 a useful method to separate components (compounds)

of a mixture.
 an aqueous solution is usually brought into contact
with another organic solvent.
 exclusively immiscible with one another.
 Transfer of solute/solutes from one liquid into another
liquid phase.
 also known as solvent extraction and partitioning.
 Ease of use,
 Faster extraction
 Decreased volume of solvent, and
 Their superior ability to
concentrate the analytes.
 Liquids are placed in the separating funnel
 Moderate shaking (moderately) Increase the surface area
between the phases
 After completing extraction -liquids are allowed to separate
 Denser phase settling to the bottom of the separating funnel
 Shaking allows greater area of contact between the two
immiscible liquids, resulting in faster equilibration of the
solute substance(s) between the two liquids.
 The mixture is brought into contact with a solvent in which
◦ the substance of interest is soluble, but
◦ the other substances present are insoluble.
 Solute in the solution has more affinity toward the added
solvent.
Feed solution/phase:
◦ Initial solution containing one (or more) solute(s)
◦ Solute(s)+Solvent 1
◦ Solvent 2 is added in feed phase to perform extraction

Extract: Solvent that is enriched in solute(s) is called extract. Solvent

is evaporated to collect and measure the amount of the solute
Solvent 2+Solute(s)
Raffinate: The feed solution that is depleted in solute(s). If the
extraction process is repeated, the Raffinate becomes the feed
phase.
 The distribution constant (or partition ratio) (KD), is the
equilibrium constant for the distribution of an analyte in two
immiscible solvents.
 Most organic compounds are more soluble in organic solvents
 Some organic compounds are more soluble in water.
 At a certain temperature, the ratio of concentrations of a
solute in each solvent is always constant. This ratio is
distribution coefficient, K.

 Sol 1 and Sol 2 are immiscible liquids.

 Suppose compound has K=2 between Sol 1 and Sol 2

 30 particles of are distributed between 100 mL volume

of Sol 1 and Sol 2.
 300 particles of are distributed between 100mL volume
of Sol 1 and Sol 2. No matter how much solute there is,
the distribution coefficient K remains constant, equal
to 2.

 Find out how much particle is distributed in each

solvent.
 And what happen when you double the volume of
second solvent?
Calculation:
Let the X amount will be extracted in Solvent 2. Total
number is 300. Therefore, 300-X amount is in Solvent
1. Diff Coff is 2.
Sol 1= 100 mL and Sol 2 = 100 mL
K= (X/100)/(300-X)/100=2
Or, X=2(300-X)
Or, X=600-2X
Or, 3X=600
Or, X=200
 When you double the volume of solvent 2 (i.e., 200 mL of
solvent 2 and 100 mL of solvent 1)

 Let the X amount will be extracted in Solvent 2. Total number is

300. Therefore, 300-X amount is in Solvent 1. Diff Coff is 2.
Sol 1= 100 mL and Sol 2 = 200 mL
K= (X/200)/(300-X)/100=2
Or, X=2(300-X)X2
Or, X=1200-4X
Or, 5X=1200
Or, X=240 in Sol 2 and (300-240=60) in Sol 1
 Five grams of Compound A is dissolved in 90 mL of water.
The distribution coefficient for Compound A between hexanes
and water is 5 (in other words, KCompound A(hexanes/water) = 5)

1. How much of Compound A will be in the hexanes if you

extract it from the water one time with 90 mL of hexanes?
2. How much of Compound A will be in the hexanes if you
extract it from the water with three sequential extractions
using 30 mL of hexanes each time, and then combine the
hexanes extracts?
1. How much of Compound A will be in the hexanes if you extract it from the
water one time with 90 mL of hexanes?
K = 5 = x g in 90 mL/5-x g in 90 mL
5 = x/5-x (90 mL cancels)
x = 4.2 g
2. How much of Compound A will be in the hexanes if you extract it from the
water with three sequential extractions using 30 mL of hexanes each time,
and then combine the hexanes extracts?
K = 5 = x1 g in 30 mL hexanes/5-x1 g in 90 mL water
5 = 3x1/5-x1
x1 = 3.1 g
Now, there is 5 - 3.1 g or 1.9 g of the compound in the water, therefore:
K = 5 = x2 g in 30 mL hexanes/1.9-x2 g in 90 mL of water
5 = 3x2/1.9-x2
x2 = 1.2 g
Now, there is 1.9-1.2 g or 0.7 g of the compound in the water, therefore:
K = 5 = x3 g in 30 mL hexanes/0.7-x3 g in 90 mL of water
5 = 3x3/0.7-x3
x3 = 0.44 g
Now, add x1, x2 and x3: 3.1 + 1.2 + 0.44 g, and you get 4.74 g. Compare
this value with the 4.2 g obtained with one extraction with 90 mL of
hexanes (a, above), and you see why the efficiency of extraction is
improved if you split the organic extraction solvent up into several portions
and do multiple extractions.
 Nernst Distribution Law
“At constant temperature, a solute distributes itself
between two immiscible solvents only in a particular
ratio”
 This law is one of the laws applying to ideal dilute
solutions.
 It was discovered by W. Nernst in 1890.
 Two general types of LLE:
 1. Organic solvent extraction: an organic solvent
with a high affinity for the desired compound is used to
extract the compound from another solution.
 2. Acid-base extraction: An organic acid or base is
extracted from an organic solvent by using an aqueous
solution of an inorganic base or acid, respectively.
 A neutralization occurs which converts the compound
into an ionic, water-soluble salt.
 Transfer from organic phase to aqueous phase.
 Separatory Funnel extractions are performed to extract
compounds either into or from an aqueous layer.
 A separatory funnel is a useful apparatus for LLE.
 Mix and separate two immiscible liquids in this glassware.
 A number of factors exert a positive influence 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.
Emulsion formation is a problem when dealing with the extraction
of drugs from biological or pharmaceutical formulations which
tend to emulsify even upon moderate shaking due to presence of
emulsion stabilizers in the formulation.

These Emulsion Stabilizers are –

 Finely Divided Powders: coat the droplet with molecules
 Surfactant: surrounds opposite ion results emulsion
 Ionic Species: get absorbed at the interface of the droplets
resulting in a net charge on the droplets
 Moderate Shaking
 The solvents must be shaken moderately, so that the
phases are dispersed in each other for solute transfer but
then again forms separate layers.
 High Density Difference
 Density Difference between the solvents chosen must be
high so that they do not form emulsion upon dispersion
 Removal of Finely Divided Solids
 Finely divided Solids tend to stabilize the emulsion
Formation by coating the droplets.
 So, before extraction these solids must be removed from
feed phase by filtration.
 Avoiding High pH Range
 Since, Emulsification occurs more frequently and easily in
Extreme pH range (i.e. below 4 – Extremely Acidic and
above 9 – Extremely Basic); these ranges should be avoided
and kept between 4 to 9.
 Removal of Surfactant by Using Adsorbents
 To remove Surfactants, a thin bed of adsorbents (E.g.
Alumina, Silica Gel) can be used through which the feed
phase can be passed through.
 However, use of such adsorbents must be avoided which
can adsorb the solute.
 Mechanical Means
In case of simple emulsion, coalescence can be achieved by
mechanically creating turbulence on the surface of the droplets by
stirring with a glass rod
 Centrifugation
Centrifugation is a process of separation by the application of
Centrifugal Force based on the density difference between the
phases.
 Addition of Mono – or Di – valent Cation:

Saturated Solution of Mono – valent or Di – valent Salts (E.g.

NaCl or CaCl2) can be added to break down the emulsion by
increasing the ionic strength of Water / Aqueous Phase / Feed
Phase
 Addition of Ethanol or Higher Alcohol
 Addition of Ethanol or higher alcohol increases coalescence in
emulsion by increasing the interfacial tension between phases.
 Silicone – Defoaming Agent
 Addition of Silicone Defoaming Agent helps in breaking the emulsion.
 Sudden Cooling or Thermal Shock
 Sudden temperature drop or freezing (i.e. giving a thermal shock) of
emulsion mostly enhances the interfacial tension between the two
immiscible phases thereby causing coalescence.
 Alteration of Solvent Ratio
 Coalescence of an emulsion can be achieved by altering the ratio of
solvents prevailing in the dispersed phase.
 It can be done by slowly adding solvents.
 Thin – Bed of Adsorbent
 A thin bed of adsorbents (E.g. Alumina, Silica Gel) can be used
through which the feed phase can be passed through to break the
emulsion.
 Liquid – Liquid Washing is a process of separation of
impurities from the extract or reaction medium
containing the target solute and also the impurities.
 The process can be used to remove impurities from a
reaction medium.

 Impurities to be removed via Liquid – Liquid Washing

can be of 2 type –
◦ Byproduct
◦ Catalyst
Steps of Liquid-Liquid Washing
 Steps involved in the Liquid – Liquid Washing
are –
◦ Reaction Work–up
◦ Separation of Target Solute from the Reaction
medium by adding Organic Solvent
◦ Removal of Impurities
 Reaction Work-up
◦ Reaction of Phenol and Acetic anhydride results in the
formation of Phenol acetate and Acetic Acid which is
catalysed by Triethylamine.
 Separation of target solute from the reaction
medium
◦ Before performing the separation, it must be considered
that solubility of the target compound in organic solvent
must be higher than the solubility of impurities.
◦ So, solvent should be selected in such a way.
◦ In case of this reaction, the target compound Phenol
acetate is insoluble in water and soluble in Ether which
is higher than that of both Acetic Acid and
Triethylamine.
◦ So, Ether can be the organic solvent of choice to
separate Target Solute from the Reaction medium.
 Removal of impurities
◦ Selection of Solvents to remove impurities depends on the
properties of impurities.
◦ Impurities of acidic nature can be removed by adding
saturated aqueous solution of a Strong Base in the organic
extract. E.g. Acetic Acid (A Weak Acid) can be removed by
adding saturated aqueous solution of NaHCO3 in Ether
extract of Phenol acetate.
◦ As a result, Sodium acetate will be formed which is salt of
Acetic Acid and soluble in water from the saturated aqueous
solution of NaHCO3.