5552507 liquid liquid extraction

8/6/2019 5552507 Liquid Liquid Extraction

1/36

Liquid-Liquid extraction is a versatile anddependable separation technique wherein an

aqueous solution is usually brought into contactwith another organic solvent, exclusivelyimmiscible with the former, so as to affect alegitimate and actual transfer of either one or

more solutes into the latter.

Introduction:

Separations technique is superior to othersdue to ease of use, faster extraction times,decreased volumes of solvent, and their

superior ability to concentrate the analytes.


2/36

Separatory funnel

Liquidliquid extractions are usually

accomplished with a separatoryfunnel. The two liquids are placed in

the separatory funnel and shaken to

increase the surface area between the

phases. When the extraction iscomplete, the liquids are allowed to

separate, with the denser phase

settling to the bottom of the

separatory funnel.

Invariably such separations may be performed by shaking

the two liquids in a separatory funnel for a few minutes; and

may be extended either to large quantities of pharmaceutical

substances or trace levels.


3/36


4/36

Liquid-liquid extraction has been employed predominantly

and effectively not only for the pre-concentration and

isolation of a single chemical entity just before its actual

estimation, but also for the extraction of classes of organiccompounds or groups of metals, just prior to their usual

estimation either by chromatographic techniques or by

atomic-absorption methods.

The behavioral pattern of two immiscible solvents, say a

and b, is essentially nonideal with respect to one another.Now, if a third substance is made to dissolve in a two-phase

mixture of the solvents (i.e., a and b), it may behave

ideally in either phases provided its concentration in each

individual phase is approximately small.

THEORY


5/36

Therefore, under these prevailing experimental parameters

the ratio of the mole fractions of the solute in the two

respective immiscible phases (a and b) is found to be a

constant which is absolutely independent of the quantity ofsolute present.

It is termed as the Nernst Distribution Law or the Partition

Law and may be expressed as follows:

KP =[A]a

[B]b=

Concentration of solute in solvent a

Concentration of solute in solvent bwhere,

[A]a = Mole fraction of solute A in Phase a[B]b = Mole fraction of solute B in Phase b, and

Kp = A constant.The constant (KP) is also known as the distribution coefficient

or the partition coefficient.


6/36

The Partition Law offers the following two limitations,

namely:

(a) It is not thermodynamically rigorous i.e., it takes

no cognizance of the activities of the different species. Inother words, it is solely applicable to very dilute solutions in

which case the ratio of the activities almost approaches

unity, and

(b) It does not hold good when the distributing

substances encounters association or distribution in either

phases (i.e., a and b).

In liquid-liquid extractions the following two aspects are

very crucial and important, namely:

(a) Error due to the Volume Change, and

(b) Effectiveness of an Extraction.


7/36

In a situation wherein two immiscible solvents are employed

in an extraction, the volumes of the two individual phasesafter attainment of equilibrium may be appreciably different

in comparison to the initial volumes of the solvents used.

Therefore, a number of procedures have been adopted toavoid error due to the volume change incurred thereby,

namely:

a) ERROR DUE TO THE VOLUME CHANGE

(i) Measure the volume of the phase employed for the

analysis and incorporate this volume in the calculations.

(ii) Separate the phase quantitatively and subsequently

dilute to a known volume.


8/36


9/36

after simplifying and rearranging-

Kp =

M1

M2=

x-y

V1( )

y

V2

Kp =x

V1( )

y

V2y-

V1

x

y

V2

V1= -

V2

V1

xy

V2V1

= -( 1 )

or Kp

V1

V2=

x

y- 1

or Kp

V1

V2

=x

y+ 1

or Kp

V1

V2=

x

y+ 1( )

-1= f

where,

f = fraction not extracted


10/36

From the above equation it is quite evident that the fraction

extracted is absolutely independent of the initial solute

concentration. Hence, the fraction left unextracted after n

extraction may be given by the following expression-

Kp

V1

V2+1( )

-n=fn

FACTORS INFLUENCE SOLVENT


11/36

A number of cardinal factors exert a positiveinfluence on the phenomenon of solvent

extraction, namely:(a) Effect of temperature and inert solutes,(b) Effect of pH on extraction,(c) Effect of ion-pair formation, and

(d) Effect of synergistic extraction.

FACTORS INFLUENCE SOLVENTEXTRACTION

(a) Effect of temperature and inert solutesThe physical as well as chemical

interactions of a solute is capable of changing

its apparent partition coefficient between a pairof solvents. Therefore, it is absolutely necessaryto take this into consideration while selecting anappropriate extraction-system.

Th titi ffi i t ll t


12/36

The partition coefficients are normally notsensitive to temperature when the two solventsin question are more or less immiscible and also

the concentrations are fairly low in both thephases.Thus, the effect of temperature on the

partition coefficient may be estimated

conveniently from its effect on the solubilities ofthe substance in the two respective solvents.

KP =S1

=Solubility of solute in solvent a

Solubility of solute in solvent bS2The effect of inert solutes, such as :

calcium chloride, magnesium chloride andsucrose, can also be employed judiciously and

efficaciously in solutions to difficult extractionroblems.


13/36

They allow efficient extractions from thewater into such solvents as acetone, ethanoland methanol that are found to be completely

miscible with water in the absence of salt.The three inert solutes to be the best

agents for salting acetone out of water. It hasbeen observed that the acetone layer thatseparated from a saturated aqueous solution ofCaCl2 exclusively contained 0.32 0.01% water

(v/v) and 212 ppm salt (w/w) at equilibrium.

(b) Effect of pH on extractionGenerally, it has been found that the

organic acids and bases exist in aqueoussolution as equilibrium mixtures of their

respective neutral as well as ionic forms.


14/36

Thus, these neutral and ionic forms may nohave the same identical partition coefficients ina second solvent; therefore, the quantity of a

substance being extracted solely depends uponthe position of the acid-base equilibrium andultimately upon the pH of the resulting solution.

In conclusion, it may be observed that the

PH for an extraction system must be selected insuch a fashion so that the maximum quantity ofthe analyte is present in the extractable form,that obviously suggests that the analyte shouldalways be in the form of either a free base or afree acid.


15/36

(c) Effect of ion-pair formation

In true sense, ion-pair may be regarded asa close association of an anion and cation, and

therefore, extraction is usually takes placeeither in a polar or a non-polar solvent.

In reality, the ion-pairs are invariablyformed by the union between comparatively

large organic anions and (much smaller)cations.Interestingly, the resulting ion-pairs havebeen found to show their appreciable solubility

in polar solvents ; and hence, these species maybe extracted conveniently under suchexperimental parameters where neitherindividual component ion could.


16/36

A few vital criteria for the formation of animproved aqueous extractable ionic species are:

Formation of a neutral metal-chelate

complex or by ion association, and Creation of larger and more hydrophobic

molecular species.

Example: Cu2+ with acetylacetonate forms afairly stable ring compound:


17/36

(d) Effect of synergistic extractionSynergistic extraction: It may be

defined as the process whereby two different

reagents when employed together are capableof extracting a metal ion with a distinct andmarked efficiency, in comparison to a conditionwhen the same two reagents are used

individually.Example: Complexation of Mn2+ with dithizoneand pyridine

It has been observed that the complexformed by Mn2+ with dithizone alone is of nopractical analytical utility because of the factthat it undergoes decomposition very quickly.


18/36

However, the addition of a base, such aspyridine into the Mn2+ plus dithizone complexyields a red-complex, which is fairly stable to

oxidation & light; and, therefore, forms the basisfor a very sensitive photometric methodemployed in estimating trace amounts of Mn2+.

Following is the chemical reaction of the abovecomplex formation:


19/36

EMULSION PROBLEM ENCOUNTERED INEXTRACTIONEmulsion:

Emulsion may be defined as-a dispersedsystem containing at least two immiscible liquidphases.

The effective and meaningful extraction of

a solute is rendered almost impossible whenthere is an emulsion formation during anextraction process. Emulsion formation makesthe separation of the two phases difficult.

Actually, emulsion formation is a frequentand serious problem when dealing with theextraction of drugs from biological as well as

pharmaceutical formulations.

Emulsion formation enhances the area of


20/36

Emulsion formation enhances the area ofthe interface between the two immisciblesolvents and as a result also enhances the free

energy of the system, which may be designatedby the following expression:Free energy = x A

where,

= Interfacial tensionA = Change in surface area resulting from

emulsificationObviously the lowest free energy is given

by the most stable state for a system at constantpressure and, therefore, in due course anemulsion shall break spontaneously to the two-layered system.

F l l l i


21/36

The breaking of an emulsion (coalescence)could be a slow process. There are a number of

factors which may be responsible for the slow-coalescence of an emulsion, namely:

(b) Usually surfactants decrease the

interfacial tension between the two immiscibleliquids which help in stabilizing an emulsion

(a) Finely divided powders of albumin,gelatin and natural gums have a tendency to

coat the droplets formed in an emulsion whichultimately prevent them from coalescing

Factor causes slow-coalescence emulsion

(c) Ionic species may get absorbed at theinterface of two immiscible layers resulting in the

formation of a net charge on the droplets.


22/36

In fact, there are many natural andsynthetic substances that are profuselyincorporated in the formulation of drugs which

are found to stabilize emulsions either by coatingthe droplets or by minimizing the interfacialtension, namely:

Because all droplets shall essentially bear thesimilar charge, naturally they will repel oneanother thereby preventing coalescence.

(i) Coating the droplets: e.g., starch, acacia,silica, gelatin, finely divided talc, and

(ii) Minimizing the interfacial tension: e.g.,mono-and di-glycerides ; stearates and sorbitanmonoleate.

P ti f l i f ti


23/36

It has been observed that once an emulsionis formed it is difficult to break the emulsion.

Therefore, it is absolutely necessary toconcentrate to the following guidelines, as far aspossible, in order to avoid forming emulsions inthe course of an extraction process:(1) Very cautious & gentle agitation and

employing a sufficiently large liquid-liquidinterface provides a reasonably good extraction.Especially when the two-liquid layers have alarge contact surface in an extraction process,

vigorous or thorough shaking of the two phasesis not required at all.

Prevention of emulsion formation

(2) The removal of any finely dividedinsoluble material (s) in a liquid phase must be

done by filtration before carrying out theextraction rocess.

(3) Always prefer and use such solvent pairs


24/36

(3) Always prefer and use such solvent pairsthat have a large density difference and a highinterfacial tension, for instance: water and

hexane, as they are less prone to emulsionproblems. In contrast, such solvent pairs aswater and benzene should not be used in theextraction process.(4) When performing extraction from water

always ensure not to work at pH extremes andparticularly at high pH ranges to avoidemulsification.

(5) In cases of acute emulsion problems

substances like anion exchangers, alumina orsilica gel are used specifically to resolve theproblem by adsorption of the emulsifying agents.


25/36

In fact, it would be advisable to employ thetechnique of column chromatography for theeffective separation of the analyte as compared

to an extraction process.

Following are the various techniquesinvariably used to break an emulsion or to

achieve coalescence:

Process of Breaking of an emulsion(coalescence)

(1) Mechanical means: Coalescence may beachieved by mechanically creating turbulence onthe surfaces of the droplets either by passing the

emulsion through a bed of glass-wool or simplyby stirring with the help of a glass-rod.

ens t es o t e two qu s are apprec a y


26/36

ens t es o t e two qu s are apprec a ydifferent coalescence may be achieved bycentrifugation.

(3) Addition of monovalent and divalentions: Relatively simple emulsions are broken byadding monovalent salts like sodium chloride;whereas charge-stabilized emulsions are

specifically sensitive to the divalent ions, suchas: CaCl2, MgCl2 etc.

(4) Ethanol or higher alcohol: Addition ofsmall quantities of either ethanol or sometimes ahigher homologous alcohol aid in coalescing anemulsion.

(5) Silicone- defoaming agent: A few drops

of the silicone-defoaming agent sometimes help

(6) Sudden cooling of emulsion (thermal


27/36

(7) Altering the ratio of solvents:Coalescence of an emulsion may also beachieved either by altering the ratio of theprevailing dispersed phase or even by partialevaporation of the solvent.(8) Thin-bed of an adsorbent: Sometimes

simply passing of an emulsion through a thin-bedof an adsorbent remarkably helps in achievingcoalescence. The analyte must not be absorbedfrom either solvent.

(6) Sudden cooling of emulsion (thermalshock): Sudden temperature drop or freezing(i.e., giving a thermal shock) of an emulsion

mostly enhances the interfacial tension betweenthe two immiscible phases thereby causingcoalescence.


28/36

ASSAY METHODS BASED ON LIQUID-LIQUIDEXTRACTION

A number of specific elements may be

determined quantitatively based on liquid-liquidextraction method or solvent-extractiontechnique, namely:(a) Determination of Copper (I) as the neo-cuproin

complex

(b) Determination of Iron (III) as the 8-hydroxyquinoline complex or Iron (III) oxinate

(c) Determination of Lead (I) by the dithizone method(d) Determination of Molybdenum (VI) by the

thiocyanate method(e) Determination of Nickel (II):

- as dimethylglyoxime complex, and- by synergistic extraction.


29/36

(1) Transfer 10 0 ml of the sample solution


30/36

(1) Transfer 10.0 ml of the sample solution(containing upto 200 mcg of copper) in aseparatory funnel, add 5 ml of hydroxyammoniumchloride solution to inhibit the reduction of Cu (II)to Cu(I).

(2) To the resulting solution add 10 ml of sodiumcitrate solution to enable complexation of anyother metals that may be present.

(3) Add ammonia solution gradually until the pH isabout 4.0 followed by 10 ml neo-cuproin solution.

(4) Shake for about 30 seconds with 10 ml ofchloroform and allow the layers to separate.

(5) Repeat the extraction with a further 5 ml ofchloroform.


31/36

(6) Finally, measure the absorbance at 457 nmagainst a blank on the reagents that have beenused identically to the sample.

DETERMINATION OF IRON (III) AS THE 8-HYDROXY QUINOLATE COMPLEX [ IRON (III)OXINATE]Theory:Iron (III) upto an extent of 50-200 mcg can beextracted effectively from an aqueous solution with a1% solution of 8-hydroxyquinoline in chloroform bycarrying out a double extraction when the pH of theresulting aqueous solution ranges between 2 and 10.

Evidently, between pH 2.0 to 2.5 metals like Ni, Co, Ce(III) and Al do not interfere at all. However, iron (III)oxinate is dark-coloured in chloroform and absorbs at470 nm.


32/36

(2) Pl 50 l f h l i ( 100 f F ) i


33/36

(2) Place 50 ml of the solution (~100 mcg of Fe) in a100-ml separatory funnel, and add to it 10 ml of 1%oxine solution, and shake for 1 minute.

(3) Separate the chloroform layer.

(4) Transfer a portion of the chloroform layer to a 1 cmabsorption cell and determine the absorbance at 470nm in a UV-spectrophotometer, employing the solvent

(chloroform) as a blank or reference, and

(5) Repeat the extraction with a further 10 ml quantityof 1% oxine solution, and measure the absorbanceagain so as to confirm whether all the iron was

extracted or not. Usually three extractions suffice thecomplete extraction of Fe (III).

DETERMINATIONS OF NICKEL (II)


34/36

DETERMINATIONS OF NICKEL (II)

Theory:

Dithizone and 1, 10-phenanthroline help in thesynergistic extraction of Ni (II) both quantitatively andrapidly over a wide range of pH between 5.5 to 11.0 togive rise to a dark colored mixed-ligand complex thatabsorbs at 520 nm.

Materials Required:1. Ammonium nickel sulphate: 0.0135 g2. Phthalate or acetate buffer (pH 6): 5ml3. Dilute ammonia solution4. Chloroform: 15 ml

5. Sodium hydroxide (0.1 M): 10.0 mlProcedure:(1) To 5 ml of a solution containing from 1 to 10 mcg ofNickel (II) add 5 ml of a phthalate or acetate buffer.

Synergistic Extraction

(2) If the sample is acidic carefully adjust the pH to 6 0


35/36

(2) If the sample is acidic, carefully adjust the pH to 6.0with dilute ammonia solution.

(3) To the resulting solution add 15 ml of chloroform

solution of dithizone and 1,10-phenanthroline.(4) Moderately shake the two phases for 5 minutes in aseparatory funnel, allow them to separate distinctly intoaqueous and chloroform layers.

(5) Excess dithizone may be removed from thechloroform layer by back-extraction with 10 ml of 0.1 MNaOH, (a through shaking for 60 seconds will sufficethis extraction).

(6) Once again separate the chloroform layer (lower)and measure its absorbance in a 1 cm absorption cell at520 nm vs an identically treated blank.

(7) Fi ll d lib ti i t d d Ni


36/36

(7) Finally, draw a calibration curve using standard Ni(II) solution containing 2, 4, 6, 8, and 10 mcg in 10 ml(obeying Beers Law).

Partition coefficient (KD)A partition or distribution coefficient (KD) is the ratio of

concentrations of a compound in the two phases of a

mixture of two immiscible solvents at equilibrium.

Hence, these coefficients are a measure of differential

solubility of the compound between these two solvents.

The partition coefficient is a measures of how

hydrophilic ("water loving") or hydrophobic ("water

hating") a chemical substance is.

5552507 liquid liquid extraction

Documents