO, T OA, A liquat 3 36)/(hexane, d odecane,

isooctane, oleyl alcohol)

[228]

2-Phenylethanol Sacharomyces cerevisiae Oleic acid [238]

Alcohol (reduction of ketone) Three enzymes 10 single component organic solvents [286]

Higher alcohols as isotridecanol and oleyl alcohol are

preferable modifiers or diluents for extractants when consid-

ering toxicity. Their higher viscosity is less favourable and

possibly compromise to use them in combination with the

diluent of lower viscosity as dodecane fraction could work.

3.5. Co-transport and competitive transport (selectivity)

Co-extraction of mineral acids and other components of

the feed can influence transport rate of target acid and its

purity. Co-extraction of H2SO4and competitive extraction of

HCL during pertraction of lactic acid and MPCA was studied

by Kubisova et al.[291]and in papers[90,292], respectively.

In pertraction of MPCA from feeds with mixed salts and

constant ionic strength the flux of MPCA through BLM with

carrier TOA dropped by one order of magnitude when the

concentration of chlorides increased from 0 to 1 kmol m3.

The ratio of the fluxes of mineral acids to the flux of MPCA

increased from 1 to 4[112]. Thus, in MBSE of MPCA with

amines it is important to avoid the presence of chlorides in

the treated solution.

Competitive uptakes of lactic acid and glucose have been

measured for the extractant Alamine 336 in various diluents

[293].The extent of water coextraction depends strongly on

the diluent used, and larger amounts of water coextracted

correspondto larger uptakes of glucose. Co-extraction during

reactive extraction of phenylalanine using Aliquat 336 was

studied in paper[294].

Water transport or formation (in neutralisation reactions)

should be taken into account in material balances of the sys-

tem[26,89,90,137].It decreases the concentration factor of

the target solute achieved in extractive separation.

4. Membrane contactors

There are two main types of hollow fiber (HF) contactors,

those with parallel flow or cross-flow of phases. A cylindrical

HF contactor with cross-flow of phases is shown in Fig. 7.

More details on their construction and sizes available are

presented in the producer web site [295]. Reviews on two-

phase HF contactors are presented in works [5,10,11,296].

Three phase HF contactors for pertraction are described in

papers[6,2729,297].

HF contactors have a large interfacial area per unit vol-

ume of the contactor without requirement of dispergation of

one phase, what can be advantageous in systems sensitive to

emulgation[123,163].The volume ratio of phases could be

varied practically without limitations. Disadvantage of HFcontactors is connected with additional mass-transfer resis-

tance introduced by porous wall(s) immobilising L/L inter-

face(s). Some problems with swelling of HF and especially

of potting material of HF in solvents may occur.

The function of contactors in the simultaneous MBSE and

MBSS with an arrangement as shown in Fig. 3,is coupled.

They react similarly as a pertractor with a supported liquid

membrane. The differences are only in the overall resistance

in the pertractor, which is smaller. In addition, it is not nec-

essary in PT to pump the solvent in its circulation loop, as it

is used in the simultaneous MBSE and MBSS process.


18/30


Fig. 7. Hollow fiber contactor with cross-flow of phases (Liqui Cel Extra-Flow, Celgard).

4.1. Factors affecting the performance of contactors

Both composition of the feed and its pH can greatly in-

fluence the transport rate in extraction. Components, which

compete the transport of target solute(s) should be avoided

or kept at minimum concentration, see Section3.5.The ef-fect of components of the fermentation broth, especially of

biosurfactants, on mass transfer in liquidliquid extraction

studied Pursell et al.[298].Adsorption film of surfactants on

interface decreases the extraction rate. The influence of com-

position of the solvent on the performance of contactors was

already discussed.

Hydrodynamic conditions in HF contactors play an im-

portant role in selection of optimal process parameters for

MBSE. In MBSE of organic acids, it is useless to increase

the linear feed velocity in fibers of HF contactors much above

4 c m s1 [12,89,111,137]. The optimum shell side Reynolds

number in MBSE of butyric acid is about 0.9 [100]. ForMPCA this value is only about 0.2, as shown in Fig. 8b,

and for MBSE of phenylalanine by a solvent with D2EHPA

the optimum value ofReshellis around 2[299]. Typically, the

dependence of the overall length of fibers (number of con-

tactors) in MBSE plus MBSS goes through a minimum, as

shown inFig. 8b. From these data it is clear that the role of

hydrodynamic conditions in HF contactors may not be so de-

cisive in MBSE and MBSS of organic acids comparing with

solutes with a very high distribution coefficient, like some

metals.

The composition of the stripping solution, e.g. stripping

reagent type[123,126]and its concentration in the stripping

solution[90,95,123]may considerably influence the perfor-

mance of the stripper. Themost important is to have an excess

of reagent and to avoid the formation of a boundary layer de-

pleted in the reagent.

4.2. Modelling and mass-transfer characteristics

In modelling and simulation of MBSE and MBSS of or-

ganic acids with reactive extractants (carriers) it is important

to take into account the kinetics of extraction andstripping re-

actions, as will be discussed below. The concentration depen-

dence of the distribution coefficient of organic acids, which

cannotbe small,should be taken into account, as well. This in-

fluences the value of the concentration driving force and may

result in the concentration dependent overall mass-transfer

coefficient, see Eq.(1).

Models considering constant mass-transfer

coefficient in MBSE are presented in papers[9,10,105,106,108,116,117,124,133,162,165,300]. Models

considering variable distribution coefficients are presented

in papers [124,133]. Models of MBSE and/or MBSS

taking into account reaction kinetics of formation and

decomposition of the extractantacid complex(es) in

extraction and stripping L/L interfaces are presented in

papers [12,90,97,100,145,301]. Reaction kinetics resis-

tances were included in model of pertraction in papers

[26,29,302].

Using diffusion and kinetic resistances in a series ap-

proach; the following equations have been derived for the

overall mass-transfer resistance in MBSE[90,111]. For thesteady state or quasi-steady state conditions, when fluxes in

the individual boundary layers are equal (accumulation in

boundary layers can be neglected), the following relation can

be derived for the overall mass-transfer resistance in MBSE,

taking into account the resistance connected with the kinet-

ics of the reaction of formation of the permeantextractant

complex

Re =1

Ke=

e

kF+

Ai,e

Aw,ekSwD+

Ai,ee

Ao,ekSbD+

1

re(1)

where the overall mass-transfer resistance is composed of

four individual resistances. The overall mass-transfer coeffi-

cient is defined for concentrations in the aqueous phase and

the effective surface area of L/L interface

ne = KeAeie

cF

cS

DS

(2)

The kinetics of formation and decomposition of the

permeantextractant complex(es) via interfacial reactions

can be in the first approximation described by the first-order

rate equations[12,29,90,100]

ne = reAi,eecFS (3)

ns = rsAi,sscSR (4)


19/30


where cFS is the concentration of MPCA in the feed phase

close to the extraction interface andcSR is the acid concen-

tration in the solvent close to the stripping interface. The rate

constants reand rs are, de facto, lumpedparameters reflecting

the kinetics of interfacial reactions of the complex formation

or decomposition, equilibrium and the kinetics of competi-

tive adsorption or desorption of molecules of the complexesand the free extractant molecules on/from the interface. Dif-

ferent approaches were used in papers where in modelling of

extraction or MBSE and MBSS reaction kinetics have been

taken into account. Reactions on the L/L interface are con-

sidered in papers on MBSE of lactic and citric acids [97],

butyric acid[99,100], MPCA[89,90], penicillin G[303]and

phenylalanine[137]. Homogeneous reactions of acid with

an extractant were supposed in papers devoted to MBSE of

penicillin G[145]and phenylalanine[219]and extraction of

lactic acid[259,304].

In the case when the kinetics of the stripping reaction

influences the overall resistance in MBSS and for situations

with a zero resistance in the stripping solution boundary layer(excess of reagent), the following equation was derived

Rs =1

Ks=

Ai,ss

Ao,skSb+

Ai,s

Aw,skSw+

1

rs(5)

Eqs. (1)and(5)represent the diffusion-reaction models of

MBSE and MBSS, and without the last terms for resistance

based on the reaction kinetics, they represent the diffusion

models for the estimation of the overall mass-transfer resis-

tance or the overall mass-transfer coefficients in these pro-

cesses. The estimation of the individual mass-transfer coef-

ficients is discussed in papers[5,10,11,100].

Mass-transfer characteristics of two-phase HF contactorsin several systems are presented in Table 13. Data for contac-

tors Liqui Cel (Celgard) with cross-flow of phases of labora-

tory size 2.5 in. 8 in. and pilot plant contactors 4 in. 13 in.

and 4 in. 28 in. (which can be used also for smaller produc-

tion plants) are available for some systems. The values of

the lumped rate constants of extraction and stripping reac-

tions, defined by Eqs.(3)and(4), for some organic acids and

solvents are listed inTable 14.

It is evident from Table 13 that in most systems the

value of the overall mass-transfer coefficient in stripping is

lower, not seldom one order of magnitude, comparing with

MBSE. This is connected with a slower decomposition of the

extractantacid complex on stripping interface. The values of

the lumped rate constants on extraction interface are higher

than the rate constants for stripping reactions, as documented

inTable 14.The only exception among

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